Jaw pain

- in the middle of a meal is characteristic for temporal arteritis. The lumen of the
arteries narrow and cannot respond to increased blood requirement during the
meal. Tongue pain during meals (tongue claudication) may also occur.
-Temporal arteritis presents in elderly patients (mean age of onset is 65 years
old). The most common symptom is headache. It can be accompanied by scalp
tenderness, especially pronounced during hair combing. The inflamed temporal
artery can sometimes be palpated as a firm, painful subcutaneous cord in the
temporal region. Jaw and tongue claudication, fever, malaise and weight loss
may be present. 50% of patients also complain of muscle pain and morning
stiffness (due to polymyalgia rheumatica).
-The index of suspicion for temporal arteritis should be high. Treatment should
be started as soon as possible to prevent vision loss. The vision loss is painless,
monocular and may lead to permanent blindness. Erythrocyte sedimentation rate
(ESR) should be determined if temporal arteritis is suspected. It is almost always
significantly elevated (often > 100 mm/hr).
-Temporal artery biopsy is necessary for definitive diagnosis.
-Corticosteroid treatment should be started ASAP to prevent possible vision loss.
http://video.google.com/videoplay?docid=-2645662225255385165#

Aortic stenosis
=systolic diamond-shaped (crescendo-decrescendo) murmur
- The most common cause of this valvular disease is degenerative (senile)
calcification of the aortic valve leaflets. Calcific aortic stenosis is a result of
prolonged hemodynamic stress on the aortic valves leading to inflammation of
the valvular tissue overtime. It is common in patients older than 65 years old.
-Physical examination of the patient with aortic stenosis reveals small and slow
rise in the carotid pulse during systole (pulsus parvus et tardus), a diminished
aortic component of S2 sound, and a harsh systolic crescendo-decrescendo
murmur. The murmur is best heard at the right upper sternal border.
http://www.merck.com/mmpe/multimed...peed=256&Plugin=WMP&Error=

Burkitt lymphoma
- EBV causes latent infection and immortalization of B-cells. A crucial step in the
transformation of infected cells is the balanced t(8:14) translocation, which
generally requires a background of immunodeficiency (e.g. immunosuppressive
medications, HIV infection).
-The histology for Burkitt lymphoma: diffuse medium-sized lymphocytes
producing the characteristic “starry sky” appearance, a high proliferation
index represented by the high Ki-67 fraction (99%), and increased apoptosis.
- The EBV genome is identified in 50% of all systemic B-cell lymphomas and
almost all primary CNS lymphomas occurring in HIV patients. There is little
evidence of a direct effect of HIV in AIDS-associated lymphomas.
http://www.webpathology.com/image.asp?n=14&Case=389
Angiogenesis in neoplastic and granulation tissue
- The key growth factors that promote angiogenesis in neoplastic and granulation
tissue are vascular endothelial growth factor (VEGF) and fibroblast growth factor
(EGE).
- Proinflammatory cytokines (like IL-1 and INF-y) can indirectly promote
angiogenesis through increased vascular endothelial growth factor (VEGF) and
fibroblast growth factor (FGF). Proinflammatory cytokines (like IL-1 and INF-y)
can indirectly promote angiogenesis through increased VEGF expression. The
laminin in basement membranes may pose a physical barrier to the sprouting of
new blood vessels.
http://www.researchvegf.com/researchvegf/images/VEGF-ligand.jpg
http://www.nature.com/nrc/journal/v6/n4/images/nrc1836-f4.jpg

Invasive breast carcinoma

- typically presents as a mammographic finding or a palpable mass. Larger
tumors may be adherent to the chest wall. Nipple inversion is observed when the
tumor invades the central region of the breast, and skin retraction is identified
when the cancer infiltrates the suspensory Cooper ligaments. Should the
lymphatic drainage become impeded by tumor, lymphedema and pitting and
thickening of the skin-- such that it adopts the appearance of an orange peel
(peau d’orange) -- may occur. The peau d’orange finding is particularly
common in patients with inflammatory breast cancer.
http://ocbreastcare.com/mediac/400_0/media/10302.jpg
http://tgmouse.compmed.ucdavis.edu...MM2000/BRCA-1/slide158.jpg

Carbon tetrachloride (CCl4)

=causes free radical injury. Like many other toxic substances CCl4 is oxidized by
the P450 oxidase system in the liver. The result is the formation of the free
radical CCl3, which reacts with structural lipids of cell membranes. The result is
lipid degradation and hydrogen peroxide (H202) formation. This process is called
lipid peroxidation. The peroxides go on to form new radicals, continuing the
vicious circle of lipid degradation. Carbon tetrachloride cell injury develops
rapidly and leads to swelling of the endoplasmic reticulum, destruction of
mitochondria, and increased permeability of cell membranes. These processes
culminate in hepatocyte necrosis.
- Mitochondrial dysfunction occurs in CCl4 intoxication as a result of free radical
injury
Catecholamine-secreting tumors
= repeated paroxysmal episodes, which resolve without intervention, are
characteristic of pheochromocytoma, a catecholamine producing tumor of the
adrenal medulla. It is unclear why the catecholamine-secretion by
pheochromocytomas is so often episodic.
-Classically, a patient with pheochromocytoma will present with intermittent
headaches, hypertension, diaphoresis and pallor or flushing. In between these
episodes, blood pressure maybe normal. Episodic hypertension is a very
important clinical clue in the diagnosis of pheochromocytoma. The differential
diagnosis includes autonomic dysfunction, cocaine abuse, withdrawal from
clonidine and beta-blockers, and panic attacks.
- The Rule of 10s is helpful in remembering the features of pheochromocytoma.
Roughly 10% of pheochromocytomas occur as part of hereditary syndromes
(e.g. MEN 2 A and B, von Hippel Lindau disease), 10% of pheochromocytomas
are bilateral, and 10% are extra-adrenal. Only 10% of pheochromocytomas are
malignant; the majority =benign.
http://www.healcentral.org/content...ma%20pheochromocytoma3.JPG

Panic attacks
= episodic symptoms including apprehension, shortness of breath, chest pain
,diaphoresis, tremors and a feeling of impending doom. However affected
individuals typically experience their first panic attacks at an earlier age (mean
age at first presentation is around 24 years). Additionally panic attacks are twice
as common in females as compared to males.
- Furthermore the rise in blood pressure seen in panic attacks is typically an
isolated systolic increase rather than the combined systolic and diastolic
hypertension

