Disease Cheat Sheet

Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications
cryosurgery, topicals (5-FU,

sun exposure skin type I, age > 70, field
Hypertrophic AK (thickened), pigmented AK, small, raised scaly spots on chronically sun-exposed skin; UV induced mutations in p53 cause unrestrained growth and imiquimod, PDT w/ photosensitizer Most common precursor to
Actinic Keratoses (AK) immunosuppression disease on upper limbs/ head/ Histology? Surface changes at epidermis
actinic chelitis (lips) scattered, thick erythematous patches damage to repair genes prevents tumor rejection ALA, chemical peel, reduction of SCC
genetic conditions neck
immunosuppressants to safe levels
Chronic UVB exposure,

Nodular (can be pigmented in darker pts) immunosuppression,
UVB causes direct DNA damage to p53 and overexpression of surgical excision, Moh's, PDT w/
inherited conditions 750,000 new cases/yr,
originate from keratinocytes from epidermis or follicular bcl-2, which prevents apoptosis; carcinoma of follicular male, older age, fair complexion, ALA, radiation tx (for non-operable),
Basal Cell Carcinoma Superficial (more scaly, less thick) (Gorlin Goltz basal cell growing incidence
epithelium; unlikely to metastasize; most common skin cancer keratinocytes tendency to burn, outdoor Clinical topical tx for field dz (5-FU,
(BCC) nevus syndrome, XP), among younger ages
& found above clavicle occupation imiquimod), reduction of
Morpheaform (scarring, loss of pigment; chronic arsenism, patch (30-40s)
immunosuppressants to safe levels
MORE AGGRESSIVE) mutations, previous
BCC
Deficiency in patch (negative regulator of Shh) causes

constitutive action of positive regulator (Shh), increasing
Vismodegib (targets Shh to
incidence of BCC
Basal Cell Nevus TONS of BCCs as child, megaloblastomas, palmar pits, bifid decrease tumor size; but still Loss of taste (and ultimately
N/A
Syndrome (BCNS) ribs, frontal bossing of scalp residual tumor so perhaps anorexia) is a side effect of tx
Shh binds and inhibits patch; without patch, smoothened
development of resistance)
causes increased transcription of GLI-1,2,3, causing increased
cell proliferation
Chronic UVB exp

Originates from interfollicular keratinocytes following direct DNA
chem carcinogens surgical excision, Moh's, PDT w/
damage to p53 from UVB; SCC make VEGF so highly Heart/lung transplant recipients
Worrisome when recurrent, location on genetic disorders 250,000 new cases/yr; ALA, radiation tx (for non-operable),
Asymptomatic until fast growing --> painful, grows faster than angiogenic
Squamous Cell forehead / temple/ ear/ lip, large size (>2cm), immunosuppression growing incidence topical tx for field dz (5-FU,
BCC, ulceration/ verruca-like, common in transplant pts, Chronic lymphocytic leukemia
Carcinoma (SCC) poor differentiation, invasion (in-transit met to HPV among younger ages imiquimod, cryosurgery), reduction
metastatic potential Apoptosis loss possibly due to ROS resistance of SCC
lymphatic channels), perineural invasion chronic inflam (leg (30-40s) of immunosuppressants to safe
XP
ulcers, DLE, levels
Genetic predisposition for loss of p53 (XP, HPV)
osteomyelitis)
genetic mutations (MC1R
mutations- red hair &
predispose to B-raf mut;
familial loss of p16)
less common than other skin cancers (BCC>SCC>>MM)
Malignant tumor arising spontaneously from melanocytes in young adults
basal epidermis or from dysplastic nevi; dysplastic nevi then ALM can sometimes FH of MM or DN
SSMM (common, pagetoid - migration to place not typically
undergoes radial growth where it becomes invasive until able to occur in conjuction with UV light Evaluation includes history, TBSE,
found, trunk of men, legs of female; regression = loss of 4% of cancer cases, but
Superficial spreading melanoma (SSMM) grow vertically; once vertical growth phase reached, the tumor vitiligo (autoimmune rptd childhood sunburns LN exam, CXR, routine labs, & MRI
pigment/scarring) more than 75% of skin
has high metastatic potential dz); associated with # (>50) & size (>5mm) of nevi brain/CT of chest (for late-stage) HIGH risk for metastasis
cancer deaths; 5th &
Nodular melanoma (NM) mutations in C-kit CN
- NM (no radial growth- often ulcerated, rapidly growing, can 7th most common
Malignant Melanoma Associated with oxidative damage from UVA PMH of MM Histology? Sun exposure signs (loss of elastin fibers, solar Surgical removal/ excisional bx later detection and higher stage
lack pigment; trunk of men, invades through dermal/epidermal cancers in men &
(MM) Lentigo maligna melanoma (LMM) - Melanoma in sun- high SES elastosis - abnl elastin in upper dermis) associated with higher mortality
jx); women; 70,000 new
Staging depends on Breslow's depth, ulceration, # mitotic protected areas can Skin types 1&2 Sentinel LN bx to stage metastasis
cases/yr; primarily
"know your ABCDEs" Acral lentiginous melanoma (ALM) - hands, figures, lymphatic/ vasculature entry result from mutations in latitude Excisional (or incisional punch) bx for Breslow's depth to LNs (used for melanomas Pts with p16 mutations have
- LMM (sun exposed areas; slowest growth rate and longest younger adults;
feet, mouth, genitals b-raf or N-ras DNA repair defects >1.0mm in depth) increased risk of pancreatic
radial growth stage); usually appears as growing freckle, increased incidence
B-raf mutation --> loss of PTEN --> activation of oncogene Akt - oncogenes immunosuppression cancer too!
freckle in unusual place, or freckle that crosses anatomic due to recreational
Mucosal melanoma (very rare!) -> transformation of radial/noninvasive melanoma to Braf inhibitors (PLX4032) -
boundaries habits
vertical/invasive MM LACK MUTATIONS IN NM in middle-aged men; prolongs survival but not curative
p53
- ALM (palms, soles, subungal; Hutchinson's sign,
N-ras mutation --> activation of oncogene Akt LMM in older pts w/ chronic UVB
melanonychia striata, abnl nail)
exposure & age spots;
ALM more common in dark/Asian

pts
uniform pigmentation, symmetrical shape, sharply demarcated

Benign Nevi Arise from melanocytes
borders, wide distribution and colors
Dysplastic nevus syndrome (DN) - multiple
benign with characteristics of precursor melanoma: irregular
Dysplastic Nevi family members w/ melanoma and multiple DN can be sporadic or familial b-raf mutations
growth, variation in color/size, multiple asymmetric lesions
in pt (also have only one copy of p16)
Prophylactic removal during teen

Present at birth or within first year of life; important to monitor
Congenital Nevi Giant Melanocytic Nevus Relative risk for melanoma depends on size of CN N-ras mutations years; staged surgical removals if
changes in size/color/symmetry
large
Defective NER (nucleotide excision repair); New tx include mimics of

Xeroderma marked increase in skin malignancies at young age, At least 10 DNA repair
N/A photolyases (enzymes in other High rate of MM, SCC, freckles
pigmentosum (XP) photosensitivity, impaired DNA damage repair systems defects
accumulation of oxidative and DNA damage organisms that repair CPDs)
Histology?
Determined by total UVB energy absorbed (ind of duration) Failed or incomplete
Endothelial swelling, decreased langerhans, neutrophil
repair of thymine dimers Major risk factor for non-
recruitment, apoptotic keratinocytes (bright pink)
Sunburn N/A Inflammation, erythema Inflammation (cytokines, histamine, prostaglandins, serotonin) --> mutations in p53 melanoma and melanoma skin
cause redness; increased adhesion protein expression --> (higher risk for non- cancers
areas of hyperplasia (thickened stratum corneum,
immune cell recruitment melanoma skin cancers)
epidermis, dermis)
Change in existing melanin (immediate pigment darkening

caused by redistribution of melanin - IPD, persistent pigment
darkening- PPD)
Sun tan N/A
New melanin (delayed tanning) formed when keratinocytes
release MSH in response to UVR; MSH binds MC1R on
melanocytes --> increased melanin production and proliferation
mutations in filaggrin
(which binds to keratin)
Excess stratum corneum due to altered epidermal
Ichthyosis N/A Inherited disease causing generalized scaling and thickened skin causes
differentiation
bundling/collapsing of
keratin fibers
Localized scaly plaques, can be raised; less prone to infections
Psoriasis Excess stratum corneum from low epidermal turnover
(abundant AMPs)
Epidermolysis bullosa Inherited disorder w/ defects in cellular attachments, causing

(General) blisters on hands and feet
(EB) epidermis to no longer stick to dermis
Superficial blistering within the epidermis caused by
disorganization of keratin intermediate filament network
Less severe bc blistering in higher skin layers Genetic defects w/
Dominant mutation causes complete disruption of the keratin keratin (arginine at Histology? Cytolytic fracture / cleavage plane below the
EB Simplex
more superficial (but painful blisters), non-scarring, localized to polymer (even if you have one nl K14) position G of alpha-helix nuclei of basal cells --> aggregation of keratin fibers
hands/ feet/ extremities, no mucus membrane involvement heptad is mutated)
Recessive mutation causes truncated protein or loss of protein
but not as problematic
Very serious bc blistering in middle skin layers premature stop codon

in laminin 5 genes
Generalized blisters at birth, periorificial granulation tissue, nail
Junctional Blistering in the lamina lucida Can be lethal in early childhood
shedding/dystrophy, denuded areas, enamel defects, growth sometimes defects w/
retardation, anemia, epithelial blistering of mucosal collagen 17 or B4/a6
membranes (Resp, GI, GU) integrins
Subepidermal blistering w/ scarring
Dystrophic (Recessive-RDEB or Dominant- milia (cysts on newborns) that scar upon healing, Premature stop codon
Subepidermal blistering Severe scarring
DDEB) absent/dystrophic nails, Mitten deformities (fusion of finger scar in collagen VII genes
tissue (RDEB)); mucosal surfaces involved, malnutrition, growth
retardation, anemia
Autoimmune-mediated blistering disease caused by antibody Autoantibodies against
Epidermolysis bullosa acquisita Significant scarring
deposition against collagen VII Collagen VII
Bullous pemphigoid (BP) Histology? Subepidermal blister (white space btwn
blistering disease where epidermis is lifting off of basement epidermis & dermis) (sub-basal split), healthy
Autoimmune blistering disorder where antibodies are directed
membrane; usually on lower extremities of older patients Autoantibodies against epidermis, +eosinophils (pink)
Bullous pemphigoid at hemidesmosomes (sub-basal) so loss of epidermal
BPAG1 and/or BPAG2
attachment to basement membrane
Itchy, tense blisters (do not break easily!), Dx confirmed w/ immunofluorescent Abs binding to
basement membrane
Histology? Subepidermal blister (white space btwn
Autoimmune blistering disorder where antibodies are directed Autoantibodies against epidermis & dermis) (sub-basal split), healthy
red line along gingivial sulcus (white picket fence), no
Mucus membrane pemphigoid at hemidesmosomes (sub-basal) so loss of epidermal BPAG2, laminins, epidermis, +eosinophils (pink)
scarring
attachment to basement membrane integrins
Dx confirmed w/ immunofluorescent Abs
severe ocular disease, symblepharon (fibrous bands where Severe inflammation of the eye causes thick & fibrous scarring Possible blindness as skin covers
Ocular cicatricial pemphigoid
eyelid fuses to conjunctiva) that fuses with the eye conjunctiva as symblepharon cornea if no aggressive treatment
Pemphigus Histology? Basal epidermis still attached to BM, and rete
Immunosuppressants,
Inter-epidermal blisters, jagged & flaccid blisters w/ positive Autoimmune blistering disorder where antibodies (IgG) are ridges still visible but huge white space above represents
Autoantibodies against corticosteroids; new therapies
Nikolsky sign (easy to deform w/ slight pressure), attacking intra-epidermal (suprabasal) proteins of desmosome, blister (suprabasal split) side effects of steroids; high
Pemphigus vulgaris desmoglein 3 and/or (tyrosine kinase inhibitors to
hyperpigmentation in healing areas, not too much scarring, resulting in compromised cell-cell adhesion [basal layer splits fatality w/o tx
desmoglein 1 increase resistance to pemphigus
severe nail disease, oral lesions from spinous layer] Chicken wire appearance w/ direct
IgG)
immunofluorescence
Autoimmune blistering disoder where antibodies (IgG) attack
intra-epidermal (suprabasal) proteins of the desmosome, Autoantibodies against Immunosuppressants,
Pemphigus foliaceus side effects of steroids
resulting in compromised cell-cell adhesion [basal layer splits desmoglein 1 corticosteroids
from spinous layer]
Ectodermal Dysplasia Mutation in
Loss of desmosomal cadherin organization and mediation of desomosomal
N/A Fragility syndrome
subsequent adhesion cytoplasmic plaque
protein (plakophilin)
Tyrosinase mutation causes inability of melanocytes to produce Histology? Melanocytes present (just not making
Albinism N/A Hypopigmentation
melanin melanin!)
Hypopigmentation - usually splotchy; symmetrical involvement of Autoimmune destruction of melanocytes produces decreased
Vitiligo N/A Histology? No melanocytes seen
body parts or absent melanocytes
Keloid N/A Exuberant scar usually from trauma Excessive collagen in the dermis African American race Histology? Dermis has taken over!
Panniculitis N/A Inflammation of subcutaneous adipose tissue
Yellowing, hyperkeratosis of nails; possible presence of debris Tinea unguium (see
onychomycosis N/A Fungal infection of nail Histology? KOH prep or PAS stain reveals hyphae
under nails Dermatophytosis)
Dermatitis Edematous epidermis causes skin to become swollen, raised, Histology? Epidermal spongiosis (intercellular edema;
General Inflammation of skin
inflamed --> erythema and itchiness white)
severe inflammation and edema causes edema fluid to leak Histology? Spongiosis causing fluid-filled vesicles
Acute dermatitis (eczema) oozing, crusted vesicles (poison ivy)
from skin surface --> oozing & crusting (subcorneal vesicles)
Chronic dermatitis Lichenification Histology? Acanthosis of epidermis (thickening)
Histology? Marked acanthosis, elongation of rete
Subacute dermatitis Lichenification and spongiosis with crusting on surface
ridges, spongiosis
Hypersensitive, twitchy skin - overreaction to various stimuli,
Complications due to abnl barrier
causes skin to turn red--> white when scratched; same
function of skin or abnl immune
"twitchiness" also seen in lung/nasal membranes
response?
Moisturizers for xerosis, anti-
Abnormal cytoskeleton? Mutation in filaggrin causes abnl inflammatory cortisone creams; if
Once child outgrows 20% of children, 1% of Secondary infections of AD skin
barrier fx so increased dryness; mutation also causes no relief to those, systemic
chronic, pruritic dermatitis that waxes & wanes; face & extensor AD, can have asthma/ adults with S. aureus, MRSA, HSV
bundling/collapsing of keratin fibers immunosuppressants for severe
extremities of infants; flexural surfaces of older children/adults; allergies later; higher "childhood eczema"; 2- (tingling, stinging at lesion),
Atopic Dermatitis (AD) More common if parent has AD cases (prednisone, cyclosporin);
lichenification and linear excoriations can be present (chronic); prev in developed 3x more common now; molluscum --> pustulosis or
Aberrant inflammatory response? abundance of TH2 cells in oral antibiotics for presence of
xerosis, dermatographism countries suggest more developed folliculitis, weeping/oozing/yellow
dermal inflammatory infiltrate secondary infections; acyclovir for
environmental factor countries crust
secondary HSV infections
- have less AMPs due to
Hygiene hypothesis? overreaction upon antigen exposure due (especially if periorbital)
acute/chronic lesions!
to "too clean" of environment
Food allergies
Probably all of these!
Abnormal circulation in skin comprises the skin barrier, causing
dryness and inflammation --> itch --> LSC & SD
Xerosis, erythema, red-brown discoloration from hemosiderin
OLD theory - SD caused by stasis and hypoxia, but pts actually
deposits and degraded extravasated RBCs, dilated superficial
have high flow rate and oxygen Often require hospitalization for tx of
Stasis Dermatitis (SD) veins; often involves medial ankle, possible Venous insufficiency Can be complicated by LSC
venous ulcers
lipodermatosclerosis (hard feeling from underlying fat
Abnormal microcirculation - increased permeability of dermal
necrosis); hypopigmentation, ulceration
capillaries allows leakage of fibrinogen, which polymerizes to
fibrin to form fibrin cuff around capillaries --> ultimately
inflammation
May or may not have underlying primary dermatitis; skin itches
Can complicate other types of
Lichen Simplex Chronicus (LSC) Lichenification of skin, very pruritic beginning chronic scatching cycle that causes the skin to Histology? Acanthotic
dermatitis
lichenify
1. irritant - not allergic,
Itching, redness, erythematous papules; possible spongiosis and but burned/inflamed by Avoid irritant/allergen; wash
edema --> crusted vesicles; 1. substance (occur in immediately after exposure;
Contact Dermatitis
2. Allergic - patient becomes sensitized from previous allergen anyone exposed) calomine to soothe/dry out
1. Irritant Patch testing
Diaper dermatitis (irritant, also caused by Candida), poison ivy exposure (no rash at first exposure); upon re-exposure to 2. Allergic - allergy (AVOID sensitizers like topical
2. Allergic (ACD)
ACD - due to oleoresin in Rhus group of plants); nickel ACD antigen, there is a delayed-hypersensitivity reaction response (poison ivy, benadryl/Caladryl); topical
neomycin ACD; formaldehyde ACD does not occur in corticosteroid
everybody)
Inflammation of skin related to host response to normal P. ovale Anti- fungals controling
Seborrheic Dermatitis variation of dandruff, can be on scalp/face Do NOT give topical steroids!
flora Pityrosporum carriage
Starts w/ occlusion of follicle and formation of
microcomedone, leading to hyperkeratosis of the opening that
Topical/oral antibiotics (reduce
blocks eggressive sebum. Cyst forms with sebaceous material,
bacterial density and macrophage
forming comedone. Follicular unit further expands, allowing
Propionibacteria acnes activation)
Acne N/A growth of Propionibacterium acnes and inflammation that Possible scarring
(nl skin flora)
leads to follicular wall rupture
Retinoic acid (downregulates TLR2
expression on monocytes)
Inflammation mediated by bacteria intxn w/ TLR2 on
monocytes
Colonization at birth that peaks in early adult life with increased
hyper- or hypopigmented patches with readily inducible scale; sebaceous gland activity Malassezia furfur (P. People living in warm/ humid
Tinea versicolor N/A chest & back; warm/moist environment; usually asymptomatic ovale, P.orbiculare; nl climates have higher bacterial
but may be pruritic Unclear factors trigger overgrowth & conversion of yeast to skin yeast) carriage
pathogenic hyphal form
Hot/humid environment
AB use People living in warm/humid Histology? Massive infiltration of neutrophils around hair
Pityrosporum folliculitis Follicular centered inflammation on chest or back Inflammation of hair follicle due to fungal colonization/infection Responds to anti-fungal tx Do NOT give topical steroids!
Immunosuppressant climates follicle
Hi sebum prod
Bacterial folliculitis Chronic S. aureus carrier
Bacterial folliculitis Follicular centered pustules or erythematous papules that are Bacterial infection of hair follicles transmitted from direct S. aureus, occlusion of Irritation Clinical (pustules/papules w/ hair follicle in middle) Topical Abs
Abscess formation
slightly pruritic and/or tender contact with infected person or autoinoculation non-dermatologic areas Shaving Gram stain/Cx Oral Abs (if extensive, recurrent)
Occlusion
Self-limited Sx usually don't require
Exposure to Pseudomonas in water that has not been Pseudomonas tx
Hot tub folliculitis Diffuse folliculitis Clinical
sufficiently chlorinated aeruginosa
May give Ciprofloxacin if needed
Localized? Topical antibacterial
cream (Mupirocin)
Bullous impetigo (S. aureus) Childhood
Small vesicles/pustules, erosions w/ golden honey-colored Superficial bacterial infection of epidermis caused by S. Increased incidence in Clinical (honey crust)
Impetigo S. aureus, GAS Crowded areas Rare
crust aureus, GAS; highly contagious (direct contact) SE, day care settings Gram stain/Cx Widespread? Oral Abs
Impetiginized eczema (2ndary inf) Heat/humidity
(Dicloxacillin, cephalexin,
erythromycin, etc)
Abs not effective until
Drainage (hot compresses or necrotic/purulent tissue is
Chronic S. aureus carrier
Furuncle (smaller) Inflammatory, tender nodules or abscesses around follicle (or surgical) DRAINED!!
Continuum from folliculitis --> furuncle --> carbuncle that is Folliculitis Clinical
Furuncles/ Carbuncles underlying tissue if carbuncle) that is purulent or necrotic; S. aureus
transmitted via autoinoculation/direct contact Obesity Gram stain/Cx
Carbuncle (larger!) hot/red, fluctuant (compressible) Oral Abs (dicloxacillin, Recurrence
Immunodeficiency
Cephalexin, Bactrim)
Bacteremia (rare)
Increased prevalence
"Spider bite phenomenon"
as SSTI, furunculosis; NO beta-lactams, possible adjunct
can cause infections in therapy Erythromycin & methicillin
CA-MRSA Looks like spider bite, furuncle, abscesses, pyomyositis, cellulitis Bacterial infection caused by methicillin resistant S. aureus CA-MRSA Pts lack typical risk factors Culture w/ sensitivity testing
pts typically lacking resisitant
RFs for MRSA Use Bactrim or clindamycin
asymptomatic --> fatal
(hospital/prison/ sports)
Histology? Fungal hyphae caused by dermatophytes in
Well demarcated scaly plaque w/ hyperkeratosis, may be pruritic Topical anti-fungals (Azoles, TOPICAL STEROIDS CAN
Tinea pedis (athlete's foot) Fungal infection of non-viable, keratinized structures like Often none stratum corneum
or erythematous (jock itch), moccasin scale or toe web Filamentous fungi allylamines: naftifine, terbinafine) MAKE WORSE!!!
T. unguium (onychomycosis) stratum corneum, hair, nails; transmitted person-person, Humid/occluded skin
maceration (tinea pedis), annular w/ central clearing (tinea (Microsporum, Common infection even
Dermatophytosis T. cruris (jock itch) contact with infected fomites, autoinoculation Atopy (eczema) KOH prep
corporis/faciei), alopetic patch w/ possible neck LN swelling Trichophyton, in healthy hosts Oral anti-fungals (azoles, Nail disfigurement (rare)
T. corporis/faciei (ring worm) Immunodeficiency Fungal Cx (takes wks)
(tinea capitis) Epidermophyton) allylamines, griseofulvin) for
T. capitis (cradle cap) Keratinases of fungal hyphae TOPICAL STEROIDS Wood's lamp (hair)
hair/nail infections Alopecia
Bx for histology w/ PAS stain
Verruca (warts)
VERY common Often none Spontaneously resolution (SLOW)
Verrucus (bumpy/rough), hyperkeratotic skin colored papules;
Verruca vulgaris HPV 2, 4 20% of kids have at HIV
usually asymptomatic unless 2ndary infection/inflammation Histology? Hyperkeratosis of epidermis and granular
Infection of basal layer of skin with HPV (dsDNA virus), some time Organ transplantation Various OTC tx modalities that
layer, inward bending of rete ridges, papillomatosis
resulting in the slow division of cells in the spinous layer; aren't all that effective
Hyperkeratotic papules/plaques that are less exophytic, black eventually leads to hyperkeratosis and papillomatosis (fingerlike projections of epithelia)
Verruca plantaris HPV 1 Common in adults (Salicylic acid, imiquimod, duct possible some HPV types are
macules of thrombosed capillary loops ("seeds" = lay term) tape) cancer-forming
Clinical
Transmitted from skin to skin contact, autoinoculation,
Condylomata acuminata Genital warts; flatter, gray/brown papules Bx (rare)
contaminated surfaces Paring
Filiform warts Thinlike projections common on face DNA testing to determine type of HPV present
HPV Cryosurgery
Verruca plana Pinkish warts common on hands/face Podophyllin (topical chem agent)
Spontaneous resolution (can take up
Clinical to 2y)
Crush prep
Children
Superficial poxvirus infection of epidermis only transmitted via Molluscum Bx (rare) Imiquimod
Molluscum Contagiosum N/A Umbilicated (central), small, dome-shaped, pink papules HIV
skin to skin (considered STD in young adults) contagiosum virus Canthardin (good for kids)
Sexually active young adults
Histology? Henderson-Patterson bodies (eosinophilic Liquid nitrogen
inclusion bodies) Curettage
Clinical Self-limited in immuno-competent
HSV infection of keratinized skin/mucus membranes Tzanck prep (cannot distinguish HSV from VZV) host Potential risk for wide-spread
HSV-1 (classically oral) PAINFUL, TENDER grouped vesicles or erosions on
Herpes Simplex Virus transmitted skin-skin, skin-mucosa (possible STD) Direct fluorescent antibody (CAN distinguish HSV from dissemination
erythematous base; prodrome (tingling); can occur on lips, None - pretty ubiquitous virus
(HSV) VZV) Oral antivirals for
HSV-2 (classically genital) finger (Whitlow), genitals
Latency phase, asymptomatic shedding Viral culture immunocompromised/ recurrent or Neonatal transmission
Bx (rare) severe episodes
VZV goes latent after active infection/vaccination in the ganglia POST-HERPETIC NEURALGIA
Clinical
Varicella Zoster Virus until risk factors cause reactivation of varicella zoster virus
advancing age Tzanck prep
(VZV) PAINFUL, DERMATOMAL vesicles, crusted papules, ORAL ANTI-VIRALS ASAP!! (w/I dissemination
N/A Varicella zoster virus Lifetime risk of 10-20% immunosuppression DFA (distinguish HSV from VZV)
erosions often in unilateral fashion NOT contagious (represents reactivation state) but patients first 48-72h)
Stress! Viral Cx
(Shingles) with varicella zoster can transmit chicken pox to those who transmission of varicella (chicken
Bx (rare)
have never had it pox)
Topical creams (scabicides)
Eruption caused by tunneling of mite in stratum corneum that
PRURITIC, thread like linear burrows produced by the Nursing home residents Histology? Mites (ovals) in stratum corneum
causes delayed type IV hypersensitivity response and treatment of fomites and close
tunneling of the mite; can have erythematous papules; Sarcoptes scabiei var. Children
Scabies N/A diffuse pruritic eruption after 4-8 weeks contacts Rare (psychological burden?)
commonly seen on wrists, genitals, waistline, axilla, web hominis Hospitals Mineral oil prep? Mites with oval gray eggs and fecal
spaces Close contact areas pellets
Transmitted via skin-skin contact or contact with fomites can use oral anti-parasitic if severe
(ivermectin)
Previous cutaneous damage Antibiotics that cover staph and
Group A Strep (trauma, ulceration, fissured toe strep (dicloxacillin, some
Carbuncles w/ pus present? Think S. aureus Rapidly spreading areas of edema, redness, heat; possible
Acute infection arising when organisms enter the deep Other beta-hemolytic webs, inflammatory dermatoses) EMPIRICAL KNOWLEDGE (cx not always positive, low cephalosporins- Cefazolin,
Cellulitis vesicles/bullae/cutaneous hemorrhage; systemic sx (fever,
dermis/subcutaneous layers through skin breaches strep Obesity sensitivity of needle aspiration cx) Cephalexin; vancomycin- if
Diffuse erythema w/ no pus? Think GAS tachycardia, confusion, hypotension, leukocytosis)
S. aureus (CA-MRSA) Edema (venous insufficiency, MRSA; Unasyn --> Augmentin if
lymphatic obstruction) from bite)
More common in
NOT Bactrim!
infants/ children/ elderly
Raised, sharply demarcated erythematic lesions, commonly
Eryisipelas N/A Acute infection caused by GAS entering the upper dermis Group A Strep
seen on face; acute onset Penicillin DOC
Less common than
cellulitis
Diabetic foot ulcers Acute Infection by S. aureus or B-hemolytic Streptococci clindamycin Possible CA-MRSA infection
Unasyn (ampicillin + Sulbactam- associated with worse outcomes
Often polymicrobial infection with enterococci, obligate
Chronic IV)
anaerobes, P. aeruginosa, and/or Enterobacteriaceae
Necrotizing fasciitis (NF) NSAIDs
Initially presents with cellulitis, blood-filled bullae, GAS, S. aureus, or Extensive debridement, surgery
Monomicrobial Diabetes
ecchymosis, systemic toxicity, elevated CPK anaerobic
Venous insufficiency
streptococci Monomicrobial - clindamycin +
Initial break in skin from trauma or surgery causes advancing Less common in Completely normal hosts Usually bacteremic
RED FLAGS: severe pain out of proportion w/ skin findings, Abdominal Surgeries penicillin G
infection to fascial and/or muscle compartments children 30-60% mortality
large bullae, skin necrosis/ecchymosis, wooden hard feel of subq Decubitus ulcers
tissue, numbness of skin, systemic toxicity, rapid spread w/ AB Aerobic + Anaerobic Polymicrobial - Ampicillin,
Polymicrobial Perianal ulcers
tx bowel flora clindamycin, and ciprofloxacin
Bartholin abscess
IVDU
Clostridium Historically seen with Spontaneous (hematogenous)
Rapidly progressive, toxemic infection in previously injured Blunt trauma causes non-viable tissue to lose blood supply, Aggressive surgical debridement
Gas gangrene perfringens war injuries but now h/o severe penetrating trauma gangrene from Clostridium
N/A muscle (blunt trauma), edema, crepitus (gas bubbles), creating anaerobic environment for spore-forming, gram XR shows edema and gas in soft tissue
(myonecrosis) C. novyi associated w. blunt or crush injuries septicum in pts with GI
brown bullae; abrupt pain positive rod bacteria to infect injured muscle PCN + clindamycin
C. histolyticum trauma malignancies or neutropenia
Early? Think GAS or
Clostridium
Superficial incisional Prophylactic superficial
(subq space) Inherent risk with clean antisepsis
GI or female GU
Surgical Site Infections Adverse infection associated with hospitalized patients who contaminated, contaminated,
Can be early onset or take 5-14 days surgery? Bowel flora
(SSI) Deep incisional (fascia/muscle) have undergone recent surgery or dirty-infected operative Perioperative ABs
wounds
Clean procedure? Skin
Organ/space Incision & Drainage
flora
(S. aureus, Strep sp)
Osteoporosis N/A BMD T-score < -2.5, increased incidence of fractures skeletal disorder characterized by compromised bone strength Loss of bone Age Low dose Ca/VitD Long term bisphosphonate use
(bone density & bone quality- arch, turnover, mineralization, trabeculae Postmenopause causes increased BMD but
damage accum) predisposing a person to increased risk of (microarchitectural FH of osteoporosis Estrogen increased fractures, increased
fracture deterioration) calcitonin osteonecrosis of jaw (rare)
Adjustable RF? raloxifene (estrogen Ag in bone,
With age, lose trabecular volume, #, thickness, connectivity Genetic predisposition Excessive alcohol Antag in breast) High dose calcium linked to CV
sedentary lifestyle Bisphosphonates -Alendronate, events and vascular calcification
Decreased estrogen is related to high bone turnover that Estrogen deficiency Zoledronic acid (Reclast)
results in stressful micro-cracks and loss of bone density activates immune
response Anti-RANKL Ab - Denosumab
Estrogen deficiency = oxidative stress in bone marrow =
increased ROS = activation of T cells = increasd TNF = Increased RANKL Anabolic agent-
formation of osteoclasts and bone marrow stromal cells via Forteo (teriparatide) - transient
RANKL PTH = bone formation
Odanacatib - Cat K inh
Sclerostin Ab
Pagetic bone is hemorrhagic so
Genetic predisposition
activity needs to reduced before
(chrom 18, overlap w/
surgery
3 stage of localized, chaotic(mosaic) bone remodeling: familial expansile Most people are asymptomatic
More common in people Elevated bone-specific alkaline phosphatase (overactive
misshaped legs/head, gait problems, progression over 1. osteoclastic activity osteolysis, p62
from British Isles, osteoblasts, >2x inc) Spinal cord/nerve root
time,warm to touch; moth-eaten deteriorated bone, pitting of 2. mixed osteoclastic-osteoblastic activity, where osteoblasts try mutation- nl degrades sx? NSAIDs, COX2 inh, PT,
Caucasians compressions
pagetic bone; usually involves spine/ skull, most painful in to compensate with deposition of disorganized, RANKL signaling; surgery for fx
Histology? Woven mosaic bone
pelvis/long bones hypervascularized lamellar bone Juvenile Paget's -
Polyostotic adult disease (~60y.o.) Fractures
3. exhaustive (burnout) stage (dense pagetic bone as mutated OPG) Advanced disease? Use
Paget's disease Age XR? Pagetic flame lytic lesions, cotton wool skull,
hearing loss, platybasia (softening at skull base--> headache hypercellularity of bone diminishes) osteoporosis drugs
Monostotic 200,000 cases in U.S. sclerotic + resorbed areas, inc Calvarian thickness), Osteosarcoma!! (10% of older
w/ valsalva), Pagetic steal syndrome (shunt blood to ext Problem with osteclasts (bisphosphonates, since they too
(~3% prev) picture frame vertebral bodies (thick cortex frames pts) - but no inc in non-skeletal
carotid, stroke-like sx), osteoporosis circumscripta (bone loss All results in deformity, fracture, metabolic derangement (inc #, size, nuclei, fx, kill osteoclasts)
lesion), fissure/chalk stick fractures (straight across) malignancy!
around skull), leontiasis ossea (rare, enlarged facial/jaw bones), sensitivity to vitD); nl
5-20% w/ symptoms
high output heart failure DIsorganized communication btwn osteoclasts and osteoblasts osteoblasts hypercalcemia tx if know pt will be
M>F Bone scan? show sclerotic dz hypercalcemia (immobilization)
(coupled chaotic activity) immobilized
possible involvement of
gout (23% of pts w/ gout have
slow viral inf
paget's)
Dense, brittle bone that fractures, bleeding/infections,
Cranial nerve compression -->
hypersplenism, hemolytic anemia
Autosomal recessive infantile malignant (ARO) Mutation in RANKL (rare) or ion pumps (TC1RG1, ClCN7) blindness, deafness
causes defective bone resorption and apoptosis of osteoclasts Bone overgrowth due to Infancy Osteoclast number, anemia labs Bone marrow transplantation
Osteopetrosis Count osteoclasts - RANKL mutation (low OC #) v. TC1RG1/ loss of osteoclast Death by 10y.o. if not treated
ClCN7 (nl OC #) resorptive fx
Mutation in TC1RG1 causes inability of osteoclast to secrete
Autosomal dominant (Albers-Schonberg) Spine sclerosis with sandwich vertebrae (rugger jersey Late childhood/ Fractures, osteomyelitis, possible
hydrogen ions into the bone matrix, thereby decreasing bone XR? Rugger jersey spine
(ARO) spine), variable penetrance/ severity adolescence onset nerve compression
resorption
Disproportionate (big head, small body), pectus excavatum,
Onset in infancy, early
lumbar lordosis, nail hypoplasia (missing nails) Bone overgrowth due to
Mutation/defect in cathepsin K, so osteoclasts can no longer childhood XR? Dense orbital ridge, sclerotic skull base, hypoplasia Recurrent fractures in lower
Pycnodysostosis N/A loss of osteoclast
function properly in bone resorption of facial bones, dense vertebrae w/ preservation of TVP limbs
Facial dysmorphism? Missing jaw look, large forehead, resorptive fx
Very rare!
underdeveloped nose, asymmetry
renal tubular acidosis, cerebral calcifications, hypotonia, Mutation in CAII renders the cell unable to generate protons Bone overgrowth due to UA - check for RTA
Carbonic Anhydrase II
weakness, mental subnl from CO2 and H2O, causing loss of osteoclast resorptive loss of osteoclast Autosomal recessive
deficiency
Phenotype less severe w/ age function and generalized disease resorptive fx Measured in erythrocytes
Unregulated TGF-B
causes overstimulation
Progressive Diaphyseal gradual appearance of symmetric hyperostosis on periosteal mutation in TGF-B1, a latency protein that is a normally a Variable age, severity,
Camurati-Engelmann of osteoblasts and Glucocorticoids for pain relief
disease and endosteal surfaces of long bones chronic sequesterer and inhibitor of TGF-B in bone course
excessive bone
formation
Endosteal hyperostosis Disruption of Wnt signaling system causes decreased
TALL, heavy, Dutch ancestry, syndactyly, pain w/ point
inhibition of Wnt, resulting in the inhibition of APC/GSK3 Autosomal recessive inheritance
pressure on long bones Deactivating mutation in Nl OC
Sclerosteosis complex. Now, B-catenin is active and able to promote
SOST (Wnt inhibitor) Possible inc alk phosphatase
transcription of genes involved in osteoblast differentiation, Dutch ancestry (Afrikaners)
Heavy bones!
causing osteosclerosis Possible optic atrophy, facial
Progressive asymmetrical enlargement of mandible (w/o Disruption of Wnt signaling system causes decreased nerve palsy, deafness
dental malocclusion like osteopet), pain w/ point pressure on inhibition of Wnt, resulting in the inhibition of APC/GSK3
Deactivating mutation in Nl OC
Van Buchem longbones complex. Now, B-catenin is active and able to promote Autosomal recessive inheritance
SOST (Wnt inhibitor) Possible inc alk phosphatase
transcription of genes involved in osteoblast differentiation,
Heavy bones! causing osteosclerosis
BMD T-score >0, no fractures, nl bone remodeling, flat forehead, Disruption of Wnt signaling system causes decreased
elongated mandible, toras palatinus (bony protrusion of palate), inhibition of Wnt, resulting in the inhibition of APC/GSK3 Mutation in LRP5,
Worth type benign presentation complex. Now, B-catenin is active and able to promote prevents binding of Autosomal dominant inheritance
transcription of genes involved in osteoblast differentiation, DKK1 (Wnt inhibitor)
Heavy bones! causing osteosclerosis
Inflammatory swelling of soft tissues that eventually transforms
into encasement of bone during first decade of life via Patients usually die of R heart
Soft tissue swelling that progressively turns to bone esp at sites Excessive BMP
endochondral ossification failure, Pulmonary HTN
Fibrodysplasia ossificans of injury (avoid trauma!!); malformed great toe, progressive stimulation -->
N/A NO BIOPSY!!!!
progressive (FOP) heterotopic ossification pattern; spares heart/ diaphragm/ increased osteoblast
Missense mutation of ACVR/ALK2 inactivates binding site for Require wheelchair by 3rd
extraocular muscles formation
inhibitor (FKBP12), causing excessive and constitutive BMP decade
stimulation
Osteomyelitis occurs rapidly over days-wks, new bone pain at site of inf, Infection of the bone via hematogenous entry, contiguous
Acute More common in kids XR? Moth eaten appearance of bone
swelling spread, or inoculation via trauma
Surgical debridement, drainage,
obliteration of dead space, wound
Occurs over weeks/months/yrs; necrotic bone w/ loss of coverage
Chronic untreated acute osteomyelitis Ortho surgeries Assess response after tx with ESR, CRP
vascular supply, swelling
Cure = resolution of signs and sx
for >1y
Hematogenous bactermic seeding of bone, swelling, long bones (kids), In presence of bacteremia, bacteria may get trapped in small Kids- S. aureus, GBS MOST common in kids IVDU - novel organisms in unique Adults - elevated ESR/CRP Kids - use AB that covers TB can cause Pott's disease in
vertebrae (adults), periosteal abscesses in kids end vessels. In kids, bacteria enter venous sinusoids of (infants), CoAN staph sites staph/strep (empirical) spine
metaphysis in long bones via leaky capillary fenestrations. In XR? Takes a while to show signs, but periosteal
Long bones - fever, chills, malaise, soft tissue swelling and pain adults, bacteria often seed in vertebral bodies (well- Elderly- S. aureus, elevation, areas of demineralization, loss of sharp CT guided needle bx (adults) for
vascularized) or bugs can drain from Batson's venous Gram- bony margins, moth eaten appearance, possible soft Cx
Vertebrae- neck/back pain, localized tenderness, low/absent plexus (from urinary tract) tissue swelling
fever, neurological deficits (epidural abscess) Immunocomp - fungi 4-6 wks AB tx
IV DRUG USERS? Sternoclavicular joint, SI joint, pubic CT? sensitive MSSA- nafcillin, oxacillin
bones IVDU- S. aureus, P. Bone scan? Early dz (lots FPs) MRSA- vanco, dapto
aeruginosa, Serratia MRI? GOLD Standard! detects early changes & abnl Strep- PCN G, ceftriaxone, cefazolin
soft tissu; adjacent vertebrae involvement Enteric GNs- Cipro, ceftriaxone
Sickle cell- S. aureus, Serratia, Pseudomonas-
Salmonella ceftazidime, cefepime, piperacillin-
tazobactam
Anaerobes- clinda, metronidazole
Surgical debridement if necrotic
increasing pain, skull/mandible/ small bones hand/ long Possible polymicrobial Imaging hard to interpret bc surrounding soft tissue inf Revascularization
bones/feet, mild fever, minimal drainage (see diabetic foot ulcer Chronic skin ulcers (arterial
Bacterial infection from localized ulceration/ trauma travel bacteria) MOST common in sclerotic dz), trauma, diabetes, Bone scan sometimes reveals contiguous spread from Amputation/ surgical debridement
Contiguous
Diabetic osteomyelitis? Painless (due to peripheral neuropathy further to the bone adults post-op ortho surgery, chronic ulcer site
in most DM pts) ulcer extending to bone, mild cellulitis, Mixed gram+/-, edema Abs for 4-8wks (Avoid empiric ab
crepitance [If it probes to the bone, it's osteomyelitis] anaerobes Bone sample for culture tx)
Septic arthritis Acute bacterial Recent trauma (animal/ human

Joint drainage (serial taps, open
S. aureus bites)
swollen, hot, monoarticular arthritis w/ passive motion; less Generally hematogeous spread of bacteria or possible Tap joint? Elevated WBC procedure)
Streptococci Immunocompromised
uncommon - fever/chills iatrogenic spread (joint injections for RA/OA) Gram stain & cx
GN rods RA/gout/sickle cell
Systemic Abs 2-4wks
IVDU
Chronic septic arthritis Mycobacteria (Tb)
Lyme disease
Other infectious diseases causing arthritis Fungi
Rubella, mumps,
parvovirus
Bactermic form:
Dermatitis that coincides w/ pustules/papules that are
Sexually active young adult
sometimes hemorrhagic; centrifugic distribution, fever, F>M
Timing associated with menses
Disseminated gonococcial infection (DGI) tenosynovitis, polyarthalgia/arthritis Arthritis associated with gonococcal bacteremia Neisseria gonorrhoeae Cultures from mucosal sites IV ceftriaxone
Pts w/ terminal complement
declining incidence
deficiencies
Localized form:
purulent arthritis (1,2 joints)
Prosthetic joint infection Acute onset joint pain, effusion, erythema, warmth, fever Acute contiguous infection from virulent pathogens seeded after S. aureus, Rising incidence w/ Joint replacement XR? Lucency at bone/cement interface, loose cemented One-step procedures (remove and
surgery Streptococci, Gram - increased joint prosthesis replace prosthesis at same time)
Early (<3m after surgery)
rods, enterococci, replacement surgeries
anaerobes, fungi (rare) Synovial fluid aspiration? Elevated WBCs w/ increased Two step procedures
Low grade sx, implant loosening, chronic joint pain Chronic contiguous infection from less virulent pathogens CoNS (form biofilms neutrophils (debridement, removal, then
seeded after surgery; well) replacement later)
Delayed (3-24m)
Synovial fluid Cx may be negative if biofilm formation
usually biofilm-forming pathogens debridement and retention (stable
Hematogenous seeding from variety of sources (skin, resp, S. aureus, Sonication of removed prosthesis for cx joint w/ early inf)
dental, UTI) Streptococci, Gram -
Late (>2y)
rods, enterococci, long term Ab (3-6m) for all
anaerobes, fungi (rare)
Ehlers Danlos Syndrome 1/5000 individuals; Clinical exam for manifestations
(EDS) classical form is most Tx manifesting sx
Skin & joint hypermobility (Beighton's score >5 for joints), common Beighton score Low-resistance exercise to increase
Mutation in collagen type V (COL5A1, COL5A2), disrupting
Classical atrophic scarring (not well healed), easy bruising, Autosomal dominant muscle tone
structural integrity of connective tissues
smooth/velvety skin, hypotonia & decreased motor development baseline echocardiogram for kids <10 y.o. Vit. C & D, Ca supplem
Avoid high impact force
Evaluate clotting factors
Hypermobile joints but do not have major/minor skin findings,
Clinical & FH only
Hypermobility soft skin w/ only minor extensibility, absence of skin/soft tissue Unclear but haploinsufficiency of tenascin X(TNXB) Autosomal dominant inheritance
No genetic testing
abnl
Severe generalized hypermobility, congenital bilateral hip Mutation in collagen type I (COL1A1, COL1A2) causes
Arthrochalasia Autosomal dominant inheritance Clinical genetic testing
dislocation, tissue fragility and skin hyperextensibility abnormal processing of amino terminal ends
Very severe - dissection of carotid
artery, arterial/digestive/ uterine
Arterial, digestive, uterine rupture/fragility, characteristic
fragility or rupture
facial appearance (acrogeria, tightened skin over face, hollow Autosomal dominant inheritance
Dominant-negative mutations in pro-a1(III) chain of collagen
Vascular cheeks, thin upper lip and skin), extensive bruising, spontaneous Family history Clinical genetic testing Celiprolol (cardioprotective)
type 3 80% develop significant med
pneumo/hemothorax, hypermobility of small joints, talipes Sudden death in close relative
probs by age 40
equinovarus (clubfoot)
Sudden death (median age 48)
Autosomal recessive
Dermatosparaxis Severe skin fragility, sagging/redundant skin, large hernias Deficiency in type I procollagen N-peptidase Clinical findings only (no genetic test!)
inheritance
Generalized joint laxity, severe hypotonia and scoliosis at Mutation in PLOD1 causes decreased lysyl hydroxylase in Decreased lysyl Autosomal recessive
Kyphoscoliosis Clinical genetic testing
birth, scleral fragility, rupture of ocular globe dermis and loss of connective tissue cross-linking capabilities hydroxylase inheritance
Extremely tall (arm span longer than height), long fingers, Connective tissue disorder caused by missense mutations in Currently testing use of angiotensin
Clinical exam tests? Walker Murdoch wrist sign,
Marfan Syndrome N/A dilated aortic root, ectopia lentis-dislocated lens, pectus FBN-1 gene on q15, disrupting TGF-B-fibrillin complex and Abnl Fibrillin protein II type I receptor antagonist
Steinberg thumb sign
carinatum OR pectus excavatum increasing amount of active TGF-B (Losartan)
Cleft palate, bifid uvula, midfacial hypolasia (underdeveloped 3 collagen genes:
Autosomal dominant inheritance
Stickler Syndrome cheek bones, flattening of midface), high myopia causing retinal Mutations in any of COL2A1, COL11A1, Genetic testing
Multiple family members affected
detachment, early onset arthritis, MVP, later hearing loss COL11A2
Type 1 - mild sx, fx w/ minor trauma, no bony deformities,

bluish-grey sclerae
Treat fx but avoid immobilization
Type II - perinatal lethal form, multiple fx in utero, dark blue Group of heritable conditions characterized by bone fragility
for long periods of time!
sclerae and low bone mass; usually caused by mutations that silence XR? Wormian bones
Type I Point mutations with Type II - perinatal lethal
one allele, resulting in decreased amount of normal type I
Osteogenesis Imperfecta Type II dominant-negative Most autosomal dominant Use light-weight casts
Type III- may have in utero fx or fx @ birth, thin ribs, popcorn collagen synthesized Prev? 6-7/100,00 Skin bx? Analyze structure/quantity of type 1 collagen
(OI) Type III effects cause structural inheritance Use high-risk Obs to manage
epiphyses, short stature, hearing loss common,
Type IV defects in collagen PT pregnancy
dentinogenesis imperfecta (gray/brown teeth that break easily Mutations in COL1A1 and COL1A2; especially, substitution of molecular genetic testing
and look translucent) any amino acid for glycine disrupts collagen helical molecule
rodding
Type IV- mild-mod, maybe DI, sclerae nl or grey, some hearing
loss
Short stature w/ disproportionately short arms/legs, Mutations in FGFR3 genes cause excessive signaling of Compression of spinal cord/
Achondroplasia N/A macrocephaly, frontal bossing, mid-face hypoplasia, hypotonia FGFR3, resulting in impaired chondrocyte fx w/I epiphyseal Dominant inheritance pattern upper airway obstruction
in infancy, delayed developmental milestones growth plates increased risk of death in infancy
Pain in femur/tibia/vertebrae @ night, relieved by NSAIDs

Histology? central nidus of woven, hemorrhagic bone
surrounded by reactive sclerosis
Osteoid Osteoma Benign BENIGN Males age 10-25 Remove to prevent recurrence
CT? sclerotic bone on outside w/ pinpoint middle nidus
>2cm? Osteoblastoma
(Endochondroma - inside bone; Chondroma - outside bone)
Chondroma / Residual bits of cartilage that were displaced during XR? Popcorn calcifications
Benign Incidental finding after fx None - benign
Endochondroma development Histology? Benign cartilage
Most common bone tumor, cartilaginous entity, medullary Occurs when bits of cartilage from the physis that get Histology? Cartilage cap, bone marrow inside If cartilage cap >1cm, start to
Osteochondroma Benign canal is contiguous all the way thru stalk, usually stop incorporated into the bone begin to grow, producing a stalk in Autosomal dominant disease worry about development into
growing w/ pt the bone XR? Benign polypoid projections from cortical bone chondrosarcoma (RARE)
Increased alkaline phosphatase
Osteoblastic XR? Lysis, blastic sclerotic bone, or even mixed; ill

Fibroblastic defined border (R/O osteomyelitis), elevated
Kids: occurs around knee
Chrondroblastic periosteum (periosteal rxn) Neoadjuvant therapy (Chemo
Adults: axial skeleton
Telangiectatic before surgery) 80% of metastases are to the
Osteosarcoma M>F
Parosteal Histology? Periosteal rxn lungs
Occur in the metaphysis, knee pain/swelling (loss of
Periosteal Tumor resection, prosthesis
ROM),weight loss (disseminated), pathologic fx w/ nl activity
Central low-grade MRI? Soft tissue extension
Secondary
CT? metastases
Trunk/pelvis/long bones; pain, swelling, resistant to

radiation/chemo (low blood supply/growth), possible M=F
Chondrosarcoma XR? Popcorn calcification Surgery only
dedifferentiation (abrupt transition from low--> high grade 35-60 y.o.
tumor)
VERY VERY RARE
Translocation btwn EWS gene and FLI1 gene so ETS DNA Histology? "small round blue cell tumor"
M>F
Ewing sarcoma Flat or long bones of young children binds at ETS DBD spot, causing loss of RNA recognitiion motif
Adolescents/ young
from EWS Imaging? Onion skin appearance
adults
Muscular dystrophy Caused by X-linked recessive mutation of dystrophin, resulting Histology? Increased CT, fibrofatty and macrophage Associated w/ dilated
Most common MD,
Pseudohypertrophy (large calves), scoliosis, lumbar in absent (or <5%) dystrophin. W/o dystrophin, the infiltration, variable muscle fiber size and abnl cells, bluish cardiomyopathy
especially in children Steroids at early age prolongs ability
Duchenne MD lordosis, protuberant abdomen, toe walking, Gower's sign, sarcolemic membranes are leaky, there's secondary Absent dystrophin fibers are regenerating (inc DNA)
to walk
mental deficits inflammation from necrosis, and cycles of degeneration & No cure! Limited life
1/3000 live births
regeneration. CK levels 10-100x>nl expectancy
Variable onset (5-15y.o.), similar symptoms as DMD but later
Becker's MD X-linked recessive mutation resulting in decreased dystrophin Decreased dystrophin 1/30,000 live births Similar histology to DMD Longer life expectancy (40-60y.o.)
onset and less severe
Maternal anticipation, asymmetric distal weaknes w/
Maternal anticipation
myotonia, pt can make a fist but can't open it back up easily; Autosomal dominant inheritance associated with trinucleotide Multisystem disorder; possible
Myotonic dystrophy type I (increases number of 5-20/100,000 live births Clinical exam
frontal balding, cataracts, cardiac conduction probs, endocrine CTG repeats in myotonin-protein kinase gene on C19 complete heart block
CTG rpts)
dysfunction (hypogonadism, insulinR), GI hypomotility
Autosomal dominant dz caused by point mutations of the
Nl CK because not a lot of muscle degen/regen Known association w/ malignant
hypotonia, poor feeding, high arched palate, delayed motor ryanodine receptor gene on 19q, encoding the Ca-release Asymptomatic but affected
Autosomal dominant hyperthermia- fever, muscle
Congenital Myopathy Central core disease milestones, joint contractures, resp probs, pectus carinatum (bird channel of the sarcoplasmic reticulum of skeletal muscle; mother --> drastic increase in none
defect in ryanodine Histology? Central cores appear as central/ eccentric rigidity/necrosis, lactic acidosis
chest) mutations of this gene also account for some cases of trinucleotide rpts
areas of muscle fibers w/o oxidative enzyme activity (excessive Ca release)
inherited malignant hyperthermia
Metabolic myopathy
exercise intolerance w/ premature fatigue in anaerobic ex,
myophosphorylase deficiency, preventing the breakdown of Defect in glycogen
McArdle's disease stiffness/weakness in exercising muscles relieved by rest; Histology? Abnormal deposits of glycogen
glycogen to glucose (glycogen cannot be converted to G6P) breakdown
rhabdomyolysis w/ intense ex, second wind phenomenon
Diagnosis needed to treat pts and
Recurrent rhabdomyolysis in adults after prolonged exercise Deficiency in enzyme required for transport of LCFA from nl CK and EMG; dx requires direct measure of muscle
Carnitine palmitoyltransferase II deficiency M>F avoid recurrent hospital
or fasting, proximal weakness later in life cytosol to mitochondria CPT or genetic testing
admissions for renal failure
Maternal transmission, extra-muscular manifestations (in
tissues/organs w/ high met rates)
Furrowed brow, high-arched eyebrows

Histology? Ragged red fibers representing abnl
Mitochondrial myopathy Abnormal amounts of mitochondria
excess mitochondria
Progressive External Opthalmoplegia (PEO) - ptosis,
opthalmoparesis
MELAS - stroke <40, encephalopathy, RRF, lactic acidosis
MERRF- myoclonus, epilepsy, ataxia, ragged red fibers
Inflammatory myopathy Histology? Perifascicular atrophy, inflammation of
dermal-epidermal jx (interface dermatitis)
Histology of Gottron's papules? Increased stratum

cornum thickening, interface dermatitis Increased risk of malignancy in
Heliotrope rash (periocular edema + violet color) on sun-
Humoral immune process against vascular endothelium, +/-4 yrs before/after dx
exposed areas; Gottron's papules (red, thickened plaque-like 1/100,000
resulting in the deposition of C5b-9 MAC from complement -- Elevated muscle enzymes corticosteroids
rashes on extensor surfaces), nailbed hemorrhages,
> CD4+ T cell and B cell response --> ischemic muscle Myositis specific Abs (Anti Jo-1- worse prognosis, Anti Methotrexate, azathioprine (LT) Interstitial lung disease
violaceous erythema (shawl sign), dilated capillary loops of Complement mediated F>M
Dermatomyositis injury Mi-2 -better prognosis) IV immunoglobulins
proximal nail folds, cutaneous calcinosis (ROCK hard) ischemic muscle injury
Diaphragm/ intercostal
Kids (more calcinosis)
DM = DZ of body attacking blood vessels around muscle, Bx evidence? Necrosis, upregulation of MAC around photoprotection weakness --> resp arrest
SYMMETRIC WEAKNESS OF PROXIMAL MUSCLES (usually & adults
causing watershed inflammation around muscle. blood vessels, regeneration, varied fibers, inflammation
lower extremities first, then upper extremities)
around blood vessel (not in the muscle fibers) (CD4+ Cardiac rhythm disturbance
T/B cells)
XR? Calcinosis
MRI? Muscle inflammation
Cell mediated immune response within the muscle
Proximal muscle weakness, no rash (more of just ruling out Histology? CD8+ T cell/mo infiltration in NORMAL
Polymyositis (endomysial inflammation) involving T cells & Corticosteroids
other myopathies) looking muscle!
macrophages
Most common acquired myopathy >50y.o; Distal and
Histology? Centrally-placed nuclei, red-rimmed
Inclusion body myopathy asymmetric weakness of finger/wrist flexors, knee extensors, ?
vacuoles (fibers w/ holes in them)
ankle dorsiflexors
Myopathy from following "toxins": Alcohol, Statins, Colchicine,
Toxic Myopathy
Glucocorticoids, AZT
Myopathy associated with following systemic diseases:
Myopathies from Hypokalemia, Hypophosphatemia, Critical illness myopathy, or
systemic dz endocrine disorders (thyroid dz, parathyroid dz, adrenal
disorders, hypopituitarism, acromegaly)
F>M Elevated ESR/CRP
Genetic component
Dx critieria: Extremely unlikely in Thrombocytosis (hi platelets)
Polygenic (environment & genetics) (HLA-DR)
Persistent proximal pain (>1m) involving (neck, shoulders, pts <50y.o. Nl CPK
Polymyalgia Rheumatica Can be associated w/ Giant cell Corticosteroids (Should be RAPID
N/A pelvic girdle- 2), >1h morning stiffness, abrupt onset of illness Anemia of chronic dz
(PR) Activation of innate immune system leads to elevated levels of Genetic polymorphisms arteritis response if right dx)
(<2wks), age>50, Rapid response to low dose prednisone, NE descent: Negative ANA, RF
TNF in adhesion molecules &
elevated ESR, absence of other disorders (flu, hypothyroidism) 20-53/100,000 in pts
TNF
>50 (less in Italians) Clinical dx
Pt education
Pain perception Clinical? Should not see weakness! Dramatic
Widespread and migratory pain/tenderness; waxes & wanes, Anti-inflammatory/ analgesic meds
No inflammation or tissue pathology! thresholds decreased Prev? 4% of population pain/tenderness at pressure points
other nonspecifc MSK sx (IBS, headaches), fatigue, weight (not better than placebo)
(abnl neurochem) First degree relatives w/ FM (8x
change, night sweats, weakness, SLEEP PROBLEMS, trouble AVOID NARCOTICS
Abnl neurochemistry affects pain perception; mood & sleep F>>M (10:1) higher risk!) No anemia
Fibromyalgia (FM) Soft tissue pain disorder concentrating, TMJ, ENT sx, nondermatomal parasthesias tricyclics (muscle relaxant, antidep)
disturbance along w/ changes in HPA axis causes decreased Physical/emotional Nl CPK, aldolase
Serotonin reuptake inh
blood flow to thalamus (pain perception center), resulting in triggers can precede or Peak onset Mutations in serotonin gene Nl ESR/CRP
Chronic widespread pain involving ALL 4 quadrants and Lyrica (decrease perception of pain)
decreased pain thresholds aggravate sx (virus, 30-55y.o. Nl thyroid studies
axial skeleton; Presence of 11/18 tender points FITNESS TRAINING! (low impact
trauma, dep/anx) Negative ANA, RF
aerobics and muscle strength)
Clinical exam? Prodrome malaise/fatigue, stiffness that

Extra-articular manifestations?
improves w/ activity, non-reducable deformities (swan-
NSAIDS Heart - pericarditis,
neck, boutonniere, trigger finger, MCP subluxation, atherosclerosis
increased angiogenesis to joint space, Hyperplastic synovia, ulnar dev, hammer toes)
Aberrant immune response in genetically predisposed person Lung - pleural effusion, interstitial
hypertrophic synoviocytes, painful overgrown synovia DMARDS:
leads to synovial inflammation and destruction of the joint lung dz
(PANNUS) Elevated ESR/CRP -Immunosuppressants (MTX,
Skin - nodules, vasculitis
First degree relatives w/ RA Anemia leflunomide, azathioprine)
Genetic & environmental factors--> innate immunity-- Prev? 1% of pop Neuro- carpal tunnel (Bilateral),
Morning stiffness (>1h), 3+ joint arthritis, hand joint arthritis, HLA-DR4 (shared epitope- HLA- Thrombocytosis - secondary agents
>macrophages--> T cells through TNFa and osteoclasts F>M (2.5:1) cervical myelopathy, entrapment
symmetric, rheumatoid nodules (extensor surfaces, pressure DRB1) +RF (80-85%, worse dz) (hydroxychloroquine,
through RANKL; when DCs get to lymphoid organs, they Peak onset? neuropathy
Rheumatoid Arthritis points), +RF, XR changes SMOKING!!! (2 copies of SE + Anti-CCP (90-95%SP) glucocorticoids)
activate T/B cells that release inflammatory factors/antibodies 35-50y.o. Heme- anemic, thrombocytosis,
[4/7 criteria for 6+ wks to R/O inf] smoker = 21x RA risk) >2000 WBCs in joint fluid -TNFa antagonists (Etanercept,
into the joint. Cytokines, Proteinases, cathepsins RA in men <45 FELTY'S TRIAD (RA,
periodontal dz XR? periarticular osteopenia, uniform narrowing Infliximab, Adalimumab,
responsible for joint destruction. RANKL increases unusual! leukopenia, splenomegaly)
Fusiform swelling, SPARES THE DIP JOINT! mucosal surface toxicity around joint, marginal erosions, C1-C2 subluxation, Golimumab)
osteoclasts causing bone erosion. Bone- osteopenia
ulnar dev -IL-1R Antagonists (Anakinra)
Eye- inflammation
Systemic sx (fever/malaise, poor energy, weight loss, tissue -T cell costimulatory blockers
Kidney - rare
damage in other organs) (Abatacept)
-Combo tx
Risk for neuro damage w/ C1-C2
subluxation
W/ age, side chains in cartilage shrink and hold less water =

less resilience & more dessication = stress fx & fissures
Use-related pain, loss of ROM
Focal loss of articular
Morning stiffness <30min 1. Edema of ECM w/ loss of chondrocytes & smooth cartilage Nl ESR/CRP/platelets
cartilage followed by
Bouchards (PIP) & Heberdens (DIP) nodes causing microcracks Trauma Nl hematocrit Acetaminophen
hypertrophism of
Crepitus 2. Microcracks deepen to form vertical fissures & pits Infection <2000 WBC in joint fluid NSAIDs
Osteoarthritis Degenerative joint disease underlying bone and Older individuals
Mild effusion (but NOT warm) 3. Fissures loosen & fragment, forming erosions & mild Crystsal dz XR? Osteophytes (bone spurs), asymmetric joint
formation of
Mal-alignment of joints (bowlegged-varus; knock-kneed-valgus) synovial inflammation (from MMPs). As body tries to repair, Neuropathy space narrowing, NO PERIARTICULAR Eventual joint replacement surgery
osteophytes at joint
it scleroses and forms osteophytes. OSTEOPENIA!
margin
SPARES MCP joints!!
Chondrocytes try to make new collagen but there is a shift
towards collagen 1, 3, 10 --> shortened proteoglycans (less
H2O retention)
Overproduction of uric acid? (~10%)

High nucleic acid turnover in predisposed populations
(Paget's, psoriasis, leukemia, etc) or problems with purine Prev? Males
synthesis (overproduction of PRPP synthetase, deficiency 5-28/1000; females 1- NSAIDs- Indomethacin (acute pain
of salvage enzyme HGPRT) 6/1000 relief)
Crystals in WBCs = active gout flare >6.7mg/dL solubility of
Episodic monoarticular ALWAYS TAP JOINT & CULTURE FLUID! (yellow Initial tx for chronic gout can
Hyperuricemia (except during flare) monosodium urate crystals
Underexcretion of uric acid? (~90%) Equal incidence after parallel crystals) Colchicine (acute pain relief, actually increase the severity/freq
Paget's, Psoriasis
Gout Polyarticular hereditary factors, certain meds, or other conditions cause Hyperuricemia, tophi menopause! prophylactic w/ LT meds) of acute attacks so take
Painful/red/swollen joints/bursa, appears like certain cancers
difficulties excreting uric acid XR? Nl mineralization, punched out erosions w/ prophylactic colchicine
cellulitis/septic joint, fever/leukocytosis, podagra (1st MTP), excessive alcohol intake
Tophaceous gout M>F (5:1) sclerotic borders, overhanging edges Probenecid (chronic gout) simultaneously
tophi (distal joints, bursa; look like white dots, feel like gravel) Co-infection of joint
Hyperuricemia --> tophi (uric acid deposition that are engulfed
by granulocytes) --> inflammation (NALP3 inflammasome)--> Age onset? M 40-50; F Allopurinol (chronic gout)
lactate production & pH drop --> formation of more crystals --> postmenopause
more inflammatory cells recruited --> renal damage if deposited
on tubules
Serositis (pleuritis, pericarditis)
Oral ulcers (PAINLESS, often on hard palate)
Arthritis (reducable deformities, polyarticular, symmetric)
Photosensitivity (erythema on distal hands, sparing knuckles,
retroauricular, submental regions) Rashes? Topical steroids
Blood d/o (hemolytic anemia, leukopenia, lymphopenia, Joint pain? NSAIDs
Unclear but thought to be of 2 mechanisms:
thrombocytopenia)
1. Autoantibody-mediated inflammation (autoantibodies form
Renal d/o (proteinuria, cellular casts) FH (mostly sporadic tho) Others?
immune complexes that drive complement consumption,
+ANA Chronic inflammatory Environmental factors (uv light,
causing inflammation) F>M (9:1)
Systemic Lupus Immunologic d/o (anti-DNA, anti-SM, anti-phospholipid Abs) systemic autoimmune drugs, infections, smoking, silica) Positive ANA, anti-RNP, anti-Ro/La, positive direct Antimalarials (hydroxychloroquine)
Peak incidence ages 15- Accelerated atherosclerosis
Erythematosus (SLE) Neurologic (seizures, psychosis) dz characterized by anti- Race - A.A., hispanics Coombs, low complement
2. Autoantibodies to phospholipids produce 40y.o.
Malar rash (spares nasal labial folds!) nuclear autoantibodies Systemic corticosteroids for serious
hypercoaguble state and clots (antiphospholipid syndrome -
Discoid rash (erythematous scaling;atrophy, follicular plugging, Prev? 1/2000 complications
thrombosis, pregnancy morbidity, anti-cardiolipin Abs,
dispigmentation; isolated? cutaneous lupus)
paradoxical prolonged PTT)
Immunosuppressants for steroid-
Chronic fatigue! resistance
Raynaud's
periungal erythema
Cutaneous vasculitis (palpable purpura)
Seen w/I first few months of life

Thrombocytopenia
Neonatal lupus Mom w/ lupus congenital heart block
erythematous pathces that form blanchable rings on Anti-rho antibodies
head/neck
Drug-induced lupus Lack skin findings, systemic arthalgias/inflammation induced/triggered by procainaminde, hydralazine, quinidine Positive ANA
Scleroderma (SS) Major organ involvement!
Lung impairment (dyspnea on

proximal scleroderma (hardening of skin) Positive ANA, Anti-Scl-70 (nucleolar pattern ANA), Anti-
Unclear but key features? Endothelial cell damage (vascular exertion, cough, pulmonary
extensive fibrosis, sclerodactyly (skin tightening due to fibrotic centromere
injury), inflammation precedes fibrosis, excess deposition F>M fibrosis)
changes --> ischemia & pitting of fingertips--> autoamputation)
of collagen by fibroblasts --> all lead to impaired fx of skin,
facial disfigurement (microstomia - pursed mouth, lip Cell mediated and
(General) lungs, affected organs Onset age? 30-50y.o.
retraction, beaked nose) humoral immunity XR? Bone resoprtion of digits, subcutaneous calcinosis
(somewhat older than Widemouth diverticuli
mat telangiectasias
Autoimmune mediated diffuse fibrosis of skin & internal lupus)
dilated capillary loops at proximal nail folds
organs Watermelon stomach
leukoderma (salt&pepper skin), calcinosis
(telangiectases in stomach)
pericarditis, arrythmias
Pulmonary fibrosis (caused by
PFTs detect poor gas exchange
fibrosing alveolitis, pulmonary
XR? Interstitial fibrosis
Widespread skin involvement & rapid progression vasculopathy)- early onset
CT? ground glass opacities in lung
SRC? ACE inh
Crackles w/ inhalation Dysphagia, GERD (from fibrotic
SRC histology? Sheared RBCs, narrowing of lumen, wall GERD? PPIs
Onset of skin changes w/I 1 year of Raynauds esophagus)
fibrosis MSK? NSAIDs, PT, low dose
Diffuse Truncal & acral skin involvement
steroids (but watch renal!)
Scleroderma renal crisis (SRC) -
SRC - anti-RNA pol III Raynauds? Smoking cessation
malignant hypertension, renal
Lungs? Heavy immunosuppression
insufficiency, microangiopathic
Anti-Scl-70 Ab
hemolytic anemia - tx ACE inh
Tendon friction rubs
GERD? PPIs
Localized skin involvement (distal/upper extremities), nail fold Pulmonary hypertension (no
MSK? NSAIDs, PT, low dose
involvement, slower pace of progression fibrosis) - later onset
steroids (but watch renal!)
Limited (CREST) Anti-centromere Abs
Raynaud's? Smoking cessation
Calcinosis, Raynaud's (long duration), Esophageal Dysphagia, GERD (from fibrotic
PAH? Oxygen, calcium channel
dysmotility, Sclerodactyly, Telangiectases esophagus)
blockers, prostacyclin derivatives
morphea (erythematous plaques that are proximal, skin Histology? Nl epidermis but extensive collagen
Localized cutaneous SS
discoloration/firmness/induration) deposition & loss of epidermal appendage structures
Scleroderma + one or more features of other connective tissue
disease
Overlap syndromes Anti-RNP Abs
Mixed connective tissue disease (MCTD) - SLE, SS,
polymyositis, & positive anti-RNP
NSAIDs & glucocortocoids for pain
& inflammation
Chronic inflammation causes bone formation and erosion -->
fusion of joints (ossification of annulus fibrosus in vertebrae) Immunosuppressants only help
peripheral arthritis
Molecular mimicry impt- genetically susceptible person w/ HLA-
Axial arthritis (bilateral sacroilitis, spondylitis), arthritis of
B27 is exposed to unkwn antigen that causes an immune TNF inhibitors relieve axial arthritis
girdle joints, acute anterior uveitis (inflamed iris), extraskeltal response that exhibits cross-reactivity w/ self tissues, causing
manifestations (aortic insufficiency, conduction abnl, decreased clinical expression of spondyloarthropathy (joint dz of
chest wall expansion, spinal cord compression, cauda equina XR? Fuzzy, hard to trace bone margins of SI joint,
vertebral column) M>F
Ankylosing Spondylitis syndrome) HLA-B27 bamboo spine (syndesmophytes- new bone formed in Pneumonia, loss of flexion at back
Age onset? 20s
inappropriate location cause fusion through T-spine)
High levels of TNFa in SI joints, peripheral joints, & serum
Loss of nl spine curvature & ability to flex
of affected pts.
Symptoms progress upwards (start in SI joint --> cervical spine)
Enthesitis = primary hallmark of Spondyloarthropathies;
causes dz bc 1.Inflammation, 2. Deregulated osteoclast activity
--> bone erosion, 3. dysregulated endochondral bone formation
at sites of enthesopathy, causing syndesmophyte formation
Classic - DIP joints of hands & feet
Arthritis mutilans w/ sacroilitis

Peripheral polyarthritis (symmetrical), asymmetrical XR? Pencil and cup formation (peripheral phalynx
Symmetric polyarthritis (indistinguishable
sacroilitis & spondylitis, dactylitis (sausage digits- PIP Inflammatory arthritis associated w/ psoriasis whittled down to pencil joint and distally has extra bone
from RA except RF-)
Psoriatic Arthritis swelling & inflammation), arthritis mutilans (teloscoping digits- HLA-B27 formation to where it looks like a cup), erosion of entire
just skin bc bone has been eroded away), conjunctivitis, iritis, (see AS path) bone in digit (telescoping), excess bone formation
Asymmetric, pauciarticular (<4), small joint
enthesitis, psoriatic nails near where tendon would insert (enthesitis evidence)
involvement w/ sausage digits
Ankylosing spondylitis w/ or w/o peripheral

arthritis but +psoriasis
"Can't see, can't pee, can't climb a tree"
Arthritis, enthesopathy, tendonitis, Sterile joint inflammation that develops after infection (throat,
tenosynovitis, osteitis, myalgia, skin GU, GI infections - Chlamydia, Salmonella, Shigella,
Reiter's / Reactive M=F Spontaneous recovery, but can have
(kertoderma blenorrhagicum- palms & soles, Campylobacter, Yersinia, C.dificile) HLA-B27
arthritis young adults recurrences
whitish pustule that develops scales; Circinate
balanitis- painless, shallow erythematous ulcer (See AS path)
on gland skin) & mucus membrane lesions,
uveitis, conjunctivitis,
NSAIDs & glucocortocoids for pain

peripheral joint arthritis (pauciarticular, mostly asymmetrical, & inflammation
joint activity parallels bowel dz, enthesopathies), axial Arthritis associated with Crohn's Dz & ulcerative colitis
Inflammatory bowel Immunosuppressants only help
involvement (identical to AS, joint activity does not parallel HLA-B27
associated arthritis peripheral arthritis
bowel dz); extra-articular features (erythema nodosum- (See AS path)
PAINFUL, pyoderma - deep ulcer w/ lots of pus, uveitis)
TNF inhibitors relieve axial arthritis
Screening / Education
Protective clothing, daily use of

sunscreen, no sunbathing/ tanning
bed, vit D supplementation for
immunocomp; screening for field
disease changes - CAPABLE OF
DEVELOPING INTO SCC

immunocomp; screening for
recurrent BCC

immunocomp;
Importance for early detection and

treatment (cure rates >90%)
Staging - 0 (tumor in epidermis),

1&2 (thicker but limited to skin), 3
(LN), 4 (metastatic, systemic-
median survival of 7.5m)
Emphasize prevention (sunscreen,

protective clothing, avoid mid-day
sun, self-skin exams, TBSE, vit D
supplemenation)
Need to talk to parents about how

size of congenital nevi can affect risk
for development of MM; surgical
options (staged removals, grafting);
monitor CHANGES in lesion
Oral form of Mucus Membrane

Pemphigoid has better prognosis
(very little scarring)
Pretty good prognosis with treatment
Worrisome in diabetics or pts with

autoimmune dz
Prevention to avoid recurrence-

Antibmicrobial washes, bleach
bathes
Avoid gross hot tubs!
Prevention (bleach baths, treating

chronic carrier state w/ nasal Ab
creams)
Prevention (bleach baths, treating

chronic carrier state w/ nasal Ab
creams)
Examine (& possibly treat)

home/school for infected
contacts!
Screen for STDs in young adults
Avoid skin-skin contact during active

outbreaks
Prevention with immunization w/

zoster in people > 50y.o.
GAS/GBS screening for women

undergoing C/S
Adjustment of risk factors (excessive

alcohol, sedentary lifestyle)
Prophylactic bisphosphonate
treatment prior to surgery!!!
Stay active!!
Diagnosis is impt in case patient

needs surgery ever- need to be
aware of risk for malignant
hyperthermia w/ anesthesia
age/gender appropriate cancer

screening
Avoid sun exposure, use sunscreen!
Counsel on posture, stretching,

spinal extension exercises
high risk for traumatic fractures

Disease Clinical Variants Defining Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications
Characteristics
Pulmonary Edema tachypnea, hypoxia abnl accumulation of fluid in Thickened Hydrostatic: risk CXR: Hydrostatic: Resolution? increased hospital
hydrostatic pulm the lung outside of the membranes = factors for heart bilat interstitial Hydrostatic: intact stay (leading to other
edema: fluid vasculature diffusion; LV heart dz markings @ basal alv epithelium pumps comorbidities) and
accumulates in low P, hi failure (MI, chronic lung/ perihilar area; fluid out w/ Na/K high mortality for
comp areas (perihilar Hydrostatic edema (most CHF), renal failure, Kerly's B lines ATPase; permeability edema
interstitium, alv common): Increased hydrostatic IV fluids (horizontal lines tx underlying cause;
interstitium, alveolus); pressure (due to LV heart failure) towards edge of XR),
bronchospasm seen = Pulm edema --> backup of injury to capillaries enlarged heart;
more commonly, sx of fluid into pulm vasculature --> (free radicals, Permeability - patchy, Permeability: alv
congestive heart failure, blood vessel distention by J- chemicals) asymm infiltrates, nl epithelium injured so
cardiac dysfxn, fluid receptors --> tachypnea heart takes longer to
overload, NO PRE- Starlings law histology: resolve; tx primary
EXISTING ACUTE Permeability edema (more reasons for edema: Hydrostatic - alv injury cause, manage
TRAUMA severe): direct injury to gradient btwn spaces filled w/ pink fluid balance,
capillaries (ALI, ARDS) - capillary & edema, nl anatomy; supportive care
permeability pulm capillary leakage into interstitial interstitial hydrost permeability: dense
edema: diffuse leakage of space overflows the alveolus pressure; liver appearance, abnl
fluid (patchy, bilateral with proteinaceous fluid (can gradient btwn anatomy,
accumulation), be caused by pneumonia, interstitial fluid & heterogenous
gravitational gradient aspiration, inhalation, sepsis, oncotic press, patchiness,RBCs/
(more edema at base); trauma, pancreatitis, transfusion) leakiness of WBCs, separation of
protein leakage; acute capillaries; interstitium w/ protein
inf, no CHF lymphatic flow coat (pink hyaline
membrane)
Obstructive lung Emphysema, chronic severe dynamic compression --> ability to move air PFTs: FEV1/FVC<70,
disease bronchitis, asthma hyperinflation as a compensatory out of lungs is FVC, FEV,
mechanism to get more air out - impaired so takes concavity on exp limb
allows increased lung recoil so longer of flow-vol, volumes
lung can expel more air; (due to air trapping),
destroyed alveoli--> decreased spirogram shows slow
functional space & DLCO initial upstroke & late
vol changes; DLCO
Restrictive lung Parenchymal lung reduced lung volumes less total volume PFTs: nl or >70
disease disease (interstitial lung but no problems FEV1/FVC; FVC,
dz); nonparenchymal with air flow FEV, spirogram
(chest wall disorder; shows no late vol
muscular weakness; less changes/ rapid
shifted towards RV) upstroke, flow-volume
has VC, volumes
shift towards RV
neuromuscular dz:
somewhat higher RV,
low IC
pulmonary vascular PFTs: FVC nl/, FEV1
disorder nl, FEV1/FVC nl, TLC
nl/, RV nl, DLCO
Central Airway Extra-thoracic obstruction Plateau on inspiration; Equal pressure point has Patm > Paw during Tracheomalacia, PFT: Plateau in insp
Obstruction disease/ obstruction variable migration depending on inspiration reduces laryngeal limb
outside of the lung transmural pressure; reduced airflow and causes paralysis,
airflow during inspiration aw collapse; nl laryngeal edema,
expiration tracheal
(-)P inside the airway sucks strictures from
trachea walls in while Patm ET tube, tracheal
around trachea pulls airways stenosis,
closed) OBESITY
Characteristics
Intra-thoracic obstruction Plateau on expiration Equal pressure point has Ppl > Paw during Tracheal lesions, PFT: plateau in exp
variable migration depending on expiration reduces tracheal tumors, limb
transmural pressure; reduced airflow and causes tracheomalacia,
airflow during expiration aw collapse; nl tracheal
inspiration inflammation,
mediastinal
asthma lymph nodes
Characteristics
Fixed lesion Plateau on inspiration & Equal pressure point migrates large tumor Subglottic PFT: plateau in exp &
expiration independently of location/ stenosis, goiter, insp limbs
pressure relationships tracheal stricture
COPD Emphysema Airflow limitation that is exposure to smoke = activation capillary surface #4 mortality in hyper- PFT: see obstructive management? hoarseness =
not fully reversible, of alveolar macrophages = area = diffusion; world & USA responsiveness, dz; lung vol (TLC & Prevent dz common side effect of
(blow a balloon up and progressive, and release of chemotactic factors = cell mediators? lung growth, RV, inspiratory progression, relieve steroids
release it? No air flows associated w/ abnl recruitment of D13 = release of Epithelial cells, F>M exposure to capacity), DLCO sx, improve ex
out bc loss of elastic inflammatory response proteases (presence of protease macrophages, tobacco smoke/ all persons >45 y.o. tolerance, improve Could require oxygen,
recoil) to noxious inhibitors less effective due to CD8+ (TH1), middle aged occupational w/ chronic cough/ health status, pulmonary
particles/gases tobacco) = destruction of neutrophils (~50y.o.) dusts & chems/ sputum production & prevent/ treat rehabilitation, lung
alveolar wall infections/ SES - exposure/ risk factor exacerbations, volume reduction
hyperinflation of lungs SMOKING (USA) develops in about nutrition hx should be tested reduce mortality surgery, and/or lung
(low diaphragm position, Alveoli destruction = VQ Air pollution 15% of smokers for airflow limitation transplantation
hyper-resonance, distant mismatch, alveolar ventilation, (global) (even if no dyspnea) - drugs generally
breath/heart sounds, tetherings that support airway = less effective cor pulmonale
spirometry = gold
barrel chest), dypsnea or dynamic airway decreased elastic std
acute chest illness Short acting
compression = abnl recoil CXR: retrosternal air
(initially DOE but then enlargement of small airways bronchodilators (B-
space ( lucency), flat
starts to affect DALYs), (bullae = sac-like agonists - albuterol,
diaphragm, bullous
wheezing, prolonged abnormalities) levalbuterol,
changes,
expiratory time, Severe metaproterenol,
hyperinflation
(pursed-lip breathing, problems with driving pressure pirbuterol;
accessory muscle use, (decreased elastic recoil) anticholinergics like
CT R/Os alt dx
retraction of intercostal ipatropium)
and/or airflow resistance
spaces), tripod position
long acting
bronchodilators (B-
agonists - salmeterol,
A1AT deficiency DOE, cough, wheezing, A1AT def (protease inhibitor that most common alpha1- CXR: radiolucency in formoterol)
panacinar emphysema early presentation prevents destruction of alveolar phenotype? PiZZ antitrypsin base of lung
wall)--> loss of a1 globulin (Z allele is a single deficiency, FH (vs. diffuse sometimes
point mutation that of A1AT def, emphysema in other phosphodiesterase
causes severe dz) smoke, dust, variants) inhibitors
kerosine, PiSZ (theophyline,
smokers roflumilast)
Chronic bronchitis typically presented as exposure to smoke = activation SMOKING PFT: see obstructive
anti-inflammatory
overweight, cyanotic, of alveolar macrophages = dz
inhaled steroids
edematous, productive release of chemotactic factors = loss of elastic
(fluticasone,
cough, dyspnea at rest recruitment of neutrophils = recoil responds poorly to
budesonide,
release of proteases (presence meds
mometasone)
chronic productive of protease inhibitors less
cough for 3 consecutive effective due to
home O2 if
months for 2 tobacco/infection) = mucus
hypoxemic
consecutive years hypersecretion
(prevents cor
pulmonale)
Characteristics
Asthma exercise-induced asthma Airflow obstruction hygiene hypothesis: early inflammatory cell PFT: exp arm has peak flow meters for varying levels of
(15-30min post exercise- (wheezing, prolong forced exposure to infectious agents= mediators? Epith concavity; FEV1/FVC home monitoring severity (intermittent,
short sprints; vagal reflex) expiratory time), lung TH1 response= suppression of cells, mast cells, <70 but other values mild persistent,
hyperinflation (low TH2 activation= allergy CD4+ (TH2), highly variable; maintenance meds moderate persistent,
allergic asthma diaphragm position, /asthma frequency; people less eosin, IL4, IgE, significant (inhaled severe persistent)
hyperresonance, distant likely to be exposed to these bronchodilator corticosteroids +
nocturnal asthma (vagal heart/breath sounds) infections today= TH2 cells Factors response (loss of LABA - avoid chronic
reflex) mediate onset of asthma contributing to FVC, FEV1, leukotrieneR steroid use
severe disease? severity? FEV1/FVC; nl DLCO) blockers - Singulair,
immediate Type I IgE Accessory resp muscles, Airway remodeling occurs in Environmental theophylline, Xolair)
mediated retraction of intercostal pts w/ uncontrolled chronic (animal/insect/ methacholine + rescue meds
bronchoconstriction spaces asthma (older pts) mold/outdoor challenge (high NPV (SABA - albuterol)
allergens), so R/O asthma in pt w/ Short term oral
chronic, inflammatory morphological changes in occupational exp, atypical sx) steroids
airway dz w/ recurrent asthma (hyperplastic mucus indoor/ outdoor (prednisone) for
sz (esp @ night, early gland/goblet cells, infiltration of pollutants, foods/ CXR: nl flareups
AM; widespread/ inflammatory cells, thick BM, preservatives,
varying obstruction; edema, fibrosis, epithelial certain meds, subQ allergen
damage) = Smooth muscle infections, immunotherapy if
hypertrophy = reversible immunotherapy allergic asthma
bronchoconstriction, hyper- cold= vagal reflex
responsive airflow limitation = ACh = broncho-
constriction
Characteristics
Hypoxia Acute PIO2:FIO2
Chronic 2,3-DPG
Primary cilia TRIAD: L-R pattern defective ciliary action lining the Autosomal
dyskinesia (PCD), defects (situs inversus), respiratory tract, fallopian tubes, recessive mutation
immotile ciliary chronic sinusitis/ and sperm flagella in gene hydin
syndrome, bronchiectasis,
Kartagener male/female infertility; failed dynein
syndrome (KS) motors or central
hydrocephaly (CSF pair assembly =
doesn't move in brain cilia paralysis
ventricles)
Pneumothorax Spontaneous (Primary - Collapsed lung (air btwn (Subplural alveoli rupture into trauma, active CXR: increased Small PTX in healthy Tension PTX is
(atelectasis - partial absence of lung disease; visceral & parietal pleura); pleural space) Hole in the lung-- inspiration lucency, tension person? Observe, medical emergency!!
collapse of lung, Secondary - complication sudden onset of > Ppl = 0 (since now in pnemothorax can push supplemental O2 Causes shift of
collapse of alveoli) of underlying lung dz like
dypsnea (less efficient connection w/ atm, & no flow); heart over to opposite mediastinum =
COPD) muscle fx); focal area of when the pt inspires, pressure -- side; acquires soft Large PTX or increased
absent breath sounds, > more (-) but lung does not tissue (gray-white) symptomatic person? interthoracic pressure
Tension (causes heart to hyperresonant inflate; w/o (-)Ppl, the lung density, thin white Chest tube = disrupts systemic
push to opposite side) percussion, decreased collapses line (Spont) placement, circulation
lung vol, hypoxemia (VQ emergent
Traumatic (Penetrating mismatch), Pleuritic Histology: 2nd spont decompression w/
trauma, iatrogenic) chest pain!! PTX has rupture of needle (esp for
subpleural Tension PTX!)
Tension? Hi RR, HR; low emphysematous
BP (due to low venous blebs in lung apices Repeated PTXs?
return), trachea shifts to Pleurodesis
opposite side MRI: ruptured bullae (installment of
from emphysema (2 sclerosing agent -talc-
spont) so visceral & parietal
surfaces adhere)
Flail chest Multiple rib fractures, some ribs trauma Bind and fixate the ribsPoor prognosis due to
Upon inspiration, ribs go free-flowing; causes air to move ineffective ventilation
in & try to deflate the lung; back & forth rather than pulling
upon expiration, ribs go air from outside into the chest
out & try to inflate the lung
Lung bullae Balls of air in lung Destruction of alveoli in Emphysema CXR: bilateral balls of
emphysema/ lung dz cause air
damaged areas to fill with air &
bulge
Pneumo- gas in the interstices of Non-subpleural alveolar rupture Tracheo-bronchial CXR: air along L heart
mediastinum mediastinum with air pouring into the tree/ esophagus border, continuous
mediastinum; rupture of trachea/ rupture from diaphragm sign
main bronchi; dissection of air trauma/ prolonged
from neck/abdomen vomiting
Pneumopericardium Air in the pericardial Fistula btwn 2 Requires immediate

space (around heart); structures; identification and
muffled heart sounds Ventilators treatment, or else
death!
Pneumoperitoneum CXR: Air collection
btwn right diaphragm
& liver or peritoneal
cavity
Lung cavities Pulmonary nodules Infection; vasculitis; CXR: Abnormal lucencies w/I lung parenchyma
(<3cm); pulmonary tumors
masses (>3cm);
consolidation (think
pneumonia)
Characteristics
Atelectasis Mediastinum pulled Collapse of alveoli or partial lung Obstructive Atx of CXR: Complete
towards affected side --> VQ mismatch hypoxemia whole lung? Opacification
on CXR (perfusion, low ventilation) OR R- Cancer, mucus Hemithorax;
->L shunt hypoxemia plug, foreign body consolidation
Alveolitis infiltration of lymphocytes & Viral, mycoplasma Histology: thickened

monocytes expands the pneumoniae, septa due to
interstitium hypersensitivity infiltration of
rxns inflammatory cells;
either spontaneously resolves or empty alveolus
persists (if persists, leads to space
interstitial fibrosis)
Pleural effusion Transudative (occur Mediastinum pushed pathological accumulation of Kidney, heart, liver 1.5 million pleural CXR: Complete
when systemic imbalance away from affected side fluid in pleural space, which failure effusions yrly Opacification
of Starling's forces - inc becomes a vulnerable place due Hemithorax; blunted
hydrostatic press, dec Common sx? Dyspnea to large size & surface area, malignancy, PNA/ costophrenic angle,
serum onc press) - low (increased inefficiency of negative pressure pulls fluid in, Infxn, PE, post meniscus sign (upside
protein content resp muscles, NOT and relatively leaky borders from surgical down U), loss of nl
hypoxemia), cough, gap jx btwn mesothelial cells structures at lung base
Exudative (occur when pleuritic chest pain TB (global cause)
local dz stimulates pleural Starling's forces: Pcap (CHF, thoracentesis!! (dx &
fluid formation; inc cap Decreased breath sounds vol overload), cap oncotic tx effects)
perm -pneumonia; over area of pleural pressure (cirrhosis, nephrotic
obstruct of lymph effusion (Base of lung), synd), Lymphatic clearance Light's criteria >1
drainage - cancer); dullness to percussion (lung cancer, lymphoma) exudative
capillary barrier disrupted
so high protein content Increased permeability - Cell types:
pleural dz, malignancy, infxn Neutrophils? inf/symp
causes; Lymphocytes?
decreased pleural pressure cancer, TB; RBCs:
(atelectasis, trapped lung) - fluid hemorrhagic
moves into lung (malignancy, TB, PE,
trauma), hemothorax
Hepatic hydrothorax transudative pleural liver related pleural effusion due cirrhosis, liver diuretics do not attempt
effusion to high portal pressure (from failure pleurodesis!!
cirrhosis usually) Beta blocker to
ascites decrease portal
RUQ pressure
transplant
Parapneumonic Exudative pleural Pleural effusion ipsilaterally Pneumonias 40% of bacterial Thickened visceral Antiobiotics for complicated bloody
Effusions (PPE) effusion associated with underlying pneumonia membrane (makes exudative stage; surgical procedure
pneumonia; due to inflammed develop PPE lung expansion chest tube drainage
no bacteria or pus in visceral fluid (inc fluid prod, less difficult) for fibrinopurulent
pleural fluid resorption) stage; decortication
for organized stage
3 stages:
1. exudative: inflammatory/
capillary leakage, tx w/ Abx
2. fibrinopurulent: loculations,
requires chest tube drainage
3. organized: scarring, pleural
peel formation, requires surgical
decortication
Characteristics
Empyema Exudative pleural effusion Infection (collection of pus) in CXR: distinguish from Drainage
pleural space neoplasm (which
always appears
spherical) - empyema
will look different
based on viewing
position
Thoracentesis: gross
pus or positive gram
stain, pleural fluid
Malignant Pleural Exudative pleural hematogenous metastases to 2nd most common cultures (always
pleural fluid low
cytology pleurodesis high recurrence rate,
effusion effusion parietal pleura cause for positive in 60-80% usually represent an
exudative effusion advanced malignancy
cancer cells erode through possible pleural bx
visceral pleura
cancer cells occlude lymphatics
Chylothorax Exudative pleural disruption of thoracic duct or LN trauma or

effusion dissection; represents high lipid CANCER!
content in pleural space
turbid, milky white
pleural effusion; does
not smell (empyema), no
pus
Pulmonary Arterial PAH mPAP >= 25 Proliferation, vasoconstriction, idiopathic (see CXR: right heart oral anticoagulants, Pts with HIV or
Hypertension (PAH) PWP <= 15 thrombosis, remodeling below), heritable enlargement diuretics, scleroderma need
No significant obstructive/ (BMPR2, Alk1, supplemental O2, aggressive tx
(WHO Group 1) restrictive lung dz, left d/os like CTD (Scleroderma), endoglin), drug/ EKG: signs of right digoxin for CHF,
heart dz, or HIV(s vascular mediators to toxin induced heart strain (high R inotropes for Class IV
thromboembolic dz favor vasoconstriction), (amphetamines, wave in V1 suggests
portopulmonary dz ( portal cocaine, St. John's increased ventricular prostacyclins,
vein press, backflows to heart), wort), other mass) endothelin
congenital heart dz (atrial- disorders, antagonists, PDE-5
septal defect shunts systemic persistent Doppler Echo: inhibitors
blood into pulm circ), pulmonary HTN of bulging of RV
schistosomiasis (eggs from newborns septum, regurgitant monitor tx effects via
organism occlude pulm artery, (foramen ovale tricuspid valve, exercise capacity,
remodeling), chronic hemolytic doesn't close) enlarged RV hemodynamic
anemia ( NO = improvement,
vasoconstriction) Right heart functional class,
Endothelin pathway: in PAH= catheterization: Echo, QoL
vasoconstriction & smooth evaluation of mPAP &
muscle hypertrophy PCW
Nitric oxide pathway: in PAH,
nl causes vasodilation, broken Blood tests for
down by phosphodiesterase underlying causes
Characteristics
Idiopathic Pulmonary slowly progressive Significant overgrowth in Unknown? 20-30 y.o. histology? Intimal/ see PAH High mortality without
Arterial Hypertension DOE, syncope w/ endothelial layer of pulmonary smooth muscle/ treatment (median
exertion, chest pain, arterioles (vascular F>M (2:1) adventitia survival 2.8 yrs) - cor
palpitations remodeling) = obstruction of hypertrophy & pulmonale
blood flow (plexiform lesions) = formation of
loud pulmonic valve pulmonary vascular resistance plexiform lesions
closure (P2), tricuspid (PVR is too high!!), problems
regurgitation murmur w/ perfusion
on LSB, right sided fourth
heart sound (increased natural hx? Pre-symptomatic
press through tricuspid (RV hypertrophy to compensate
valve), right ventricular for increased PVR, allows CO to
heave, peripheral keep up), symptomatic
edema, ascites, JVD (vascular remodeling causes
decreased CO, while PAP &
PVR continue to increase),
declining (loss of PAP =
declining CO & cor pulmonale)
Pulmonary veno- shared similarities with venular proliferation on post- left-sided see PAH
occlusive disease PAH capillary side (left heart) leads to predominant dz
(PVOD) narrowed lumen of small
pulmonary veins -->
(WHO Group 1') development of pulmonary
infiltrates, edema, severe
hypoxemia
Pulmonary arterial Valvular diseases, mPAP >= 25 increased mPAP and PVR due no meds approved
hypertension from systemic dysfunction, PWP > 15 to vasomotor constriction or for this population
Left heart disease diastolic dysfunction pulmonary vascular remodeling
(WHO Group 2)
Pulmonary arterial severely decreased chronic hypoxemia leads to COPD, ILD, mixed see PAH
hypertension from DLCO shunting of blood away from restrictive/
lung disease/ non-ventilated areas and obstructive lung
hypoxia increased backflow to RV (L-R dzs, sleep apnea,
shunt); increases alveolar
(WHO Group 3) vasoconstriction of pulmonary hypoventilation
arteries disorders, chronic
exposure to hi
loss of pulmonary vasculature altitudes,
(COPD) increases workload for developmental abnl
remaining vessels
Chronic DOE after asymptomatic uncommon, subacute incidence of younger age, 10% of pts have only PAH that is
Thromboembolic period of months - years manifestation of pulmonary CTEPH happens larger PE, antiphospholipid curable!!
Pulmonary HTN embolic disease that evolves via w/I 2y of acute idiopathic VTE, antibody syndrome (pulmonary
(CTEPH) proximal pulmonary artery VTE hx of previous thrombo-
obstruction from failed clot PE Dx requires VQ scan endarterectomy) -
(WHO Group 4) resolution --> remodeling to (shows areas of mechanically dissect
increase pressure backflow to mismatched flow) clot off the artery
RV
Characteristics
Pulmonary arterial miscellaneous diseases that all Chronic see PAH
hypertension w/ cause PAH myeloproliferative
unclear or dz, splenectomy,
multifactoral causes sarcoidosis, LAM,
pulmonary
(WHO Group 5) langerhans cell
histiocytosis,
glycogen storage
diseases, hyper/
hypothyroidism,
end stage renal dz
Hepatopulmonary Secondary to liver Diffusion-perfusion impairment = Liver disease supplemental oxygen can cause R-->L
syndrome disease overdistention of capillary = (causes shunting w/ severe
RBCs escape w.o oxygen vasodilation & pulmonary vascular
traveling to other side (bc capillary over- dilation
capillary is too wide) = R-L shunt distention)
hypoxemia (PVR is too low!!)
Hyperventilation / increased effective minute Brain: hypocapnia --> Physiologic NOT related to RR treat underlying
Hypocapnia ventilation = PaCO2 < 35 vasoconstriction --> causes? Hypoxia, disease, brown
(hypocapnia) hyperexcitability of neurons and acidosis, irritants Diagnostics? paper bag
poor perfusion to brain --> (P.E., inhalants), Pregnancy test, ABG (increases blood
neuro signs (seizures, seizures CHF (J-receptors) (pH, pO2, HCO3-, CO2 because closed
syncope, visual changes, pCO2), kussmaul system),
dizziness), CV signs <3: hypocapnia --> demand, Non-physiologic breathing (slow deep reassurance,
(arrythmia, chest pain), O2 delivery = electrical causes? Pain, breathing classic in sedation?
increased work of abnormality --> arrythmia anxiety, acidosis)
breathing, dypsnea, psychogenic
muscle weakness, Lung: hypocapnia --> smooth
parasthesias, carpopedal muscle contraction and mucus sepsis, PE,
spasm, tetany, NO edema (stiffer, more resistant) -> pregnancy
HEADACHES hyperventilation, dypsnea &
work of breathing
nl/ hi pO2, nl pCO2 w/
sleep-psych hypervent
Hypoventilation / decreased effective hypoventilation = acute CO2 = Brain: congenital Central cause? Nl Respiratory do not give
Hypercapnia minute ventilation = pH = O2 central PFT, nl muscle fx, acidosis? Correct w/ supplemental
PaCO2 > 45 hypoventilation impaired hypoxic drive drug antagonist, oxygen to patients
(hypercapnia) chronic hypercapnia? pH w/ (hirchsprung's dz), (problems with intubate with chronic
time, kidney compensates w/ hypothyroid, unconscious breathing Central alveolar hypercapnia (only
central alveolar HCO3; RBCs (polycythemia), sedatives/narcotics only) hypoventilation? drive to breathe is
hypoventilation? No baroreceptor sensitivity (high / benzos, Neuromuscular Respiratory hypoxia!!)
dypsnea, hypoxemia PCO2 causes less minute anesthesia, cause? FEV1, stimulants,
secondary to hypercapnia ventilation than expected); rely Ondine's curse; FVC, TLC, RV diaphragmatic
on secondary drive to breath muscle & PNS: (restrictive pattern), pacing, nocturnal
neuromuscular (hypoxia) ALS, MG, MD, weak muscle fx (low ventilation
hypoventilation? kyphoscoliosis, pressure, forces, neuromuscular?
Orthopnea (loss of 2 consequences? -HCO3, obesity MVV), rapid shallow NO stimulants, tx
diaphragm fx), cor cerebral vasodilation hypoventilation Lung dz cause? underlying condition,
pulmonale (terminal (headaches), sleep arousal syndrome; lung: obst/rest pattern on nocturnal ventilation
event) (sleep disturbance, COPD, Asthma, PFT, nl muscle pulm? Treat
bronchiectasis, strength but low underlying dz,
somnolence), Hb desaturation/
pulm fibrosis MVV/endurance; careful O2
erythropoiesis (cyanosis,
polycythemia), pulm hypoxic drive alone w/ supplementation,
common cause for chronic hypercapnia nocturnal ventilation
vasoconstriction (pulm HTN, cor
resp acidosis?
pulmonale)
DRUGS, stroke
Characteristics
Hypoxemia General FIO2; Check A-A gradient
hypoventilation;
diffusion
impairment; VQ
mismatch; shunt (R-
L), altitude induced
hypoxemia
hypoventilation induced PaCO2 > 45 mmHg; nl A- elevated PaCO2 means there is extra-pulmonary usually corrects with
hypoxemia a gradient, responds to less amount of O2 in the causes small doses of O2
increased FiO2 alveolus = less O2 that will move (FiO2); correct with
from alveoli to pulmonary drug antagonist
capillary = hypoxemia; no (opoid antidote)
abnormalities in gas exchange
VQ mismatch hypoxemia increased A-a gradient, disease process causes hi ventilation, low patients respond to
nl PaCO2 (unless severe amplification of VQ mismatch, perfusion (PE) increased FiO2
hypoxemia), respond to where composition of alveolar
increased FiO2 gas varies in different lung low ventilation, hi
regions, causing hypoxemia perfusion
(pneumonia, PE-
CHF, ALI/ARDS,
atelectasis,
pulmonary fibrosis,
COPD)
Right to Left Shunt severe hypoxemia that is blood moves from right side of anatomic shunt
hypoxemia not readily fixed with heart to left side of heart without (intracardiac
increased FiO2, being oxygenated (extreme form shunts, pulmonary
increased A-a gradient, nl of VQ mismatch) AV malformations,
PaCO2 hepatopulmonary
syndrome)
physiologic shunt
(atelectasis,
pneumonia,
ALI/ARDS)
Diffusion limitation increased A-a gradient, difficulty moving the oxygen out interstitial lung
hypoxemia exercise-induced of the alveoli and into the disease,
hypoxemia, usually pulmonary capillary pulmonary
responds to FiO2 fibrosis
increases exercise-induced hypoxemia?
Blood moves faster during
exercise, so not enough time for
O2 to diffuse from alveoli to
capillaries; nl there are
compensation mechanisms
(dilate cap surface area,
increase alveolar O2 content)
but in these patients,
compensatory mechanisms
are impaired
Characteristics
Acute respiratory Acute lung injury (ALI) defining criteria? Acute lung injury --> flooding of nl CXR? Possible at-risk dx? 300<PaO2/FiO2<200 manage underlying mortality ~30-40%,
failure (ARF) Acute respiratory distress alveoli w/ edematous fluid = VQ causes = CNS Direct lung CXR: bilateral cause long recovery time
syndrome (ARDS) mismatch, shunting, & capillary
Acute onset post "at risk" event (stroke, drug injury (aspiration infiltrates
dx leakage; decreased surfactant OD, head injury), of GI contents, ABG: worsening CO2 provide supportive
Bilat infiltrates on CXR
production/function; all leads to neuromusc dz, pulmonary and O2 levels despite care
PaO2/FiO2<300 (ALI) stiff lungs from diffuse airway obst contusion, increased oxygenation
PaO2/FiO2<200 (ARDS) alveolar damage & pulm (asthma, COPD), pneumonia/ restore oxygenation
edema --> respiratory load = PE sepsis); indirect to better levels
No LA HTN (no evidence worse alv ventilation = lung lung injury (non- (PaO2 of 55-60, O2
of CHF) compliance (low compliance abnl CXR? pulm sepsis, sat 88-90%)
means more pressure required Possible causes = abdominal
to make a change in vol) ALI/ARDS, trauma, multiple intubation & low tidal
aspiration, fx, hyper- volume mech
pneumonia, transfusion) ventilation if
hydrostatic pulm necessary
edema, obst lung
dz (nl/abnl CXR),
PE (nl/abnl CXR),
pneumothorax
Pulmonary loss of capillary volume ILD DLCO

hypertension gross: thickened
pulmonary arteries
(white macaroni)
Pulmonary chest pain, dyspnea, Large clots increase the 600,000 PE, 1 same as those DLCO anti-coagulation!! increased mortality if
embolism apprehension, syncope, pressure of RV, which cannot million silent PE; for DVT (short term - LMWH PE+shock
cough, hemoptysis, compensate to acute changes in 3rd most common Well's criteria: >6pts = heparin, unfract
sweats pressures --> enlargement of CV disease in US high risk (78%), 2-6 heparin; long-term - 65% of people die w/I
RV --> decreased preload & pts= mod risk (28%), coumadin) 1st hr of dx
contraction of LV (can't fill <2pts = low risk
anymore) --> decreased CO (3.4%); modified (>4 Thrombolytics if Thrombolytics
pts = PE likely!!) low BP (shock contraind in pts >80,
virchow's triad state) major surg w/I 7d,
Christopher study: major trauma w/I 10d,
low modified Wells = TIA/ neurosurgery in
D-dimer (nl - done; last 6m, GI bleed in
abnl - CT scan), CT last 3m, uncontrolled
scan (nl - done, HTN, known bleeding
positive -tx); hi disorder
modified Wells = CT
scan (nl - done; Thrombolytics have
positive- tx) increased risk of
intercranial
Alternatives? VQ hemorrhage
scan, abnl pulm
angiography
Characteristics
Deep Vein swollen leg, tenderness in direct injury to deep veins or occurs in deep 2 million cases, Trauma, spinal Well's criteria: >3 pts Prox/ pelvic DVT? AVOID giving anti-
Thrombosis leg near deep veins, endothelial cell activation --> veins of pelvis and 1/1000 per yr; cord injury, ortho = high risk (75% Catheter-directed coagulation
unilateral swelling >3cm, activation of tissue factor (TF) -- proximal thigh M>F, blacks more surgery, Gyn chance of DVT), 1-2 thrombolysis prophylaxis to spinal
unilateral pitting edema > activation of extrinsic affected surgery, critical pts (moderate risk), <1 surgery patients
coagulation cascade --> care pt (low risk) Obj confirmed DVT?
activates VIIa --> activates Fast-acting anti-
thrombin --> cross-linked fibrin Immobilization, Suspect DVT? coagulation
clot bone fxs, age, D-dimer (R/Os (LMWH) for 5 days,
prior DVT, thrombosis) - abnl? also start vitK antag
Virchow's triad: vessel wall cancer, varicose Ultrasound of whole (coumadin),
damage, venous stasis veins, leg - abnl? Rpt 1 compression
(stagnant blood coagulates), anesthesia, week later stockings
increased blood coagulability severe COPD,
(cancer, Factor V Leiden) high estrogen 3m follow up duration of anti-
states, HIT, regardless coagulation depends
thrombophilias on rev/irrev cause
Pulmonary fibrosis increased membrane thickness, DLCO

increased VQ mismatch
hypoxemia, increased diffusion histology: blue-pink
limitations (fibrosis prevents O2 color as collagen
movement out of alveoli and into deposits develop
capillary) fibrosis; thick, stiff
looking alveolar
chronic inflammation = increased spaces; temporal
cytokines = induced fibroblast heterogeneity
secretion of collagen = fibrous (normal septum next
scarring to disease septum)
gross: honeycombing
(bumpy cobblestone
pleura; tethering of
fibrin); traction
bronchiectasis (dilated
bronchi)
Obesity "Pickwinian's syndrome" morbid obesity, increased capillary blood volume DLCO weight loss cor pulmonale
hypoventilation sleepiness &
syndrome hypoventilation during difficult to reverse
day, hypercapnia,
cyanosis,
hypersomnolence
Acute "Croup" sound horrible but inflammation of larynx, trachea viral uncommon in kids Clinical dx, can make Spontaneous inflammation can
Laryngotracheitis ventilating ok < 6m (maternal child worse by trying resolution w/ extend into lower
Parainfluenza viruses 1-3 are extrathoracic Abs) to get CXR hydration, anti- airways/bronchi =
starts w/ rhinorrhea/ sore most common agent (>75%) obstruction pyretics, humidified laryngeal tracheal
throat/ mild fever --> peaks btwn 18- CXR: steeple sign air bronchitis
barking cough w/ less common? RSV, influenza, 24m (narrowing of
inspiratory stridor --> adenovirus, herpesvirus (more subglottic region) severe cases? Oral
resp stridor, severe illness) most common corticosteroids,
tachypnea/cardia, nasal cause of upper nebulized
flaring, retractions --> inc preceded by coryza-like airway epinephrine for
distress--> fatigue, illnesses/URIs before croup obstruction in immediate
cyanosis, biphasic onset kids symptomatic relief
stridor --> silent airway (does nothing for tx
tota obst) though!!)
Characteristics
Epiglottitis dyspnea, stridor, tripod bacterial cellulitis of superior reduced can occur at any "Beefy red" & secure airway!! MEDICAL
position glottis structures vaccination rates age, but most swollen epiglottis w/ EMERGENCY!! High
common in kids < bronchoscopy Do NOT inspect risk of death (if
abrupt onset w/ early Haemophilus influenzae type 5 y.o. airway or place IV edema progresses
toxicity B (Hib) - but more rare now that thumb sign on lateral enough to position
preceding URI there's vaccination XR (but really would intubation by most epiglottis over the
(sometimes), very sore never get bc could experienced person airway)
throat w/ choking B-hemolytic streps (A, B, C) worsen obstruction) -
sensation, difficulty Staph aureus swollen, enlarged IV fluids, labs, Hib manifestations
swallowing, drooling, epiglottis antibiotics (3rd gen elsewhere (meningitis,
respiratory distress, other organisms cause more cephalosporin), otitis, pnuemonia,
anxiety, high fever, gradual onset but slower airway/blood cellulitis)
muffled voice recovery cultures, rifampin
(dysphagia), toxic prophylaxis for
appearance close contacts, NO
nebulized
epinephrine
Foreign Body sudden cough/ wheeze typically objects are aspirated foreign objects peanuts, CXR: hyperinflation remove foreign
Aspiration after eating or playing down the right main bronchus popcorn, of affected airway object
(although sometimes because shorter and straighter hotwheels, any (air trapping) OR
onset may be insidious) than left bronchus small toy completely nl CXR!!
persistent cough or intrathoracic obstruction Atelectasis w/

wheeze, aspiration
current/persistent
pneumonia, decreased
breath sounds, delayed
air entry
Bronchiolitis tachypnea (RR>50,60), inflammation of bronchioles, RSV, followed by most commonly in daycare, CXR: hyperinflation hospitalize young Many develop
chest retractions, cough, intrathoracic obstruction parainfluenza children <2 y.o. hospital, ICU, (air trapping), flat child if it looks like recurrent wheezing
wheezing, prolonged regional diaphragm, RSV bc high that may be
expiratory phase, caused by RSV --> necrosis of Most common differences, peribronchial incidence of sleep associated with
crackles, signficant resp airway epithelium --> influx of cause of hospital premature thickening, apnea --> SIDS persistent
distress, apnea in young inflammatory cells --> release admission for <1 infants, winter or collapsed lung abnormalities in
infants, irritable, of inflammatory mediators = y.o. late fall birth (RUL), dense possible O2 lung function
dehydration edema = narrowing of airways month, M>F, infiltrates behind supplementation
anatomic abnl, heart (frank
usually limited to URI in respiratory droplet transmission malnutrition, consolidation, fluids (hypertonic
healthy infants; in <40% metabolic/ pneumonia) saline), hold feeds,
it progresses to genetic humidified O2,
bronchiolitis diseases, SES infection control
no routine
bronchodilators,
antivirals,
corticosteroids, or
antibiotics
Childhood wheezing Transient early wheeze early wheezing but sx NOT FH of ?

resolve btwn ages 3-5 asthma
reduced lung fx
before
respiratory
event
(prematurity, day
care, prenatal
maternal
smoking, post
natal smoking
exposure)
Non-atopic wheeze lower lung fx earlier in life associated w/ viral respiratory RSV, rhinovirus preschool age ?
that improves w/ age; tract infections kids
generally resolves by
age 6
Characteristics
Ig-associated wheeze Wheezing before age 6 atopy, increased airway hyper- FH of asthma, inhaled
(asthma) responsiveness, & elevated allergy, elevated corticosteroids
IgE; more persistent disease IgE @ age1,
w/ early exposure to allergens early
sensitization to
decreased risk w/ exposure to mold, obese
other children (daycare) and females,
animal exposure maternal
prenatal smoking
Cystic fibrosis Multisystem disorder - autosomal recessive mutation >1500 CFTR muts Most common life- 1/3200 births in Sweat test Spirometry Life expectancy
reproductive (congenital in long arm of chrom 7 creates but 50% of pts are shortening genetic whites (pilocarpine CFTR modulators ~40y.o. but improving
bilateral absence of vas gene product CFTR, which is homozygous for dz in Caucasians iontophoresis) - nl (Ivacaftor, VX-809, w. earlier dx and
deferens, decreased an ATP dependent chloride delta508 mutation ~40; CF ~90-100 PTC124) better tx
female fertility), sweat channel and also regulates in CFTR (deletion 30,000 aw clearance
glands (increased salt ENaC (CFTR: regulates in phenylalanine); Americans, Gentoyping (specific, (dornase alfa, Increased tendency
sweat content), GI movement of salt & H2O 60,000 cases not sensitive) hypertonic saline, for infections (never
(pancreatic insuff, across membrane) Class I (nonsense globally; bronchodilators, PT) really eradicated, just
meconium ileus, intest mutation); Class II Newborn screening Aerosilized abs for controlled) - Staph,
obstruction, biliary Abnl CFTR = decreased Cl (protein (measures IRT exacerbations H.flu, Pseudomonas
obstruct, DM) secretion = increased Na degradation by combined w/ Anti-inflammatories
reabsorption = decreased proteosome; genotyping; confirmed (prednisone, Pulmonary
sinusitis, nasal polyps, airway surface liquid = milder); Class III by sweat test) macrolides- exacerbations
chronic bronchitis dysfunctional cilia, chronic &IV (defective Psuedomonas) usually require
(leads to atelectasis, mucus infection, & airway regulation but Late stage PE findings Nutrition: caloric hospitalization
bronchiectasis, inflammation (due to hyper- CFTR makes it to (respiratory failure, foods, appetite (better adherence w/
pneumothorax, response inflammatory cell surface; FTT, malnutrition, stimul, tx constipat, aw clearance
hemoptysis, resp mildest); Class V steathorrhea) pancreatic enzymes therapies)
response) --> bronchiectasis
failure) (linsuff production & PPIs to minimize
of functioning CT: air trapping, malabsorp prednisone leads to
protein); Class VI bronchiectasis yearly CT scans @ decreased loss of lung
(accelerated age 1 fx but toxic w/ chronic
protein turnover) lung transplant use
Bronchiectasis irreversible lung damage CT: cysts

Gross pathology:
irreversible damage
Interstitial Lung Dry cough, DOE, Injury results in inflammation & connective tissue PFTs: restrictive
Disease (ILD) - insidious onset, end tissue remodeling in lung - if diseases, pattern (low TLC0,
general overview inspiratory crackles @ uncontrolled, tissue progresses exposures decreased DLCO
lung bases, possible to fibrosis & scarring of lung contributing to (thickened alv
digital clubbing, no hypersensitivity membrane)
wheezing pneumonitis, CXR: bilateral reticular
drug/smoking infitrates, basilar distn,
induced, radiation, small lung vol
toxic inhalation CT: diffuse ground
glass infiltrate, mixed
unk causes? IPF, pattern (consolidation
other idiopathic + GG), reticular
interstitial peripheral infiltrates;
pneumonias (COP, honeycombing
NSIP, LIP, AIP), (advanced fibrosis),
sarcoidosis, traction bronchiectasis
eosinophilic ABG: hypoxemia
pneumonia, rare
(LAM, PLCH, PAP)
Characteristics
Idiopathic Interstitial Idiopathic Pulmonary Chronic, progressive, "repeated cycles" of epithelial Unknown? high mortality!! Age (>50) DX = exclusion of No FDA approved About 50% survival
Pneumonias fibrosis fibrosing, interstitial activation or injury by some familial pulm other causes, +UIP med tx after 2 years dx; 15-
unknown agent Older adults, M>F fibrosis pattern on HRCT/bx 20% 5 yr survival
limited to lungs! 128,000 pts (US) smoking CXR: restrictive steroids
Dyspnea (insidious but 40,000 new GERD findings (smaller lung HARMFUL!!
progressively worsening); cases/yr exp to metal volumes), fibrotic
non productive cough 25-30/100,000 dust, wood dust, changes treat GERD
(difficult to control), solvents CT: honeycombing,
clubbing, decreased reticulation, traction Enroll in clinical
breath sounds, bilateral bronchiectasis, trials
crackles subpleural & basilar
changes Evaluate for lung
DDx? Other ILD, histology: dense transplant
connective tissue dz (RA, fibrosis + honey-
scleroderma), combing, subpleural O2
occupational exposure, involv, temporal supplementation,
meds (MTX, bleomycin, heterogeneity, pulm rehab,
nitrofurantoin) fibroblastic foci vaccination for
flu/pneumonia, tx
comorbidities,
maintain BMI
Desquamative interstitial Chronic onset of dyspnea M>F, mean age >90% of cases CXR: nl in 1/5 pts smoking cessation mortality rate 20-30%;
pneumonia (DIP) & cough; sometimes 45 y.o. involve CT: diffuse/patchy mean survival 12
clubbing smokers! ground glass steroids sometimes years
opacifications effective
PFTs: restriction + low
DLCO
histology: increased
alveolar
macrophages,
pigmented
Acute interstitial
pneumonia (AIP)
Respiratory bronchiolitis
interstitial lung disease
Cryptogenic organizing localized or diffuse consequence of infection or a/w CTD, drugs, CTDs CT: multiple patchy responsive to
pneumonia (COP) inhalational injury idiopathic consolidations; steroids!! (~6m)
"Bronchiolitis obliterans fibrous plugs filling airway sometimes GG
organizing pneumonia" into alveoli
BOOP Histology? Fibrous
sometimes present w/ plugging of airway
fever (after which Abs
don't help)
Lymphocytic interstitial
pneumonia (LIP)
Non-specific interstitial chronic onset of dyspnea varying degrees of inflammation Females > Males; Connective CT: UIP pattern better prognosis
pneumonia (NSIP) & cough; sometimes fever & fibrosis w/I alveolar walls, younger mean age tissue diseases HRCT: reticular than UIP!!
temporally uniform of onset (46-55) (more females!), infiltrates, peripheral
HSP, other & basilar distn, ++ Good results with
exposures ground glass, NO steroids
HONEYCOMBING,
TEMPORALLY
UNIFORM
Histology?
Inflammatory cells,
fibrosis, uniform
thickening of lung
interstitium
Characteristics
Drug-induced ILD Lung toxicity in response to Talc in illicit drugs remove responsible
antibiotics (nitrofurantoin), anti- drug!
inflammatory agents
(methotrexate,
cyclophosphamide), cardiac
drugs (amiodarone),
chemotherapeutic agents
(bleomycin, busulfan),
recreational drugs
Hypersensitivity Farmer's lung non-necrotozing immunologic-mediated, Microbial agents Non-smokers Histology: must stop may progress to
Pneumonitis Pigeon breeder's lung granulomatous dz inflammatory reaction around (bacteria, fungi, bronchiocentric exposure!! Only chronic HP w/ end
(extrinsic allergic Humidifier lung small airways in response to amoeba, atypical lymphoplastic then will steroids be stage fibrosis &
alveolitis) NO WHEEZING! inhaled antigen (organic dust) mycobacteria), infiltration, poorly effective honeycombing
NOT multisystemic (like Animal proteins formed non-
sarcoidosis) early stage: type III mediated (bird antigens), low necrotizing
Acute HP (sx w/i 48h, self- & high MW granulomas,
resolving, recurring late stage: type IV delayed- chemicals mutlinucleated giant
episodes more severe, type hypersensitivity reaction cells around
nonspecific sx; against antigen bronchioles,
tachypnea, tachycardia,
fine crackles), does not involve IgE CXR: may be normal
subacute/ intermittent CT: sometimes nl
HP (gradual sx, low dose HRCT: mid to UL s
rptd exp, sx resolve w/i (chronic HP), fibrosis/
24h of removal from honeycomb (chronic
agent, tachypnea, HP), any pattern (GG,
crackles) chronic HP retic, nodul, consolidn)
(chronic exp, prod cough, IgG- not spec/ sens
DOE, weight loss, BAL: CD8
tachypnea, crackles, predominance (diff
irreversible after removal from sarcoid)
of agent)
Sarcoidosis asymptomatic multi-organ (hilar/ mediastinal Unknown? 3x higher Some genetichistology: nodular spontaneous should always stain
LNs, lungs, liver, spleen) incidence/ severity component (HLA
aggregate of mo w/o resolution but tissue bx with acid
Non-infectious, non- granulomatous dz of unknown in African II on necrotizing center; management differs fast for bacilli to
necrotizing granuloma etiology Americans chromosome 6periphery of based on location of avoid missing TB
Systemic disease, non- short arm) lymphocytes (wreath involvement (early TB looks very
specific & variable abnl immune response to unk Scandavian arrangement of similar to sarcoidosis)
presentation (lungs, skin) antigens --> increased countries decreased risk nuclei), glucocorticoids if
Heerfordt's syndrome: proliferation of CD4+ T helper in HIV pts! multinucleated giant worsening pulm sx,
parotid swelling, uveitis, cells in involved tissues = young person's cells worse lung fx,
Bell's Palsy, fever recruitment of macrophages = disease (age<50) Worse CXR: changes in CXR; 6-
Lofgren's triad: arthritis, formation of granuloma prognosis? Pts lymphadenopathy in 12m
erythema nodosum, F>M >40y.o, A.A., young person;
hilar adenopathy - good CD4+ alveolitis hypercalcemia, interstitial fibrosis; lung transplant if
prognosis nephrosclerosis, determines staging (0- stage 4
extrapulm dz no pulm inv, 4-
The sicker a person irreversible fibrosis),
appears on presentation, nodular sarcoids
the better the prognosis! PFT: any pattern but
classic (nl ratio, low
DLCO, restriction or
mixed pattern)
BAL: increased
lymphocytes, >3:1
ratio of CD4:CD8
Characteristics
Pneumoconsioses Asbestosis diffuse fibrosis inhalation of asbestos body Asbestos body industries that Histology: alveolitis & amphibole body a/w
(occupational lung (amphibole more pathogenic mine, fabricate, development of giant mesothelioma
dz) DOE, productive cough than serpentine) causes the or install cells, interstitial
recruitment of macrophages --> asbestos fibrosis asbestos exposure
failed attempt to phagocytose --> (roofing, also increases risk for
formation of fibrogenic cytokines - insulation, bronchogenic
-> gradual development fibrosis brakes, carcinoma, benign
shipyards) pleural plaques
(marker of asbestos
exp), and
mesothelioma
Coal workers CT: diffuse nodules
pneumoconiosis
Silicosis nodular fibrosis nodular fibrosis that gradually 10-15 years of mining and histology: nodular high incidence of TB
develops following the inhalation silica exposure processing of type pattern of (silicosis =
increased susceptibility of cystalline silica in ores; stone fibrosis, silica macrophage wasting
to TB!!! occupational settings --> intxt cutting/ particles (needle like dz so can't fight off
w/ epithelial cells & polishing, structures) visible TB)
macrophages --> phagocytosis sandblasting, under polarized lens
of silica particles --> activation / working w/ slight risk for
release of mediators by abrasives carcinoma
macrophages --> eventual (pottery)
death of macrophages --> cor pulmonale
fibrosis
Berylliosis NON-NECROTIZING acute & chronic exposure to mining & industry Histology? Appears
GRANULOMAS (similar beryllium in fluorescent light just like sarcoidosis,
to sarcoidosis) bulbs, mining & industry --> would require
hypersensitivity reaction special testing to
distinguish
Anthracosis usually harmless except massive amounts of carbon

in coal miners w/ massive pigment in the lung
exposure
Community acquired detectable on gram stain; Strep pneumo enters human Strep pneumo, H. Blacks > Whites Elderly & CXR: lobar Macrolides Strep pneumo is #1
pneumonia (CAP) - abrupt onset of host via airborne droplet influenzae, others risk increases with infants consolidation, pleural
(arithromycin), cause of meningitis in
Typical pneumonia fever/chills, dyspnea, spread --> person can become age HIV, diabetes, effusions sometimes doxycycline, 3rd all age groups
(Pneumococcal cough (productive, asymptomatic carrier (children) splenic gen
pneumonia) purulent, sometimes or become locally infected (ear, dysfunction Sputum gram stain: cephalosporins, can also cause other
blood-tinged, rusty sinuses) (SSD), cirrhosis, many neutrophils, sometimes clinical syndromes
sputum - classic for S. defective gram+ cocci in pairs fluoroquinolone (bacteremia, otitis
pneumo), localized lobar Aspiration of nasopharyngeal antibodies; & chains media, sinusitis,
infiltrate, elevated carriage --> pneumonia settling African/ Native bronchitis, bacterial
systemic WBC, fever, in the alveoli Americans (due blood cx positive in peritonitis, bone/joint
pleuritic more to SES) 20% of patients infs, endocarditis)
Strep pneumo can invade the
blood stream and enter joints Increased rate of b-
(septic joint) or meninges lactam resistance
(menigitis) (altered PBPs)
CAP - Atypical general can't be seen on gram Mycoplasma

pneumonia stain, require special pneumoniae,
media to grow in cx, dry Legionella,
cough, dyspnea, patchy Chlamydia
infiltrates, milder pneumoniae, viral
(EXCEPT Legionella),
insidious onset w/ URI
sx
Characteristics
Legionella Pontiac fever - acute, Enters alveolar macrophages L. pneumophilia = rare in healthy Smokers or Gram stain: Gram - Fluoroquinolones
self-limiting flu-like illness; thru coiling phagocytosis, Gram negative, children, young people with rod that does not stain (Levofloxacin,
high attack rate among multiplies in the phagosomes, aerobic, non-spore adults damaged well; requires fuchsin, moxifloxacin,
exposed reaches critical mass, then lyses forming, mucociliary silver stains for ciprofloxacin)
the macrophage unencapsulated defenses visualization
Legionnaires' dz - mild bacilli (COPD) Macrolide
respiratory dz to severe, transmitted to humans via Legionella urinary (Azithromycin)
life-threatening aerosolization of immuno-deficient antigen - + in 80-90%
pneumonia; HI fever, contaminated water of dz Alternatives?
malaise, myalgias, age> 50 Doxycycline
anorexia, headache, Cell mediated immunity = host culture on selective
diarrhea, dry cough, defense media - slow but GS NO B-LACTAMS!!
hyponatremia, pleural
effusion serology- slow...
Mycoplasma pneumoniae 2-3 week incubation transmitted via person-to-person YOUNG PEOPLE! older adults with Empiric dx due to No tx for localized immune mediated
period, insidious onset, droplet spread (5-20 years old) bronchitis or difficult cx URIs (without systemic
"walking pneumonia" fever, malaise, headache, pneumonia; pneumonia) manifestations
persistent cough, focal pneumonia closed cold agglutinins: (Derm- SJS, CNS-
myalgias, disparity btwn populations antibodies to RBC I Ag B-LACTAMS do not encephalitis, Heme -
CXR and physical (military recruits, = agglutination of work (no cell wall!!) hemolytic anemia,
findings (few) boarding RBCs at 4 degs C MSK- myalgias,
schools, dorms) Pneumonia arthalgias, etc)
Antigen & NA present? Use
detection kits (future) macrolides
(erthromycin,
azithromycin),
doxycycline (adults),
fluoroquinolones
(adults)
Chlamydia pneumoniae re-infection possible, Infectious spores (EB) attach >1/4 of no seasonal CXR: patchy infiltrates Empirical tx
asymptomatic carriage, and enter host cell, endocytosed pneumonias in variation
21 day incubation period; and transformed into school-aged kids CBC: nl WBC doxycycline,
mild URI sx followed by metabolically active RBs; RB macrolides,
prolonged cough, multiply via binary fission; RBs cell cx not really tried fluoroquinolones
malaise, no fever really, transformed into EB to make
nl WBC count cytoplasmic inclusion, after PCR/NA techniques NO B-lactams!!
which the EB's are released to (Future)
infect next host cell
person to person droplet

spread
Coxiella burnetti (Q fever) often asymptomatic focal pneumonia caused by histology? interstitial
inhalation of aerosols of birth & alveolar infiltrates
products from sheep, cattle, of macrophages
goats, cats, rabbits
lymphocytic response due to

intracellular nature of organism
Characteristics
Viral pneumonias difficult to detect but may diffuse alveolar damage & CMV? Adenovirus?
precede bacterial necrosis caused by CMV, HSV, Immunocompro Exudates w/ necrosis
pneumonia adenovirus, or measles virus mised individuals & hemorr; intranuclr
inclusions w/ blurred
nuclr membrane -
smudge cell;
CMV? Intra-alveolar
hemorr, edema,
cytomegalic cells
(large cells with
intranuclr &
cytoplasm
inclusions)
HSV? Eosins w/ halo
Measles? multinucl
giant cells w/ intranuclr
inclusions w/ indistinct
halo & cytoplasm
inclusions
Pneumocystis jirovecii focal infiltrates fungal pneumonia that invades immunocompro Histology? Looks
pneumonia (PCP) immunocompromised hosts with mised pts (AIDS, bubbly with widened
CD4 T cell count <200 (presence transplant, alveolar septa due to
of PCP = AIDS dx) cancer, steroids) inflammatory cells;
characteristic cysts
seen w/ silver
staining
Necrotizing inflammation & pus that can be caused by aspiration of S. aureus, S. Immunocompro Gross: cavitation antimicrobial scarring --> fibrosis
Pneumonia (Lung has been walled off; infective material (especially pyogenes, mise; transplant (gangrene of lung) w/
Abscess) characterized by cough, when cough reflex is depressed); Pseudomonas, surrounding fibrosis, R/O carcinoma
fever, foul-smelling antecedent bacterial POLY-MICROBIAL pus filled
purulent sputum, digital pneumonia; septic embolism; extension into brain,
clubbing neoplasm (postobstructive CXR: abscess hemorrhage
pneumonia) formation
Histology: alveolar
space filled w/ PMNs
Aspiration (severe necrotizing Aspiration of gastric contents Polymicrobial debilitated pts Histology: High mortality
pneumonia bronchopneumonia) or oral flora resulting in a hemoptysis &
necrotizing pneumonia that has unconscious necrosis lung abscess in
chemical (irritant) and pts those who do
polymicrobial components survive
repeated
vomiting
Characteristics
Tuberculosis Active TB Pulmonary TB: insidious person to person transmission Mycobacterium 1.5 million HIV Acid Fast Bacillus RIPE = Rifampin, Lots of undetected TB
onset of prolonged of airborne droplets, especially tuberculosis deaths/yr; 2nd poor, crowded, Broth cx w/ Ab isoniazid, cases globally so
Latent TB (not all cough, pleuritic chest with prolonged exposure; 3 leading cause of poorly ventilated susceptibility - GS pyrazinamide, need single point of
organisms are eradicated pain, hemoptysis, fever, outcomes with exp? 1. active TB death after HIV; settings DNA probes on ethambutol for 6-9m- care test (GeneXpert -
but immune system night sweats, weight/ inf, 2. latent inf, 3. no inf #1 cause of death malnutrition smear + specimens drug susc TB RT-PCR $$)
controls inf; not infectious appetite loss, fatigue in HIV pts (NAAT - hi sen/spc)
but at risk for reactivation most infectious pts? Cough + immunosuppress to ID species (TB - start on 4 drugs if MDR-TB (resistance
in future) TB + HIV: extrapulmonary AFB smear+ most cases in ed (TNF-a rough colonies) suspicious of TB, to at least INH + RIF)
dz, atypical CXR findings Asia & Africa inhibitors, CXR: typical UL once have
primary progressive dz (LL & interstitial infiltrates, MTB enters alv macrophages prednisone) infiltrates;variable susceptibilities, can XDR-TB (resistance
(inf followed by active dz adenopathy) and replicate in phagosome HIV epidemic is patterns (hilar cut back to 2 drugs (4 to INH, RIF, +
usually in HIV pts) (leads to asymptomatic driving TB recent inf w/ adenopathy, bilat drugs - 2m, 2 drugs - fluoroquinolones/
Miliary TB = disseminated bacteremia & multiple seeding coinfection latent TB (<2y) infiltrates, cavitary UL) 2m) injectable Abs)
(looks like millet seeds in sites); ~3wks later, TH1 in HIV coinfected;
the lung) response is mounted (due to inc substance abuse miliary nodules cavitations on CXR: resistance = higher
IL-12); TH1 cells make IFN-y histology: 4 drugs -2m, 2drugs- morbidity, mortality,
NECROTIZING which stimulates macrophages DM, renal failure, necrotizing 7m cost
GRANULOMAS to contain the MTB inf --> cancer, chemo, granulomas in
formation of necrotizing silicosis, fibrotic center, AFB stain= DOT!!! immune reconstitution
granulomas, hypersensitivity, changes on CXR "red snappers", inflammatory
& tissue destruction Ghon focus, Ghon LTBI - tx with INH for syndrome (IRIS) -
complex, cavitations 9 months (or INH/RIF response in TB-HIV
(caseous) for 1x q 12wks) pts started on ARVs
Atypical M. avium intracelluaire Hot tub lung, pre-existing HIV, COPD/other Multi-drug therapy DIFFICULT TO
Mycobacteria complex (MAC) lung conditions lung dz ERADICATE
susceptible; especially
aggressive in AIDS pts
(feverish, night sweats,
weight loss)
non-AIDS pts rarely

become infected (but if
so, productive cough +/-
weight loss/fever)
Granulomatous Cryptococcus granulomatous caused by Cryptococcus opportunistic Gross: caseous

fungal diseases inflammatory response neoformans, which is an infection! necrosis of lung just
(very similar to TB encapsulated yeast and like TB
clinically, transmited to humans via
pathologically) inhalation of soil & bird Histology: yeast
droppings (spheres)
dimorphic: mold in surrounded by clear
the cold, yeast in the space (capsule),
heat! which can be stained
with mucicarmin -
GEOGRAPHIC capsules turn pink
localization
Histoplasmosis narrow based budding Inhalation of histoplasma Ohio & nl & immuno- Histology: calcified
capsulatum causes isolation of Mississippi River compromised pts necrosis,
only spores into the lung, after which valleys unencapsulated
immunocompromised the fungi intracellularly reside organisms seen w/
individuals progress w/ in macrophages silver stain inside
production of alveolar
granulomas Histoplasmoma - localized lung macrophages,
lesion that becomes walled off narrow based
and calcified budding if
NOT really capsulated! chronic fibrosing replicating
histoplasmosis - aw centered
fibrosing lung dz
Histoplasma pneumonia -
granulomatous pneumonia
Disseminated histoplasmosis-
resembles miliary TB
Characteristics
Coccoidoidomycosis multiple budding inhalation of spores from Southwest & Histology? Large
Coccidiodes immitis causes Western US organism containg
various dz presentation, delayed type hypersensitivity to secondary
mostly asymptomatic the fungus component
(80% of people in (spherule w/
endemic areas infected) endospores) -
but some people can multiple budding
have lung lesions, fever,
cough, pleuritic pains,
erythema multiforme
Blastomycosis broad based budding Inhalation of spores from Southeastern & Histology? Broad Spontaneous
Blastomyces dermatitidis, south central US based budding resolution, or can
Pulmonary, skin, & bone producing various dz persist as a chronic
lesions presentations CXR: UL involvement lesion
pulm sx (productive
cough, chest pain,
abdominal pain, night
sweats, chills, anorexia,
weight loss)
Wegener's resembles TB but must unknown but probably represents M=F, mean age of Histology (surg bx): corticosteroids + if untreated, mortality
Granulomatosis be distinguished bc diff T cell mediated 40 y.o, more cavitation, cyclo-phosphamide w/I 1 year
tx hypersensitivity reaction to common in necrotizing
inhaled infectious or Caucasians granulomas, alveolar CXR/CT to monitor poor prognosis related
Necrotizing systemic environmental agents (due to hemorrhage w/ response to tx to # sites involved,
vasculitis response to immunosuppressive capillaritis, medium- renal involvement,
agents) small vessel vasculitis Can give age, delay in dx,
ELK Triad: azathioprine & MTX medication
Ear/nose/throat, Lung, Blood test ANCA to maintain remission intolerance
Kidney involvement (cytoplasmic,
perinuclear): IgG
saddle nose deformity autoantibody w/
ANCA associated specificity against anti-
vasculitis neutrophil granules &
lysosomes in
const sx (fever, migratory monocytes; useful
arthalgias, malaise, marker for dz activity
anorexia, weight loss); & evaluation of
ENT sx (sinusitis, otitis), systemic vasculitis;
pulm sx (cough, + in other dz!!
wheezing, stridor,
dyspnea, hemoptysis)
Foreign Body Diffuse pulmonary emboli entrapped foreign material (not talc from IVDU IVDU Histology?
Granulomas blood clot!) in pulmonary Multinucleated giant
vasculature Iatrogenic (in- cells, birefringent
dwelling catheter, (polarized light will
IV line, silicone show talc)
from breast
implants)
Localized parenchymal tissue reaction to foreign Histology? Lipids in

mass material, commonly seen with alveoli cause
aspiration pneumonia or lipoid formation of
pneumonia (lipid in the lung) granulomas
Characteristics
Influenza virus Incubation period (2d_, person-to-person, airborne 5-20% of US Elderly Rapid Antigen Oseltamivir/Tamiflu More complications &
(Orthomyxoviridae) abrupt onset, shedding transmission of influenza virus population gets flu (seasonal flu) Detection - poor (tx, prophylaxis) mortality in elderly
of virus 1d before & 5d from symptomatic or each yr; 36,000 Middle aged sensitivity
after sx begin asymptomatic hosts deaths/yr (>90% adults (H1N1) Tamiflu allergy? EXCEPTION: deaths
in people >65 yo) Viral cx - takes a few Zanamivir/Relenza from H1N1 were
HI fever, severe days middle aged adults
myalgias, headache, Tamiflu resistant flu
chills, cough, DOE, GI PCR (future) subtype? primary viral
sx Amantadine, pneumonia,
Rimantadine secondary bacterial
pneumonia, otitis
media, Reye's
Syndrome (aspirin
+flu), myopericarditis,
?encephalitis
Characteristics
Parainfluenzae virus Laryngo- 20% of resp infs in young children No specific antiviral
(Paramyxoviridae) tracheobronchitis kids, very few in
(Croup) adults no vaccine
Bronchiolitis (RSV first, supportive care

then parainfluenza)
Less common cause of

pneumonia
Respiratory severe lower respiratory droplet transmission and direct community severe inf risk diagnosed via Cx, Ribavirin hi secondary
Syncytial Virus tract disease in infants contact outbreaks in late increased w/ kids antigen detection, (aerosolized form for infection rates
(RSV) fall to early who have cong PCR infants, oral form for
(Paramyxoviridae) bronchiolitis, spring heart failure, transplant pop) inhaled form of
bronchopneumonia, underlying pulm ribavirin can cause
bronchitis in older dz, premature supportive care bronchospasms in
children/adults birth transplant pts
incubation period of 2-8 significant resp

days; viral shedding for pathogen in
1-2 weeks or longer transplant pop
Human clinically indistinguishable illnesses similar to RSV; seasonal (winter/spring) pattern elderly, Molecular detection w/ severe lung dz in lung
metapneumovirus from RSV coinfection w/ RSV = where it is transmitted by close immunocomp, PCR transplant pts
(paramyxoviridae) severe illness contact young children
upper & lower

respiratory tract
infections
Adenovirus 50% of inf are spread by droplet nuclei, fecal- Cx less valuable Infection control
asymptomatic oral route, and can persist for because virus may not
some time in the environment be shed for years after Antiviral therapy
Infants: pharyngitis, otitis inf cidofovir for
media, pneumonia, infected epithelial cells undergo disseminated sx
diarrhea necrosis --> intense direct antigen assay
inflammatory responses --> for conjunctivitis
Children: URI, possible viremia
pneumonia, diarrhea, PCR
hemorrhagic cystitis Latent infection that can
reactivate & cause severe inf in
Adults: URI, pneumonia, transplant pts
conjunctivitis (pink eye)
Immunocomp:
pneumonia,
gastroenteritis,
hemorrhagic cystitis,
hepatitis, interstitial
nephritis
Common cold Rhinovirus 30-50% of common colds circulate in spring, PCR

(Picornaviridae) summer, early fall
Coronavirus 10-30% of common colds SARS = virus endemic in bats circulate in fall, PCR
that crossed into humans via winter
SARS (severe acute intermediary (cats); risk of
respiratory syndrome) transmission greatest around
day 10 of illness; HCWs were
high risk group for acquisition
Characteristics
Sleep apnea Central Sleep Apnea cessation of airflow during nl - reset of CO2 setpoint hi altitude (longer maintain resp drive
sleep due to cessation of during sleep (transient period - periods of sleep (respiratory
respiratory effort as result PaCO2 is below apnea threshold apnea) stimulants -
of decreased ventilatory = min vent = PaCO2 to apnea theophylline,
motor output threshold = minute ventilation hypercapnia, progesteron;
chronic increase metabolic
nl or slightly lower PaCO2 Chronic hypoventilation = hypoventilation acidosis by
levels during the day, impaired CO2 drive since have alkalinizing urine -
chronic hypercapnia @ hi PaCO2 levels = cyclical sleep CHF (Cheyne- best for altitude
night onset central apnea ( apnea Stokes,inc induced)
time, arousal) feedback delay)
Cheyne-Stokes treat underlying
respiration in normocapneic CSA, PaCO2 Increased conditions (CHF -
becomes higher than setpoint= hypersensitivity/ CPAP mask)
hyperventilate = PaCO2 loop gain (from
becomes too low = oversensitive
hypoventilation (Cheyne-Stokes medulla,
respirations) = Increased exaggerated output
feedback delay (brain to resp muscles, or
responding to old news and overefficiency of
tends to overcompensate) or lungs in gas
LOOP GAIN (small stimulus = exchange)
gigantor response!!)
Obstructive Sleep Apnea complete blockage of Aw becomes more compliant, Obesity (narrow 20 million MRI: narrowed CPAP (changes 30% noncomplicance
airway despite efforts to pharynx narrows, and resistance airways), large Americans, many pharynx behind tongue negative airway to CPAP
breathe to breathing increases with neck, thick tongue, undiagnosed; 95% pressure to positive,
sleep; in OSA, muscle tone URIs, nasal trauma of all sleep apnea STOP BANG so distends the
SNORING that wakes up can't compensate to keep the questionnaire pharynx during
bed partner aw open so increased snoring negative (Snoring, Tired, inspiration)
and OSA oropharyngeal Observed apneas,
clinical features: left press (small Pressure - HTN, pharyngeoplasty
heart failure, unexplained as pts start to snore and try pharyngeal cavity, BMI>35, Age>50, (effective in 50% of
nocturnal death, harder to breathe out, increased hi pharyngeal neck circumference, pts but very painful,
pulmonary hypertension, resistance outside of thorax and compliance, gender -male) - last resort option)
right heart failure, chronic negative pressure inside pharynx decreased upper increased risk for OSA
hypoventilation, pulls airway closed = less airflow aw muscle activity) if 3/8 factors mandibular
excessive daytime = transient hypoxia, advancement
sleepiness, restless hypercapnia, acidosis = devices (makes
sleep arousal from sleep snoring difficult by
holding tongue down)
sleep onset -> apnea -> hypoxia,
hypercapnia, acidosis -> arousal weight loss
from sleep -> resumption of
airflow -> return to sleep -> cycle
starts over
Pursed lip breathing

(creates increased
pressure near mouth that
changes press
gradient;Ppl>Paw occurs
higher in the trachea
where it's
noncompressible)
SMOKING
CESSATION!!!
Reduction of risk
factors, Flu vaccine
Lifestyle modifications
most impt tx (other
treamtnes not too
effective)
Flu & pneumococcal

vaccines; possible
augmentation therapy
of missing protein PiZZ
($$)
SMOKING
CESSATION!!!
Reduction of risk
factors, flu vaccine
asthma control
parameters? No daytime
sx (<2x/wk), no limitation
of DALYs/exercise, no
nocturnal sx, no need for
reliever tx (<2x/wk),
nl/near nl lung fx, no
exacerbations
mandatory patient
education and
environmental control;
comorbidity treatment
high level therapy then

step down
Prognosis? Class I (no

limitation w/ exertion),
Class II (mild limitation
but no probs at rest),
Class III (marked
limitation of activity),
Class IV (no physical
activity possible)
DVT prophylaxis
(intermittent sequential
compression device -
adherence issues; anti-
coagulation - LDUH,
LMWH heparin, factor Xa
inhibitors)
infection control practices

at home mandatory!!
(must clean everything)
Prophylactic treatment for

close contacts
RSV prophylaxis
(Synagis) - monthly IM
injections during RSV
season, $$, given to
children who meet certain
criteria (infants born <28
wks gestation, those
born 29-32 wks
gestation during RSV
season, those born 32-
36 wks gestation & risk
factors - daycare,
school age siblings; full
term kids < 2y.o. w/
CLD, CF, CHD)
importance of nutrition &

exercise
breathing techniques to
augment airway
clearance
lung transplantation -
patients feel better but
still have persistent
diseases (complicated by
chronic lung rej &
bronchiolitis obliterans)
23 valent
Polysaccharide vaccine
- T cell independent (no
memory produced, not
fully functional in infants) -
used in older children/
adults with risk factors; all
adults > 65
Protein conjugate
vaccine - T cell
dependent (effective
memory cell response;
better at protecting
against localized dz;
reduces carriage in kids);
13 valent conjugate for
routine infant use and
adults > 50 years old
HIV testing to ALL pts

with TB
Start ARVs ASAP (w/I 2

weeks) for HIV+ pts
SCREEN ALL CLOSE

CONTACTS w/ TST
(requires 2 tests, cross
reacts with BCG vaccine)
or IGRA (does not cross-
react with BCG vaccine;
single step so better for
homeless)
TST cutoff: 5mm= HIV,
immunodef, contacts w/
TB inf indi; 10mm =
immigrants, HCWs, IDU;
15mm = nl
IGRA = IFN-y release
assay (T cells, if exposed
to TB Ags, will release
IFNy if inf)
Inactivated split vaccine

(trivalent) - one A H3N2,
one A H1N1, one B strain
- contraind w/ allergy to
chicken eggs or
Guillian Barre
Live attent Nasal spray

mist (better mucosal
immunity) - contraind in
people w/ reactive aw
dz or pregnancy
vaccination for
everyone >6m
Fluzone Hi dose - new

vaccine for pts > 65 y.o.
(4x dose & greater
efficacy)
Vaccinate HCWs!!
RSV prophylaxis
(Synagis, mAB) - high
risk infants/premies
vaccination w/ oral live

attentuatd virus for
military recruits
Left to right Atrial septal parasternal impulse Hole in wall btwn 2 atria --> volume Down syndrome diastolic septal occluder right heart failure;
shunts defect (severe); fixed splitting of overload on RV; 85% of ASDs occur in the (primum defect) murmur across Afib; pulmonary
(oxygenated S2 (inspiration & fossa ovalis - secundum (loss of tissue = tricuspid; hypertension
blood flows thru expiration); diastolic hole between atria); primum defects are systolic (increased amt of
a defect)- murmur at tricuspid missing the upper cushion between atria; murmur across blood in RH and
acyanotic! (severe) O2 step up in RA oxygenation; RVVO -- pulmonic = PA)
> RV dilation more severe
increased preload on right heart
Ventricular septal high pitched holosystolic membranous defect (high in septum) = Down usually closes if small,
defect murmur (LLSE); displaced hole betwn RV & LV --> blood moves syndrome; spontaneously by asymptomatic; if
apex (if severe); diastolic directly into PA --> LVVO --> LV dilation maternal alcohol age 10-12; if not, large, pt will have
rumble (increased preload in left heart); O2 step intake; clamshell occluder dyspnea, slow
up in RV trauma/MI growth, shunt
(muscular reversal (cyanotic;
muscular defect (lower part of septum; defect) Eisenmengers); HF,
holes in septum) --> blood moves directly IE
into RV --> RVVO (parasternal lift, systolic
murmur over tricuspid area)
Patent ductus nl at birth but closes w/I 48 normally functions to move blood from rubella, CXR: inc cardiac HF, Eisenmengers
arteriosus hours descending aorta to placenta and closes premature birth, silhouette (deoxy blood in left
w/I 2 weeks of birth; after birth, it's a high altitude (displaced apex heart from PA -->
continuous murmur ULSE remaining fistula between aorta (hi press) from LVVO) aorta movement
diastolic rumble (MV) and pulmonary artery (low press) --> causes PA
displaced apex PAVO & LVVO (if severe); O2 step up in Angiogram: blood hypertrophy = inc
PA moves from PA PA press = unoxy
into aorta blood in left heart =
cyanosis)
Patent foramen normally functions to move 90% of blood increased right septal occluder DVTs, MI, &
ovale from RA to LA (shunts away from lungs); heart pressure cryptogenic stroke!!
congenital abnl when it never seals off; (valsalva,
PFO stays open so blood (AND clots) can exercise)
pass through to LA pushes more
blood across
PFO & into LA!
Right to left Tetralogy of Fallot cyanotic skin during congenital abnl from the incomplete CXR: hyperlucent central cyanosis,
shunts crying/feeding closure of intrauterine cnxtn btwn pulm lungs (lack of blood clubbing,
(de-oxy blood artery & aorta --> decreased pulmnary getting to the hypoxemia, growth
flows into 4 parts: blood flow lungs) retardation,
systemic circ)- 1. LARGE VSD polycythemia
cyanotic! 2. PS (RVOT obst) more severe PS = more RVOT obstruction (thrombosis, CVA),
3. RVH PH, paradoxical
4. AO override embolus
Eisenmenger L-->R shunt that eventually reverses to R--
>L (acyanotic --> cyanotic shunt w/
increased pressure)
Vascular/ Bicuspid aortic
Valvular valve
congenital pulmonic stenosis late peaking systolic narrowing of pulmonic valve blocks blood usually part of
disease murmur from leaving RV --> increased afterload on tetralogy of
parasternal lift RV --> RVPO --> RVH fallot
big "a" wave
Noonan's
syndrome
Tachycardia Sinus, atrial, HR > 100bpm increased heart rate shortens diastole,
ventricular reduces LV filling, and reduces coronary
artery filling
Atrial Fibrillation Paroxysmal, no atrial activity so loss of atrial contraction = blood stagnation RA/LA dilation; 3-4% of pts > 70 EKG: fast, irreg Thrombi/ emboli
chronic immediate loss of 20-25% or stasis in left atrium/ left atrium SA node years old fibrillatory waves in formation
of cardiac output, grossly appendage = increased risk for inhibition; middle, NOT P-
irregular, rapid rate (110- thrombi/emboli hyperthyroidism waves
180) PE: pulse deficit,
S1 intensity
variation
Systemic Arterial Primary / asymptomatic BP level that increases risk for CVD and Age (vessels 60 million male gender EKG pre-hypertension? damage to target
Hypertension Essential systolic BP target organ damage (pressure overload stiffen, need Americans (but women R/O secondary Lifestyle mods organs
(idiopathic) makes heart work harder to maintain CO; more pressure catch up after causes (UA, FBS, (less salt, exercise,
PE: normal position apex, increased peripheral resistance causes for blood flow) menopauses), Hct, K/creatinine/ diet); modify risk MI, atherosclerosis,
different contour to apex vascular inelasticity/stiffness; kidneys & Idiopathic African calcium, lipid factors (smoking, aortic dissection,
retina affected; aortic dissection; LVH/ (95%) Americans, profile) obesity, lipidemia, stroke,
pre-hypertension (120- CAD/ HF/ Afib; stroke/ TIA) Coarct (5-7%), increased age, diabetes) retina/kidney
139/80-89) white coat obesity, changes
Stage 1 (140-159/ 90-99) high pressure in aorta = obstruction after effect, environmental hard to treat bc
Stage 2 (>160/>100) aortic valve = LVPO = LVH = increased medications, (stroke belt), systolic BP is less
incidence of MI & atherosclerosis alcohol, salt, hereditary likely to decrease,
PE: BP in BOTH arms, decreased K or kidney or while diastolic BP
check weight/ waist decreased aorta complicance (stiffer aorta) Ca intake, smooth muscle quickly goes down
circumference, fundoscopy, [inc systolic BP = inc pulse wave velocity insulin defects, FH w/ meds (causes
bruits, heart/lung/neuro from loss of elasticity; dec diastolic BP = resistance, syncope)
exams; loss of elasticity = stiffened LV = less sedentary
S4 (LVH causes decreased ventricular relaxation] lifestyle
LV cavity size so atrial kick
needs to push more blood
in), sustained apical
impulse
Secondary (about renal (abnl BUN,

5% of HTN) creatinine, UA),
renovascular,
coarct,
endocrine
(pheochromocyt
oma, Cushing's,
PTH disease),
drugs, obstruct
sleep apnea
Malignant DBP > 120 mm Hg arteriolar effects on brain causes Renal disease,
Hypertension hemorrhage, thrombosis, or ischemia accelerated mild
presents w/ acute HTN
pulmonary edema, renal
failure, cerebral probs
(blurry vision, stroke)
Hypertensive patients present w/ acute Cocaine!
Emergency CVA (SAH, cerebral
infarction), cardiac probs
(ACS, HF, acute pulm
edema), aortic dissection,
retinopathy, pregnancy
Aortic dissection proximal large difference between in patients w/ HTN, the intima is damaged uncontrolled cocaine, EKG nitroprusside 50% of patients w/
dissection blood pressures of each and friable (cystic medial necrosis= HTN (95%), pregnancy CT w/ contrast (lowers BP) & beta proximal AD will die
(proximal to left arm (but same BP in each degenerative changes in media); high bicuspid aortic TEE (intimal flap) blockers (lowers w/I 48h
subclavian a; arm does NOT R/O AD!) pressure/ shear force from LV tears the valve, Marfan's, CXR (wide shear stress) until
ascending aorta) intima and separates it from the media, AMA pregnancy, mediastinum bc EMERGENCY AR, pericardial
cold leg, tearing chest creating a false lumen Turner now have 2 aortic surgery effusion w/
pain through the back & syndrome, lumens --> aortic tamponade
is maximal at onset coarct dilation)
bleeding into
can also present w/ stroke, pericardium, infarct,
MI, tamponade shock
distal dissection can only treat

medically by
lowering BP and
dropping shear
force (beta-
blockers)
Aortic heart is sheared at the ligamentum trauma
transection arteriosum
Abdominal severe back pain, other necrosis of all layers of aorta from MMP Marfan's, 6% of individuals tobacco use, Endovascular progressive
Aortic vascular sx (erectile activation --> profound inflammatory syphilis, > age 70 FH, M>>>F, repair (catheter aneurysm
Aneurysms dysfunction, intermittent response (T cell & monocyte activation) idiopathic, white middle based, stent expansion despite
(AAA) claudication, lower atherosclerosis aged men, material), open tx
peripheral disease) most commonly located below renal (cholesterol + age surgical (graft
arteries (infrarenal) angiotensin II) material) aneurysm >5cm =
most patients are amputees increased risk of
ASYMPTOMATIC! -aorta is exposed to deformation/ strain; (asymmetric future treatments: mortality
increased BP = increased strain; shear reversal of external polymer + (PERFORM
PE: pulsating abdominal stress of blood flow (viscous drag of blood blood flow) doxycycline to SURGERY!!)
mass flow across aorta surface): low and/or provide
oscillatory shear stress= disturbed blood mechanical risk of surgical
flow = increased atherosclerosis = matrix support and inhibit repair? Damage to
dysregulation = accumulation/ adherence MMPs spinal arteries -->
of macrophages = propagation of spinal ischemia/
inflammation into media & adventitia; paralysis
-increased expression of AngII
receptors and VCAM-1 on abdominal
aorta w/ increased disturbed flow (low
or oscillatory shear stress)
Peripheral large difference between disorders of circulatory system to Atherosclerosis 10 million tobacco use, hi Duplex US: risk factor life expectancy
Vascular blood pressures of each extremities, viscera, & head Americans; 5% chol, HTN, increased stenosis modification, reduced 10 years
Disease arm of people > 55 DM, obesity, & velocity; used to aspirin, control of in patients w/ PVD
claudication (stress claudication - blood supply is limited due to have sedentary, check intervention DM/BP/ chol,
ischemia in legs; ischemia so pts have calf pain w/ exercise - claudication male gender, success exercise increased risk for
predictable pain/ -> rest pain --> ulceration --> gangrene --> age death from stroke,
tightness/ weak/ limb loss CT angiography: ACEI, antiplatelet MI
tiredness) anatomic vessel (aspirin,
narrowing clopidogrel) decreased ABI =
Ankle-brachial index (abnl increased risk of
< 0.9 represents surgery: mortality
obstruction) endarterectomy,
bypass, HEMORRHAGE w/
thrombectomy, procedures
ligation; catheter-
directed
Carotid Artery symptomatic? Stroke, TIA atherosclerosis of internal carotid artery: recent MI duplex US:carotid symptomatic: 50-75% stroke -->
Disease (amaurosis fugax - pieces of plaque embolize and enter unstable artery bifurcation treat/ surgery if carotid stenosis!!
transient monocular internal carotid artery --> brain angina stroke involves
blindness, transient uncompensate CT angiograph - <1/2 or 1/3 of BP control impt
weakness) d CHF stenosis of carotid hemisphere; for pre& post-
severe valvular asymptomatic: operative status
dz (aortic operate once (o/w inc risk of
stenosis) stroke risk > stroke & hyper-
surgery risk perfusion syndrome -
poor BBB)
Meds: statins,
plavix, BBs shunt use if
incomplete circle of
surgery: carotid Willis? only if
revascularization + seizure or loss of
patching neuro capabilities
perioperative
Endarterectomy -
higher MI rate
Stenting - higher
stroke rate
Coarctation radial- femoral asynchrony; distal to subclavian; pressure overload --> Turner rib notching (large HTN
leg fatigue LVH syndrome intercostal artery
erodes rib)
apex in nl location but diff
contour
Aortic Acute AR: very little hx: decreased DIASTOLIC PROBLEM problem w/ CXR: enlarged LV ACUTE AR =
regurgitation sudden large exercise tolerance, maybe aortic root that silhouette, surgical
(AR) regurgitant some fatigue, some DOE Abnl regurgitation of blood from aorta to LV pulls leaflets enlarged aortic emergency!! Use
volume on nl LV sx: chronic vasodilation occurring during diastole (retrograde apart (acute- bump (chronic AR vasodilators
= no (warm, diaphoresis), high diastolic flow =loss of isovolumic AD, aortic only); no cardiac (nitroprusside;
compensation output state (head bobbing, relaxation = LVVO >> LVPO) --> higher transection; silhouette & pulm decrease
time for neck pulsations) preload, somewhat higher afterload (hence chronic - edema (acute AR) afterload) while
noncompliant LV acute AR: shock, acute the mildly hypertrophied LV too per Marfan's, Aortic EKG: enlarged LV waiting
= hi LVEDP (LV pulm edema LaPlace's Law) = higher LV contractility aneurysm, (LVVO)
dilation) = early PE: hyperkinetic carotid w/ (SV), compliance, & wall stress syphilis) ECHO: degree of CHRONIC AR =
closure of MV = bifid pulse; displaced apical AR (backwards reduce afterload;
low SV = hi HR impulse (dilated LV), early eccentric hypertrophy (dilation/ LVEDV + problem w/ AV diastolic flow) + surgery if
decrescendo murmur that some hypertrophy) - pressure in LV is leaflets (acute- cause usually symptomatic
masks S2 (longer murmur, much higher if dilation only, so endocarditis, Cath: rapid
Austin- Flint diastolic compensates w/ mild hypertrophy trauma; chronic - decrease in aortic
rumble, wide pulse bicuspid valve, pressure
pressure = more severe) Austin-Flint diastolic rumble -mid-diastole; rheumatic HD,
*acute AR - nl carotid, nl nl MV is wide open w/ diastole but hi LVP AV prolapse)
apex location, diastolic causes MV to close sooner; distinguish
murmur @ URSE, Austin from MS diastolic rumble bc NO OS or
Flint @ apex presystolic accentuation
Aortic stenosis subvalvular narrowing of aortic valve SYSTOLIC PROBLEM but DIASTOLIC increased age, mild AS: NO exercise stress aortic valve inc LAP -> inc
(AS) (HCM, area < 3cm DYSFXN bicuspid valve, >1.5cm test! replacement afterload = inc LV
membranous AS, endothelial disruption (leaflet injury from rheumatic heart mod AS: (percutaneous, dysfxn = LVVO +
narrow LVOT); CO maintained @ rest, atherosclerosis calcification or wear & tear) dz 1.0-1.5cm CXR: nl cardiac surgical) LVPO that
supravalvular; NOT @ exercise --> entry of inflamm cells & lipids --> severe AS: silhouette backtracks into
VALVULAR LVOT obst sx: angina, sclerosis --> stenosis <1.0cm, mid to EKG: LVH NO exercise!! pulm system =
effort syncope (fixed orifice late systolic ECHO: thickened systolic HF!
+ vasodilation), DOE (LV blood flow across AV impeded during murmur ventricle; abnl AV Very limited meds
failure) systole (inc afterload)--> LVPO--> (tri-leaflet & Mortality >90% after
PE: hypokinetic carotid, concentric LVH --> dec compliance of LV a/w coarct in calcified; bicuspid sx develop
hypotension (low PP), nl (inc LVEDP) --> LA hypertrophy & diastolic Turner's & +/- calcifcation)
neck veins, nl location dysfxn syndrome, cath: lower AV aortic regurgitation,
apex, sustained PMI, mitral annular pressure (100/80); Afib, endocarditis,
palpable S4, systolic calcification, hi LV press (200/20- sudden death
ejection murmur,decreased heart block 40)
aortic sound @ URSE, S4 (conduction
@ apex, +/- paradoxical probs), aortic
split diss (w/
bicuspid AV)
Mitral asymptomatic for years SYSTOLIC PROBLEM MV apparatus CXR: acute MR decrease
regurgitation until LV dysfxn parts: (pulm edema), afterload, surgical
(MR) Retrograde systolic flow from LV to LA = hi 1. annulus chronic MR (LV + repair/replacement
Sx: fatigue + weakness LAP + hi LA volume = hi LV volume when (aging, HTN) LA enlargement) for chronic MR
(low CO); acute MR - pulm blood pumped backwards returns to LV 2. LV dilation EKG: LA
edema during diastole = pure LVVO (hi LVEDV, (large distance enlargement + LVH acute MR:
PE: nl carotid (less blood NO afterload) = loss of isovolumic from pap ECHO: MR cause nitroprusside,
but coming out faster so contraction muscles) + severity grade EMERGENCY
feels nl), nl venous system, 3. leaflets (MVP, Cath: acute MR: surgery
enlarged & laterally CHRONIC MR: Compensatory RHD, large v wave =
displaced apex (LVVO = LV mechanisms = eccentric hypertrophy (LV endocarditis, increased PCWP =
dilation), S3, mid-diastolic dilation + some LVH) = higher SAM in HCM) increased LA
rumble, holosystolic compliance (LVEDV w/o LVEDP) = early 4. chordae pressure
murmur @ apex that effect of higher SV and EF; eventually LA tendonae
intensifies w/ handgrip dilates = prevention of hi PAP but (trauma,
decreases CO --> Afib +/- thrombi endocarditis)
Acute MR: pulm edema, 5. papillary
decrescendo systolic ACUTE MR: non-compensated LV so muscles (MI,
murmur, nl apical impulse, regurgitated blood goes all the way back rupture, dilated
S3+S4, parasternal lift towards lungs --> pulm edema CM)
(RV dilation)
Mitral stenosis mild MS area dyspnea (hi LAP = pulm DIASTOLIC PROBLEM Rheumatic Pathology: fused diuretics for HF, afib (chronic hi LAP
(MS) >1.5cm; severe venous HTN); orthopnea/ Heart Disease commissures BB for afib, = LA dilation), right
MS area <1.0cm PND, acute pulmonary obstruction to flow from LA to LV, impeding (remember CXR: LA anticoagulation for heart failure,
edema, fatigue (low CO), LA emptying (hi LAP) and causing impaired CANCER enlargement, afib; thromboemboli,
palpitations (Afib) LV filling (hi LVEDP) mneumonic; interstitial edema, hoarseness if LA
PE: hypotensive, low PP Carditis, Kerly's B lines percutaneous gets so large it
(low CO), hypokinetic symptoms from LA distensibility (small Arthritis, (pulm edema), balloon valvoplasty impedes recurrent
carotid, giant "a" wave thick-walled LA = inceased pressure = Nodules, prominent pulm or valve laryngeal n.
(PAH) or big "cv" wave dilation of LA = increased volume Chorea, arteries replacement
(TR), parasternal heave Erythema EKG: LA more severe if
(hi RV pressure), loud S1 migranatum, enlargement w/ earlier opening snap
at aortic area (prominent Rheumatic possible Afib, RV or longer diastolic
MV closure sound), loud fever) hypertrophy if PAH rumble
P2 +/- PR murmur developed
(Graham-Steele - PAH), Echo: thickened
TR murmur +/- S3 (if mitral leaflets +
severe), OS (after S2, abnl fusion of
tensing of chordae & commisures,
stenotic leaflets w/ MV possible intra-atrial
opening)/ diastolic rumble thrombus
w/ presystolic
accentulation @ apex
Mitral Valve Hx: usually asymptomatic, SYSTOLIC PROLAPSE familial type due 2-4% of women ECHO: posterior 95% are benign so endocarditis,
Prolapse (MVP) atypical chest pain (sticks, to Marfan's displacement of reassurance!! progressive MR,
stabs), palpitations billowing of mitral leaflets into the LA syndrome or one or both mitral fibrin emboli to
during ventricular systole due to CTD (Ehler's- leaflets during If symptomatic, eye/brain (abnl
PE: "click + murmur" (may protrusion of enlarged/thickened valve Danlos) systole use beta-blockers leaflets can collect
be absent)= mid-systolic leaflets (esp the posterior leaflet) OR microthrombi),
click (leaflets popping back) thin/elongated chordae tendonae that if severe MR arrythmias,
DYNAMIC auscultations: fail to keep leaflets in apposition when (uncommon), valve spontaneous
pregnancy, handgrip, cavity is reduced during ejection repair preferred chordae tear
squatting increase LV over replacement
cavity = later/shorter LV needs to be large for chordae to match Men over age 45
murmur; Valsalva, (since elongated in MVP); therefore, have increased
standing = decrease LV increased LV cavity (maneuvers like risk for thickened
cavity = earlier/longer squatting, handgrip) has less mitral leaflets & MR
murmur; pectus regurgitation
excavatum
Tricuspid PE: "cv" regurgitant wave, acute - infective

Regurgitation parasternal heave (RV endocarditis;
dilation), holosystolic chronic - RHD,
murmur that increases w/ carcinoid
inspiration @ tricuspid syndrome
area; S3 or mid-diastolic
rumble if severe pulmonary
hypertension
from MS or RHF
Tricuspid PE: giant "a" wave, RHD, carcinoid extremely rare!