Carcinoid syndrome
= results from excessive production of 5-hydroxytryptamine, usually from a
metastatic mid-gut neuroendocrine tumor. These patients typically present with
facial flushing bronchospasm and diarrhea. Hypotension is present rather than
hypertension.
http://www.pathconsultddx.com/pathCon/largeImage?pii=S1559-
8675(06)70133-4&figureId=fig1
http://www.pathconsultddx.com/pathCon/largeImage?pii=S1559-
8675(06)70133-4&figureId=fig4
Congenital QT-interval prolongation
= often the result of mutations of the genes coding for cardiac cell potassium or
sodium channels. Various congenital long-OT syndromes are recognized, with
Jervell and Lange-Nielsen syndrome as one of the most prominent.
- This autosomal recessive condition is accompanied by congenital neurosensory
deafness. The QT-interval prolongation predisposes the patient to syncopal
episodes and possible sudden cardiac death due to torsades de pointes (a
ventricular tachyarrhythmia).
http://www.geneticheartdisease.org/jpegs/lqts_four.gif
http://www.mykentuckyheart.com/images/pictures/qt_syndrome.gif

Kartagener’s syndrome
=A familial syndrome associated with bronchiectasis
= immotile cilia due to a microtubular dynein arm defect. Infertility, recurrent
sinusitis, and bronchiectasis result. Although this syndrome is sometimes
associated with situs inversus, there are no associated cardiac
electrophysiological abnormalities.
http://www.mypacs.net/cases/DEXTRO...ENERS-SYNDROME-632514.html

Syndactyly= failure of the digits to separate

=the most common congenital upper limb deformity. The second most common
deformity is a constriction band syndrome which interrupts the fetal blood supply
to the distal limbs and causes amputation of fingers (or toes). Most upper-limb
deformities are the result of developmental accidents of unknown etiology and
are non-syndromic, i.e. not associated with congenital abnormalities in other
organ systems.
http://upload.wikimedia.org/wikipe...two_fingers_right_hand.JPG
http://www.handsport.us/images/constriction-bands.jpg

Multiple telangiectasias
= Osler-Weber-Rendu disease (aka Hereditary Hemorrhagic Telangiectasia), an
autosomal dominant condition in which vascular telangiectasias are found in the
skin and mucous membranes of the lips, oronasopharynx, and respiratory,
gastrointestinal, and urinary tracts.
-Their rupture may cause epistaxis, GI bleeding, or hematuria.
http://www.residentandstaff.com/issues/articles/2005-08_09.asp

MEN 2B
= multiple endocrine neoplasia type 2B
= Marfanoid habitus, tall and slender with disproportionately long arms, legs,
and fingers.
-The flesh-colored nodules on his lips and tongue are likely mucosal neuromas,
which are unencapsulated, thickened proliferations of neural tissue.
-The history of total thyroidectomy is suggestive of a thyroid malignancy,
because benign thyroid masses are usually treated medically or with partial
thyroidectomy. This constellation of clinical findings is consistent with multiple
endocrine neoplasia type 2B (MEN 2B).
http://www.ispub.com/ispub/ijd/vol...th_keloids/keloid-fig2.jpg
http://cnx.org/content/m14901/latest/

Neurofibromatosis type 1
= multiple café-au-lait spots, cutaneous neurofibromas, axillary or inguinal
freckling, optic glioma, iris hamartomas, and osseous lesions.
http://www.nature.com/eye/journal/v19/n3/fig_tab/6701478f1.html
Neurofibromatosis type 2 (the more “central” form)
= bilateral acoustic neuromas, brain meningiomas, and schwannomas of the
dorsal roots in the spinal cord.
http://www.brighamandwomens.org/ne...estibular%20Schwannoma.jpg

Multiple endocrine neoplasia type 1 (MEN 1)= the “3 Ps.”

=autosomal dominant condition characterized by tumors of the parathyroid
gland tumors of the anterior pituitary gland, and tumors of the pancreas. MEN is
not associated with thyroid cancer or perioral nodules.

Neurosyphilis
=a condition that occurs in less than 10% of patients with tertiary syphilis.
- occurs 20-30 years after an untreated syphilis infection. Demyelination of the
dorsal columns in the spinal cord causes a loss of vibratory and position senses.
Loss of these senses is usually compensated for by visual clues, but sensory
ataxia prevails in the dark (demonstrated by this patient’s frequent
stumbling at night).
-Involvement of the dorsal roots causes loss of pain sensation, paresthesias, and
painful crises. Areflexia and loss of bladder function can also occur. On physical
examination, Argyll Robertson pupil and positive Romberg sign are found.

Hypertrophic cardiomyopathy (HCM)

= idiopathic hypertrophic subaortic stenosis
= exertional syncope, harsh systolic murmur, and asymmetric septal
hypertrophy in a young man
= an autosomal dominant Mendelian-inherited condition in at least 50% of cases
- Most cases of HCM are thought to result from mutations in genes for cardiac
sarcomere proteins, such as components of the thick or thin filaments.
- Dynamic ventricular out flow tract obstruction is seen in about 25% of patients
with HCM. On echocardiography, there is systolic anterior motion (SAM) of the
anterior leaflet of the mitral valve such that it comes abnormally close to the
interventricular septum as it bulges into the left ventricular (LV) outflow tract.
The bulging is the result of asymmetric septal hypertrophy (ASH). The
magnitude of the abnormal systolic LV to aorta pressure gradient correlates with
the degree of SAM of the anterior mitral leaflet. The systolic murmur heard in
patient with HCM is a systolic ejection murmur produced by the LV out flow tract
obstruction.
http://www.scmr.org/caseoftheweek/2008/case08-21.html
http://www.sahha.gov.mt/showdoc.as...ilesource=4&file=fig03.jpg
http://www.mdconsult.com/das/book/...0-2450-7..50441-2..gr2.jpg

Peripheral neuropathy - diabetes mellitus

- It occurs in both type 1 and 2 diabetes and is associated with poor glycemic
control and/or long duration of the disease. The most important mechanisms of
the development of diabetic neuropathy are the following:
1. Non-enzymatic glycosylation of proteins leads to increased thickness,
hyalinization, and narrowing of the walls of the arteries. These changes lead to
diabetic microangiopathy of endoneural arterioles. Ischemic nerve damage
follows.
2. Intracellular hyperglycemia occurs in peripheral nerves. Accumulating glucose
is converted into sorbitol and fructose by aldose reductase. Sorbitol increases
cell osmolarity and facilitates water influx into the cell. The result is osmotic
damage to axons and Schwann cells.