Stenosis diastolic rumble that syndrome, RA
increases w/ inspiration at myxoma
tricuspid area, OS at
tricuspid area
Pulmonic PE: giant "a" wave, congenital

Stenosis parasternal lift, soft P2/ES (Tetralogy of
that increases with Fallot), carcinoid
inspiration, systolic murmur syndrome
@ pulmonic listening area
Pulmonary PE: hi pitched diastolic severe PAH,

Regurgitation blowing murmur congenital
Left ventricular sustained apical impulse increased pressure overload on LV causes HTN Diastolic
hypertrophy normal placed PMI increased wall thickness and decreased LV AS dysfunction (thick
palpable S2 (presystolic cavity HOCM ventricle walls =
component) coarctation decreased
Pregnancy, compliance = small
exercise (nl) cavity = decreased
filling during
diastole!)
myocardial ischemia
(decreased
coronary blood flow)
systolic dysfunction
(late! Due to
narrowed pulse
pressure)
Peripartum No pre-existing heart postpartum 1/3000-4000 AMA, ECHO standard heart highest mortality in
cardio-myopathy disease; presentation thyroiditis pregnancies multiparity, CXR failure mgmt; anti- 1st 3 months
(PPCM) during last month or multiple thyroid panel coagulation until
postpartum gestations, pregnancy ends LV thrombi (1/8 risk)
obesity, HTN/ --> stroke
cough, dyspnea, fatigue pre-eclampsia,
PE: JVD, tachycardia, tocolysis w/ b-
S3/S4, +/- edema agonists
Acute Serous (scant Pain is worsened w/ inflammation has 3 outcomes: ATRIUM EKG: diffuse ST post-MI pericarditis
Pericarditis cells; early acute position (lying down)/ 1. local vasodilation & transudation of (A = AIDS/ Auto- elevation that (tx w/ hi dose
inflammatory expiration/ swallowing serous fluid immune dz, T = disappear as aspirin)
pericarditis) 2. increased vascular permeability (protein tumor/ trauma/ patient recovers;
Fibrinous pericardial rub + soft spills into pericardial fluid) TB; R = diffuse T abnl that NSAIDS,
(plasma proteins heart sounds 3. Leukocyte exudation (neutrophils, Radiation/ persist for some colchicine if
+ thickened/ mononuclear cells) rheumatic fever; time chronic pericarditis
fused visceral & pain relieved by leaning I = idiopathic/ ECHO: +/-
parietal forward post-MI pericarditis: inf/ infarct; U = pericardial effusion
pericardium;TB/ 1. early onset (<1wk post-MI) - inflamm uremia from
chronic inflamm) from infarction spreads/extends into renal failure; M
Purulent pericardium = meds)
(uncommon, 2. Dressler syndrome (>2wks post-MI) -
bacterial inf) antigens from dying myocytes = activated
Hemorrhagic autoimmune reseponse = inflammation of
(bloody pericardium
pericardial
inflamm due to
TB, aortic
dissection, tumor,
trauma, uremia)
Pericardial Symptomatic - accumulate Silent or symptomatic? idiopathic, Fluid analysis to treat underlying
effusion lots of fluid quickly under hi 1. volume of fluid malignancies, R/O malignancy disorder (dialysis
press (chest trauma); 2. rate of fluid accumulation radiation, viral for uremia)
asymptomatic - accumulate 3. compliance of pericardium causes, TB TTE: pericardial
fluid slowly so that collections Observe
pericardium stretches w/o Increased capillary permeability (quantifies volume asymptomatic
marked increase in (hypothyroidism), increased capillary of fluid, determines effusions
pressure hydrostatic pressure (HF; lymphatics are if ventricular filling
unable to handle extra fluid), or decreased is impaired, & pericardiocentesis
muffled heart sounds, plasma oncotic pressure (nephrotic guides pericardio- for therapeutic
reduced intensity friction syndrome - low blood proteins) = abnormal centesis) drainage &
rub, Ewart sign (dullness to fluid in the pericardium = increased analysis
percussion over posterior pressure in a non-distensible sac --> EKG: electrical
left lung by scapula) enormous compression force on the heart alternans (QRS pericardial window
(cardiac tamponade) complex height procedure
varies from beat to
beat)
Cardiac CC: breathlessness pericardial fluid under acute increased any cause of TTE: smaller, Pericardio- life-threatening
tamponade (decreased CO & max pressure compresses the heart continously acute compressed, & centesis; emergency!! (if
increased EDPs = through cardiac cycle, limiting ventricular pericarditis can collapsed RV pericardial window worsens, there is no
increased press in alveoli); filling --> increased venous pressure to progress to during diastole procedure filling during diastole
low output state (shock- compensate for decreased filling --> tamponade (removal of = zero CO =
like), hypotension, equalization of diastolic pressures to (ATRIUM); catheterization = pericardium pulseless arrest)
tachycardia intrapericardial pressure (IPP=LVEDP= acute gold standard allowing fluid to
LAP = PCWP=PAP=RVEDP=RAP) hemorrhage drain freely into
BECK'S TRIAD: (acute mediastinum *
Hypotension, increased ascending aortic absorbed by
JVP (elevated venous dissection, blunt lymphatics;
pressure; deep "x", flat trauma, LV simultaneous bx)
"y" - decreased filling of rupture)
ventricles), muffled heart
sounds
pulsus paradoxus
(decreased systolic BP of
>10 w/ inspiration)
Constrictive deep Y descent; physiologic abnormalities during diastole; chronic changes Pathology: pericardial can have effusive-
pericarditis pressures are equalized rigid/ scarred pericardium prevents from pericardium stripping surgery constrictive
& elevated (LVEDP = normal mid-late filling of cardiac inflammation; becomes pericarditis
PCWP = PAP= RVEDP = chambers (early filling only!) --> filling is idiopathic immovable shell w/ (tamponade
RAP) arrested --> increased systemic venous pericarditis (post- fused/ thick layers physiology -->
perssure & signs of RHF; impaired filling of viral); radiation, from chronic effusion drainage --
cirrhotic appearance LV = reduced SV & CO = hypotension TB, RA, inflamm > constriction
(ankle/leg edema, ascites, bacterial inf physiology)
hepatomegaly); CXR: calcified
tachycardia, hypotension, pericardium
decreased pulse pressure,
inc CVP, Kussmaul (inc Catheterization:
JVP w/ inspiration), elevation &
difficult to find PMI, early equalization of
to mid diastole knock pressures, dip &
plateau in early
diastole, y descent
in RA, discordance
in RV & LV
pressures w.
inspiration
Arteriosclerosis Medial calcific affects arteries of lower calcification of the tunica media, the intermittent age > 40-50
sclerosis extremities and genitalia; muscular coat of the artery episodes of
does NOT produce HTN?
ischemia
Arteriolo-sclerosis disorders of small thickening of the arteriole wall that results marker of HTN;
arterioles, particularly in the in some degree of ischemia common in
kidney diabetes
Atherosclerosis vulnerable, hi risk plaques? accumulation of lipid, inflammatory cells, & fatty streaks localized flow pathology: gross myocardial
Large extracellular lipid ECM (collagen) in the arterial intima (large seen in 50% of abnl, increased large arteries ischemia,
content, thin fibrous cap, & muscular arteries at bends, branches) teens and >85% LDL, HTN, (yellow spots = claudication; sites
high content of of people over smoking, foam cells; fatty for thrombus
inflammatory cells localized flow abnl --> turbulent flow in age 20 diabetes (all streaks; friable development (mural
(lymph/monocytes) arterial system --> endothelial dysfxn--> increase ROS cracks/ fissures) thrombus in aorta
increased ROS production, decreased NO and decrease common in HTN,
production --> increased permeability of NO) histology: clear smoking men);
Stable plaque? Smaller lipid lipids & inflamm cells,expression of VCAM cells in intima (fatty abdominal aortic
core, larger fibrous cellular Monocytes --> macrophages in the tissue age streaks - early aneurysm
matrix, less inflammation by M-CSF; macrophages have scavenger male gender lesions), bubbly
receptors that internalize LDL --> foam foam cells; if top of plaque
renal arteries often spared! cells, LDL is oxidized to cholesterol & histiocyte giant ruptures, lipids are
cholesteryl esters; foam cells die, cells surround released into
releasing cytokines and leaving cholesterol circulation and
cholesterol crystals, which stimulate crystals; new activate
collagen & plaque formation; cytokines matrix being thrombosis -->
are fibrogenic so increases ECM deposited; ischemia, MI
secretion (collagen) --> plaque muscular arteries -
formation fibrous cap & lipid other complications
pool (stable v. if embolization of
unstable plaques) plaque material
Chronic Stable Stable Angina chest/ jaw discomfort reduced perfusion from chronic stenosis; AS high LDL, low stress test: ST Lifestyle MI @ sites of
Coronary Artery pectoris provoked by exercise that ischemia results from increased oxygen HDL, FH, depression modification, PCI, unremarkable
Disease lasts 4-5mins; stable sx & demand (exertion) but disappears w/ rest waist (ischemia) & area CABG, medical lesions
predictable onset; no sx in a predictable fashion circumference of ischemia therapy
at rest (W>35; M>40), (suggests anatomic single occlusion =
PE: during angina, you >75% stenosis usually but no plaque smoking, HTN, stenosis) PCI if intolerable diffuse disease
might hear a new S4, S3, disruption or thrombus formation prior known angina despite
or paradoxically split S2; CAD Resting EKG maximal med tx & CABG decreases
MR; abnl PMI (if LV Unlikely to rupture: thick fibrous cap, less CT angiography anatomy that risk for rpt
dysfxn); elevated JVP (if inflammatory cells, lots SMCs, intact Cardiac cath if + doesn't require interventions
RV dysfxn) endothelium stress test CABG; older pts-
asymptomatic often in hi risk for CABG no diff btwn PCI &
women & diabetics; histology: med w/ # MIs;
infarct risk does NOT increased CABG if left main no diff btwn PCI &
correlate w/ amt of proliferative SMCs coronary narrowing CABG for pt
occlusion!; and fibrous tissue; (>50%) or 3 vessel survival
reduced blood flow does does not look CAD
not cause cells to die like vulnerable bc lipid MI, CHF,
in MI! --> instead, core is far from Meds: increase life arrythmias, valve
dysfunctional myocytes lumen & thick (BBs, statins, dysfxn, LV
fibrous cap aspirin); reduce sx thrombus,
by dec O2 demand myocardial rupture
(BBs, CCBs,
Prinzmetal angina uncommon, episodic, coronary artery vasospasm, not much nitrates)
occurs at rest atherosclerosis & no thrombus/plaque
formation
Unstable angina progressively worse sx & frequent plaque rupture with thrombus variable
pectoris pain more formation; partially occlusive thrombus stenosis
frequent/intense w/ less
exertion starts as lumen compression w/ little lipid
core but grows with lipid deposit increasing
persistent, unrelenting pain -->thin fibrous cap-->subject to rupture-->
for several hours (due to thrombus formation--> vulnerable plaque
rupture plaque) contributing to MI, sudden death
Rupture? thin fibrous cap, increased

inflammatory cells, fewer SMCs, large lipid
deposits, eroded endothelium
Ischemic Heart (General) imbalance of O2 supply and demand atherosclerotic 500,000 DM, HTN,
disease (also CAD (90%), deaths/yr in U.S; smoking,
includes angina heart perfused by coronary arteries coronary artery 250,000 die lipidemia, age
but see above) from outside --> inside vasospasm before reaching (although 10%
(cocaine), hospital of MI in
coronary artery age<40)
emboli;
exacerbations -
myocardial
hypertrophy,
shock, anemia,
tachycardia
Transmural MI entire thickness of variabe stenosis but unstable plaque disruption of most common MI 6am-11am EKG: deep Q prognosis depends 30% overall
ventricular wall affected by with disruption & consequent occlusive endothelium (catecholamine waves; ST abnl on infarct size, mortality- 1st year
the MI thrombus forming on the plaque --> s are highest (STEMI, NSTEMI) site, extent; quality
myocardial wall damage athero- and platelets of LV fxn, extent of RV infarction
chest pain, weak rapid sclerosis stickiest!) labs: elevated CK- vascular disease, infarct extension -
pulse, dyspnea, 1. disruption of plaque mb & troponin I/ T ability to perfuse new necrosis next
diaphoresis 2. fissure/cracking of plaque exposes non-atheroscl viable myocardium to the infarct region;
thrombogenic areas (collagen, vWF, FN) causes: 0-12h no changes; infarct expansion -
3. platelets adhere, becoming activated arrythmia, 24h (dark mottling; first medical dilation of infarct
and aggregated coronary art coag necrosis - contact time to region; contractile
4. coagulation cascade is activated vasospasm, loss of nuclei) balloon! dysfxn, arrythmias,
(fibronogen --> fibrin via thrombin) coronary art 1-3d (mottling w/ pericarditis,
5. occlusive thrombus forms emboli, anemia, yellow center; myocardial rupture
6. downstream ischemia --> depletion of hypotension, neutrophils) (highest risk 4-7
ATP --> loss of contractility --> irreversible CABG, coronary 3-10d (red border, days post-MI; most
cell injury (20-40min; not all cells affected stent thrombosis yellow center/ often at vent free
equally - epicenter cells > peripheral cells) - neutrophils & wall, also vent
-> microvascular injury (>1h) macrophages) septum - L-R shunt-
14d (red-gray/ & papillary muscle -
NSTEMI: partial occlusion granulation tissue) acute MR), vent
STEMI: complete occlusion >3m (scar) aneurysm, mural
thrombus, pap
muscle dysfxn, late
Subendocardial most susceptible to variable stenosis, variable plaque EKG: do not CHF
MI ischemia bc farthest away disruption causes partially occlusive always elicit
thrombus that damages the changes; non-Q-
subendocardium but not the areas closest wave MI
to blood supply
ischemic progressive heart failure ischemic myocardial damage from elderly patients
cardiomyopathy due to ischemic myocardial coronary artery disease (atherosclerosis)
damage or previous MI --> enlarged LV
(hypertrophic, dilated) --> lack of perfusion -
-> heart remodeling
Sudden death unexpected death from severe stenosis with frequent plaque lethal
cardiac cause early after or disruption and large occlusive thrombus --> arrhythmia; non-
w/o onset of sx fibrotic scarred myocardium that cannot atheroscl
conduct electricity efficiently causes
(congenital abnl,
AS, MVP,
myocarditis,
dilated CM,
hypertrophic
CM, PH,
conduction abnl,
isolated
hypertrophy)
Dyslipidemia (General) secondary DIET, genetic increased LDL:HDL

causes? errors of predicts higher risk
Diabetes, metabolism, for CV event
hypothyroidism, metabolic
liver dz, kidney causes (insulin
dz, progestins/ resistance -
steroid drugs pre diabetes;
hypothyroidism
hormones),
drug side
effects,
smoking
Familial Hyper- high fasting triglyceride defect in LPL or its cofactor apoC-II so autosomal 1 in 1 million kids low triglyceride diet
chylomicronemia levels and low LDL levels cannot break down chylomicrons (>90% of recessive
TGs) mutation in LPL nutrition referral
pediatric presentation w/ gene or ApoC-II
chronic abdominal pain gene
(pancreatitis),
hepatomegaly, xanthomas
Familial Hyper- abnl high LDL defects in LDLR so LDL is not taken up by autosomal 1 in 500 homozygous no specific aggressive + early increased risk for
cholesterolemia (heterozygote LDL > 200; the liver; instead, LDL remains exceedingly dominant FH patients mutation testing tx (combo therapy CV event even at
homozygotes LDL > 500) high in the bloodstream; more LDL in mutation in have more but cascade of statin + young age
circulation = more LDL that is able to pass LDLR severe risk & genetic testing for cholesterol
cutaneous manifestations through endothelium into the intimal layer dz (little or no family risk absorption
(xanthelasma, corneal of arterial wall --> atherosclerosis LDLR) assessment impt inhibitor); niacin;
arcus, thickened Achille's) LDL apheresis
premature vascular dz
Vasculitis (General) can affect the skin inflammatory damage to the blood vessels, secondary autoimmune dz Histology:
(purpuric, non-blanching resulting in hemorrhage (extravasation of causes (meds, (SLE, RA, fibrinoid necrosis
papules/macules), lung RBCs) & possibly ischemia if damage to infections) dermato- &
(hemoptysis), GI (bloody larger vessels myositis), leukocytoclastic
stools, melena), renal meds/toxins, vasculitis
(hematuria) skin is the most commonly affected site infections (neutrophils!)
Cutaneous purpuric lesions, non- lower extremity vasculitis from blood &
vasculitis blanching, ulceration/ extravasated erythrocytes that infiltrated
necrosis seen sometimes the tissue
(vascular damage &
ischemia)
lower legs = primary site
Giant cell Large vessel vasculitis not well understood elderly patients histology (hi false high dose
(temporal) (>60 y.o.), positive rate): NO corticosteroids for
arteritis scalp pain/tenderness females 3:1 NEUTROPHILS, months (reduce
distributed along mostly inflammation and
temporal artery, visual histiocytes & prevent
disturbances/blindness (if lymphocytes subsequent
opthalmic a involved), granulomas, sequelae)
polymyalgia rheumatica destruction of
in upper neck/shoulders internal elastic
lamina &
"hunched over elderly narrowing of
person w/ lateral vascular lumen,
headache" eosinophilic line
Elevated ESR/CRP
Takayasu arteritis Large vessel vasculitis aorta & major branches become inflamed more common in histology: NO unpredictable
(aorta & subclavian a) w/ granulomatous infiltrates so arteries do Asia, patients < NEUTROPHILS, course: rapid
not distend or carry pulse wave 40 y.o., mostly progression +
Pulseless disease, low Females 7:1 histiocytes & quiescent stages
blood pressure, ocular lymphocytes
disturbances, carotid granulomas
tenderness (cannot be
distinguished from
temporal arteritis
histologically)
Elevated ESR
polyarteritis medium vessel vasculitis not well understood HepB elevated BUN or
nodosa (PAN) creatinine, HepB
systemic sx (fever, weight antigen, ANCA
loss, HTN, abdominal pain/ negative
melena, neuropathy,
myalgias, purpuric skin histology:
lesions), NO lung necrotizing
involvement vasculitis of
medium sized
vessels
Kawasaki disease medium vessel vasculitis not well understood may be a/w pediatric anti-endothelial IV IgG and approximately 50%
strep/ staph presentation antibodies aspirin to reduce of cases will have
multisystemic sx infection inflammation and CV involvement
(polymorphous skin ANCA negative avoid sequelae
eruption, erythema of lifelong risk for
conjunctiva/oral coronary artery
mucosa/tongue aneurysm
"strawberry tongue",
cervical MI in kids!!
lymphadenopathy, edema
in hands/feet,
desquamation of
fingertips/toes)
CV INVOLVEMENT!
(myocarditis --> CHF,
coronary vasculitis -->
ischemic dz/infarct,
aneurysms)
Wegener's small vessel vasculitis not well understood middle aged; pathology: cavitary
granulomatosis males 3:2 lesion in lung
ELK: Ear/nose/throat
(URI, saddle nose UA: hematuria,
deformity), Lung (cough, red cell cast in
hemoptysis, cavitary urine
necrotizing lesions),
Kidney involvement c-ANCA positive
(hematuria, proteinuria) (proteinase-3)
other multisystemic histology:

manifestations? vasculitis w/
Cutaneous, middle ear, necrotizing
peripheral nerves, CNS, granulomatous
ocular, oral cavity (midline inflammation
destructive lesions)
Allergic small vessel vasculitis not well understood Young adults; history of peripheral
granulomatosis M>F asthma or eosinophilia,
(Churg-Strauss) Multisystemic disorder allergic elevated ESR
(fever, cardiac rhinitis
involvement - arrythmia, p-ANCA positive
ventricular insufficiency,
coronary arteritis, histology: vasculitis
peri/myocarditis), w/ necrotizing
pulmonary infiltrates (non- granulomatous
cavitating), renal inflammation &
glomerulonephritis) abundant
eosinophils,
involves dermis &
subcutis
(cutaneous only
involves superficial
layers)
Henoch- small vessel vasculitis not well understood possibly children <10 Immunoflourescenc
Schonlein infection or drug y.o., M>F e: IgA deposition
purpura Multisystemic disorder related in vessel walls
(cutaneous purpura w/
leukocytoclastic vasculitis, ANCA negative
abdominal pain - bloody
stools, melena; arthalgias, UA: hematuria,
renal glomerulonephritis) proteinuria
histology:
leukocytoclastic
vasculitis of
superficial skin (not
specific)
Microscopic small vessel vasculitis not well understood possibly Adults Elevated ESR,
polyangitis infection related anemia, renal
diagnosis of exclusion (strep), drug failure
(overlaps w/ PAN) related?
UA: hematuria,
Multisystemic vasculitis proteinuria
(cutaneous purpura,
abdominal pain, p-ANCA or c-
pulmonary involvement!!! ANCA positive
- hemoptysis,
intrapulmonary
hemorrhage, renal
glomerulonephritis,
myalgias)
pulmonary involvement
distinguishes from PAN
Cocaine- ear vasculitis COCAINE elevated serologies

associated contaminant common in cocaine
vasculitis (levamisole) abuse (anti-
histones, c-ANCA
& p-ANCA, dsDNA)
- human neutrophil
elastase cross
reacts w/ ANCA
impt to do urine
drug screen!!
Histology:
leukocytoclastic
vasculitis, focal
thrombosis
Heart failure (General) dyspnea, orthopnea, acute HF: no compensatory changes from Ischemic 5 million CXR: cardiomegaly development of
PND, PM dry cough; body yet so cardiac output =/= peripheral cardio- Americans have if chronic HF kidney failure (nl
3 characteristic stomach/ liver tissue metabolic demand; elevated SVR myopathy CHF, 1 million (cardiac creatinine = 1) -
sx: congestion (early satiety, (vasoconstriction; "cold") & LVEDP (inc (atherosclerosis! hospitalizations/ remodeling) most impt
1. impaired CO anorexia, n/v), edema afterload; decreased filling of LV; PCWP > !) yr negative
(weak pump) (ascites, pulm edema, 18); expanded plasma volume ("wet"); Elevated BNP (nl prognostic factor!
2. venous periph edema); cold "noisy" - no lymphatic compensation=fluid hi CO <100)
congestion extremities (inc leaks into alveoli (PE, rales, increased RR, conditions Afib (atria become
3. overall fluid catecholamines= dyspnea) ("warm, wet"): inflamed/scarred/
retention vasoconstriction = low CO); chronic HF: "silent" - compensatory hyperthyroidism, dilated) - use
tachycardia/pneic mech (inc colloid pressure = enhanced anemia, AV cardioversion!
def: inability of lymphatics so no rales! retain more salt = fistula, Paget's,
heart to pump PE: JVD (inc cardiac filling renal failure) = maintained CO, SV but inc Beri-Beri
blood forward to pressures & volume); rales LVEDP; <3remodeling!
meet metabolic (basilar; acute CHF); Right sided HF: inc RA pressure (>10 mm low CO
oxygenation pleural effusions (chronic Hg); a/w sleep apnea, COPD, cor conditions
demand of CHF); distended abdomen/ pulmonale, PE, severe pulmonary ("cold, wet"):
tissues while hepatomegaly; peripheral hypertension, left HF valvular dz,
maintaining nl edema; S3, displaced Left sided HF: inc LVEDP due to intrinsic dilated CMP,
filling pressures PMI, MR (if severe LH dz; sx of lung congestion (not so much HTN, CAD
backwards! dilation) peripheral) & low CO (cold, clammy
extemities, low urine output)
Systolic heart reduced EF (LVEF < 40- impaired contractility, volume overload CAD, HTN, triad of meds
failure 50%) = impaired (increased sodium = inc total body water), dilated CMP, (carvedilol - BB;
contractility w/ & pulm congestion valvular dysfxn lisinopril,
progressive dilation & spironolactone)
eccentric remodeling thin walled,
dilated ventricle decrease afterload
Almost all pts w/ systolic = improved SV =
dysfxn have comcomitant less ischemia; =
diastolic dysfxn reduced preload =
(impaired relaxation) reduced
remodeling
Diastolic heart impaired relaxation = diastolic dysfxn (abnl distensibility, hypertensive increased requires clinical no treatment, just presence of
failure elevated LVEDP; nl LV relaxation, or filling of LV) + CMP, HOCM, prevalence w/ evidence of symptom relief symptoms = worse
volume, concentric signs/symptoms of HF amyloidosis age impaired RV prognosis
remodeling, EF > 50% relaxation or LV be careful w/
Abnormalites in LV diastolic dysfxn? hypertrophied, passive stiffness: diuretics (pts have high comorbidity
can be just as symptomatic slowed/delayed/incomplete relaxation; enlarged, small/ stiff LVs so burden (usually
as sHF if patients have decreased early diastolic suction/recoil; thickened elevated BNP diuretics can elderly patients w/
mod-severe diastolic dysfxn increased LA pressure during early filling; cardiac CXR: pulm edema cause LV dHF)
shift of filling from early to late diastole; myocytes ECHO: R/O other underfilling -->
impaired rate/extent of LV filling; inability to causes for hypotension, majority of dHF
augment relaxation w/ exercise; increased impaired LV filling; syncope, falls!) patients die from
LVEDP, LAEDP, PVEDP at rest/exercise shows LA non-cardiac causes
enlargement, nl EF control BP,
w/ diastolic dysfxn, filling is impaired bc ventricular rate &
ventricle doesn't relax; therefore, early heart cath = gold rhythm
rapid filling phase is delayed and need std but invasive;
compensation by atrial contraction use ECHO
(atrial kick) instead
Heart failure w/ 60% of HF patients have asymptomatic diastolic dysfunction increased age elderly women
normal EF nl EF (ventricular filling) associated w/ restrictive (age has a w/ HTN, DM,
(HFnEF) CM, HCM, infiltrative CM greater impact or both, CAD,
on ventricular Afib
diastolic dysfxn = abnl diastolic filling than on
distensibility, relaxation, or filling of LV EF or systolic
fxn)
Cardio- (General) any disease of the heart Acquired (CAD,
myopathies muscle, leading to HTN, valvular,
decreased fxn viral, alcohol,
chemo,
peripartum,
infiltrative);
genetic
(hypertrophic,
dilated,
arrythymogenic,
restrictive, non-
compaction)
Hypertensive dilated, thick heart on african

cardiomyopathy ECHO americans
increased diastolic
pressure (>85 or 90)
Familial dilated dilated LV (nl 4-5cm) autosomal dominant mutation in younger age (20- multiple family genetic testing CHF tx (BB, ACEI, CHF, arrhythmias
cardiomyopathy causes poor systolic fxn myosin heavy chain or troponin T 30s) members diuretics) (ventricular
(can barely contract) affected tachycardia)
ICD (internal
PE: displaced PMI, S3 cardiac defibrillator
to prevent SCD)
LVAD or transplant
if unresponsive to
meds
Arrhythmogenic autosomal dominant mutation in 1 per 1000-2500 genetic testing SCD

Right Ventricle desmoplakin, plakophilin-2, desmoglein-2 ECHO: dilated RV
Cardiomyopathy clustering of EKG: epsilon Ventricular
(ARVC) dilated and poorly fxning RV; fibro-fatty cases in Veneto waves in ST tachycardia
replacement of myocardium region of Italy segment (delayed
depolarization)
aneurysms of RV
wall on cardiac
MRI, angiogram
pathology: buildup
of scar tissue;
white and yellow
fibrosis (RV muscle
replaced w/ fibrotic
tissue)
Restrictive sx of CHF (dyspnea, non-dilated, non-hypertrophied LV w/ idiopathic ECHO: huge, thin

cardiomyopathy volume overload, edema) advanced diastolic dysfxn (thin walled, infiltrative dz dilated atria w/
stiff ventricle that can't relax during (amyloid, normal appearing
very difficult to diastole) sarcoid) ventricles and
distinguish from prior radiation normal systolic
pericardial constriction stiffness in ventricle causes chronically function
elevated atrial pressures (dilated atria)
Left Ventricle decreased LV function, Embryological problem where the LV wall variable increased risk for
Noncompaction increased LV dilation is not compacted properly so has genetics, LV dilation, CHF,
appearance of crypts, recesses, craters sporadic thromboembolic
(similar to RV) rather than being smooth events
(like normal LV)
sarcomeric mutations but also other

nonsarcomeric mutations implicated
Hypertrophic most common of all autosomal dominant sarcomeric LVOT 1 in 500 adults family history histology:collagen, HR,(-) inotropy most common
Cardiomyopathy genetic cardiac dz mutation (B-myosin heavy chain, myosin obstruction of HCM/SCD myocyte disarray (BB, CCBs,diso- cause of SCD in
binding protein C, troponin T) that causes EKG: pyramide) athletes!
LV thickening (appears LV hypertrophy in absence of another SAM associatd Brockenbrough's (especially if
later in life) identifiable cause MR (systolic sign (PVC --> surgical myectomy- intramural scarring --
anterior motion press gradient --> remove part of > Vtach)
heterogenous Increased LV pressure (higher than aortic of MV) aortic press drop), septum= widen MV-
hypertrophy pressure) during systole sucks MV in tall QRS, invert T septum gap; Increased collagen
(interventricular septum; obstructing the LVOT Diastolic ECHO: thick LV alcohol septal = increased
septal base, ventricle, squatting--> standing makes murmur dysfunction wall w/ nl systolic ablation- induce MI arrhythmia risk
apex) worse (decreased preload = less venous fxn; SAM of MV; in basal septum=
Sx: dyspnea, angina, return = LV cavity shrinks = smaller aortic midsystolic fibrosis/shrinking)
syncope (drop in BP, VT, distance btwn MV and septum = worsened notching (late
SAM) obstruction); valsalva increases ejection from obst) ICD: indicated if
PE: holosystolic murmur intrathoracic pressure = decreased preload Doppler: turbulent aborted SCD or
(MR;from obst of MV) that = smaller LV cavity = worse obstruction flow (MV sustained VT; 2+
worsens w/ squatting--> bisfeirens pulse (early rapid ejection of obstruction in risk factors (FH,
standing, valsava, blood from ventricle followed by MV LVOT), possible unexplained
handgrip; S4 (atrial kick obstruction; LV overcomes obst so late MR (MV pulled syncope, wall
against stiff ventricle); ejection of blood) open in systole) thickness >30mm,
bisferiens pulse Pathology: abnl BP drop,
calloused IVS from nonsustained VT
MV hitting
Non-neoplastic Thrombi most common masses in nonbacterial thrombotic endocarditis - fibrin- MI, DVT hyper-
Cardiac masses heart! composed thrombi on valves that do NOT coagulable
destroy the normal anatomic structure of states; Afib (or
valve other rhythm
disorders)
post-MI thrombus, paradoxical embolus
(thrombus from a DVT enters systemic
circulation via PFO)
Tuberculoma normally TB will affect the
pericardium but there is
potential for it to appear as
a myocardial lesion
Infective
endocarditis
Primary cardiac (General) diagnosis often dependent anatomic site? Mostly atria (due to very rare delayed dx bc mimic
tumors on anatomic location myxomas - most common cardiac tumor) many dz that impair
(pericardium, myocardium, cardiac fxn
endocardium) majority are benign (due to myxomas)
clinical manifestations: most common pediatric cardiac tumor?

impaired cardiac fxn, fever, Rhabdomyoma
inc ESR, emboli
most common malignant cardiac tumor?
Angiosarcoma
Cardiac myxomas most common primary cytokine 10% are macroscopic: embolus (stroke, GI
tumor associated (IL- inherited pedunculated infarct, distal
6) (multiple (move w/ position, toe/finger infarct)
found most commonly in myxomas - pressure) or
LA think Carney sessile (no
complex/ movement), can be
possible MV dysfunction; NAME/ LAMB - bilateral/ multiple
usually solitary (if multiple, see below) (more likely to be
could be syndromic syndromic), +/-
association); systemic calcifications
manifestations (fever,
malaise, ESR) microscopic:
myxoid (gelatinous)
matrix, variable
cellularity, mucin-
secreting cells
Carney/LAMB/NAME autosomal dominant mutation that results genetic FH differentiate from

genetic syndromes w/ in cardiac myxomas(multiples), other lentigenes-
myxomas cutaneous myxomas (multiple papules causing
around eyes), lentigenes (freckle like syndromes:
lesions - different from sun induced bc LEOPARD - no
occur also in axilla, etc), melanotic cardiac myxomas
schwannomas (neural tumors), blue nevi, w/ this syndrome:
endocrine d/o (Cushings, etc), breast & lentigenes, EKG
testicular disorders abnormalities,
ocular
hypertelorism,
pulmonary
stenosis, gonadal
hypoplasia,
retarded
growth,deafness
cardiac most common pediatric can occur spontaneously but often caused tuberous macroscopic:
rhabdomyomas tumors by tuberous sclerosis sclerosis circumscribed
ventricular mass
involves the ventricles; (not encapsulated),
usually multiple; clinical white-yellow &
features depend on size of waxy appearing
tumor; spontaneous
remission often; a/w
tuberous sclerosis
(autosomal dom
neurocutaneous syndrome
w/ CNS tumors/seizures,
rhabdomyomas of heart,
mental impairment,
cutaneous lesoins, renal
tmors)
Primary cardiac malignant! vague sx mean age Macroscopic: resection is not most of the time,
sarcomas (dyspnea, chest pain, around 40 y.o., angiosarcoma curative the sarcoma is
tamponade, palpitations), M=F; rare to see (violaceous/ confined to the
1. angiosarcoma usually in atria childhood reddish purple heart bc low
2. pleomorphic sarcomas color - blood survival (pts dont
undifferentiated Angiosarcoma = most forming tumor) survive long enough
sarcoma common cardiac sarcoma; for metastasis)
3. rhabdo- infiltrative mass in RA , microscopic:
myosarcoma early mets (usually lungs); rhabdo- angiosarcomas
3m survival myosarcoma has have early
pleomorphic undiff rhabdomyoblast metstasis (lungs,
sarcoma: = cell origin is (eccentric nuclei + vertebrae, liver
unknown, occurs in atrium eosinophilic brain)
(commonly posterior cytoplasm)
wall), low survival mean survival 7m-
Rhabdomyosarcoma = 2y
atrial & ventricular lesions,
mimics atrial myxoma,
mean ages affected 20-
30s; survival 1.5-6m
Metastatic tumors clinically uncommon, Lymphatic spread: epithelial tumors, highly

to heart usually incidental finding melanoma metastatic
on autopsy cancers?
hematogenous spread: sarcomas, Melanoma
usually involve melanoma, renal cell carcinoma
pericardium intermediate
direct extension: mediastinal tumors metastatic
sx: dyspnea, pleural/ cancers?
pericardial effusions intracavitary extension to IVC or RA Breast & lung
(breast/ lung ca), (direct extension): hepatocellular cancers, RCC,
arrhythmias, outflow obst, carcinoma, renal cell carcinoma, adrenal leukemia/
ischemic disease (tumor tumors, uterine tumors lymphoma,
emboli), pericarditis sarcomas
melanomas --> myocardium
multiple melanoma mets lung, breast --> pericardium (hence low metastatic
+ new heart finding - think pericardial effusions), sometimes cancers?
cardiac metastasis myocardium Prostate, GI,
sarcomas --> myocardium, sometimes hepatocellular,
hx of lung/breast cancer pericardium pancreatic,
+ pericardial effusion or leukemia/lymphoma --> anywhere ovarian
pericarditis - think cardiac squamous cell carcinoma --> endocardium
metastasis
Pulmonary LEOPARD
stenosis syndrome
Deep vein often asymptomatic Virchow's Triad: Venous stasis + venous stasis- 2 million/yr pregnancy, High Wells' score? immediated LMWH chronic swelling,
thrombosis Intimal (endothelial) injury + immobilization, male gender, D-dimer (if nl, no or heparin, overlap pain, skin
unilateral calf swelling Hypercoagulable state other (age>40, African further testing but with oral ulceration, recurrent
(large clots overwhelm varicose veins, Americans 3m f/u; if abnl - anticoagulation episodes of DVT,
lymphatics); calf Wells' Clinical Prediction Rule for DVT: severe COPD, US); US (if nl - 3m (coumadin), IVC pulmonary emboli!
tenderness, positive active cancer (rx<6m) = 1 anesthesia, MI, f/u; if abnl - treat + filter (if cannot take
Homan's sign (inflamed leg paralysis/ immob = 1 obesity) 3m f/u) anticoag)
venous wall), venous bedridden >3d from surgery = 1 endothel inj-
cords local tenderness along deep veins = 1 surgery, gen
unilateral swelling (>3cm), pitting = 1 inflamm, prior
collateral superficial veins = 1 DVT, central
alternative dx more likely = -2 line, trauma,
**High risk (>3pts), mod risk (1-2pts), low major venous
risk (<1pt) surgery,
smoking;
hypercoag -
cancer, hi
estrogen, IBD,
sepsis, blood
transfus, HIT,
primary
thrombophilias
Pulmonary dyspnea, pleuritic chest acute RV afterload increased (dilation, pulmonary 3rd most Virchow's ECHO: RVPO anticoagulants decreased CO and
embolism pain, cough, ischemia, RV dysfxn) --> increased RV artery common CV triad (large PE) BP --> Vtach, Vfib
apprehension, syncope, volume --> decreased LV distensibility --> obstruction;Chro illness in US; spiral CT: best! thrombolytics pulseless activity to
rales/crackles, decreased LV preload --> dec CO nic pulmonary 25% mortality if (patient in shock; heart
tachycardia, diaphoresis/ hemodynamic response determined by: hypertension w/ untreated If low to int wells - contraindicated in
hemoptysis (if severe!) 1. amt of vasculature occluded recurrent get D-dimer (if nl - age>80, major pulm hemorrhage,
2. underlying cardiopulm status emboli; done; if abnl - get surgery in pats 7 acute cor pulmonale
3. neurohormonal adaptations (make PE paradoxical CT) days, major trauma
worse!!) emboli (PFO, in 10 days, TIA/
ASD); chronic If int to high Wells- CVA, GI bleed in 3
Wells' clinical pred for PE: Sx of DVT (3), thromboembolic get CT scan (if nl, months, uncont
other dx less likely than PE (3), HR> dz PE excluded; if HTN, known
100bpm (1.5), immob/ surgery past 4wks abnl - treat for PE) bleeding disorder)
(1.5), previous DVT/PE (1.5), hemoptysis
(1), malignancy (1)
- score 4+ intermediate to hi risk; score <4
intermediate to low risk
Pulmonary 1. PAH (primary) dyspnea on exertion, Fixed obstruction in lungs prevent flow stiffened LV younger CXR: enlarged RV, #4 is surgically poor survival, cor
arterial fatigue, angina, syncope from right to left heart = reduced CO = causes inc LA people, female prominent right treatable (pulm pulmonale, atrial
hypertension 2. Pulm venous (fixed CO so BP drops w/ reduced oxygen transport = hypoxia in pressure = inc gender (#1) heart border (RA) thrombo- arrhythmias,
HTN (Left heart vasodilation; arrythmias), lungs = increased work of breathing & PAP (#2) ECHO: dilated endartectomy) paradoxical emboli,
dysfxn) edema (RV failure) ischemia (angina) large RV and #2 needs BB, chronic severe
sarcoidosis, flattened septum ACEI, diuretics hypoxia from
3. PH w/ lung dz clubbing, small carotid pulmonary arterial hypertension (primary) - hyper/ compressing LV nitrates shunting, cerebral
pulse, giant "a" or "cv" PAP > 25 mmHg, normal PCWP (<15; hypothyroidism, Cath: increased #1 requires heart & abcess, sudden
4. PH w/ chronic wave, absent PMI, RV lift general pulm hypertension has ANY wedge renal dz (#5) RVEDP, PAP lung transplant; death
thromboemboli @ LSE, palpable PA press), always elevated transpulmonary CCBs if
impulse @ ULSE, loud gradient idiopathic (#1) Pathology (#1): vasoresponsive
5. PH from direct S2P, ejection sound, SMC proliferation
effect on pulm Graham Steele diastolic mediators: increased activity of (endothelin) & diuretics to prevent
vasculature but murmur (ULSE), right vasoconstrictors (endothelin 1), reduced vascular RHF;
unclear cause sided S3 (RVH), TR activity of vasodilators (prostacyclin, NO) remodeling anticoagulants to
murmur prevent clots;
digoxin if
arrhythmias,
exercise,
supplemental O2 if
hypoxic
Screening /
Education
Screening /
Education
5 mm Hg
increase in DBP
or SBP = 20-
30% increase in
CVD
increased SBP
= decreased
survival
BP monitoring at
home (night BP
nl dips 10-20%;
non-dippers
have increased
risk of CVD)
Screening /
Education
DHHS: screen
men aged 65-75
who have ever
smoked w/ 1x
abdominal US; if
positive, yearly
screening
recommended
Society of
vascular
surgery: screen
all men btwn
age 60-85, all
women age 60-
85 w/ CV risk
factors, and all
men/women
over age 50 w/
+FH for AAA
with abdominal
US
if you see PVD,

make sure the
patient isn't
going to have a
stroke/ MI - their
legs can wait!
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
50% maternal
mortality w/
subsequent
pregnancies if
CM persists
avoid combined
oral
contraceptives
increased risk of
recurrence!
Screening /
Education
Screening /
Education
Screening /
Education
functional class:
Class I - angina
w/ strenuous ex
Class II - angina
w/ walking or
stairs; or > 2
blocks on level
ground;
Class III: angina
w/ one flight of
stairs or
<2blocks
Class IV: angina
w/ walking
around house or
at rest
BP control;
SMOKING
CESSATION,
weigh reduction,
daily exercise,
lipid mgmt (diet)
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Stages: A = at
risk (DM, HTN,
etc); B =
asymptomatic
ventricular
dysfxn; C =
symptomatic
dysfxn; D = end
stage HF
Can't move
between stages;
but can move
between
functional
classes
Screening /
Education
competitive
sports restriction
common cause
of SCD in
athletes
Screening /
Education
competitive
sports restriction
ALL first degree

relatives need to
be screened
Screening of
adolescents &
competitive
athletes q 12-
18m
Screening of
adults q 5y
Screening /
Education
Screening /
Education
Screening /
Education
DVT
prophylaxis -
mechanical,
medical (anti-
coagulation!-
unfractionated
heparin,
LMWH)
Screening /
Education
Periodontal disease immunodeficient can loss of tooth supporting tissues dental plaque/host interaction systemic diseases (Chediak- 65% of US adult
have rapidly (gingiva, periodontal ligament, Higashi, chronic population
progressive forms bone, cementum) --> mobile granulomatous dz,
teeth neutropenia, DM, HIV)
Odontogenic infection Mandibular infection --> mixed microflora infection within and mid-face infection, swelling
submandibular sace involvement around the teeth, usually secondary to [maxillary anterior infxn] or
--> Ludwig's angina (airway dental caries airway compromise
compromise due to displacement [mandibular infxn]
of tongue)
bacterial endocarditis
Maxillary infection --> midface (GAS; HACEK); CNS
(facial veins) --> cavernous abscess or septic embolus
sinus thrombosis
HSV (General) Primary oral herpetic lesions (1- HSV-1, HSV-2; dormant virus resides in Antibodies in 90% of Clinically & histologically
2% of infected) trigeminal nerve sensory ganglion U.S. population indistinguishable for Varicella
Zoster
3Ms: multinucleated cells,

nuclear molding, chromatin
margination; lots of
eosinophils
Primary Herpetic multiple, painful, ulcerated 1-2% of population that comes in contact HSV Young children Self-resolving +/- acyclovir Hospitalization for
Gingivostomatitis vesicles on lips, gingiva, palate, with HSV will develop this entity dehydration
tongue; high fever; cervical
lymphadenopathy; distinguish
from impetigo or eczema by
PAIN
Secondary oral vermillion border of lips; if in HSV 40% of U.S. population prophylaxis w/ acyclovir immunocompromised have
herpetic lesions mouth, exclusively on attached more widespread lesions
gingiva (never on movable
mucosa!), hard palate, or tongue
sometimes prodrome present

(tingling prior to lesion)
Aphthous stomatitis occurs on movable mucosa stress induced; associated with Crohn's ?? Not known 20-60% of population High SES, self-resolving +/- can become a functional
(labial/buccal mucosa, soft disease immunocomp corticosteroids problem if large
palate, floor of mouth) (more severe)
appear round or oval with yellow

center and erythematous border
Behcet syndrome multiple oral, genital ulcerations HLA types B5, B27, B12
+/- relatpsing iridocyclitis (eye)
can have recurrent arthritis &

thrombotic CVD
Oral Squamous Cell Ulcerative, most common URT malignancy tobacco!! Can also have a M>>>F; 5th-6th decade; age, tobacco use surgical + adjunct prognosis related to stage
Carcinoma exophytic, plaque synergistic effect w/ alcohol; 2-4% of all U.S. radiation/chemo (overall 5y survival 20-60%)
like occurs most commonly on Plummer-Vinson syndrome, malignancies
lateral and ventral borders of betel leaf (India), HPV increased risk for 2nd
tongue (NEVER the dorsal primary tumor
tongue), floor of mouth, soft
palate and less commonly on surgery often causes
gingiva and buccal mucosa functional impairment
Premalignant oral Leukoplakia white patch oral hyperkeratosis or callous but some VERY common 1-17% of the dysplastic
lesions degree of dysplasia lesions can transform to
anatomic site can increase malignancies
lesion risk: lateral tongue,
central tongue, floor of mouth,
soft palate
Erythroplakia red patch (large, red persistent VERY uncommon almost always a/w in situ
lesion) or invasive SCC
Oral/ sinonasal hard palate, maxillary gingiva; VERY rare compared to 20% 5y survival
melanoma maxillary sinus cutaneous melanoma
Ameloblastoma arises from enamel forming most common en bloc resection (treated as if can be fatal if affect maxilla
tissues; benign but locally odontogenic neoplasm malignancy because so
destructive; posterior destructive)
mandible
Salivary gland (general) parotid gland (usually benign),
neoplasm submandibular gland (50%
benign), sublingual (malignant
mostly), and minor glands
(malignant mostly)
Salivary gland
neoplasm
Pleomorphic most common type of benign F>M varied histopathology

adenoma salivary gland neoplasm
85% occur in parotid

Warthin tumor Most common bilateral tumor contain salivary and lymphoid tissue M>F smoking!!!
commonly in parotid
Mucoepidermoid most common malignant histology: large deposits of 40% 5y survival but grade-
carcinoma salivary neoplasm (60-90% mucin dependent prognosis
occur in parotid despite parotid
glands nl having benign lesions)
Adenoid cystic extremely aggressive; minor histology: perineural invasion high recurrence rate
carcinoma glands; invasive growth
pattern
Paranasal sinus Squamous cell Maxillary sinus most frequently smoking, nickel, chromium,
neoplasms carcinoma affected wood working industry (soft
wood)
Adenocarcinoma Nasal cavity & maxillary sinus smoking, nickel, chromium, uncommon
wood working industry (hard
wood)
Gastroesophageal symptoms or tissue damage due external factors (diet, fatty foods, smoking, diet, obesity, smoking, 10% of population diet, obesity, CT PPI trial (hi dose x 30d) - if lifestyle mods (avoid trigger erosive esophagitis/ reflux
reflux (GERD) to reflux of gastric contents into meds - b-agonists); diminished globally; 15-44% of disorders, response, taper to tolerable foods, small frequent meals, esophagitis (inflamm of
esophagus esophageal clearance (defective impaired esophageal mucosa Americans affected CVD/asthma (b- dose; if no response, use quit smoking) esophagus from stomach
peristalsis, saliva); gastric factors resistance monthly agonists), DM endopscopy to r/o mucosal d/o contents)
sx: heartburn, regurg, chest (overproduction of acid - meds, H.pylori; H2 blockers, PPIs, antacids esophageal strictures
pain; dysphagia, water brash bile acid; gastric emptying - DM; gastric Endoscopy - negative in 50% for breakthrough sx (narrowing due to
(increased salivation); atypical distention - causes LES to relax more); of patients w/ GERD inflammation)
sx (laryngitis, hoarseness, defective anti-reflux barrier surgery (Nissen esophageal
chronic cough, asthma, dental (PROLONGED transient LES gold std - ambulatory pH test fundoplication) - adenocarcinoma
erosions, laryngeal cancer) relaxations, low resting pressures of LES - (done in pts w. refract/ atyp sx complications in 5-10% (ileus, Barrett's esophagus (see
scleroderma, CT d/o) --> overall causes or typ sx if neg endoscope) pneumothorax, gas bloat below)
impaired esophageal mucosa resistance syndrome, diarrhea)
Barrett's esophagus Barrett's mucosa (normal complication of untreated GERD (>5 years GERD more common in middle histology: intestinal Barretts --> dysplasia ->
squamous epithelium of of moderate to severe symptoms; 3x/week to older aged Caucasian metaplasia (columnar esophageal
esophagus replaced by intestinal to daily) men epithelium + Goblet cells + adenocarcinoma
columnar epithelium) villus pattern development)
endoscope: salmon colored
mucosa above Zline
Barium swallow: narrowing of

esophageal lumen, nodular
appearance (could not R/O
adenocarcinoma v. Barrett's...
need endoscopy & bx)
Eosinophilic acute dysphagia and food infiltrative disorder -possible that certain hx of atopy endoscope: food + concentric PPIs, steroids (oral flonase),
Esophagitis impaction foods trigger eosinophilic infiltration of (asthma, allergic esophageal rings + linear mast cell inhibitors, allergy
esophageal body rhinitis, eczema); furrows referral
younger men
pathology: >15 eosinophiles
per field (distinguishes from
reflux esophagitis, which can
also have eosinophils)
Candida esophagitis odynophagia (painful swallowing) candida immunocomp endoscopy: coated white anti-fungals (Fluconazole)
+ dysphagia (HIV, chemo, plaques w/ raw erythema
chronic steroid below
use - asthmatics)
barium swallow: shaggy
appearance; pan esophageal
deep, penetrating ulcers
histology: pseudohyphae
Viral esophagitis odynophagia (painful swallowing) Herpes, CMV immunocomp Endoscopy: herpes - multiple
+ dysphagia (HIV, chemo, clustered ulcers; CMV - large
chronic steroid ulcers
use - asthmatics)
Barium swallow: herpes: small
shallow ulcers w/ nl esophagus
between the ulcers; CMV: deep
large penetrating ulcers >1cm
in size
histology: herpes -
multinucleated giant cells w/
chromatin pushed to periphery;
CMV - viral inclusion bodies w/
surrounding halos - owl's eye
appearance
esophageal (General) progressive dysphagia, weight Barium swallow: apple core

neoplasm loss, +/- chest pain/cough/ lesions
hematemesis
Squamous cell weight loss, aspiration (if TEE Surface epithelium dysplasia from smoking, alcohol [synergistic most common type gross: irregular, ulcerative metastasis (middle
carcinoma fistula), hemorrhage exposure to mutating agents --> in situ effect] --> mutations in p53 worldwide lesion in middle 1/3 of esop; esophagus --> mediastinal,
SCC --> invasive SCC polypoid SCC occur in upper paratracheal LN; lower 1/3
HPV, chronic esophagitis; 6/100,000 in U.S. 1/3 esop --> perigastric, celiac
dietary carcinogens (aflatoxin) LNs; upper 1/3 --> cervical
histology: no glands; LNs)
keratinized/ squamous
pearl;equipotent replicative hemorrhage & sepsis
ability; mitotic figures, loss of nl tracheo-esophageal fistulas
maturation and polarity; chronic
inflamm cells present
Esophageal GERD, Barrett's more common now due Caucasians gross: white mucosa replaced
adenocarcinoma to Barrett's by red mucosa from stomach;
firm; oval/long appearance;
ulcerative
histology: glandular structures

eroding through esophageal
wall
GI stromal tumors begin in the muscularis propria mutation in c-kit gross: umbilicated ulceration at surgical resection
(GIST) (interstitial cells of Cajal - organ surface
myenteric plexusi) of large tumors & metastases
esophagus, stomach, or treated by Imantinib
intestine; then protrude through (Gleevec)
submucosa & mucosa into
lumen
bleeding
Small cell carcinoma
Melanoma
Primary esophageal Achalasia dysphagia to liquids and solids aperistalsis of the esophagus, resulting in Manometry: failed relaxation Endoscopic pneumatic
motility disorders but worse w/ solids; regurgitation; non-progressive contractions and failed of LES (no drop in LES dilation; botox injection in LES
chest pain; cough/ heartburn opening of LES pressure) and absent during endoscopy (short term)
peristalsis
inflammatory infiltration of myenteric Medical tx: CCBs, nitrates
plexus --> defective NO --> chronic Barium swallow: bird's beak, [overall less effective]
excitation --> chronically closed LES dilated/distended esophagus
full of debris
endoscopy: pinhole opening

of LES
Esophageal varices life threatening bleeding variceal rupture produces massive cirrhosis, portal hypertension gross: enlarged venous endoscopic sclerosing or
hemorrhage into esoph lumen channels @ GE junction; banding
ruptured submucosal veins
Esophageal bleeding (hematemesis) longitudinal tears at the GE junction from alcoholic binge chronic alcoholics; most patients have co-
lacerations (Mallory- severe retching or vomiting acute illness w/ existing hiatal hernia
Weiss tears) increased (stomach slips into
vomiting esophageal hiatus)
Peptic ulcer disease gastric, duodenal NSAIDs cause mostly gastric imbalance btwn aggressive (acid, increased gastric acid 5-10% lifetime H. pylori, NSAIDs, short trial of PPIs/H2 blockers If due to H. pylori - need to Bleeding (most common; 15-
ulcers (worse with food) pepsin) & defensive (protective mucus secretion (nl in gastric ulcers, prevalence smoking, Zollinger- eradicate H. pylori so use PPI20% of PUD pts;
layer) factors in gastroduodenal mucosa 30% increase in duodenal Ellison test for H. pylori (urea breath (omeprazol) + 2 antibiotics hematochezia- red or coffee
H. pylori causes mostly duodenal ulcers); test, IgG serology if patient (amoxicillin, clarithromycin) as
grounds, hematemesis,
ulcers (relieved by food) prostaglandins - inhibit gastric acid NSAID-induced NEVER treated before, stool first line melena; a/w NSAID intake;
production AND maintain protective H. pylori & NSAIDs!! ulceration: incr antigen test; invasive - biopsy) usually self-resolving;
vague abd discomfort surface layer (meds - NSAIDs that risk w/ age>60, 2nd line (rescue therapy): endoscopy for dx/tx but no
complaints; usually decrease prostaglandins weaken concurrent steroid stop NSAIDs omeprazol + bismuth + effect on mort)
asymptomatic but most common protective layer...); NSAIDs also directly use, incr duration tetracycline + metronizadole Perforation (sudden severe
sx = dyspepsia (upper damage epithelium & dosage, immediate endoscopy ONLY if epigastric pain, peritonitis -
abdomen- fullness, bloating, anticoagulation weight loss, bleeding, n/v, age If due to NSAIDs, stop rebound tenderness,
distention, nausea; 1-3h H. pylori adheres to gastric mucosa and use, prior hx of > 45 w/ dyspepsia NSAIDs!! rigidity, gurarding; dx: XR/CT
postprandial, middle of the produces urease and consequently PUD shows free air under
night, improves w/ antacids) ammonium to protect from acidic environ; barium swallow: smooth/ Surgery?? (vagotomy + diaphragm; requires
inflammation --> ulcer formation; affects uniform collection of barium drainage procedures- surgery!!)
duodenal mucosa by instigating representing ulcerations in decrease vagal stimulation to Obstruction (due to inflam,
metaplasia [destroys D cells] of duodenal stomach wall parietal cells, followed by edema, scarring; n/v 30-60m
mucosa to gastric mucosa antrectomy/pyloroplasty/ postprandial, bloating, early
gastrojejunostomy to help satiety; succession splash;
empty stomach) requires surgery!!)
Penetrating ulcer (severe
persistent pain, pancreatitis)
Gastritis Acute gastritis sudden inflammation of stomach transient mucosal inflammatory process Alcohol, NSAIDs, ischemia
lining due to numerous etiologies
asymptomatic or variable disruption of mucus layer protective

epigastric pain, n/v mechanisms (reduced mucin synthesis,
reduced bicarbonate secretion, direct
injury by chem/alcohol ingestion
Chronic gastritis less severe symptoms than chronic presence of etiologic agent --> H. pylori, autoimmune histology: overwhelming amt of increased risk of dysplasia
acute gastritis but persistent mucosal atrophy --> intestinal metaplasia gastritis, chronic alcohol inflammatory cells; intestinal and adenocarcinoma w/
abuse, radiation, post surgical metaplasia (Goblet cells); can intestinal metaplasia
sometimes see H. pylori w.i
gastric gland
Autoimmune gastritis antibodies against gastric autoimmune gastritis - lymphocytes 10% of chronic gastritis F>M
parietal cells; pernicious anemia; damage cells in the stomach (most
vit B12 deficiency commonly the parietal cells), causing
atrophic gastritis
Gastric polyps Hamartomatous majority of gastric polyps (80- glandular hyperplasia associated with Peutz-Jegher found most commonly in histology: regenerative, dilated
90%) syndrome (intestinal/gastric people 50-60y.o. gland but not neoplastic
non-neoplastic but may be polyps + peri-oral
regenerative pigmentation), FAP (fundic
gland polyps; adenomatous
polyps in large intestine that
become adenocarcinomas)
Adenomatous 10% of gastric polyps usually progress from atrophy and larger size lesion
neoplastic; unrestricted intestinal metaplasia (commonly in the = increased risk
growth with malignant background of chronic gastritis) adenocarcinoma
potential
Gastric (General) most common malignant environmental factors leading cause of cancer Staging: depth of invasion
adenocarcinoma gastric tumor (90-95%) (H.pylori, hi nitrate/nitrite diet, death globally, more
hi smoked/salty diet, smoking, common in Japan, Chile, (Tis = in situ; T1 = lamina
usually in antrum/pylorus, lack of fruits/veggies, low SES) China, Russia propria/submucosa; T2 =
lesser curvature although muscularis propria; T3 =
cardia tumors are arising due to host factors (chronic gastritis, M>F; usually >50 y.o.. serosa; T4 = adjacent
Barrett's esophagus intestinal metaplasia, structures)
adenomatous gastric polyps,
exophytic, flat, or ulcerative Barrett's esophagus, partial
gastrectomy, Menetrier
disease)
Genetic factors (+FH, HNPCC-

DNA mismatch repair gene
mut; familial gastric cancer
syndrome- E cadherin mut;
autoimmune gastritis)
Intestinal type most common type a/w: intestinal metaplasia from older patients w/ gross: solitary lesions,
environmental factors; chronic gastritis; known risk factors exophytic but nl stomach
slightly better prognosis than and adenomatous polyps ruggal folds
diffuse type
histology: arise from intestinal
metaplasia, some signet/donut
signs, large hyperchromatic
cells, irregular nuclear contour;
formation of glands
Diffuse type usually diagnosed at a high E-cadherin mutations (CDH1 gene) --> younger patients with gross: thick stomach wall,
stage so worse prognosis loss of cell adherence no known risk factors enhanced ruggae (linitis
(plus easily invades due to besides perhaps plastica morph), flatter
lack of adherence molecules) genetics lesions
M=F histology: lots of signet ring/

donut signs (eccentric nuclei-
jammed to side by mucin);
cells appear to be falling apart
due to loss of cadherin
Gastric lymphomas MALT lymphoma Low grade chronic inflammation --> lymphoid stimulus H. pylori Histology: normal cells antibiotic therapy (get rid of H. good prognosis; however,
--> clonal proliferation of small B (uniform, typical) but dense pylori then MALT lymphoma tumors with translocation
lymphocytes --> development of lymphocyte infiltration resolves) t11:18 have worse
lymphoma prognosis
Diffuse large B-cell high grade arise de novo or in MALT lymphoma histology: dense sheets of surgery, chemo, radiation poor prognosis
lymphoma lymphocytes; hyperchomatic
cells w/ irregular nuclear
contours
Gastric carcinoids symptoms depend on neuroendocrine tumors a/w endocrine cell MEN-1, ZE syndrome
hormones being produced hyperplasia, chronic atrophic gastritis, or (excessive gastrin -->
Zollinger-Ellison syndrome increased gastric acid levels;
often secrete gastrin extensive PUD)
rare in stomach (more common

in SI & lungs)
patients can present w/

duodenal ulcers, diarrhea if ZE
Menetrier Disease weight loss, diarrhea, peripheral excessive secretion of TGF-a ?? Unknown VERY rare gross: hypertrophy of gastric increased risk of
edema (transforming growth factor), causing folds adenocarcinoma
diffuse hyperplasia of foveolar epithelium M>F; 30-50 y.o.
hypochlorhydria (low gastric of body/fundus of stomach histology: foveolar
acid in stomach) hyperplasia
Malrotation most common congenital GI 1% of congenital Upper GI series: No duodenal Ladd procedure (required for
malformation population (incidence C- loop (ligament of Treitz ALL malrotations regardless
ranges from 1/6000 - doesn't cross the midline) of symptoms)
majority are asymp 1/200)
Newborns: bilious emesis, late M slightly more than F

stage signs (hematemesis,
hematochezia, tenderness/pain, majority diagnosed w/ 1
peritonitis, shock = intestinal year of life but some go
necrosis) = very poor prog undetected until
incidental find on GI
Older kids/adults: intermittent imaging/surgery
vomiting, abd pain, volvulus,
pancreatitis, enteropathy,
peritonitis
Intestinal atresia bilious emesis IMMEDIATELY maldevelopment (muscular, neurological, associated with 30% of Down XR: double bubble = surgical emergency!!
following birth = hi grade or both) of GI tract likely due to Syndrome cases duodenal atresia
obstruction chromosomal abnormality although not
truly elucidated
Abd distention = mod grade
obstruction
intermitt abd pain + failure to

thrive = partial obstruction/
atresia
Congenital babies born nl but display non- diffuse hypertrophy and hyperplasia of first more common in males benign course post-surgical none, usually resolves post-
hypertrophic pyloric bilious emesis @ ~1m part of pylorus --> narrowed channel splitting of pyloric muscle surgery
stenosis between antrum and duodenum
often misdiagnosed as GERD
Hirchsprung's Rectosigmoid area is most arrest of neural crest cell migration --> autosomal recessive and 1/5000 positive FH rectal biopsy - ganglion resection of aganglionic lifelong implications
disease (aganglionic affected (constipation, stool aganglionic zone of bowel (no ganglions in dominant mutations sometimes cells? HD pts have no segments
bowel) overflow) myenteric plexus despite normal muscle M>F in short segment; ganglion cells and nerve 15% of HD babies have
layers) RET (receptor tyrosine M=F in long segment dz hypertrophy other associated
15% have total colonic HD (high kinase) - associated w/ MEN congenital anomalies :(
grade obstruction) lacks inhibitory parasympathetic type Iia Barium enema: determines
innervation; absent NOS in myenteric transition area where no high complication risk post-
5-10% have total colonic + small plexus therefore reduced nitric oxide contraction/distention surgery: strictures,
bowel HD (hi mortality at birth) [anal sphincter cannot relax so unable impactions, soiling,
to defecate] anorectal manometry: constipation
Presentation: delayed passing differentiates normal v. abnl
of meconium, abd distention, functioning bowel by recto-anal
constipation, vomiting, +/- inhibitory reflex
diarrhea
starts @ birth (unlike funct

constip) and rarely has fecal
soiling (unlike funct constip
again)
Gilbert syndrome Elevated indirect reduced UDP glucoronyl transferase precipiated by fasting, stress, Prevalence ~ 5%; M>F family history increased indirect bilirubin none
(unconjugated) bilirubin; activity causes impaired conjugation of EtOH
benign - asymptomatic bilirubin
jaundice
Crigler Najjar Type 1 elevated indirect (unconjugated) completely absent UDP glucoronyl
Syndrome bilirubin transferase activity
severe/fatal
Type 2 elevated indirect (unconjugated) reduced UDP glucoronyl transferase
bilirubin; activity
less severe (Arias syndrome)

Neonatal neonatal jaundice blood group incompatability between mom blue fluorescent light
hyperbilirubinemia (unconjugated & baby PLUS newborn's inadequate UDP- exposure (increases
hyperbilirubinemia) --> glucoronyl transferase activity conversion of bili in skin to
kernicterus (toxic more polar/water soluble
encephalopathy) isomers)
IM injection of tin-
mesoporphyrin (inhibits heme
oxygenase to prevent
formation of bilirubin)
Viral hepatitis Hepatitis A viral prodrome (fatigue, n/v, non-enveloped RNA virus that is contaminated food products poor hygiene, increased ALT (liver damage) NO risk for chronic
arth/myalgias, headache) transmitted via fecal-oral route and then (fecal-oral) overcrowding, infection or cirrhosis!!!
followed by jaundice 1-2 weeks replicates in the liver; most infectious institutions, IgM - suggests new/acute
later during incubation period (minimal endemic countries infection
infectivity once jaundice occurs) (Latin America,
Africa, Asia), food IgG persists to provide total
outbreaks immunity
Hepatitis B small DNA virus that is transmitted U.S. - horizontal transmission cases in U.S. are usually endemic countries IgM = acute infection boost immune response via risk of chronic infection,
primarily through blood and sexual of body fluids (IVDU, needle immigrants or vertical (Africa, Asia) pegylated interfeon or cirrhosis, liver failure, &
exposure, then replicating (using active stick- HCW, unprotected sex; transmission to infants HBeAg = active infection nucleoside/tide analogs ($$) HCC
viral reverse transcriptase w/ high MSM) born in U.S. by middle aged (infectious state)
mutation rate) in liver or extrahepatic immigrant moms adults (not some drugs have activity risk of chronicity
reservoirs Globally - horizontal vaccinated) will anti-HBs + no anti-HBc = against HBV and HIV determined by age of
transmission + vertical 400 million carriers in have higher vaccination infection acquisition
surface proteins: HBeAg, HBsAg, HBcAg, transmission world (75% in Asia) chance for acute pregnant? Tenofovir in 3rd (younger individuals w/ Hep
DNA polymerase infection anti-HBc + HBsAg = chronic trimester; give infant HBIG + B = hi risk for chronic hep B)
test immigrants from infection HepB vaccine w/I 12h of
LONG incubation period; may be endemic region, MSM, birth #1 cause for cirrhosis &
contagious up to 15 weeks post- multiple sex partners, IVDU, anti-HBc = represents natural HCC globally
symptoms inmates, dialysis pts, HIV pts, infection (either acutely or
pregnant women, close chronically)
contacts of known cases, pts
w/ abnl liver enzymes
Hepatitis C ssRNA virus from flavivirus family (same blood transfusions before leading cause of liver if exposed, 80% histology: progression of pegylated interferon + HIGH likelihood of chronic
as dengue, WNV) that is transmitted 1992, IVDU, unk risk factors transplant for cirrhosis of people will fibrosis --> cirrhosis if chronic ribavirin infection w/ subsequent
primarily through blood and infects (sharing razors/toothbrush, in U.S. develop chronic (stellate cells, collagen bridges) risk of cirrhosis, liver
hepatocytes + B lymphocytes; replicates in piercings, tattoos, etc) hepatitis, after new therapy: peg interferon + failure, & HCC
liver using RNA dependent RNA pol (hi 4 million U.S. people which 15% of ribavirin + protease inhibitor
mutation rate) other: needlesticks in HCW, have been exposed; 3.2 these will (telaprevir/ bocepravir) decompensated cirrhosis
vertical transmission, non- million U.S. people have develop cirrhosis (ascites, encephalopathy,
sexual household contact, chronic HepC and 1% will varices)
sexual transmission develop HCC
Hepatitis D enveloped ssRNA virus known as a delta IVDU, blood transfusion treat hepatitis B to get rid of
agent because only propagates in the hepD
presence of Hepatitis B!!
Transmitted via blood or sex (usually

exposed to HepB & HepD at same time)
Hepatitis E non-eveloped ssRNA virus that is contaminated food products CAN BE FATAL IN
transmitted via fecal-oral route and can (fecal-oral) PREGNANT WOMEN!!!
be detected in stool/bile/liver;
does NOT cause chronic infection
(Alcohol) hepatic occurs w. moderate-marked alcohol shunts toward lipid biosynthesis hepatic steatosis: alcohol, gross: hepatomegaly, yellow, benign course usually
steatosis EtOH intake (due to increased NADH and decreased protein deficiency, drugs, greasy surface
FA oxidation), but lipid assembly and pregnancy (3rd trimester),
asymp in most cases secretion are impaired (decreased MT infection (hepC, HIV), Reye's histology: intra & extrahepatic
transport; altered membrane permeability) syndrome, parenteral nutrition, lipid accumulation; no necrosis,
clinical presentation: DM, NASH +/- fibrosis
hepatomegaly, elevated liver also increased peripheral catabolism of
enzymes fat, which causes fatty acids to be
delivered to the liver where they
REVERSIBLE! accumulated (steatosis)
Alcohol hepatitis acute onset following binge excessive alcohol increases formation gross: steatosis typically 10-20% risk of death
drinking of toxic metabolites, overwhelming liver's present (represents hx of
metabolic ability; mitochondria & MT alcohol abuse), +/-
minimal --> severe symptoms dysfunction hepatomegaly (unless cirrhotic)
(malaise, fever, abd pain, tender
liver, elevated hepatic enzymes - liver is more susceptible to injury in the histology: hepatocyte
AST/ALT >2; peripheral setting of reduced glutathione levels swelling/necrosis, Mallory
neutrophilia) bodies (bright pink inclusions
increased endotoxin release from gut representing aggregates of
bacteria reaches liver via portal circulation cytokeratin; also seen in
Wilson's dz & cholestasis),
neutrophilic infiltrate;
possible steatosis & fibrosis
Alcohol-related represents years of EtOH not really understood may be synergistic w/ other 10-15% of alcoholics ?? Liver enzyme elevation increased HCC risk
hepatic cirrhosis abuse diseases (hepB, hepC, (no current marker for (loss/death of hepatocytes so
alcohol injury/inflammation --> pro-fibrotic autoimmune hep, susceptibility) not really too many left to be
clinical presentation: weight loss, cytokines --> release of growth factors and hemochromatosis, drugs- MTX, injured)
anorexia, malaise, ascites, increased collagen production --> amiodarone)
jaundice, peripheral edema, fibrosis decreased liver synthetic
portal HTN, esophageal varices, function tests
liver will be hard to palpate bc synergistic pathogenesis
shrunken size gross: decreased size, diffuse
nodularity, brown/ green
IRREVERSIBLE!! pigmentation (bile stasis)
histology: marked fibrosis,

regenerative nodules, variable
inflamm infiltrate, bile stasis;
trichrome stain identifies
collagen
Drug-induced liver dose-dependent Hy's law: >10% of patients w/ >900 drugs implicated; many drugs have antibiotics, anti-seizure meds relatively low incidence Adults histology: massive/zonal withdraw offending agent Acute liver failure,
injury (DILI) (acetaminophen --> DILI + jaundice progress to cholestatic or hepatocellular signature (phenytoin), HIV meds (ARVs), obesity necrosis, inflammation (if + transplantation, death
accumulation of death or transplantation, even toxicity (after which they cause elevated hyperthyroidism drugs malnutrition eosinophils, think liver transplant (acute liver
NAPQI) after cessation of drug liver enzymes) (propylthiouracil), amiodarone, pregnancy hypersensitivity), granulomas, failure)
MTX, NSAIDs, antifungals, INH other drugs steatosis (microvesicular has
unpredictable timeline of DILI metabolic: accumulation of toxic (increased age), statins (very alcohol worse prognosis), N-acetylcysteine
presentation; can mimic metabolites in hepatocytes; steatosis; few causes of DILI but do hx of DILI phospholipidosis (deposition of (Mucomyst) if
autoimmune hepatitis autoimmune (methyldopa); mitochondrial elevate LFTs in 1-3% of genetics phospholipids in hepatocytes), acetaminophen toxicity
toxicity (HIV meds, amiodarone) patients) PMH of liver dz SOS (sinusoidal obstructive
[iver injury] elevated LFT, acute syndrome; fibrosis around steroids if autoimmune
liver failure, hepatic necrosis hypersensitivity: a/w rash, fever, dependent on drug, environ highest risk central vein); more damage in hepatitis
eosinophilia, extra hepatic manifestations (diet, toxins, exposures), and profile? Obese F zone 3
[cholestatic injury] - elevated [sulfonamides, amoxicillin-clavulanate, host (age, gender, weight, > 50y.o. who carnitine if valproic acid
bili, ALP, pruritis, jaundice phenytoin, HIV meds] genetics, immune diseases) drinks EtOH dx of exclusion toxicity
factors
minocycline - acute hepatitis & Acetaminophen toxicity results because monitor LFTs in patients taking
SJS, chronic hepatitis, acute depletion of glutathione, so liver is no patients w/ comorbidities like INH
Drug-induced liver Hy's law: >10% of patients w/ >900 drugs implicated; many drugs have antibiotics, anti-seizure meds relatively low incidence Adults histology: massive/zonal withdraw offending agent Acute liver failure,
Disease
injury (DILI) Clinical Variants DILI
Defining Characteristics
+ jaundice progress to cholestatic orPathogenesis
hepatocellular signature Etiologies
(phenytoin), HIV meds (ARVs), Epidemiology Risk factors
obesity necrosis,Lab/Imaging
inflammation (if + Treatment Complications
transplantation, death
death or transplantation, even toxicity (after which they cause elevated hyperthyroidism drugs malnutrition eosinophils, think liver transplant (acute liver
after cessation of drug liver enzymes) (propylthiouracil), amiodarone, pregnancy hypersensitivity), granulomas, failure)
Idiosyncratic MTX, NSAIDs, antifungals, INH other drugs steatosis (microvesicular has
(individualized; unpredictable timeline of DILI metabolic: accumulation of toxic (increased age), statins (very alcohol worse prognosis), N-acetylcysteine
immune-mediated) presentation; can mimic metabolites in hepatocytes; steatosis; few causes of DILI but do hx of DILI phospholipidosis (deposition of (Mucomyst) if
autoimmune hepatitis autoimmune (methyldopa); mitochondrial elevate LFTs in 1-3% of genetics phospholipids in hepatocytes), acetaminophen toxicity
toxicity (HIV meds, amiodarone) patients) PMH of liver dz SOS (sinusoidal obstructive
[iver injury] elevated LFT, acute syndrome; fibrosis around steroids if autoimmune
liver failure, hepatic necrosis hypersensitivity: a/w rash, fever, dependent on drug, environ highest risk central vein); more damage in hepatitis
eosinophilia, extra hepatic manifestations (diet, toxins, exposures), and profile? Obese F zone 3
[cholestatic injury] - elevated [sulfonamides, amoxicillin-clavulanate, host (age, gender, weight, > 50y.o. who carnitine if valproic acid
bili, ALP, pruritis, jaundice phenytoin, HIV meds] genetics, immune diseases) drinks EtOH dx of exclusion toxicity
factors
minocycline - acute hepatitis & Acetaminophen toxicity results because monitor LFTs in patients taking
SJS, chronic hepatitis, acute depletion of glutathione, so liver is no patients w/ comorbidities like INH
liver failure, cholestatic hepatitis longer able to clear NAPQI (toxic met) HepB, hepC are at greater risk!
cocaine - liver necrosis & acyte
hepatitis
Non-alcoholic Fatty steatosis --> steatohepatitis -->
"two hit hypothesis" - insuline resistance metabolic syndrome 20% prevalence in U.S. metabolic elevated ALT (AST/ALT <1) weight loss & metabolic
Liver Disease cirrhosis increases fatty acid delivery to liver; (obesity, DM, dyslipidemia) syndrome control (treat DM w/
(NAFLD) oxidative stress increases free radical U/S: increased echogenicity metformin, treat dyslipidemia
usually asymptomatic, fatigue, formation --> lipid peroxidation --> cellular from fatty infiltrate w/ statins)
RUQ pain; damage
biopsy: steatosis, inflammation,
central obesity, hepatomegaly fibrosis
Wilson's disease pediatric or young adult gene defect responsible for copper autosomal recessive 1/30,000 people low serum ceruloplasmin (nl diet: eliminate copper rich
presentation w/ liver disease transport --> decreased biliary excretion of inheritance carries copper but is broken foods (organ meats, shellfish,
copper --> increased copper deposition age of onset typically 15- down if copper is not attached) chocolate, mushrooms, nuts)
hepatic (variable - abnl liver throughout body --> increased oxidative 25
enzymes --> cirrhosis & portal stress & damage KF rings on slit-lamp eye lifelong chelation
HTN), neurological (rigidity, exam
spasticity, tremors, ataxia), liver transplant is curative
hematologic(hemolytic anemia), increased 24h copper excretion
psych (depression, psychosis), in urine
opthalmologic (Kayser-
Fleischer rings, sunflower
cataracts)
Autoimmune hepatitis fatigue, hepatomegaly, aberrant immune response directed genetic predisposition, 200,000 U.S. patients; Elevated transaminases, increase immunosuppression 87% remission within 3y of
jaundice towards own hepatocytes --> exposure to unk environmental F>M; average age 20-40 elevated IgG, +ANA/SMA/ (prednisone, combo therapy) treatment
hepatocellular disorder, inflammation, & factor liver-kidney microsomal-1
a/w other autoimmune fibrosis antibodies (1 of the 3 usually)
disorders (thyroid disease)
histology: interface hepatitis,
hepatic rosettes (small gland
like clusters of surviving
hepatocytes within
inflammatory infiltrate),
variable fibrosis depending
on dz stage
MUST exclude other dx

Primary Biliary autoimmune disorder aberrant immune response directed at own 5/100,000 elevated ALP, nl or mildly ursodeoxycholic acid slowly progressive disease
Cirrhosis (PBC) characterized by progressive biliary epithelial cells (small bile ducts) elevated transminases, IgM, (synthetic bile acid - 32% risk leading to cirrhosis in 10-
destruction of intrahepatic bile F>M hypercholesterolemia, fat reduction in death/ liver 20 years
ducts (microscopic injury) median age of dx 50-55 soluble vitamin deficiency transplantation)
(ADEK), anti-mitochondrial
fatigue, pruritis, jaundice (10%), antibody (AMA)
hepatomegaly, xanthelasma/
xanthomas, associated histology: bile duct destruction
autoimmune disorders (thyroid, w/ mononuclear cell
Sjogren's, scleroderma, inflamm inflammatory infiltrate
arthritis), maldigestive fatty
diarrhea
Primary Sclerosing sx: fatigue, pruritis, jaundice, autoimmune disorder characterized by 8.5/100,000 elevated ALP, mild elevations liver transplant! irreversible damage to bile
Cholangitis (PSC) weight loss, fever, fibrosing inflammation of both intrahepatic in transaminases ducts --> cholestasis -->
hepatomegaly, splenomegaly, AND extrahepatic bile ducts M>F cirrhosis
hyperpigmentation, xanthomas cholangiogram: multiple bile
avg age of dx 40 duct strictures w/ proximal increased risk of
majority of patients have IBD dilations (beaded cholangiocarcinoma
(UC) appearance) - "beating of the
bile ducts" median survival 12-16
years post dx
Glycogen storage GSD-1 hypoglycemia very quickly mutation in either GLUT2 or glucose-6- uric acidosis, lactic acidosis, nutritional management
disease after last meal, hepatomegaly phosphatase --> hypoglycemia (glucose-6- elevated triglycericides (continuous night feeding via
(glycogen stores build up bc phosphate cannot be converted to glucose ng tube; uncooked corn starch
cannot be broken down), OR glucose cannot be transported out of liver biopsy (measure amt of before bed; frequent feedings)
seizures at age 3-4m, failure to liver for usage) glucose-6-phosphatase)
thrive, increased uric acid, liver transplant when dietary
lactic acidosis, and increased treatment fails or when
triglyceride levels adenomas develop
Tyrosinemia type 1 severe liver dz in young infants defective enzyme (FAH) causes buildup of newborn screening (elevated NTBC (inhibits buildup of
(bleeding problems - unable to toxic metabolite FAA; FAA is converted to tyrosine --> repeat and check toxic substances)
produce clotting factors; FTT) another toxin SAA for urine SAA)
dietary (reduce protein
neurological problems, renal intake)
involvement
Lysosomal storage Gaucher's disease, progressive hepatomegaly, enzyme replacement therapy

disease Fabry's disease, Tay- splenomegaly, loss of (unless child has a deletion
Sach's disease developmental skills, abnormal mutation, then they would
facial features develop an immune response
and require induced immune
tolerance)
Alpha1- antitrypsin most common inborn dz alpha 1 antitrypsin binds and promotes family history minimize enviromental factors
deficiency (A1AT) affecting the liver degradation of serum proteases; produced (smoking, occupational lung
mainly in liver but functions in lung to hazards)
neonatal hepatitis (usually inhibit elastase; mutation in this enzyme
spontaneously resolves but can causes A1AT clumping --> inflammatory IV augmentation therapy (anti-
cause chronic response - response enzyme therapy) - helps lung
fibrosis) fxn but not liver disease
lack of protein in lung --> COPD (malformed protein is still
also a/w early onset COPD in mutant protein in liver --> toxicity being produced)
non-smokers
Hereditary iron overload syndrome --> liver homozygous missense mutation in C282 1/250 people have monitor serum ferritin or frequent phlebotomy to cirrhosis, HCC, diabetes
hemochromatosis injury, fibrosis, cirrhosis, HCC tyrosine OR heterozygous missense mutation but not transferrin saturation remove RBCs (and hence (toxicity to pancreas),
mutation in C282Y/H63D everyone asymptomatic drop iron levels)
fatigue, hyperpigmentation, RUQ
pain, arthritis/joint swelling, gene involved normally encodes HFE,
impotence which regulates iron by modulating activity
of ferroportin on enterocytes (absorb Fe)
and hepatocytes/macrophages (store Fe);
hi Fe = increased HFE = decreased

ferroportin = less absorption of Fe
in patients w/ missense mutation, low

HFE levels cause increased ferroportin
and consequently absorption of Fe
Cirrhosis compensated radiographic signs scarred liver --> distorted sinusoidal chronic abnl LFTs, histology: regenerative
characteristic of cirrhosis but architecture --> increased resistance and hx of chronic liver nodules surrounded by
no symptoms disturbed blood flow --> shunting of disease extensive scarring or fibrotic
coronary vein blood flow AWAY from liver tissue
chronic liver disease (hi resistance) --> engorgement of
manifestations (muscle wasting/ gastroesophageal plexus --> variceal liver insufficiency
cachexia, spider angiomas - bleeding (hypoalbuminemia, increased
portal-systemic collaterals; INR, hyperbilirubinemia)
palmar erythema, blood in portal vein is also shunted away
gynecomastia) from liver --> increased back pressure on Doppler U/S (ICU pts only) -
mesenteric venous drainage of gut --> splenomegaly, cirrhotic liver
palpable left liver lobe, small splanchnic hemodynamic derangement contour, reversed blood flow
liver span (percussion),
splenomegaly, MRI - nodular liver,
thrombocytopenia splenomegaly, varices
(hi resistance) --> engorgement of
gastroesophageal plexus --> variceal
bleeding
blood in portal vein is also shunted away

from liver --> increased back pressure on
mesenteric venous drainage of gut -->
splanchnic hemodynamic derangement
decompensated Cirrhotic changes + no biopsy needed (imaging + chronic ascites? Minimize cerebral vasodilation
SYMPTOMS symptoms sufficient) sodium diet; diuretics, (hepatic encephalopathy),
paracentesis (especially if peripheral vasodilation
compensated signs + jaundice, ascites fluid - serum albumin ACS), TIPS (if refractory (shock), pulmonary
ascites, asterixis (hepatic to ascites gradient (SAAG) > ascites) vasodilation (portopulmonary
encephalopathy) 1.1 (hydrostatic process hypetension,
suggesting transudative early antibiotics if SBP hepatopulmonary syndrome,
ascites; if less than 1.1. think hepatic hydrothorax),
neoplasm or infectious cause metabolic/ hemodynamic
of ascites) derangements
abdominal compartment
syndrome (restrictive lung
physiology)
spontaneous bacterial
peritonitis: > 250
neutrophil count in
pericentesis
hypoglycemia (BAD sign)
Portal hypertension variceal hemorrhage, ascites, splanchnic vasodilation (increased cirrhosis (increased low platelet count systemic manifestations;
splenomegaly flow) + scarred/fibrotic liver (increased resistance in sinusoidal space) (thrombocytopenia) splanchnic vasodilation -->
resistance + stellate cell mediated pathologic shunting of blood
sinusoidal vasoconstriction) = increased Other causes? Portal/ splenic Hepatic pressure venous away from liver --> increased
portal pressure vein thrombosis, gradient (HVPG) = WHVP cardiac output into
schistosomiasis, veno- (wedge pressure) - FHVP (free splanchnics --> decreased
as back pressure to gut increases, gut occlusive disease, Budd-Chiari hepatic pressure); nl 3-5 mmHg effective arterial blood
bacteria are translocated and enter volume --> compensatory
mesenteric lymph nodes, where they upregulation of
increase NO production; more NO = neurohormonal systems
splanchnic arterial vasodilation (RAAS, SNS, ADH) --> inc
intravascular volume (renal
vasoconstriction or Na/H2O
retention) --> hepatorenal
syndrome OR ascites/
hyponatremia
hepatic neurologic & psychiatric conversion of ammonia (which is not Infection, GI bleed, serum ammonia level not eliminate ammonia production reversible with treatment!
encephalopathy dysfunction in presence of eliminated by dysfunctional liver) to dehydration sensitive but can use serial sources using lactulose,
decompensated cirrhosis glutamine --> astrocyte swelling & altered levels to measure treatment rifaximin, or metronidazole
neurotransmission response
hyperammonemic state
different dz manifestations
depending on setting of acute or
chronic liver dz; acute liver dz
(development of intracranial
HTN & cerebral edema -->
herniation); chronic liver dz
(less injury bc upregulation of
ammonia backup systems)
Cirrhotic resembles septic hypotension hemodynamic circulation due to peripheral

cardiomyopathy (low BP = low SVR) vasodilation and sympathetic activation
causes decreased arterial blood volume,
compensatory mechanisms will systolic & diastolic dysfunction,
be seen: tachycardia, wide conductance abnormalities, and impaired
pulse pressure, bounding B-adrenergic receptor function
pulses, hypotensive
Hepatopulmonary abnormal dilation of pulmonary dilation of basal pulmonary vasculature bubble study - detection of supplemental O2 with curative
syndrome (HPS) vasculature causing hypoxemia impedes diffusion mediated transfer of microbubbles in left heart liver transplantation
(in absence of radiographic oxygen after 3-6 cardiac cycles (in
shunt lesion) contrast to 1 cycle if
intracardiac shunt lesion)
Platypnea (SOB when upright;
opposite of CHF patients)
Portopulmonary pulmonary hypertension in the unk?? Vascular injury/ inflammation ECHO (screens) + RH Diuresis, prostaglandin
Hypertension setting of decompensated mediated by serum factors abnormally catheterization (confirms) therapy if acute RV failure
(PPHTN) cirrhosis --> right heart failure persist in hepatic outflow
Liver transplantation does not
RHF, ascites, pulm edema, immediately reverse PPHTN
peripheral edema (so patients must continue
prostaglandins) - difference
btwn HPS & PPHTN
Hepatic hydrothorax transudative pleural effusion accumulation of ascitic fluid in pleural CXR Thoracentesis respiratory faulure
resulting from ascites tracking space, particularly right hemithorax -->
across diaphragm into negative right sided pleural effusion diuretics spontaneous bacterial
intrathoracic space empyema
TIPS = transjugular
dyspnea, hypoxemia intrahepatic portosystemic
shunt
Variceal hemorrhage hematemesis, hematochezia significant portal hypertension causes endoscopy splanchnic vasoconstrictors
back flow of blood to gastroesophageal (ocreotide), BB to decrease
plexus --> varice formation --> rupture --> HR, empiric antibiotics
potentially fatal hemorrhage
Band ligation via endoscopy if
esophageal varices
TIPS if failed variceal banding

or gastric varices
Hepatorenal functional renal failure in splanchnic vasodilation--> decreased terlipressin (splanchnic

Syndrome (HRS) presence of decompensated effective arterial blood volume (per the vasoconstrictor)
cirrhosis kidneys) --> compensatory mechanisms
by kidneys --> functional renal failure
structurally normal kidneys
Annular pancreas incomplete rotation of ventral normally in embryologic development, 1/20,000 surgical bypass of the area associated with other
pancreatic bud ventral portion of pancreas fuses with wrapped around the congenital anomalies (Down
dorsal part of pancreas duodenum syndrome, duodenal
infants: n/v, FTT, feeding atresia, congenital heart
problems Here, incomplete rotation so despite the defects,
ventral and dorsal pancreas attaching, tracheoesophageal fistula)
adults: PUD, duodenal stenosis, the ventral part remains in the initial
pancreatitis position and wraps around second part can have strictures/
of duodenum obstruction in duodenum
Pancreas Divisum most common congenital failed fusion of dorsal and ventral 5-7% of population endoscopic or surgical
anomaly of pancreas pancreatic ducts sphincterectomy, stent
placement
most pts are asymptomatic; normally, main pancreas duct drains into
recurrent pancreatitis or major papilla but in divisum, the ducts do
chronic idiopathic pancreatitis not fuse properly so majority of pancreas
drains into minor papilla --> pressure
buildup and pancreatitis
Ectopic pancreas accesory pancreas 1-2% of population
most people are asymptomatic
can cause nodules or tiny

polypoid lesions in other parts of
GI tract
Congenital pancreatic most are asymptomatic but if anomalous development of pancreatic very rare! surgical resection if
cysts symptomatic, it will occur before ductal system symptomatic
age 2 (abdominal distention,
n/v, jaundice, pancreatitis)
Cholelithiasis Cholesterol (80%) intense RUQ/epigastric pain 1. secretion of free cholesterol into bile; 2. gallbladder hypomotility (at 10-15% of men > 60y.o.; age, obesity, child U/S - 98% sensitivity no intervention if acute cholecystitis
(gallstones) that radiates to back about 1h hypersecretion (increased chol synthesis risk? Pregnant, long term 20-40% of women > 60 bearing, estrogen MRI - better or equivalent to asymptomatic gallstone ileus
black pigment postprandial and/or decreased bile acid secretion) of parenteral nutrition, rapid y.o. use, OCPs, DM, U/S biliary pancreatitis (distal
(cirrhosis, hemolysis, cholesterol from liver into the bile, forming weight loss, hormonal hyper- cholecystectomy + R/O impaction)
pancreatitis) sometimes n/v cholesterol vesicles and eventually treatments like ocreotide - F>M triglyceridemia, complications Acute cholangitis
crystallizations acromegaly) IBD, terminal Choledocholithiasis
brown pigment ileum disease, ursodeoxycholic acid Mirizzi syndrome
(biliary infections) cholesterol supersaturation (chol>> bile other (secondary bile acid that
acids), accelerated nucleation, comorbidities reduces chol secretion into
gallbladder hypomotility (biliary sludge) bile)
FFFF (fat, female,
40s, fertile)
Biliary colic ACUTE cholelithiasis intermittent obstruction of cystic duct; may U/S gold standard diagnosis recurrent? Elective
or may not have gallbladder inflammation cholecystectomy +/-
RUQ/epigastric pain that intraoperative cholangiogram
radiates to right to clear out any stones in bile
shoulder/scapula; worse with duct if needed
meals, steady pain (15-60min)
that slowly resolves; NL
physical exam (+/- RUQ
tenderness); nl labs;
Acute Cholecystitis most common complication of chronic obstruction of gallbladder outlet by 1/3 of patients with cholelithiasis mostly clinical diagnosis but cholecystectomy + antibiotics majority of people have no
gallstones gallstone --> bile stasis --> severe gallstones U/S is accurate in up to 88%: (Gram negatives), IV fluids complications
inflammation --> damage to gallbladder gallstones + gallbladder wall
positive Murphy's sign mucosa thickening/edema + diabetics can have
(inspiratory halt upon palpation distended lumen gangrenous cholecystitis
of gallbladder); palpable acalculus cholecystitis - inflammation +
gallbladder in some due to hypomotility of gallbladder but no stone Elevated WBC, mild jaundice gallbladder empyema
inflammation; right subcostal (usually ICU or intubated patients) (slightly elevated bili), slightly
tenderness elevated AST/ALT/ALP perforation (distention,
RUQ pain - dull, persistent ache ischemia, pericholecystic
that radiates to right scapula; If U/S is questionable, proceed fluid collection --> abscess)
lasts longer than 6hours; n/v with HIDA scan (would not see
fever, elevated WBC any radioactivity in gallbladder -
diagnostic of acute
cholecystitis)
Choledocholithiasis often asymptomatic but wil have intermittent obstruction of common bile mild hyperbilirubinemia, ERCP + cholecystectomy
abnl labs/imaging duct (usually due to gallstones but small elevated ALP, transient (unless high risk patients -
minority arise de novo) AST/ALT spike would suggest these will have ERCP +
jaundice, pruritis, cholangitis passage of stone into URSA to dissolve the stones)
(if bacterial infection too) duodenum
U/S - identifies common bile

duct stones in 50% of patients
ERCP - diagnostic &

therapeutic
Cholangitis Charcot's triad (fever, RUQ impacted stone in common bile duct leads elevated WBC, bilirubin, ALP1. IV antibiotics
pain, jaundice) to permanent obstruction (unlike positive blood cultures 2. Elective ERCP to remove
choledocholithiasis - mobile stones); stone
Reynold's pentad (charcot's + increased pressure above the stone --> EUS/MRCP (regular U/S would 3. PCT if ERCP unsuccessful
altered mental status + bacterial proliferation --> septicemia miss bile duct stones) 4. cholecystectomy (after
hypotension) (gram negative bugs like E.coli, Klebsiella, infection cleared and stone is
Pseudomonas, Enterococcus, Clostridium) CT if worried about out)
complications
Gallstone ileus abdominal distention, usually in stone forms fistula between gallbladder remove stone + hi mortality/morbidity
elderly so delayed diagnosis due and small bowel, escapes the gallbladder, cholecystectomy
to other comorbidities and then migrates to become obstructed in
terminal ileum
Mirizzi Syndrome common hepatic duct obstruction by stone Cholecystectomy + ERCP or
in the cystic duct (stone from the outside cholangiogram to open the
obstructs the hepatic duct) bile duct
Irritable Bowel abdominal pain for at least 3 caused by increased intestinal motility --> heightened sensitivity due to 1. reassurance +
Syndrome (IBS) months, with onset at least 6 altered visceral sensation through enteric stressors lifestyle/dietary mods
months ago, that improves w/ and extrinsic nervous system --> 2. increased severity? Agents
defecation and is associated dysregulation of brain-gut communication that treat motility (anti-
w/ change in frequency or form diarrheals, anti-constipation)
of stool!! more of a psychiatric problem 3. no response to above?
Psych referral for pain
NO STRUCTURAL management
ABNORMALITIES
involves small and large

intestine
NOT a/w fever or dehydration!!

Acute pancreatitis epigastric pain (severe, nl have protective mechanisms against gallbladder stones that have abdominal pain + elevated supportive care, IV fluids, no damage to pancreas;
persistent) that radiates to pancreatitis (inactive enzyme produce as migrated to become obstructed lipase/ amylase pain meds majority of patients do NOT
back or left scapula proenzymes - can only be activated by in the Ampulla of Vater have any complications
enterokinase in small intestine; trypsin (pancreatic duct + common bile Gallstone pancreatitis? ERCP if gallstone in common
n/v, possible jaundice (if stones inhibitors to prevent auto-digestion) duct) Elevated bilirubin, liver bile duct systemic response: ARDS,
in common bile duct), enzymes, lipase/amylase, pleural effusion, acute renal
tachycardia insult (gallstones, alcohol) --> loss of alcohol WBC, + gallstones on antibiotics if infected/necrosis failure, myocardial
protective mechanisms --> proenzyme idiopathic imaging depression, metabolic
self-limiting!! activation --> digestion of pancreas --> other (drug induced - cholecystectomy if infected complications
acute changes --> ischemia --> release of dideoxyinosine/DDI, 6- (after antibiotics)
inflammatory mediators --> systemic mercaptopurine/ mortality in <20%
response (sometimes if severe) azathrioprine), iatrogenic - cessation of alcohol if etiology
ERCP, sphincter of Oddi, high early complications (DIC,
lipids, infection, pancreas shock, multiple organ
divisum, autoimmune, CF, failure); later complications
trauma, neoplasm) after 1 wk (pseudocyst,
increased pancreatic
infections, sepsis,
hemorrhage)
Chronic pancreatitis weight loss, n/v, anorexia, hereditary pancreatitis? Gene mutations in alcohol Autoimmune pancreatitis? control pain (NSAIDs, permanent damage to
abdominal pain (although some PRSS1, SPINK1 (PST1) idiopathic Swollen pancreas on CT, narcotics, intestinal uncoated pancreas
patients are relatively painless), others (hereditary, CF, +ANA, +IgG4 pancreatic enzyme therapy)
maldigestive diarrhea CF? gene mutation in CFTR causes pancreas divisum, pseudocysts, pancreatic
(steatorrhea, azotorrhea), impaired chloride conductance --> thick autoimmune) Structural: dilated pancreatic control diarrhea (intestinal ascites, pancreatic fistula,
pancreatic diabetes secretions/ mucus --> blocks pancreatic duct or dilated side branch of coated pancreatic enzyme splenic vein thrombosis
duct pancreatic duct on imaging; therapy)
calcium deposits throughout
autoimmune pancreatitis? Lymphocyte pancreas head (ERCP, CT,
infiltration causes fibrosis of pancreas --> U/S)
pancreatic dysfunction
Functional: parenchymal
changes denoted by
secretin/CCK test
Acute diverticulitis visceral dull pain that localizes antibiotics, surgical resection
and becomes severe of affected colon
somatoparietal pain in LLQ
constipation, diarrhea, fever
more common in sigmoid and

descending colon
Acute mesenteric sudden onset, crampy loss of vascular supply by superior/ inferior superior mesenteric artery endoscopy: huge ulcers due to
ischemia epigastric & periumbilical pain, mesenteric arteries embolus loss of blood supply
diarrhea, vomiting, bloating,
melena BUT minimal nonocclusive mesenteric
abdominal findings ischemia
diarrhea, vomiting, melena
pain out of proportion to

findings
Abdominal Aortic acute sudden onset severe mid-
Aneurysm (AAA) abdominal "tearing" pain
pulsatile, tender abdominal

mass
lightheaded, diaphoresis, nausea
Celiac disease affects duodenum > ileum immune response to gliaden fraction of gluten allergy 1/100 Irish / European iron, folate, fat-soluble gluten- free diet
gluten --> tissue transglutaminase (tTG) descent vitamin deficiencies
malabsorptive fatty diarrhea, alters gluten peptides when encountering a/w autoimmune disorders family history steroids in refractory cases
iron deficiency anemia, DQ2 or DQ8 --> formation of complexes (SLE, DM type I, RA, thyroid serum tissue transglutaminase
osteopenia, bloating, dermatitis that activate T cells --> inflammation & disease) (tTG) or anti-endomysial replace deficient vitamins
herpetaformis (IgA deposits on villi destruction antibody
skin) Endoscopy: scalloped pattern
histology: flattened/ atrophied

mucosal villi; lymphocytic &
plasma cell infiltration;
hyperplasia of crypts
Benign liver Cavernous most common benign liver vascular tumor defined by the proliferation gross: enlarged blood vessels NO needle biopsy (could possible that they could
neoplasms hemangioma neoplasm of blood vessels in the cavernous; appear as cause bleeding!) spontaneously rupture but
exophytic red/blue spongy very rare
masses that rise and push up surgical excision after > 9-
against capsule; no evidence 10cm
of cirrhosis
histology: multiple large

vascular channels (full of blood
or thrombosed)
Hepatic adenoma most patients who have these benign neoplasm of hepatocytes women of childbearing age age, OCPs histology: no inflammatory Bleeding risk!! (especially
present with hemorrhaged who have used OCPs infiltrates; glycogen, no bile subcapsular adenomas)
hepatic adenoma - sudden RUQ ducts visible
pain Common cause for sudden
gross: very bloody mass peritoneal hemorrhage in
young women
increased risk for HCC
Non-neoplastic often mistaken for neoplasms result from vascular malformation after women of histology: focal nodular
hepatocellular local vascular injury or AVM reproductive age hyperplasia, LOTS of bile
nodules ducts
gross: central scar (stellate

shaped)
Hepatocellular [FYI: most common most common primary malignant cirrhosis gross: large nodule arising prognosis best if single
carcinoma malignant neoplasm neoplasm hemochromatosis through a cirrhotic-appearing tumor is <2cm in size and
of liver? Metastatic liver capsule; multifocal good liver function
carcinomas from silent hepatomegaly (if non- chronic HBV or HCV carcinoma areas only in HCC
GI/colon, breast, cirrhotics), rapid increase in chronic alcoholism from chronic hep/ cirrhosis;
lung] liver size, worsened ascites, aflatoxin exposure o/w HCC is solitary lesion
increased pain hemochromatosis
histology: liver lobule cords
become 4-5 cells thick,
mitotic figures; markedly
enlarged and fatty appearing
cells; vascular invasion (worse
prognosis)
elevated alpha-fetoprotein
Cholangiocarcinoma markedly distended abdomen type of adenocarcinoma involving PSC, cysts of biliary tree, histology: formation of
from ascites (obstruction of intrahepatic and extrahepatic bile ducts chronic infection w/ liver haphazard glandular
lymphatic drainage --> large fluid fluke structures
accumulation) majority arise from extrahepatic biliary
tract, especially at hilum (Klatskin tumors CIRRHOSIS PATIENTS DO gross: dilated duct lumen from
jaundice - common hepatic duct) NOT HAVE INCREASED obstruction
RISK!
Adenocarcinoma of more common than arises in patients with recurrent trauma usually occurs in presence of Hispanics, Native histology: malginant lesions
gallbladder cholangiocarcinoma and inflammation due to chronic gallstones Americans have loss of cell polarity,
cholecystitis and/or cholelithiasis eccentric nuclei, &
hypochromatic areas;
resembles glandular structures
Cystic pancreatic serous cystic females; generally benign Female

neoplasms neoplasms
mucinous cystic Females Female
neoplasms
less predictable biologic
behavior
solid pesudopapillary young females YOUNG
tumors FEMALES
mostly indolent but some have
aggressive growth
Pancreatoblastoma malignant tumor of epithelial and mesenchymal elements KIDS!!! (rare
infancy/childhood cases in adults,
who would have
worse prognosis)
Pancreatic ductal most common malignancy of etiologic agent causes genetic mutations environmental: cigarete 4th leading cause of age (older patients elevated CA 19-9 surgery for symptom relief but <5% 5y prognosis
adenocarcinoma pancreas (80-90%) in k-ras oncogene, p15 tumor suppressor, smoking, petroleum product cancer death 60-80 y.o.) majority are surgically
p53 tumor suppressor, DPC4, BRCA2 exp, lack of fruits/veggies, gross: area of scarring/fibrosis unresectable Staging (T1- limited to
asymptomatic until late stage alcohol (due to chronic genetics: 1st around growing tumor pancreas, small; T2 - limited
then present with epigastric progression from PanIN to pancreatitis) degree relatives (yellowish/whitish and firm to to pancreas, larger; T3-
pain, unexplained weight loss, adenocarcinoma w/ hx, HNPCC, touch) - same fibrosis as beyond pancreas but not yet
painless jaundice, + - PanIN- 1: mild dysplasia (Her-2neu, host: chronic pancreatitis, hereditary breast/ chronic pancreatitis! celiac axis or SMA; T4 -
Trousseau's sign (migratory Kras) diabetes, pancreatic ovarian cancer beyond pancreas, involving
thrombophlebitis) - PanIN-2: moderate dysplasia (p16) intraepithelial neoplasia (BRCA2), familial Histology: fibrous tissue + abnl celiac axis and/or SMA)
- PanIN-3: severe dysplasia (p53, BRCA3, (PanIN) atypical mole epithelial cells (resembles
DPC4) syndrome, Peutz- chronic pancreatitis)
Jegher's
distributed most commonly in pancreas syndrome,
head, but time of diagnosis, they have hereditary
metastasized to liver, LNs, peritoneum pancreatitis
Pancreatic Acinar rare malignant tumor arise from acinar cells - secrete digestive poor prognosis but slightly
Cell carcinoma enzymes better than ductal
tumors secrete lipase/ trypsin/ adenocarcinoma
amylase
subcutaneous fat necrosis in

the skin (painful)
Pancreatic Islet Cell majority are functional (secrete 2% of all pancreatic gross: abundant blood supply malignancy determined by
Neoplasms enzymes that determine Insulinoma - body & tail, usually benign; tumors (unlike adenocarcinomas which hormone secreted, size of
symptoms) hard to control hypoglycemia; abnl HI are more white/ yellowish) tumor, & aggressiveness
insulin secretion
15-35% are silent (subclinical gastrinoma - 2/3 malignant, excess acid histology: monotonous
hormone levels) production --> PUD; Zollinger-Ellison appearing
syndrome
associated w/ MEN-1 VIPoma- watery diarrhea + hypokalemia
syndrome + achlorhydria
Glucagonoma - body & tail, malignant,
difficult to predict biologic refractory hyperglycemia/ diabetes,
behavior necrolytic migratory erythema
Somatostinoma - inhibitory so shuts
everything down; DM, steatorrhea,
hypochlorhydria, cholithiasis
Clostridium dificile inflammatory diarrhea - toxigenic, gram positive spore forming Antibiotic induced diarrhea! Antibiotic use, CT: pericolonic stranding & Metronidazole (Flagyl) if mild- shock, toxic megacolon,
characterized by tender LLQ, anaerobic bacillus hospital setting, colonic wall thickening - moderate perforation, sepsis, & death
increased frequency in bowel elderly, indicating infectious process
movements colonization --> disruption of normal flora chemotherapy, oral vancomycin for severe
by antibiotics --> toxin elaboration surgery, positive C. dif toxins (A/B) on cases
pseudomembranous colitis (particularly toxin B) --> diarrhea & colitis Ulcerative colitis PCR
probiotics decrease
a/w fever, dehydration, recurrence
tachycardia
Giardia lamblia (Flagellate) majority of cases are cysts in environment/water are ingested -- contaminated water supplies; found worldwide daycare, camping stool microscopy for O&P metronidazole or tinidazole
asymptomatic > once in GI tract, they develop streams, ponds (near [toxicity/ side effect =
trophozoites that attach to duodenal/ reservoirs - beavers, muskrats) disulfuram effect = nausea
1-2 week incubation period jejunal mucosa --> local inflammation & and severe symptoms]
villi blunting --> hypersecretion & daycare centers
symptoms: malabsorptive malabsorption
diarrhea, steatorrhea, cramps,
bloating, nausea, weight loss,
vomiting, fever
Entamoeba bloody stools (inflammatory), ingestion of cysts from environment leds immigrants & travelers to stool microscopy & metronidazole for extra-intestinal
histolytica dysentery to development of trophozoites in large developing world immunoantigens trophozoites; paranomycin manifestations (amoebic
colon --> invasion into epithelia (unlike for cysts liver/lung/ brain abscess)
Giardia, which is local and stays in liver abscess aspirate =
duodenum/jejunum) "anchovy paste" - rust colored
Apicomplexa Cryptosporidium self-limiting watery diarrhea (can sexual & asexual stage contaminated surface water or global histology: small round oocysts Nitazoxanide (NTZ)
parasites parvum be very mild) water supplies seen with AFB stain; within
epithelial cells but do not
immunosuppresed have chronic invade farther than this barrier
Isospora belli refractory illness w/ high mostly tropical regions histology: shaped like an "I" but TMP-SMX (trimethoprim-
recurrence rate has 2 nuclei sulfamethoxazole; Bactrim)
Cyclospora contaminated fruits & veggies mostly tropical regions histology: small round oocysts
cayetanesis seen with AFB stain; within
epithelial cells but do not
invade farther than this barrier
Microsporidia Enterocytozoan fungal organisms that produce pathology global histology: polar tubules ALB (albendazole), FMG
bienusi when spores are inhaled or ingested (fumagillin)
self-limiting watery diarrhea (can
be very mild)
immunosuppresed have chronic

refractory illness w/ high
recurrence rate
Microsporidia fungal organisms that produce pathology global histology: polar tubules ALB (albendazole), FMG
when spores are inhaled or ingested (fumagillin)
Encephalitozoon
intestinalis
Strongyloides (Nematodes) symptoms: itchy rash/ ground infection from skin penertration by larvae soil tropical, subtropical poor sanitation serology IVERMECTIN (binds to
stercoralis itch (initial penetration), larva in soil --> larvae migrate to blood, gaining areas; southern US places glutamate-gated chloride
currens (serpentigous mobile access to alveoli & lungs--> move towards biopsy would show adult channels causing parasite
rash), urticaria; Loeffler's trachea where they are swallowed --> barefeet worm burrowing in small paralysis & death)
syndrome (wheezing, transitory reach GI tract (small bowel) --> larvae bowel
pulm infiltrates, eosinophilia), GI mature and burrow in duodenum & immunocomp at
symptoms (if high worm burden: jejunum --> lay eggs that hatch in the risk for
abdominal pain, diarrhea, intestine --> autoinfection --> hyperinfection
malabsorption) hyperinfection syndrome syndrome
hyperinfection - fever, abd

pain, wheezing, dyspnea,
hemoptysis, sepsis
Other nematodes Ascariasis most common infection ingestion of eggs poor sanitation stool exam +/- eosinophils ALB (albendazole- inhibits
worldwide places polymerization of tubulin &
migrates from skin & lung as adult worm to tubulin dependent glucose
asymptomatic unless high worm jejenum uptake), MBZ (mebendazole)
burden --> obstruction
Enterobiasis pinworm ingestion of eggs --> infection of colon & daycare!!! scotch tape - characteristic ALB, MBZ
anus eggs
most common helminth in U.S.
female nematodes migrate out of rectum
ANAL ITCHING to the anus, where they lay eggs
Trichuriasis whipworm invades & destroys colon mucosa, causing tropical areas stool exam +/- eosinophils
colitis & rectal prolapse
colitis (bloody stools), rectal
prolapse infects cecum & colon
Hookworm major contributor to global acquired through skin, after which the 700 million people
malnourishment worm uses teeth to attach to lungs & small affected; primarily
bowel mucosa developing countries
high worm burden --> significant
blood loss, low albumin, and low
nutrients
Cestodes/ flatworms Taenia solium cysticercosis --> epilepsy PORK
Taenia saginata BEEF
Echinococcus hyatid cysts DOG, SHEEP
Diphyllobothrium vitamin B12 deficiency, FRESHWATER FISH
latum macrocytic anemia
Blood flukes Schistosomiasis swimmer's itchy, Katayama FRESHWATER
fever, chronic dz
Liver flukes Clonorchis sinensis increased risk of RAW FRESHWATER FISH
Cholangiocarcinoma
Fasciola hepatica RUQ pain, fever, jaundice WATERCRESS
E. coli ETEC (Traveler's occur usually after travel to heat labile enterotoxin causes increased contaminated food & water hydration; antimotility
diarrhea) resource poor country; short- cAMP secretion --> secretion of chloride meds; fluoroquinolones
lived secretory diarrhea into lumen --> water follows chloride (CIPRO)
(hence watery diarrhea)
EHEC (SHEC; E.coli hemorrhagic colitis (bloody Shiga cytotoxin damages cells/brush food, water, & person-to- appears colorless on sorbitol SUPPORTIVE CARE ONLY Hemolytic uremic
O157:H7) diarrhea) border/ mucosa --> bloody colitis person transmission agar plate; Shiga toxin assay (antibiotics are syndrome (HUS) =
contraindicated) anemia,thrombocytopenia,
renal failure [1wk post
diarrhea; more common in
children, but 12% affected
require dialysis or die from
ESRD]
Salmonella Salmonella typhi typhoid fever contaminated human sewage seen often during
environmental crises
Salmonella self-limited acute enterocolitis; contaminated food with animal elderly, ANTIBIOTIC TX NOT decreased gastric acidity
typhimurium 6-48h post-food ingestion & waste immunocomp, RECOMMENDED in lowers infectious dose -
Salmonella lasts 3-7days invasive disease, uncomplicated gastroenteritis increased susceptibility
enteritidis Sickle cell (could increase organism
watery stools, abdominal carriage)
cramping, n/v
Food Poisoning immediate disease about 1-16h preformed toxins (S. aureus - potato
post ingestion salad, cream pastries, mayo; Bacillus
cereus - fried rice, spores)
n/v, watery or inflammatory
diarrhea, abdominal cramps quickly produced toxins (C. perfringens,
B. cereus)
microbial contamination of food

products (V.cholera - shellfish; ETEC,
EHEC- ground beef, raw veggies, unpast
juice; Salmonella - poultry, eggs, beef,
dairy, peanuts; Campylobacter - poultry,
raw milk; Shigella; Vibrio parahemolyticus -
mollusks, crustaceans; norovirus)
Rotavirus primary cause of acute nonenveloped dsRNA virus fecal-oral; possible airborne 600-850K deaths/ year antigen assays, RT-PCR, rehydration
gastroenteritis in young spread globall culture
children in U.S.
winter season
Vomiting, fever, watery diarrhea
--> dehydration & electrolyte abnl
Norovirus most common cause of relatively low infectious dose so easy to fecal-oral; aerosol-vomitus; cruise ships supportive treatment only
foodborne outbreaks spread from person to person fomites; contaminated food
investigated
sudden onset N/V; short lasting

watery diarrhea
Small bowel acute onset, intermittent post-operative intra-abdominal Elevated WBC count; abnl IV fluids, correct serum
obstruction abdominal pain; vomiting adhesions; hernias (bowel leaves serum electrolytes; renal failure electrolytes; NG tube
(bilious, fecal), obstipation, peritoneal cavity and becomes (decompress stomach,
abdominal distention obstructed); neoplasms;congenital XR: dilated SB loops minimize further distention)
atresia/stenosis, inflammatory causes CT: dilated SB loops +
PE: periods of increased bowel (IBD, ischemia, diverticulitis, radiation, transition point where complete SBO +/- evidence of
sounds followed by intervals of drugs), intussusception (bowel telescopes obstruction occurs peritonitis - systemic Abs +
quiet; hi pitched or musical BS; into another part of the bowel); gallstones, laparotomy
abdominal tenderness; guarding volvulus, metastasis, endometriosis, air fluid levels
(strangulation/ bowel abscess partial SBO - above
ischemia); systemic recommendations unless no
manifestions of dehydration improvement, then proceed to
(tachycardia, tachypnea, AMS, surgery
oliguria, hypotension)
Large Bowel sigmiod colon & cecum are malignancy, volvulus, stricture CT, barium studies, XR IV fluids, correct serum
Obstruction (colonic) most common sites for colonic secondary to diverticulitis; Crohn's, electrolytes; NG tube
volvulus endometriosis, intussusception, extrinsic colonic obstruction secondary (decompress stomach,
tumors, fecal impaction to malignancy? Dilated colon minimize further distention)
periumbilical/ hypogastric abd until tumor, after which colon
pain, abd distention, diarrhea or narrows off (should use Benign strictures - surgery
obstipation colonoscopy to biopsy tumor)
malignant strictures - surgery
benign colonic strictures? sigmoid volvulus? Bent inner or colonic stents
Thinner stool tube appearance + dilated
colon sigmoid volvulus -
malignant colonic strictures? protoscopic/colonoscopic
Hematochezia, iron def anemia, decompression; rectal tube;
weakness, weight loss, vomiting, sigmoid resection &
insiduous onset coloproctostomy
cecal volvulus - NO
COLONOSCOPY; cecostomy,
resection
Bowel ileus failure of nl intestinal motility postoperative; inflammatory (diverticulitis, XR/CT: presence of gas in NPO until symptoms resolve;
in absence of obtructing lesion pancreatitis), metabolic (abnl electrolytes); stomach, SI, colon + dilated NG tube; correct electrolytes;
neurogenic, meds (narcotics) small bowel limit narcotics; get patient
poorly localized abdominal pain, moving out of bed!
abdominal distention, n/v, no mechanical obstruction!!
obstipation
hypoactive bowel sounds

acute colonic pseudo severe abdominal distention critically ill patients dilation of ALL segments of
correct reversible causes; mortality 0-32%
obstruction with absence of stool/gas colon neostigmine (AChE
passage inhibitor), endoscopic
decompression, percutaneous
cecostomy, surgical
decompression
Inflammatory bowel Crohn's disease RLQ pain, weight loss, affects any portion of GI tract; skip persistent infection (H. pylori, highest prevalence in Caucasians CBC, elevated ESR/CRP, low induction of remission? mostly affects ileocolic
disease arthritis/arthalgias, watery lesions, spares rectum, transmural invasive E. coli, Listeria), Europe & North America albumin if weight loss Steroids, antibiotics area/terminal ileum, small
diarrhea inflammation; granulomas defective mucosal integrity Ashkenazi Jews; bowel, & colon but can affect
(altered mucus, increased M=F colonoscopy: severe maintenance of remission? ANY part of GI tract
inflammatory; obstructing; disruption of intestinal epithelial barrier + perm, impaired resolution), SMOKING in inflammation leading to Antibiotics + 6MP/AZA (stomach, esophagus)
fistulizing/microperforating dysregulated immune response --> dysregulated immune Crohn's disease ulcerations/ obstruction (inhibit purine biosyn in B & T
subtypes secretion of IL-23 by macrophages --> response, dysbiosis cells) + biologics (antibodies
induction of TH17 cells to activate IL-17 -- (decreased protective bacteria, NSAIDs histology: transmural inflamm against cytokines & adhesion
extraintestinal manifestations? > abnormal processing of antigens increased pathogenic bacteria) process w/ lymphocyte molecules)
FTT, erythema nodosum (deficient autophagy) genetic infiltrates; non-necrotizing
(extensor surfaces), pyoderma predisposition granulomas
gangrenosum, monoart/ CARD15/NOD2 mutation - a/w ileocolonic
asymm/ large joint peripheral dz; early onset; early surgery; early
arthritis, uveitis, episcleritis, recurrence post-surgery; familial CD
PSC (more in UC; runs
independent course from IBD),
sacroileitis, ankylosing
spondylitis
Ulcerative colitis bloody diarrhea, tenesmus, only involves colon, rectum ALWAYS CBC: microcytic anemia; low induction of remission? 40% proctitis alone; 30% left
LLQ pain, rectal bleeding, involves, continuous distribution in albumin (if weight loss), Steroids, 5-ASA (reduce sided disease; 30%
arthritis/ arthalgias involved area (no skip lesions), elevated ESR/CRP, stool prostaglandins) pancolitis
inflammation in mucosa only culture to R/O infection;
extraintestinal manifestations? endoscopy w/ bx Maintenance of remission? intractable disease;
FTT, erythema nodosum disruption of intestinal epithelial barrier + 5-ASA, 6MP/AZA, biologics hemorrhage; perforation;
(extensor surfaces), pyoderma dysregulated immune response --> endoscopy: mild (erythema, toxic megacolon; colon
gangrenosum, monoart/ secretion of IL-23 by macrophages --> preserved circular muscles); extremely severe? Colectomy cancer (correlates w/
asymm/ large joint peripheral induction of TH17 cells to activate IL-17 -- moderate (edema, duration, extent, severity of
arthritis, uveitis, episcleritis, > defective epithelial barrier function inflammatory cell infiltrate, UC)
PSC (more in UC; runs bleeding/ ulcerations); severe
independent course from IBD), (denuded mucosa, blunted
sacroileitis, ankylosing haustrations, thickend w/
spondylitis inflamm material)
histology: erosion of mucosa,

crypt abscesses (due to
neutrophilic infiltration)
Acute appendicitis early: non-specific, dull obstruction of appendix lumen by fecolith 250,000 cases per year elevated WBC count pre-op antibiotics + perforation --> peritonitis,
periumbilical pain --> appendix distention, inflammation & in US immediate appendectomy if abscess formation, sepsis
later: well-localized RUQ pain @ infection CT: donut sign = thickened sx present for 24-72h
McBurney's point, n/v, fever ages 10-30 appendix wall
if sx longer than 5d, delayed
M>F surgery in lieu of long course
antibiotics
Diverticulosis herniations of mucosa and submucosa western world low fiber diet
through defects in muscularis; usually in
sigmoid colon age!!
Diverticulitis complicated diverticulitis - microscopic or macroscopic perforation of 10-25% of patients w/ CT - complicated will show uncomplicated? Cipro + 20-40% of patients will have
perforation, abscess, diverticulum (usually via erosion of wall by diverticulosis peritonitis, perforation, abscess metronidazole, colonoscopy a second attack, after which
fistulization fecoliths or by increased intraluminal formation after recovery complications are more likely
pressure)
uncomplicated - inflammation complicated? Peritonitis (IV
w/o complications; MAJORITY antibiotics + surgical
of cases exploration); abscess requires
drainage
LLQ pain & tenderness; low
grade fever surgery (laparoscopic
resection) after complicated
episode or 2-3 episodes of
uncomplicated;
immunosuppressed
Screening /
Education
certain foods or trauma

can precipitate the lesion
cancers a/w HPV have

better prognosis though!
Screening /
Education
Screening /
Education
Prognosis determined by
depth of invasion
Prognosis determined by
depth of invasion
aggressive behavior
determined by size and
number of mitoses
Screening /
Education
indications for surgery

(PUD bleeding): massive
hemorrhage leading to
shock; prolonged blood
loss w/ more than 6 units
transfusion; recurrent
bleeding despite
endoscopic tx; recurrent
bleeding during
hospitalization
Screening /
Education
Screening /
Education
IgG antibody
vaccination to protect
against HepA
vaccination [IM injection

@ 0, 1, 6 months]
provides HBaAg -
required for all HCWs
Hepatitis B
immunoglobulin (HBIG)
- offered to high risk
patients, exposed
infants, or liver
transplant patients
(before new liver in, 1
week post-transplant)
Screening /
Education
screen all baby

boomers!!
1. R/O other causes of

liver disease
2. consider every drug/
med/ herbal
3. stop all non-essential
meds
4. known common
patterns (INH, statins,
etc)
5. Know potential
specific treatments
6. DO NOT
RECHALLENGE
(exception: tylenol)
1. R/O other causes of
Screening /
liver disease
Education
2. consider every drug/
med/ herbal
3. stop all non-essential
meds
4. known common
patterns (INH, statins,
etc)
5. Know potential
specific treatments
6. DO NOT
RECHALLENGE
(exception: tylenol)
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Ranson criteria for

severity upon
admission: initial
admission- assess
patients age > 55, WBC,
AST, LDH enzymes, &
glucose; within 48h,
assess Ht, Ca++, BUN,
pO2, fluid deficit, base
deficit; if initial and/or
48h labs meet criteria,
can figure out morbidity
& mortality
Screening /
Education
Screening /
Education
Screening /
Education
bottled beverages; avoid

ice & uncooked food
cook ground beef; avoid

food cross
contamination; hand
wash after all animal
contact; diaper hygiene
at pools
Screening /
Education
live, oral vaccines for

infants (Rotarix)
Screening /
Education
Disease Clinical Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Screening /
Variants Education
Fanconi's metabolic acidosis (bicarb proximal tubule dysfunction from global Cystinosis (auto
Syndrome wasting), hypophosphatemia defect in all PT transporters recessive; most
(Ricket's - bow legged, prominent common cause in
forehead, wrist widening, FTT; childhood)
osteomalacia), glucosuria, low
serum uric acid, amino aciduria
Secondary Adrenal metabolic alkalosis, hypokalemia, adrenal gland autonomously produces

causes of adenoma refractory HTN aldosterone, without signals from ATII; thus,
hypertension aldosterone is constitutively active despite
volume repletion. Aldosterone then acts on
CCD to increase Na+ reabsorption and K+
secretion [excess aldosterone effect]
(listing) A- obstructive sleep Apnea,

Adrenal glands (cortex -
aldosterone, cortisol; medulla -
pheochromocytoma)
B - bruits (renal artery stenosis),
bad kidneys
C- catecholamines, coarct of
aorta, Cushing's syndrome
D - drugs, diet
E - erythropoietin excess,
endocrine (thyroid, growth
hormone)
Liddle severe HTN from Na retention, 1/2 of collecting duct sodium channels have autosomal dominant
syndrome low aldosterone & renin levels, mutation that renders them constitutively disorder
hypokalemia, metabolic alkalosis active despite normal volume levels and no
aldosterone present; hence, constant CD
sodium reabsorption and K, H secretion
Congenital 21-hydroxylase life-threatening hyperkalemia, volume depletion --> renin secretion --> ATII autosomal recessive usually diagnosed @ birth w/ NBS synthetic aldosterone
adrenal deficiency profound metabolic acidosis, production; however, the adrenal gland has disorder infusion
hyperplasia hyponatremia, severe volume genetic defect in which it cannot respond to
depletion ATII to make aldosterone [aldosterone
deficiency/ absence]
Pseudohypo- elevated aldosterone levels, absence of functional sodium channels in autosomal recessive
aldosteronism hyponatremia, profound cortical collecting duct, thus CCD cells do not disorder
Type I metabolic acidosis, hyperkalemia reabsorb Na or secrete K despite very high
levels of aldosterone [aldosterone
deficiency/ absence]
Gitelman similar symptoms to side effects genetic defect in Na/Cl cotransporter in DCT autosomal recessive check magnesium because replace K, Mg losses;
syndrome of thiazide diuretics (same transporter that is blocked w/ disorder hypomagnesemia can cause restore intravascular
thiazides) refractory hypokalemia volume w/ salt
volume depletion, hypokalemia,
metabolic alkalosis,
hypomagnesemia, salt cravings,
hypocalciuria, hyponatremia
Bartter early age presentation genetic defect in NKCC co-transporter in TAL autosomal recessive
syndrome similar sx to side effects of loop of loop of Henle, causing volume depletion disorder
diuretics and aldosterone production
hyponatremia, hypokalemia,
hypochloridemia, metabolic
alkalosis, hypercalciuria
Variants Education
Hyponatremia seizures (neuro emergency) or decreased effective circulating volume from electrolyte panel, calculate serum acute - water restriction seizures
can be gradual onset (intact true volume loss (GI loss) or perceived osmolality (<150 mL/day),
neuro exam) volume loss (edematous states - CHF, hypertonic saline, loop overcorrection can
cirrhosis, nephrotic syndrome), thiazides, thyroid function tests, med hx, urine diuretic (creates cause CPM
SIAD, cortisol deficiency, hypothyroidism, osmolality isoosmotic medulla,
primary (psychogenic) polydipsia, decreased preventing water
solute intake (beer potomania), or reset reabsorpton), Vaptan (V2
osmostat receptor antagonist- $$)
chronic (tumor)- water

restriction (though
horrible QoL), hi salt/ hi
protein diet, loop diuretic,
demeclocycline
(contraind in liver dz),
urea, lithium (manic
depressive d/o), vaptan
Syndrome of 1. normovolemic, mildly normally, ADH is released with hypovolemia CNS disorders, Imaging of head/lungs, normal urine Treat sodium deficit (Na+ hyponatremia can
Inappropriate hypervolemic (NEVER (hi serum osmolality), resulting in the pulmonary disorders, osmolality, low serum osmolality, needed = 0.6x body cause seizures,
Anti-Diuresis hypovolemic) retention of water; however, patients with ectopic ADH hyponatremia weight (kg) x (120- cerebral edema
(SIAD) 2. nl renal, adrenal, and thyroid SIAD have hyponatremia with very production, meds plasma Na)
functions concentrated urine - suggesting that ADH is (chlorpropamide, overcorrection of
3. serum hypotonicity WITHOUT active despite normal or hypertonic volume cyclo-phosphamide normal saline is sodium levels can
maximally dilute urine (patients levels (would expect very dilute urine in low IV, carbamezepine) contraindicated!! cause central
have inappropriately serum osmolality situations) pontine neurolysis
concentrated urine) 3% hypertonic saline + (CPM)
loop diuretic
Hypernatremia water loss (insensible loss from skin, lungs;
renal loss from DI, osmotic diuresis; GI loss,
loss into cells from seizures, severe exercise,
rhabdomyolysis)
hypertonic saline IV
Central complete, polyuria, dilute urine, problem with the production (damage to idiopathic, water deprivation study (water exogenous ADH helpful
diabetes partial hypernatremia hypothalamus) or secretion of ADH (damage hypothalamus deprivation = increased plasma for complete and partial
insipidus to posterior pituitary) trauma, hypoxic osmolality but NO concurrent central DI [dDAVP -
encephalopathy, increase in urine osmolality) desmopressin nasal
post- spray; vasopressin
hypophysectomy, tannate in oil, aqueous
neoplastic vasopressin]
infiltration,
sarcoidosis, partial central DI - can
Sheehan's syndrome also use chlorpropamide,
carbamezipine, or
clofibrate
Nephrogenic Congenital high urine output (20L/day), X- linked mutation in V2 vasopressin receptor children hydration + low sodium
diabetes bladder enlargement & OR autosomal recessive mutation in diet
insipidus obstruction (from attempts to aquaporin P2 water channels causes failure
retain urine), hypernatremia to respond to ADH, thus water is not
reabsorbed (water wasting)
Acquired - polyuria, dilute urine, destruction of renal medulla (papillary water deprivation study (water not responsive to
complete, hypernatremia necrosis) from sickle cell anemia, analgesic deprivation = increased plasma exogenous ADH
partial nephropathy, or renal failure osmolality but NO concurrent (because problem with
increase in urine osmolality) end-organ!)
osmotic diuretics like glucose, mannitol, urea
thiazide diuretics + low
electrolyte abnl (hypercalcemia, sodium diet (decreases
hypokalemia) overall urine output by
keeping mild volume
depletion state and
increasing PCT
reabsorption)
Variants Education
Edematous CHF edema Na retention: Chronic CHF = decreased

states baroreceptor sensitivity & increased
SNS/RAAS activity = increased PTC
reabsorption of Na, H2O = decreased
delivery of Na, H2O to distal tubule =
activation of aldosterone (failure to escape
ald) = even more Na, H2O retention =
increased cardiac filling pressure
water retention: chronic CHF = non- osmotic

ADH release = activation of V1 receptor
(heart remodeling, coronary constriction,
vasoconstriction, myocardial ischemia, and
increased cardiac afterload) and V2 receptor
(water retention in CCD, increased preload) =
worsening wall stress
Cirrhosis ascites early cirrhosis results in hepatocyte damage hepatorenal

and NO release = splanchnic arterial syndrome (cirrhosis
vasodilation and mechanical obstruction to = portal HTN =
portal flow = portal hypertension (portal press splanchnic
> 12mmHg) = activation of SNS (NE), RAAS, vasodilation =
& ADH = Na & H2O retention = ascites = stimulation of vaso-
increased plasma volume and cardiac output constriction in
kidney =
hepatorenal
syndrome)
Nephrotic (general) severe proteinuria (>3.5g / 24h Derangement in the glomerular capillary Primary glomerular
95% of cases UA renal failure
syndrome urine), low serum albumin, walls increased permeability to plasma disease in children 24h urine protein infection (Staph,
generalized edema (due to loss proteins massive proteinuria and loss of related to albumin blood test, lipid panel pneumococci; loss
of oncotic pressure from loss of albumin (so much that the liver cant catch systemic disease w/ primary glom renal biopsy w/ immunofluorescence of proteins like Ig,
large blood proteins), up) loss of albumin (oncotic pressure) renal manifestations dz (only 60% complement)
hyperlipidemia (triggered by causes leakiness of the vasculature (DM, SLE, of adult
hypoalbuminemia), hyperlipiduria edema Amyloidosis, drugs - cases) thrombosis, thrombo-
gold, penicillamine, embolism (loss of
Liver realizes that so much protein is being heroin; infection - 40% of adult anticoagulant
lost and ramps up production of lipoproteins; malaria, syphilis, cases from factors)
increased production accompanied by hep, HIV; systemic dz
abnormal transport and decreased malignancy - w/ renal
catabolism leads to hyperlipidemia carcinoma, manifestation
lymphoma, s
melanoma; misc -
bee sting allergy)
Congenital onset of nephrotic syndrome genetics most resistant to most death secondary to
Nephrotic (massive proteinuria, common in treatments; severe cases sepsis
Syndrome hypoalbuminemia) within the first Finland require bilateral
3 months of life, but usually nephrectomies and other complications -
within a few days subsequent lifelong hyper-coagulopathy,
dialysis infection, stroke
a/w premature birth, large
placenta, skeletal deformities,
poor motor development,
progressive renal failure
Membranous elevated creatinine vast majority are onset ages Renal bx: PAS - increased mesangial ACEI + steroids (or
nephropathy primary/ idiopathic 30-50 y.o. matrix, thickened capillary loops; immunosuppresants like
subepithelial dense deposits Silver stain - thickend GBM, cyclophosphamide if not
and thickened GBM 15% of cases are One of most glomerular spikes response)
result of systemic dz common EM: subepithelial immune complex
60% of pts will have persistent (autoimmune - SLE, primary deposits; thickened GBM
proteinuria (10-30% may have infxn - hepB/C, glomerular IF: granular subepithelial deposits for
partial --> complete remission); syphilis, malaria, causes of IgG along capillary loops
40% develop progressive renal schistomiasis; drugs - nephrotic
insufficiency or ESRD penicillamine, syndrome in
captopril, gold, Hg, adults
NSAIDs;
malignancies - colon,
lung, melanoma)
Variants Education
Minimal normal biopsy findings EXCEPT epithelial cell (podocyte) injury most Creatinine: nl (nl GFR) steroids (90% resolution) <5% develop
change diffuse foot process effacement common chronic renal failure
disease nephrotic LM: nl glomerulus
insidious onset in o/w healthy syndrome in IF: none
kids; proteinuria w/ preserved kids EM: diffuse foot process effacement
kidney function (fusion)
Focal important to distinguish from primary /idiopathic renal bx: scarred interstitium poor response to steroids 50% have renal
Segmental minimal change dz!!! (thyroidization), pink dense obsolete failure in 10y
Glomerulo- secondary (HIV- & scarred glomeruli; focal/ segmental
sclerosis Sclerosis involving segments collapsing variant of scarring of glomerulus 20% rapidly
(FSGS) of some, but not all, glomeruli FSGS; heroin use, (proteinaceous collection of hyaline progress to ESRD in
(hence focal/segmental) HTN, reflux in the sclerotic segment @ higher 2y
nephropathy, power)
Abnl creatinine (abnl renal unilateral renal recurrence in 25-
function), can have RBCs/ agenesis/ dysplasia; IF: none 50% of transplants
hematuria on UA (in addition to primary EM: diffuse foot process effacement
typical nephrotic syndrome sx), glomerulopathies, + focal/segmental sclerosis of
HTN SCC, renal glomerulus
transplant, diabetic
little tendency for spontaneous nephropathy,
remission obesity)
Nephritic (general) hematuria (gross, microscopic,

presentation +/- RBC casts in UA),
acute renal failure (azotemia -
increased BUN; oliguria),
HTN,
+/- proteinuria,
+/- edema,
usually secondary to acute GN
Acute post- very similar to expt acute serum similar to EASS strains of group A B- decreasing serology: elevated anti-streptolysin >95% of kids recover w/ <1% of kids do not
streptococcal sickness! hemolytic freq in U.S. O (ASO) titers, hypo- conservative tx (self- improve, become
GN (post- one-shot antigenemia results in deposition streptococci complementemia, +/- cryoglobulins limiting dz) severely oliguric,
infectious GN) Abrupt onset of malaise, fever, of circulating immune complexes in Children 6- and develop rapidly
nausea, oliguria, & hematuria 1-4 glomeruli and activation of classical pathway 10 y.o. but histology: diffuse (>50%) progressive GN
weeks after streptococcal of complement also adults proliferation of glomeruli,
infection of pharynx or skin hypercellularity (PMNs), RBC casts in
(impetigo) also has in-situ formation of immune tubules; endocapillary proliferation
complexes from cross-rxn of anti-strep
coca-cola colored urine antibodies w/ glomerular antigens EM: sparsely distributed
subepithelial humps, mesangial
RBC casts in urine, mild immune deposits
proteinuria, periorbital edema,
mild-mod HTN IF: starry sky for IgG, C3
Membrano- variable presentation (hematuria, kids > adults histology: diffuse proliferative GN none very effective few spont
proliferative mild proteinuria, mixed nephrotic- w/ lobular appearance; mesangial remissions
GN Type I nephritic) proliferation, thickened capillary
(MPGN1) loops, variable endocapillary prolif slowly progressive
MPGN is predominantly but unremitting (50%
hematuric but an be IF: granular pattern of C3 develop chron renal
nephrotic/nephritic; poor deposition failure in 10 y)
prognosis in contrast to APSGN;
characterized by diffuse EM: subENDOthelial immune
proliferative GN but looks like deposits, mesangial
APSGN under LM; predominantly interpositioning w/ formation of
C3 deposition; subendothelial new GBM
immune deposits under EM;
mesangial interpositioning and
silver stain: tram-tracking
tram-tracking by silver stain
Variants Education
Membrano- looks similar to Type I under LM abnormalities suggest activation of LM: diffuse proliferative GN w/ lobular
proliferative alternative complement pathway: decreased appearance (just like type I)
GN Type II dense deposit disease - serum C3 but normal C1, C4; diminished
(MPGN2) linearized bands of C3 levels of factor B and properdin (components linearized bands within the GBM
deposits of alternative complement pathway)
IF: linearized C3 dense deposits
a/w partial lipodystrophy C3 convertase cleaves C3 to C3bBb; along peripheral capillary loops,
C3 convertase normally stabilized by some mesangial deposits
hypocomplementemia for C3 properdin & C3NeF = C3 nephritic factor
only!! (70% of patients w/ MPGN2) to keep
alternative pathway active
C3NeF = autoantibody that binds to C3

convertase, stabilizing the convertase and
protecting it from enzymatic degradation;
thus, persistent C3 degradation and
hypocomplementemia
Crescentic GN Anti- GBM dz: limited to kidneys, in-situ antibody formation to fixed antigen in IF: linear IgG appearance along
(Anti-GBM, rapidly progressive GN (RPGN) non-collagenous domain of Collagen type IV glomerular capillary loops
Goodpasture's w/ nephritic presentation and in GBM
dz) ARF histology: cellular crescents
ruptured GBM from antibodies attacking anti- (parietal epithelial cell proliferation)
Goodpasture's: involves NC1 domain causes destruction of collagen
kidneys & lungs (pulmonary- type IV and release of fibrin, stimulating the
renal syndrome - ARDs + proliferation of parietal epithelial cells and
RPGN) formation of cellular crescents
similar to expt anti-GBM dz
Goodpasture's dz: anti-NC1 domain Abs

cross react w/ pulmonary BMs, causing
rupture and pulmonary hemorrhage
Systemic Diabetes Type I (10%) - deficiency of Diabetic nephropathy: affects glomeruli, 25.8 million renal bx: inc mesangial matrix, atherosclerosis year 2: kidney
diseases w/ mellitus - insulin secretion vessels, & tubointerstitium children and hypercellularity, glomerular (AAA, MI, PVD); enlarges,
renal diabetic Type II (80-90%) - peripheral 1. High level of glucose causes non- adults in the hyalinosis, slit-like lumen, amputation; HTN; increased GFR
manifestations nephropathy insulin resistance, inadeq enzymatic glycosylation of proteins, creating U.S. glomerular microaneurysms, CVA, stroke;
pancreas compensatory advanced glycosylation end-products that hyaline arteriolo-sclerosis of retinopathy, year 5: GFR
response can result in tissue damage afferent & efferent glomerular peripheral drops and
Early events: microalbuminuria, 2. Hyperglycemia activates PKC, inducing arterioles, thickened tubular BM neuropathy, plateaus
hyperfiltration (inc GFR), kidney activation of pro-angiogenic molecules like (tubulointerstitial scarring) infection,
enlargement, inc mesangial VEGF IF: none nephropathy year 15-25:
matrix & GBM thickening 3. Hyperglycemia disturbs the polyol EM: greatly expanded mesangium, steady decline in
pathway, causing the metabolism of sorbitol thick GBM, foot process effacement leading cause of GFR (leading to
diffuse/nodular GS, glom and decreased intracellular antioxidant time course: thick GBM --> diffuse kidney failure massive
hyalinosis lesions, glom capillary reserves, increasing susceptibility to free mesang sclerosis --> nodular proteinuria)
microaneurysms, interstitial radical damage glomerulo-sclerosis (Kimmelstiel- papillary necrosis
fibrosis, tubular atrophy, hyaline Wilson nodules) (acute
ateriolo-sclerosis, accelerated pyelonephritis seen
atherosclerosis more in DM but also
PN w/ obst and
NSAID abuse)
Systemic lupus general: unpredictable lupus breakdown of central and peripheral self- renal serologies: ANA, anti-dsDNA; anti-
erythematous - flares (hematologic sx, arthritis, tolerance --> autoimmunity resulting in a wide involvement Sm;hypo-complementemia
lupus skin rash, fever, fatigue, weight range of autoantibodies 30-90% of histology: endocap proliferation;
nephritis loss, renal involvement, etc.) SLE patients cellular crescents, karyorrhexis,
fibrinoid necrosis (pink fibrin
anti-dsDNA - suggests kidney material), wire loops, pseudothrombi
involvement (pink globs)
Class II: LM (meangial expansion;
Class II (mesangio-proliferative- IF & EM (mesang deposits - IgG)
benign presentation), IV (diffuse Class IV: >50% of glomeruli have
LN- sx + active sed UA + histologic activity, subend dep
proteinuria, dec GFR, elev creat Class V: granular IF of glom cap
& serologies, hypocomp), V loops, subepit dep w/ spike form,
(membranous LN) uniform thickened cap loops
Variants Education
Microscopic P-ANCA vasculitis systemic necrotizing vasculitis of small precipitating immune histology: leukocytoclastic vasculitis
polyangitis vessels (arterioles, venules, capillaries) reaction (PCN, (fibrinoid necrosis, transmural
palpable purpura - skin, mucus microbes- Strep, arteritis, fibrinoid arteriolitis); acute
membranes, lungs, brain, heart, autoantibodies against myeloperoxidase heterologous necrotizing GN (segmental fibrinoid
GI, kidneys, nerves, muscle proteins, tumor necrosis of glomerulus w/ +/-
Pauci-immune mechanism: presumed antigens) formation of cellular crescents)
clinical features depend on immune mech but no IF or EM evidence of
involved organ system: immune complex deposition in organs
hemoptysis, arthalgia, abd pain,
hematuria/ proteinuria,
hemorrhage, muscle pain/
weakness
kidneys: leukocytoclastic
vasculitis and acute
necrotizing (and often
crescentic) GN
Wegener's Classic triad (acute necrotizing autoantibodies directed against proteinase-3 M>F histology: transmural arteritis +
granulomatosis granulomas of ENT, lungs - affecting both small and medium sized granulomatous vasculitis
hemoptysis; necrotizing vessels avg age 40;
vasculitis of small & med peak incid in
vessels; acute 50y.o.'s
necrotizing/crescentic GN)
C-ANCA
mimics TB -necrotizing
granulomas, cavitary lesions
Henoch- palpable cutaneous purpura deposition of polymeric IgA1 within arterioles unknown children & cutaneous bx: fibrinoid necrosis of
Schonlein (usually on lower half of body); causes leukocytoclastic vasculitis and young adults blood vessel (fibrinoid arteriolitis) +
Purpura (HSP) - arthritis, acute abd pain (+/- activation of alternative complement pathway perivascular cuffing of inflamm cells
HSP nephritis bloody diarrhea), HSP nephritis
(IgA nephropathy; hematuria + IF: IgA within dermal capillaries
proteinuria)
kidney bx: mesangial prolif,
mesangial dense deposits; IF:
deposition of IgA in mesangium
Plasma cell multifocal destructive bone proliferation of a single B-cell clone that 50-60 y.o. bx: atypical plasma cells in bone generally poor
myeloma tumors composed of plasma cells synthesizes and secretes a single marrow (lots of neoplastic Ig and light prognosis
(multiple --> osteoplastic breakdown homogenous immunoglobulin or its fragments chains in cytoplasm; forms
myeloma) - manifested most often in (plasma cell dyscrasia) cytoplasmic inclusions - Russell
light chain vertebral column (lower back), bodies)
cast ribs, skull, pelvis, femur, clavicle, proliferation and survival of myeloma cells
nephropathy scapula dependent on IL-6 (hi IL-6 levels a/w poor XR: buckshot lesions of the
prognosis & chromosomal abberations) calvarium
unbound light chains become
filtered in the urine as Bence- neoplastic plasma cells make excess M-protein (neoplastic Ig) + Bence-
Jones proteinuria fragments of light or heavy chains along with Jones protein (kappa chain) in
the complete Ig serum/urine (respectively) protein
bone pain/ fractures due to electrophoresis
osteoclastic lesions, excess light chains cross glomerular filtration
hypercalcemia, anemia/ barrier, eventually occluding and damaging histo: light chain cast nephropathy w/
thrombocytopenia, inc the renal tubules eosiniphilic casts (light pink blobs)
infection susceptibility & ATN
Variants Education
Glomeruloneph Experimental single injection of Ag (acute After injection of antigen, the concentration biopsy: diffuse proliferative GN
ritis acute serum antigenemia) drops precipitously as Ag becomes bound to (>50% of glomeruli have lesions),
sickness stereotypical course circulating Ab, forming immune complexes; heavy mononuclear infiltrate,
(similar to self-limited, short duration more immune complexes = more GN; as free endothelial cell swelling,
human post- Ag is cleared, GN frequency drops subepithelial humps
streptococcal deposition of circulating plasma
GN) soluble immune complexes in the C3 complement also activated by immune IF: IgG mesangial deposits + starry
glomeruli; dense deposits in complexes; specifically, the classical pathway sky pattern
mesangium, endothelial wall is activated, allowing formation of MACs and
subsequent direct injury (lytic pores),
used as model for post- activation/ recruitment of neutrophils &
streptococcal GN in humans monocytes --> inflammation
Heymann In situ formation of immune circulating Abs bind in situ target antigen = bx: foot process effacement,
nephritis complexes megalin (rats)= scavenger receptor on subepithelial deposits w/ regular
(idiopathic podocytes & PT brush border that mediates periodicity and spike formation
membranous expt model for idiopathic endocytosis of protein, lipoproteins, calcium, (chronic antigenemia)
nephropathy in membranous nephropathy in and certain drugs
humans) humans, target antigen = PLA2 IF: granular IgG and C3 deposits
receptor antibodies then shed and aggregate on the along capillary loops with relative
EBM, condensing into subepithelial deposits periodicity
and causing foot process effacement
Masugi in situ formation of immune Animal model: Anti-GBM antibodies are EM: NO dense deposits (Immune
Nephritis (Anti- complexes preformed in animals, extracted, and injected complexes planted in each ind
GBM disease) into other animals; target heparan sulfate, anionic site; unable to aggregate)
Anti-GBM dz does occur in stripping the GBM of its anionic charge -->
humans, but target Ag = NC1 of formation of immune complexes within GBM, IF: linear IF for IgG along capillary
collagen type IV activating complement and causing GN loops
IgA asymptomatic & persistent alteration in IgA type I, resulting loss of most bx: proliferation of mesangial cells no effective tx 50% ultimately die
Nephropathy hematuria (gross or micro), +/- glycosylation pattern --> underglycosylation common GN (>3 cells in mesangial matrix) from ESRD
(IgAN, Berger's proteinuria; mesangiopathic dz --> aggregation into polymeric IgA1 --> in developing IF: IgA deposition in mesangium (although dz is
disease) uptake by MPS and activation of mesangial world EM: mesangial immune deposits, decades in length)
usually manifests as slow cell proliferation/expansion (Western attenuated GBM
insidious progression towards Pacific rim)
ESRD
Hyperkalemia EKG abnormalities (can be life redistribution - K+ moves from inside --> crush injuries EKG - peaked T waves, flattened P 1. stabilize cardiac Ca IV is avoid potassium
threatening - SCD), weakness outside of cells; due to rhabdomyolysis, waves, prolonged QRS duration; R/O membrane (esp if serious contraindicated if pt in diet for 6
(diminished reflexes, strength), necrosis, cell death, tumor lysis, DKA, pseudohyperkalemia (hyperkalemia EKG changes) - give on digoxin!! months
respiratory failure from hyperosmolar hyperglycemic state (HHS), but no EKG changes; due to hi calcium (Ca gluconate by (artichokes,
diaphragm paralysis insulin deficiency, resp acidosis, non-org WBCs, platelets, or hemolysis) periph IV) Do not mix Ca IV w/ avocados, tomato
metab acidosis, solvent drag (impt for 2. redistribute K+ by NaHCO3 solutions paste, OJ,
hyperkal in DKA, HHS) transtubular K+ gradient (nl 6-12; if giving insulin (causes K+ (causes precipitation potatoes, milk,
hyperkalemic and TTKG is hi - to go back into cells) or of CaCO3) bananas, steak,
reduced excretion - decreased effective suggests extra-renal etiology) B2 agonists hamburger, etc)
volume (less urine output so less excretion of 3. remove K+ by giving
K+), primary/ secondary hypoaldosteronism, kayexalate/sorbitol (bind
tubular mineralicorticoid resistance, acute K+, causing diarrhea) or
kidney injury, oliguria (low urine output), hemodialysis
meds (ACE, NSAIDs, K+ sparing diuretics,
bactrim);
increased intake (usually only if abnl kidneys)

Variants Education
Hypokalemia weakness, muscle cramps, decreased intake - starvation If HTN, think about EKG shows U waves after T waves for mild cases, oral
palpitations, fatigue, constipation, redistribution - insulin, B2 agonists, conditions w/ inc management preferred
resp impairment (if severe) pseudohypokalemia (large # abnl leukocytes) aldosterone TTKG > 4 suggests renal loss over IV
non-renal K+ loss - diarrhea, severe burns, secretion (renal - KCl if from diuretics, vol
profuse sweating artery stenosis, Check acid-base status (acidosis - depletion
renal K+ loss - diuretics, vomiting, hyper-aldosteronism, renal tubular acidosis, DKA, meds) (if - KP if phosphorus
mineralicorticoid excess, renal dysfxn Liddle's syndrome) alkalosis, then measure BP; hi BP - depletion
mineralicorticoid excess, Liddle - KHCO3 if acidosis
if normal BP, think syndrome; low/nl BP - loop/ thiazide - K Citrate if renal stone
about diuretics, diuretics, Bartter syndrome, prevention
Gitelmans, Bartter Gitelman's syndrome, vomiting)
syndrome, vomiting If must give IV, you need
to have less than 60
mmol K in 1L IV fluid
given at a rate of 10
mmol/h
Chronic Kidney Diabetes, CVD = leading Staging:
Disease (CKD) HTN cause of death 1. kidney damage
w/ nl or inc GFR
decreased life (>90)
expectancy 2. mild dec GFR
(60-89) + kidney
damage
3. moderate dec
GFR (30-59)
4. severe dec
GFR (15-29)
5. Kidney failure
(GFR<15)
Renal agenesis unilateral normal function but late failure to form ureteric bud or induce sporadic inheritance 1/1000
complications of differentiation of metanephrogenic blastema births; 3:1
glomerulosclerosis M:F
minority of cases due to involution of
dysplastic kidneys
bilateral in utero demise or death shortly sporadic inheritance 1/4000

after birth due to renal or births; 2:1
pulmonary insufficiency (Potter M:F
syndrome)
associated 2ndary anomalies of