-Peripheral neuropathy, the most common type of diabetic neuropathy, causes

pain or loss of feeling in the toes, feet, legs, hands, and arms.
-Autonomic neuropathy causes changes in digestion, bowel and bladder function,
sexual response, and perspiration. It can also affect the nerves that serve the
heart and control blood pressure, as well as nerves in the lungs and eyes.
Autonomic neuropathy can also cause hypoglycemia unawareness, a condition in
which people no longer experience the warning symptoms of low blood glucose
levels.
-Proximal neuropathy causes pain in the thighs, hips, or buttocks and leads to
weakness in the legs.
-Focal neuropathy results in the sudden weakness of one nerve or a group of
nerves, causing muscle weakness or pain. Any nerve in the body can be
affected.Symptoms may include:

double vision
eye pain
paralysis on one side of the face (Bell's palsy)
severe pain in a certain area, such as the lower back or leg(s)
chest or abdominal pain that is sometimes mistaken for another condition such
as heart attack or appendicitis
Focal neuropathy is painful and unpredictable, however, it tends to improve by
itself over weeks or months and does not tend to cause long-term damage.
http://www5.aaos.org/oko/description.cfm?topic=FOO027

DIFF:
-Endoneural inflammatory infiltration of the peripheral nerves is characteristic of
Guillain-Barre syndrome. Segmental demyelination is another typical pathologic
finding.
-The mutation of a myelin protein gene is the pathogenesis of Charcot- Tooth
disease, a so-called “neural form” of muscular atrophy. Charcot-Marie-
Tooth disease often presents with weakness of foot dorsiflexion due to
involvement of the common peroneal nerve.
- Entrapment of a nerve within an anatomic compartment leads to compression
neuropathy. The most common example is carpal tunnel syndrome, which occurs
due to compression of the median nerve at the wrist.
http://www.pyroenergen.com/article...carpal-tunnel-syndrome.gif
http://www.hughston.com/hha/b_15_3_2a.jpg
http://www.cubital-tunnel.com/cms/.../stories/cubitaltunnel.jpg
-Abnormal signal transmission at the neuromuscular junction is characteristic of
myasthenia gravis and Lambert-Eaton syndrome. Antibodies against
acetylcholine receptors of the neuromuscular junction are the cause of
myasthenia gravis. Lambert-Eaton syndrome is a paraneoplastic condition
associated with antibodies against presynaptic calcium channels.

CNS damage
- One of the main functions of astrocytes is participation in tissue repair. In an
event of irreversible neuronal damage and neuronal death, astrocytes proliferate
at the site of injury. This process is called astrocytosis (or gliosis) and is a
universal response of the CNS to severe damage. Proliferating astrocytes are
enlarged and contain a large number of fibrils and glycogen granules. Their
nuclei are large, vesicular and display prominent nucleoli. Proliferated astrocytes
replace lost neurons and compensate for their volume. Later, after the neuronal
death, astrocytic processes form a closely connected firm meshwork called a
gliotic scar.
http://hdroster.iu.edu/AboutHD/brainAndHD.asp
http://www.pathguy.com/sol/01368.jpg
DIFF:
- Fibroblast migration to a site of injury occurs in the peripheral nervous system,
not in the CNS where tissue repair is a function of astrocytes.
- Neither vascular hyalinization nor amyloid deposition is a component of normal
tissue repair. Both of these processes are pathologic.

Multicystic kidney dysplasia

= multiple cysts of varying size in the kidney and the absence of a normal
pelvocaliceal system. The condition is associated with ureteral or ureteropelvic
atresia and the affected kidney is nonfunctional. Abdominal ultrasound of fetus
or newborn is diagnostic.
http://www.humpath.com/IMG/jpg/bil...renal_dysplasia_03_1-2.jpg

Horseshoe kidney
=The abnormal fusion of kidneys at poles (usually, the lower poles)
-The isthmus of renal tissue is anterior to the great vessels and is easily detected
on abdominal ultrasonography.
http://www.foxhallmri.com/case/horseshoe.htm

Potter syndrome
=pulmonary hypoplasia, Potter facies (flattened nose, recessed chin, prominent
epicanthal folds, and low-set ears), limb defects, and cardiovascular
abnormalities. Renal defects that lead to Potter syndrome are usually profound
(and would be easily seen on ultrasound) bilateral renal agenesis, infantile
polycystic kidney disease
http://www.utm.edu/staff/nlillega/phil%20350_files/image005.gif
http://www.gfmer.ch/genetic_diseas...ist.php?offset=45&cat3=661

Systemic inflammatory response

- When an injury occurs, local neutrophils and macrophages release tumor
necrosis factor-alpha (TNF-α), IL-1 and IL-6 into circulation. These particular
cytokines mediate systemic inflammatory response, in part by stimulating
hepatic production of acute phase reactants (eg, Fibrinogen, ferritin, C-reactive
protein, serum amyloid A, serum amyloid P, complement factors). Many acute-
phase proteins bind to microbes and fix complement. When increased the acute-
phase protein fibrinogen causes erythrocytes to form stacks (rouleaux) that
sediment at a faster rate than do individual erythrocytes. This aggregation rate
is termed the erythrocyte sedimentation rate, or ESR, and is a non-specific
marker of inflammation.
http://homepage.ntlworld.com/pshin..._data/Rouleaux%20Blood.JPG

Platelet-activating factor (PAF)

-typically causes vasoconstriction, bronchoconstriction, and platelet stimulation.
In very small amounts PAF causes vasodilation and increased vascular
permeability. PAF also enhances leukocyte adhesion to endothelium, chemotaxis,
phagocytosis, and degranulation.
http://ai.jsaweb.jp/fulltext/048020103/img/048020103_f01.gif

Hypertensive crisis
= persistent diastolic pressure exceeding 130 mmHg that is often associated
with acute vascular damage. Hyperplastic arteriolosclerosis which can result from
diastolic pressures >120—130 mmHg, presents as onion-like concentric
thickening of the walls of arterioles as a result of laminated smooth muscle cells
(SMC) and reduplicated basement membranes. The renal arteriolar stenosis of
hyperplastic arteriolosclerosis decreases glomerular perfusion and GFR thus
activating the renin-angiotensin aldosterone system. A further increase in blood
pressure ensues, producing a vicious cycle and malignant nephrosclerosis.
-When the rise in pressure causes retinal hemorrhages exudates, or papilledema,
accelerated- malignant hypertension is present. Patients may also have
hypertensive encephalopathy characterized by headache, irritability, alterations
in consciousness, and other signs of central nervous dysfunction.
http://doctorxdrive2.jeeran.com/images/0016.jpg
http://www.nature.com/nrrheum/jour...g_tab/ncprheum0268_F6.html