Potter syndrome: absent fetal
urine --> reduced amniotic fluid
production (oligohydramnios),
characteristic facial features
(beak nose, skin folds under
eyes, flat/low set ears), limb
deformities, pulmonary
hypoplasia, amnion nodosum
Renal unilateral - no problems very rare

hypoplasia
bilateral - variable degree of
renal insufficiency, hypertension
<6 pyramids (nl 10); kidney

weight < 50% of expected
weight for age
Renal atrophy diminutive kidney less likely to be hypoplasia
more likely to be caused by renal artery

atherosclerosis, especially in adults
Variants Education
Renal ectopia kidney in abnl anatomic location sporadic (very rarely 1/900 increased risk of UTI
(NOT T11-L1) familial) from stasis
simple - pelvic, increased risk of

subdiaphragmatic, thoracic injury
crossed - with or without fusion
a/w other GU malformations
Horseshoe incidental finding most of time; fused lower (95%) or upper (5%) poles; sporadic 1/400-600 incidental finding during imaging, slight risk of
kidney generally normal fxn (even used fusion during development prevents rotation surgery, autopsy infections, kidney
for transplantation) so renal pelvis faces anteriorly stones, and renal
pelvis tumors
unable to migrate out of pelvic cavity
because inferior mesenteric artery blocks increased risk of
them Wilms tumor
(isthmus)
Renal tubular Type I (DT) normal anion gap acidosis; distal tubule nl secretes H+ for the formation Hereditary (auto UAG > 0 (not much NH4+) easy to correct w/ low
acidosis moderate renal failure (GFR 20- of carbonic acid, which is broken down into recessive mutation doses of HCO3-
50), impaired NH4+ and CO2 & H2O by CA; problems with distal in Cl/HCO3-
phosphate excretion tubule prevents H+ secretion so unable to exchanger),
maximally acidify (because does not have interstitial nephritis
urine is not maximally acidic ammonia for the H+ to attach and be (lead/lithium/
(pH > 5.3), severe serum excreted in urine) the urine for excretion of analgesic abuse;
acidosis (HCO3- <10), acid --> acidosis autoimmune -
hypokalemia Sjogren's, RA, SLE,
PBC, thyroiditis;
nephrocalcinosis;
drugs - amphotericin
B, toluene)
Type 2 (PT) normal anion gap acidosis; Problems in proximal tubule prevent Childhood UAG > 0 (not much NH4+) requires high doses of
moderate renal failure (GFR 20- reabsorption of HCO3- and the formation ofhereditary dz HCO3- to correct!!
50), impaired NH4+ and ammonia from glutamine --> acidosis (cystinosis,
phosphate excretion tyrosinemia, GSD,
Wilson's, Lowe's,
variable urine pH (diet dep), galactosemia),
serum bicarb 14-20, normal/low carbonic anhydrase
K+ inhibitors
(acetozolamide,
topiramate),
interstitial nephritis
(rare), renal
transplant rejection
(very rare),
amyloidosis, multiple
myeloma
Type 4 normal anion gap acidosis; low renin, hypoaldosteronism, or aldosterone drugs (ACEI, AngII UAG > 0 (not much NH4+) fix hyperkalemia - usually
moderate renal failure (GFR 20- resistance prevents the secretion of K+ inhibitors, fixes the acidosis (if not,
50), impaired NH4+ and (hyperkalemia), indirectly causing charge aldosterone minimal HCO3- needed)
phosphate excretion exchange during which causes H+ to enter antagonists)
the cells [low aldosterone prevents K+
maximally acidic urine (pH < secretion; hi K+ blocks ammonium
5.3), mild acidosis (HCO3- production, so H+ in urine is not bound to
>15), hyperkalemia ammonia --> maximally acidic urine]
Variants Education
Lactic acidosis Type A LA high anion gap acidosis increased L-lactate production from no Krebs altered redox states,
cycle --> leads to decreased tissue increased metabolic
oxygenation rate (sepsis,
seizures, exercise,
shivering, cancer,
hypoglycemia,
thiamine def),
decreased O2
delivery (shock,
sepsis, CO toxicity),
hereditary metabolic
defects
(mitochondrial
myopathies)
Type B LA high anion gap acidosis decreased L-lactate destruction liver disease, ETOH,
renal failure,
metformin, salycilate
OD
Ketoacidosis Diabetic KA high anion gap acidosis pancreatic beta cell destruction causes urine nitroprusside test detects
decreased insulin, increased glucagon --> acetone and acetoacetate
leading to the formation of acetoacetate and
B-hydroxybutyrate serum ketone test detects B-
Alcoholic KA high anion gap acidosis Decreased carb intake causes decreased hydroxybutyrate (DKA - 75%; AKA
insulin; decreased gluconeogenesis causes >90%)
increased glucagon; ethanol results in
increased lipolysis and free fatty acids
Metabolic Generation (bicarb addition or acid loss; chloride sensitive spot urine to determine if chloride chloride supplementation
alkalosis anion drag) or maintenance (prevention of metabolic alkalosis sensitive or chloride resistant [Ucl > reverses the alkalosis (if
bicarb excretion) from bicarb 20 mEq/L implies chloride resistant chloride sensitive)
load/drag (calcium met alk]
Generation: vomiting, NG suction, alkali syndrome) or
increased distal Na+ delivery in volume decreased EABV hi FP rate for Ucl > 20 so check Uk (if
depleted states (loop/ thiazide diuretics, (vomiting, increased < 30, replete K+ and rpt Ucl) and
nonreabsorb anions), respiratory comp (post Na+ delivery- HTN (if no HTN, recheck Ucl)
chronic hypercapnia), alkali consumption/ diuretics, post-
admin; mineralocorticoid excess, MC excess hypercapnic state,
syndromes (Bartters, pseudo-hyperald) hypercalcemia)
Maintenance: low EABV (chloride deficiency - chloride resistant

activates RAAS preventing base secretion & metabolic alkalosis
increasing HCO3 reabs secondary to Na+; (hi renin: renal artery
insuff Cl- to exchange w/ HCO3 in distal stenosis, malignant
nephron), pathologic mineralocorticoid HTN; low renin:
excess, severe hypokalemia primary
aldosteronism,
Cushing's syndrome,
Liddle syndrome)
Benign renal Papillary a/w long term hemodialysis common; pathology: small (<5 mm diameter),
neoplasms (cortical) and papillary RCC incidence well circumscribed lesions
adenoma increased w/
age histology: finger like projections
(fibrovascular projections)
Angio- usually one large mass; if benign neoplasm composed of thick walled <1% of renal histology: angioma + myoma + < 4cm size: follow w/ CT spont retro-
myolipoma multiple mass - suggests blood vessels, smooth muscle, and fat tumors lipoma scan or surgery if peritoneal
tuberous sclerosis!! growing rapidly hemorrhage (pts
usually in present w/ severe
Can present w/ pain or hematuria adults > 4cm size: surgical back pain)
removal to prevent
complications
Oncocytoma usually unilateral, but if multifocal 4-7% of adult pathology: well described lesion w/ majority are
or bilateral - think syndromes renal brown central stellate scar asymptomatic but if large,
epithelial might need surgical
uniform population of pink cells tumors histology: numerous cells w/ removal if compressing
abundant cytoplasm (low NC ratio) adjacent structures
loose fibrous stroma mixed w/I age > 50 y.o and no nuclear pleomorphism
tumor cells usually
M:F 2:1
Variants Education
Malignant renal (general) "classic triad" (<10% of patients) - sporadic - single lesion, unilateral lesions, 30K new US smoking, often found incidentally w/ imaging! hereditary? CT imaging poor prognosis if not staging (based
neoplasms abdominal mass, hematuria, onset 60-70 y.o., males cases / yr HTN, to monitor dz detected early! on tumor size!!):
flank pain obesity, Path: necrosis + hemorrhage progression; nephron T1 = good
hereditary - multiple lesions, bilateral lesions, 12K US meds sparing surgery, radical Can cause tumor prognosis; T4 =
85% are renal cell carcinomas earlier onset in life, M=F deaths/ yr (diuretics), nephrectomy, thrombus if enters bad prognosis
(clear cell, papillary) acquired cryotherapy (if not renal vein, IVC, RA
usually > 50 renal cystic surgery candidate);
1% are bilateral (majority are y.o. dz (dialysis), screen family members
unilateral!) occupat exp
M>F (asbestos,
paraneoplastic syndromes - petroleum,
hypercalcemia, elevated LFTs cadmium,
(Stauffer's syndrome), anemia, lead),
erythro/ thrombocytosis genetics
(VHL)
Conventional most common type of renal genetic mutation or deletion in 3p25 locus 65,000 smoking, pathology: very fatty (yellow) partial nephrectomy metastases Fuhrman nuclear
(clear cell) cancer (70%) of von Hippel Lindau gene (VHL gene) --> cases, 13500 obesity in appearing lesion (nephron sparing (LUNGS, lymph grading system
RCC tumors that arise from proximal convoluted deaths in women, surgery) nodes, liver, bone, (Grade IV - bad!!)
majority are unilateral tubules U.S. HTN, VHL histology: clear tumor adrenals, - prognostic
disease (intracytoplasmic lipids & radical nephrectomy contralateral kidney, combined w/
Rising (develop glycogen), very round nuclei, pale cryoablation (small brain, heart, spleen, staging (see
incidence RCC in 50% cytoplasm, highly vascularized tumor, poor surgical intestine, skin) above)
of cases), (chicken wire vasculature) candidates)
usually > 50 hereditary
y.o. RCC w/o high grade tumors will actually
VHL, appear darker from increased nuclei,
M>F tuberous atypical mitotic figures, and spindle
sclerosis cell differentiation
Papillary renal associated with trisomy 7, trisomy 17, or hereditary papillary 10-20% of path: hemorrhagic (sometimes
cell carcinoma loss of Y chromosome!! carcinoma (VERY adults RCCs necrotic) appearance
rare)
Tumors arise from proximal OR distal males 3:1 histology: large tumor w/ papillary
convoluted tubules structures (finger like vasculature;
fibrovascular cords); calcium
deposits, infiltration of macrophages /
histiocytes
Urothelilal hematuria arises from renal pelvis (collecting system - adults (7% of smoking histology: papillary tumor arising from nephroureterectomy
carcinoma urothelium) primary renal urothelial lining (NOT renal tubules),
(transitional 40-50% of cases have co- cancers) phenacetin presence of fibrovascular cords
cell carcinoma) existing bladder urothelial tumors nephropathy
70% males
most common tumor of renal thorotrast
collecting system and ureter mean age 70 radiologic
dye
cyclophosph
amide
horseshoe
kidney
Inherited von Hippel increased risk of clear cell RCC autosomal dominant mutation in VHL gene
disorders of Lindau (VHL) (3p25); variable expression & reduced
RCC syndrome retinal angiomas, CNS penetrance
hemangioblastomas,
endolymphatic sac tumors, mutations promote transcription of vascular
epididymal tumors, growth factors --> unusual vascular tumors
pheochromocytomas, pancreatic
cysts, renal cysts, clear cell RCC 20% de novo mutations (neg FH does not
R/O VHL!!)
Hereditary increased risk of papillary type 1

papillary renal RCC
cell cancer
Hereditary increased risk for papillary type 2 FH gene codes for fumerase hydratase 10-16% risk
leiomyomatosis RCC enzyme; RCC
RCC
benign skin leiomyomata, benign autosomal dominant w/ close to 100%
uterine fibroids, aggressive type penetrance for SOME manifestation of
2 papillary RCC syndrome
Variants Education
Birt-Hogg-Dube variable risk for oncocytoma autosomal dominant mutation in BHD gene
(17p11.2), disrupting BHD protein which
fibrofolliculomas, pulmonary makes folliculin
cysts, renal cysts, RCC, colon
cancer, spontaneous penetrance of cancer is lower than some of
pneumothorax the other syndrome manifestations
not a/w certain pathological type of RCC

Familial Renal increased risk for oncocytoma
Oncocytoma
Lynch increased risk for CRC &
Syndrome endometrial/ovarian cancer;
transitional cell pathology
Wilms' tumor pediatric - 90% < age 6 most histology: triphasic (blastema, nephrectomy and/or very aggressive, a/w
(nephroblastom common epithelium, stroma); very chemotherapy poor prognosis
a) presents as large abdominal kidney tumor multinucleated, + mitotic figures
mass of childhood lung metastases
(cough) or
a/w syndromes: WAGR 1/8K-10K traumatic rupture
syndrome (Wilms' tumor,
Aniridia, GU anomalies, mental no gender
Retardation); Denys-Drash preference
syndrome (gonadal dysgenesis -
male pseudohermaphroditism;
glomerulosclerosis, Wilms
tumor); Beckwith-Wiedemann
syndrome (exophthalmos,
macroglossia, gigantism,
hemihypertrophy)
Tuberous a/w harmatomas, mental autosomal dominant neurocutanous disorder increased risk for
sclerosis retardation, infantile/ childhood from mutations in TSC1 and TSC2 genes RCC (clear cell or
seizures, cutaneous others)
angiofibromas, heart
(rhabdomyomas), lung (LAM) a/w ADPKD
if see angiomyoplipomas on
kidneys - think tuberous
sclerosis!
Bladder exposed bladder --> increased developmental defect in lower abdominal wall infection
exstrophy and anterior wall of bladder from the failure of
risk of infections & ulceration
the cloacal membrane to properly ulceration
glandular or squamous differentiate --> exposure of bladder to
metaplasia --> adenocarcinoma body surface (opened sac) adeno-carcinoma
or squamous cell carcinoma
squamous cell
bladder is on outside of patient carcinoma
(no skin covering bladder -
mesenchymal defect) death - esp if no
access to HC
(developing world)
Acute cystitis triad: urinary frequency + lower younger women (pregnant) - head of fetus Infectious: E.coli, older men histology: thickened urothelium, broad spectrum Abs, pyelonephritis!!!
abd pain + dysuria (pain/ compresses distal aspect of bladder, leading candida or infiltration of histiocytes/PMNs removal/treatment of
burning during urination) to obstruction and urinary retention cryptococcus in younger obstruction
immunocomp, women of
inflammation of urothelium older men - benign prostatic hyperplasia adenovirus, reproductive
leads to compression of urethra, causing chlamydia, age
urinary retention and infection mycoplasma
immunosupp
non-infectious:
chemo, radiation,
trauma
Variants Education
Schistosomiasi world's leading cause of ova are deposited in veins of muscularis Schistosoma Africa & histology: pink cytoplasm & granules hydroureter,
s hematuria and bladder cancer propria, leading to degeneration and hematobium - Middle East represent eosinophils; squamous hydronephrosis,
inflammation common in Egypt metaplasia w/ Schisto oval bladder ulcers,
(water borne bacterial infections,
early changes - necrosis, eosinophils w/ parasite; lodges in cystoscopy renal failure
mucosal ulceration pelvic veins around
bladder) squamous cell
later changes - fibrosis w/ lymphocytes, carcinoma
histiocytes, foreign body granulomas,
dystrophic calcification; squamous
metaplasia leads to squamous cell carcinoma
Hemorrhagic irritative voiding symptoms, gross destruction of overlying vessels in bladder --> cyclo- histology: hemorrhage of bladder may require cystectomy if death secondary to
cystitis hematuria (Med emergency!!) excessive bleeding phosphamide, bleeding will not stop! severe hemorrhage
radiation
HSV, CMV,
adenovirus
Polypoid benign course once injury source chronically inflamed bladder w/ grossly noted bladder histology: can see polyps + remove source of injury
cystitis removed polypoid lesions w/ edema or papillary catheterization, edematous area from subepithelial
lesions fistulous tracts fluid accumulation (polypoid)
Malakoplakia benign lesions occuring most defects in phagocytic or degradative E. coli immuno- histology: large histiocytes & small
commonly in bladder but also functions of histiocytes in response to GN Proteus comp, extracytoplasmic calculospherules
ureters, urethra, renal pelvis, etc. bacteria women (Michaelis-Gutmann bodies - look
like eyeballs!)
Cystitis cystica common incidental finding; reactive phenomenon that implies infection of chronic cystitis histology: glandular (intestinal) remote risk of
et glandularis mostly benign the bladder & presence of glandular bladder exstrophy metaplasia adenocarcinoma
structures ureteral
reimplantation
neurogenic bladder
Squamous Non- occurs commonly in females, bladder trigone in females becomes
metaplasia of keratinizing particularly at bladder trigone glycogenated, or lined by squamous
bladder (glycogenated) epithelium instead of urothelium
benign - not a/w SCC
Keratinizing long-standing cases may be schistosoma histology: hyperkeratosis
associated with squamous cell infection (globally)
carcinoma
long standing in
dwelling catheters
(US)
Bladder cancer (general) painless hematuria Normal urothelium --> dysplasia smoking, chronic most smoking histology: dysplasia - enlarged bleeding, staging:
(preneoplastic atypia - transformation to abnl cystitis (SCC), common arylamines urothelium obstruction, pTa & pTis = non-
urothelial carcinomas are the appearing nucleus) --> carcinoma (CIS flat chemical exposure, urinary tract(dyes) metastasis invasive (>95%
most common bladder cancers lesions OR noninvasive papillary lesions) --> cyclophosphamide, cancer Schistosoma 5y survival); T1-
(>90%) invasion radiation hematobium T4 based on
4th most (70% cases depth of tumor
common are SCC) invasion
cause of Phenacetin
cancer death use
in males long term
cyclophosph
M>F amide use
Urothelial malignant presence of cytotologically malignant cells histology: cells at least 5x size of
carcinoma in regardless of quantity stromal lymphocytes, enlarged/
situ (CIS) noninvasive flat cancer hyperchromatic nuclei, discohesion
as grade increases, the cells become more (shedding), prominence of vessels,
hematuria discohesive and can end up in urine high N/C ratio (CIS cells have very
little cytoplasm), pagetoid cells
(malignant cells interspersed w/
benign cells)
urine cytology - can sometimes show

CIS if discohesive
Urothelial benign uncommon lesion seen discrete papillary growth w/ central visible on cytoscopy (but need histo
papilloma in younger patients fibrovascular core lined by urothelium of to tell if malignant or benign lesion)
normal thickness and cytology
small size (3.0 mm) histology: finger like projections w/
presence of umbrella cells and
abundant cytoplasm (low N/C ratio)
Variants Education
Low grade malignant histology: finger like projections w/

papillary cohesive epithelial cell lining;
urothelial non-invasive usually fibrovascular core w/ blood
carcinoma vessels, few mitotic figures
orderly arrangement w/ minimal
variation in polarity; minimal
atypia (scattered enlarged
hyperchromatic nuclei), few
mitotic figures
High grade malignant histology: scattered single cells does tumor invade
papillary (discohesion), apoptotic bodies, muscularis propria? NO -
urothelial usually invasive increased # mitotic figures, nuclear local chemotherapeutic
carcinoma polymorphism, hyperchromatic (Dark agents; YES - cystectomy
overall disorderly arrangement w/ appearing), increased vasculature or cystoprostectomy
irregular clusters of cells & fused
papillae; marked atypia (similar look for invasion for grading
to CIS), numerous mitotic figures; purposes (lamina propria - T1,better
discohesive single cells prognosis; muscularis propria -
infiltration of thick muscle bundles,
numerus thick walled blood vessels -
poor prognosis)
Squamous cell malignant dedifferentiation long term 5% of smoking,

carcinoma catheterization bladder Schisto
background of keratinizing squamous tumors in infection,
metaplasia Schistosoma US; 75% of chronic
hematobium bladder catheter
tumors in placement
bladder exstrophy Egypt, Sudan
smoking
Adeno- malignant can sometimes arise from urachus (dome of glands + mucin
carcinoma the bladder, connected from ligament of
gland forming - produces mucin umbilicus) or other parts of bladder wall
Small cell malignant histology: high N/C ratio but small

carcinoma cells; necrosis (pink), rapid
proliferation
Renal Unilateral acute - painful renal colic + obstruction affects distal tubules, impairing urinary stasis,
obstruction CVA tenderness urine concentrating ability and response to decreased renal
ADH; decreased secretion of H+, excretion of function (reversibility
chronic - silent phosphate and K+ related inversely to
bilateral fluid overload, weight gain, impaired urine concentrating ability followed amount of time
less pain than unilateral by marked diuresis & natriuresis after release obstructed), HTN,
obstruction postobst diuresis,
UPJ occasionally, acute symptoms chronic obstruction that occasionally causes may spontaneously electrolyte abnl
acute symptoms resolve in infants
hydronephrosis
renal distention increases abnormal muscle developmenet, crossing
susceptibility to trauma vessel that kinks ureter
Nephrolithiasis calcium oxalate - most common, crystals form in the urine when certain genetic urinary removal of stone, ureteral stones -
can occur @ any pH substances reach supersaturation at a predisposition, stasis, increased fluid intake usually at UPJ,
Struvite (MAP) stones - rare, particular pH and temperature dehydration dehydration, crossing of iliacs,
seen in people w/ recurrent infection, uretero-vesical
infxns; require alkaline pH if crystals are retained, they can aggregate to metabolic junction (most
Calcium phosphate stones - RTA form stones states common), ureteral
patients; require alkaline pH (hyper- orifice
Uric acid stones - require acidicIBS + calcium oxalate stones - disrupted calciuria,
pH (only stones to be treated by bowel mucosa so unable to absorb bile salts hypo- acute obstruction =
pH adjustment) = excess bile salts in bowel lumen = bile salts citraturia, pain, infection,
Cysteine stones - genetic abnl bind calcium = loss of calcium increases hyper- chronic obstruction
oxalate absorption, favoring formation of oxaluria, = loss of kidney
IBS patients at risk for calcium calcium oxalate stones hyperfunction
oxalate AND uric acid stones uricosuria)
IBS + uric acid stones - diarrhea =
dehydration = low urine volume + decreased immobilized,
pH, favoring formation of uric acid stones RTA,
sarcoidosis,
hyper-PTH,
short bowel
syndrome
Variants Education
Kidney Pyelonephritis Acute - fever, chills, n/v, abd women w/ Microscopy: WBC casts IV antibiotic therapy - obstruction (stones)
infections pain, diarrhea, anorexia, FH or PMH Fluoroquinoles preferred
hypotension, flank pain, CVA of recurrent CT Imaging if persistent sx despite tx over TMP-SMX [Cipro]
tenderness, WBCs on UA; inpt UTIs; men (R/O complications)
mgmt if dizziness when w/ GU abnl; uncomplicated? Same as
standing, dehydration, n/v, & diabetics; cystitis but for 10-14days
confusion + signs of PN elderly (depends on local
resistance to TMP-SMX)
Chronic - loss of renal
parenchyma
Pyonephrosis infection + obstruction

(secondary to stagnant pus
building up in the collecting
system)
Emphysematou EMERGENCY - requires acute air filled pockets within kidney parenchyma diabetes CT shows gas formation within the urgent nephrectomy 70% mortality even
s drainage due to infiltration of gas-forming bacteria kidney w/ app Abs
pyelonephritis
severe necrotizing infection due
to anaerobic, gas forming
uropathogens
Abscess Perinephric - occurs secondary perinephric -
to obstruction of inf kidney; E.coli renal calculi,
or Proteus DM, prior
GU sx
Intrarenal - comp of ascending
PN or hematogenous seeding of
kidneys; S. aureus
Others TB infection, fungal infection of
kidney
Urinary unable to void urine problem w/ bladder not being able to neurologic issues;
retention squeeze (detrusor muscle) or obstruction of certain drugs;
bladder outflow pathway prostate
enlargement;
urethral stricture;
trauma (urethral
disruption)
Urinary (general) involuntary loss of urine leakage of urine despite higher brain function
incontinence through urethral meatus
treatment dependent on type of

incontinence & cause
Stress Stress incontinence - increased abd pressure coughing, laughing,
stressing the ureter sneezing, valsalva
Urge Urge incontience - accompanied by sudden bladder infection
urge to void; bladder irritation (infection)
causes strong bladder spasms
Overflow overflow incontinence - bladder has reached diabetes
capacity (autonomic neuropathy in diabetics)
Total Total incontinence - complete inability to hold complicated developing

urine; fistula or ectopic ureter childbirth countries
FEMALES
Vesicoureteral bidirectional urine flow congenital bladder anomaly genetics
reflux
stasis --> infection, scarring, (when the bladder squeezes, urine moves
chronic pyelonephritis back up to kidneys; when pt voids, increased
vesicular pressure pushes urine back up to
the kidney)
Urethral pathologic narrowing of the urethra inflammatory, trauma males (long obstruction
stricture interrupting flow of urine (stasis) and possible (catheters, straddle urethra)
obstruction injury, pelvic fx),
STDs (gonorrhea
urethritis), prior
instrumentation
Urethral cancer Squamous cell carcinoma is most only urologic

common type cancer more
common in
obstructive symptoms females; very
rare!
Variants Education
Benign occurs most commonly in enlargement of prostate gland from presence of age prostate exam reduce symptoms & limit stasis of urine =
prostatic transition zone upregulation of androgen-R (inc prod of DHT) androgens (DHT - progression infxn, stone, renal
hypertrophy/ = overgrowth of stromal tissue, inhibition of testosterone cystoscopy for bladder diverticulum dysfxn, urinary
hyperplasia obstructive sx (prostatism)- glandular cell apoptosis = hyperplasia converted to DHT by watching waiting retention, bleeding
(BPH) hesistancy, weak stream, stromal cells via 5a gross: nodular hyperplasia, medial
dribbling, straining to pass glands & stroma enlarge = compression of reductase) lobe hypertrophy, hypertrophied meds (a-adrenergic uncontrolled BPH
urine, prolonged micturition prostatic urethra = need for higher pressure detrusor muscle blockers- open the ext can cause infection,
(urination), feeling of in order to open the bladder neck & pass urethral sphincter & cancer, stones
incomplete bladder emptying urine = bladder muscle hypertrophy histology: hyperplasia of stroma (fibro- relaxes smooth muscle,
(interruption of primary (weakened) & thickening (trabeculation) + muscular) & glands 5a-reductase inhibitors - catheterization if
stream), urinary retention diverticula = functional degeneration (can't decrease DHT to shrink urinary retention
store urine or empty easily) prostate; anti-
irritative sx - (less specific for cholinergics - relax the
BPH) urgency, frequency, 2 main pathophys mechanisms: blockage of bladder to prevent
nocturia, urge incontinence outflow tract (= obstruction) & bladder uregency; combo tx)
(make sure you R/O cancer!!) hypertrophy/ diverticula
surgery (TURP -
irritative sx due to hypersensitivity of bladder transurethral resection of
prostate)
Prostate cancer occurs most commonly in require androgens in order to progress BPH highest age, FH, PSA screening (measurable levels bone scan for metastatic metastasis to earlier screening
peripheral zone (posterior part) incidence of race (African increase in pathologic states) lesions regional LNs in for African
patterns of spread: direct local extension all US male Americans), pelvic area, bones, Americans
adenocarcinoma into seminal vesicles (T3) or base of cancers diet if elevated - needle biopsy for radical prostatectomy w/ then solid organs
bladder (T4); lymphatic spread occurs (outside of (lycopene grading (Gleason score - <6 is better removal of LNs + [except liver - rare!!]
most are very slow growing first to pelvic / obturator LNs; skin Ca) maybe prognosis but rarely see that) radiation
(although some can be hematogenous spread (vertebrae, pelvis, protective) surgery can cut
biologically aggressive) proximal femur) 2nd leading histo: large prominent nucleoli, poorly anti-androgen tx (scrotal cavernous nerves
cause of differentiated glands that start to orchiectomy, estrogen, (ED) leading to
if metastasize to bone, usually osteoblastic cancer grow together GnRH analogues) impotence;
so a/w elevated serum alkaline phosphatase deaths in incontinence
men
estrogen increases
hypercoag (coronary
art thrombosis)
Scrotal hydrocele acute testicular/scrotal pain, serous fluid surrounding the testes from the if torsioned, untwist the testicular torsion
swellings nausea, vomiting (think perineum space; fluid came down with the spermatic cord (dead testis from
testicular torsion! Occurs most testis in the tunica vaginalis lack of bloodflow)
in adolescents or perinatal)
internal spermatic fascia and tunica vaginalis
hydrocele occurs inside the wrapped around the testis, filling it full of fluid
testis so feels like a huge mass
spermatocele / spermatocele occurs outside blocked cysts or ducts from the epididymis
epididymal cyst the testis so almost feels like
extra testicle
varicocele blood filled, enlarged veins dilation of veins of spermatic cord 10-15% of unilateral right
(pampiniform plexus) men; 10% of varicocele
more common on left side, most these are concerning bc
common cause of male occurs more commonly on left side because bilateral probably due to
infertility the right gonadal vein actually drains into the pressure on the
vena cava; left gonadal vein is more at a right vena cava directly
angle so more prone to static flow from valve from kidney tumor or
dysfunction retroperitoneal mass
benign solid outside the testis

mass
malignant solid within the testis parenchyma involves most commonly the germ cells peak un- U/S - abnl heterogeneity, hypo & removal of surgery can result in
mass (seminiferous tubules) incidence in descended hyperechoicity (should nl look like retroperitoneal LNs (both cutting of
(testicular usually discovered by abnl self males aged testes snow on TV) sides since L to R sympathetics -->
cancer) exam 15-34 genetics spread) - interaorto-caval retrograde
HIV path - central necrosis area w/ LNs, retrocaval LNs, right ejaculation
atrophy surrounding tumor paracaval LNs
FH?
Trauma? chemo
removal of testis
Variants Education
Male infertility male infertility occurs in 50% of varicoceles most

infertile couples common factor
Epididymitis sudden scrotal pain & swelling acute inflammation of the epididymis that is any age Flouroquinolones (Cipro)
often caused by reflux of urine through the
ejaculatory duct
Erectile inability to achieve and/or problem w/ vascular, neurologic, sometimes send for exercise in earlier
dysfunction maintain an erection sufficient psychogenic, or endocrine factors cardio referral ages prevents
for sexual function ED
tx patient, partner, &
couple
PDE5 inhibitors
(sildenafil, vardenafil,
tadalafil, avanafil) -
contraind if pt is on
nitrates
Peyronie's curvature of penis - usually on acquired abnl curvature of the penis during genetic 10% of men
disease dorsal side erection that interferes w/ sexual intercourse, predisposition but by age of 50-
causing psychological stress to the patient thought to be a/w 60
interferes w/ intercourse, pain trauma
can happen early, often a/w ED right hook, left hook, upward bend, downward mostly
in later stages (veins that bend, hourglass Caucasians
maintain erection can become but other
compressed) repetitive trauma through intercourse in races too
predisposed individual causes micro tear in
corpus cavernosum or tunica ablicans,
leading to formation of scar/ fibrosis
Penile cancer almost always occur in spread by local extension rather than rare
uncircumcised males lymphatics (however,
1% of
usually squamous cell cancers in
carcinoma (bc skin cancers) Africa are
penile)
Urinary tract (general) urinary frequency, urgency, mechanism: ascending route (bacteria in loss of nl bacterial women @ genetics (P Urine microscopy - clean catch, treat all sx patients! void after
infections and burning on urination perineum travel up urinary tract; 90% of UTIs; flora (Abs), higer risk group Ag on midstream; pyuria (>5-10 intercourse;
bowel flora - E. coli, GN rods, enterococci, environment of (shorter RBCs & WBC/mm^3), WBC casts 1. Trimetoprim/ cranberry juice/
E. coli is the most frequent Candida); hematogenous route (secondary bladder, disruptions urethra, uroepith Sulfamethoxazole supp to reduce
cause of UTIs!! seeding of urinary tract from primary in urine flow sexual cells) UA - LE+ (any inflam etiology), (Bactrim) OR sx; intravag
bacteremia; S. aureus, Candida, TB) (obstruction, activity, nitrite+ (nitrate reducing bacteria) [if fluoroquinolones (Cipro) estradiol in
Elderly - often have asympt vesicoureteral pregnancy); both LE & nitrite are neg, >97% 2. Amoxicillin, postmenop
bacteriuria,so need to find E. coli > Proteus > Klebsiella reflux), foreign males most predictive value that UTI is NOT Cephalosporins, women; correct
signs/sx of UTI - elevated WBC S. saprophyticus (5-15% of cystitis in young bodies common as present] nitrofurantoin underlying
count, fever, AMS sexually active F) infants structural abnl;
Ureaplasma urealyticum, Mycoplasma (suggests Gram stain - hi sens & spec but rarely correct underlying risk Ab prophylaxis
hominis - produce sx but hard to culture GU abnl) done unless requested factors (LAST RESORT)
(culture neg)
healthcare/Ab associated - Enterobacter, elderly (inc urine cx - atyp present, early sx of pregnancy? 7d w/
Pseudomonas, Enterococci, Candida, S. bactereriuria, recurrence after tx, clinical susp for amoxicillin/ oral
epidermidis, Corynebacteria Estrogen, pyelonephritis, recurrent infxn prev cephalosporin,
Adenovirus causes hemorrhagic cystitis in prostatic treated w/ Abs nitrofurantoin, or TMP-
kids & BMT pts secretions; SMX; avoid
comorbid flouroquinolones!!
conditions) lower threshold for
hospitalization
Symptomatic kids: non-spec sx; fever,
bacteriuria/ incontinence, FTT, vomiting D/C indwelling devices
uncomplicated adults: urgency, frequency, ASAP
UTI dysuria
elderly: worsening incontinence,
abd pain, AMS, FTT
Variants Education
Complicated patients who need longer course urinary stasis and obstruction are primary remove underlying indwelling devices 1. insert
UTIs (e.g. of therapy, interventional mechanisms for complicated UTIs mechanism (catheter, can become havens catheters only for
catheter- procedures, have pathogens w/ obstruction) for biofilms; appropriate
associated Ab resistance, or secondary biofilm formation by uropathogens can cause encrusted indications
UTIs) complications chronic bacterial presence on devices minimize unneccessary 2. remove ASAP
(catheters) --> resistance tx (asymp bacteriuria) 3. properly train
those who
Limit Ab use unless insert/maintain
underlying process is 4. aseptic
resolved! technique
5. maintain
Avoid routinely changing closed drainage
catheter bags, system
antibmicrobial 6. maintain
prophylaxis, bladder unobst urine flow
irrigation, antiseptic 7. hand hygiene
solutions in drainage
bags, routine screening
for asympt bacteriuria
GU elevated WBC without secondary seeding from hematogenous 15% of homeless imaging: renal/ GU mass, may respond to TB
tuberculosis microbial growth (sterile spread of TB (only 20-30% have concomitant extrapulm TB calcifications, or stricture therapy but usually
pyuria) pulm TB) to involve the lower GU tract disease requires surgery bc very
(epididymis, testis, bladder, ureter, and Urine AFB culture or biopsy extensive dz by time dx
prostate)
Asymptomatic positive urine cultures in absence significance? Presence during preg changes in GU tract prevalence catheters Only time you treat
bacteriuria of clinical signs or symptoms increases risk of PN, a/w bacteremia during (occur w/ age) inc w/ age asymp bacteriuria:
procedural manipulation of GU tract; a/w GU Kids: workup for
treatment requires symptoms!!! abnl in kids; higher mortality rates in catheters --> asympt congenital/ obstruct abnl
hospitalized patients Candiduria Pregnancy: treat bc hi
risk fo PN &
complications
Pre-op pts: treat to avoid
bacteremia
otherwise, remove
catheters if source (and
no longer needed)
Cystitis lower tract infection if local TMP-SMX

resistance <20%: TMP-
frequency, urgency, SMX DS BID x3d
suprapubic pain, dysuria,
gross hematuria If local resistance >20%:
Cipro 250 PO BID;
Levofloxacin 250 daily
x3d; Nitrofurantoin x7d
Vaginitis, gradual onset of milder dysuria, sexual mandatory pelvic exam for vag d/c
urethritis +/- freq and/or urgency; dysuria history of or lesions (Chlamydia/ gonorrhea,
w/o pyuria new HSV, trichomonas, BV)
partners or
hi risk
sexual
practice
Prostatitis Acute bacterial very severe clinical onset - unclear mechanism - possibly due to urethral GN enteric very small urine cx: increased WBCs and treat based on culture Prostate abscess
prostatitis fevers, chills, perineal pain, reflux or post-GU instrumentation organisms (E.coli) proportion of positive culture results
(Type I) back pain, UTI sx, possible prostate
obstruction cases would NOT want prostate initial therapy: IV Ab
specimen (tenderness of prostate; (fluoroquinolones)
PE: VERY tender prostate inc risk for bacteremia) later therapy: oral Ab
PSA - mod to marked elevation R/O complications if

unresponsive
Chronic indolent course - may present as Ureaplasma, prostate massage: less inflammation treat based on culture
bacterial recurrent UTI Chlamydia but positive culture results
prostatitis
(Type II) semen culture if prostate massage fluoroquinolones,
uncomfortable sometimes doxycycline
or macrolides
Variants Education
Chronic pelvic most frequently seen conditions usually negative culture but some
pain, no (>90%) inflamm cells present after prostate
detectable massage
inflamm sometimes evidence of WBCs &
(Type III) inflamm cells in expressed
prostatic secretions; no active
bacterial process
Asymptomatic incidental finding related to culture negative, less likely to see
inflamm elevated PSA inflamm cells
(Type IV)
Autosomal large, fluid filled cysts and autosomal dominant mutation in PKD1 gene PKD2 patients have 12.5 million more severe CT/MRI: fluid filled sacs w/ nl renal massive enlargement & hemorrhage of cysts
dominant enlarged kidneys BUT nl renal (which lies very close to TSC2 gene so better prognosis than peeps disease in parenchyma on either side; enlarged variable cyst burden - acute onset of pain
polycystic fxn (differentiates from acquired patients can have tuberous sclerosis too!) + PKD1 worldwide men kidneys before loss of renal fxn localized to kidney
kidney disease PKD) second acquired mutation =phenotype so hard to decide when
(ADPKD) M=F to treat ESRD
a/w tuberous sclerosis 10-15% spont PKD1 mutations
comp of polycystic
U/S criteria for dx: +FH and 3 phenotype: renal cysts, liver cysts, asymp liver dz (ascites,
cysts distributed bilaterally in pt intracranial aneurysms, HTN, proteinuria portal hypertension,
<40y.o., 4 cysts in pt 40-60y.o.; 8 varices, hepatic
cysts >60y.o.; no FH and 5 ARPKD (PKD2) appears same venous obst, liver
cysts bilaterally w/ consistent cyst infection)
phenotype loss of primary cilia fxn: altered
mechanosensation of Ca+2 currents HTN, gross
extral-renal: liver cystic dz hematuria, pain,
(massive polycystic liver dz - altered mitotic orient & cell polarity nephrolithiasis, UTI -
females, mild renal involvement, long before dec
more hospitalizations), cystic epith cells: dedifferentiated, no GFR!
intracranial aneurysms, HTN, polarization, abnl cell matrix proteins, hi rate
of div & apop, form cysts instead of tubules,
proteinuria
secrete fluid
Acute renal (general) clinical definitions vary based on rapid inability of kidney to maintain excretion Hx: n/v/d/bleeding - true vol CT for complications inc mortality risk?
failure/ acute creatinine, urine output, or need of nitrogenous wastes, fluid balance by depletion; CHF, liver/ renal dz - dec Pts who need
kidney injury for renal replacement therapy excretion of free water, and acid/base EABV; new edema, HTN, rash, urine renal perfusion (give vol, dialysis, increased
balance color - acute GN; meds - ATN, AIN; treat primary prob if dec age, multiple organ
RIFLE - risk, injury, failure, loss, IV contrast - ATN; stones/ prostate dzEABV); change drug system failure,
ESRD causes of anuria - prerenal (bilateral renal a - postrenal; diff urine vol - anuria dosing; dietary malignancies
occlusion), intrinsic (acute GN, renal cortical restrictions, early
Stage 1 - inc serum Cr >0.3 necrosis, ATN - rare); postrenal (bilateral PE: volume status (orthostatics, skin nephrology consult, poor renal recovery?
mg/dL above baseline ureteral obstruction, bladder neck obst, obstr turgor, JVD/S3/rub; crackles; corticosteroids (acute Oliguric/ anuric
Stage 2 - serum Cr >200-300% in kidney) distended bladder; enlarged prostate; GN); plasmapheresis ARF, renal cortical
above baseline ext edema/ cyanosis (anti-GBM) necrosis,
Stage 3 - serum Cr >300% or atheroembolic renal
4.0mg/dL UA & microscopy (muddy casts - dialysis if acidotic, abnl infarct
ATN; uric acid cryst- tumor lysis; electrolytes, ARF from
nonoliguric: urine vol >400 mL/d calcium oxalate - ethylene glycol intoxications, overload in
oliguric: urine vol 100-400 ingest anuric patients, uremia
anuric: urine vol <100 [AEIOU]
Prerenal ARF caused by hypoperfusion of glomerulus; true volume increased BUN/Cr ratio, Uosm >500,
azotemia decreased glomerular capillary hydrostatic depletion Una <20, FENA <1%; FEurea <35%
pressure decreased EABV
severe renal
true vol depletion - GI loss (v/d, upper/low vasoconst
bleed); renal loss (diuretics, DI), skin/resp occlusion of renal
loss (insensible, burns), sequestration into arteries
3rd space (crush injuries, acute pancreatitis,
internal hemorrhage)
dec EABV - CHF/MI (low CO), AV fistula (hi

CO), advanced liver disease (nl-hi CO), early
sepsis (hi CO)
Variants Education
Intrinsic Renal ATN, AIN, acute GN or vasculitis, ATN - prolonged ischemia or toxins leading ATN - ischemic path: muddy brown casts - ATN;
Failure acute renovascular dz to tubular damage (PT or TAL); decreased causes, eosin infiltrate + edema between
Kf, decreased hydrostatic glomerular nephrotoxins (Abs, tubules - AIN
pressure, increased hydrostatic pressure in contrast dyes, heavy
BC; hemodynamic - vasoconst of blood metals, chemo BUN/Cr ratio 10-15:1; Uosm <350;
supply, tubular obst, backleak of urine; cell agents; myoglobin, Una >40; FENA >2; FEurea >50
fate - injured tubular cells = loss of polarity = Hg, calcium
apop/nec; interactive cell bio - injured phosphate stones,
tubular cells interact, releasing inflamm uric acid)
mediators & cytotoxins
AIN - drugs
AIN - immune mediated injury in the (NSAIDs, Abs,
interstitium; non-oliguric diuretics, others);
Infxn (PN), immuno
(SLE, rejection), infilt
(sarcoid, leuk,
lymphoma)
Postrenal mechanical or functional obstruction to flow; UUT - U/S for obstruction

failure increased hydrostatic pressure in BC nephrolithiasis,
blood clot,
retroperitoneal
fibrosis, malignancy
LUT - stricture, BPH,

prostate Ca
Neurogenic - DM,
anticholinergics,
neurologic d/o
Disease Clinical Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications
Variants
Diabetes (general) 3Ps (polyuria - osmotic hyperglycemia & glycosuria due
pancreas: inc Inc urine volume + hi SG Diabetic ketoacidosis,
mellitus diuresis, polydypsia- to inability to oxidize/utilize
glucagon, dec (polyuria); inc BUN:Cr ratio hypoglycemia, see
rehydration, polyphagia- carbs + disturbance in insulin
insulin (catabolic state, chronic complications
replenish carbs), weight function + imperfect fat secretion dehydration), + urine below
loss (urine carb loss), combustion (hi ketones) fat: dec glucose (weight loss), +
fatigue (unable to utilize glucose ketones (fruity odor,
nutrients pass into the urine
glucose), blurred vision, dry uptake, inc lipolysis), ABG: low pH, low
mouth, dry skin, poor (weight loss, polyphagia); FFA output HCO3-, low pCO2
wound healing, impotence, dehydration bc body H2O is muscle: dec (metabolic acidosis w/ resp
tachypnea (metab acidosis used to eliminate extracell glucose uptake compensation)
compensation), fruity odor glucose in the urine liver: inc
(increased breakdown of hepatic
fats to form ketones) dec intracell glucose = dec glucose output
energy; body attempts to inc gut: slowed
chronic hyperglycemia: 3Ps intracell glucose and dec gastric motility,
+ severe cachexia (unable extracell glucose (osmotic inc glucose
to drive glucose intracell) diuresis); as unable to use uptake
glucose, body attempts to brain: dec
increase energy by using fats = satiety, ANS
ketones = acid = DKA reg
Type 1 DM excessive urination, progressive autoimmune 0.3% general DR 3/4 genotype Serum glucose (>200 mg/dL subcutaneous insulin DKA
excessive thirst, fatigue, destruction of B-cells --> insulin Caucasian (HLA) - 8-10x w/ sx; >125 mg/dL fasting) therapy that mimics
weight loss deficiency (causing the population higher risk physiologic insulin
opposite of insulin - rather than Large urine ketones; (continuous insulin - pump
storing energy, the body tries to 20/100,000 FH: 15% w/ positive antibodies (anti- or basal injection w/ bolus
make glucose & breaks down +FH; ident twins GAD65 Ab- these pts have injection at meals)
glycogen, fats, & protein) bimodal age (25-50%), highest risk for T1DM; islet
distn (4-6y, 10- siblings (5% cell Ab, insulin auto-Ab)
CD4, CD8, & MOs infiltrate & 14y) risk), father
accumulate in islet cells --> (6%), mom (3%)
insulitis; unk triggering event
occurs promoting autoimmune Whites
destruction of islet cells colder climate
clinical manifestations when 80-

90% B-cells destroyed
Type 2 DM metabolic syndrome: MODY: mutations w/ B-cell fxn = polygenic muts 24 million strong FH, FBS > 126 OR 2h 75g OGTT dec insulin resistance:
waist circum > 32"F or T2DM in nl weight kids w/ -FH in TCF7-L2 diabetics inminority groups, > 200 OR random BG > 200 lifestyle mods (diet- dec
typical T2DM: inability of B-cells to
38"M + any 2 factors (HTN, (dec insulin U.S. in 2012overweight, no w/ sx caloric intake, ex,
overcome insulin resistance (dec
low HDL <40M or <50F, secretion) + physical activity, metformin, TZDs)
insulin action - same amt of insulin =
hyperlipidemia >150, less response) & dec insulin dec insulin prevalence is pregnancy A1C > 6.5%
impaired FBS >100) - a/w secretion action (resist highest in Repair dual defect: inc
underlying insulin insulin resist (aging, weight, via inactivity + older people Diet: more trans insulin action (metformin,
resistance inc risk of CVD sedentary activity) compensated early obesity) (60+) but fat, more sat fat, TZDs); inc insulin
& DM by inc in beta cell fxn; beta cell fxn highest higher glycemic secretion (B-cell
falls = inc glucose levels (1. post- inc IHL a/w dec incidence in load (less fruits, enhancers, insulin - basal
prandial, 2. pre-prandial)
insulin action impaired but insulin action; middle aged veggies, more & bolus, incretins - assist
insulin resist: post-receptor defects
does not get much worse (dec phosph after insulin binds); hi inc oxid stress (40-59) fat) B-cells)
btwn pre-diabetes to DM; triglyc deposit = inc DAG accum = a/w inc B-cell
insulin secretion dec dec insulin signaling; sequest of apop, dec Native B-cell rest for pre-DM (dec
significantly w/ impaired GLUT4 inside the cell insulin syn & Americans> insulin resistance, glucose
glucose tolerance, insulin secretion defects: no 1st secret blacks> levels, inflamm/ox stress/
suggesting dual defects in phase, blunted 2nd phase; hyper- hispanics >> ER stress) = dec need for
insulinemia
T2DM dec insulin, inc Asians> endogenous insulin and
islet cell dysfxn: inc glucagon, dec
insulin glucagon post whites less B-cell apoptosis =
DKA, inc FBS, inc obese adipose tissue = inc oxid prandial (opp dec progression of DM
postprand gluc stress from inc NADPH oxidase of nl)
Variants
Gestational carbohydrate intolerance - maternal hyperglycemia --> fetal 7% of all FH of DM universal screening 24-28 A1: 30kcal/kg/day diet frequently resolves
diabetes -> hyperglycemia with hyperinsulinemia --> inc pregnancies h/o macrosomia weeks: 1h 50g glucose BMI>30: 30% caloric after delivery
onset during pregnancy production of fetal fat cells --> complicated obesity challenge test (>140 - 80% restriction
obesity --> insulin resistance --> by GD AMA (>35y.o.) of GDM, 14% FP; >130 - 90% Maternal comps - HTN
A1: controlled w/ diet & ex impaired glucose tolerance in h/o poor of GDM, 25%FP; >200 - nutritional counseling. Ex d/o (pre-eclampsia,
A2: require meds for control childhood --> DM 1/3 of GDM obstetric diagnosed w/ GDM & do not during pregnancy, eclampsia); C/S;
patients will outcome need 3h GTT) maintain FBS < 95 & 2h stillbirth; trauma
macrosomia (excessive fat insulin resistance increases as have DM h/o GD postprandial <120
deposition on fetal pregnancy progresses (higher postpartum ethnicity (AA, if failed 1h glucola, then fetal comps -
shoulders & trunk due to the maternal glucose levels = hispanic, NA, PI) give 3h GTT (diagnosis A2s: lifestyle mods + macrosomia,
stimulation by IGF-I & 2) worse fetal outcomes) 50% of GDM requires 2 abnl blood glyburide (low doses 2.5 hyperbilirubinemia,
patients will draws: fasting > 95, 1h > mg --> 10 mg); if still not operative delivery,
develop DM 180, 2h > 155, 3h > 140) controlled, add insulin shoulder dystocia,
within 10y of UA: check for ketonuria (does not cross placenta) birth trauma, neonatal
affected hypoglycemia, resp
pregnancy OCP postpartum, distress syndrome,
postpartum screening: if
preconceptual glycemic childhood obesity
DM - refer to endocrinology;
if nl - assess q 3y, counsel control imperative (diet,
ex, behavioral mods to
for weight loss; if impaired -
avoid GDM recurrence)
weight loss, activity,
nutrition, metformin, assess
Diabetic severe insulin deficiency increased gluconeogenesis medical illness, T1DM q 1y
elevated anion gap -
Ketoacidosis causes hyperglycemia stress, or metabolic acidosis
(DKA) nth degree of diabetes sx: omission of hyperglycemia (usually >
massive polyuria, massive increased lipolysis = release of insulin 300)
dehydration, life threatening FFA, inc B-oxidation of FFA = ketosis
electrolyte shifts and inc acetyl CoA which is pseudo-hyponatremia
metabolic acidosis converted to ketone bodies in (dilutional), hyperkalemia
the liver pre-renal azotemia
Chronic Retinopathy microvascular insulin is not needed for glucose

complications utilization in the
of DM microvasculature; inc glucose =
Nephro- microvascular inc metabolism to sorbitol &
pathy fructose = inc osmolarity = inc
Neuropathy microvascular water = osmotic cell injury
CAD, macrovascular inc glycation products (HbA1C)
ischemic react w/ arterial wall
heart dz components, cross link
collagen, & inc arterial stiffness
inc LDL promotes

atherogenesis
Hypoglycemia (general) most common complication clinical syndrome w/ diverse low blood glucose (sx oral glucose (tablets, neurological
causes related to decreased usually when <60 mg/dL; sugary sodas), glucagon compromise or mental
ANS sx: sweating, anxiety, plasma glucose levels brain fxn impaired < 50 (if seizures or coma), IV retardation
nausea, trembling, feelings mg/dL) + presence of glucose (if compromised
of warmth eventually leads to cortisol, GH, epinephrine airway)
neuroglycopenia (low sugar in
neuroglycopenia: dizziness, the brain) urine or serum ketones -
fatigue, HA, confusion, ketotic or non-ketotic
difficulty speaking, unable hypoglycemia
to concentrate, seizures,
coma
Variants
Ketotic hypo- Ketones in urine or serum substrate limited: unavailable Substrate-
glycemia carbs/ poor storage = unable to limited
fast for a long time w/o Hormone
becoming ketotic (MSUD) deficiencies
Hormone deficiency: panhyopo- GSDs
pituitarism (GH, ACTH def), D/Os of gluco-
glucagon def, epi def, cortisol neogenesis
def (Addison's, congenital
adrenal hyperplasia) Drugs -
Others: drug-induced, systemic alcohol,
d/o (can't meet body's energy salicylates,
demands), liver disorders (can't quinine,
make or use glucose - hepatitis, valproic acid,
cirrhosis) insulin
Alcohol? metab by alcohol

dehydrogenase in liver, requires
NAD+; results in NADPH
accumulation, inhibiting
gluconeogenesis by inh malate --
> OAA
Non-ketotic hyperinsulinism shuts down the hyperinsulinism

hypo- production of ketones Fatty acid ox
glycemia D/O
d/o in fatty acid oxidation carnitine or
prevents the generation of CPT I or II
ketones (Acyl dehydrogenase deficiency
deficiencies like MCADD)
carnitine (akee fruit - Jamaican

vomiting sickness) or CPT
deficiencies prevent the
shuttling of fatty acids into
mitochondria
Medium Chain presents at 3-24 months autosomal recessive mutations 1/15,000 avoid periods of reduced
Acyl (peak at 15 months), in ACADM gene that results in carb intake (problematic
Dehydrogenas during periods of fasting abnormality in B-oxidation --> when sleeping)
e Deficiency or sickness non-ketotic hypoglycemia
(MCADD)
Hyper- Congenital PHHI = persistent mutations in ABCC8 gene K-ATP channel 1/40,000 GOF GDH mutation: pancreatectomy if AR K- autosomal recessive K-
insulinism hyperinsulinemic (SUR1) causes abnl of the outer mutation hyperinsulinism + ATP mutation of clonal ATP mutations are
hypoglycemia of infancy subunit (50-60% of cases) or (SUR1/Kir6.2) K-ATP >> hyperammonemia (which loss of heterozygosity most severe (diffuse
the KCNJ11 gene (kir6.2) GDH > does not inc w/ protein islet cell hyperplasia)
dx w/i 1st weeks of life; causes abnl in the inner subunit; glutamate glucokinase feeds) diazoxide TID if mild AD while autosomal
transient to severe; inability these mutations cause K-ATP dehydrogenas K-ATP, GDH, or dominant K-ATP muts
to maintain glucose levels channel to be permanently e mutation intra-arterial calcium glucokinase mutations are more mild
despite oral or IV closed, so insulin is (AD) gluconate infusion:
supplementation constitutively released determine insulin levels carb load before protein severe developmental
glucokinase across pancreas (splenic a, (Leucine) intake if GDH disorders and mental
also called nesidioblastosis, GOF muts (activated by leucine) mutation (AD) SMA, gastroduodenal a, mutation retardation from lack
B-cell hyperplasia, B-cell of glutamate dehydrogenase = celiac axis); areas of of blood sugar to brain
dysmaturation syndrome inc oxid of glutamate = inc a- highest insulin levels are acute tx: oral glucose
ketoglutarate, ATP, & insulin prob location of faulty (best if possible) of sugary most patients with
glucokinase mut - enzymes and must be liquids or IV glucose diffuse areas of
decreased glucose GOF muts of glucokinase hyperinsulinism will
removed surgically (focal or
threshold for insulin to (glucose sensor, 1st step in chronic tx: diazoxide, develop DM
diffuse lesions)
shut down glycogen synthesis & glycolysis) ocreotide (somatostatin),
= activation of insulin until BG is hi calorie feeds, surgery;
PET scan to eval high
GDH mut - inc NH3 levels around 40 HRT
uptake at high insulin
concentrations (only avail
at CHOP)
Variants
Acquired Whipples triad suggests exogenous delivery to someone Exogenous glucose tablets, IV reactive hypoglycemia
insulinoma who doesnt need insulin = delivery glucose, or glucagon (if can be a precursor to
(hypoglycemia + hypoglycemia seizing or unconscious) T2DM
symptoms - weakness, insulinoma
tremors, sweating, hunger, insulinoma = tumor that
palpitations, weight gain, secretes insulin retroperitoneal
exercise induced, CNS sx, tumors
psychiatric probs, relief w/ retroperitoneal tumors = tumors
glucose) that mediate IGF-2, which binds reactive
insulin receptors hypoglycemia
reactive hypoglycemia =
ingestion of simple sugars w/o
fats or carbs = insulin spike that
easily takes up simple sugars
Hypothyroidism (general) underproduction of reduced production of T3 & Hashimotos iodine def = elderly primary: low T3, T4; Levothyroxine diabetes,
T3&T4 T4 thyroiditis, most common extremely hi TSH (Synthroid, 1.6ug/kg atherosclerosis,
subacute cause globally (compensation to increase body weight)- pure T4;
reduced metabolic state, primary: thyroid gland is thyroiditis, diet of hypo- TH) DOC for replacement/ slow titration of
dec CO, lethargy, dec affected iodine def, thyroidism suppression, keep TSH Levothyroxin in elderly
appetite w/ inc weight secondary: pituitary is affected lithium OD hi TSH/TRH could possibly WNL, watch free T4 w/ to avoid complications
gain, coarse hair, mental (TSH deficiency, pituitary tumor) (rare),congenit F>M, cause prolactinemia sec/ tert hypothyroidism w/ coronary heart
slowness, dry skin, slow tertiary: hypothalamus is al errors of TH increased disease
pulse (brachycardia), affected (tumors, infiltrative dz) release/ prevalence w/ secondary: low T3, T4; low Liothyroxine (Cytomel) -
cool/dry/ puffy skin, droopy synthesis age TSH pure T3; used ONLY for
eyelids, large tongue, +/- most common causes? (rare), acute/severe hypothyroid
goiter, thinning of lateral 1/3 Autoimmune dz, radioiodine radiation 10% of elderly (Myxedema coma)
of eyebrows, constipation, or thyroidectomy, pituitary exposure,
cold intolerance, insufficiency iatrogenic Liotrix (Euthroid, Thyrola) -
(radioactive mixture of T4/T3 in 4:1, no
KIDS: same sx as adults iodine tx or advantage
BUT poor linear growth, surgery
excess weight gain, & ablation), Thyroid (USP) and
poor school performance postpartum thyroglobulin (Proloid) -
thyroiditis dried animal thyroid; not
recommended
Congenital Failure to thrive! thyroid gland dysgenesis or thyroid gland newborn screen - confirm thyroid hormone CRETINISM = mental
agenesis - most common dysgenesis or w/ TSH (extremely hi if no (Levothyroxine) retardation if not
impaired development of cause agenesis thyroid hormone present) & increases growth & treated early!!!
CNS & skeleton, severe serum free T4 mental development - if Signs?? Impaired
mental retardation, short dyshormogenesis - deficiency or lingual thyroid unsure, treat shortly after skeletal/CNS
stature, coarse facial absence of TPO birth bc brain growth 80- development)
features, protruding tongue 85% complete by 3y.o.
& umbilical, +/- goiter if risk of bleeding if
dyshormogenesis treat moms if maternal removal of lingual
thyroid deficiency thyroid
Hashimoto's most common cause of autoimmune destruction of the 2nd most low T3, T4; hi TSH; positive
thyroiditis hypothyroidism in thyroid common thyroid antibodies (TPO)
FEMALES cause of
defect of T cells causes hypoT AFTER
goiter. production of anti-thyroid iatrogenic!
antibodies that are cytotoxic to
the thyroid gland
Subclinical Painful thyroid following initial thyrotoxicosis followed by NO uptake on I-123 scan transient - supportive care rarely progresses to
URI or viral infection hypothyroid state & treatment of underlying overt hypothyroidism
dz
postpartum Painless thyroid abrupt onset of thyrotoxicosis;
progresses to hypothyroidism in
40-50% of patients
Variants
Hyper- (general) overproduction of T3&T4 exaggerated T3 and T4 Graves dz 85% of the hi T4, T3; undetectable TSH Thioureylenes osteoporosis, bone fx
thyroidism production causes suppressed (young F) - cases caused (compensation to decrease (Propylthiouracil or
inc metabolic state, TSH (negative feedback) see below by Graves TH) Methimazole/Tapazole)
nervousness, insomnia, toxic,
fatigue, irregular heart beat 5-10% of pts will have nl T4 but multinodular I-123 scan: hot nodules
(afib), tachycardia, inc exaggerated T3 (T3 toxicosis) goiter
appetite w/ dramatic weight (elderly) - see brain MRI if pituitary tumor
loss, heat intolerance, pituitary tumors can sometimes below suspected (hi T4/T3, hi TSH)
exopthalmos, +/- goiter, cause inc T3, T4, AND TSH! TH overdose
hyperhidrosis, alopecia, (most should try & get I-123 scan
hyperdefecation, abnl LFTs, common on all hyperthyroid patients
osteopenia, hi Ca, tremors, cause!) (not all thyrotoxic patients
proximal myopathy, thyroid tumor, are hyperthyroid - i.e.
periodic paralysis, subacute subacute thyroiditis)
onycholysis (separation of thyroiditis,
fingernail) postpartum
thyroiditis,
painless
thyroiditis
amiodarone
Graves most common cause of autoimmune disorder resulting a/w HLA-B8 & F>M (7:1) FH hi T4, T3; undetectable TSH, "cool down" with anti- blindness and
disease spontaneous in the production of anti-TSH DR3, other positive TSI (thyroid thyroid drugs; 50% of pts decreased ocular
hyperthyroidism under 40 receptor antibodies (thyroid autoimmune 2% US stimulated IgG), goiter will be cured w/ meds vision if exophthalmos
years old stimulating immunoglobulin d/o women alone not treated!
IgG) that bind TSH-receptor and possible T3 toxicosis (inc in
diffuse toxic goiter, mimics natural TSH; thus, T3 only) med tx: propanolol Radioactive iodine -->
exophthalmos (protrusion thyroid produces TH (tachycardia, inhibits hypothyroidism
of eyeball from thickening Hot, diffuse nodule on I-123 conversion of T4 to T3),
of retro-orbital tissues), scan anti-thyroid meds
thyroid "stare" (stare from (methimazole, PTU for
the spasm of levator pregnant women ONLY),
palpebrae muscle form inc GCs (inhibit T4-->T3)
B-adrenergic stimulation),
pretibial myxedema usually require
(orange peel appearance radioactive iodine
on lower legs from
mucopolysaccaride surgery also option
infiltration: non-pitting
edema), onycholysis, Afib
(most common sx in
elderly)
Toxic amount of TH made is autonomous functioning 2% of low iodine intake I-123: hot nodule w/
adenoma related to mass of nodule "single" thyroid nodule hyperthyroid complete to partial
cases supression of paranodular
thyroid tissue
Thyroid storm tachycardia, fibrillation,sudden acute exacerbation of Propanolol +

(Thyro- shock, heart failure thyrotoxicosis secondary to thioureylenes + large
toxicosis) severe hyperthyroidism and doses of Lugol's
upregulation of metabolism/
sympathetic nervous system
Thyroglossal mass in midline of neck + remnants that occur when duct histology: variable
duct cyst thyroid tissue present does not sufficiently close epithelium cyst lining (non-
descript cuboidal,
sometimes squamous)
Lateral aberrant lateral to usually metastasis from histology: lymphoid tissue
thyroid sternocleidomastoid papillary thyroid carcinoma + thyroid glands
Variants
Goiter (general) enlargement of the in low iodine areas, TH cannot endemic endemic areas histology: large colloid Iodine if related to iodine
thyroid gland be produced so hypothalamus (iodine (Alps, Andes, lakes w/ involuted areas of def
increases TSH secretion = deficiency, Himalayas; variable appearance,
increased growth of thyroid goitrogens!), iodine def = TSH surrounded by smaller
gland sporadic, = hyperplasia) thyroid follicles
familial
causes in developed countries:
diffuse simple goiter, Graves,
Hashimotos, subacute
thyroiditis, multinodular
goiter, malignancy, genetic
Diffuse diffuse, symmetrical diffuse non-toxic: diffuse F>M FH of Graves euthyroid - nontoxic
enlargement hyperplasia w/o nodularity;
usually related to goitrogens hyperthyroid - Graves
Toxic (Graves disease) (Ca, Fl, veggies), may develop
Non-toxic (simple) in multinodular gross: Graves - red,
hyperactive appearing
diffuse toxic (Graves dz): a/w thyroid
autoimmune dz histology: Graves -
scalloping (clefts around
colloid), inc # cells &
hyperplasia
Multi- nodular, lumpy autonomous function of nodular older age I-123: hot nodules - anti-thyroid meds hypothyroidism if tx w/
nodular enlargement thyroid tissue --> multinodular prevent sx BUT DO NOT radioactive iodine
hyperthyroidism (toxic) PE: can sometimes feel CURE DZ!! (although less
Toxic (Plummer's dz) lumpy thyroid gland, but common than Graves
non-toxic (simple) 25% of patients have non- Radioactive iodine +/- patients)
palpable surgery (only if trouble
toxic sx: unexplained swallowing, compression
weight loss, depression, U/S of trachea) - surgery can
Afib sometimes be better
option if VERY large
Thyroid benign / non- solitary or part of occur in almost any thyroid carcinoma, palpable usually euthyroid
nodules neoplastic multinodular goiter disorder benign nodules in 6% require fine needle
hyperplasia women, 2% aspiration cytology to define
R/O malignancy by 50% - non-neoplastic colloid men hyperplasia OR malignant
measuring TH & TSH - if nodules epithelium
abnl do fine needle 30% - adenomas (benign
aspiration (also done if epithelial follicular neoplasms; I-123 scan: nl thyroid nod will
nodule > 1cm) slow growing, rarely fxnal) have diffuse filling/uptake;
10% - carcinoma "cold" nodules (no iodine
follicular adenomas - 5% - benign cysts uptake - VERY concerning
uniform follicular pattern; no for Ca)
goitrous nodules (if present, gross: if uniform tan/ gooey
think multinodular goiter), material w/o capsule - colloid
complete fibrous capsule, nodule; capsule w/ complete
sharp demarcations, no integrity - adenoma; thick
vascular or transcapsular capsules - malignancy
invasion!!! histology: uniform w/o
transcapsular invasion
(adenoma)
Variants
Thyroid papillary - sporadic, PMH of normal follicular cells --> uncommon radiation to neck histology: Papillary thyroidectomy, papillary carcinoma -
carcinoma neck radiation; slow adenomas under influence of but increased (fibrovascular core lined by radioactive iodine lymphogenic spread
growing, good prognosis RAS oncogenes --> subset of incidence w/I genetic epithelial cells; finger-like;
follicular - more aggressive adenomas progress into past 20 years, (medullary) enlarged, optically clear cells Thyroid replacement follicular carcinoma -
but good prognosis; follicular carcinomas F>M w/ intranuclear grooves; little therapy if angio-invasion/
common in iodine def pre-existing orphan Annie's eyes - hypothyroidism results vascular spread to
countries normal follicular cells --> young- mid thyroid disease Psammoma bodies); bone & lungs
medullary - arise from C- papillary carcinomas under age females (hashimotos - Follicular (hard to diff from whole body scan post
cells (parafollicular cells influence of RET mutations (papillary) malignant adenoma; vascular &/or surgery total thyroidectomy -
secrete calcitonin), lymphoma, transcaps invasion; Hurthle required exogenous
neuroendocrine neoplasm pre-existing follicular or papillary Papillary (75- carcinoma) cells - more agg lesions); serum thyroglobulin - hormone replacement
(MEN IIa, MEN IIb, non- cancer acquires p53 mutation 80%), Medullary (C- cell tumor marker after total
MEN) w/ amyloid deposition to become anaplastic follicular (10- elderly hyperplasia, amyloid thyroidectomy
undifferentiated - no carcinomas (hi grade!!) 20%), un- (malignant deposition, neuroendocrine +
follicular/ papillary morph, differentiated lymphoma, stains - calcitonin, ectopic
elderly, rapid growth, local (1-5%), undiff hormones)
invasion, poor prognosis medullary (3- carcinoma) gross: transcapsular invasion
Malignant lymphoma- 5%) (follicular!!); necrosis
elderly women, a/w (malignant lymphoma)
Hashimotos thyroiditis
Thyroiditis Acute inflammation of the thyroid very rare immunocomp

caused by bacteria or fungus
Chronic Hashimoto's thyroiditis a/w other autoimmune d/o: <1% familial histology: lymphocytic inc risk for thyroid
deficiency of suppressor T thyroiditis, reactive carcinoma &
cells --> immunologic abnl F>M follicular centers (germinal malignant lymphoma
(anti-microsomal centers); destruction of
autoantibody) --> thyroid thyroid follicles, Hurthle
destruction cells (abundant pink
reactive cytoplasm),
fibrosis
gross: enlarged thyroid,
bosselated (bumpy) w/
creamy surface from
lymphocytes
serum autoantibodies: anti-
microsomal,
antithyroglobulin, anti TSH-
R, blocking antibodies
Subacute DeQuervain's / uncertain - possibly post-viral F>M hyperthyroidism followed

granulomatous thyroiditis by hypothyroidism (if gland
inflammation causes stops functioning)
small goiter AND hyperthyroidism from rapid
DIFFUSE PAIN!! (unable to release of TH histology: granulomatous
palpate bc of pain), fever of giant cells w/ lymphocyte
unknown origin TRANSIENT - complete infiltrate (no giant cells seen
resolution over 2-6 months in Hashimotos!)
hyperthyroidism state -->
hypothyroidism state I-123: no uptake
(sometimes) (inflammation of thyroid
responsible for
hyperthyroidism)
Fibrous Riedel's thyroiditis long-term inflammation --> VERY rare gross: woody hard area
fibrosis --> destruction of thyroid around periphery of thyroid
woody/ stone hard gland and adjacent neck gland
thyroid gland structures
clinically resembles malignancy

Variants
Postpartum painless thyroiditis very high recurrence hi T3/T4 (hyperthyroidism), severe depression
appearing 1-2m post- common!! rate! low TSH, positive anti-
delivery, lasts 2-5m thyroid antibodies; followed
often by hypothyroid phase!
goiter increases 1-2m
postpartum, fatigue/
moodiness (hard to dx!!)
hyperthyroidism state -->

hypothyroidism state
Multiple MEN1 recurrent stomach ulcers, germline mutation in menin Autosomal 0.25% dx: 2 or more of "3Ps" + total parathyroidectomy pancreatic islet cell
endocrine (Werners hypercalcuria w/ (tumor suppressor gene) - dominant population relative w/ 1P & autotransplant tumors (usually
neoplasm syndrome) nephrolithiasis, chromosome 11 multiple, small, &
headaches, bitemporal all ages, no 4 gland hyperplasia PPIs if gastrinoma; benign) can become
visual field loss, other early signs of menin sex pref (sporadic dz only has single ocreotide or malignant
hypercalcemia mutation? Facial parathyroid adenoma) pancreatectomy if
3Ps: pituitary adenomas angiofibromas & 80% manifest insulinoma hi surg failure &
(prolactinomas most collagenomas tumor by 5th genetic screening if mutation recurrence
common), hyper- decade known in the family
parathyroidism (4 gland necrolytic migratory
hyperplasia from 2ndary first erythema - if
hyper-parathyroidism manifestation glucagonoma
leading to hypercalcemia), s occur earlier
pancreatic islet cell than in
tumors (gastrinomas --> sporadic dz
ZE syndrome-inc gastric
acid secretion & PUD from
gastrinoma; insulinomas -->
hypoglycemia)
adrenal hyperplasia
MEN2A medullary thyroid germline mutation in RET path: medullary thyroid prophylactic some variants of
carcinoma or hyperplasia oncogene (tyrosine kinase carcinoma will be thyroidectomy MEN2A have
of thyroid C cells + pheo- receptor) immunoreactive for Hirschsprungs dz
chromocytoma (adrenal calcitonin (megacolon from
medullary tumor) + lower intestinal
parathyroid neoplasms obstruction) or
(adenoma or hyperplasia) cutaneous lichen
amyloidosis (upper
back)
MEN2B Pheochromocytoma + germline mutation in RET calcitonin secretion prophylactic
thyroid medullary oncogene thyroidectomy
carcinoma (or C- cell
hyperplasia) + mucosal
neuromas (neural tissue
nodules in GI tract or
mouth) + marfanoid
habitus
Osteitis fibrosa hypercalcemia, excessive bone resorption by XR: thin cortex & bone
cystica pathological fractures, osteoclasts related to cysts
bone pain parathyroid overactivity -->
dissecting osteitis in cancellous path: dissecting osteitis
hyperparathyroid bone bone --> osteoblastic bone
disease formation (fibrous replacement
results in weakened bone and
scarring)
Variants
Hypocalcemia (general) tetany (neuromusc hypoparathyroidism (insuff low Mg+2, low low total calcium, high acute - IV calcium
irritability, musc cramps, activity of parathyroid = low albumin (binds phosphorus gluconate
tonic-clonic seizure; PTH, hypocalcemia), calcium so can PTH deficiency - low Ca, low
elicited musc contractions pseudohypoparathyroidism cause PTH chronic - calcium
w/ Chvostek & Trousseau (active parathyroid gland but unadjusted low PTH resistance or renal carbonate
signs), ocular abnl unresponsive end organs), total calcium) failure - low Ca, high PTH
(cataracts, papilledema, vit D def/insufficiency, vit D vitamin D - if PTH
pseudotumor cerebri), dependent rickets I & II meds (Lasix, ALGORITHM: problem, give calcitriol; if
prolonged QT interval & (genetic deficiency of 1-a calcitonin, anti- low PTH? hypoPTH (gland vitD deficient, give
nonspecific T wave hydroxylase prevents activation neoplastic defect, no PTH production, cholecalciferol (precursor)
changes, anxiety, of vit D in kidney), end organ agents, anti- prob w/ CaR);
confusion, depression, resistance to vit D; convulsants, nl PTH? hypoPTH, transient
intracranial sx (basal renal failure (unable to make citrated blood hypoPTH;
ganglia calcification, RBCs, active vit D; can't products) hi PTH? Renal failure, vitD
parkinsonism), dental reabsorb Ca or eliminate P = inc deficiency (would mean PTH
manifestations (dental PTH) is less effective at raising
hypoplasia, failure of activating defects (GOF) in calcium so parathyroids
eruption), macrocytic CaR of parathyroids(takes a would continue to release
megaloblastic anemia, lower calcium to induce PTH; more...)
diarrhea would have nl PTH levels); PTH
resistance
Familial inherited activating mutation of
hypercalcuric calcium-sensing receptor on
hypocalcemia parathyroid chief cells; results in
constitutive supression of PTH
release and low serum calcium
levels
Hypercalcemia (general) sx related to sites of parathyroid hormone related excess PTHrP hi PTH? symptomatic - fluids
calcium action/reg: (primary or tertiary (cancers) Hyperparathyroidism, followed by furosemide
("stones, bones, groans, hyperparathyroidism - SEE causes release familial hypocalcuric once volume is
psychic overtones") BELOW) of PTH hypercalcemia corrected; calcitonin
- bone: fxs, osteoporosis, vitamin D related (vitD IM/SC (acute relief),
osteomalacia, osteitis intoxication; granulomatous dz low PTH? Tumor induced bisphosphonates
fibrosa cystica like sarcoidosis, TB) (PTHrP), granulomatous dz (slower relief); GCs (if
-kidney: nephrolithiasis, malignancies (ectopic hormone or lymphoma, bone myeloma, granulomatous
nephrocalcinosis, polyuria production - PTHrP; osteolytic metastases, meds dz, or vitD toxicity),
- CNS: depression, metastases) dialysis - last resort
seizures, obtundation, Meds (thiazides, lithium, bone mineral density test
muscular contractions antacids) for osteoporosis
- EKG changes (shortened genetic (CaR mutations -
QT interval) inactivating) 24h urine calcium &
- GI: gallstones, acute hyperthyroidism creatinine clearance for
pancreatitis, peptic ulcers kidney fxn
Hyper- most common cause of humoral hypercalcemia of SCC - lung LOW PTH, hi Ca (nl
calcemia symptomatic malignancy (HHM) - major cancer, RCC, feedback system, but hi
from hypercalcemia cause of severe hypercalcemia, lymphomas. calcium from hi PTHrP)
malignancy usually due to ectopic PTHrP Local bone
PTH independent metastasis often have low albumin
hypercalcemia osteolytic metastases: ectopic from breast Ca from malnourishment/
PTHrP from SCC, RCC, or myeloma weight loss
FATIGUE, polyuria lymphomas, HTLV; vitD
producing tumors MRI or CXR to find
(lymphomas), ectopic PTH malignancy
tumors, local osteolysis
(breast Ca or myeloma
metastasizes to bone)
Variants
hyper- PTH independent Granulomas make 1a- TB, sarcoid,
calcemia hypercalcemia hydroxyase = increased 1a- lymphomas,
from hydroxylase activity = increased fungal infection
granuloma production of vitamin D =
dz increased calcium absorption
Familial PTH dependent inherited inactivating mutation Hispanic FH low 24h urine excretion of benign condition that
hypocalcuric hypercalcemia of the calcium-sensing receptor origin calcium usually doesnt require tx
hypercalcemia on parathyroid chief cells;
results in constitutive release of
PTH and high serum calcium
levels
CaR senses low calcium when

the Ca levels are actually
normal --> causes hi PTH, hi
calcium
Hyper- Primary PTH dependent lesions directly to the parathyroid 25/100,000 hi PTH, hi Ca, hi 24h urine parathyroid adenomas are brown tumors of
parathyroidism hypercalcemia parathyroid gland cause adenoma cases in U.S. excretion of Ca treated by surgical hyper-
excessive PTH release excision IF criteria met parathyroidism
most often - diffuse/ nodular Females 3:1 path of parathyroid (Ca > 11.5, reduced (reactive mass formed
asymptomatic parathyroid adenomas = most hyperplasia adenoma: small tumor w/ kidney fxn, T-score on secondarily to
hypercalcemia common cause of asymp encapsulated growth BMD <-2.5, age <50) microfractures and
hypercalcemia; usually parathyroid pattern, lack of nl fat hemorrhages as a
sporadic, solitary lesions carcinoma component of PT, uniform if do not meet surgical result of
Can also cause STONES, diagnosed incidentally; often (rare) cells w/ round nuclei (tumor criteria, monitor blood multinucleated giant
BONES, GROANS, have mutations in cyclin D1 nests w/ dense chromatin), tests every 6 months cells and fibrous
PSYCHIC OVERTONES (promotes cell division), menin rare mitoses tissue influx)
(MEN1), RET (MEN2)
path of parathyroid osteitis fibrosa
carcinoma: much larger cystica (see above)
than adenoma; bland
cytology (may have fibrosis,
scarring within tumor nests,
subtle infiltrative growth);
local invasion & metastasis
Secondary dialysis patients! chronic hypocalcemia --> renal failure PTH > 500 REQUIRES parathyroidectomy if PTH
hyperstimulation of the medical intervention cannot be controlled w/
parathyroid gland --> vit D deficiency meds
hyperplasia of parathyroid and
increased/chronic release of
PTH
Tertiary possibly associated w/ accumulation of mutations from

duration of dialysis; can secondary
occur in post-kidney hyperparathyroidism
transplant patients hyperplasia leads to the
development of calcium-
independent lesion
Variants
Hypo- primary insuff activity of dysfunctional or hypofunctional low (or nl) PTH, low slow infusion of IV calcium
parathyroidism parathyroid gland = low parathyroid gland usually calcium, hi phosphate (too fast can cause
PTH and hypocalcemia related to an autoimmune cardiac probs + burns)
process, infiltrative process
decreased serum PTH (hemochromatosis, Wilson's dz - oral vitD (if low PTH -
(deficienct PTH secretion) copper, aluminum, breast which means that 1a-
cancer metastasis, hydroxylase cannot be
granulomatous dz), or activated to make active
magnesium deficiency vitD)
(chronic alcholism, malnutrition,
TPN, diuretics - thiazides, recheck calcium levels in
furosemide, familial) 3m (if rise in Ca,
suggests transient
hypoPTH)
Iatrogenic history of neck surgery, removal of parathyroids from most common

thyroidectomy, cervical surgery (thyroidectomy), TPN, cause of
lymph node dissection thyroid ablation w/ radiation hypocalcemia
Congenital DiGeorge syndrome absence of 3rd & 4th agenesis/ digeorge - if patient's calcium levels DiGeorge syndrome -
(pharyngeal pouch pharyngeal pouches, the dysgenesis of 1:5500 (M=F) rise after 3m of meds, abdominal aortic
maldevelopment) - embryological origin of parathyroids; suggests transient arches, VSDs life
posteriorly rotated ear, parathyroids transient hypoPTH threatening after birth;
flat nasal bridge, (maternal immune dysfxn (abnl
hypertelorism (lots of DiGeorge syndrome - defect in hyper- thymus development)
space btwn eyes), small chromosome 22; 95% de novo calcemia
chin mutation shuts down
baby's PTH),
Velocardiofacial syndrome syndromes
Familial candidiasis, recessive autoimmune regulator