Gower’s sign
= Using the support of one’s hands to raise from a squat or from a chair
(because of proximal muscle weakness)
- Distal muscle hypertrophy, such as the calf enlargement ,allows affected
children to overcome proximal muscle weakness. (Later, fat and connective
tissue contribute to the enlargement.) Gower’s sign and calf enlargement in
a male child between 3 and 6 years of age indicates Duchenne muscular
dystrophy.
-Muscular dystrophy is a term that applies to the various diseases that manifest
with progressive muscular weakness. Duchenne muscular dystrophy is the most
common form. The genetic basic of Duchenne muscular dystrophy is mutation or
deletion of the gene that codes for the protein dystrophin. This gene is located
on the X chromosome. Duchenne muscular dystrophy is, therefore, X-linked and
is also recessive. Generally, only males are affected, while females are carriers.
-Dystrophin is a structural component of skeletal muscle fibers. It links a
component of the cytoskeleton (actin) to transmembrane proteins (α- and β-
dystrophiglycans) that are connected to the extracellular matrix. Loss of
dystrophin results in cellular injury (myonecrosis). The histologic presentation of
Duchenne muscular dystrophy is widespread muscle necrosis. On light
microscopy, variation of muscle fiber size and angulated fibers are seen. Some
fibers have centrally located (internalized) nuclei.
http://jennyndesign.com/DMD/dystrophin.JPG
http://www.mja.com.au/public/issue...9_031103/byr10494_fm-1.gif
http://neuropathology.neoucom.edu/.../QuizPics51-75/68M-dmd.JPG
http://upload.wikimedia.org/wikipe...nne-muscular-dystrophy.jpg

Acute tubular necrosis (ATN)

-ischemic injury to the kidneys, which is represented by increased BUN and
creatinine and oliguria (low urine output). Ischemic injury is often not universal:
some parts of the nephron are physiologically more susceptible to hypoxia than
others. Proximal tubules and the thick ascending limb of Henle’s loop are
located in the outer medulla of the kidney, an area that even under normal
conditions has a low blood supply. In addition, the proximal tubules and
ascending limb participate in the active (ATP-consuming) transport of ions. When
oxygen delivery to the kidney is compromised, these portions of nephron will
suffer first.
-Histologically overt ATN is characterized by flattening of the epithelial cells, loss
of the brush border in proximal tubular cells, and subsequent cell necrosis and
denudation of tubular basement membrane (TBM). Muddy brown casts which are
pathognomonic for ATN are a variant of granular pigmented casts.
http://www.pathguy.com/lectures/atn.jpg
http://cnserver0.nkf.med.ualberta....rier/Vol1/Fig.%2010-10.jpg
http://courses.washington.edu/hubio562/urinaly/mb1.html

Tetanus
- Culture of various specimen types does not frequently yield the organism and
may take several days; remember that C. tetani will only be found locally at the
wound into which they were inoculated.
-On history it is important to determine the immunization status of the patient
and the length of time since the last tetanus vaccine. In adults, booster
immunization is recommended every 10 years. Additionally the route of entry of
C. tetani is usually trauma, for example a piercing wound, a burn, illicit drug use,
contaminated soil, ora motor vehicle accident, so a recent history of a
penetrating trauma is important to elicit. Physical exam may reveal masseter
muscle spasm (“trismus” or “lockjaw”), facial grimacing “risus
sardonicus”), muscle spasms, extension of truncal muscles resulting in
opisthotonos.
http://www.airahospital.org/wp-con...09/06/risus-sardonicus.jpg
http://www.medical-look.com/diseases_images/tetanus.gif
- Blood cultures are not of much use in the diagnosis of tetanus as the disease is
caused by toxin released from a local wound infection. The organism is
infrequently isolated from the blood, and when it does grow it will take 2- 3 days
to identify. Patients with tetanus require immediate treatment based on a
presumptive diagnosis based on history and physical.

Meconium ileus
=Bilious vomiting, abdominal distention, air fluid levels, and small bowel
dilatation all indicate small bowel obstruction (SBO). The intraoperative finding of
an inspissated green mass suggests that the distal ileum has been obstructed by
dehydrated meconium. Thus, this infant is suffering from meconium ileus.
-Cystic fibrosis (CE) is the most common cause of meconium ileus. In 5-10% of
patients with CE the diagnosis is made soon after birth because of this
complication. Abnormalities in chloride, sodium, and water transport by the
ductal epithelium of intestinal mucous glands cause isotonic dehydration of the
lumen contents. The result is secretion of abnormally viscous mucus into the
small bowel. In the US, cardiorespiratory complications (e.g. pneumonia
bronchiectasis, bronchitic obstructive pulmonary disease, and cor pulmonale)
account for 80% of deaths due to CE.
http://www.learningradiology.com/a...0Ileus/mecileuscorrect.htm
http://bms.brown.edu/pedisurg/imag...l/MeconiumIleusPellets.jpg

Migratory thrombophlebitis
- should always make you think “cancer.”
- Hypercoagulability is a very common paraneoplastic syndrome seen most
commonly in adenocarcinomas of the pancreas, colon, or lung.
-Hypercoagulability occurs because adenocarcinomas produce a thromboplastin-
like substance that is capable of causing chronic intravascular coagulations that
are both disseminated and tend to migrate. Migratory superficial
thrombophlebitis is “Trousseau’s sign.”
http://www.residentandstaff.com/issues/articles/2007-06_05.asp

Communicating hydrocephalus
=Symmetrical enlargement of the ventricles
- usually occurs secondary to dysfunction or obliteration of subarachnoid villi.
This dysfunction is usually a sequelae of meningeal infection (including
tuberculosis meningitis) or subarachnoid intra ventricular hemorrhage.
http://neuroanimations.com/Hydrocephalus/Commun_Med.html
- The path of CSI flow is as follows: lateral ventricles — interventricular
foramen of Monro —the third ventricle — cerebral aqueduct — the fourth
ventricle — the foramina of Luschka and Magendie — subarachnoid space. In
the subarachnoid space CSF is absorbed by arachnoid granulations and then
enters the venous sinuses. The dynamic balance between production and
absorption of CSF allows stable intracranial volume (120-150 ml) and pressure
(50-180 mm H20).
If the normal flow of CSF from the ventriculi to the subarachnoid space is
disrupted, non-communicating hydrocephalus occurs. Ventriculi above the
obstruction are enlarged, while those below the obstruction are normal.
-Congenital anomalies, such as aqueductal stenosis, Arnold-Chiari or Dandy-
Walker malformations, cause non-communicating hydrocephalus. In all cases,
the obstacle to CSF flow exists within the ventriculi.
- Communicating hydrocephalus is far more common than choroid plexus
papilloma

Villous adenoma
-Although most of colon adenomas are asymptomatic, larger ones can cause a
number of symptoms:
1. Lower intestinal bleeding causes guaiac-positive stool (fecal occult blood
testing) and microcytic hypochromic anemia. The bleeding is usually unknown to
the patient, but overt bleeding may also occur.
2. Partial intestinal obstruction can manifest with bowel habit changes, crampy
abdominal pain, constipation, and abdominal distention.
3. Villous adenomas may secrete large amounts of mucus, leading to secretory
diarrhea . If the stool volume is large, diarrhea may cause hypovolemia and
electrolyte imbalances.
4. Villous adenomas have a high risk of progression to adenocarcinoma.
http://farm4.static.flickr.com/3103/2653200355_9502991760.jpg

Primary hyperaldosteronism and "aldosterone escape"

=primary mineralocorticoid excess
- plasma renin activity is suppressed and plasma aldosterone is likely to be
elevated. Excessive mineralocorticoid secretion from tumors or hyperplasia of
the zona glomerulosa leads to sodium retention, potassium loss, and bicarbonate
retention. Hypokalemia and metabolic alkalosis are common. Hypernatremia,
however, is rare, because of the phenomenon of “aldosterone escape”
whereby increased sodium and chloride absorption leads to intravascular
hypervolemia that in turn causes release of atrial natriuretic peptide, which
causes diuresis and eventual compensatory sodium loss. For this reason these
patients do not typically have edema on physical examination.
-In summary, these patients have hypertension, hypokalemia, suppressed renin
and non-suppressible aldosterone.
DIFF
- Hyponatremia and hypokalemia with metabolic alkalosis are suggestive of
diuretic use. Diuretics lead to urinary losses of sodium potassium and chloride,
as well as increased absorption of bicarbonate due to volume contraction
(“contraction alkalosis”).
- Isolated hyponatremia in the setting of normal potassium and bicarbonate is
most likely the result of SIADH (the syndrome of inappropriate ADH secretion).
- Normal serum sodium, hypokalemia and metabolic acidosis are suggestive of
renal tubular acidosis.
- primary adrenocortical insufficiency= hyponatremia, hyperkalemia,
hypochloremia, and metabolic acidosis.

Medullary sponge kidney (MSK)

= relatively common and benign congenital disorder, characterized by cystic
dilatations of the medullary collecting ducts. The renal cortex is typically spared.
-The etiology of this disorder is not known. Most patients are asymptomatic. The
disease is usually identified during a routine imaging procedure, such as an
intravenous pyelogram .
- some patients develop kidney stones, hematuria, or urinary tract infections
secondary to this condition. Kidney stones are the most common complication of
the disease. (60% of MSK patients have kidney stones; 12% of patients with
kidney stones have MSK.)
- kidneys rarely progress to CRF. When MSK patients do develop CRF, it is
usually due to recurrent urinary tract infections or obstruction.
http://www.aboutkidneystone.info/g...edullary_sponge_kidney.jpg

Graves disease
-Infiltrative dermopathy (i.e. pretibial myxedema) and proptosis are quite
specific for Graves disease. Atrial fibrillation, hand tremors, increased alkaline
phosphatase, and heat intolerance can be present in hyperthyroidism from any
etiology.
- “pretibial myxedema” describes a diffuse, non-pitting edema and
thickening of the skin, usually present over the tibia associated primarily with
Graves disease;
http://www.pathguy.com/sol/25472.jpg
- however, the term “myxedema” describes the overall disease process of
hypothyroidism.
http://www.jcrows.com/hypothyroidismafter4.jpg
-Exophthalmos and pretibial myxedema are not seen with other causes of
hyperthyroidism, such as a toxic multinodular goiter or a toxic thyroid nodule.
- The hepatic inflammation associated with Graves disease causes an additional
slight increase of alkaline phosphatase. Remember also that the antithyroid drug
methimazole can lead to cholestasis, which causes alkaline phosphatase levels to
increase.
Bacterial endocarditis
- erythematous, sometimes hemorrhagic, macules on the sole of the foot are
likely Janeway lesions. Janeway lesions are the result of septic embolization from
infected cardiac valve vegetations. These microemboli tend to localize to the
palms and soles, and the resultant lesions are painless.
-Janeway lesions are composed of bacteria, neutrophils, necrotic material, and
subcutaneous hemorrhage. On histologic examination, subcutaneous
microabscesses are apparent.
-In contrast to Janeway lesions Osler nodes are painful papulopustules found in
the pulps of the fingers and toes.
http://4.bp.blogspot.com/_nFuCC8zh...EY/s400/janeway_lesion.jpg
http://2.bp.blogspot.com/_nFuCC8zh...FR8c/s400/osler_s_node.jpg
DIFF:
- A hypersensitivity-type vasculitis (microscopic polyangiitis) could cause
cutaneous purpuric maculopapule or nodules (palpable purpura)
http://vasculitis.med.jhu.edu/typesof/images/purpura_MPA.jpg
- A neoplastic proliferation of cells of vascular origin = Kaposi’s sarcoma
http://www.daviddarling.info/encyclopedia/K/Kaposis_sarcoma.html
- Granulomatous inflammation can produce cutaneous lesions in miliary
tuberculosis, sarcoidosis, and leprosy.
http://www.nlm.nih.gov/medlineplus/ency/imagepages/2534.htm
http://upload.wikimedia.org/wikipe...ated_cutaneous_lesions.jpg

Hypercalcemia
- The most common cause of hypercalcemia in the outpatient setting is primary
hyperparathyroidism secondary to a benign parathyroid adenoma.
- the differential diagnosis must include multiple endocrine neoplasia (MEN)
syndrome. MEN 1 is characterized by tumors of the pituitary, parathyroid gland,
and pancreas (the “3 Ps”).
http://www.pathology.med.ohio-stat.../Images/10531/PAXIT017.JPG

Hodgkin’s disease (HD)

=either nontender lymphadenopathy or have lymphadenopathy incidentally
detected on routine chest x-ray
-many patients develop associated systemic symptoms (B symptoms).
- HD has a bimodal age distribution with one peak in the second and third
decades of life and another peak in the fifth decade.
-The complete blood count and peripheral blood smear are usually unremarkable
in most patients. Only a lymph node biopsy can definitively distinguish this
malignancy from benign causes of lymphadenopathy. The key to diagnosing HD
is detection of the characteristic Reed-Sternberg (PS) cell on H&E preparation.
RS cells have ample cytoplasm, bibbed or double nuclei, and inclusion-like
eosinophilic nucleoli. RS cells are seen against a background of lymphocytes,
histiocytes and eosinophils in classic HD.
http://gemininotcancer.files.wordp...ocyte_nci-vol-7172-300.jpg
http://www.healthoma.com/images/po...gkins-disease-pictures.jpg

Large B-cell lymphoma

= diffuse sheets of large lymphocytes with nuclei at least 5x the size of small
lymphocytes.
http://www.mabthera.com/portal/eip...selargeb-celllymphomadlbcl

Pericarditis
-The chest pain of pericarditis is sharp and pleuritic in nature, and
characteristically decreases when the patient sits up and leans forward.
-Fibrinous or serofibrinous pericarditis is the most common variant, and the
pericardial friction rub is the most striking physical finding. In most instances,
this type of pericarditis is caused by myocardial infarction, rheumatic fever, or
uremia, though a viral infection may occasionally cause a fibrinous exudate to
accumulate in the pericardial space.
http://www.merck.com/media/mmpe/figures/MMPE_07CVS_78_01_eps.gif

Kussmaul’s sign
- During inspiration the jugular venous pressure and level of distension normally
decrease. Kussmaul’s sign is a paradoxical increase in the jugular venous
pressure with inspiration. Kussmaul’s sign is found most often in patients
with chronic constrictive pericarditis, a condition that takes months or years to
develop.
-The differential diagnosis for Kussmaul’s sign includes cardiac tamponade,
restrictive cardiomyopathy, severe right-sided heart failure, and tricuspid
stenosis.