(APS-I) hypoparathyroidism, gene (AIRE) mutations cause
Addison disease autoimmune polyendocrine
syndrome 1
Pseudo increased serum PTH end organ resistance to PTH low Ca, hi phos, hi PTH, nl
(PTH resistance) due to renal fxn, low 1,25(OH)2-
Type 1a = Pseudohypo- production of abnl PTH vitD, problems w/ other
parathyroidism (abnl molecule that does not hormones that work
biochem findings) + properly interact w/ receptor through G proteins (TSH,
Albright's hereditary (abnl alpha subunit of G LH, FSH)
osteodystrophy (AHO) protein - GNAS1 gene)
(short stature, obesity, XR of hands: short
brachymetaphalangia, metacarpals
calcifications, mental
retadation)
Variants
Vitamin D rickets: bowed legs, normal bone development limited 1 billion decreased 1,25(OH)2 vit D bone disease/ inc fx
deficiency / kyphosis, enlarged involves mixture of osteoid (non-
sunlight worldwide OR total 25(OH) vitD2/D3 - (osteoporosis - bone
insufficiency epiphyses, metaphyseal mineralized component of exposure, better indicator bc longer resorption > bone
flaring, thickened wrists collagen, chondroitin sulfate, &inadequate half life formation), rickets/
from hi bone turnover, osteocalcin) with mineralized dietary intake, osteomalacia
rickettic rosary (palpable component (calcium phosphate) kidney dz low Ca, low phos (bc vitD (osteoid does not
nodules on ribs) (increased increases GI absorption of mineralize --> "soft
vit D deficiency = dec calcium, excretion of Ca + phos; also nl PTH bone"), cancer, CVD,
osteomalacia in adults phosphate absorption = poor phos + inability causes kidney excretion of T2DM, autoimmunity
mineralization of bone --> to create active phos), hi alkaline
def = vitD < 50 mmol/L rickets in kids or vitD), GI dz phosphatase; however,
insuff = vitD < 75 mmol/L osteomalacia in adults (dec rickets dx REQUIRES
absorption), radiographic changes
nutritional vitD deficiency, def in vitD
hypophosphatemic rickets, 25- enzymes/ XR: cupping/ metaphyseal
OHase def; 1,25-OHase def receptors, flaring
(renal failure), resistance to resistance to
calcitriol vitD
Hypo- respiratory & cardiac arrest decreased absorption of hi PTH low vitD3, low serum give VitD (increases
phosphatemia (lack of ATP) phosphate (vitD def, vitD phosphate, & phosphate & calcium
dependent rickets I&II, alcohol, hi FGF-23 (low phosphaturia? Check MRI absorption, preventing
bone pain, weakness, refeeding syndrome) P, low vitD3) of head/chest/pelvis for PTH action)
pathologic fx tumor (suspect oncogenic
increased urinary loss of low vitD3 osteomalacia), could also
phosphate (hyper- suggest PHEX mutation
parathyroidism, RTAs, DKA; PHEX mutation preventing FGF-23
oncogenic osteomalacia - degradation (suspect X-
tumors that make FGF-23; X- linked hypophosphatemic
linked hypophosphatemic rickets or autosomal
rickets - mutation in PHEX dominant
prevents FGF-23 degradation; hypophosphatemic rickets)
autosomal dominant
hypophosphatemic rickets -
FGF-23 resistant to PHEX
degradation)
transcellular (respiratory
alkalosis, leukemia)
Hyper- increased intake (TPN,

phosphatemia phosphate enemas)
decreased excretion (usually

chronic kidney disease,
hypoparathyroidism)
excess bone resorption
transcellular shift (tumor lysis,

rhabdo)
Variants
Pituitary (general) microadenomas (usually mass effect macroadenomas - MENI (menin most common histology: loss of cellular macroadenomas are pituitary apoplexy -
adenoma secrete hormones) - <1cm; grow so large that impinge the mutation), in adults (40- heterogeneity, loss of harder to manage (mass pituitary adenoma
prolactinomas, corticotroph optic chiasm, which supplies the other mutations 50 y.o.; M=F) glandular structure (sheet effect) infarction from
adenomas, somatotroph medial aspects of the globe and (CREB, Gs like proliferation, neurocytic expansion --> severe
adenomas responsible for lateral portions protein, loss of rosettes around vessels, headache & loss of
of visual field (lateral field Rb, excessive papillary config, or ribbon vision (MED
macroadenomas (usually deficits) growth factor appearance), enlarged EMERGENCY!!
present w/ mass effect production) nuclei; if severe necrosis/ Interferes w/ ACTH
without syndromic effect) evasion of apoptosis -> hemorrhage think apoplexy! secretion)
>1cm - bitemporal unlimited replicative potential -
heminopsia, diplopia > growth signal independence MRI: homogenously pressure/mass effects,
(CN3, 4, 6 palsy), -> anti-growth insensitivity -> contrast enhancing (no hypersecretion of
headache sustained survival -> cystic components or hormones
adenoma formation calcifications)
order of hormone
disruption: GH--> LH/FSH --
> TSH --> ACTH
Prolactin- galactorrhea, adenomas that secrete prolactin 30% of increased serum prolactin Treatment IF macro- mass effect can
oma amenorrhea, decreased pituitary (usually > 200 ng/mL) & adenoma, mass effect, interfere w/ secretion
libido, infertility, occur in 20% of patients with adenomas positive immuno- fxnal compromise of other pituitary
amenorrhea/ MEN1 syndrome histochemistry for prolactin (infertility, galactorrhea); hormones
hypogonadism, (brown = positive) o/w monitor
osteoporosis, reduced prolactin inhibits
facial hair in men possible decrease in FSH, dopamine agonists gonadotropin release
LH; possible (Bromocripitine, & steroid prod in end
hypopituitarism depending Cabergoline) for tx of organs -->
on size of prolactinoma microadenomas amenorrhea or
secondary
R/O secondary causes surgery if macroadenoma hypogonadism in
(kidney, liver tests; TSH; w/ critical mass effect men
pregnancy test, med eval) (loss of vision, rapid
progression, spread to osteoporosis
MRI of pituitary for mass ICA), young pt w/ potential
for cure, no response/ recurrence (16%)
tolerance for med tx,
recurrence surgery - loss of
anterior / posterior pit
fxn (DI)
Non- no clinical manifestations 20% of
functional pituitary
adenomas
Corticotroph Cushing's disease microadenoma that secretes 15% of
(obesity, stria, HTN, acne, excess ACTH pituitary
DM) adenomas
Variants
Somato- Gigantism (if adenoma adenoma that secretes excess 15% of elevated IGF-1 (even after usually macroadenomas acromegaly:
troph occurs in childhood before GH pituitary age- matching to requiring debulking
closure of epiphyses) adenomas references) surgery - 1st option! cardiomyopathy,
GH over production leads to obstructive sleep
acromegaly (if adenoma gigantism or acromegaly; OGTT suppression test meds: somatostatin apnea, diabetes,
occurs AFTER closure of most likely due to pituitary (hyperglycemia) results in analogs (ocreotide), GH colon cancer,
epiphyses) - large feet, adenoma sustained elevation of GH receptor antagonists increased malignancy
coarse/ enlarged /spongy (nl the GH level would be (Pegvisomant),
hands, auditory probs, can also have mixed GH & reduced w/ hyperglycemia) dopamine agonists (if panhypopituitarism
thickened skin/ lips, wide prolactin secreting adenomas dual prolactin & GH after radiation tx
nasal bridge, furrowed (better prognosis than GH impaired glucose secretion) (causes loss of GH,
brow), proportionally adenoma alone) intolerance then FSH/LH, TSH,
enlarged organs, arthritis, radiation for residual dz or ACTH)
neuropathy insidious onset - check suboptimal response to
pictures of pt from years surgery & meds
before
Gonado- excess secreted by 5% of pituitary

troph adenoma could cause adenomas
precocious puberty
Thyrotroph 1% of pituitary
adenomas
Pituitary overgrowth of cells of one

hyperplasia type, leading to hormone
hypersecretion without
presence of obvious tumor
Cranio- suprasellar tumor proliferative or neoplastic somatic cell more MRI: cystic components + difficult to resect (due to radiation can cause
pharyngioma conversion of cysts in mutations in B- common in calcifications oily substance secretion & pan hypopituitarism
"intermediate lobe" --> ectopic catenin gene kids (ages 10- keratin) (lifelong hormone
remnants of pharangeal 16) Histology: usually don't see replacement therapy)
epithelium epithelium in the brain but surgery + radiation
10% of all this has epithelium (from proximity to 3rd
hemorrhagic mass in pediatric Rathke's cleft) lined w/ ventricle/ optic nerves/
suprastellar space that intracranial basal lamina that create optic chiasm/
impinges on CNS structures -- tumors keratinaceous material (wet hypothalamus
> calcifications, squamous keratin nodules that
differentiation undergo calcification), large size, locally
cystic spaces w/ oily invasive, recurrence
substance/ cholesterol risk
deposits
Rathke's cleft located within sellar hyperplasia of cystic structures histology: lined by single
cysts space or extends into of intermediate lobe of pituitary layer of columnar ciliated
suprasellar space epithelium, everything else
is cyst fluid
single cell layer (simple)
cyst
Pituitary aggressive lesions that <5% of

carcinoma invade soft tissue structure, masses
vasculature, & bony
structures
Variants
Germinoma suprasellar tumor histology: clear tumor cells
w/ large nuclei, prominent
nucleoli, positive
lymphocytic infiltrate &
granulomatous
inflammation, positive for
PLAP, c-kit, Oct4 markers,
similar pathologic features
as testicle/ovary neoplasms
MRI:homogenous &
compact suprasellar mass
Pituicytoma suprasellar tumor that arise from posterior pituitary histology: stains positive
resembles glial tumors (pituicytes) for GFAP (glial fibular acidic
protein - IF of glial cells)
Granular cell suprasellar tumor arises from posterior pituitary histology: large pink, surgical resection low, grade benign
tumor gland lysosome filled benign lesions
tumor cells that PAS
positive
ADH deficiency Diabetes excessive urinary loss of central causes: loss of acquired hi serum osm, low urine
Insipidus solute-free water posterior pituitary function --> central osm; urine osm < serum
deficiency of ADH (neurosurgery, osm (DILUTE urine bc no
excessive thirst/ H2O head trauma, ADH & H2O reabs; nl expect
intake (polydipsia), nephrogenic causes: end tumors, hi serum osm to cause inc
polyuria (>2.5L/d), organ resistance to ADH infiltrative dz, urine osm)
hypernatremia, idiopathic)
hyperosmolarity acquired water deprivation test - once
nephrogenic plasma osm > 295, give ADH;
(hyper- central cause of DI if low
calcemia, serum ADH but responsive to
hypokalemia, ADH ; nephrogenic cause if hi
lithium use, serum ADH but NOT
amyloidosis, responsive to ADH
Sjogrens)
Congenital R/O psychogenic polydipsia
nephrogenic (hi fluid intake & polyuria)- no
(defective V2- ADH resp, low urine osm &
R; aquaporin serum osm
mutation)
Variants
ADH excess Syndrome of gradual onset of dilutional inappropriate (nl/hi) malignancy hyponatremia w/ inapp low
Inapprop hyponatremia (mild sx: concentration of ADH for low (small cell lung - plasma osm
ADH headaches, muscle plasma osmolality --> water para-neoplastic
(SIADH) cramps, nausea, lethargy; retention & hypo-osmolality synd; non-pulm urine osm > plasma osm
severe sx: AMS, seizures, despite euvolemic status cancers), CNS (would nl expect dilute
coma, death!) d/o (mass urine if low plasma osm)
lesions, inflam
dz - SLE, exclude secondary causes
meningitis, of hyponatremia (hypovol,
degenerative hypotension, generalized
dz, subarach edema d/o, renal/ adrenal
hemorrhage, insuff, hypothyroidism)
trauma)
renal sodium excretion > 20
drugs, pulm dz mmols
(TB, pneumo,
mech
ventilation),
other (AIDS)
Short stature (general) analyze growth velocity, malnutrition (ask re: 24h nl causes: 90% of blood or urine test: IGF-1 & WAIT - most improves w/
final height prediction (mid dietary intake), systemic genetic/ referrals are IGF-BP3, free T4 & TSH time; counseling, improve
parental height, bone age) illness (chronic renal failure, familial, const normal caloric delivery, GI/
congenital heart disease w/ hi delay of GH stimulation testing genetics eval??
Final ht = MPH +/- 3.9" output or cyanosis, anemia, growth, most common
males: (5"+ moms ht + IBD); skeletal dysplasia improper cause for Bone age: XR of LEFT wrist HRT??
dads ht)/2 (estimate body proportions), measurement failure to & hand (girls: 95% of ht at BA
females: (moms ht + dads chromosomal aneuploidy grow?? GC 13; boys: 95% of ht at BA
ht - 5)/2 (Turners syndrome), hormone abnl causes: excess 14.5)
const delay - nl growth deficiency/resistance, poor weight (Cushings)
velocity, delayed bone age idiopathic gain,
genetic - nl growth velocity, osteochondro-
nl bone age (-2sd) dysplasia,
hormone probs - poor genetic
linear growth, adequate/ syndromes,
excessive weight gain, hormone
delayed BA, increased problems
weight: height percentile (thyroid def,
GH def, GC
excess)
Variants
hypo- GHRH deficiency hypo- GHRH def = low basal GH,
thalamic thalamus IGF-1, & IGF-BP3
defect (GHRH def,
somatostatin no GH released following
excess), indirect stimulation testing
pituitary (hypoglycemia, a-2 agonist,
(GHRH L-DOPA)
receptors, GH-
1 gene to +GH released w/ direct
encode GH, administration of GHRH (if
transc factors intact blood supply of
like Pit-1, anterior pituitary), ghrelin,
PROP1, or GHRP
HESX1);
target (GH-
receptors,
intact Jak/Stat
pathway, intact
IGF-1 and IGF-
BP3 response
systems)
Pituitary GH deficiency possible cranio- low basal GH, IGF-1, & IGF- treat w/ GH until growth
defect pharyngioma BP3 complete; may need as an
adult also
no GH released following
indirect stimulation testing
no GH released with direct

admin of GHRH
End organ GH receptor mutations GH receptor low IGF-1 levels, HI basal

defect (deletion, non-functional) mutations? and stimulated GH levels
prevents end organs from (Laron
responding to GH Syndrome) low levels of GHBP
(extracellular domain of GH
receptor that has broken
off) - suggest GH
insensitivity rather than
problem w/ GH
Hypo- (general) central defects in tumors - craniopharyngioma, congenital or

pituitarism pituitary hormones (all or optic glioma, pituitary adenoma acquired - use
partial) trauma - physical abuse, MVA age of onset,
(usually posterior & anterior medical hx,
defects bc severed neural stalk) imaging,
inflammation - histiocytosis, associated
hypophysitis findings, &
cranial radiation - usually impairment of
knocks GH out first visual fields to
Idiopathic assess
inborn errors of pituitary
development - septic optic suspect
dysplasia (SOD) - incomplete genetic cause
development of if early onset,
hypothalamus, septum no hx of
pellucidum, & optic nerves trauma/
radiation,
distinct growth
& hormone
phenotypes,
founder effect
Variants
MPHD Multiple pituitary consider transcription factors genetic - AR
hormone deficiency involved in pituitary mutation
development -
multiple sibling involvement SHH - expect
w/ normal parents holoprosencephaly; HESX1 -
a/w SOD; LHX3 & LHX4
Pit1 mutations - early & involves loss of less hormones;
extreme growth retardation, PIT1 & PROP1 (PROP1 is
spont puberty necessary for appearance of
Pit1; PROP 1 promotes
PROP1 mutations - no development of lineage cell
pubertal stage, abnl rosy precursors in anterior pituitary)
cheeks, severe
hypothyroidism
Precocious (general) signs of clinical puberty increased sex steroids caloric intake early maternal evaluate girls/boys showing GnRH agonist (lupron) advanced bone age
puberty (breast/ testicular (excess menarche, low clinical pub before 7y(white) early but finish
development and/or pubic central or non-central (see adipose) birth weight, inc or 6y (black) / 9.5y treat underlying problem growing so end up
hair) below) weight gain respectively (eliminate exposure to being smaller than
(obesity) in Check urinary/GI tract if agents, surgery for tumor/ expected
causes of early menarche childhood, bleeding; Check estrogen / cysts, treat hormone abnl
(vaginal bleeding) w/o other international testosterone; Growth like CAH/ hypothyroidism)
signs of puberty?? FOREIGN adoption, velocity? Growth chart?
BODY, trauma, ovarian cysts, estrogenic Significant weight gain? ketoconazole - inhibits
McCune Albright chemicals, (more chol = more androgen synthesis
absence of androgens) Check neuro/
father in fundoscopic exam; check
household, for physical signs of
FEMALES puberty
If child has muscle
development, check testes
size - think non-central cause
if small (if central - enlarged
testes bc stimulation w/
FSH/LH)
Central gonadotropin - dependent (inc
FSH & LH, inc testosterone or
estradiol)
idiopathic (>90% females, 45%

males)
CNS abnormality -
hypothalamic/ pituitary mass,
cerebral malformation, injury/
head trauma
Early exposure to sex

steroids (inc bone age w/
estrogen or testosterone)
Variants
Non-central gonadotropin - independent
(decreased FSH/LH, increased
testosterone or estradiol)
autonomous gonadal
activation- McCune-Albright
Syndrome (GNAS activating;
see below), activating mutation
of LH receptor gene
adrenal d/o - CAH, adrenal
tumor (muscle development +
small testes)
exogenous exposure to sex
steroids
Tumor - ovarian cysts
(Granulosa cell / androgen
producing), Leydig cell tumors
in testicle, hCG producing
tumors in liver
van Wyk-Grumbach syndrome
(see below)
McCune- early non-central puberty + activating mutation in GNAS mutation in the XR: smoked out appearance aromatase inhibitors (dec
Albright hyperthyroidism causes ovary/testicle to gene that on XR of femur estrogen), SERM
Syndrome develop independently of codes for the (tamoxifen - blocks
TRIAD: non-central stimulation by gonadotropins - alpha subunit estrogen receptor)
precocious puberty, caf- -> secretion of estradiol/ of the
au-lait skin findings, testosterone--> precocious stimulatory G however, tx is
hyperostosis fibrous puberty protein (Gsa) controversial as this d/o
dysplasia usually does not
Excess estrogen exposure = progress
increased growth velocity &
marked advancement in skeletal
maturity
ovary will be hyperfunctional

for some time but then
involutes; once brain senses
that bone age is appropriate,
pulsatile GnRH & LH/FSH
secretion will begin,
normalizing puberty
Van Wyk- only condition w/ dec T4 = inc TRH = inc TSH &
Grumbach precocious puberty w/o Prolactin
Syndrome bone age advancement
(growth arrest)!! TSH shares alpha subunit w/
FSH so FSH also increases =
Primary hypothyroid + increased estradiol in ovary
precocious non-central
puberty
Variants
Turner Short stature, primary phenotype that occurs in paternal non- 1:2500 live amniocentesis: abnl short stature - GH hypothyroidism,
Syndrome amenorrhea, infertility patients w/ one normal X disjunction female births chromosomes replacement T1DM, T2DM,
Clinical clues? Pterygium chromosome & complete/ partial karyotype: One X osteoporosis,
colli (abnl ear), cystic absence of the other X structural most chromosome with absent 46th premature ovarian failure - premature death
hygroma (fluid filled mass - chromosome = 45X OR 46X, chrom abnl common chromosome add androgens when (related to CVD,
prenatal U/S), acral structurally abnl X OR mosaics (iso- recognizable PE: signs of coarct & HF appropriate for puberty coarct), aortic
lymphedema (nail chromosome = cause of (crackles, displaced apical dissection, ovarian
dysplasia, puffy feet), aorta lymphatics drainage prob --> 2q's - long spont Ab impulse, hepatomegaly, early multi-disciplinary failure/ dysgenesis
coarctation (HTN, CHF, cystic hygroma, non-pitting arms, no p - systolic click), non-pitting interactions w/ cardio,
cardiomegaly, pulm edema edema short arm; ring median age of edema (sign of lymph prob) psych, ENT, progressive
AFTER ductus closes), chromosome) dx? 15 y.o. Pelvic XR - maldeveloped endocrinology, etc sensorineural
cervical hypoplasia, hi arched palate --> feeding/ head of femur, displaced from deafness, probs w/
congenital hip speech problems, dental foramen - DISLOCATED HIP social intxns & visual/
dislocation, horseshoe crowding ECHO - bicuspid aortic valve spatial defects
kidney, hi arched palate, Renal/pelvic U/S - horsehoe
shield chest, gene dosage effect - SHOX kidney, duplicated UT Y chrom mosaics - inc
hypogonadism, (pseudoautosomal region) risk for gonado-
sensorineural deafness, deficiency --> skeletal abnl & blastomas -->
Madelung deformity, short stature dysgerminoma -
strabismus (cross eyed) require ovary
removal!!
Polycystic secondary amenorrhea, androgens cause early 6-10% FH DX OF EXCLUSION: weight loss & exercise increased risk of
ovary hirsutism/acne, infertility, follicular arrest & atresia --> prevalence supportive data? for insulin resistance & endometrial cancer
syndrome obesity, hyperlipidemia, oliganovulation, infertility, & Hyperandrogenism, hirsutism (can also use (unopposed estrogen),
(PCOS) insulin resistance cysts on ovaries accounts for oligoanovulation, polycystic OCPs) DM, CVD, obstetric
~75% ovaries on U/S, obesity, risks, depression,
Diagnosis REQUIRES 2 of androgens provoke anovulatory IR/DM, hi LH/FSH ratio metformin for anxiety, infertility
3 criteria: oligomenorrhea, accelerated GnRH pulsatility, infertility hyperinsulinemia &
any evidence of causing enhanced release of possible improved
hyperandrogenism LH and subsequent production response to clomid
(clinical hirsutism, acne; of more ovarian androgens
biochem findings), PCOS ovarian wedge resection
appearing ovaries on U/S insulin resistance might also be for hyperandrogenemia
(>12 cysts, 2-9 mm) underlying mechanism for
PCOS - hyperinsulinemia clomiphene,
acanthosis nigricans might potentiate LH response gonadotropins, or
to produce aromatase inhibitors for
hyperandrogenemia anovulation
live birth rate better w/

clomid + met or clomid
alone (NOT met alone)
Variants
Abnormal (general) any disruption from structural or functional PALM-COEIM 2nd most perimenopause Pregnancy test!!! Anovulatory bleeding:
uterine normal cycle (24-35d x 4- abnormality?? P (polyp), A common CBC (R/O anemia, progesterone (oral tx,
bleeding (AUB) 6d, 30 ml blood loss) (adenomyosis reason for thrombocytopenia) Mirena IUD) - induces
Ovulatory v. anovulatory?? Ask ), L (leio- OB/GYN TSH (hypo/hyperthyroidism regular bleeding &
oligomenorrhea - cycle about timing (ovulatory bleeding myomas) M visits a/w AUB) prevents endomet
intervals > 35 days more regular due to (malignancy, cervical cancer screening hyperplasia (opposes
polymenorrhea - cycle programmed shedding of hyperplasia), C most chlamydia (hi risk patients) estrogen), combined
intervals < 24d corpus luteum) (coagulopathy common screening for bleeding d/o OCPs, estrogen tx (only if
menorrhagia - normal ), O (ovulat cause of (adolescents) hemorrhaging w/ low
intervals but excessive flow absent menstrual flow during pill dysfxn), E adolescent endometrial bx (>40 y.o., hematocrit), D&C
or duration free week of OCP - think (endometrial), hospital prolonged anovulation) (hemodynamically
metrorrhagia - irregular progesterone breakthrough I (Iatrogenic), admissions transvaginal U/S (hi risk for unstable)
intervals, normal flow or bleeding (use short interval of M (Mullerian cancer/ hyperplasia if Ovulatory bleeding:
duration estrogen) anomalies) endometrial stripe > 5 mm) NSAIDs (dec
menometrorrhagia - hysteroscopy (dx, tx prostaglandin), OCPs,
irregular intervals, symptomatic intrauterine Mirena IUD, GnRH
excessive flow or duration pathology) agonists (preop pts),
antifibrinolytics
Menstrual diaries (tranexamic acid)
surgery: endometrial
ablation, hysterectomy
Polyps intermenstrual spotting benign growths, can cause
intermenstrual spotting, can be
hyperplastic in menopausal
women
Adeno- painful periods endometrial glands that grow diagnosed with pathology
myosis into the myometrium (muscle) of only!
the uterus, making the uterus
globular
Leio- primarily benign but can benign tumor from the smooth most common
myomas convert to tumor (rare) muscle of the uterus lesion
(fibroids) myometrium causing AUB
submucosal fibroids (in in
uterus) have severe reproductive
bleeding aged women
Malignancy postmenopausal bleeding endometrial cancer - bleeding obese, elderly,

- must R/O endometrial most likely due to atrophy post-
cancer menopausal,
PCOS
ovarian neoplasms often
functional tumors
(granulosa cell, thecoma)
Coagulo- often in adolescents or von Willebrand factor, ristocetin 20% w/ heavy CBC/platelets
pathy patients with chronic AUB cofactor menstrual prothrombin time
bleeding have partial thromboplastin time
certain meds (warfarin, heparin, underlying
NSAIDs, herbals - gingko, bleeding d/o
ginseng, motherwort)
Ovulatory nl H/P/O axis, nl steroid local abnl prostaglandin

dysfunction hormones synthesis, increased tissue
plasminogen activator (TPA)
activity, increased local
fibrinolytic activity
Endocrino- usually PCOS bleeding due to unopposed PCOS

pathy estrogen
Endometrial endometritis, hyperplasia
Variants
Inflammatory bleeding without relation vulvitis, vaginitis, cervicitis,
to menses endometritis, salpingitis, PID
a/w signs of infections

Iatrogenic foreign bodies (children), coital
lacerations, trauma
Pregnancy bleeding + PAIN - think implantation bleeding 1-2d snowstorm pattern on U/S -
bleeding ECTOPIC!! following missed menses (often molar pregnancy
mistaken as menses)
Uterus S>D, quant b-hCG gestational sac seen
> 100,000 - think MOLAR ectopic pregnancy, molar outside of the uterus -
pregnancy! pregnancy ectopic pregnancy
20-25% of women spot/ bleed

during 1st trimester
Hypertension Chronic hi BP before pregnancy, or mosy
during HTN <20 weeks gestational age common med
pregnancy comp of
systolic > 140, diastolic > pregnancy
90 predating pregnancy
or identified before 20 6-8% of all
weeks gestation live births
if PNC began at > 20 17.6% of

weeks and she has HTN > maternal
12 weeks postpartum, deaths in U.S.
considered chronic HTN
(diagnosed post-hoc)
Gestational hi BP >20 weeks

HTN gestational age
BP > 140/90, occuring

after 20 weeks without
proteinuria
Pre- hi BP > 20 weeks AND BP > 140/90, occuring after 20 requires maternal starts w/ up & down BP, DELIVERY!! HELLP: liver
eclampsia PROTEINURIA weeks gestation with placenta!! extremes of age progresses to >140/90, then hematomas, DIC
proteinuria (> 300 mg/24h proteinuria followed by If <32 weeks, give fetal risks: IUGR,
collection) 1st child signs & sx of severe pre- antenatal oligohydramnios
severe pre-eclampsia sx: eclampsia; if left untreated, corticosteroids & (decreased amniotic
oliguria of 500mL in 24h, severe: 1+ of following criteria chronic HTN, will progress to eclampsia stabilize w/ MgSO4 (anti- fluid = dec urine output
cerebral/ visual (BP>160/110 >2x, 6 h apart vascular seizures), anti- from blood flow shunt
disturbance, pulmonary while on bedrest OR proteinuria disease, DM hypertensives, & LD to brain/heart/adrenals
edema or cyanosis, of >5g/24h OR proteinuria of bedrest for 48h before & away from kidneys),
epigastric or RUQ pain, >3g in 2 random urines >4h hx of HTN in delivering placental
impaired liver function, apart) pregnancy infarct/abruption,
thrombocytopenia (platelets prematurity
< 100,000), fetal growth vasoconstriction/ vasospasm minority groups consequences,
restriction [circul vasoconstrictors + endog uteroplacental
vasoconstrictors -> endothelial insufficiency, perinatal
HELLP syndrome damage (dec prostacyclin, inc death
(>24wks): hemolysis, TbxA2) --> primary DIC] maternal risks: CNS
elevated liver enzymes, low problems (stroke,
platelets improper trophoblast seizures), DIC, C/S,
implantation --> immunologic renal failure, hepatic
response failure, death
Eclampsia mild or severe pre- cause of stabilization (MgSO4,

eclampsia PLUS maternal antihypertensives),
SEIZURES!!! mortality assessment for maternal
sequelae, and delivery
Variants
Atypical pre- vague RUQ or epigastric
eclampsia discomfort, small
headache, incidental
thrombocytopenia
new swelling of legs,

general sick appearance
Spontaneous 1st trimester bleeding aneuploidy - monosomy X0 or 50% of 1st Type & Cross - Rhogam if usually no intervention is
abortion trisomy 16 trimester Rh- required; however, if
Threatened bleeding tissue remains (missed) -
Inevitable - os is wide D&C or medical tx
open, lots of blood
missed/incomplete - some heavy bleeding? D&C
tissue still present
Complete - uterus is empty
and hCG levels drop off
following day
Ectopic 1st trimester bleeding pregnancy/ implantation of Chlamydia - 1-2% prior ectopic, Type & Cross - Rhogam Rh- Unstable? Send directly to 10% mortality w/
pregnancy gestational sac OUTSIDE of the replicates prevalence PID, surgery, OR rupture
Bleeding + pain!! uterus intracell & endometriosis Transvaginal U/S -
lyses cells endometrial stripe w/ no Certain ectopic? INFERTILITY
Adnexal mass + tenderness interstitial tubal pregnancy gestational sac; gest sac in Methotrexate (1st line!), chronic pain
most dangerous bc least fallopian tube/ outside uterus surgery
rupture?? Unstable vitals, distensible!
positive pregnancy test, Blood in belly - ruptured
diffuse tenderness, Ampullary end of Fallopian ectopic
bleeding (low HCT) tube and abdomen most
conducive to embryonic Arias-Stella reaction -
development hyperplastic endometrial
cells; stroma with decidua
but no chorionic villi /
placenta= pregnancy but
outside of uterus
gross: decidual cast -

partially necrotic membranous
tissue expelled from vagina
Placental 3rd trimester bleeding separation of placenta from 15% of 3rd trauma, U/S NOT helpful, dx is immediate hospitalization, Fetal prematurity
abruption AND PAIN!!! uterus trim bleeding smoking/ clinical (NO CERVICAL IV access/ fluids/ type & (Resp distress
cocaine, EXAM!!) cross syndrome,
10% have no bleeding 1:120 multiparity, HTN, intraventricular
(blood could be retained deliveries prior abruption, Deliver if unstable (vag hemorrhage,
behind the placenta) AMA or C/S) enterocolitis,
blindness),
increased uterine stable? Expectantly
contractions manage fetal anemia,
fetal hypoxia (cerebral

palsy, seizures),
maternal hemorrhage
shock,
DIC (abruption)
fetal anemia,
Disease Clinical Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment fetalComplications
hypoxia (cerebral
Variants palsy, seizures),
Placenta previa 3rd trimester bleeding placenta covers the internal 10% of 3rd multiparity, prior NO CERVICAL EXAM!!! immediate hospitalization,
cervical os trim bleeding C/S, prior D&C, IV access/ fluids/ type & maternal hemorrhage
PAINLESS bleeding smoking, prior U/S cross shock,
0.5% of births previa, AMA
C/S delivery if unstable DIC (abruption)
or term
Stable & pre-term?

expectantly manage,
eventual C/S
Postpartum blood loss with delivery most loss after separation of non- 5% of uterine atony: hi evaluate uterine fundus - IV access/fluids/ type &
hemorrhage placenta; control the contraction contracting deliveries parity, bogginess? cross immediately
(involution) of uterus & uterus overdistention
coagulation/ thrombus formation (UTERINE uterine atony - (twins, Inspect for lacerations if atony? Pitocin-like
ATONY) most common macrosomia), uterus is firm feeling oxytocin, prostaglandins
uterine atony = lack of involution cause of post- prolonged labor,
or contraction down genital tract partum rapid labor, evaluate the placenta &
laceration hemorrhage prolonged use of explore uterus
genital tract lacerations - induction
caused by large baby, retained agents,
compound presentation, placental chorioamnionitis,
episiotomy, operative delivery, fragments prior history
or rapid labor
coagulation retained
disorders placental frags:
prior C/S, uterine
curretage,
accreta
Ovarian cancer Germ cell & abdominal discomfort & most are spontaneous cases, hereditary Leading FH of ovarian CA-125 (low specificity, If mass on PE, increased no screening test so
stromal cell distention (usually although 5-10% have hereditary breast & cause of cancer, useful if hi clinical CA-125, and suspicious patients present at
(more advanced stage), component ovarian cancer death for gyn advanced age, suspicion) + U/S --> SURGERY later stage (Stage III) --
common in dyspepsia, urinary (BRCA1) malig nulliparity, transvaginal U/S to assess (exploratory surgery, > higher mortality
younger frequency, weight loss, abnl unknown etiology North American/ pelvis (best in peri & maximal tumor reduction,
women) bleeding, pelvic pressure, 1/70 women North European postmenopausal women) biopsies)
back pain, asymptomatic protective factors? Multiparity, descent, PMH of
epithelial mass OCP use, breast feeding breast/ colon/ palpable mass on pelvic + postoperative
(most [increased risk of ovarian uterine cancer exam treatment w/ IV
aggressive cancer a/w increased chemotherapy or clinical
form, more ovulatory cycles, so events trials
common in that decrease # cycles
older protective]
women)
Endometrial primarily affecting estrogen sensitive neoplasm - increased most age > 60 endometrial biopsy - surgery - TAH
cancer peri/postmenopausal unopposed estrogenic estrogen common gyn obesity perform if abnl bleeding +
women stimulation of endometrium synthesis malignancy unopposed >4mm endometrial
(obesity, in U.S. estrogen thickness on U/S; abnl
postmenopausal protective factors? OCP, granulosa cell chronic bleeding + tamoxifen use;
bleeding, leucorrhea (thick smoking (gross) tumors) anovulation post-menopausal bleeding;
white discharge), (PCOS) change in bleeding pattern
pain/pressure tamoxifen (breast cancer decreased tamoxifen use in women on HRT or peri-
chemoagent) - selective estrogen endometrial menopausal
endometrioid type - most estrogen receptor that has metabolism hyperplasia
common histology type and antagonistic effect on breast (hepatic dz) (atypical
CURATIVE! BUT agonist effect on complex)
endometrium inapprop HRT
(estrogen only)
Variants
Cervical cancer Squamous abnl bleeding, discharge HPV 16 & 18 globally, most low SES (access Pap smears - screen for Stage I-II A: radical stage I - cervix
(80-90%) common gyn to screening) dysplasia surgery/ hysterectomy + Stage II - upper vag
POST-COITAL BLEEDING malignancy additional cervical tissue Stage III - lower vag
adeno- (lower in U.S. young age at 1st Colposcopy
carcinoma back/ flank pain, bc screening) sexual exposure Stage IIB - IV: each stage has A
(10-20%) hematuria, dysuria - (duration of Biopsy chemo+radiation (vertical progression)
advanced stages 3rd most HPV) and B (lateral
small cell & common gyn CXR - R/O lung metastasis progression)
sarcomas malignancy multiple sexual IVP - analyze kidney
(worst partners, function larger masses, more
prognosis) cigarette invasive/
smoking, high vascularized, lymph
risk male node involvement =
partner, worse prognosis
persistent HPV/
HIV infection surgical comps?
ureteral injury, fistulae,
bladder/ rectal dysfxn,
DVT, bleeding
Germ cell Ovarian Dys- dysplastic germ cells unilateral germ cell tumor young women, gross: solid, yellow, radiosensitive, treated malignant but good
tumors of ovary germinoma (similar to testicular often a/w lobulated/ septated tumor; conservatively (R/O mixed prognosis
seminoma) pregnancy no necrosis germ cell tumor!!)
usually NO hormone histology: large nucleus &

production nucleoli; lobular
appearance
Endodermal young women gross: solid tumor w/ combo of chemo, malignant tumor
sinus (yolk multiple areas of necrosis radiation, & surgery
sac) tumor improve 5y survival
histology: Schiller Duval
body (central vessel
surrounded by tumor cells),
globules with alpha-feto
protein
AFP - hi but decrease post-

surgery (unless some
tumor remaining)
embryonal histology: embryoid body

carcinoma
poly-
embryoma
Chorio- markedly hemorrhagic arise from trophoblasts gross: marked hemorrhage gestational: methotrexate
carcinoma sensitive, better
produces hCG!! gestational: arise from histology: prognosis
placenta & products of syncytiotrophoblasts that
+pregnancy test in men! conception stain brown for hCG non-gestational: NOT
responsive to
non-gestational: arise from monitor w/ hCG methotrexate, worse
germ cell tumor prognosis
Variants
Ovarian (general) benign teratomas? Brain germ cell tumors that make gross: torsion of cystic
Teratoma & choroid plexus (non- somatic tissue - hemorrhage w/ hair, etc? teratoma (acute abd
functioning) think teratoma infarction pain resulting form
- cystic teratoma - filled w/ vasculature
sacrococcygeal teratoma - yellow solidified sebum (nl strangulation -->
sacral growth in newborns in skin); some have teeth - teratoma
at risk for rupture hemorrhagic
- multiple glial nodules? infarction)
Benign teratoma (brain)
teratomas w/ teeth -
at risk for rupture
Immature solid, cystic, or both immature teratomas are gross: solid - hemorrhagic
arrested in embryonic & necrotic
solid - malignant development - BAD!!
histology: neuroepithelial
rosettes (immature brain
glial tissue, resembles brain
tissue in newborns)
Mature solid or cystic (dermoid cyst postmenopausal teratoma -
or dermoid cyst w/ SCC
malignant transformation -
postmenopausal women)
monodermal struma ovarii struma ovarii: benign but struma ovarii: looks like check opposite ovary -
functioning thyroid in a thyroid tissue but also has if similar appearance,
carcinoid (serotonin-like teratoma carcinoid appearance check intestines for
substances) metastasis
ovarian carcinoid in a
teratoma? Monotonous w/o
necrosis
Ovarian initially benign but usually gross: soft, nodular tumor hysterectomy!! malignancy shown by
Granulosa cell produces estrogens that is solid, yellow, & recurrence > 15 years
tumor (GCT) (rarely androgens) - hemorrhagic later
FEMINIZATION
histology: Exner bodies a/w uterine
estrogen can cause AUB (small acinar arrangement endometrioid
in post-menopausal w/ tumor cells surrounding carcinoma
women; gland) (unopposed
menometrorrhagia estrogen)
(irregular, excessive
periods) in reproductive
aged women; early
puberty in young women
Ovarian Theca MOSTLY benign! gross: solid yellow mass

cell tumor WITHOUT necrosis!
Usually produces
estrogens Histology: benign spindle
shaped cells (Theca cells)
that stain red for fat (steroid
production)
Ovarian usually benign but can gross: solid, white firm
fibroma produce Meigs syndrome mass
(ascites, pleural effusion,
benign ovarian fibroma) histology: benign spindle
shaped cells
CXR: ipsilateral
hydrothorax
Variants
Sertoli- Leydig benign masculinizing histology large columnar
cell tumor of tumor --> clitormegaly, cells (Sertoli cells, Leydig
ovary hirsutism cells); Leydig cells have
Reinke crystals (androgen
producing)
Germ cell (general) testicular mass but may germ cell tumors that present in chromosome 90% of 15-34 year old CXR: check for mediastinal radical orchidectomy + MALIGNANT in
tumors of also arise in anterior prepubertal males may be 12 abnl testicular males masses in Klinefelters pts chemo/radiation adults
testes mediastinum benign (mature teratomas) or neoplasms
low grade malignant (yolk sac Caucasians hCG & alpha-feto protein
tumors) cryptorchidism are markers for spread of
familial germ cell or recurrence
adult germ cell tumors = clustering following orchidectomy
MALIGNANT!
testicular
dysgenesis
(Klinefelters)
Intratubular immediate precursor preinvasive form of germ cell 5% of cryptorchidism, histology: enlarged nuclei 50% of men who
germ cell lesion for all types of tumors contralateral prior germ cell develop ITGCN will
neoplasia germ cell tumors of testis testes of men neoplasm develop invasive
(ITGCN) found as focal lesion in 2% of who had (contralaterally) germ cell tumors w/I
cryptorchid testis & biopsies orchiectomy 5y
performed for infertility testing for germ cell
neoplasm
Seminoma asymptomatic, most common pure type, DO NOT BIOPSY!!! Risk radical inguinal best prognosis - 95%
sometimes pain/ resembles spermatogonium spreading germ cell tumor orchiectomy, followed cure rate
discomfort by radiation to
histology: fried egg cells like abdominal LNs
spermatogonia
embryonal composed of primitive gross: varigated appearance NOT radiosensitive;
carcinoma undifferentiated epithelia & hemorrhage respond to orchiectomy
+ post-surgery chemo
histology: epithelial cells, no
spermatogonia (no fried eggs)
Teratoma composed of tissue components gross: tumors of the testis w/

resembling normal or immature cartilage, hemorrhage if
organ tissue mixed w/ embryonal
carcinoma
can be associated w/ embryonal
carcinoma or other components
(yolk sac, choriocarcinoma)
Sex cord Sertoli- usually benign; often 5% of 90% are benign!

stromal tumors Leydig cell hormonally active (may testicular
of testes tumors produce androgens & neoplasms
estrogens)
Leydig cells -->

testosterone (precocious
puberty)
Leydig cell or Sertoli cell

tumors --> gynecomastia
in adults
Variants
Squamous cell uncircumcised males > precursor lesion? Carcinoma in HPV <1% of male poor genital Bowenoid papulosis - HPV
carcinoma of age 40 w/ poor hygiene & situ = Bowen disease = solitary cancers in hygiene in related precursor lesion
penis chronic penile infections gray or erythematous plaque U.S. uncircumcised (rarely progresses)
related to HPV 16 men;
phimosis - inability to More Bowen disease -gray or
retract prepuce/foreskin Bowenoid papulosis - rare common in HPV 16&18 erythematous plaque; risk of
progression to SCC Asia, Africa, invasion 10%
S. America other HPV -
SCC = slow growing, locally genital warts histology: loss of polarity,
invasive lesion; metastasis mitotic figures, disorganized
may occur at inguinal & iliac growth that occupies full
LNs but widespread thickness of epithelium (rather
dissemination uncommon than more abundant
cytoplasm at top like nl);
KERATIN PEARLS
Carcinoma of topical exposure to coal
scrotum tars/ soot
Periductal inflammatory, benign development of inflammatory middle aged - histology: inflammatory cell
mastitis lesion in large ducts of cells in the periductal area of older women infiltration, weakened duct
breast breast tissue
sagging of the breast

Duct ectasia non-bloody, gritty dilation of duct due to dried out histology: dilation / stretch No predisposition to
bilateral nipple discharge secretions of duct w/ dried out carcinoma!
secretions
NO PAIN
Papilloma unilateral, non-milky proliferative lesion gross: pale, moist small risk of
nipple discharge from 1 papilloma from collecting carcinoma
duct orifice, +/- blood duct development
histology: nodule that

projects into the duct w/
proteinaceous secretions
(pink lines), blood supply
present (fibrovascular
core), epithelial +
myoepithelial layers present
Papillary unilateral, bloody nipple clonal lesion (no myoepithelial ~ 60 years old histology: fibrovascular usually good
carcinoma discharge cells) with vascular supply core, epithelial lining prognosis bc bloody
WITHOUT myoepithelial discharge is alarming
layer; overlapping nuclei enough to seek help
Variants
Cysts (breasts) dense firm breasts w/ non-proliferative lesions arising VERY reproductive gross: dark orange aspiration if extremely recurrence
palpable (sometimes from terminal ductule units common! aged women structures (cysts) that are painful
tender) lumps & frequent firm & tender, swell during
gross cysts exaggerated response of breast luteal phase of cycle;
stroma & epithelium to cycling of bumpy stroma from
hormones during reproductive collagen response to
years hormones
hormones make TDLUs more histology: pink secretions

edematous; cysts change seen in TDLUs, expansion
monthly w/ each cycle; and interconnection of
however, TDLUs do not dry TDLUs; apocrine cells +
out btwn pregnancies so calcifications - benign
always a baseline secretion findings
that increases in luteal phase
of cycle --> increased
pressure and secretion build
up --> cyst formation
Fibroadenoma BENIGN solid mass that non-proliferative lesions arising teenagers histology: sometimes large
is movable within the from terminal ductule units African calcifications (sclerosis w/
breast tissue Americans age - benign!)
arise in TDLUs in response to
hormones --> hypertrophy of needle core biopsy: sharp
lobules (stroma, ductules, demarcation of lesion w/
ducts) --> fibroadenoma characteristic feature of
formation enlarged duct, ductules, &
stroma
Phyllodes more cellular lesion in non-proliferative lesions arising > age 40 histology: very cellular MUST BE TOTALLY absolutely recurrent
tumor women after age 40 from terminal ductule units stroma that grows in leaf- EXCISED so excision required!
like pattern
Adenosis lumpy breasts due to proliferative lesions arising in women age 30- usually picked up on usually does not require
cyclical hormone TDLUs 40 mammogram due to routine f/u - no RR of
changes calcification formation malignancy
adenosis = increase in lobular development
Benign units
Sclerosing sclerotic collagenous proliferative lesions arising in very low probability
adenosis material causes FIRM TDLUs of becoming
breasts malignant!
Usual proliferative lesions arising in histology: proliferation of Benign lesion w/
hyperplasia TDLUs; increased number of both epithelial & minimal risk of
cells WITHOUT MUTATION!! myoepithelial cells into the malignancy
lumen (creates bridges),
phenotypic mixture of cells
(linear, oval, narrowed
spaces) but no pattern of
identical mutations
mammogram: calcifications
in the lobule unit spaces
Variants
Atypical (general) non-obligate precursor proliferative lesions arising in deletions in histology: has some excision of lesion w/ increased risk for
hyperplasia lesion for DCIS (some TDLUs; consistent mutations chromosomes cytologic features of low needle core biopsy DCIS or invasive
(ADH) ductal, capable of progressing into in certain chromosomes 16 &17 --> grade DCIS; usual carcinoma
lobular DCIS) "Roman hyperplasia + clonal lesions
begins w/ proliferation (usual bridge" like Roman bridges!
hyperplasia) --> deletions in structure SMALLER than DCIS;
chromosome 16 & 17 --> calcifications in lumen of
atypical hyperplasia spaces
Ductal Low grade non-motile mass on atypical hyperplasia + deletions in histology: monoclonal Complete excision + very hi risk for
Carcinoma In breast exam persistent mutations --> low chromosomes population of low radiation development into
Situ (DCIS) grade DCIS 16 &17 --> grade,mutated cells; round/ invasive ductal
"Roman punched out spaces carcinoma (if not
bridge" (Arches of Roman Bridge!); excised adequately w/
structure calcium phosphate crystals clean margins)
(stain purple), no
myoepithelial layer!
invasion present? small

patches of monoclonal cells
lacking myoepithelial layer
outside of the main DCIS
lesion
mammogram: atypical
pattern of calcifications
(jagged + small round
calcifications)
High grade usually ER/PR negative & NOT related to ADH histology: no punched out do NOT respond well to hi risk of invasion!!!
HER2/neu amplification spaces like low grade; fast estrogen antagonists like
mutation positive HER2/neu amplification growth --> disintegration of tamoxifen Recurrence w/I 3y if
mutations in duct epithelial -- nuclei; necrotic material in not adequately
non-motile mass on > high grade DCIS lumen (pink material respond to chemo like excised
breast exam representing disintegrating Herceptin (Trastuzumab)
nuclei) = comedo necrosis;
positive stain for HER2/neu
overamplification
mammogram: calcifications
that form mold/cast in duct
(linear calcifications)
gross: linear pattern;

necrotic material in the duct
(yellow)
Paget's disease UNILATERAL red/ scaly/ DCIS in the ductal system histology: DCIS riding AVOID corticosteroids may or may not be
of the nipple erosive nipple leading to the nipple towards nipple in the duct; invasive
dilated blood vessels
appear moist (hence, redness), scaly
appearing surface, DCIS
cells perforating the
epithelial layer
Variants
Infiltrating Low grade receptors for estrogen & low grade DCIS--> infiltrating gross: firm, immobile mass suppressed by anti- potential to invade
ductal progesterone ductal carcinoma, grade 1 w/ irregular spiculations estrogen drugs lymphatic spaces!
carcinoma, over time due to digestion of (tamoxifen)
non-motile mass basement membrane and mammogram: spiculations
acquisition of vascular supply (stars) @ periphery
histology: infiltrating
pattern w/ remnants of
DCIS; fibrotic (lots of
collagen! byproduct of
vascularization); low grade
nuclei, gland formation
invasive into stroma
High grade not estrogen/ progesterone progression of high grade determined by

responsive (ER/PR DCIS to poorly differentiated differentiation (gland
negative), positive lesions like infiltrating ductal formation), nuclear
HER2/neu amplification carcinoma grade 3 anaplasia, and mitotic
figures
non-motile mass
histology: poor gland
formation, necrotic cells,
mitotic figures
Atypical lobular precursor lesion to LCIS! histology: ductule spaces

hyperplasia full of round cells
(ALH)
Lobular non-calcifying lesion so progresses from ALH deletion of mammogram: no

carcinoma in hard to find!! precursor!! gene for E- calcifications
situ (LCIS) cadherin
ALL LACK E-CADHERIN = adhesion histology: proliferation of
poorly cohesive!! molecules round cells within the
lobule (bag of marbles)
Infiltrating diffuse spread within the progression from LCIS 10% of mammogram: no responds to tamoxifen!! bilateral risk!!! (if
lobular breast (lack of E-cadherin) invasive calcifications - difficult to lesion in one breast,
carcinoma breast detect! check same spot on
no masses or carcinomas the other brest w/
calcifications (i.e. woman Gross: looks like fatty biopsy!)
w/ consistent fibrous breast but can't see
mammograms suddenly lesion
has a 2.5 cm carcinoma)
histology: tumor cells
low grade bc ER/PR arranged in linear fashion
positive and HER2/neu or concentric circles (bull's
negative!! eye)
Induration might be felt

on breast exam
Medullary firm, small round mass round infiltrating ductal BRCA1/2 2-3% of histology: rounded pretty good prognosis
carcinoma carcinomas commonly seen infiltrating carcinomas w/ lymphocytic but confused for
ER/PR negative, HER2 in patients w/ BRCA1 or ductal infiltration! fibroadenoma often!
negative or positive BRCA2 mutations carcinomas
Variants
Mucinous rounded periphery women ages 55- mammogram: round good prognosis if
(colloid) lesions that also 60 years old calcifications (looks like properly diagnosed!!
carcinoma resemble fibroadenomas fibroadenoma)
(BUT fibroadenomas
appear at younger age gross: infiltrating mucinous
usually & would have been (wet, sticky appearing) w/
noticed in earlier hemorrhage
mammograms)
histology: islands of DCIS
ER/PR positive lesions floating in mucin
(clear); vasular supply
Breast cancer (general) - BRCA1/2 mutations - FH related to the number of estrogen #1 cancer increased age tamoxifen & raloxifene - staged based on
see above breast cancer < age 50, uninterrupted menstrual periods exposure among U.S. reduces breast cancer tumor grade, ER/PR
for deets FH of papillary ovarian (hence more estrogen (endogenous women; #2 Caucasians risk by 50%; increase stattus, HER2 status,
cancer; triple negative exposure) or exogenous) cause of (after age 45; bone density; however, lymph node status
(ER/PR, HER2) cancer before age 45, a/w increased risk for (axillary lymph nodes
pregnancy is protective in the hi risk mortality in AA have higher thromboembolic events first!!)
long-run mutations women risk) > AA> NA,
(BRCA1,2; Hispanic, Asian localized tumor - excision, greater number of
PTEN, TP53) radiation to primary site + axillary nodes =
mortality early menarche, lymphatics, consideration worst prognosis
greatest in AA nulliparity, late of systemic tx
women menopause, presence of axillary
OCP (but partial mastectomy w/ or other LNs is the
affects 1/8 decreased risk local radiation therapy most impt risk factor
women for endo/ovarian (preferred over radical for recurrence &
Ca), estrogen mastectomy) mortality
replacement tx,
obesity, alcohol, sentinel LN studies
FH
Dysmenorrhea (general) painful menstrual period, primary / idiopathic - without 50% of OCPs
cramping lower abd pain pelvic pathology menstruating
(radiates to the back & women NSAIDs for moderate pain
legs), plus GI, neurological secondary - underlying pelvic
symptoms, & malaise pathology (endometriosis, 5-10% -
ovarian cysts) dysmen
A/w cyclical periods!! affects QoL
Variants
Primary appears within 1-2 yrs of incresaed endometrial PE: nl except some prostaglandin
menarche when ovulatory prostaglandin production tenderness synthetase inhibitors
cycles are established
PGF2a + PGE2 hi in secretory confirm cyclical nature of NSAIDs taken prior to or
Pain occurs few hrs prior endometrium due to decline of pain, R/O underlying pelvic at onset of pain,
or just after onset of progesterone levels in late pathology continuously ever 6-8h to
period, lasts 48-72h luteal phase prevent reformation of PG
suprapubic cramping, increased uterine tone + hi No response to NSAIDs

lumbosacral backache amplitude contractions = after 3-6 cycles? OCPs
(radiates to anterior thigh), reduced blood flow = ischemic (suppress endometrial
colicky pain (improves w/ pain proliferation, thus dec PG
massage, movement), rare synthesis)
n/v/d
others? Tinge unit,
paracervical block, uterine
nerve ablation (last resort)
spontaneous resolution
post-delivery
Secondary occurs many years after underlying pathology: PE: abd & vaginal exam analgesics
onset of menarche endometriosis, adenomyosis, may reveal underlying
fibroids, congenital uterine lesion treatment of underlying
pain begins 3-5d prior to anomalies (bicornuate, septate, cause
period, relieved by period non-communicating horn), U/S of vaginal/abd,
onset cervical stenosis, endometrial laparoscopy, hysteroscopy
polyps, PID
less likely to respond to
NSAIDs or OCPs
Chronic Pelvic (general) non-cyclical pain > 6m multi-factorial 15% of h/o sexual or impt to do rectovaginal & multidisciplinary (bc 50% of women have
Pain GYN: endometriosis, pelvic reproductive physical abuse bimanual exam in these usually multiple causes of comorbid psych
adhesions, PID, adeno- age women patients! pain) diseases
myosis,uterine myomas PTSD (DEPRESSION!)
GI: IBS, IBD, constipation, Laparoscopy - nl in 35-40%, include mental health
colitis, diverticulitis drug/alcohol endometriosis in 30%, provider (counseling +
Urologic: IC, chronic UTI, abuse pelvic adhesions in 25% med tx way more effective
urinary calculi, radiation cystitis than med tx alone!)
MSK: pelvic floor pain,
fibromyalgia, low back pain, 1. NSAIDs
nerve pain 2. consideration of
narcotics
3. chronic pain meds
(gabapentin, topamax,
valproic acid, anti-
depressants)
Variants
Endo- pain worsens w/ age endometrial tissues (glands & Endometrial - cause of FH, increased PE: possible to find tender presumptive tx before
metriosis stroma) that occur outside the retrograde chronic pelvic exposure to pelvic structures, fixed laparoscopy (interrupt
severity of pelvic pain =/= uterus menstruation, pain in young menstruation retroverted uterus, adnexal menstrual cycle) -
pathology by laparoscopy lymphatic women (early menarche, masses, nodularity along monophasic OCP (daily
Immunologic abnl cause inc dissemination, nulliparity), flow uterosacral ligament hi dose progestin) / vag
pelvic pain, infertility presence of circulating vascular 3-15% of obstruction, ring/ patch for 3m
autoantibodies, inc # dissemination, general obesity Laparoscopy - gold
peritoneal macrophages, dec direct invasion, population; 20- standard NSAIDs, Depo-Provera,
T-cell reactivity & NK activit uretotubal 50% of GnRH analogs (Lupron,
most common area? infertile others? Elevated Ca-125, Synarel, Zoladex)
Posterior cul-de-sac protective factors? Habits that in situ population U/S
decrease peripheral estrogen (congenital) - surgery? Laparoscopic
(exercise, smoking) celomic destruction of lesions,
metaplasia, bilateral uterosacral
Wolffian duct ligament resection,
remnants, hysterectomy
Mullerian duct
remnants
Pelvic bands of scar tissue form infection, pelvic exclude other pathology, hi fiber diet (avoid stool
adhesions between two pelvic organs --> surgery, laparoscopy, consistent buildup)
(asherman's infertility & chronic pain trauma history
syndrome) surgical lysis (dense
adhesions)
Pelvic pain worsens w/ prolonged incompetence of valves & women aged 20- CT or U/S diagnosis surery, laparoscopy,
venous standing, post-coital dilation of ovarian veins, other 45 w/ multiparity pelvic vein embolization
congestion veins draining pelvis
syndrome dull pelvic pain/ pressure/
heaviness - relieved by
lying down
+/- vulvar or upper thigh

varicosities
Pelvic floor pelvic floor muscles - Interstitial PE: examination of pelvic pain meds, physical
dysfunction myofascial pain usually cystitis (80%) floor muscles --> therapy, trigger point
involving levator ani tenderness and pain in injections, Botox injections
bladder, vagina, vulva, or
perineum
Sexually (general) syphilis: primary = chancre/
GC infects mucus glands - bacteria 19 million new 15-24 year olds NAATs more sensitive syphilis? Penicillin +/- HIV women: asymptomatic
transmitted painless ulcer; secondary endocervix (NO ECTOCERVIX (gonorrhea, cases/ yr (however, not FDA treatment if indicated dz --> reproductive
infections = rash, condyloma, involvement), endometrium, chlamydia, MSM (LGV, approved for all receptive health consequences
alopecia, mouth lesions; fallopian tubes, oral - minor syphilis, CT/GC, HepC, sites) (infertility, stillbirth,
active or latent disease salivary glands (mouth = chancroid) syphilis) premature birth,
gonococcal oral pharyngitis), viruses (HIV, urethral cultures congenital
Granuloma inguinale: septic vasculitis & arthritis, HPV, HSV, hep racial minorities transmission - HSV,
Klebsiella granulomatis; conjunctivitis (bilateral A/B/C) GN diplococci - GC HIV, syphilis); cervical
small painless papule that involvement in infants; can parasites HIV+ cancer, PID
eventually forms beefy- cause blindness) (Trichomona, DONOVAN BODIES: (untreated
red granulomatous ulcer pubic lice) Granulosum inguinale; easily chlamydia)
that bleeds easily; subq treatable
spread --> elephantiasis HIV transmission
of external genitalia PE: purulent d/c from os??
GC; mucopurulent d/c from lues maligna -
os?? CT malignant syphilis in
immunocompromised
GC: bartholinitis -->

Bartholins cyst or
abscess (if pus filled)
Variants
Urethricitis dysuria, urinary gonorrhea, chlamydia, GC (5-20%), Gram stain: increased polys Azithromycin - 1g PO Writer's syndrome -
frequency, intermittent Mycoplasma genitalium CT (15-40%), (>5 per HPF), GN once if NGU infection OR Keratoderma
penile discharge NGU (non intracellular diplococci doxycycline 100mg/ PO blenorrhagica
gonoccocal (Gonorrhea - suff for dx in bid x7d (autoimmune
painful meatus? HSV urethritis - all men only!) syndrome w/ rash
other agents) recurrent or persistent after CT infection)
GC/CT NAAT infection (30% of pts) - re-
treat if non-compliant, conjunctivitis? a/w
think Trichomonas or CT autoinoculation
resistant ureaplasma or
mycoplasma
Cervicitis frequently asymptomatic chlamydia, gonorrhea, chlamydia PE: purulent / mucopurulent azithromycin - 1g PO
trichomonas, herpes, BV endocervical exudate; once OR doxycycline
easily induced endocervical 100mg/ PO bid x7d
bleeding
NAAT for GC/CT &

trichomonas or wet mount
culture for trich/ BV
Genital elevated edge lesion - CT syphilis, herpes, chlamydia majority due Granuloma - underlying dz syphilis serology, herpes empiric treatment for most possible
ulcers (LGV), H. ducreyi (chancroid), to HSV or mostly in (immunocomp, culture/ PCR serology likely agent - clinical/ epi superinfection w/
circular, VERY painful Granuloma inguinale syphilis Caribbean Crohns), staph or co-infection
lesion, erythematous edge, residence, travel HSV - acyclovir (pt + (HSV + syphilis)
firm bilateral & tender HSV - white plaques, noninfectious HSV - 1/4 hx partner)
LNs - HSV hemorrhage/ erythema, sources? young people HSV = chronic lifelong
inflammation (causing vaginal Yeast, fixed # partners infection; transmission
firm, painless, demarcated d/c), swelling, + painful ulcers; drug eruption, thru subclinical
edge, non-tender bilateral reactivation?? psoriasis shedding
LNs - syphilis Hypopigmentation, scalloped/
"hamburger meat lesions" HSV2 - a/w risk of HIV
irregular shaped, painful acquisition
lesion, tender & unilateral Chancroid - tender papule w/
LNs - Chancroid erythema that becomes pustular
then ulcerated; bulboes appear
irregular shape lesion + in LN regions after resolution
pseudobuboes (LNs) - of ulcers
Granulosum inguinale
Syphilis - PAINLESS ulcers;
firm & volcano appearing
Vaginal Trich: frothy/gray smelly Trichomonas, bacterial Trich (15-20%), Trich: pH>4.5; wet mount: Trich: metronidazole, HIV increased HIV risk w/
discharge d/c; strawberry cervix vaginosis BV (40-45%; motile flagellated protozoa screening trich
a/w sex), vulvo- w/ many WBCs
Candidiasis: cottage vaginitis: vaginal D/C, vulvar vaginal BV: metronidazole
cheese d/c itching, irritation, odor candidiasis (20- Candidiasis: pH<4.5; wet
BV: fishy odor 25%) mount: few WBCs; KOH:
pseudohyphae
BV: positive KOH whiff test;

wet mount: Clue cells
Genital HPV HPV low risk
warts types 6&11
Proctitis inflamed rectum w/ blood gonorrhea, chlamydia, syphilis, MSM, women w/

& pus herpes rectal
intercourse
mucoid anal discharge,
rectal bleeding
Variants
PID lower abdominal pain Pelvic inflammatory disease - chlamydia, 1M women/yr PE: severe PID can have tubal inflammation -->
AND uterine/ adnexal/ infection & inflammation of gonorrhea, BV swollen uterus/ tubes w/ scarring & loss of
cervical motion uterus, fallopian tubes, ovaries, extruded pus function = tubal
tenderness, dysuria, & adjacent tissues others: factor infertility,
purulent vaginal d/c mycoplasma, ectopic pregnancy,
anaerobes, chronic pelvic pain
HSV,
actinomyces, NO USE OF IUD!!!
mycobacteria IUD + PID = TUBAL
(TB) ABSCESS
FORMATION
DGI monoarticular septic disseminated gonococcal very complement
arthritis of large joints; infection uncommon deficiency
tenosynovitis/ dermatitis (decline in patients
(rash); 1-3% w/ mucosal etiologic
infection; fever/ chills strains for unk younger,
reason) sexually active
septic vasculitis - pustula women
(pus filled vesicle)
Tubo-ovarian sepsis symptoms (fever, PID + IUD vaginorectal exam: pus IV antibiotics first followed
abscess shaking chills, tachycardia, palpated btwn rectum & by draining/ removal of
elevated WBC), lower abd uterus abscess
pain, mild rebound, large
tender adnexal mass gross: ovary, multiple usually requires removal
thickened luteal cysts & of uterus and ovaries bc
abscess fibroids present!
path: actinomyces if a/w IUD
Pyosalpinx Fallopian tube filled with pus

Hydrosalpinx Fallopian tube dilated with gross: retort shaped
watery fluid
path: villi of fallopian tube are
pressed into a flat lining
(short broad & thickened
papillae)
Adrenal (general) hyponatremia, loss of cortisol production confirm low cortisol; check GC replacement - Addisonian crisis -
insufficiency hypercalcemia, hyponatremia- dilution of Na by ACTH levels (primary v. hydrocortisone, cortisone
hypotension, fever,
weakness/ fatigue/ excess free water (nl cortisol secondary) acetate, prednisone (less
AMS, abd pain, joint
anorexia, weight loss, inhibits ADH prod); weight loss - ACTH stimulation test preferred bc long t1/2) pain - saline volume
postural hypotension, (acute = weight gain from expansion, hi dose
nausea, diarrhea, edema & H2O retention) chronic MC replacement (primary hydrocortisone IV
myalgia/ arthalgia adrenal insuff has diarrhea so insuff only) - (achieves GC & MC
H2O loss; hypercalcemia - unk; fludrocortisone effects)
postural hypotension - no
cortisol = vasodilation = adjust for surgery/ minor
syncope stress/ fever - double daily
requirements
Variants
Primary Symptoms above in gen adrenal destruction --> unable autoimmune, 0.3% of TB HI ACTH (pit trying to chronic replacement of hyperpigmentation
(ADDISONS category + adrenal to respond to ACTH --> insuff TB, adrenal patients stimulate adrenals but GC & MC does NOT resolve
) calcification (fungal/ TB leukodystroph Addisons; adrenals unresp) even post-tx
cause), vitiligo infectious - TB, HIV, CMV, histo, y, hereditary/ 85% of pts
(autoimmune attack of candidiasis; adrenal idiopathic who die from short cosyntropin test - IV
melanocytes), hemorrhage - Waterhouse- TB have ACTH will cause no change
hyperpigmentation (ACTH Friderichsen syndrome, others?? HIV, adrenal involv in cortisol secretion
binds melanocytes), trauma, coag d/o, antiphosph hemorrh
hyperkalemia (loss of zona syndrome; autoimmune: infarction,
glomerulosa = loss of polyglandular autoimmine sarcoid/
aldosterone = inc K+) I&II; hereditary: congenital amyloid,
adrenal hyperplasia, adrenal hemochromato
leukodystrophy/ sis, thrombosis
myeloneuropathy; infiltrative:
sarcoid, amyloid,
hemochromatosis; iatrogenic:
adrenalectomy, steroid synt
inhibitors
Secondary NORMAL POTASSIUM hypothalamic/pit dysfxn --> no HIV, LOW ACTH (unable to Chronic replacement of
LEVELS!!!! + symptoms ACTH produced or secreted --> iatrogenic produce so adrenals aren't GC
above in general category no stimulation of adrenals --> (most stimulated)
insuff common!!) -
prolonged GC short cosyntropin test - IV
no ACTH = adrenal atrophy = treatment ACTH will cause slight
adrenal insuff increase in cortisol
HP axis dz secretion (suggests partial
Stopping GCs suddenly will (tumors of pit, insuff)
cause adrenal insuff - MUST hypothalamus,
wean these patients & test for infiltrative dz, Long Cosyntropin test -
HPA axis responsiveness trauma) repeated ACTH infusion
awakens the atrophic
adrenals and shows
cortisol secretion - reversal
of atrophy proves
secondary adr insuff
Adrenal adrenal insuff (see above) gross: caseous necrosis

tuberculosis histology: Acid fast stain for
Mycobacterium tuberculosis
bacilli (red fish)
Autoimmune adrenal insuff (see above) polyendocrinopathies; isolated usually not biopsied but would
adrenal autoimmune adrenalitis see lymphocytic infiltration
disease
Waterhouse- acute hemorrhagic a/w systemic more gross: hemorrhage of
Friderichsen necrosis /infarct of infection: common in adrenals
syndrome adrenal glands as a Neisseria children
complication of DIC meningitidis, histology: massive
Pseudomonas, extravasation of RBCs in
child presents w/ adrenal H.influenzae, cortex
insufficiency + infection + Staph
pic of hemorrhagic
adrenals
Variants
Polyglandular Type I adrenal insuff (see above) antibodies form to 17a & 21- autosomal
Autoimmune + mucocutaneous hydroxylase recessive
Disease (PGA) candidiasis (thrush) +
hypoparathyroid disease AIRE gene mutation
Other disorders?
Pernicious anemia,
alopecia, malabsorption,
chronic active hepatitis
CHILDHOOD
Type II adrenal insuff (see above) unknown gene mutation but autosomal HLA B8 (DW3),
+ thyroid problems chromosme 2q33 linkage dominant DR3, DR4
(Hashimoto's), T1DM, &
gonad disorders + vitligo
ADULT ONSET
Adrenal Leuko- 10% of all adrenal insuff abnl peroxisomal transporter = X-linked 25-35% of neuropsychiatric testing
dystrophy cases defective oxidation of very long recessive "idiopathic"
chain fatty acids = mutation of Addisons now MRI for prognosis
progressive neurological accumulation of lipid in ABCD1 gene known as mild
loss adrenal, brain, gonads, spinal (MALES only) ALD
cord
Adrenal myeloneuropathy
- later onset variant w/
slower progression (ABCD2
gene)
Congenital (general) most common cause of enzymatic defect in steroid

Adrenal ambiguous genitalia biosynthesis --> impaired
Hyperplasia cortisol secretion --> chronic
(CAH) ACTH stimulation --> adrenal
gland hypertrophy -->
overproduction of androgens/
testosterone
21- adrenal insuff, ambiguous loss of 21-hydroxylase prevents autosomal most Cortrosyn stimulation surgery for females
hydroxylase genitalia, hirsutism, salt- formation of recessive common of testing = gold standard for
deficiency wasting hypotension deoxycorticosterone from CAH!! dx - measures 17-OH replace cortisol
progesterone (no aldosterone progesterone & cortisol levels (hydrocortisone), replace
NO CORTISOL OR made) and formation of 11- 1:15,000 pre& post stimulation aldosterone if needed
ALDOSTERONE; EXCESS deoxycortisol from 17 (fludrocortisone)
TESTOSTERONE/ hydroxyprogesterone (no
ANDROGENS!! cortisol made)
shunts pathway towards

formation of sex hormones
(DHT, estradiol, etc)
Variants
11B adrenal insuff, severe loss of 11B-hydroxylase
hydroxylase HTN + ambiguous prevents formation of
deficiency genitalia corticosterone & aldosterone =
accumulation of
NO ALDOSTERONE & deoxycortisone, which is able
CORTISOL; HOWEVER, to bind aldosterone receptor
DEOXYCORTICOSTERON and act as a powerful
E STILL ABLE TO BIND mineralocorticoid = HTN
MR
11B- hydroxylase also used to
make cortisol from 11-
deoxycortisol, thus these
patients will have adrenal insuff
and accumulation of 11-
deoxycortisol
pathway is shunted towards

the androgens
17a- adrenal insuff, ambiguous loss of 17a-hydroxylase affects

hydroxylase genitalia, sexual adrenal production early in the
deficiency infantilism, primary steroid pathway; pregnenolone
amenorrhea, HTN or progesterone cannot be
converted into their subsequent
NO CORTISOL OR SEX forms, so no cortisol or sex
ANDROGENS; EXCESS androgens are made
ALDOSTERONE
thus, the pathway shunts
towards aldosterone
production only
3B-hydroxy- adrenal insuff, bilateral loss of 3B-hydroxysteroid much less

steroid adrenal hyperplasia, dehydrogenase results in common
dehydrogen ambiguous genitalia, salt decreased production of all 3
ase II wasting hypotension groups of adrenal steroids,
which include
NO CORTISOL, mineralocorticoids,
ANDROGENS, OR glucocorticoids, and sex
ALDOSTERONE steroids
the lack of cortisol secretion

leads to elevated ACTH, which
results in the bilateral adrenal
hyperplasia
Variants
Cushing (general) adrenocortical hyper- adrenal androgen production - constitutive hi 24h urine free cortisol adrenal disease: 50% of ACTH-
syndrome/ function -> androstenedione production -- activation of (excess cortisol > capacity of adrenalectomy (last producing bronchial
disease > hirsutism, amenorrhea, cAMP CBG) - elev even @ midnight resort) + radiation carcinoids suppress
Cushing dz (pituitary) v. virilization, & acne; excess etiology? measure plasma w/ dexamethasone
Cushing syndrome cortisol binds aldosterone ACTH ACTH (<10 - autonomous pituitary disease: trans- (exception to the non-
receptors --> HTN, edema, producing adrenal activity; > 200 - sphenoidal resection + pituitary causes
central obesity (thin hypokalemic alkalosis tumor in ant pit ectopic ACTH tumor); radiation being non-
extremities), moon facies, (aldosterone stimulates K+ petrosal sinus samples suppressible)
hirsutism, HTN, weakness, wasting); cortisol stimulates functional (detect gradients of ACTH med tx: steroid synthesis petrosal sampling -
osteoporosis, appetite --> obesity adrenal lelves peripherally), inhibitors (block risk for thrombosis &
hyperglycemia, peripheral cortisol --> insulin resistance neoplasm suppression/ stimulation 11BHSD1); GR bleeding
insulin resistance, impaired (not understood); protein (adenoma, tests (pituitary adenomas antagonists
LH/FSH release, increased wasting --> proximal myopathy; carcinoma) - will be suppressed w/ (mifepristone), psych illness <-->
appetite, skin thinning, ACTH stimulates melanocytes primary exogen ACTH; non-pituitary adrenolytic drugs, hypercortisolism
decreased linear growth --> hyperpigmentation; cortisol adrenal tumors causes are NOT inhibitors of ACTH
(kids), neuropsych probs, affects collagen --> thin skin, suppressed) (exogen CRF release (carbergoline,
immune suppresion, skin stria; cortisol inc bone iatrogenic stimulates pituitary to make pasireotide)
striae on abd, resorption --> osteoporosis, ACTH - if pituitary cause)
erythematous face, oily renal stones paraneoplastic adrenal CT if ACTH < 10 for
hair, dorsocervical (small cell lung adrenal sizes/ masses
buffalo hump Ca)
Pituitary Cushing disease caused by 70-80% of gross: enlarged cortex of pituitary disease: trans- complications of trans-
ACTH ACTH producing endogenous adrenal sphenoidal resection + sphenoidal resection?
production microadenoma (maj), Cushings radiation Transient DI
corticotroph cell hyperplasia, 20> plasma ACTH < 200 (disruption of post pit),
hypothalamic corticotrophin Females 5:1 medical suppression w/ post-surgery cortisol CSF leak, meningitis
releasing hormone tumor dexamethasone (presence supplementation until HPA
of negative feedback still so axis recovers panhypopituitarism
ACTH induces adrenocortical urine free cortisol from radiation
hyperplasia suppressed) - distinguishes therapy (90%
Cushing dz from syndrome patients over 10y
ACTH producing adenomas still time frame)
under negative feedback but CRH stimulation test:
new setpoint, requiring much elevated ACTH prod (if give
more cortisol to stop secretion CRH, still stimulates ACTH
of ACTH --> bilateral adrenal prod from ant pituitary - just at
hyperplasia a new set point)
Ectopic ovarian tumor or pancreatic plasma ACTH > 200 treat underlying cancer
ACTH tumor produces ACTH,
overstimulating the gland and Imaging of other organ
shutting down pituitary systems for masses
production of ACTH (HPA axis
no longer under negative
feedback)
Carney Cushing syndrome autosomal dominant gene
complex heterozygous inactivating rearrangement
hypercortisolism + mutation of regulatory subunit of
lentiginosis (spotty PKA --> cortisol production &
pigmentation) + cardiac Cushing syndrome
myxoma, endocrine
tumors (adrenal cortical, autonomous cAMP pathway
GH, or thyroid adenomas/ stimulation downstream
carcinomas, melanocytic
schwanomas, testicular or
breast ductal carcinomas
Variants
Adreno-cortical (general) kids: most often functional - loss of heterozygosity involving autosomal very rare plasma ACTH < 10 (ACTH adrenalectomy (last panhypopituitarism
adenoma -> Cushing syndrome + tumor suppressor gene leading dominant independent cause for resort) + radiation from radiation therapy
virilization to activation of cAMP signal; mutation hypercortisolism) (90% patients over
succession of mutations cause 10y time frame)
adults: functional & non- progression from: need CT scan of adrenals for
functional; Cushing> hyperplasia --> adenoma --> masses Nelson's syndrome -
hyperaldosteronism > carcinoma unrepressed growth of
virilization pituitary adenoma
from hi ACTH levels
(complication of
adrenalectomy)
Conn HTN, hypokalemia, aldosterone-producing F>M gross: solitary encapsulated

syndrome alkalosis, hi urinary adrenocortical adenoma nodules (yellow-tan on cut
potassium adenomas in section), >1cm if
kids usually macroscopic; adreno-
occur at age cortical nodules (<1cm, not-
<5 encapsulated; multiple &
bilateral)
histology: lipid rich cortical

cells; cannot determine if
functional by visual inspection
Adreno-cortical usually functional in kids; excess cortisol shuts off a/w Beckwith- kids: ~4y.o. gross: large mass + adrenalectomy + radiation very poor prognosis
carcinoma functional or non-functional pituitary ACTH, causing adrenal Wiedemann adults: ~45yo hemorrhage + necrosis in (med survival ~2y)
in adults atrophy syndrome, La cortical section (yellow)
Fraumeni F>M histology: sheets of
Cushing +/- virilization >> syndrome eosinophilic to clear cells; hi
hyperaldosteronism (p53 mutation), very rare nuclear polymorphism,
& hemi- compared to atypical mitotic figures,
most common cause of hypertrophy adenomas necrosis of larger cells
Cushings in kids
plasma ACTH < 10 (ACTH
independent cause for
hypercortisolism)
need CT scan of adrenals for

masses
Adrenal adrenal mets from primary CXR: check for lung mass
metastasis lung, breast, or kidney
cancer
Bilateral, nonfunctional
adrenal masses in older
individuals - THINK METS!
Secondary (general) resistant HTN (BP>140/90 hyper- most common

hypertension w/ full doses of >3 meds + aldosteronism, causes?
suddent onset + MC excess, Hyper-
younger/older age at onset) pheo- aldosterone,
chromocytoma, renal dz
renal artery
stenosis, renal
disease,
endocrine
causes
(Cushings,
hypo/hyper-
thyroidism,
OSA)
Variants
Pheochromo onset of HTN at young age, adrenal medullary syndromes: rare urinary catecholamine preoperative - 50% 5y survival in
cytoma episodic HTN, (neuroendocrine) tumor arising MEN2, neuro- metabolites (vanillylmandelic alpha-adrenergic malignant tumors
palpitations, tachycardia, from chromaffin cells = fibromatosis, usually adults acid, metanephrines) - might blockers (lowers
tremor, weakness, pallor, production of catecholamines von Hippel- (50y.o.) require rpt testing bc episodic BP&catech surges; certain drugs can
anxiety (adrenergic stim), = stimulation of alpha & beta Lindau, Sturge- nature of tumor Phenoxy-benzamine, interfere w/
retinopathy, hyperglycemia, receptors = inc BP, Weber Clonidine suppression test- terazosin) catecholamine assay
polyuria/ polydypsia, chest contractility, & HR = distinguishes pheo from false B-adrenergic blockers so might need to
pain, nausea, hyper- cerebrovascular & positive inc in catech (only start AFTER a- change meds around
reninemia (orthostatic cardiovascular consequences MRI/CT nodules? last option blockers; used for
hypotension), ileus gross: gray-tan tachycardia)
hemorrhagic mass > 1cm;
Classic triad?? bilateral in familial cases (a/w SURGERY required!!
Palpitations w/ tachycardia, syndromes); displacement of
headache, perspiration cortex
(drenching sweats) histology: polygonal -
spindle cells, nested
pattern (Zellballen),
Rule of 10s: 10% a/w extensive vascular pattern,
syndrome, 10% bilateral, variable nuclear
10% kids, 10% malignant pleomorphism
Hyperaldost adrenocortical Conn's syndrome - HTN, aldosterone 2-15% aldosterone:renin ratio adenoma? Surgery
eronism hyperfunction hypokalemia, alkalosis, producing prevalence (nl<20; >20 suggests (curative)
kaliuresis; suppressed renin w/ adrenal autonomous prod of
severe HTN, hypokalemia, high aldosterone adenoma, aldosterone) medical mgmt?
alkalosis, low renin, hi bilateral aldactone, epleronone,
aldosterone Renin nl converts adrenal confirm hyperald w/ oral salt amilioride (K+ sparing)
angiotensinogen to angiotensin hyperplasia, loading --> should shut down
I; ACE converts angI to angII; hypertensive aldosterone (if not
angII stimulates the adrenals to forms of CAH suppressed, suggests
secrete aldosterone; (11B &17a autonomous prod of ald)
aldosterone increases sodium hydroxlase
retention and potassium def), adrenal CT scan of abdomen
excretion cancers bilateral adrenal vein
sampling (aldo:cortisol > 4
suggests adenoma)
Gluco- adrenal adenoma + HTN + translocation in which the gene autosomal RARE: <1% FH hemorrhagic genetic testing for GRA lowest dose of long-
corticoid hypokalemia involved in cortisol production is dominant of hyperald stroke (uncont mutation on all pts w/ history acting steroid
remedial transferred to the gene involved cases HTN) of hyperald, strokes at young (dexamethasone,
hyperaldoste aymptomatic severe HTN in aldosterone production --> age, or onset of HTN at young prednisone) to control BP
ronism in child or young adult; aldosterone being produced age
family h/o hemorrhagic in response to ACTH
stroke; profound
hypokalemia w/ thiazide ACTH DRIVES
admin ALDOSTERONE SYNTHESIS
Deoxycortic deoxycorticosterone is made in

osterone the zona fasciculata in response
HTN to ACTH; elevated levels of
deoxycorticosterone seen in
adrenomas, adrenal
carcinomas, or CAH
thus, this MC is able to

contribute to HTN
Variants
Liddle severe HTN, hypokalemia, mutation in gamma or beta autosomal low renin & aldosterone
syndrome low aldosterone & low subunits of amilioride sensitive dominant (RAAS system not part of the
renin renal sodium epithelial channels mutation etiology of this syndrome)
in distal nephron --> ENaC
channels stay open longer
increasing Na reabsorption &
decreasing Na excretion
Syndrome of childhood: low birth cortisol circulates at much AME type 1 - normal BP control & tx of
Apparent weight, failure to thrive, higher levels than aldosterone; cortisol levels, normal ACTH hypokalemia
MC Excess short stature, severe HTN cortisol has equal affinity for MR feedback regulation (problem
(AME) + hypokalemic alkalosis is with cortisol supression of cortisol w/
HTN normally prevented by 11B- breakdown!!); hi urinary dexamethasone
AME Type 1 - decrease or HSD2 by converting cortisol to cortisol metabolites
absence of 11B-HSD2 cortisone, which is unable to (elevated ratio of cortisol spirinolactone
bind MR; nonfunctional 11B- metabs: cortisone metabs)
AME Type 2 - milder HSD2 from mutations cause kidney transplant
phenotype w/ expression as cortisol to bind MR and
young age; milder alteration activate aldosterone
in urinary products and response, despite generally
HTN decreased aldosterone activity
Licorice mineralocorticoid excess licorice contains glycyrrhizinic stop offending agent & BP
HTN acid, with active metabolite of reverts to normal
glycyrrhetinic acid = potent
HTN, hypokalemia, low inhibiot of 11B-HSD2
renin & aldosterone,
increase in cortisol found in candy, chewing gum,
metabolites & decrease in & chewing tobacco
cortisone
Virilizing adrenocortical excess sex hormones
syndromes hyperfunction
Sexual pain Dys- recurrent or persistent vulvovaginal atrophy - often vulvo/ vulvodynia = estrogen creams (unless
disorders pareunia involuntary genital pain results from menopause (loss vestibulodynia most common contraind) if related to
associated w/ sexual of estrogen = loss of keratin & = cause of atrophy
intercourse epithelial lining of vaginal wall = hypersensitivity dyspareunia
thinning, loss of lubrication & to yeast, address etiologies - if not
vulvodynia - genital blood flow = tearing w/ allergic helpful, surgical excision
hypersensitivity to touch, penile penetration) response, of vestibule (which is
erythema, pain w/ HPV, genital mesodermal derivative so
penetration vulvodynia/ vestibulodynia = rash, autoimm, might be reacting
inflammation of vulva or estrogen def differently to surrounding
vestibule tissues) & reconnection to
inf = HSV, other tissues
infection HPV, GC, CT,
PID, UTI, BV, tx infections
trich,
candidiasis
Vaginismus signs? Unconcumated recurrent or persistent childhood vaginal dilators,

marriage, difficulty w/ involuntary spasm/ trauma psychogenic therapy,
pelvic exam, difficulty contraction of muscles muscle relaxatants
placing tampons surrounding introitus prevent
penile insertion -> personal
distress;
Variants
Sexual desire Hypoactive persistent or recurrent a/w menopause - reduced menopause menopause, treat only if distressful!
disorders sexual deficiency or absence of androgen production = (natural or OCP side
desire sexual fantasies and reduced testosterone = surgical) effect?? Flibanserin - although not
disorder desire for sexual activity decreased libido FDA approved
(HSDD) meds (OCPs,
a/w OCPs - inhibition of SSRIs - inhibit low dose testosterone
gonadotropins = reduced pleasure
production of estrogen & pathways) Wellbutrin (Buproprion) -
androgens + inc synthesis of blocks reuptake of
steroid hormone binding dopamine; give in combo
globulin = reduced w/ SSRI to compensate
testosterone for dec libido
Dopamine = excitatory for

sexual desire/arousal
Serotonin = inhibitory for

sexual desire/ arousal
Sexual persistent or recurrent

aversion extreme aversion to, and
disorder avoidance of, all genital
sexual contact w/
appropriate sexual
partner
Sexual arousal persistent or recurrent arousal is mediated by psychogenic - possible female use for
disorder inability to attain or relaxation of arteriolar sexual trauma, PDE-5 inhibitors
maintain an adequate smooth muscles (NO, VIP poor (Sildenafil, tadalafil) to
lubrication - swelling mediated) in genitals that relationship, prevent the breakdown
response of sexual increases blood flow into drugs of cGMP
excitement clitoris and vaginal epithelium
organic - DM,
Dysfxn? Inadequate afferent PVD, metabolic
and/or efferent neural syndrome,
transmission to sexual obesity
organs (psychogenic or
organic) OR inadequate
response of erectile & vaginal
tissue (insufficient release of
NO or VIP; downregulated
smooth muscle receptors;
insufficient second messenger
regulation of relaxation)
Orgasmic Female persistent or recurrent directed masturbation

disorder Orgasmic delay or absence of program (if lifelong d/o),
Disorder organsm following nl sexual
excitement phase relationship therapy (if
situational d/o),
orgasmic capacity <
reasonable for age, sex education about sexual
experience, and fxn & response,
adequacy of stimulation
anxiety reduction
techniques,
testosterone/ DHEA/ local

estrogen/ oxytocin
Variants
Paratesticular Hydrocele painless enlargement of accumulation of fluid in tunica congenital or most common prior surgery, gross: distended testis full of
disorders scrotum that vaginalis that surrounds testis acquired cause of neoplasm/ inf of fluid; thin membrane so able
transilluminates scrotal testis/ to see veins & tunica
congenital hydroceles: occur enlargement epididymis, vaginalis
lymphatic obstruction during first year of life as patent trauma
processus vaginalis fails to usually 1st
close, allowing fluid to enter & year of life -
distend tunica vaginalis; a/w congenital
inguinal hernia more
common
acquired hydroceles: usually
due to lymphatic obstruction
from trauma, prior surgery,
neoplasms, or infection of
testis/ epididymis; a/w
parasites (filariasis) in tropical
parts of world
Varicocele painless dilation & dilation of vein plexus in 10% of young PE: veins engorge w/ blood a/w infertility (inc
tortousity of veins spermatic cord adults when standing termpature in scrotum -
optimal
more common on left side spermatogenesis is
of scrotum (right spermatic more efficient at lower
vein drains into IVC at a temps)
narrow angle so less probs
w/ drainage; left spermatic
vein --> L renal vein = long
column of blood that rests
atop valves)
Spermato- cyst formation in small cysts that arise from NOT a/w infertility!!
cele epididymis efferent (testis --> meatus) BENIGN!
ductal system of testis,
hard, pea-sized nodules particularly epididymis
above the testis
Epididymitis inflammation of often arises from direct young men - most gross: purulent exodate in the untreated gonococcal
epididymis extesion of UTIs from gonococcal & common epididymis (above the testis) epididymitis -->
prostatic urethra or prostate chlamydial intrascrotal if gonococcal epididymis abscess
enlarged & TENDER infections inflamm d/o
epididymis with advanced infection, testis spread to testicles
may also become infected & older men -
difficult to distinguish from E.coli, M. infertility if chronic
epididymis; fibrosis & chronic tuberculosis scarring &
obstruction of epididymis obstruction
duct may result --> infertility
Testicular EXTREME PAIN that may twisting of spermatic cord = 2nd decade of gross: necrotic testis, surgery to manually testicular infarction /
torsion occur spontaneously during compression of venous life edematous spermatic cord untwist spermatic cord necrosis if not
sleep or be related to minor drainage = vascular surgically managed in
injury engorgement & congestion = minor injury? time!
infarction of testis
urologic surgical Bilateral risk so
EMERGENCY!! anomaly of testicular gubernaculum is
suspension - gubernaculum fixed on both testes
attached horizontally instead of
at the bottom of the testis
Variants
Cryptorchidism condition where one or usually arrested along the 3% of male histology: atrophy of orchiopexy if not repaired within 2
more testis has not inguinal canal (dangerous bc infants at birth cryptorchid testis after 2y w.o years --> testicular
descended to its nl this area is injury prone), treatment; fibrosis of atrophy & fibrosis -->
position in the scrotal sac sometimes the top of the seminiferous tubules infertility (low sperm
scrotum, and even less counts)
commonly the abdomen
INC risk of germ cell
tumors (5-10x) - this
risk never returns to
baseline, even after
orchiopexy
Orchitis Bacterial inflammation of testis extension of bacterial infection

from epididymis
Syphilitic inflammation of testis infiltration of lymphocytes
causes obliteration of small
blood vessels --> tubular
atrophy & fibrosis
Mumps enlarged & PAINFUL testis viral mumps infection --> mumps 30% of post- fertility usually
orchitis lymphocytic infiltration --> childhood virus pubertal preserved in
edema & pain --> focal atrophy males w/ unilateral infections
in 50% of involved testis mumps
Infertility Primary - no one year of unprotected Oligospermia: exogenous 1/12 couples scar tissue sperm analysis induce ovulation (meds =
prior preg intercourse w/o testosterone- dec (Asherman's), (oligospermia, immotile clomiphine - SERM;
conception spermatogenesis from inh of 35% - male submucosal sperm), ovulation detection letrazole (aromatase
Secondary - LH/FSH; lack of GnRH neurons- factor, 35% - fibroids, uterine (basal body temp chart, urine inh); injections of
preg in the Kallman's syndrome; congenital tubal factor; anomaly, LH surge, endometrial bx, mid FSH/LH or hCG)
past bilateral absence of vas 15%- endometriosis, luteal serum progesterone
deferens - CF, abnl ovulatory PCOS, >3ng/mL), eval anovulation insemination (sperm is
mesonephric duct diff; dysfxn, 5%- Kallman's (preg test, FSH/LH, OCPs, placed directly onto uterus
Klinefelters - low testosterone, cervical syndrome, CF, prolactin, TSH, androgens, near ovulation time)
elev FSH factor; 10% renal agenesis, Cushings, acromegaly, CAH),
immotile sperm: primary ciliary unexplained Klinefelters, eval tubal/ uterine/ IVF
dyskinisia - Kartagener Turner peritoneal factors
syndrome syndrome (hysteroscopy, other (gestational carriers,
drugs: CCBs hysterosalpingogram, donor gametes, donor
ovulatory dysfxn: anovulation laparoscopy); ovarian embryo, oocyte
(PCOS, androgen excess, low reserve testing (Day3 FSH & cryopreservation, ovarian
gonadotropins, hi prolactin, estradiol, clomiphene transplant)
diminished ovarian reserve, challenge, inhibin B, AMH,
primary ovarian insuff, antral follicle count)
hypothyroidism
tubal/uterine dz: PID,
appendectomy, TB, DES exp,
hydrosalpinges, endometriosis
Ovarian reserve:
Male infertility Supra- above the testis problems with hypothalamus - no gonado- histology: anatomic
testicular GnRH; pituitary gland - lack of tropins seminiferous tubules but no
results from gonadotropins; systemic active spermatogenesis;
abnormalities in organs diseases that suppress Leydig cells are
that regulate hormonal & spermatogenesis (those a/w indistinguishable from
metabolic aspects of fever) stromal cells
spermatogenesis
result in immature
seminiferous tubules - no
signs of spermatocyte
differentation (resemble those
of prepubertal testes), or
decreased spermatogenesis
Variants
Testicular disorders or lesions of testis varicocele most common histology: IDIOPATHIC?
itself cause Germ cell maturation arrest,
cryptorchid germ cell aplasia (Sertoli
varicoceles --> increased testis w/ cells only, no germ cells)
temperature = low scarring
spermatogenesis
Klinefelters
Cryptorchid testis can develop
atrophy & peritubular fibrosis idiopathic
Klinefelters syndrome - atrophy

of gonads --> fibrotic testis
Post- obstruction of excretory untreated
testicular ducts, particularly the epididymitis
epididymis
trauma
results in no spermatozoa in
the ejaculate, despite being vasectomy
made properly in the testis
Hypogonadism (general) testicular failure symptoms? central defects - hypothalamus check morning testosterone start tx around 12y.o. (low watch out for
Low testosterone in or pituitary problem w/ secretion levels, LH & FSH, prolactin, doses then dose hi and inappropriately
adulthood = dec libido, of gonadotropins semen analysis every 2weeks) normal
soft testes but nl size, testicular defects gonadotropins!! (if
dec strength/ muscle feedback loop defects - HPG v cranial imaging, bone age, testosterone low testosterone,
mass, dec body hair, HPA axes U/S of scrotum & adrenals, replacement - IM q 2w, would expect to have
gynecomastia, INABILITY genetic defects - sex neuro exam (visual fields - skin gels/ patch (cannot hi FSH/LH - suspect
TO FOCUS chromosomes, transcription R/O pituitary lesions), be given as pill bc pituitary/
factors testicular size, karyotype, dangerous to liver!) hypothalamus
pre-pubertal = small biochemical defects - adrenal med hx (anabolic steroids?), pathology)
testes, eunuchoidal v. gonad trauma (testicular or head)
skeletal proportions, hi androgen receptor defects
pitched voice, dec muscle check other pituitary
mass, delayed bone age, hormones and adrenals!
dec body hair
Hypergonad increased FSH & LH, nl pituitary & hypothalamus but congenital or
otropic hypo- decreased testosterone = primary testicular failure - acquired
gonadism primary testicular failure either congenital or acquired
Primary CONGENITAL (see
below) - genetic abnormality
(gonadal dysgenesis, Leydig
cell hyperplasia, Sertoli cell only
syndrome**, CAH); Vanishing
testes syndrome
Primary ACQUIRED -
Infectious (mumps, cocksackie
B virus, echovirus, arbovirus),
drugs (spironolactone - blocks
test synthesis; cyproterene or
ketoconazole - blocks androgen
receptor), iatrogenic (chemo
agents, radiation therapy to
abdomen), trauma
Variants
hypogonado decreased FSH & LH, testicle is functioning but congenital or
trophic hypo- decreased testosterone = insufficient signal from acquired
gonadism central (GnRH, LH) failure pituitary or hypothalamus
Secondary CONGENITAL:
gene mutations (FSH/ LH
deficiencies - PROP1), central
midline defects (cleft lip palate,
septo-optic dysplasia), Genetic
syndromes (Kallman's, Prader
Willi)
Secondary ACQUIRED: brain
abnl (trauma, infectious, tumors
- craniopharyngioma), anorexia
(malnourishment shuts down
HPG axis), systemic illness,
hemochromatosis, elevated
prolactin (inhibits FSH&LH),
obstructive sleep apnea
Gonadal congenital caused by abnormal karyotype

dysgenesis hypergonadotropic (Klinefelters - 47 XXY),
hypogonadism transcription factor deficiency
(SF-1, SRY, SOX9),
transcription factor excess (DAX-
1)
karyotype abnl or
transcription factor problems -
-> impaired development of
testis --> dysgenesis
Klinefelter's congenital 47XXY --> impaired 1:10,000 prisoners