Gastrinomas
= neuroendocrine tumors that are most commonly located in the pancreas, the
peripancreatic tissue around the head of the pancreas, or the duodenum. The
gastrin produced by these tumors stimulates gastric acid production, resulting in
gastrointestinal ulcerations, oftentimes in unusual locations such as the jejunum.
In fact the presence of jejunal ulcers is strongly suggestive of a diagnosis of
gastrinoma.
-Patients with gastrinomas also often complain of diarrhea and abdominal pain.
-The diagnosis of gastrinoma is made by measuring basal and stimulated gastrin
levels. Workup of all patients with newly diagnosed gastrinoma should include
measurement of serum calcium PTH and pituitary hormones, because of the
association with MEN-I. Proton pump inhibitors are the first-line therapy for most
gastrinomas.

Isolated amyloidosis
- Localized amyloidosis confined to the cardiac atria (isolated atrial amyloidosis,
or IAA) is due to deposition of abnormally folded (β-pleated sheet conformation)
atrial natriuretic peptide-derived proteins. The incidence of IAA increases with
age, reaching > 90% in the ninth decade. This is a form of senile cardiac
amyloidosis which may increase the risk of atrial fibrillation.
- Islet amyloid protein (amylin) is usually found in patients with localized
pancreatic amyloidosis. It is detected in the pancreatic islets of more than 90%
of patients with type 2 diabetes.
- β-amyloid protein is the 4000 Dalton peptide found in the core of the cerebral
plaques of Alzheimer disease. β-amyloid protein is also found in localized
amyloid deposits in the walls of cerebral blood vessels of Alzheimer patients as
well as in patients with cerebral amyloid angiopathy (CAA).

DIFF:
-Deposition of immune globulin light chains, especially 1-light chains and their
fragments is responsible for primary systemic (not localized) amyloidosis.
Primary systemic amyloidosis arises in association with monoclonal B- cell
proliferations (e.g. multiple myeloma) and causes systemic amyloid deposition
involving the heart, as well as the skin, tongue, gastrointestinal tract, kidney,
and peripheral nerves. Immunoglobulin light chains of either the Y or the K
variety (Bence Jones proteins) may also be found in the serum and urine.
http://www.ajronline.org/cgi/content/full/179/2/536/FIG2
http://www.proteotech.com/amyloid_pop2.html

Craniopharyngiomas
= tumors arising from remnants of Rathke’s pouch. The anterior pituitary is
formed from an out-pouching of the pharyngeal roof and is called Rathke’s
pouch. The posterior pituitary gland arises from an extension of the
hypothalamic neurons. Together, the anterior and posterior pituitary glands lie in
the sella turcica at the skull base.
-During the time of pituitary development, remnants of Rathke’s pouch cells
can remain in the diencephalon (the posterior region of the forebrain). Neoplastic
transformation of these “pouch cells” is called a craniopharyngioma.
-Typically, craniopharyngiomas have three components: solid, comprised of the
actual tumor cells; cystic filled with “machinery oil” liquid; and a calcified
component. Any suprasellar mass with three components is highly suggestive of
craniopharyngioma.
-Craniopharyngioma symptoms include headaches, visual field defects, and
hypopituitarism, evidenced by growth retardation. Ultimately, compression of the
pituitary stock by craniopharyngioma leads to hyperprolactinemia by loss of
dopaminergic inhibition. Craniopharyngiomas are usually tumors of childhood,
being most frequently discovered between the ages of 5 and 10 years of age.
http://www.pathguy.com/lectures/craniopharyngioma.jpg
http://radiopaedia.org/uploads/images/0000/0781/Craniopharyngioma.thumb.jp
g
http://biology.clc.uc.edu/Fankhauser/Labs/Anatomy_&_Physiology/A&P202/Endo
crine_System/histology_jpgs/pituitary_40x_P2252250lbd.JPG

Amyloid associated with Alzheimer disease

= is called A3 amyloid, which is a product synthesized by the cleavage of APP
(amyloid precursor protein). APP is a normal component of neuronal membranes.

1. Amyloid deposits in brain parenchyma form senile plaques. The core of these
structures is composed of A3 amyloid.
2. Amyloid deposits in vascular walls lead to amyloid angiopathy. These deposits
damage the media and adventitia of cerebral vessels and cause thickening of the
basal membrane, stenosis of the vessel lumen and fragmentation of the internal
elastic lamina.
-Both senile plaques and amyloid angiopathy may also be seen in the brain
tissue of healthy elderly individuals.
http://www.elements4health.com/images/stories/conditions/amyloid-plaque-
formation.jpg
http://radiographics.rsna.org/content/26/5/1517/F1.expansion?ck=nck
http://wiki.cns.org/wiki/images/9/9c/CAA2.gif

Vascular dementia (also called multi-infarct dementia)

=the second most common cause of dementia after Alzheimer disease. It results
from brain injury sustained during multiple cerebral infarcts. Vascular dementia
is associated with hypertension, multiple ischemic strokes and systemic
atherosclerosis. The presence of amyloid is not characteristic.
http://www.annals-general-psychiatry.com/content/2/1/8/figure/F1

Hypertensive heart disease

= concentric hypertrophy
- Concentric hypertrophy uniformly thickens the ventricular wall while the outer
dimensions of the ventricle remain almost unchanged, thus resulting in a
narrowed ventricular cavity size. Concentric hypertrophy results from chronic
elevation of the ventricular pressure during systole (pressure overload), as is
typically seen in hypertension due to the increased LV afterload.
http://omeweb2.ucdavis.edu/pmd/robbins/cvd5/cvd530.htm
http://firstaidteam.com/usmlerximages/d/61-
3/USMLERxConcentric+left+ventricular+hypertrophy.gif

Wolff—Parkinson—White syndrome
=an electrophysiological abnormality of atrioventricular cardiac conduction.
These patients have accessory pathways which directly connect the atria and
ventricles and bypass the AV node. This results in pre-excitation and
arrhythmias.
http://rezidentiat.3x.ro/eng/tulbritmeng.files/image034.gif

Rb protein
An increase in the activity of enzymes responsible for DNA synthesis signifies
that the cell is in the S phase of the cell cycle. The transition from GI to S phase
is one of the two primary cell cycle checkpoints that ensure “quality
control” of the DNA. Cells with damaged DNA are not allowed to enter the S
phase.
-Retinoblastoma (Rb) protein is a regulator of the G1 —.S phase transition. The
Rb protein is present in one of two forms: active (hypo phosphorylated) or
inactive (hyper phosphorylated). The resting cells in the G0 phase contain active
(hypo phosphorylated) Rb protein.
1. When the cell is stimulated by growth factor, activation of cyclin D, cyclin E
and the corresponding cyclin kinases (CDK 4 and 6) occurs and the Rb protein is
hyper phosphorylated (rendering it inactive). Hyper phosphorylated Rb releases
E2F transcription factor, which allows the cell to progress through the G1 —.S
checkpoint.
2. If the Rb protein is hypo phosphorylated (active), it binds to the E2F
transcription factor. This complex inhibits the transcription of genes necessary
for G1 —S transition. Active Rb protein, therefore serves as a “brake”
that stops the cell from dividing.
http://www.nature.com/nrc/journal/v3/n7/images/nrc1123-f3.gif
http://www.nature.com/emboj/journal/v23/n24/fig_tab/7600481f2.html

Bullous pemphigoid
=Primarily a disease of the elderly
=autoimmune condition characterized by antibodies that attack
hemidesmosomes along the basement membrane of the dermal-epidermal
junction. The activity of these autoantibodies results in complement fixation, and
the recruited neutrophils and eosinophils can cause significant tissue injury.
Eventually, a subepidermal, non acantholytic blister appears in conjunction with
superficial edema and perivascular lymphocytic infiltrate.
-Vacuolations in the basal cell layer coalesce to form the fluid-filled blisters that
are the hallmark of bullous pemphigoid.
-Clinically, the lesions of bullous pemphigoid are serous fluid-filled, tense bullae
on bases of normal to erythematous skin typically measuring 2 cm in diameter.
The most common sites of involvement on the body include the inner thighs,
flexor aspects of the forearms, axillae, groin, and lower abdomen.
http://www.americangeriatrics.org/directory/ABIM/GRS/Fig56_4.jpg
http://missinglink.ucsf.edu/lm/DermatologyGlossary/img/Dermatology
%20Glossary/Glossary%20Histo
%20Images/bullous_pemphigoid_higher_power_thumb.jpg
http://missinglink.ucsf.edu/lm/DermatologyGlossary/img/Dermatology
%20Glossary/Glossary%20Histo%20Images/bullous_pemphigoid_low_power.jpg

Malabsorption
- The main clinical manifestation of this syndrome is steatorrhea: foul-smelling
bulky, greasy stool that contains large amounts of fat. Excess fat content will
cause the stool to float in the toilet bowl. Weight loss and symptoms of various
nutritional deficiencies are common.
-Anemia may result from iron folate, and/or vitamin B12 deficiency.
-Fat-soluble vitamins (K, A, D, and E) may also be lost. Vitamin K deficiency may
cause petechiae and easy bruising.
-Decreased calcium and vitamin D absorption leads to bone pain.
-Muscle wasting and edema (protein deficiency) hyperkeratosis (vitamin A
deficiency), and tetany (due to hypocalcaemia) can occur.
-Multiple disorders that cause malabsorption are divided into the following major
groups:
1. Pancreatic exocrine insufficiency: chronic pancreatitis and cystic fibrosis
belong to this group of disorders. Diminished production of digestive pancreatic
enzymes leads to impaired hydrolysis of nutrients in the small intestine.
2. Intestinal mucosal defects: examples are celiac disease, tropical sprue
Whipple disease, Crohn disease and many others. Structural defect or injury to
the intestinal epithelial cells hampers nutrient transport from the intestinal lumen
and/or from intestinal cells to peripheral organs.
3. Bacterial proliferation in the small bowel occurs in afferent loop syndrome
diverticulosis, and diabetic neuropathy. Bacteria compete for nutrients causing
relative nutrient deficiency.
-The first step in screening for malabsorption is Sudan lll stain . Quantitative
analysis for fecal fat is used to confirm the diagnosis (>7gm/day of excreted fat
is diagnostic for malabsorption). Further diagnostic steps are then taken to
identify the primary cause of malabsorption.

Cell cycle
=the sequence of events that separates one cell division from the next. It
consists of an inactive phase, interphase, and mitosis.
1. G 0 phase is the stage in which the cell cycle is suspended. The cells are
resting and do not divide.
2. Interphase comprises 90% of the cell cycle and is the stage in which the cell
prepares for division. Interphase is subdivided into the G1 phase (ie, synthesis of
RNA protein, lipid, and carbohydrate), S phase (ie, DNA replication), and the G2
phase (ie, ATP synthesis).
3. Mitosis (M) is the stage in which the cell divides into two daughter cells.
At both the G1 to S phase transition and the G2 to M phase transition, the cell
cycle can be stopped. These stages are called “checkpoints” and are
regulated by cyclins and cyclin-dependent kinases that screen for DNA damage
or abnormalities. Cells with normal DNA are allowed to proceed through the
checkpoint, while cells with damaged DNA trigger DNA repair mechanisms. If the
DNA damage is too substantial to be repaired, the cell undergoes apoptosis.
-The Rb (retinoblastoma) tumor suppressor gene located on chromosome 13q14
encodes a nuclear phosphoprotein that regulates the G1 —S checkpoint. -Rb
protein can be in an active (Hypophosphorylated) state or an inactive
(hyperphosphorylated) state. The inactivated Rb protein allows the cell to
proceed through the G1 —.S checkpoint. The activated Rb protein, in contrast,
stops the cell cycle. Abnormal phosphorylation of Rb protein results in its
inactivation, thereby allowing cells with damaged DNA to proceed through the G1
—S checkpoint and then divide. Mutations of the Rb protein have been linked to
retinoblastoma, osteosarcoma, breast adenocarcinoma, small cell carcinoma of
the lung, and bladder carcinoma.
http://www.mun.ca/biology/desmid/b...L2060/BIOL2060-19/1936.jpg

Wegener’s granulomatosis
= Necrotizing vasculitis of the upper and lower respiratory tract (causing nasal
ulcerations, sinusitis hemoptysis) and rapidly progressive
glomerulonephritis—producing a variable degree of renal failure—is
characteristic of Wegener’s granulomatosis. This disease is associated with
C-ANCAs, which may target neutrophil proteinase 3.
- Cytoplasmic staining antineutrophil cytoplasmic antibodies (c-ANCAs) are
virtually pathognomonic for Wegener’s, with a better than 90% specificity
and sensitivity. C-ANCA may also be useful as a quantitative measure of disease
activity.
http://www.nature.com/ki/journal/v64/n6/fig_tab/4494120f3.html
http://brighamrad.harvard.edu/Cases/bwh/images/344/path1.jpg
http://www.som.tulane.edu/classwar...8/Lung_Review/Lung-56.html
DIFF:
- Goodpasture syndrome is sometimes called anti-glomerular basement
membrane (GBM) antibody disease. Presenting clinical manifestations of
Goodpasture syndrome are hemoptysis, radiographic focal pulmonary
consolidations and a glomerulonephritis that may rapidly progress to renal
failure. Upper respiratory tract ulceration is not characteristic.
Lung cancer
-One reason for this high mortality rate is the early hematogenous spread of the
tumor.
-The adrenals are the most common site of hematogenous spread of lung
cancer. Adrenal metastases account for more than half of all metastases of lung
neoplasms. They may be unilateral or bilateral and are almost always
asymptomatic. Symptoms of hypoadrenalism (dizziness, weakness, hypotension)
occur only with extensive bilateral metastases. Early detection of adrenal
metastases is important because it determines the treatment strategy. The
presence of adrenal metastases indicates stage IV disease, which should be
treated with chemotherapy.
-Liver metastases represent about 30% of the metastases of lung cancers.
-Other common sites of lung cancer metastases include: bone, brain, and the
contralateral lung.