Syndrome hypergonadotropic seminiferous tubules
hypogonadism from
gonadal dysgenesis
increased limb length,

decreased verbal IQ, "odd" -
impulsive behavior
Leydig cell congenital 46XY but inactivating autosomal

hyperplasia hypergonadotropic mutations of LH receptor --> recessive
hypogonadism female phenotype mutations of
LH receptor
male LH required for Leydig cells to
pseudohermaphroditism produce testosterone
Sertoli Cell congenital Germ cell aplasia/ DelCastillo nl testosterone & LH; HI
Only Syndrome hypergonadotropic syndrome FSH
hypogonadism
sertoli cells are not NO seminiferous tubules or
Male sterility without functioning --> impaired sperm!
sexual abnormality & nl sperm production
secondary sex
characterisitics normal secondary sexual
characteristics bc nl
testosterone & LH levels
Variants
Vanishing congenital nl 46XY karyotype but absent low testosterone, hi FSH &
Testes hypergonadotropic testes (anorchia), due to LH
Syndrome hypogonadism prenatal testicular torsion or
INSUL3 transcription factor
defect
regression of testes during 8-

14w gestation
Septo-optic congenital de Morsier's syndrome -->
dysplasia hypogonadotrophic absent septum pellucidum
hypogonadism
optic nerve hypoplasia,

potential hypopituitarism
Kallman's congenital problem w/ KAL gene (codes for 1:10,000

Syndrome hypogonadotrophic adhesion molecule) = loss of
hypogonadism migration of cells required to M>F 5:1
make GnRH
HYPOSMIA OR ANOSMIA
(loss of smell) a/w
hypogonadism bc same
anatomic location as
olfactory bulb
Hyper- (general) androgen excess, acne, early pubertal development anabolic treat cause often also have low
gonadism virilization, anger, small from excessive androgen steroids HDL so at risk for CVD
testes secretion inhibit testosterone w/
GC (if adrenal cause),
endogenous (central surgery (if tumor), or
precocious puberty, adrenal discontinuation of meds
gland abnormality, androgen (if exogenous anabolic
secreting tumor) steroids)
exogenous (anabolic steroids)
Menopause natural final menstruation during oocyte atresia occurs early estradiol < 20 pg/mL; FSH > treatment only if endometrial
dimacteric phase (no around age menopause? 50-100 symptoms impact QoL; hyperplasia & cancer if
menses for 1y w/ inc FSH) menstrual cycle changes: 50 Smoking, use lowest effective dose continuous estrogen
follicular phase shortens, inhibin surgery, hypothyroidism becomes of HRT; can also use exposure w/o enough
perimenopausal women is lower so FSH levels rise, genetics, more common transdermal / transvag progesterone in
can sometimes have estradiol & progesterone radiation/ chemo admin of HT to reduce perimenopausal
irregular & heavy bleeding decrease --> irregular & exp, endometrial bx if blood clot risk women
anovulatory cycles autoimmune, postmenopausal bleeding
reduced estrogen med induced Mirena IUD - lowest contraind for HRT?
effects? Hot flashes, decreased androgen levels: (Lupron) DEXA scans for osteoporosis systemic dose of Hormone sensitive
atrophy (vaginal, uterus & androstenedione, testosterone, progestin cancer, unexplained
ovaries, urinary tract, & DHEAS leads to decreased uterine bleeding, acute
breasts, hair, skin), estradiol levels androgen therapy - risks liver dz, hx of DVT/PE,
osteoporosis, psychological uncertain but thought to confirmed CVD,
changes, loss of be beneficial for dec libido uncontrolled HTN,
cardioprotection & neuronal migraine w/ aura or
protection alternatives to HRT? TIA
SSRIs, clonidine
vaginal estrogen or
lubricants for atrophy &
dyspaurenia
osteoporosis tx: estrogen,

bisphosphonates,
SERMs, calcitonin,
calcium & vit D
supplements, exercise
SSRIs, clonidine
vaginal estrogen or
Disease Clinical Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment
lubricants for atrophy & Complications
Variants dyspaurenia
Premature Primary ovarian idiopathic premature or
insufficiency (maj), Turners primary osteoporosis tx: estrogen,
syndrome, ovarian insuff bisphosphonates,
chemotherapy, occurs <40 SERMs, calcitonin,
familial, pelvic calcium & vit D
surgery, 1% of women supplements, exercise
gonadal
dysgenesis
(46XY),
galactosemia,
pelvic
irradiation
Variants
Screening /
Education
daily glucose
monitoring,
realistic BG
targets, healthy
lifestyle (diet,
ex), office visits
q 3-4m for
evaluation of
retina, lower
extremities, CV,
& routine
screening (A1C,
TFTs, lipids)
Prevention -
1.autoimm
2. prevent dz in
those w/
autoimm
3. intervene to
preserve islet
cells
OGTT = most
sens way to dx
pre-diabetes or
diabetes (post
prand gluc rises
first)
gluc monitoring
& self-mgmt of
insulin
adjustments for
stress, ex,
sickness, diet
CVD risk factors

and
complications
screening
Screening /
Education
A1s are at low
risk for IU
demise; do not
need
antepartum
surveillance or
early elective
induction
A2s: antenatal
surveillance w/
US & NST at 32
weeks until
delivery,
2x/week
PP: screen 6-
12 wks w/ 75g
2h OGTT (DM if
FBS >126, 2h >
200)
pre-preg ex a/w
lower GDM risk
prevent w/ early
INTENSIVE
glucose control
Screening /
Education
Screening /
Education
every patient
over age 60
should have
TSH checked!
Increase
levothyroxine
dose by 30% in
pregnant
patients!!
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
recurrent
parathyroid dz
possible
Screening /
Education
Screening /
Education
Screening /
Education
rarely malignant
dopamine
agonists limited
during
pregnancy (no
progression of
microadenoma
during
pregnancy
despite
estrogen
stimulation)
surgical
debulking of
macro-
adenomas prior
to pregnancy bc
can worsen
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
routine
evaluation?
Cardiovasc
screen,
anticipatory
mgmt for aortic
dissection,
thyroid function,
celiac screen,
FSH/LH, renal
& liver fxn,
DEXA, psych
consults, blood
glucose/ fasting
lipids, ENT/
audiology
Screening /
Education
Screening /
Education
Screening /
Education
expectant
management &
reassurance
Screening /
Education
Stages:
I - ovaries only
II - pelvis,
ovaries
III - abdomen,
lymph nodes,
superficial liver
IV - outside of
abdomen,
parenchymal
liver
lower survival
w/ higher stage
Screening /
Education
yearly paps
beginning ages
21-29; if low-
risk, paps every
2-3yrs after age
30 if 3 normals
in a row
stop paps at
70y.o. if no abnl
in last 10 years
& 3nls in a row
stop paps if
hysterectomy &
no h/o CIN2/3
Screening /
Education
Screening /
Education
continue to
monitor other
testicle if prior
germ cell tumor!
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
yearly
mammograms
for women >
age 40
breast exams q
3y for women
20-40; yearly
age > 40
hi risk women -
yearly MRI of
breasts
Screening /
Education
Screening /
Education
female
screening- CT
(sex active <24;
at risk >25),
gonorrhea /
HIV/syphilis (at
risk), cervical
Ca (all sex
active women
w/ cervix)
pregnant
women - CT if
at risk or less
<24; syphilis,
HepB
MSM - yearly if
sex active:
syphilis, HIV,
GC/CT, hep;
selective males
Screening /
Education
screen women
< 25 for
chlamydia!
PROTECTIVE
SEX!!
Gardisal
quadrivalent
vaccine
Screening /
Education
Chlamydia =
leading
preventable
cause of tubal
factor infertility
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
check testes
regularly to
screen for
development of
neoplasms,
even after
orchiopexy!
Pre-implantation
genetic
diagnosis
(PGD) -
aneuploidy
screen, single
gene defect,
HLA matching,
sex selection
Screening /
Education
Screening /
Education
Screening /
Education
CVD &
osteoporosis
screening
Screening /
Education
Screening /
Education
Variants
Aplastic anemia all cell lines are down!! premalignant condition w/ loss of Paroxysmal BM: hypocellular (empty sometimes infections - unable to
self renewal (affects the stem cell) nocturnal marrow), fat vacuoles only; hi immunosuppression helps generate new
hemoglobinuria power reveals lymphs only restore cell lines lymphocytes
(PNH), (suggest that whole myeloid line
Fanconi's is gone) allogeneic stem cell
anemia transplant
CBC: loss of all cell lines
Myelo- (general) expansion in peripheral blood premalignant condition w/
proliferative = high counts of affected growth advantage and loss of
syndromes myeloid line apoptosis; injury occurs at a level
(MPS) beyond stem cell
splenomegaly
mutations in tyrosine kinase -->
increased proliferation but
INTACT differentiation
Chronic pre-malignant disorder caused by fusion protein (BCR- CBC: all cells lines present & in eradicated Philadelphia can progress to AML
myelogenous ABL gene) formed via t(9;22) excess; always hi WBC chromosome (causative (blastic phase)
leukemia typically presents w/ [Philadelphia chromosome] - (leukocytosis) agent), prevent progression
(CML) splenomegaly + whole dz is driven by mutation in to blast phase (AML) mean survival of chronic
leukocytosis (nl plt & Hb) BCR-ABL (probs w/ adhesion so smear: increased lymphocytes, phase = 4-6y
abnl myeloid cells leave marrow; WBCs at every level of targeted therapy against
splenomegaly, inhibition of apoptosis; activation maturation BCR-ABL via tyrosine resistance to Imatinib by
hepatomegaly if adv, early of proliferation & differentiation via Cytogenetics: t(9;22) kinase inhibitors (Imatinib/ cancer cells (pump drug
satiety (big spleen/liver RAF-MEK-MAPK) FISH: fusion protein Gleevec, Dasatinib, out of cell, produce
compresses stomach; good PCR: ABL-BCR gene Nilotinib) more BCR-ABL, develop
appetite but weight loss bc proliferative disorder of mutations to prevent
early satiety) hematopoietic stem cells without flow is not diagnostic, BM bx Allogeneic HSCT if resistant drug MOA)
3 phases of presentation: arrest in maturation; due to does not need to be done; to imatinib
chronic phase (maj of single molecular abnormality confirmed w/ karyotype/ FISH/
patients; asymptomatic but PCR
abnl CBC), accelerated
phase (symptomatic, difficult
to control leukocytosis),
blastic phase (acute
leukemia, terminal & poor
prognosis)
only leukemia w/
thrombosis
Essential nonfunctional platelets --> 50% JAK2 elevated platelet count pegylated interferon - some patients transform
thrombo- bleeding mutation (>450K) suppresses abnl to polycythemia vera
cytosis hematopoiesis
splenomegaly MUST R/O iron deficiency (iron some patients, over
studies), other MPDs (CML, time, can develop
PRV) myelofibrosis
Poly-cythemia elevated WBC, Hb, Hct, inappropriate absolute JAK2 mutation Diagnosis: Hb > 18.5 (males) or pegylated interferon -
rubra vera platelet counts + aqua polycythemia (EPO independent 16.5 (females), Jak2 mutation, suppresses abnl some patients, over
(PRV) induced pruritis colony growth) from mutation in inc WBCs, inc platelets, low hematopoiesis time, can develop
JAK2/STAT pathway --> EPO, splenomegaly, myelofibrosis
splenomegaly, thrombosis upregulated transcription of thrombosis (common &
lineage specific myeloid genes unusual locations)
for WBCs, RBCs, platelets
(basically myeloid cell line
expansion)
Variants
Primary anemia, splenomegaly, fibroblasts prompted to make extra JAK2 mutation tear drop RBCs (dacrocytes), JAK2 inhibitors - useful for
myelofibrosis elevated or decreased WBC fibrous tissue --> filling of bone immature granulocytes, reducing spleen size and
& platelets marrow w/ fibrotic tissue --> nucleated RBCs improving symptoms; not
hematopoiesis then occurs at helpful for clone reduction
portal hypertension other sites (extramedullary "dry tap" on marrow aspiration
hematopoiesis) (scarring of marrow)
hypercellular marrow + fibrous

tissue
Myelo-dysplastic Refractory subacute presentation premalignant condition where an radiation, more prior chemo/ Smear: abnormal segmentation Stem cell transplant frequently progresses
syndromes anemia (w/ or ("feeling bad") w/ anemia +/- insult (damage to bone marrow) cigarettes common in radiation of WBCs (Pelger-Huet to AML (30% of cases)
(MDS) w/o ringed neutropenia, affects differentiation and elderly treatment nucleus, hypogranular), immune suppression for the
sideroblasts) thrombocytopenia (1, 2, 3 maturation of myeloid line --> hypolobated megakaryocytes small proportion of patients Prognosis depends on
cell lines affected) clonal hematopoiesis --> that have immune proportion of blasts in
refractory cytoplasmic & nuclear asynchrony - BM bx: ringed sideroblasts, dysregulation & hypocellular bone marrow,
anemia w/ anemia, bleeding, -> immune dysregulation, altered excess blasts marrow cytogenetic features,
multilineage infections cytokines --> decreased & number of
dysplasia hematopoiesis & delivery of demethylation drugs like cytopenias
mature blood cells to periphery --> azacitidine
refractory leukemic transformation
anemia w/
excess blasts apoptosis is shifted to bone
marrow = inappropriate cell
5q syndrome death before delivery to
peripheral blood
Acute completely immunodeficient mutation in early progenitor Primary: 1/150,000 CBC: possible hi WBC if driven eradicate AML & restore poor cytogenics or
myelogenous (pancytopenia) myeloid cell causes complete exposure to by blasts, low or nl WBC if hematopoiesis normal cytogenics but
leukemia (AML) replacement of bone marrow with chemicals bimodal age arrested development; low 1. induction therapy poor mutational risk
anemia sx - fatigue, DOE, no normal lineages being made; (benzene - distribution RBCs & platelets (anthracycline, cytarabine) profile - do not survive
roaring in ears (Hb<6); low cells no longer have nl function shoes, rubber), (15-59) smear: Auer rods, blasts (all 2. check therapy response, beyond 2 years &
WBC (feveres, infection), low (immature blasts); clonal, radiation, cells look alike), low platelets & establish risk stratification require transplant!
platelets (bleeding, bruising), proliferative, & arrested hereditary RBCs, low WBCs if cells stuck 3. consolidation therapy
bone pain (wakes patient at differentiation --> impaired (Fanconi's, in marrow; hi WBCs if cells are 4. Observe patients; if poor Worse survival out of
night), hyperviscosity production of nl blood cells Down's) in blood prognosis while on the leukemias
(mental status change, vision, (stuck in progenitor cell phase) BM bx: hypercellular, >3% consolidation therapy, HSCT
dyspnea, spont bleeding), Secondary: primary granules hyperleukocytosis -->
chloroma (skin infiltration by cytogenic abnormalities chemotherapy, flow cytometry: express CD13, CNS injury & pulm
leukemia) common - poor prognosis = hematologic dz CD33, CD117, HLA-DR+ leukostasis
chrom 5, 7, 8 or complex; (CML, MDS) FISH: t(15:17)
exam: pallor, petechiaes, intermediate = nl karyotype; good
ecchymosis, splenomegaly, = t(15;17), t(8;21) prog&tx response - cytogenic &
lymphadenopathy, gingival molecular markers; WBC # at
hyperplasia (monocytic presentation, age, subtype, LDH
leukemia), perirectal abscess, > 700, poor initial reponse to tx
skin nodules
genetic profiling for intermediate
risk patients
Variants
Acute malignant d/o of lymphoid stem cell gives rise to slightly more genetic - most higher SES, CBC - normocytic anemia w/ low prognostic factors - initial tumor lysis syndrome -
lymphocytic progenitor cells that mature lymphoid progenitor cell sensitivity to B common Down's retic count; thrombocytopenia, present (age hi risk if <1 or rapid cell death and
leukemia (ALL) completely replace the that proliferates out of control cell hyper- childhoodsyndrome, leukopenia, possible >10; WBC hi risk if turnover causes
marrow --> pancytopenia sensitization (FH malignancy
radiation leukocytosis (malignant cells) >50,000); location of dz (hi phosphorus and
genetic & environmental of autoimmune exposure, late Peripheral smear: blasts in risk if CNS positive), potassium to be
S/S: anemia (dec energy, combination of etiologies dz) 2.8/100,000 common periph blood (20% of pts do immunophenotype - T cell or released; calcium and
CHF), thrombocytopenia infections, FH not have blasts in periphery at biphenotypic higher risk; uric acid can block
(hemorrhage - mucosal; lack of pathogen exposure as an environmental - 2-3y.o. of time of dx) cytogenetics - favorable kidneys
petechiae, bruising), infant, with subsequent delayed lack of exposure (peak autoimmune BM morphology: hypercellular w/ (TEL-AML), hyperdiploid;
leukopenia (infxn, fever), exposure to pathogens at time of to pathogens in incidence) dz monotonous cells resembling unfavorable (MLL - mixed oncologic
systemic involvement increased lymphoid proliferation -- infancy M>F slightly lymphocytes leukemia, t(9;22)), 4w tx emergencies: tumor
(fever, weight loss, malaise, > extremely robust response BM flow cytometry: blasts > assessment - slow early lysis syndrome (renal
decreased activity), others - trisomy 25% = confirmed dx; CD20 responders or induction failure), anterior
extramedullary involvement 21, high birth clonal population failure need intensification mediastinal mass (T cell
(lymphadenopathy, hepato- rate, ionizing PCR: TEL-AML rearrangement disease - block airway
splenomegaly, bone/ joint radiation, "late" LDH: elevated (marker of cell use of maintenance tx and compress SVC),
pain- bilateral; CNS sx - common inf, turnover) (administer low dose drugs hyperleukocytosis
chloromas, leukemic topo-isomerase tumor lysis labs 1.5-2.5y) - hallmark of ALL (cause sludging -->
meningitis, renal failure, II inhibiters CXR, lumbar puncture (CNS?) stroke, ARDS), sepsis
edema, skin or testicular LFTs, coag screen CNS prophylaxis
masses)
Chronic lymphadenopathy + mutation in B cells post antigen 3/100,000 MBL flow cytometry: cell population important to observe Richter's transformation
lymphocytic elevated WBC/ ALC exposure in the lymph node --> per yr (monoclonal B CD19+ (B cells), CD5+ (T cells asymptomatic patients!! (1% per year) - evolve
leukemia (CLL) clonal B cells arrested in the B-cell cell but occurs briefly in B cell into large cell lymphoma
infections - decreased differentiation pathway, Caucasian> lymphocytosis development), CD23; poor treatment indicated if: Rai 3,
polyclonal immunoglobulins intermediate between pre-B cells AA>Asian ) prognosis a/w CD38+, ZAP70, 4; lymphocyte count doubles staging:
and mature B cells; in the CBC: extremely elevated ALC/ <1y, B symptoms, high risk Rai 0 = low risk;
autoimmune disorders - peripheral blood, these cells patients > WBC (>5000 circulating cells molecular studies lymphocytosis only, med
AIHA, ITP, Evan's syndrome resemble mature lymphocytes age 60 w/ CLL phenotype) survival 14y
smear: high number of mature Treatment includes Rai 1 = intermed risk;
neoplastic B cells do not most lymphocytes; smudge cells fludarabine or chlorambucil lymphadenopathy, med
differentiate into functioning common (fragile cells that have burst), in older patients survival 7y
plasma cells = overall RBC abnormalities Rai 2 = intermed risk;
hypogammaglobulinemia leukemia & (polychromatic, nucleated, HSCT for poor prognosis lymphadenopathy +
most microspherocytes - represent disease spleno/hepatomegaly;
common BM response) med survival 7y
cause of LN bx: well differentiated Rai 3 = anemia, med
general lymphocytes; diffuse primary & survival 4y
lymph- secondary follicles Rai 4 =
adenopathy FISH: poor prognosis a/w 17p thrombocytopenia, med
in adult > &11q deletion survival 4y
60 SPEP: hypogammaglobulinemia
Monoclonal B- precursor to CLL 6-15% of age detectable clonal CLL cells at 1.2-1.4% of MBL
cell relatives of (increased less than 5000 becomes CLL
Lymphocytosis CLL patients CLL clones)
Variants
Plasma Cell fatigue, bone pain, renal plasma cell dyscrasia (B cell MGUS 4.3/100,000 CBC: low WBC, anemia, autologous transplant incurable!
Myeloma dysfunction, hypercalcemia, malignancies) common because thrombocytopenia
recurrent infections w/ germinal centers have such AA> Chemistries: hypercalcemia, hi Thalidomide, Staged by Beta-2
encapsulated organisms high error rates! Caucasians total protein but nl albumin, hi lenalidomide, bortezomib microglobulin (total body
(H.influenzae, Strep pneumo) globulin most impt for remission burden of plasma cells)
malignant plasma cells --> median age Smear: Rouleaux formation of rates & improved & albumin; cytogenetics
1. decreased normal 66y.o. RBCs, +/- plasma cells outcomes for high risk mutations
immunoglobulins --> recurrent Skeletal survey: compression
infections fractures, osteopenia, lytic
2. marrow infiltration --> anemia, lesions
thrombocytopenia SPEP: IgG kappa paraprotein
3. bone destruction from the present at high levels
release of IL-1 (osteoclast (monoclonal gammopathy)
activating factor) --> lytic lesions, BM bx: plasma cells in bone
pathologic fractures, osteopenia, marrow (>10%)
hypercalcemia DX REQUIRES: presence of
4. monoclonal immunoglobulins + serum/ urine M protein, clonal
hyperviscosity of blood (decreased bone marrow plasma cells,
blood flow) + hypercalcemia + organ/ tissue impairment
amyloid (light chains converted to (CRAB = increased plasma
amyloid) --> renal failure calcium, renal insuff, anemia,
lytic bone lesions)
Monoclonal precursor to myeloma!!! <10% plasma cells in marrow, observation 1/3 of MGUS patients
Gammopathy of <3g monoclonal protein, progres to myeloma -
Undetermined Fight infections fine bc normal absent CRAB! obligated to observe and
Significance polyclonal Ig's not decreased; follow these patients!!
(MGUS) no lytic lesions,
hypercalcemia, or organ
damage (CRAB); < 10%
plasma cells in marrow
Evan's syndrome autoimmune hemolytic a/w ALPS, SLE

anemia + ITP (other
autoimmune dz)
Lymphomas (general) painless swelling of LNs, B malignancies arising from cells of should always order HIV test if
symptoms (unexplained lymphatic system (lymph nodes, suspect lymphoma!!
fever, drenching night sweats, spleen, thymus, MALT); can move
unexplained weight loss > to the bone marrow
10% of body weight),
constant fatigue, alcohol majority are B cell origin, very
induced pruritis, reddened few are T cell origin
patches of skin
Variants
Hodgkin's asymmetric contiguous LN involvement bimodal later exposure autoimmune cytopenias (ITP, Localized disease (Stage 1) - Ann Arbor staging:
lymphoma lymphadenopathy (90% of suggests spread via lymphatic age to EBV, HIV, AIHA), immune deficiencies extended field radiation Stage 1 = single LN
cases - firm, rubbery, motile; system distribution iatrogenic region; Stage 2 = 2 LN
supraclavicular, lower (15-34; >50) immunosupp anemia of chronic Stage 2,3 disease - regions on same side of
cervical), rare Reed Sternberg cell - releases , higher SES inflammation, elevated ESR, combination chemo + diaphragm; Stage 3 =
hepatosplenomegaly, cytokines that cause severe elevated LDH radiation to residual areas LNs on both sides of
extranodal manifestations inflammation, fever, deranged diaphragm; Stage 4 =
(rare except in HIV+ or immune system LN bx: Reed Sternberg cell Stage 4 disease - diffuse/ disseminated
advanced stage), B (transformed post-germinal B combination chemo cocktail involvement of
symptoms (1/3 of cases), cell w/ EBV transcripts present) (ABVD) extralymphatic organ
painful lymph node when
drinking alcohol Staging: PET scan + CT, bone If relapse occurs >1 year, w/ treatment, 5y
marrow biopsy retreat as new HL patient; if survival: Stage 1- 90%,
relapse occurs <1 year, Stage 2- ~90%, Stage 3 -
chemo + autologous HSCT 85%, Stage 4- 75%
no treatment - death!!
(mass effect, immune
dysreg, profound
anemia)
secondary
malignancies, CAD
Non- adults - diffuse large B cell spreads hematologically so see risk factors most age (50-60 LN bx: Diffuse large B cell - CHOPR = Ann Arbor staging:
Hodgkin's lymphoma (AGGRESSIVE), random lymphadenopathy common y.o.), large abnl lymphocytes that Cyclophosphamide, hydroxy Stage 1 = single LN
lymphoma follicular lymphoma HIV a/w type of environment replace nl LN architecture, light doxirubicin, oncovin region; Stage 2 = 2 LN
(INDOLENT) indolent / low grade - dec increased lymphoma; al exposure chain restricted; follicular (Vincristine), prednisone, regions on same side of
kids - burkitt's lymphoma apoptosis; aggressive / Burkitt's (chemicals - lymphoma - nodular/ follicular rituximab diaphragm; Stage 3 =
(VERY AGGRESSIVE), intermediate grade - dec lymphomas, 4% of new fertilizer, pattern, cytogenetics show LNs on both sides of
diffuse large B cell, apoptosis, slightly inc mitosis; very
very malignancie pesticides, t(14;18); Burkitt's lymphoma - If relapse, HSCT - 50% can diaphragm; Stage 4 =
lymphoblastic aggressive / high grade - decaggressive s, rising solvents), monomorphic cell population w/ be cured if respond to diffuse/ dissem involv of
apoptosis, VERY inc mitosis plasmablastic incidence chemotherap vacuoles + c-myc salvage + transplant extralymphatic organ
indolent - usually present as lymphomas, y, radiation, rearrangement Indolent - survival mos -
diffuse lymphadenopathy & follicular lymphomas usually aggressive Burkitt immune recommend observing yrs w/o tx; observation
involve the BM have translocation 14;18 (moves diffuse large B lymphoma - suppression, BM bx: not std of care, but if indolent NHL like follicular after chemo; incurable
Ig heavy chain next to Bcl-2 = cell lymphomas peaks in HIV/AIDS, abnl lymphocytes automatically lymphoma if aggressive - survival
hepC a/w splenic marginal marked overexpression of Bcl2 = kids age 11; autoimmune stage IV disease asymptomatic; once wks - mos w/o tx; combo
zone lymphoma; H. pylori a/w anti-apoptotic) adults at dz (Sjogrens, symptomatic, use rituximab chemo outpt; >50% cure
MALToma - both respond to age > 30 - Hashimotos, determine prognosis via IPI = (improves lifespan) rate
tx of infectious agent Burkitt lymphoma - B cell fastest RA, Celiac), inc risk is age > 60, very aggressive -
neoplasm w/ translocation 8;14 growing infectious performance status 2-4, survival days to weeks;
mycosis fungoidies - mature places heavy chain next to c- malignancy (HTLV1, EBV, elevated LDH, extranodal combo chemo inpt; cure
T cell lymphoma --> Myc oncogene; endemic (Africa) !! human involvement, Ann Arbor stage 3- rate >50%
disfiguring skin lesions --> forms a/w jaw swelling & EBV; herpes virus 4 3% follicular
Sezary syndrome (end non-endemic (a/w HIV, EBV 8, hepC, lymphomas transform
stage) negative) H.pylori) to aggressive forms
Fever Low risk Solid tumors, ALL/NHL in GN bacteremia from enteric Ceftazadime (3rd gen
neutropenia remission, neutropenia < source (Pseudomonas) cephalosporin)
7days, expected neutropenia
< 10days, no localization
Fever
neutropenia
Variants
High risk ALL/NHL in induction, AML, GN bacteremia (Pseudomonas), GN enterics, GN bacteremia: ceftazadime
evidence of sepsis (chills), GP bacteremia (Staph, Strep) Staph/ Strep,
mouth sores (mucositis), high Anaerobes GP bacteremia: vancomycin
dose cytarabine, localized abdominal symptoms present?
(central line, GI, rectum) GN bacteremia (Pseudomonas), other sources? abdominal symptoms:
GP bacteremia (Staph, Strep), or HSV, varicella, meropenum (anaerobes,
require very aggressive Anaerobes dysphagia Pseudo), vancomycin, +/-
antibiotic treatment!! (fungal, CMV, tobramycin
unstable? Tachycardia, HSV), yeasts/
hypotension, respiratory molds unstable: meropenum,
distress vancomycin, amikacin
(double coverage against
perirectal abscess, port pocket pseudo)
infection
Typhlitis RLQ pain, obstruction, GI bacterial overgrowth syndrome in CT: thickened bowel wall from BSA
bleed, pneumatosis/ the intestine (usually cecum) --> fluid/ air/ bacteria within the
perforation increased risk of sepsis and GI lumen management of
manifestations constipation/ diarrhea
abdominal pain in the
setting of neutropenia = monitor coags
emergency!! pain mgmt, nutrition
Tumor lysis electrolyte imbalance + renal Normally, potassium load is hyperkalemia, IV fluids + urate oxidase + hypocalcemia -->
syndrome failure excreted by the kidneys; however, hyperphosphatemia, IV calcium gluconade/ muscle spasm, heart
the administration of hypocalcemia, hyperuricemia chloride if seizure/ heart failure, seizures
chemotherapy causes the release failure + amphogel +
of DNA, phosphorus, and treatments for hyperkalemia hyperuricemia &
potassium hyperphosphatemia --
> renal failure
DNA gets further metabolized to
uric acid via xanthine oxidase hyperkalemia -->
arrhythmias (sine wave,
Calcium and phosphorus can Torsaud's)
complex & precipitate --> kidney
stones & renal failure
inability to excrete potassium -->

cardiac manifestations
Hyper- WBC > 100K treatment for tumor lysis tumor lysis syndrome,
leukocytosis syndrome - hydration, urate neurological changes
AML: 5-22% patients; oxidase (stroke, CNS bleed),
clinically significant at > 200K - respiratory distress
-> CNS injury (cerebral maintain platelet count > 20-
hemorrhage, thrombosis), 50K (dilutional effect w/
pulmonary leukostasis (similar transfusion)
to ARDS)
exchange transfusion
ALL: 9-13% patients, (plasmapheresis, double
significant at >300K; exchange)
complications related to tumor
lysis syndrome
Variants
Mediastinal tripod position, accessory CXR!! sedation is

mass muscle usage - suggests contraindicated!!
airway compression (presents
w/ cough, dysphagia,
orthopnea, hoarseness,
wheezing)
SVC syndrome - obstruction

of venous return to the heart --
> compression, thrombosis,
prevention of cerebral
perfusion (presents w/ edema
of upper extremities, head;
AMS changes, acute
respiratory changes - PE)
Spinal cord back pain, decreased chloromas = masses of WBCs in 3-5% of

compression strength, increased leukemia patients; can encroach newly
reflexes, sensory changes, on spinal column, causing diagnosed
rectal tone paralysis oncology
patients
Thrombo- petechiae (platelet dysfxn or
dec platelet prod by marrow: platelets <150K
cytopenia severely low platelet counts),
primary: marrow failure (SAA),
purpura (platelet d/o, coagMPDs, lymphoprolif dz, MDS; Normal WBC & Hb? Check
d/o, nonhemostatic dz like secondary: meds, chemo, rad, peripheral smear
Cushing's, collagen-vascular,
alcohol, vitB12/ folate def, marrow - nl RBC morphology, platelets
scurvy, age) infiltration, viral infxn (HIV, hep), nl or increased in size -
liver dz (dec TPO) consider drug induced, ITP,
accelerated destruct of infection induced, congenital
platelets: non-immune: DIC, thrombocytopenia
TTP, HUS, vasculitis, abnl laminar - fragmented RBCs - consider
flow, drug- induced platelet hemolytic anemias (DIC, TTP)
consump; immune: primary: ITP; - clumped platelets - redraw in
secondary: HIT, glycoprotein sodium citrate or heparin
antiplatelet Abs, CTDs,
lymphoproliferative d/o, infxns, Abnl Hb & WBC? - bone
neonatal alloimmune marrow exam
thrombocytopenia, post-
transfusion purpura
platelet sequestration (spleen)
dilutional thrombocytopenia
(blood transfusions)
pseudo-thrombocytopenia
(clumping of platelets)
Immune thrombo- Newly heterogeneous autoimmune primary immune-mediated 1.5- CBC: platelets < 100K prevent/ stop bleeding if
cytopenia (ITP) diagnosed d/o characterized by: destruction of platelets in 4/100,000 Smear: dec # platelets, large present
(<3m, mostly isolated thrombocytopenia, peripheral blood per year platelets
kids) no underlying cause, +/- BM bx: increased increase platelet count (but
bleeding manifestations anti-platelet antibodies produced avg age 20- megakaryocytes; done only if not to nl levels, just enough
persistent by B cells adhere to platelets & 50 suspect other abnl to stop bleeding)
(3m-1y) mucosal bleeding, target them for destruction; Check HIV & Hep serologies!
previously healthy, usually antibodies also inhibit Check for other autoimmune maintain platelet count >
chronic (>1y, follows infection megakaryocyte maturation/ d/o: Anti-phospholipid 30K for stable hemostasis
mostly adults) proliferation, block release of antibodies, TSH, ANA
platelets 1. steroids, IVIG, Anti-D if
pt is Rh+
most kids spontaneously remit; 2. splenectomy, immune
most adults have chronic or suppression, chemo,
persistent ITP rituximab, TPO receptor
agonists
Variants
Heparin-induced heparin attaches to platelet factor pre-test clinical scoring system: requires IMMEDIATE thrombotic events!!
thrombo- 4 (which is released from 4Ts (thrombocytopenia: discontinuation of heparin
cytopenia (HIT) platelets); heparin + PF4 attaches platelets fall >50% reaching & use of alternative anti- Life & limb threatening
to IgG to form immune complex nadir >20K; timing: clear onset coagulation therapy!! condition
btwn days 5-10; thrombosis:
immune complex attacks the new thrombosis confirmed, skin Treat thromboembolic event
platelet --> immune mediated necrosis, acute reaction; other
platelet destruction & removal causes: none apparent) - low continue anti-coagulation
of platelets by splenic score (<3 pts) a/w up to 1.6% after d/c from hospital -
macrophages +HIT assay, intermediate (4-5 thrombosis risk remains
pts) a/w 8-28%, & high (6-8
at same time, there is platelet pts) a/w 21-100% HIT+ assay
activation, release of platelet
granules, platelet aggregation, &
activation of clotting cascade -->
thrombosis & significant risk of
VTE
Drug induced drugs induce antibodies or caused by direct antibody

thrombo- lupus-like syndrome formation to drug OR drug+
cytopenia protein on platelet can form
hapten, leading to platelet
destruction
Platelet splenomegaly hepatic cirrhosis w/ portal HTN thrombocytopenia
sequestration (low TPO, splenomegaly)
infiltrative diseases (MPD,

Guacher's dz)
Inflammatory dz (Sarcoid, TB)
Hyperplastic responses (chronic

hemolysis)
Dilutional blood & fluid resuscitation results replete 1 unit of platelets per
thrombo- in fall in platelet count every 5-6 units of blood
cytopenia
generally, loss of at least 1-2
blood volumes occurs before
significant decrease in platelet
count
Thalassemias (general) becomes apparent after HbF decreased production of globin
transitions to HbA chains during hemoglobin
synthesis
Alpha rarely problematic bc gene Deletion of 1 or 2 alpha genes Hb Electrophoresis: HbH
duplication (usually in African Americans as Iron studies: normal ferritin
an evolved protection against Smear: target cells,
HbH disease - severe malaria) microcytic, HbH inclusions
anemia + splenomegaly
loss of all alpha genes = no HbF = CBC: mild anemia + significant
Hb Barts = hydrops fetalis (fatal microcytosis = alpha thal
in utero) minor; low normal MCV but
hematologically normal = alpha
loss of 3 of 4 alpha genes = HbH thal carrier
disease
loss of 2 of 4 alpha genes = alpha

thalassemia minor
loss of 1 of 4 alpha genes = alpha

carrier state
Variants
Beta B+ has mutation that multiple mutations (promotor Beta thal major: blood transfusion hemochromatosis (iron
disrupts translation mutations, frame shift, splicing) --> Hb Electrophoresis: small amt or overload following blood
abnl translation --> decreased absent HbA; predominant HbF transfusions) - require
B0 has mutation that stops production of beta globin chain Smear: microcytosis, iron chelating agents
translation (B+) or no production of beta hypochromic, high RDW (very
globin chain (B0) different cell populations) cardiac dz, GI dz, & DM
B0 = beta thalassemia ------------ (from iron deposition on
major = severe transfusion excess alpha chains --> insoluble Beta thal minor: anemia w/ other organs)
dependent anemia, jaundice, & precipitates producing inclusion elevated RBC count, more
hepatosplenomegaly, bone bodies in RBCs --> membrane microcytic than anemic, nl
changes, growth retardation, damage, spleen sequestration, RDW; increased HbA2 & HbF
infections, iron overload --> & profound anemia on electrophoresis
cardiac, liver, endocrine
failure marrow amps up to make more
RBCs and expands --> frontal
B+ = beta thalassemia minor bossing, pathologic bone
= asymptomatic + fractures & deformities
splenomegaly
Hypo- (general) decreased absolute retic decreased production of

proliferative count (<75,000) or hemoglobin/ RBCs
anemias corrected reticulocyte %
(<2%)
Microcytic, normocytic, or
macrocytic (see below)
Microcytic (general) corrected retic % < 2% anemia resulting from inadequate iron
anemias MCV <80 problematic hemoglobin supply
synthesis (deficiency or
not free for
utilization), abnl
globin synthesis,
abnl assembly of
porphyrin ring
Iron weakness, fatigue, dyspnea loss of iron > absorption of iron inc blood loss Smear: microcytic
deficiency (GI - colon Ca, hypochromic RBCs
anemia PE findings: pallor, angular sx of underlying disease process excessive Iron studies: low serum iron, inc
stomatitis, glossitis, menstruation), TIBC, dec % sat, dec serum
koilonychia (spoon nails), dec iron intake ferritin
pica (diet, iron
malabsorp), inc
requirements
(pregnancy,
lactation),
unknown
Variants
Anemia of underlying problem for >6 weeks chronic 2nd most Iron studies: low serum iron, low
chronic infections (TB, common transferrin, low % saturation,
disease activated monocytes & abscess, cause of high ferritin
(ACD) macrophages --> decreased RBC syphilis), anemia,
survival & blunted response to neoplasms, hospitalize BM bx: increased RES iron
EPO --> EPO deficiency chronic d patients! storage
inflammation
inflammation induces hepcidin (arthritis, RA,
release from liver --> inhibition gout)
of ferroportin on macrophage
surface --> iron is locked in RES
(metabolically unavailable) so
cannot re-enter circulation to
make new RBCs
Thalassemia (SEE ABOVE SEPARATE autosomally inherited deficiency in most endemic high RBC & low Hb or low
CATEGORY) rate of synthesis of nl globin common malaria areas MCH
chains monogeneti
c d/o
worldwide
Sideroblastic require smear for diagnosis defect in heme synthesis --> inherited defects Smear: dimorphic picture
anemia accumulation of iron in (normal RBCs+ hypochromic
mitochondria secondary microcytic cells)
defects - pre- BM bx: ringed sideroblasts
leukemia, (rings around nucleus & iron in
drugs (INH), mitochondria)
alcohol, lead CBC: high RDW
poisoning Iron studies: high iron, nl TIBC,
high ferritin
Normocytic (general) corrected retic % < 2% anemia resulting from inadequate
anemias MCV 80-94 stem cells that become RBCs or
decreased demand for RBCs
Metabolic pregnancy = pseudoanemia; Pregnancy

dilutional - hormones secreted
cause plasma expansion, causing renal failure
measured hemoglobin to be
slightly low
renal failure = lower limit of

creatinine clearance indicates
severe kidney disease, resulting in
less EPO production, thus less
RBC & Hb production; EPO
deficiency, shortened RBC
survival, nutritional deficiency
w/ dialysis
Variants
Endocrine androgen deficiency - androgen

testosterone stimulates EPO deficiency
release from kidney; when
androgen deficient, no hypothyroidism
testosterone to stimulate EPO
adrenal failure
Hypothyroidism = reduced
thyroid hormone causes reduced
metabolic rate & decreased need
for O2 (thus Hb)
adrenal failure = corticosteroid

deficiency causes anemia
Marrow damage to bone marrow --> infections, CBC: normocytic anemia +

replacement fibrosis tumors, scar alterations of other cell lines
tissue Blood smear: early WBC, RBC
precursors; tear dropped
RBCs = infiltration
Marrow stem cells can't differentiate so aplastic anemia BM bx: fibrosis =
failure they accumulate in primitive leukemia myelofibrosis; fat cells /
forms hypocellular = SAA;
hypercellular homogenous
blasts = leukemia
Anemia of initially presents as

chronic normocytic anemia (as
disease disease progresses, it
(ACD) becomes microcytic anemia)
Macrocytic (general) corrected retic % < 2% anemia resulting from problematic

anemias MCV >94 RBC division, most likely due to
abnormal DNA synthesis
high retics are not recognized by CBC

reticulocyte as different RBCs so can cause
count increased MCV; must correct
retic count with anemia!!!
Target cells large RBCs from increased red cell liver disease, bull's eye appearance on
membrane (target cells) obstructive smear; Howell-Jolly bodies
jaundice, post (inclusions in RBCs) suggest
splenectomy splenectomy
Severe hypo- mild increase in MCV due to

thyroidism increased lipid in membrane
(usually normocytic though!!)
Variants
Megaloblastic corrected retic % < 2% problem with DNA synthesis vitB12 FH of CBC: large RDW B12 injections / oral
anemias MCV >94 folate def: THF (derived from folic deficiency, autoimmune Smear: macro-ovalocytes, supplementation
acid) converts dUMP to dTMP; folate dz (B12d) hypersegmented neutrophils,
B12 def: jaundice, angular w.o folic acid, insuff substrate deficiency, immature chromatin (more
stomatitis (cracking at corners (thymidine) to support DNA chemotherapy, euchromatin than dark
of mouth), glossitis (beefy red synthesis myelodysplastic heterochromatin), large
tongue), neurologic syndromes, platelets
irreversible probs B12 def: B12 converts hereditary Other tests: inc LDH, inc indirect
(peripheral neuropathy, probs homocysteine to methionine via defects in DNA bilirubin, inc TIBC
w/ posterior columns - methyl group from THF; w.o B12, synthesis
vibration, proprioception, conversion is blocked &THF is B12D: low serum B12, nl serum
lateral corticospinal tract trapped as N-methyl THF, a B12D = vegans, folate, inc homocysteine, inc
probs - spasticity, dementia) metabolically useless substrate; absorption probs methylmalonate;
methionine is used to make (low pancreatic autoantibodies to parietal cells/
folic acid def: SAME myelin (no B12 = demyelination & enzymes, IF/ thyroid if autoimmune
hematologic & symptoms as neuropathy) pernicious
B12D EXCEPT no anemia, small Folate def: low serum folate, nl
neurological involvement!!! Folic acid def etiologies - inadeq bowel dz - serum B12, inc homocysteine,
dietary intake (chronic alcohol, Celiacs, NL methylmalonate
elderly), inc requirements Crohns), liver
(pregnancy), imp absorption (liver dz, fish
dz, small bowel dz), def inter- tapeworm
conversion (drugs like MTX)
Acquired (general) corrected retic >2% or represents destruction increased retic count
hemolytic 75,000 (hemolysis) or loss of RBCs in
anemias circulation (bleeding - GI or GU isolated elevation of non-conj/
extravascular hemolytic tract) indirect bilirubin
anemia - destruction of
RBCs in RES--> increased increased retic count means increased LDH
indirect bilirubin, increased marrow is mounting a normal
urobilinogenin in urine, high response to the anemia decreased haptoglobins
iron % sat; increased delivery
of iron from RBC breakdown Immune mediated hemolysis - hemosiderinuria - intravascular
products antibody and/or complement
fixation to RBCs results in hemoglobinemia,
intravascular hemolytic phagocytosis by macrophages in hemoglobinuria (rare)
anemia - RBCs burst apart splenic fenestrations, bone
in the vessels --> hi plasma marrow, or liver decreased measured RBC
Hb, hi urine Hb, high LDH, survival
and iron-stained renal tubule
cells
Spleno- acquired extrinsic RBC spleen normally filters blood; if
megaly defect resulting in non- RBCs are abnormal, the spleen will
immune mediated hemolysis collect the RBCs and destroy them
in states of splenomegaly (infxn,

malignancy), the spleen will
filter the blood too effectively,
removing normal RBCs from
circulation = shortened RBC
survival = increased retic count
Variants
Fragmentatio acquired extrinsic RBC RBCs encounter an abnormal valvular/ systemic Smear: schistocytes
n hemolytic defect resulting in non- surface in circulation (heart valve, vascular illness
anemia immune mediated hemolysis fibrin deposits) --> shearing apart prosthesis,
of the RBCs severe AS, DIC,
also a/w thrombocytopenia vasculitis, RA,
SLE, TTP, HUS,
hemangiomas,
eclampsia,
malignant
hypertension,
pulm HTN
Other acquired extrinsic RBC Physical & chemical agents (burns, Smear: marble appearing RBCs
abnormalities defect resulting in nonbacterial infections) - breakdown of (physical or chemical agents),
causing immune mediated hemolysis RBCs or membrane lipids acanthocytes (abnl lipid
acquired, non- deposition w/ severe liver dz,
immune Lipid abnormalities & low phosphate), infectious
mediated hypophosphatemia - abnormal lipid agents (malaria)
deposition (liver dz) or dehydration
from abnl fxn of Na/K ATPase
(hypophosphatemia)
Infectious agents - malaria,

babesiosis
Alloimmune acquired extrinsic RBC acute transfusion reaction - transfusion acute transfusion rxn -
hemolytic defect resulting in immune major blood group incompatibility -- reactions activation of coagulation
anemia mediated hemolysis > preformed antibodies to RBCs; system, renal failure, &
when transfused w/ these RBCs, death
the Hb goes up but then
immediately falls (hemolysis)
delayed transfusion reaction -

Hb increases but then begins to
fall 7-10d later (hemolysis); pt
made new antibodies that attacked
the transfused RBCs
Autoimmune acquired extrinsic RBC Antibodies developed to self RBCs Warm Smear: microspherocytes + Warm antibody -
hemolytic defect resulting in immune antibody? increased reticulocytes, cold responsive to steroids &
anemia mediated hemolysis Warm antibody - IgG or Idiopathic, antibody AIHA has prominent splenectomy
IgG+Complement; hemolysis lymphoprolif d/o, agglutination or clumping of
warm or cold antibody AIHA occurs mainly in spleen autoimmune dz, RBCs Cold antibody -
infections Coomb's test: Warm antibody unresponsive to steroids
Cold antibody - IgM antibodies (IgG or IgG+complement), & splenectomy
so complement activation only; Cold antibody? Cold antibody (Complement
hemolysis occurs in liver/ bone Infections, only)
marrow/ other RES sites lymphoprolif d/o,
idiopathic,
paroxysmal cold
hemoglobinurea
(actually IgG
mediated cold
antibody AIHA)
Variants
Drug induced acquired extrinsic RBC Hapten-Penicillin type - Antibody Hapten

hemolytic defect resulting in immune against a drug that is bound to penicllin type?
anemia mediated hemolysis RBC --> IgG positive Coomb's Penicillins,
cephalosporins,
Innocent Bystander type (most ceftriaxone
common!) - antibody against the
drug forms an immune complex Innocent
that adheres to RBC surface --> bystander
complement positive Coomb's type?
Sulfonamides,
Autoimmune-Aldomet type (very quinidine,
rare now since don't really use phenothiazines
these meds) autoantibody to Rh
components of RBC --> IgG Autoimmine -
positive Coomb's Aldomet type -
L-DOPA,
aldomet for HTN
Inherited (general) corrected retic >2% or intrinsic defect in RBC leads to

hemolytic 75,000 hemolysis
anemias
neonatal jaundice, recurrent gallstones? Increased Hb
"hepatitis", personal or FH of breakdown = inc indirect bili = inc
premature gallstones/ bile salts = inc pigmented
anemias/ splenectomy/ or gallstones --> cholecystectomy
specific dz; chronic or
recurrent symptoms that have problem w/ membrane? Hereditary
not been adequately spherocytosis, elliptocytosis,
addressed pyropoikilocytosis
problem w/ hemoglobin? sickle cell

anemia
problem w/ enzymes? G6PD

deficiency
Hereditary hemolytic anemia (mild to disorder in RBC membrane autosomal Smear: microspherocytes, splenectomy helps with
sphero- severe) shaped causing "marble shaped" dominant, elevated retic count (looks just symptoms but morphological
cytosis RBCs sometimes AR like AIHA so need Coomb's changes persist
aplastic crisis w/ infection test to R/O)
(ParvoB19), which stops osmotic fragility - hemolysis at
RBC production for 7-10d higher concentrations (membrane
(usually childhood is already very leaky)
presentation)
abnl cytoskeleton proteins -
deficiencies in proteins that bind to
spectrin (which is the foundation of
the protein matrix)
Hereditary hemolytic anemia (mild to abnl spectrin interactions with autosomal Smear: elliptical RBCs (if >20%
elliptocytosis moderate) other matrix proteins dominant = diagnosis)
high phenotypic variability

within families
Hereditary severe hemolytic anemia major deletions in portions of autosomal Smear: fragments of RBCs,
pyropoikilo- spectrin molecule = abnormal recessive worse w/ heat
cytosis abnormal RBC shape with fragments of RBCs
heat
Variants
Sickle cell hemolytic anemia mutation in 6th position of beta 8-10% of Hb electrophoresis: HbS only hydroxyurea - increases stroke, sepsis, sickle
disease increased severity of globin chain where valine is African (Sickle cell disease), HbS + HbA production of HbF to nephropathy
infections (s. pneumo, substituted for glutamic acid = Americans (sickle cell trait), HbS + HbC (Hb interfere w/ sickle cell
meningitis) Sickle cells polymerize during SC disease) polymerization & reduce #1 cause of death?
tissue infarction w/ organ states of deoxygenation, pain is the frequency of sickle events Acute Chest Syndrome
failure (leg ulcers, stroke, increased MCHC, acidosis, or most
nephropathy) increased temperature; severe pain mgmt - nonopiods
severe pain episodes (bone polymerization makes RBCs complicatio (absolute dose ceiling),
degeneration from sickling --> rigid & unable to circulate well -- n opiods (no abs dose ceiling)
arthritic pain & loss of > mechanical destruction in (disability,
function; sudden onset pain in circulation, plugging of small healthcare
extremities & back) vessels --> ischemia & pain $)
Sickle cell carriers - severe infxns - fever inc sickling,

asymptomatic except when inc S.pneumo (which can cause
exposed to severe hypoxia or sepsis in these pts!), inc
dehydration meningtiis
Hb SC dz - milder sickle Stroke - occlusion of large vessels
anemia, mild probs in sickle nephropathy - sickled
childhood so might present RBCs disrupt vasa recta &
later in life glomeruli
Leg ulcers, sickle pain
G6PD can present w/ drug-induced Mature RBCs depend on a.a. 7-8% of Smear: bitocytes, staining of
deficiency hemolytic anemia (anti- anaerobic glycosis for ATP substitutions, African Heinz body inclusions
malarials, sulfonamides), generation, reducing capacity deletions, or Americans,
Mediterranean favism, (requires NADPH & NADH) insertions 10-15% of
congenital nonspherocytic resulting in Mediterrane
hemolytic anemia, neonatal In G6PD def, there is inadeq G6PD instability, an heritage
jaundice, hemolysis w/ infxns NADPH so Hb and proteins defective
or DKA become oxidized and precipitate enzyme fxn, or
in RBC --> inclusions of Hb that combos
bind RBC membrane (Heinz
bodies)
Transfusion nearly uniformly fatal occurs if immunocompromised severely

associated patients receive blood that is not immuno-
GvHD involves marrow, liver, skin, irradiated!! compromise
gut d; neonates
skin sloughing
Transfusion Acute often due to ABO intravascular hemolysis, STOP transfusion!! DIC, renal failure
reactions hemolytic incompatability, most likely complement mediated, IgM
transfusion due to clerical error (mis- Flush w/ IVF
rxn identification of patient)
Check CBC to monitor
Sx: fevers, chills, back pain, platelets & Hb, check renal
hypotension, n/v fxn labs and coagulation
studies
Delayed 3-10d after transfusion of antibody not detected pre- antibodies to ARF, DIC
hemolytic blood that appeared transfusion (Anamnestic antibody Rh, Kidd, Duffy
transfusion compatible response) --> intravascular and/or minor antigens
rxn extravascular hemolysis
often asymptomatic w/
fever, mild jaundice, anemia
Variants
Febrile One degree Celsius rise in occurs from cytokine release from STOP transfusion!!
reaction temperature to the febrile WBCs in the unit being transfused,
range antibodies to donor WBCs, or
bacterial contamination
cannot be distinguished
from fever in acute
hemolytic rxn so
transfusion must be
stopped!!
Septic unit becomes contaminated w/ Platelets -
reaction bacteria (much more likely to occur usually Staph
in platelet units which are stored at
room temp) RBCs - usually
Yersinia
enterocolitica,
Citrobacter
Urticarial rash and/or itching recipient is previously sensitized to 3% of Benadryl, then start
reactions soluble allergens in donor unit transfusions transfusion again
ONLY reaction where blood (second
can be restarted & work up most
is not mandatory common
reaction)
Anaphylactic hypotension, chills, fever, consider IgA antihistamine, epinephrine,
reactions dyspnea, n/v, diarrhea, deficiency! steroids, supportive care
urticaria
Transfusion respiratory insuff, fevers, antibody mediated situation often FFP #1 leading CXR: bilateral chest infiltrates does not improve w/
related acute chills, hypotension due to HLA antibodies present in transfusions cause of diuretics
lung injury the transfused product death from
(TRALI) mimics ARDS but resolves w/I transfusion
48h
Tranfusion fluid overload --> breathing occurs in patients w/ pre-existing improves w/ diuretics
associated problems cardiopulmonary compromise, (UNLIKE TRALI!)
circulatory perhaps a/w hypertension
overload
(TACO)
Iron overload liver/ cardiac/ endocrine each unit of RBCs contains 200mg chelation therapy (Exjade)
problems of iron; patients who are
chronically transfused (sickle cell)
have higher risk of iron overload
Aspergillosis most popular fungal infxn transmission of Aspergillus mold CT of head to check for
in HSCT pts from environmental source dissemination to brain
Colonization - non-disease CT: characterisitc halo

state; Aspergilloma = mold description of nodular
fills lung cavity & releases infiltrate
spores; a/w colonization in CF
patients
Invasive disease -
pulmonary, sinusitis,
tracheobronchitis, cutaneous,
disseminated
Variants
Mucormycosis mold w/ high mortality rate spores are inhaled and deposit on low neutropenia, MRI shows opacification of
mucosa, then germinate and incidence immunocomp sinuses, brain edema & invasion
Rhinocerebral - invade tissue; angioinvasion --> (1.7/100K) (HSCT, organ
nasocongestion, pain behind tissue necrosis transplant, CXR shows dense infiltrates; CT
eye, proptosis, AMS cancer, does NOT have halo infiltrates
autoimmune like Aspergillus
Pulmonary - dyspnea, fever, dz), poorly
non-productive cough, controlled DM Cx: grows very quickly,
pleuritic chest pain branching hyphae
Candidiasis most common fungal bloodstream if affects lung via hematogenous do not treat asymptomatic
infection in hospitalized infxn risk spread, can see lung abscesses UTI (unless prior to GU
patients factors? surgery, immunocomp, or
Neutropenia, white plaques on soft palate, neonates)
variety of presentations - UTI, indwelling esophagus
pneumonia, devices, symptomatic UTI -
mucocutaneous (thrush, hemodialysis, hepatosplenic candidiasis - amphotericin B or
esophagitis, diaper rash), DM, AIDS, microabscesses in liver & fluconazole
tissue, bloodstream abd surgery, spleen seen on MRI (heme-onc
critical illness, pts only)
neonate,
age>65, TPN, dx? Blood/ mucus/ bx culture,
broad
spectrum Abs
Qualitative (general) platelets present in adequate acquired causes - meds, MPS, DDAVP - synthetic
platelet disorders numbers but do not function systemic illnesses, renal dysfxn, derivative of
properly cardiopulmonary bypass ADH/vasopressin so causes
release of VWF from
Congenital causes - granule endothelium (increases
disorders, absent/ dysfunctional stickiness of plasma)
adhesion receptors
anti-fibrinolytic agents block
plasmin and prevent lysis of
fibrin within clots
COX1 aspirin, NSAIDs Aspirin = irreversible COX1

inhibitors inhibitor; platelets do not
bruising, bleeding synthesize new COX1
(anucleated) so reversal of aspirin
effect depends on platelet half life
(3-5d); after new platelets are
made, function returns
NSAIDs = reversible COX1

inhibitors; reversal of NSAID
effect depends on half life of the
drug
Clopidogrel irreversible inhibitor of ADP

(Plavix) receptor, blocks platelet activation
Uremia (renal accumulated metabolites impair dialysis corrects platelet

dysfxn) fxn of circulating platelets dysfxn
Variants
Glanzmann normal platelet count w/ absence or dysfunction of mutation within PFA - no aggregation but will
thromb- mucocutaneous bleeding integrin aIIbB3, preventing the binding site agglutinate w/ ristocetin
asthenia platelet aggregation of aIIbB3 or talin
deficiency (talin
nl exposes
binding site)
Bernard- thrombocytopenia w/ giant absence or dysfunction of PFA - aggregation but no

Soulier platelets platelet adhesive receptor agglutination w/ ristocetin
syndrome (GP1b), preventing platelet
adhesion
Absence of dense granule def - patients will PFA - loss of 2nd wave (no
platelet also have varying degrees of aggregation because deficiency
granules albinism of granules or dysfunctional
granule release)
alpha granule def - gray platelet
syndrome
Dysfunctional
granule
release
von Willebrand (general) VWF activity less than 30% certain conditions can also change autosomal low agglutination with ristocetin plasma derived factor 8
disease (VWD) = increased bleeding risk the amount of circulating vWF; ie dominant products w/ high
sympathetic response has concentrations of VWF
increased vWF in preparation for
injury DDAVP
hi vWF - stress, exercise,

pregnancy, age, acute & chronic
inflamm, DM, OCP use,
malignancy, hyperthyroidism
low vWF - hypothyroidism, blood

type O
Type 1 (75- significant bleeding history, decreased synthesis & plasma
80%) FH of inc bleeding or VWD, secretion of VWF; can also occur
low levels of VWF activity as a result of inc clearance
Type 3 (1- low factor 8 activity leading to

3%) hemarthrosis
Type 2 normal VWF levels but high circulating VWF but defective
(qualititative; decreased VWF activity function
15-20%) from:
1. decreased multimers
circulating
2. decreased binding to
factor GP1b
3. abnl binding to factor 8
4. dysfxnal hi affinity
interaction w/ GP1b
Variants
Inherited Hemophilia A = factor 8 defect in platelet surface thrombin X-linked A = 1/10K replace missing clotting 60% of patients are
hemophilia deficiency generation (factors 9 & 8 are male births factor - recombinant severe - spontaneous
required to provide platelet 20-30% = bleeds
Hemophilia B = factor 9 surface for activation by factor spontaneous B = 1/30K release of stored factor 8
deficiency 10) mutations male births w/ DDAVP 15% are moderate -
trauma/ surgery bleeds,
Bleeding into joints/ occasional joint bleeds
muscles, prolonged bleeds
from lacerations or dental 25% are mild - major
procedures, excessive trauma/ surgery bleeds,
bruising / hematomas, rare joint bleeds
bleeding w/ surgery or
trauma, intracranial 25% of hemophilia A pts
hemorrhage, kidney / GU will develop
tract bleeding spontaneous
antibodies to factor 8
other complications?
chronic hemarthrosis
w/ pain/ joint
destruction, HCV, HIV
risk
Acquired severe bleeding in pt w/ no auto-antibodies bind native factor a/w autoimmune 1.4/1million prolonged PTT, elevated control bleeding
hemophilia known bleeding problems 8 in persons without congenital conditions, mixing study (suggests
hemophilia pregnancy, mortality 6- inhibitor to intrinsic pathway eradicate inhibitor w/
bruising, mucosal bleeding, malignancy 20% factor) steroids, IVIG, rituximab
muscle bleeding (highest in
elderly)
Lupus thrombosis antibodies that inhibit phospholipid symptoms + factor 8 >10%

anticoagulant dependent coagulation; neutralized that "titers up" with dilution
by presence of excess
looks like DVT phospholipids titered up PTT post mixing!!!
Vitamin K muscle bleeding, deep blocks conversion of vit K infancy, prolonged PT, prolonged PTT, asymptomatic? Oral or IM intercerebral, GI,
deficiency bleeds dependent factors (2, 7, 9, 10, malabsorption, post mixing study corrects vitK umbilical, or ENT
protein C, protein S) to activated hyperemesis PTT bleeding
forms --> bleeding gravidarum, active bleed? Emergency!
fasting, Requires FFP then correct
alcoholism, vitK
drugs
(warfarin, Abs,
salicylates)
Liver failure liver makes all coagulation factors

(except VWF), anticoagulants
(protein C & S), and TPO
(stimulates platelet production)
liver failure = deficiency of majority

of coagulation cascade,
splenomegaly, thrombocytopenia,
bleeding
Factor 12 Hageman factor autosomal abnl PTT NO TREATMENT!!

deficiency recessive
NOT a/w bleeding
Variants
Fibrinogen increased fibrinogen? Acute prevents stable formation of cross- deficiency? Abnl PT & PTT,
abnormalities phase reactant, inflammation, linked fibrin clot OR prolonged thrombin time, abnl
pregnancy overproduction of fibrin clots fibrinogen assay
decreased fibrinogen? DIC,

liver dz, ascites, alcohol
Hemolytic #1 cause of acute renal failure formation of clots in the glomerulus Smear: schistocytes from acquired? Supportive tx
Uremic in kids acquired (90%) - infection fragmentation only
Syndrome (HUS) (prodrome of bloody diarrhea -->
classic triad - intravascular release of large vWF multimers = Atypical? Poor prognosis
hemolytic anemia increased thrombosis) w/ renal failure; cannot be
(schistocytes), genetic (atypical HUS) - mutations transplanted (intrinsic dz)
thrombocytopenia, renal in complement pathway (factor H
failure normally suppresses C3b
convertase; however, without
factor H, convertase able to
activate complement all the time
--> thrombosis)
clots generated in small vessels,

turbulent flow shears RBCs,
platelets consumed by thrombosis
& shearing --> excessive
thrombin generation & loss of
compartmentalization (diffuse
endothelial injury, loss of
endothelium = loss of inhibition)
Thrombotic pentad: hemolytic anemia absent ADAMTS13 = large Acquired - Ab plasma exchange & vWF
Thrombo- (schistocytes), multimers of VWF formed that formed to inhibitors
cytopenic thrombocytopenia, renal activate platelets = widespread ADAMTS13
Purpura (TTP) insufficiency, neurologic thrombosis (primary
changes, fever hemostasis) congenital - def
ADAMTS13
Disseminated bleeding + subclinical or uncontrolled activation of primary sepsis, elevated clotting times & FFP transfusions but watch
Intravascular clinical thrombosis & secondary hemostasis, malignancy, decreased platelet count for volume
Coagulation activation of fibrinolysis, trauma/ head
(DIC) sepsis patients! consumption of factors & injury/ burns, ELEVATED D-DIMER cryoprecipitate to keep
inhibitors, and evidence of end obstetric fibrinogen elevated
organ damage causes
(eclampsia, platelet transfusions (keep
Cytokines, TF, LPS, hemolysis, retained fetus, platelets > 50K)
acidosis, turbulence all contribute abruptio
to factor activation, endothelial placenta) ??heparin
damage, & platelet activation
others? AA,
toxins,
transfusion,
immunologic
Variants
Venous (general) abnl formation of blood clot inside age, comorbid Wells score heparin (LMWH or UFH) - anticoagulation
Thrombosis venous system (fibrin mediated) conditions UFH cleared by continued if high risk of
(OCP use, lower extremity U/S, CT of chest macrophages so no effect recurrence (i.e. no
embolism - detached intravascular HRT, to R/O PE on kidney or liver + short reason for VTE at time
solid mass that is carried by blood hospitalizati half life; LMWH is fast acting of diagnosis -
to site distant from its origin on, cancer, and more predictable but unprovoked VTE, type
surgery) renally cleared of underlying syndrome,
Virchow's triad - endothelial gender - men, elevated
injury (atherosclerosis, TTP, HIT, immobilizati bridge with warfarin (at D-dimer 1m after d/c
trauma) + abnormal blood flow on, burns, least 5 days overlap) warfarin)
(stasis from immobilization, HIT, DIC, before d/c heparin
stenosis) + hypercoagulability pregnancy post-thrombotic
(thrombophilias) syndrome (see below)
persistent
risk factors?
Inherited
thrombophilia,
acquired
thrombophilia
s, obesity,
CHF,
nephrotic
syndrome,
Superficial generally benign & self thrombosis in superficial vein low dose heparin for at least
vein limiting 4 weeks
thrombosis
(SVT) becomes more serious if
extends into deep vein
tender, palpable cord w/

surrounding erythema &
heat
Deep vein occlusion of deep veins in leg --> major risk of
thrombosis lack of venous return of blood --> embolization to lungs
(DVT) congestion & pain (PE) and post
thrombotic syndrome
(PTS)
Post- develops within 1-2 y of damage to venous valves 20-50% of common regular use of
thrombotic acute DVT; a/w poor QoL (mechanical damage from clot & pts w/ femoral or compression stockings!
syndrome inflammation provoked by acute symptomatic iliac vein DVT (must be replaced every 6
(PTS) possible ulcer formation, thrombosis) proximal months, worn daily for 2y
lower extremity swelling, vein DVT hi BMI after DVT)
pain, itching, heaviness,
edema, venous ectasia, prior
hyperpigmentation, pain w ipsilateral
calf compression venous
thrombosis
worse sx w/ activity; better
w/ rest female
older age
Anti-thrombin variable presentation but AT normally inactivates thrombin & 1% of pts anti-thrombin activity assay -
deficiency overall risk of thrombosis factor X to shut down coagulation with VTE low activity & low numbers of AT
increased 15-20x cascade; deficiency leads to (type 1) or normal numbers but
increased thrombosis 1/250-1/500 low activity (type 2)
prevalence
exclude acquired causes - liver
disease, nephrotic syndrome
Variants
Protein C variable presentation but Protein C (along with Protein S) 2-9% of make sure patient has d/c
deficiency overall risk of thrombosis normally inhibit factors 5&8 of patients w/ warfarin for 2 weeks prior to
increased 15-20x coagulation cascade VTE testing Protein C
prolonged PTT in protein C

deficient plasma
Protein S cofactor to activated protein C, 3% of pts w/ Prolonged PTT w/ protein S
deficiency enhances anticoagulant effect of VTE deficient plasma
protein C
make sure patient has d/c
deficiency a/w increased warfarin and not on hormonal
thronbosis risk therapy or pregnancy
Factor V Leiden Heterozygotes - VTE risk mutation in factor 5 gene --> APC sensitivity ratio = PTT in
increased by 5-7x resistance to factor 5 presence of protein C/ PTT in
inactivation by protein C absence of protein C
Homozygotes - VTE risk
increasd by 50x PCR based assay for specific
mutation
synergism w/ OCPs
Acquired Anti- thrombosis (1+ episodes enhanced platelet activation & lupus anti-coagulant test
thrombophilia phospholipid confirmed by imaging/ path) subsequent aggregation (requires 2 tests since
syndrome OR pregnancy morbidity insensitive): prolonged clotting
(APS) (recurrent pregnancy loss) enhanced TF expression thru time that does not correct w/
monocyte activation mixing + clotting time that
PLUS shortens w/ addition of
inhibition of protein C/S phospholipid
high anti-B2 anticoagulant pathway
glycoprotein/high aCL
antibodies/ high Lupus activation of complement
anticoagulant
Screening /
Education
Screening /
Education
remission =
residual leukemia
burder below
level of detection
cure = remission
beyond 5 years
Screening /
Education
better prognosis
than AML
COG - children's
oncology group -
guarantees
clinical research
trial for every kid
w/ leukemia
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
newborn
screening = early
diagnosis &
prompt tx of
infxns & comps
informed
reproductive
decisions for
sickle traits
PCN
prophylaxis
birth to age 5
can be
prevented if
blood is
irradiated for at
risk patients!!
Screening /
Education
avoid transfusion
of plasma
containing
products; wash
products prior
to future
transfusion,
premedicate;
transfuse from
IgA def donors if
pt is IgA def
declining
incidence due to
use of male only
FFP
Screening /
Education
Screening /
Education
Screening /
Education
give VitK to all

newborns as
prophylaxis
against
hemorrhagic
disease of
newborn
Screening /
Education
Screening /
Education
Compression
stockings
IVC filters if
contraind for
anticoagulation
Screening /
Education
Variants
Subdural usually in shaken brains tearing of the bridging veins (low coup contra CT: best for acute bleeds
hematoma pressure venous bleed that coup injuries MRI: best for subacute bleeds;
blood is often crescent increases w/ time) from MVA, falls, shows blood spread out across
shape over brain surface -- shaken baby the surface of the brain
> increased intracranial subdural space = deep to dura syndrome
pressure (nowhere for extra mater btwn dura & arachnoid
volume to escape) layers of meninges
Epidural blood accumulates rapidly, tearing of the middle meningeal blow to skull PE: lucid interval (delayed
hematoma forming a bulge between artery (high pressure rapid (baseball) neurological signs)
regions of dural attachment bleed that separates dura from
to bone --> increased skull) CT: best for acute bleeds
intracranial pressure MRI: best for subacute bleeds
epidural space = potential space
btwn dura & skull; fills w/ blood or
fluid w/ trauma
Subarachnoid sudden onset, "worse CT: blood in ventricles or other ABCs, Neurosurgical
hemorrhage, headache of life" brain areas consult
intracranial
hemorrhage
Coup contra 3 points of impact: 1) Car to brain hits skull then bounces back
coup injury tree, 2) Skull to windshield, 3) to other side of skull (primary
Brain to skull insult)--> brain bruising on both
sides --> swelling & subdural
hematoma (secondary insult) -->
Increased ICP
Brain herniation Falx cerebri brain herniates from left to

right side
Foramen brain undergoes tonsillar/ inc ICP in foramen magnum (near
magnum cerebellar herniation cerebellum & medulla) -->
herniation of cerebellum -->
pressure against medulla -->
compromise of basic
homeostasis mechanisms -->
respiratory arrest
Tentorium Uncus (bump protruding tentorium cerebelli separates primary or CT: no CSF space, severe normalize inc ICP by
cerebelli from medial temporal lobe) occipital lobe from cerebellum; inc metastatic vasogenic edema, ring elevating head, intubating &
(uncal herniates through the ICP in cerebral cortex --> uncal tumors enhancing masses, uncal hyperventilate, giving
herniation) tentorium cerebelli herniation thru tentorium herniation mannitol & dexamethasone
cerebelli --> inc pressure (reduces edema; do NOT
impaired pupillary light midbrain & CN3 --> impaired use if herniation due to
reflex (ipsilateral dilated pupillary light reflex ischemic stroke!)
pupil), Cheynes-Stokes
respirations, left decompressive surgery
decerebrate posturing, dec
consciousness
Hydrocephalus gradually inc ICP causes? 1) overproduction of CSF surgical placement of shunt
by choroid plexi, 2) not enough to divert CSF from brain
increased pressure & volume reabsorption of CSF by arachnoid
of CSF --> increased granulations, 3) blockage of CSF
ventricular volume, flow
inflammation of underlying
tissue, & decreased brain
tissue
Left (dominant) right visual field deficit
hemisphere (hemianopsia), right
lesion hemiparesis (weakness),
right hemisensory loss
(numbness), left gaze
deviation/ preference,
aphasia
Variants
Right left visual field deficit, left

(nondominant) hemiparesis, left
hemisphere hemisensory loss, left
lesion hemineglect, right gaze
deviation/ preference
Medial midbrain ptosis, diplopia, anisocoria CN3 palsy, damage to
syndrome (uneven pupils), contralateral corticospinal tract (CL
hemiparesis, contralateral hemiparesis), and damage to
UMN facial weakness corticobulbar tract (CL facial
weakness)
Lateral ipsilateral facial sensory loss, lateral medulla lesion causes infarct to the
medullary contralateral body sensory problems with spinal trigeminal vertebral artery
syndrome loss, ipsilateral ataxia, nucleus (IL facial sensation loss), or posterior
dysarthria, dysphagia, +/- spinothalamic tract (CL light inferior
hoarseness, hiccups, Horner touch & temp loss of body), cerebellar artery
syndrome inferior cerebellar peduncle (IL
ataxia), nucleus ambiguus
(dysarthria, dysphagia), and
descending autonomic tracts
(sympathetic - Horner syndrome)
Horner's ptosis, anhidrosis & flushing oculosympathetic pathway lesion above

syndrome of affected side of face, projects from hypothalamus to T1 (Pancoast
miosis (pupil constriction) lateral tegmentum (MB, pons, tumor, Brown-
medulla) to the intermediolateral Sequard
cell column of the spinal cord; syndrome, late
interruption in this pathway causes stage
Horner's syndrome syringomyelia)
Medial medullary contralateral weakness, lesion affecting the corticospinal infarct of

syndrome contralateral loss of fine tract (CL weakness), dorsal vertebral artery
touch, ipsilateral tongue column-medial lemniscus (CL or anterior
weakness loss of fine touch, vibration), and spinal artery
hypoglossal nucleus (IL tongue (posterior
weakness) circulation)
Bell's palsy recent onset of unilateral LMN lesion of facial nerve or reactivation of most
facial weakness (weak nucleus --> peripheral ipsilateral viral common
forehead, unable to close facial paralysis with inability to inflammation of mono-
eyes, weak lower face, close eye on involved side facial nerve by neuropathy
unable to wrinkle forehead on stress,
same side as lesion, emotional
ipsilateral flattened nasolabial triggers??
fold), impaired taste
(dysguesia), hyperacusis on Complication of
right AIDS, lyme dz,
HSV,
sarcoidosis,
tumors, DM
Cerebellar unilateral hearing loss, tumor impinges on pontomedullary
pontine angle peripheral facial weakness, junction, where CN 6,7,8 all exit
tumor possible development of
horizontal diplopia
Variants
Basilar pontine Locked in bilateral facial weakness, loss of CN6, 7, + bilateral

infarction syndrome inability to abduct both eyes, corticospinal involvement, as well
bilateral quadraplegia, as UMN deficits
extensor plantar responses
basilar artery supplies vasculature
pt is awake & alert but to majority of pons; infarction
quadriplegic and unable to knocks out both corticospinal
speak, swallow, or breathe tracts, spinothalamic tracts, &
posterior column tracts BUT
preserves ascending RAS (so pt
remains conscious)
intact cerebral cortex that is

unable to interact w/ external
world
Epilepsy (general) 2+ unprovoked seizures, syndromes depend on age of 1-2% of PMH of usually med responsive but co-morbidities:
generalized or focal onset, FH, MRI findings, population complex some can be refractory and depression, anxiety,
predisposing factors, EEG febrile require lobectomy unemployment, loss of
dj vu, disconnection / out of findings, chronicity, seizures as a driving privileges, social
body experience, olfactory/ clusters/cycles, severity kid, head stigma, relationships
gustatory hallucinations, trauma,
behavioral arrest, alcoholism, post-op complications:
unresponsiveness, amnesia, recreational visual deficits, memory
repetitive movements, drug use, loss (Verbal >
wandering, confusion encephalitis, visuospatial)
develop
delay, stroke,
focal brain
lesions
FH of
epilepsy
Idiopathic relatively self-limited, no underlying pathology; normal considered

(primary) medication responsive development genetic
generalized > focal

Childhood absence seizures ("spacing idiopathic generalized epilepsy EEG: 3Hz spike wave good prognosis,
Absence out") syndrome; genetic resolves by teenage
Epilepsy years
onset age: 3-8 y.o.
frequent daily seizures
normal development
Juvenile myoclonic (muscle idiopathic generalized epilepsy seizures can be most FH EEG: 4-5Hz spike wave lifelong valproic acid or requires lifelong
Myoclonic twitching), GTC seizures syndrome; genetic triggered by common lamotrigine treatment, medication
Epilepsy EtOH or lack of idioathic responsive
onset age: 13-20 y.o. sleep generalized exacerbated by AEDs like
rare GTC, myoclonic epilepsy carbamazepine &
seizures in AM phenytoin
normal development
Benign simple partial seizures or idiopathic localization related EEG: centro-temporal spikes good prognosis -
Epilepsy with secondary GTC seizures epilepsy syndrome remission by teenage
Centro- years
temporal onset age: 4-10 y.o.
spikes infrequent nocturnal
(BECTS) seizures
normal development
Variants
Symptomatic frequent seizures, difficult to structural or metabolic neurologic

control abnormalities
focal > generalized

Lennox- any type of seizures can symptomatic (structural or EEG: 1-2Hz slow spike wave poor prognosis, very
Gastaut occur (GTC, atonic, tonic) metabolic) generalized epilepsy difficult to control
Syndrome syndrome
onset age: 1-6 y.o.
very frequent seizures
a/w mental retardation &

abnormal MRI
Temporal simple partial or complex symptomatic localization related EEG: temporal spikes often refractory to meds, but poor prognosis for
Lobe partial seizures epilepsy syndrome; structural MRI: mesial temporal surgery can be curative (80- remission; often
Epilepsy (abnl MRI) or unknown (nl MRI) sclerosis (scarred 85%) refractory to meds
age of onset: ANY hippocampus)
+/- cognitive dysfunction

Nocturnal seizures occur most often mean age Carbamazepine or other
Frontal Lobe during sleep! (most of onset AED
Epilepsy common in stage2 sleep so 14y (mostly
(NFLE) early in night) kids) Safe environment
Seizure clusters (up to 70% men

20/night), occassional
daytime events in 1/3 pts, +/-
recall, stereotyped
behaviors, a/w frontal lobe
lesions
Can mimic non-REM sleep

disorders (confusional
arousals, night terrors, sleep
walking)
Focal seizures (general) symptoms vary depending on more MRI of brain with and without
location of seizure activity (i.e. common in gadolinium
temporal - hallucinations, dj adults
vu; occipital - visual (acquire risk EEG, asleep & awake
disturbances; motor cortex - factors;
disruptive motor coordination) complex
partial
aura of any kind indicates seizures)
focal onset of seizure
Simple partial no loss of consciousness small focal seizure (abnl electrical

(auras) discharges)
variable S&S (motor,
sensory, autonomic,
psychic); if temporal lobe
source - dj vu, olfactory/
gustatory hallucinations,
epigastric rising sensation
Variants
Complex loss of consciousness; focal seizure focal brain require brain MRI to look for AEDs or if refractory to
partial lasts 1-2m lesion (tumor, causative agent multiple meds, surgical
AVM, abscess, resection
automatisms (involuntary old stroke, post- EEG: focal spikes over
non-purposeful behaviors: lip trauma, mesial epileptogenic focus
smacking, repetitive arm temporal
movements, eye blinking), sclerosis, HIV
dementia,
S&S can vary depending on Alzheimer's)
area of seizure activity
(aphasa if left temporal lobe,
often occur at night if frontal
lobe)
amnesia
post-ictal confusion or
weakness
Secondarily convulsive seizure evolves from focal seizure to Todd's paralysis
generalized bilateral, convulsive seizure (transient, post-ictal
tonic-clonic hemiparesis CL to
seizure focus)
Generalized (general) abnl electrical activity starts deep more
seizures in the brain then simultaneously common in
spreads to all areas of cortex kids
Tonic-clonic loss of consciousness; most

lasts 1-2m; tonic (fall with common
muscular rigidity) followed type of
by clonic (rhythmic jerking; seizure
fast jerks then slower jerks);
cyanosis & ictal cry
(respirations inhibited)
lateral tongue bite common;

bladder/bowel incontinence;
postictal confusion
Absence brief loss of awareness; 2nd most kids EEG: 3Hz generalized spike & AEDs: ethosuximide & often misdiagnosed as
lasts 5-20s common waves valproic acid ADHD
seizure
staring spells; subtle
movements/ automaticisms
(eye blinks, head nod),
no aura
no postictal period
ALWAYS start in childhood

& resolve before adulthood
Myoclonic brief shocklke muscle may progress to

contractions in head, generalized tonic-clonic
shoulders, & upper seizure
extremities
consciousness preserved,
precipitated by waking
Clonic
Tonic
Variants
Atonic loss of consciousness, kids a/w developmental

sudden onset & lasts few delay
seconds (but very frequent
in number!!) very difficult to treat
(poor prognosis)
often a/w falls; can be subtle

(head drop); "drop attacks"
so injuries common
Psychogenic no tonic phase, clonic conversion EEG: normal brain activity

seizures jerkings do not slow down like disorders throughout
characteristic GTC seizure;
very irregular movements
last up to 45 minutes
(normally seizures last 1-2m
at most)
Stroke (general) apopletic (sudden onset) 4th leading age, M>F, Stat labs: CBC (severe anemia, IV t-PA if sx onset w/I 3h clinical pic cannot
cause of race (A.A.), thrombocytosis), chem panel window (DO NOT give tPA reliably differentiate
5SUDDENS (weakness/ death geographic (hypoglycemia?), PT & PTT if subacute ischemia or types of strokes!
numbness on one side, region (blood clotting d/o?), cardiac hemorrhage!!)
difficulty speaking or leading (Stroke belt) biomarkers (acute stroke pts at do NOT treat high BP in Prevention: HTN (ARBs,
understanding speech, cause of risk for MI), EKG (r/o acute ischemic stroke ACE-i), hyperlipidemia
difficulty walking/ dizziness/ long-term CHF (poor cardioembolic source & afib), (unless above tPA criteria of (statin), DM
loss of balance, loss of vision disability heart fxn), noncontrast CT scan of brain 185/110) (HbA1c<7%), smoking
in one or both eyes, severe cardio- (nl CT proves ischemic stroke post-tPA mgmt? ICU, BP < (nicotine patch,
headache) blacks are myopathy - cannot see acute ischemic 180/105, neuro checks for bupropion), limit alcohol,
at higher (stasis of change) ICH, avoid meds that inc diet hi in fruits/ veggies,
Act F.A.S.T. (face, arm, mortality blood), HTN, bleeding, aspirin after 24h aerobic ex (>20m,
speech, time) risk than afib, CAD, no improvement w/ IV 3x/wk), avoid
other smoking, DM, tPA? clot retrieval devices, sympathomimetic
races; EtOH, BMI intra-arterial tPA to site of agents (Claritin D) &
stroke at clot, aspirin estrogen
earlier age etiologic eval (DWI MRI,
in blacks carotid duplex, TTE, young
pts need sickle cell &
hypercoag workups)
Ischemic lack of blood flow due to clots TOAST criteria 85% of

occluding artery (deprives brain (athero- strokes
of O2 & glucose needed for sclerotic, small
energy production) vessel/ lacune,
cardio-embolic,
Large vessel causes: other,
atherosclerosis, inflammation, cryptogenic)
arteritis
THROMBO-
Small vessel/ lacunar: EMBOLISM =
lipohyalinosis, vasculitis, embolic MOST
COMMON
Cardioembolic source: CHF, afib, CAUSE!
cardiac myxomas
Cardioembol,
Other causes: coagulopathies atheroscl,
(Protein C, S def, AT3 def, sickle hypercoag,
cell, myeloprolif d/o, DIC, TTP, arterial diss/
elev homocysteine), aortic vasculitis,
dissection
small vessel
dz,
hypotension
Variants
Hemorrhagic In addition to SUDDENS, can bleeding into the brain tissues aneurysms, 10% of more fatalities than
also have vomiting & (intracerebral hemorrhage) --> arteriovenous strokes ischemic strokes
headache more than mass effect malformations,
ischemic uncont HTN,
tumors,
hemorrhagic
conversion of
infarct, amyloid
angiopathy
Sub- Headache more prominent in bleeding around the brain, into the aneurysms, 5% of
arachnoid SAH than ischemic subarachnoid space but not within AVM, idiopathic, strokes
hemorrhage the brain tissue --> raised ICP, trauma
hydrocephalus, vasospasms
Stroke Left MCA aphasia (loss of fluency, CT scan -

syndromes stroke naming, comprehension,
reading/ writing, repetition),
left gaze deviation (loss of L
FEF), R homonymous
hemianopsia (loss of L optic
radiations), R face & arm
weakness > leg weakness
Right MCA contralateral neglect (left

stroke hemineglect- denial of
weakness, limb; visual/
auditory/ sensory neglect),
right gaze deviation, left
homonymous hemianopsia
(loss of R optic radiations),
left face & arm weakness >
leg weakness
Left ACA aphasia? Apathetic, right

stroke leg weakness >> right arm
weakness
Right ACA apathetic, left leg weakness
stroke >> left arm weakness
Vertebral crossed signs (ipsilateral posterior circulation stroke MRI: hyperintensity in inferior
artery / PICA face numbness + (vertebral artery, PICA) produces cerebellar territory
stroke contralateral arm & leg lesions in brainstem
numbness), vertigo,
dizziness, n/v, Horner's PICA supplies the inferior portion
syndrome (ptosis, misosis, of the cerebellum & lateral portion
anhidrosis), ipsilateral ataxia of medulla
Basilar artery Quadriplegia or hemiplegia, basilar artery infarct produces MRI: hyperintensity in brainstem
stroke nystagmus, crossed signs, lesions in the perforators that feed
(locked in vertigo, diplopia, n/v, the brainstem; the amount of
syndrome) - ipsilateral ataxia perforators affected correlates w/
see above for symptoms
basilar
pontine
infarction
Variants
Lacunar pure motor hemiparesis (if small (<1.5 cm diameter), deep long standing CT: small round hypodensity
syndromes affects internal capsule), infarcts in territory of the deep HTN --> (darker) in deep white matter or
pure sensory stroke (if penetrating arteries lipohyalinosis --> subcortex from infarct of
affects thalamus), or ischemia penetrating arteries
sensorimotor stroke (if pure motor hemiparesis affects
between internal capsule & internal capsule & corticospinal
thalamus) tracts
ataxic hemiparesis, clumsy

hand dysarthria (weak hand
+ slurred speech)
Tremor (general) involuntary rhythmic alternating or synchronous Parkinsons, most

oscillating movements contraction of reciprocally Essential common
innervated antagonist muscles tremor, drugs movement
(lithium, valproic disorder
acid,
neuroleptics,
stroke), rubral
(stroke, MS)
Rest tremors occur during rest Parkinsonism
Postural occurs while body part is

tremors maintaining posture against
gravity
Kinetic occurs during goal-directed essential check meds!!
(action, movements tremor,
intention) physiologic
tremors (caffeine, stress,
meds, drugs)
Mixed tremor combination of above MS, stroke

tremors; rugral tremor (slow,
occurs at rest, posture, &
action)
Task specific occur during specific tasks
tremors like writing, playing musical
instruments
Rigidity increase in resistance to Parkinsonism
passive movements
stiffness but not major

disability
"lead-pipe"
"cog-wheeling"
Akinesia/ slowness / fatigue or arrest Parkinsonism

bradykinesia in ongoing movements
interferes w/ all activities

and very disabling
Variants
Dystonia involuntary sustained co-contraction of muscle agonists generalized - kids - Ashkenazi genetic testing not very helpful Anticholinergic drugs - well
muscle contractions that & antagonists genetic origin generalize jews (DYT1) bc low penetrance tolerated in kids but difficult
produce twisting/ squeezing (DYT1), kids dystonias to use in adults
movements & abnl specific dystonias? Writer's any pt w/ dystonia needs to
postures; may be cramp, DYT1 generalized focal dystonias - adults - be tested for Wilson's disease muscle relaxants, PT - less
stereotyped or repetitive; dystonia (AD w/ low penetrance) excessive use, focal (24h urine copper, eye exam for useful?
usually action induced & adults dystonias KF-rings) and given tx trial of
worsen w/ stress/ fatigue DYT1 - early onset; likelihood of dz Levodopa (check to see if Pallidal DBS - indicated in
is 0 if no sx onset by age 26 Primary Levodopa-responsive!) DYT1 generalized dystonia,
can be a/w tremor (jerky) dystonias cervical dystonia, tx
focal dystonia - action dependent refractory dystonias; slow
blepharospasm (invol (related to overuse of muscle) Wilson's onset of effect
closing of eyes), use of disease
"tricks", generalized Botulinum toxin - indicated
dystonia usually begins in Dopa- for focal dystonias
legs responsive
dystonia
contractions stop during
sleep
Chorea excessive, spontaneous Huntington's
movements that are chorea
irregularly timed, non-
repetitive, & randomly tardive
distributed dyskinesia
(iatrogenic -
involves multiple body parts Levodopa in PD
pts)
Tic repetitive, brief, rapid, Tourette's
involuntary, purposeless, & syndrome,
stereotyped movements OCD, excessive
blinking
can be suppressed
temporarily by the pt
Myoclonus rapid, shock-like, Alzheimer's

arrhythmic & repetitive disease, prion
involuntary movements disease, drugs
generalized, focal, multifocal
lasts milliseconds in duration
negative myoclonus
(asterixis) - muscle becomes
silent --> jerky flaps; result of
liver/renal disease, metabolic
d/o, or drugs
Variants
Parkinson's (Parkinsonis tremor at rest, rigidity inc output from basal ganglia = PD, stroke- high risk of falls!
disease m) (cogwheeling), inhibition of cortex induced (rapid,
bradykinesia/ akinesia stepwise prog), Dyskinesia/ dystonia
(masked face, freezing, PSP (abnl eye from Levodopa tx
difficulty getting up from movements),
chair,no arm swing, difficulty drug induced
turning), gait d/o (symmetric),
(festination/ shuffling, post toxins (MPTP),
instability, freezing, no arm drugs
swing), flexed posture, NO (neuroleptics),
voice tremor Wilson's dz,
neurodegen d/o
Other S&S: sialorrhea
(drooling), hypophonic
speech (fast, low volume),
dystonia, autonomic dysfxn,
sleep probs, depression,
micrographia
early signs? trouble

maintaining plan of action,
hyposmia
PD bradykinesia + one of loss of cells in SNc = fast loss sporadic M >= F old age, Path: SN & red nucleus look 1. protect neurons late stage? Orthostatic
cardinal features (rigidity,
of dopamine (oxid damage, (>80%), genetic MPTP, toxin pale, Lewy body formation (exercise), 2. treat sx (mild - hypotension, aspiration,
resting tremor, postural mitoch damage, inflamm, protein (<20%) 5-24/ 10^5 exposure Histology: Lewy bodies in SNc amantadine; tremor - dementia
instability) aggregation) = change in incidence (herbicides, (composed of alpha synuclein & anticholinergics; depression -
striatum anatomy (loss of genetic suscept (inc w/ aging heavy metals, found in Lewy neutrites) anti-depr, anxiety - benzos;
asymmetric mode of onset, medium spiny neurons) + environm pop) wood severe sx - dopamine
unilateral tremor factors preservs), agonists, L-
possible that PD ascends: BS to head trauma DOPA/carbidopa)
slow progression - 15y to SN to cortex
develop possible too many side effects or
Low dopa ultimately affects protective ineffective? Surgery/ DBS
NOT seen in PD: cerebellar transmission (inc basal ganglia factors? directed at thalamus,
signs, early autonomic output @ putamen = abnl firing Caffeine, internal segment of globus
failure, gaze palsy, early patterns = disrupted cortical smoking, anti- pallidus, or STN
dementia processing), striatum anatomy, inflamm drugs
other organs (cardiac denervation, treatment of non-motor sx:
oropharyngeal muscle dysfxn) depression, sleep d/o,
orthostatic hypotension, etc.
genetic? young onset, rapid
progression
sporadic? susceptibility loci
Variants
Essential tremor Action/ kinetic tremor (goes unknown 1-6% of FH beta blockers (propanolol) more rapid progression
away with rest) - present population in younger patients &
throughout ENTIRE 5x risk increased if first degree (most primidone (precursor of those without head
movement relative w/ ET common GABA receptor binding tremor (head tremor
movement barbituates) - try first in =better prognosis)
exaggerated by fatigue, d/o) elderly patients!
stress, & caffeine; side effects of BB -
diminished w/ alcohol bimodal age Surgery - but some bradycardia, dizziness;
of onset interventions do not last contraind in DM &
location: upper extremities (peaks in very long depression
> head > voice > leg/ chin early adult &
later side effects of primidone
often asymmetric adulthood) - cognitive effects (fuzzy
memory)
M=F
Progressive shock/astonished look on Parkinsonism disorder that fall very early in dz

supranuclear face, square wave jerks presents with cardinal features + course!
palsy during fixation & saccadic eye movement abnormalities
intrusions during pursuit, (gaze palsy)
unable to move eyes
vertically, slow optokinetic
nystagmus (occurs when
following an object w/ eyes),
hyperreflexia, "drunken
stumbling"
intact Doll's eye maneuver

suggests intact brainstem
Wilson's disease facial dystonia w/ retraction

of mouth, Keyser-Fleischer
rings in eyes (sunflower
cataracts), fixed dystonia
(does not improve w/ tricks)
Cerebellar Ataxia loss of coordination, Inferior olive sends information MRI of head, TSH, B12, vitE, symptomatic tx of ataxia -
syndromes dysmetria + dysrhythmia, directly to the Purkinje cells, which anti-GAD, anti-gliadin, anti- PT, ?chantix, ?riluzole -
dyssynergia, abnl normally inhibit the deep cerebellar tissue transglutaminase, reduces deep cerebellar
regulation of movement nuclei (output system of ?ceruloplasmin, anti- nuclei hyperexcitability
speed/ force/ distance cerebellum); in ataxia, the thyroglobulin, genetic testing
(movement delay, Purkinje cells become (depending on phenotype) symptomatic tx of assoc sx -
dysdiadochokinesia) disinhibited, therefore the deep swallowing, spasticity, pain,
cerebellar nucli are depression
abnl eye movements (gaze- hyperexcitable
evoked nystagmus, impaired disease modifying tx -
smooth pursuit - jerky acquired (primary) = idiopathic lithium for SCA1, dantrolene
saccades, inability to late onset cerebellar degen, MSA, for SCA2, HDAC inh & anti-
suppress vestibulo-ocular autoimmune (paraneoplastic oxidants for FRDA
reflex by fixation) degen, anti-GAD65, gluten ataxia);
(secondary) = hypothyroidism,
stroke, MS, tumor, vitE def, toxic
inherited (AD, AR,

Mitochondrial, X-linked, inborn
errors) - a/w inc genetic repeats
Variants
Toxic chronic alcohol history? Alcohol can cause midline atrophy EtOH, lithium,
syndromes Midline cerebellar atrophy, of cerebellum AEDs
legs & trunk >> arms, (phenytoin,
speech spared Acute lithium toxicity can lead to carbamazepine,
permanent cerebellar damage oxcarbazepine),
amiodarone
Machado- ataxia, dysarthria, mild autosomal dominant disease w/

Joseph ophthalmoplegia, large degree of phenotypic
Disease periocular or perioral variability & hi genetic anticipation
(MJD) = fasics, dystonia
SCA3
neuropathy, motor neuron
disease, dystonia,
parkinsonism
Friedreich's Neuro: ataxia, dysarthria, autosomal recessive ataxia with sx onset in late most Indo- supportive (balance,
ataxia areflexia (loss of strong founder effect childhood/ common European orthotics)
(FRDA) reflexes),extensor plantar (IndoEuropean races) adolescence inherited races
responses, loss of vibration/ ataxia (1/30- anti-oxidants? HDAC
position sense, others mutation in frataxin 50K) inhibitors?
(nystagmus, weakness (trinucleotide repeat GAA); inc
legs>arms, blindness, hearing repeats = inc clinical severity
loss, incontinence)
Spinal cord pathology: loss of
cardiomyopathy, glucose dorsal colums, spinocerebellar
intolerance/ DM, scoliosis, tracts, corticospinal tract
pes cavus Peripheral nerves: damage to
dorsal root ganglion
CNS: affects brainstem &
cerebellar nuclei
heart: fibrotic cardiomyopathy
(hypertrophic)
Anti-GAD stiff person syndrome, autoimmune process where

ataxia cerebellar ataxia, downward antibodies are made against
nystagmus, adult onset GAD65 --> CNS disease and
epilepsy, or autoimmune pancreas diseases like DM
encephalitis - sx vary w/
spectrum of anti-GAD
antibody burden
MSA Multiple Systems Atrophy = death within 5-10y

Parkisonism + cerebellar
ataxia + autonomic
dysfunction
Axial/ midline wide stance & gait, nodding midline problem in the cerebellum
ataxia tremor, nystagmus
syndrome
Appendicular dismetria, random alternating problem with cerebellar inputs &

ataxia movements, discoordination outputs (peduncles)
syndrome w/ limb motor dexterity
superior peduncle - midbrain
middle peduncle - pons
inferior peduncle - medulla
Variants
Huntington's slowly 90% adult onset; duration of Autosomal dominant mutation in AD inheritance 5-10/100K FH histology: substantial loss of NONE - progressive & fatal discuss end of life
disease progressive, 15-30+y the huntingtin gene, leading to w/ hi penetrance medium spiny neurons in issues
degenerative unstable expansion of CAG basal ganglia striatum, manage symptoms & social
neuro- dx requires FH or genetic repeats (nl < 26) in the polyQ huntingtin intranuclear inclusions w/ support
psychiatric confirmation + typical area gene mutation mutant Htt aggregates
d/o choreic movements Movement d/o: PT, OT,
Htt role unknown? Protein folds pathology: severe atrophy of speech & swallowing
cognitive decline: slow incorrectly --> aggregation --> caudate nucleus (but also therapy, tetrabenazine if
thinking & distractibility, dysreg transcription & abnl RNA atrophy of other brain regions) chorea affects ADLs
impaired visual spatial prod, mitoc dysfxn, & oxid Attention deficits: one task
abilities, impaired memory, damage; protein is cleaved & MRI: inc CSF (due to atrophy) @ a time, avoid meal
attention deficits, impaired forms polyglutamine fragments distractions
executive fxn (toxic!) FH & typical movement disorganization: routine, to
emotional disturbances: disorders; genetic testing if FH do lists, step by step
depression, impulsivity, unknown instructions
irritability, OCD, anxiety, decision-making: simple
psychosis, personality/ beh choices, no open ended ?
change depression: anti-
movement d/o: eye depressants, psychotx early
movement abnl, chorea, in dz
dystonia, bradykinesia impulsivity: remove
temptations (guns, alcohol,
keys), mood stabilizing
Juvenile bradykinesia prominent & 10% of meds
onset early (chorea less Huntington's
prominent), rigidity, tremor, is juvenile clinical trials
seizures, dystonia, myoclonic onset
jerks, school
failure,behavioral probs
Multiple Relapsing- Charcot's triad (SIN: autoimmune inflammation & gen leading females, MRI of brain: white plaques in Vitamin D supplements avg lifespan 65y
Sclerosis (MS) remitting Scanning speech, Intention demyelination of axons, predisposition + cause of geography CNS (lowers dz severity),
(80%), tremor/ Incontinence/ interrupting the flow of electrical abnl immune non- (inc risk if far CSF analysis: Inc IgG & manage sx men more likely to
primary Intranuclear impulses in the CNS system (EBV, traumatic from equator), oligoclonal bands from B develop chronic
progressive ophthalmoplegia, low vitD, disability in vitD def, cells (suggests BBB breach) Glatiramer acetate (GA)- progressive form of
(10%), Nystagmus) negative sx (weak/numb) - due smoker) --> abnl young smoking, Evoked potentials: slowed (lossmimics myelin so it is disease
secondary to loss of conduction (low # Na attack on CNS adults EBV+, FH, of myelin) attacked instead of actual
progressive, bladder/ bowel probs channels) --> nodal widening & HLA-DRB 1 histology: loss of myelin, myelin on axons a/w other autoimmune
progressive (constipation, urgency, disbursed electrical current = dec Th1 cells 70% gene hypocellular OR dz like thyroiditis &
relapsing incontinence), cognitive safety factor & instability of secrete IFN-y & women, beta-IFN - reduces the # of psoriasis
difficulties, depression, demyelinated axons Th17 cells 8500-10K circulating & activated T
fatigue, muscle rigidity/ secrete IL-17 & new cases sx exaceberated by temperature cells by dec MMP With every 1 clinical
stiffness, hemiparesis, remission occurs (sx Il-23, recruiting per yr & fever generation event, on average, there
hemisensory loss, vision improvement) when: inc Na+ microglial cells Natalizumab - SAM are 5-10 new lesions
changes (optic neuritis = channels, dec inflamm & NO, & that display age of genetically inhibitors (blocks a4
sudden loss of vision), pain, glial ensheathment; remyelination myelin; B cells onset: 15-50 protected? integrin, preventing T cell More attacks = more
(but shorter internodes than nl) make Abs -- Eskimos, migration across BBB) brain damage = more
ataxia, hemiparetic gait
>demyelination Native Fingolimod blocks T cells brain atrophy
(circumduction, semi-flexed
arm) positive sx (tingling, Lhermitte's) - & axonal Americans, from leaving LN
hyperexcitable response to transection Hungarians inflammatory dz -->
demyelination IV steroids for relapses neurodegenerative dz
dx: mult lesions in time &
space
Variants
Dementia (general) acquired, persistent, severe characterized by acquired AD, FTD, Lewy increased history, neuro exam, blood tests very vulnerable to
impairment of multiple areas memory impairment + body dementia, incidence w/ (B12, thyroid, syphilis, HIV), delirium
of higher brain functions (>2 performance impairment in CJD, low B12, baby imaging, clinical features
deficits in memory, functional domains (language, HIV, booming (genetics, CSF), neuropsy
language, praxis, visuospatial skills, identification neurosyphilis, population testing
visuospatial skills, skills, executive skills) organ failure,
executive fxn, emotions, hydrocephalus, 50% of Montreal cognitive assessment
personality) subdural people >85 or MMSE
hematoma, MS, have
cog complaints: altered PD, TBI, dementia logical memory (read a
consciousness, difficulty pseudodementi paragraph then talk about what
performing tasks/ finding a, TB, was read), word recall
words, disorientation in depression, (immediate & delayed), naming
familiar locations, misplacing brain tumors, test (line drawings)
objects in weird places, vascular
repeating ?, loss of initiative, infarcts executive fxn (connect the dots,
inappropriate clothing, clock drawing)
disregard for personal
appearance, personality visuospatial (intersecting
change pentagons)
Alzheimer's memory loss dramatic loss & degeneration of amyloid most age, Down CT: mesial temporal atrophy symptomatic? AChE
disease neurons containing ACh accumulation -> common syndrome, PIB: increased amyloid inhibitors (donepezil,
neuron injury--> type of head trauma, burden galanthamine, rivastigmine),
90% of AD is sporadic- with age, tau release -> dementia depression, CSF: measure biomarkers like memantine
amyloid clearance mechanisms AD clinical HTN, hyper- beta-amyloid & tau protein
slow down; amyloid aggregates symptoms F>M cholesteremia (predicts MCI conversion to AD) Neuroprotective? VitE
forming oligomers --> Beta- , hi
amyloid deposits in neuritic FAD: APOE4 homocysteine pathology: brain atrophy,
plaques --> neurotoxicity & AD gene, , low B12/ neurofibrillary tangles, senile
sx presenilin folate amyloid plaques
genes, APP
tau protein accumulates in mutations protective?
neurofibrillary tangles, which Education,
correlate w/ sx & degree of exercise, Med
dementia diet, NSAIDs,
statins, red
10% of AD has familial form: early wine
onset (<65y.o.), autosomal
dominant w/ 100% penetrance
(mutations in APP, presenilin-1,
presenilin 2, or ApoE4)
Lewy Body dementia + Parkinsonism thought to be an intermediate at risk genes? 10-20% of FH cannot be distinguished d/c anticholinergics, lower
dementia (bradykinesia/ rigidity) + syndrome between AD & PD APOE4, dementia neuropathologically from doses of dopaminergics
psych sx (hallucinations, mutation in Parkinson's dementia
delusions, depression, decreased cortical ACh & alpha- M>F AChE inhibitors,
anxiety), fluctuating striatal dopamine synuclein antidepressants, atypical
cognitive state (attention/ age of antipsychotics
arousal), other features (REM formation of amyloid plaques, onset? 50-
behavior d/o, autonomic neurofibrillay tangles, & Lewy 80
dysfxn, neuroleptic sensitivity, bodies
rapid progression compared
to PD, poorly tolerated cortical Lewy bodies & Lewy
dopaminergics) neurites widespread in DLB
(correlate w/ dementia severity); a-
distinguished from PD bc synuclein = major component of
dementia begins at around Lewy bodies
same time as dementia sx
Variants
Fronto- syndromic dx TDP-43 (normally a nuclear histology: Frontotemporal

temporal transcriptional regulator) lobar degeneration w/ lesions
dementia Behavioral variant FTD undergoes translocation to form displaying Pick bodies
(bvFTD) - 3 of following: early hyperphosphorylated (intracellular, aggregated tau
disinhibition, early apathy, cytoplasmic inclusions in FTD protein), immunoreactivity to
early loss of sympathy/ TDP-43 or FUS
empathy, early ritualistic Tau can also become
behavior, hyperorality/ diet hyperphosphorylated --> MRI: frontotemporal atrophy
changes, exec deficits w/ microtubule dysfunction (bvFTD), subtle left atrophy
sparing of memory & (PPA)
visuospatial fxns FUS unclear
Primary progressive autosomal dominant mutations

aphasia (PPA) - semantic in MAPT and progranulin
dementia, non-fluent variant,
intermittently fluent w/ word TDP a/w ALS
finding pauses Tau a/w PSP
FTD plus - FTD + ALS or

PSP
Progressive falls early in disease course;
supranuclear abnl eye movements
palsy
Delirium inability to sustain, direct, drugs/ toxins (EtOH intox/wd, I WATCH strongly dementia see patient serially over time to
or appropriately shift sedatives, opioids, DEATH associated patients evaluate fixed/fluctuating sx
attention - due to CNS anticholinergics), endocrine (infection, with
process or another organ (hypo/hyperthyroidism, withdrawal, morbidity & Psych mental status exam (ABC
system affecting CNS hypo/hyperglycemia), electrolytes trauma, CNS mortality STAMP LICKER - appearance,
(hypo/hypercalcemia, path, hypoxia, behavior, cooperation, speech,
impaired attention (waxes & hyponatremia), nutritional deficiency of thought, affect, mood,
wanes) (thiamine), organ system dysfxn vitamins, perception, level of
(CHF, MI, pneumonia, COPD, PE, endocrinopathy, consciousness, insight,
large variability in the level of pancreatitis, renal failure, UTI), acute vascul cognition, knowledge, endings -
arousal, +/- visual infectious (meningitis, insult, toxins, suicidal/ homicidal, reliability)
hallucinations, autonomic encephalitis), vascular heavy metals)
instability (hypertensive encephalopathy, MMSE or MoCA, UDS, CT scan
SAH, SDH, ICH), head trauma, brain mets (r/o head trauma), CBC, CMP
epileptic seizure (melanoma,
colon, breast,
prostate, renal
transitional cell)
Consciousness Awake & alert fully aware of self &
environment
Lethargic mildly depressed
consciousness, easily
aroused to wakefulness
Obtunded moderately depressed
consciousness, aroused w/
stimulation to answer
questions but lapses back
without verbal/ tactile
stimuli
Stuporous deeply depressed
consciousness, aroused by
vigorous & repeated stimuli
(require these stimuli to
respond)
Variants
Comatose cannot be aroused to total absence of awareness of BS: trauma, Neuro exam!! Respiratory Brain oriented ICU - balance within a few months,
consciousness despite self & environment (lack of brainstem patterns, pupillary light cerebral metabolic supply patients either die, end
stimuli used sleep/wake cycles, lack of stroke/ hemorr responses (loss suggests with cerebral metabolic up in vegetative state, or
consciousness) Both struct damage), eye demand and minimize cpds recover (various
decorticate posturing hemispheres: movements (Oculocephalic that worsen neuro damage degrees)
(flexor)- damage to upper impaired RAS in the brainstem bilateral testing, oculovestibular), &
midbrain or diencephalon OR damage to subdural motor responses (posturing)
decerebrate posturing BOTH cerebral hemispheres hematomas,
(extensor) - damange to lower from structural or large/ lots brain EEG can suggest various
midbrain/ upper pons metabolic/toxic injury tumors, inc ICP, causes (liver failure, seizure,
Cheynes- Stokes resp - liver degen dz drugs)
failure or toxic insult to brain metab/toxic:
Central neurogenic hypoxia, MRI to r/o reversible causes
hyperventilation - midbrain ischemia, hi/low
lesion gluc, hi/low Na+, Glasgow coma scale -
apneusis - ischemic stroke to hypo-thyroidism, assessed for eye opening,
pons drugs, liver verbal output, & motor response
cluster breathing - lower failure, to pain (lower score = more
pons lesion hypercarbia, comatose)
ataxic breathing - medulla sepsis,
lesion meningitis
Persistent wakefulness without brainstem functions without hypoxic pathology: diffuse laminar >3m of PVS, functional
vegetative state awareness cortical function ischemic necrosis of cerebral cortex w/ recovery is rare
(PVS) encephalopathy extensive hippocampal
intact sleep/wake cycles, eat glucose in cerebral cortex is (most common involvement
food placed in mouth, greatly reduced, to a degree cause of PVS)
smile/cry, fixates visually on incompatible w/ consciousness
objects or orients head to
auditory stimuli, non
purposeful limb movements
actions have no cognitive

content
Minimally severely altered hypoxic can be permanent or

conscious state consciousness w/ minimal ischemic transitional state
(MCS) but definite behavioral encephalopathy,
evidence of self or TBI, stroke,
environment neurodegen dz,
metabolic d/o,
reproducible evidence of tumors,
awareness (speech,yes/no congenital or
responses, purposeful developmental
behaviors like following d/o
commands)
emergence: functional
interactive communication
and/or functional use of
two different objects
Variants
Brain death documented loss of irreversible loss of all brain & Brain stem reflexes (pupillary medical record apnea test should be
consciousness (coma) + no brain stem function light, ocular movements, facial documentation: etiology & done last (risk of
brain stem reflexes + apnea sensation & motor responses, irreversibility of condition, pneumothorax,
pharyngeal/ tracheal reflexes) absent brainstem reflexes, arrhythmias, &
NO motor/facial responses absent motor response to hypotension)
to pain (nail bed pressure, apnea test (no respirations at pain, rpt neuro exam,
sternal rub, nasal tickle), CO2>60 mmHg) absence of respiration w/ hi confirmatory tests
absent pupillary response, pCO2, justification & results have hi rates of false
round/ oval pupils, no doll's confirmatory tests (cerebral of confirmatory tests, time negatives so done if
eye or caloric testing angiography, EEG, transcranial of death (time last test is clinical exam cannot be
movements (eyes stay fixed doppler u/s, isotope completed) performed properly!
in skull), absent corneal angiography) if pt cannot reliably
reflex, absent cough undergo clinical testing
response to bronchial components
suctioning
REPEAT CLINICAL EXAM!
Axonal (general) usually affects both Metabolic, majority of HbA1C or 2h GTT, TSH, B12,
polyneuropathy sensory AND motor fibers endocrine (DM), poly- serum protein electrophoresis
meds/ toxins, neuropathy (multiple myeloma), ESR/CRP
symmetric & distal: nutritional (B12
Stocking-glove distribution def), connective
(Legs>arms), absent ankle tissue (SLE,
jerks Sjogren's)
chronic (if acute, think about

vasculitis)
Diabetic burning pain, reduced pin involves small C fibers (pain), as 30% poor glycemic exclude other causes (meds, control DM, neuropathic 7x increase for diabetic
peripheral prick & temp sensation well as sensory large fibers prevalence control, toxin exposure, combordities) pain mgmt (Neurontin, foot ulcers on soles of
neuropathy (vibration, mechanical sensation) among advanced Lyrica), foot care! feet!
absent ankle jerks diabetics age, HTN, NCS, HbA1C, autonomic testing
longer Charcot's joints
symmetric distal pain/ duration of (severe diabetic
burning, mild weakness, +/- DM, neuropathy +
autonomic involvement dyslipidemia, osteopenia -->
(postural hypotension, smoking, calcification of vascular
arrhythmias, bowel/bladder heavy alcohol smooth muscle & degen
probs) intake, HLA of bones --> changes in
DR3/4 navicular bone of foot --
> dysmorphic feet
(requires joint fixation/
surgery to repair)
Myelinopathy (general) motor> sensory symptoms inflammatory cells attack myelin -- acquired: acute NCS: conduction block (20%
> segmental demyelination in both GBS, chronic drop in amplitude btwn proximal
moderate -severe weakness sensory & motor fibers --> CIDP & distal sites)
w/ normal muscle bulk eventual total demyelination
Inherited: CMT
areflexia, hypertrophic
nerves
Variants
Guillain- ACUTE ascending immune mediated process (T most no familial or NCS: absent F-waves & IV Ig, plasma exchange majority of pts
Barre weakness, absent reflexes, cells)--> inflammation & common occupation conduction block recover; 15% have NO
Syndrome can involve CN7 (facial demyelination of peripheral nerves cause of triggers NO CORTICOSTEROIDS! residual deficits, 50-65%
(GBS) paralysis) & autonomic & motor fibers of ventral roots acute identified CSF: elevated protein w/ nl are restored 2/3 normal
dysfxn (cardiac irregularities, generalized amount of cells (however, CSF Admission to ICU if fxn, 10% have
HTN, hypotension) paralysis will be nl during first 48h so autonimic dysfxn persistent severe
does not necessarily exclude weakness
PRECEDING ILLNESS (often 0.6- GBS)
GI - Campylobacter jejuni; 1.9/100K mechanical ventilation
CMV, EBV, HSV, influenza, MRI if suspect spinal cord a/w 15-30% mortality
mycoplasma), immunization, all age involvement
recent surgery or renal groups
transplantation
may be a/w Hodgkin's dz,

SLE, HIV?
Myasthenia fluctuating weakness of blocks of neuromuscular occurs at all HLA-DR3 Elevated level of serum AChR Anti-cholinesterase drugs can be a/w thymic
gravis (MG) VOLUNTARY muscles --> transmission due to ages women antibodies (sensitivity 80-90%) provide symptomatic benefit tumor, thyrotoxicosis,
diplopia, ptosis, difficulty AUTOANTIBODIES binding to RA, SLE
swallowing/ breathing AChR on postsynaptic CT scan of chest to R/O steroids if poor response to
membrane --> 1) decrease in thymoma AChE inhibitors aspiration pneumonia,
weakness may fluctuate in number of available receptors, 2) myasthenic crisis -->
intensity throughout the day less surface area due to NCS - decreased muscle thymectomy (symptomatic respiratory weakness
architectural change of response to repetitive benefit or remission) -
nl pupillary responses postsynaptic membrane --> less stimulation considered in all pts <60
ability to depolarize the
insidious onset, membrane --> chronic muscle increased strength following
exacerbated by menstrual weakness administration of AChE
period/ pregnancy inhibitor
AChR antibodies lead to
destruction of the AChR by
activating complement fixation
OR inducing endocytosis of
receptors (similar to botulinum
toxin)
Motor neuron (general) PAINLESS weakness & progressive course!

diseases atrophy
(anterior horn
cell dz, motor
neuronopathies) cramps, fasciculations
NO sensory loss, NO ptosis

or eye movement probs
cell dz, motor
neuronopathies)
Variants
Poliomyelitis 1-2d nonspecific viral neurotropic enterovirus w/ fecal oral route new cases CSF: neg in early stages, w/I 2w supportive treatment
prodrome (many pts get predisposition for ventral horn poliovirus, eradicated - pleocytosis (inc WBCs) w/
better), minority of pts get in spinal cord & motor cranial Coxsackie virus, in U.S. but lymphocytic predominance,
meningo-encephalitis nerve nuclei --> LMN echovirus, cases of elevated CSF protein
(fever, nuchal rigidity, back destruction enterovirus, post-polio
pain, AMS, +/- paralysis 3- Japanese syndrome Stool/ throat viral cultures;
10d later)--> paralytic encephalitis elevted serum antibodies
poliomyelitis - myalgias & virus, rabies
cramps --> rapidly virus, West Nile WNV - IgM antibodies or RNA in
progressive paralysis virus CSF
(asymmetric, limbs & trunk;
spares CN 3,4,6) &
autonomic dysfxn
post-polio syndrome -
slowly progressive weakness,
occurs ~35y after initial
illness;
LMN signs: muscle

weakness & atrophy,
fascics, hyporeflexia
Spinal SMA1 - Infantile/ Werdnig- progressive hereditary diseases of 4-10/100K

Muscular Hoffmann; first 6m of life--> anterior horn cells & select motor
Atrophy hypotonic (floppy) infants cranial nerve nuclei SMA1 =
(SMA) w/ prox weakness & most
areflexia, tongue fascics, SMN (survival motor neuron) 1 common
abd breathing, ventilatory on chrom 5 is deleted; severity motor
failure; can't sit of SMA depends on #SMN2 neuron dz
independently copies available (more SMN2 =
SMA2 - intermed form; age 6- less severe dz)
18m, sits independently but
can't walk; orthopedic
deformities, > survival than
SMA1, tongue fascics/
areflexia/ prox weak/ hand
tremor
SMA3 - Juvenile form/
Kugelberg-Welander; onset
>18m, nl life expectancy,
prox weakness, areflexia,
tongue & limb fascics
SMA4 - adult onset, rare,
prox weakness
Kennedy's X-linked bulbospinal mutation of androgen receptor mostly

disease muscular atrophy gene on X chromosome males
adult onset, bulbar & median age

proximal weakness, 44
lower extremity weakness

very disabling - wheelchair
dependency
ANDROGEN INSENSITIVITY
- gynecomastia, impotence,
testicular atrophy, infertility
increased incidence of DM
Variants
Amyotrophic LMN signs: weakness, progressive disorder of voluntary 90-95% 1/100K Pathology: degeneration & Riluzole - prolongs no cure - progressive
Lateral atrophy (first dorsal motor system - upper & lower sporadic; death of motor neurons; UMN - survival (2-3m); must & fatal
Sclerosis interosseous muscle, tongue, motor neuron dysfxn avg age = death of Betz cells (cortical monitor LFTs during tx
(ALS) paraspinal), hyporeflexia, 5-10% AD mid 50s spinal tract); LMN - death of variable dz course - if
muscle cramps, fascics cause unknown? anterior horn cells Nuedexta helps bulbar sx initial rapid
UMN signs: spasticity, M:F 3:2 presentation then
hyperreflexia, jaw jerk, Thought to be a continuum that El Escorial criteria (should not spasticity managed by rapid progression
Hoffman sign, Babinski's sign eventually converge to have ALS U.S. prev = be used to preclude clinical dx) baclofen
no cognitive deficit! (i.e. progressive muscular atrophy 30K 50% die w/I 3-4y
is LMN and primary lateral SSRIs, benzos for 20% live 5+y
ASYMMETRIC weakness, sclerosis is UMN; ALS is in the depression/ anxiety 10% live 10+y
local spread, NO sensory/ middle of these two)
autonomic/ eye movement PT/OT/Speech therapy FTD in 5-20%
abnormalities (spares CN bipap for breathing
3,4,6 & Onuf's nucleus)!! nutrition MOST COMMON
CAUSE OF DEATH?
non-motor sx: involuntary, Respiratory dysfxn
unprovoked laughing & (restrictive pattern; sx?
crying; depression & anxiety Inability to lay flat,
frequent nighttime
arousal, EDS, exertional
dyspnea)
Sleep apnea 10% AGE, obesity C-PAP Cardiovascular

prevalence disease (HTN) and
by age 35- lifestyle modifications stroke risk!!
40
Increased rates of
mortality
Insomnia (general) difficulty maintaining sleep 3Ps: predisposition to insomnia most behavior based tx:
(older adults) (decreased homeostatic drive or prevalent improved sleep hygiene,
pressure for sleep; anxiety/ sleep sx relaxation/ breathing
difficulty falling asleep depression/ stress/ worry about exercises, get out of bed if
(young adults) sleep), precipitating factors F>M cannot sleep, restrict time in
(acute stressors - illness, life bed to night, daytime light
events, prescriptions/ herbals/ exposure & physical activity
OTCs), perpetuating factors
(poor sleep hygiene,
counterproductive efforts to solve
sleep issues)
Narcolepsy sudden onset of sleep loss of hypocretin cells in the molecular 1/2000 Polysomnogram: short Behavioral strategies: obesity (hypocretin
(sleep attacks); inability to hypothalamus --> loss of major mimicry & people nocturnal REM latency, signs short/scheduled naps, system also related to
stay awake during the day & excitatory influence to areas certain of disruptive nocturnal sleep, consistent sleep/wake leptin, ghrelin, insulin, &
sustain wakefulness necessary for wakefulness AND infections? periodic leg movements schedule, exercise, good thyroid hormone)
loss of inhibition to PPT so sleep hygiene, avoid
fragmented sleep (unable to early REM sleep & cataplexy --> Multiple Sleep Latency Test alcohol/ caffeine/ nicotine
maintain sleep) poorly consolidated states of (MSLT) measures the amount before bed
thalamocortical arousal (wake- of time it takes to fall asleep;
sleepiness, hallucinations sleep instability) latency period < 8 minutes EDS treatment: Modafenil
upon falling asleep or suggests narcolepsy
awakening, sleep paralysis, normal sleep homeostatic cataplexy tx: Sodium
cataplexy (can be triggered mechanisms but more CSF sample lacking oxybate(date rape drug),
by emiotions; sudden fragmented episodes of sleep hypocretin SSRIs, TCAs, SNRIs
intrusion of muscle atonia; w/ REM sleep occurring right at
most specific finding!) the onset of sleep HLA testing: HLA DQB 10602
Variants
Restless leg urge to move legs, disorder of the emotional motor most often 10% of U.S. FH, women, R/O secondary causes (iron Dopaminergics higher rates of mood
syndrome (RLS) uncomfortable leg system throught he ventromedial familial (AD) population pregnancy, deficiency, diabetes, uremia) disorders (depression,
sensations, medulla; sensory dysfunction iron def oral or IV iron repletion anxiety, panic
onset/worsening of ascends to the brain in the pregnancy, 12 million anemia, polysomnogram NOT indicated! when iron def confirmed disorder)
symptoms at rest or spinothalamic tract iron & B12 Americans Northern
inactivity, relief with deficiencies, have European Check for medication increased rate of CVD
movement, worsening at Brain deficits in IRON --> RLS anemia moderate- descent aggravators (benadryl), careful (autonomic arousals
night (unable to retain or mobilize severe RLS FH, psych screening (hi # occur w/ PLMs)
iron from periphery to brain) affected pts have anxiety/dep),
neuro exam (USUALLY NL!),
Multiple SNPs in 2 of 4 genes are serum iron/ ferritin/ B12/ TSH,
related in a dose dependent ambulatory actigraphy for PLMs
fashion to # PLMs (not severity)
Rapid Eye (general) "acting out" dreams, vivid lack of atonia & presumed lack mostly men Physical measures to RBD is dangerous!!!
Movement Sleep dreams w/ good recall, violent of suppression of movement > 50y.o. ensure safety: remove
Behavior themes & behaviors common during REM sleep (unless anti- dangerous nearby objects,
Disorder (RBD) (injury to self or bed partner) dep bedrails, soothing alarm
related)
Dx? At least one of sleep Change anti-depressants
related injury, disruptive to wellbutrin
behavior by hx, or abnl
REM sleep behavior by PSG Pharm tx: Clonazepam,
AND REM sleep without Melatonin
atonia AND not better
explained by another d/o
Occurs during 2nd half of

sleep (REM sleep), nightly,
speech & dream recall?
behavior changes
depending on dream
content, a/w neurodegen dz
or narcolepsy
Acute onset Iatrogenic (anti-depressants)
Withdrawal - Alcohol (chronic

EtOH --> downregulation of GABA -
-> delirium tremors that look like
RBD); Barbituates/
benzodiazepines
structural lesions - Pontine

lesions (ischemia, hemorrhage,
tumor, demyelination,
inflammation); limbic cortex
(limbic encephalitis)
Chronic form most common RBD associated with neurological Idiopathic RBD a/w
disease - young patients future
(hypocretin def --> narcolepsy); neurodegenerative dz
older patients (alpha
synucleinopathies - PD, MSA,
LBD), idiopathic
Variants
Non-REM Confusional overlapping spectrum incomplete arousal from slow- disorders safe environment
arousal arousals (confusional arousals most wave sleep (N3) resulting in of
disorders basic, sleep walking adds dissociation between behavioral childhood avoid triggers (sleep
Sleep terrors motor activity, & sleep state (wake) and EEG (sleep) deprivation)
terrors add fear & if occur in
Somn- autonomic activation w/o adulthood, Clonazepam (reduces
ambulism memory of event) consider behaviors)
(sleep occult cause
walking) Occurs during 1st half of of arousal
sleep (N3 stage), infrequent (OSA)
(1-3x/m), no recall
Migraine (general) trigger (somehow involves vascular 28 million Consider Echo to R/O PFO, Migraine Abortive therapy
serotonin, substance P, and/or Americans polysomnogram, imaging if (take as soon as symptoms
neurokinin A) --> activation of headache persists/worsens start!) - Triptans (avoid if
trigeminal vasculature system in 18% vascular comorbidities,
brain (trigeminal nucleus caudalis) women, 6% hemiplegic variants, basilar
--> dilation of blood vessels men migraine, or pregnant);
(throbbing & pain) NSAIDs, Triptan/ NSAID
peak age: combo, Tramadol,
25-55 y Antihistamines (pregnant
women), opiates
<10% able
to fxn during Vitamin prophylaxis -
HA VitB2 (reduces pain,
Common At least 5 attacks with: edema), Mg2+, feverfew
migraine attacks lasting 4-72h, 2+
characteristics (unilateral Prophylaxis based on
location, pulsating quality, comorbidities w/
mod/severe pain, headaches: AED
aggravation/worsen w/ (Topamax, Gabapentin,
physical activity), valproic acid), Anti-HTN
nausea/vomiting OR (propanolol, CCB), Anti-
photo/phonophobia depressants (TCAs,
SSRIs, SNRIs)
cannot attribute to another
d/o IV DHE if continuous
headache (need EKG
Classic common migraine + inciting event in visual cortex --> before using - inc stroke/ MI
migraine "AURA" - visual, dysphasia, lack of blood flow at that point --? risk)
hemisensory deficits Neurologic change --> positive or
(neurological deficits negative visual phenomena regular lifestyle/ sleep,
reversible >5m but <60m) exercise, stress mgmt,
avoid triggers (chocolate,
Hemiplegic migraine symptoms w/ fully Familial - genetic w/ basilar sx FH etc)
migraine reversible motor weakness (ataxia) often present
& aphasia
Sporadic - not present in 1st or
2nd degree relative
Basilar Aura w/ 2 of following affects brainstem, or location of if symptoms persist, imaging
migraine reversible sx (dysarthria, basilar artery at ER!
vertigo, tinnitus, hypacusia,
diplopia, visual sx
simultaneously in temporal &
nasal fields of both eyes,
ataxia, dec consciousness,
bilateral paresthesias), NO
motor weakness
Cyclical vomiting at least 4x/h for 1h,
vomiting symptom free between
migraine attacks
can last 1h-5d

Variants
Benign multiple episodes of severe

Paroxysmal vertigo, occurring wihtout
Vertigo of warning & resolving
Childhood spontaneously after minutes
to hours
a/w nystagmus or vomiting,

unilateral throbbing HA may
occur
nl neuro exam & EEG

Sinus headache frontal headache headache attributed to Evidence (clinical - purulence, 90% of sinus
accompanied by pain in rhinosinusitis nasal obstruction, hyposmia, headache patients
regions of face/ ears/ teeth fever; imaging) of acute or have MIGRAINE!!
chronic rhinosinusitis
resolves within 7d after
remission or tx of
rhinosinusitis
Medication also called HA >15d/m + regular chronic overuse of medications Ibuprofen, reduce offending agents
overuse rebound or overuse of drugs used for prevents prophylaxis from being Goody's
headache drug-induced acute HA >3m + HA effective in headaches powder, tylenol consider IV abortive
headache developed/worsened during therapy if difficult for pt to
med overuse + HA resolves endure pain
within 2m after d/c meds
Tension episodic HA that occurs non-pharm prophylaxis:

headache >15d/month, lasts 30m-7d, spinal manipulation, neck
pressing/tightening (non- exercises, therapeutic
pulsating), bilateral, mild or touch/ self massage/
mod intensity, NO n/v, no stretching
photo/phonophobia
regular lifestyle/ sleep,
exercise, stress mgmt
Trigeminal Cluster severe unilateral Sumatriptan injection or
Autonomic headache orbital/supraorbital/ nasal spray (>90%
Cephalgias temporal pain lasting 15m- effective), indomethacin,
180m (EXTREME consider prednisone
INTENSITY EXCRUCIATING
UNILAT HA) Oxygen therapy
associated with one of the DHE - IM, subq, IV

following signs on the painful
side: conjunctival injection, Prophylaxis: Verapamil,
lacrimation, nasal congestion, Topiramate, Melatonin,
rhinorrhea, forehead/facial Lithium carbonate
sweating, miosis, ptosis,
eyelid edema Surgery: central
parasympathetic
freq attacks: 1 every other interruption, sensory
day to 8x/d trigeminal interruption,
radiofrequency
thermocoagulation
Chronic At least 50 attacks of severe

Paroxysmal unilateral orbital/
hemicrania supraorbital/ temporal pain
lasting 2-45m
5x/d, no predilection for night

attacks
a/w lacrimation, nasal

congestion, conjunctival
injection, rhinorrhea, ptosis
Variants
Hemicrania non-remitting, remitting Indomethacin

continua
pain 24/7 w/ +/- autonomic
sx, exacerbations w/
coexisting migraines or
cluster HA, "foreign body"
sensation in eye, ice pick
HA
Conjunctivitis (general) affects both palpebral & microbes,

epibulbar conjunctiva!! viruses, toxins,
allergens, tear
deficiency
Bacterial purulent; pain but NO S. aureus, Strep usually resolves w/I 4-5d or
blurry vision; bilateral pneumo, H.flu, sooner if use warm
Pseudomonas, compresses
Lids stuck in the AM N. gonorrhea
topical antibiotic
hyperpurulent?? N.
gonorrhea If N. gonorrhea as
causative agent -
REQUIRES systemic
antibiotics & lavage
Viral watery exudates, starts Adenovirus - Eye exam: conjunctival ADENOVIRUS:
monocular, URI +/- sore pink eye follicles (lymphoid aggregates)- Cool compresses, topical
throat, fever adenovirus decongestants or artificial
HSV tears; refer if severe pain or
pre-auricular decreased vision
lymphadenopathy - pink
eye
HSV - dendritis ulcers w/

fluorescein stain
Allergic seasonal itching of eyes, IgE mediated ocular surface OTC lubricants &
white mucus of eyes disease affecting mucus decongestants, cool
membranes (eyes & nose) compresses, topical
swollen lids, watery antihistamines
discharge, hay fever sx
HSV keratitis #1 cause of inflamm HSV destroys corneal epithelium fluorescein dye or Rose Acyclovir, steroids
blindness in U.S. and periodically bifurcates --> bengal stain shows
dendritic corneal ulcers --> DENDRITIC ulcers
Honey-crusted lesions on recruitment of antibodies -->
erythematous base (looks scarring of corneal --> blindness &
like impetigo) near recurrence even in corneal grafts
mucocutaneous junction
(eye, lips, nose)
Herpes Zoster herpetic lesions following Acyclovir
Ophthalmicus dermatome (trigeminal
distribution) - ophthalmic +
nasociliary lesions
feel "pain behind the eye"
Blepharitis chronic inflammation of lid a/w seborrheic dermatitis leading

margins --> swollen or closed to hyperkeratosis of basilar
Meibomian glands epithelium leading to problems w/
Meibomian glands
foreign body sensation,
burning, itching
crusts on lashes - Staph

blepharitis
Variants
Stye acute infection of the S.aureus

eyelid; small, tender &
painful, warm
Chalazion granulomatous NOT infectious - lipogranuloma
inflammation involving the
Meibomian gland of eyelid
usually self-limiting
Dacrycystitis purulent material through the infection of lacrimal sac region, previous facial
punctum trauma
obstructing the
nasolacrimal
passage
Dacryoadenitis prominent eye lids inflammation of lacrimal gland infxn, inflamm,
granulomatous
Orbital cellulitis periorbital redness & usually spread from infection in the hospitalization
swelling often secondary to ethmoid air cells or maxillary
sinusitis, impaired/painful sinuses
EOM, proptosis
fever, proptosis, periorbital

swelling, ophthalmoplegia
(impaired eye movements)
Subconjunctival hemorrhage/ blood in the inadvertent rubbing or Valsalva trauma, blood if associated w/ trauma -
hemorrhage conjunctiva, PAINLESS maneuvers -->small vessel thinners emergency! Otherwise,
hemorrhage in the substantia get better on own
SELF-LIMITING propria of conjunctiva
Scleritis red eye but able to see inflammatory condition in the front Wegener's, RA,
sclera vessels of the eye infections
deep, throbbing pain worse w/

touch
Hyphema bleeding INSIDE the eye = bleeding of iris or ciliary body tear of iris or
OPHTHALMIC vessels usually due to blunt sphincter
EMERGENCY! (increased ocular trauma --> blockage of muscle
IOP) aqueous outflow w/ RBCs -->
increased IOP
Hypopyon White blood cells layering corneal
out INSIDE the eye = abrasions
OPHTHALMIC (contact lenses),
EMERGENCY! previous
surgeries, septic
emboli
Corneal abrasion evident w/ Fluorescein dye denuded epithelium from abrasion - topical antibiotic
-> irregular fibers/ scarring in
stroma --> vision loss
Orbital fracture associated with blunt trauma

to the eye
edema & ecchymosis of

eyelids & periorbital region
(raccoon eye), vertical
diplopia
Variants
Optic neuritis blurry vision or loss of inflammation of the optic nerve MS F>M fundo exam: normal or swollen corticosteroids
vision, PAIN on eye disc (nl if retrobulbar optic
movement, central scotoma ages 15-45 neuritis); 3m later, optic pallor
(younger
population) MRI: acute inflammation of optic
nerve; white matter lesions &
plaques if MS
Anterior PAINLESS, permanent ischemia to optic nerve head DM, HTN, giant M=F fundo exam: swollen disc
Ischemic Optic visual loss cell arteritis
Neuropathy older
population
(age>50)
Papilledema painless, BILATERAL disc edema from raised ICP intracranial ANY age fundo exam: bilateral swelling
mass lesions, of optic nerve heads
usually spares central vision hydrocephalus,
until late meningeal Workup of bilateral disc
processes, edema + headache: 1. CT
peripheral vision lost early idiopathic, scan to r/o acute bleed; if nl, get
venous brain MRI 2. abnl MRI?
thrombosis Hydrocephalus, mass, venous
thrombosis; nl MRI? 3. get LP;
if abnl - meningitis, spinal cord
tumor; nl + hi pressure -
idiopathic intracranial
hypertension; nl + nl pressure -
no raised ICP
Central retinal sudden, PAINLESS loss of embolization of plaque material Vascular risk ESR/CRP normal (giant cell less no acute treatment
artery occlusion vision in ONE eye, RAPD from ipsilateral carotid artery or factors likely)
ophthalmic artery (smoking, secondary prevention of
"curtain coming down" - HTN, hi workup for source of emboli cerebral & ocular infarcts -
transient suspect giant cell arteritis if cholesterol) (carotid U/S or CTA, EKG, antiplatelets, carotid
elderly person c/o sudden cardiac echo) endarterectomy, mgmt of
pallor of optic disc, "cherry vision loss + temporal vascular risk factors
red" macula headaches
Central retinal sudden, painless loss of hypercoagulable DM & Chronic

vein occlusion vision, swelling of optic state HTN
disc, engorged retinal veins
with hemorrhage
Glaucoma Open angle: bilateral, progressive optic neuropathy that meds 1/50 adults FH (6x risk) penlight test: shadow Pilocarpine blindness!!!!!
painless, night blindness, is usually a/w increased intraocular (steroids), produced on nasal side (bc iris
scotomas and loss of pressure trauma, uveitis, A.A., is domed up blocking the light systemic carbonic
periperal vision --> tunnel tumors, Hispanics, across the iris); do not dilate anhydrase inhibitor to lower
vision & blindness; exam cause depends on if open angle or neovascul elderly this patient's pupil!! pressure enough for surgery
shows increased cup:disc angle closure: prolif (retinal
ratio open angle glaucoma: vein occlusion, iridotomy or ididectomy
decreased rate of aqueous outflow diabetic
Angle closure: severe pain into the canal of Schlemm retinopathy,
a/w photophobia & blurry angle closure glaucoma: carotid occlusive
vision, red eye with cloudy narrowing of anterior chamber dz)
cornea, abnl light reflex, angle
fixed/non-reactive pupil
aqueous continually being made
late stages will have loss of by ciliary body + insufficient
central vision too filtration out of the trabecular
meshwork --> increased IOP &
axonal death
(infero/superotemporal axons
affected first) --> enlarged optic
cup
Variants
Uveitis pain + blurry vision, miotic inflammation of uveal tract (iris, sarcoidosis, check CXR for hilar adenopathy
pupil, adhesions btwn iris & ciliary body, choroid) --> WBCs in ulcerative colitis, if suspect sarcoid!
anterior lens capsule, red the aqueous humor ankylosing
eye + photophobia spondylitis
Macular most common cause of degeneration of maculr retinal FH, vitamin therapy to prevent
degeneration permanent vision loss in pigment epithelium Caucasians, progression from dry-->
ELDERLY females, light wet?? (at least eat healthy!!)
dry type: thinning of retina & eyes,
slow, progressive loss of formation of yellowish white smoking,
fine vision (inability to see deposits (drusen) heart dz,
centrally, unable to see faces) HTN, UV light
wet type: extension of dry type exposure,
Drusens (yellow deposits) if where neovascularization of poor nutrition,
dry; hemorrhages if wet choroid vessels --> subretinal AGE
hemorrhage --> death of retinal
cells, blind spots & distorted
vision
CMV retinitis most common cause of
blindness in AIDS
cotton wool exudates +

retinal hemorrhages
Cataracts congenital #1 cause of worldwide epithelial cells of lens capsule advanced age, white cortical cataracts - DM cataract extraction
(rubella) blindness constantly divide --> thickening/ DM, infection, procedures (most common
hardening of lens over time --> corticosteroid smudges on retroillumination - surgery in U.S.)
adult (age- opacity of the lens cataract formation use subcapsular
related)
glare with bright lights, unable
white cortical to drive at night - think
cataracts posterior subcapsular
(DM)
posterior
subcapsular
cataract (DM,
steroid use)
Malignant Retinoblastoma - kids, Enucleation

tumors of the white eye reflex
eye
malignant melanoma -
adults
Myopia "near sightedness" = focal point falls short of the retina concave lens - causes
unable to see far so the focus of light is now in the parallel light rays to diverge,
vitreous cavity --> blurry vision moving the focal point back
to the retina
all uncontrolled diabetics have
blurry vision bc glucose enters
the lens --> osmotic change in
the lens --> myopia
Hyperopia "far sightedness" = unable eye is smaller than normal so rays convex lens - pulls the
to see close of light strike the retina BEFORE focal point forward back
they come into focus onto retina
Astigmatism abnormalities in cornea and/or glasses or toric contact lens
lens causes the eye to lose it
spherical shape
Variants
Presbyopia "wise old owl has loss of ability to accommodate, ages 40-50 reading glasses
presbyopia" which normally occurs when you
look at something close
normal accommodation occurs

when the ciliary muscle constricts,
making the lens fatter & moving
the focal point to the FRONT of
the retina (instant myopia)
(accomodation --> pupil
constriction as object moves
closer to eyes)
with age, the lens proteins

become stiffer
Rubiosis iridis Blood vessels seen in the iris Neovascularization of the lens/ iris neovascular
occuring when the retina glaucoma, DM
increased IOP undergoes ischemia --> increased (proliferative
VEGF --> increased blood vessels diabetic
in abnormal areas of the eye retinopathy),
central retinal
vein occlusion
Ectropion red eye + abnl conjunctiva eye lid turns outward exposing the
epithelium tear film and causing red eye
Extropion red eye + eye infection eye lid turns inward disrupting the
usually corneal epithelial cells and tear film
causing red eye & infection
(usually from eyelashes scratching
cornea)
Diabetic (general) requires abnl glucose for hi glucose levels -> inc aldose >70% of pts HbA1c > 7.0 tight glycemic control +
retinopathy 10-12y reductase --> inc sugar alcohol by w/ uncont control of HTN + laser
products --> loss of pericytes in DM uncontrolled therapy
#1 cause of new adult endothelium of retina --> HTN, renal
cases of blindness outpouching of blood vessels & dz,
bleeding/edema of retina pregnancy,
1. weak blood vessel walls anemia
2. edema
3. neovascularization longer
4. bleeding duration of
DM
Non- lipid exudates + lack of retinal capillary endothelial trypsin digest - macular edema (If
proliferative microaneurysms integrity --> microaneurysms + microaneurysms, capillary exudates accumulate in
fluid/ protein/ lipid exudates drop out central retina)
macular edema --> dec
visual acuity
Proliferative profound vision loss increased microthrombus

formation --> retinal ischemia -->
neovascularization of iris & release of VEGF-->
retina neovascularization into vitreous
cavity --> hemorrhage of these
pre-retinal or vitreous weak vessels --> retinal
hemorrhage detachment
Variants
HTN retinopathy av nicking, cotton wool

spots (if infarct in nerve fiber
layer), hard exudates (infarct
in deeper retinal layers),
macular stars,
hemorrhages are not
present unless GRADE 4
HTN retinopathy
Retinal painless, FLASHING lights/

detachment falling stars/ FLOATERS
followed by shadow in
periphery
Temporal (giant temporal headache + vasculitis affecting medium-sized age >50 abnl ESR/ CRP (suggests start IV steroids STAT if follow pt for
cell) arteritis transient, monocular visual vessels (usually systemic process) suspect this dx corticosteroid side
loss in ELDERLY 70s,80s) effects (BMD, etc)
SUSPECT THIS DX W/ ANY temporal artery bx to confirm Corticosteroids for 2y can
systemic symptoms (weight NEURO-OPHTHALMOGIC dx save the other eye!
loss, fatigue, headache, scalp COMPLAINT IN ELDERLY
tenderness, jaw claudication, PATIENT!!!!
hi ESR/CRP)
25% pts have ischemic

complications involving eye
& orbit (ischemic optic
neuropathy, choroidal
ischemia, central retinal
artery occlusion, diplopia,
cerebral ischemia, ocular
ischemia)
Screening /
Education
Screening /
Education
Screening /
Education
any diagnosed
seizure? No
driving or
operating heavy
machinery,
swimming,
bathing in tubs,
ladders until
seizure free
avoid alcohol,
sleep deprivation
urge AED
compliance
f/u MRI
Screening /
Education
Screening /
Education
Screening /
Education
Framingham
stroke risk score
(age, untx SBP or
tx SBP, DM,
smoking, CVD,
Afib, LVH)
2ndary
prevention?
Antiplatelet tx
(aspirin if
atheroscl, small
vessel dz),
anticoag tx
(coumadin if
cardioemb,
hypercoag),
carotid
endaterectomy if
stenosis
lifestyle mods >>

meds
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
PD progresses
within 15-20y
timeframe
Screening /
Education
Screening /
Education
Screening /
Education
genetic testing
not done in
unaffected
children at risk!
w/I 15y of dx:

80% of pts have
functional
impairment, 50%
are unable to
walk, 70% are
unable to work
Screening /
Education
Screening /
Education
Screening /
Education
patient
autonomy
Screening /
Education
must talk to
family members
about what to
expect as brain
dead testing is
done
(spontaneous
movements
after brain
death)
give family the

option to
withdraw care!
Organ donation
Screening /
Education
Screening /
Education
inactivated polio
vaccine!
progression & life

expectancy ~ age
of onset
Screening /
Education
nutritional &
caregiver
education
end of life
decisions
hospice
Screening /
Education
Screening /
Education
Concerned about
use of OCP,
stroke/ HTN/
OSA risk in
migraine
patients
Screening /
Education
Screening /
Education
VERY
CONTAGIOUS!!!
Avoid social
contacts!
Screening /
Education
Screening /
Education
comprehensive
eye exam for
everyone after
age 40
early eye exams

if FH
Screening /
Education
smoking
cessation
wear sunglasses,
get eye exams,
eat healthy,
control vascular
dz
prevention
involves
controlling
comorbidities
Screening /
Education
T1DM: dilated
eye exam q 3-5y
within dx & yearly
afterwards
T2DM: dilated
eye exam @ time
of dx, yearly
afterwards
Screening /
Education
Bacteria Classification Gram +/- Morphology Characteristics
Catalase neg
Facultative anaerobe
Streptococcus hyaluronic capsule
GAS + Cocci in pair/chains
pyogenes (mucoid appearance)
strongly B-hemolytic
Bacitracin susceptible
Catalase +
Coagulase + (good test
to distinguish S. aureus
from other Staph)
Cocci in grape-like
Staphylococcus aureus + Facultative anaerobe
clusters
Beta-hemolytic
Mannitol +
Yellow colonies
(CoPS)
Intracellular
diplococci Oxidase+
N. gonorrhea -
associated with grows w/ CO2
neutrophils
Virulence factors Diseases
Strep throat
M surface protein (anti-
(pharyngitis)
phagocytic;
Rheumatic fever
superantigen; >90
Impetigo
types)
Strep TSS
Glomerulonephritis
SPEs (superantigens
SSTIs
that superstimulate T
Cellulitis
cells --> inflam
Erysipelas
cytokines)
NF
CA-MRSA: SCCmec
type IV cassette w/
methicillin resistance;
PVL (toxin that kills
leukocytes by forming
pores in their SSTIs
membranes); PFGE Cellulitis
type USA 300 NF
SSI
General: Catalase + Endocarditis
(anti-phagocytic), Pericarditis
Pyomyositis
clumping
Meningitis
factor/techoic acid/
Food poisoning
proteins A&B
TSS
(adherence), lipases
(abscess formation),
leukocidin (lysis of
phagocytes), MANY
toxins!
Resistant to human
serum - Por1A
Population Disease Risk factors
Age
UV exposure
Type 1- 3 skin
Duration of immunosuppressants
Transplant patients Skin cancers
Intensity of immunosuppressants
HPV
Hx of skin cancer
CD4 lymphopenia
Skin break Pathogen
Human bite
Eikenella corrodens
(mouth pathogens)
Cat bite/puncture Pasteruela multocida
Dog bite/puncture C. canimorsus
Fresh water Aeromonas hydrophilia
Salt water/fish Erysipelothrix rhusiopathiae

Aquarium Mycobacterium marinum
Spa/ hot tub Psuedomonas aeruginosa
Trauma Gas gangrene
Cirrhosis & salt water Vibrio vulnificus
Edema Streptococci
Nosocomial Infections
S Serratia
P Pseudomonas
A Acinetobacter
C Citrobacter
E Enterobacter
K Klebsiella

Disease Cheat Sheet

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Disease Cheat Sheet

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Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications

cryosurgery, topicals (5-FU,

Chronic UVB exposure,

Deficiency in patch (negative regulator of Shh) causes

Chronic UVB exp

ALM more common in dark/Asian

uniform pigmentation, symmetrical shape, sharply demarcated

Prophylactic removal during teen

Defective NER (nucleotide excision repair); New tx include mimics of

Change in existing melanin (immediate pigment darkening

Epidermolysis bullosa Inherited disorder w/ defects in cellular attachments, causing

Very serious bc blistering in middle skin layers premature stop codon

Odanacatib - Cat K inh

Surgical debridement if necrotic

Septic arthritis Acute bacterial Recent trauma (animal/ human

Type 1 - mild sx, fx w/ minor trauma, no bony deformities,

Pain in femur/tibia/vertebrae @ night, relieved by NSAIDs

Osteoblastic XR? Lysis, blastic sclerotic bone, or even mixed; ill

Trunk/pelvis/long bones; pain, swelling, resistant to

Furrowed brow, high-arched eyebrows

Histology of Gottron's papules? Increased stratum

Clinical exam? Prodrome malaise/fatigue, stiffness that

W/ age, side chains in cartilage shrink and hold less water =

Overproduction of uric acid? (~10%)

Seen w/I first few months of life

Lung impairment (dyspnea on

Classic - DIP joints of hands & feet

Arthritis mutilans w/ sacroilitis

Ankylosing spondylitis w/ or w/o peripheral

"Can't see, can't pee, can't climb a tree"

NSAIDs & glucocortocoids for pain

Protective clothing, daily use of

Protective clothing, daily use of

Protective clothing, daily use of

Importance for early detection and

Staging - 0 (tumor in epidermis),

Emphasize prevention (sunscreen,

Need to talk to parents about how

Oral form of Mucus Membrane

Pretty good prognosis with treatment

Worrisome in diabetics or pts with

Prevention to avoid recurrence-

Avoid gross hot tubs!

Prevention (bleach baths, treating

Prevention (bleach baths, treating

Examine (& possibly treat)

Screen for STDs in young adults

Avoid skin-skin contact during active

Prevention with immunization w/

GAS/GBS screening for women

Adjustment of risk factors (excessive

Diagnosis is impt in case patient

age/gender appropriate cancer

Avoid sun exposure, use sunscreen!

Counsel on posture, stretching,

high risk for traumatic fractures

Pneumopericardium Air in the pericardial Fistula btwn 2 Requires immediate

Alveolitis infiltration of lymphocytes & Viral, mycoplasma Histology: thickened

cancer cells occlude lymphatics

Chylothorax Exudative pleural disruption of thoracic duct or LN trauma or

Pulmonary loss of capillary volume ILD DLCO

Pulmonary fibrosis increased membrane thickness, DLCO

persistent cough or intrathoracic obstruction Atelectasis w/