DIC
= common complication of gram-negative bacterial sepsis, acute pancreatitis,
and burn injury. In gram-negative sepsis, DIC results from activation of the
coagulation cascade by bacterial endotoxins, causing the formation of
microemboli. Peripheral smear shows fragmented RBCs (microangiopathic
hemolytic anemia) and thrombocytopenia. Lab tests show prolongation of PT,
PTT, and decreased fibrinogen, factor V, and factor VIII levels.

Selective proteinuria
=Albumin loss with minimal loss of the more bulky proteins (such as lgG and
macroglobulin)
- A filtration barrier to protein molecules is provided by the glomerular capillary
wall, which contains three components: fenestrated endothelium, the glomerular
basement membrane (GBM) and epithelial cells. The barrier is selective to size
and charge.
- Size selectivity is a feature of the dimensions of the pores. Endothelial cells
have fenestrations with an approximate radius of 40 nm. GBM pores have a
radius of 4 nm. Between the foot processes of epithelial cells there is a thin
membrane (a slit diaphragm) with pores the same size as those in the GBM. The
GBM and slit diaphragms are, therefore, the most selective determinant of
particle penetrance with regard to size.
- Charge selectivity is provided by negatively charged anions (ie. heparan sulfate
and other proteoglycans) located on endothelial cells and the GBM. They repel
negatively charged molecules such as albumin.
- Albumin is a protein with molecular weight of 70000 daltons, and a radius of
3.6 nm. Since albumin is small enough to fit through pores in the GBM the
barrier to its excretion is provided mostly by charge selectivity. In minimal
change disease (MCD), some of the negatively charged molecules that provide
charge selectivity are lost from the glomerular basement membrane.
Subsequently albumin is lost via the urine.
http://pathcuric1.swmed.edu/PathDemo/kid1/kid170.htm
http://sinoemedicalassociation.org...gery/kidney%20diseases.htm
DIFF:
- Tubular proteinuria= associated with the presence of low molecular weight
proteins such as b2- microglobulin, immunoglobulin light chains, amino acids and
retinol-binding protein. These are normally filtered by the glomerulus and almost
completely reabsorbed in the proximal tubule. They appear in urine when the
proximal tubular function is disrupted for instance in tubulointerstitial nephritis.
http://www.jci.org/articles/view/36150/files/JCI0836150.f1/medium
http://path.upmc.edu/cases/case41/images/micro14.jpg

Functional proteinuria
=caused by a change in blood flow through the glomerulus. Precipitating factors
include exercise, high fever, emotional stress or cold exposure. It is a common
cause of proteinuria in young adults with normal renal function and disappears
on repeated testing.

Orthostatic proteinuria
- predominantly occurs in older tall thin adolescents and is characterized by
increased protein excretion in the upright position but normal protein excretion
in the supine position. Albuminuria is usually less that 1.0 g/day, renal function
is normal and overnight collection of urine reveals normal albumin excretion
(less than 50 mg during 8 hour period).

Isolated proteinuria
= usually an incidental finding in an asymptomatic individual with normal renal
function and normal urinary sediment. No manifestations of systemic disease are
present.

Acute viral hepatitis

= low-grade fever, anorexia, nausea, dark colored urine, and right upper
quadrant tenderness.
- HAV is the most common cause of acute viral hepatitis in young adults.
In all cases of acute viral hepatitis, diffuse ballooning degeneration (hepatocyte
swelling), mononuclear cell infiltrates, and Councilman bodies (eosinophilic
apoptotic hepatocytes) are seen histologically. (Liver biopsy is not needed to
make the diagnosis of HAV infection, however.)
http://www.meddean.luc.edu/Lumen/meded/orfpath/images/8-4-4.jpg
http://focosi.altervista.org/apoptoticbodies.jpg

Alzheimer disease
=the most common cause of dementia. It has the following characteristic
features:
1. Prevailing clinical symptom: slow, progressive memory loss.
2. Macroscopic brain appearance: mild-to-moderate generalized brain atrophy.
3. Microscopic brain changes: neurofibrillary tangles, senile plaques, and amyloid
angiopathy.
4. Biochemical abnormalities: decreased acetylcholine levels in the hippocampus
and nucleus basalis of Meynert.
-The most important biochemical abnormality noted in Alzheimer disease is a
decrease in acetycholine level. This occurs due to the deficiency of choline
acetyltransferase. The decline in acetylcholine levels is most notable in the basal
nucleus of Meynert, which participates in memory and cognition. This nucleus is
located at the base of the forebrain and widely projects to the neocortex.
Another involved structure is the hippocampus: the major function of the
hippocampus is formation of new memories.
http://www.ahaf.org/alzheimers/abo...g/plaques-and-tangles.html
http://www.pathology.vcu.edu/WirSe.../image/dementia/tangle.jpg
http://www.anatomyatlases.org/Micr...natomy/Images/Plate361.jpg
http://www.med.harvard.edu/AANLIB/cases/case3/mr1/040.html
neuroblastoma = MC extracranial childhood cancer, 1-2 y/o
=retroperitoneal mass + HTN + anorexia, weight loss
=solid sheets of small cells with dark nuclei and scant cytoplasm (small blue
round cells)
=high catecholamines in urine
=increased number of copies of the N-myc gene
=paraneoplastic sd: opsoclonus, myoclonus, truncal ataxia

http://www.adhb.govt.nz/newborn/Te...blastoma/Neuroblastoma.jpg

http://visualsonline.cancer.gov/pr...mageid=2593&fileformat=jpg

Medulloblastoma
= the second MC brain tumor in children
=arises in the cerebellum and causes gait and limb ataxia
http://www.sflorg.com/sciencenews/images/imscn051606_02_01.jpg
http://www.sflorg.com/sciencenews/images/imscn051606_02_02.jpg

Dystonias= impaired function of the basal ganglia

-MC focal dystonia = spasmodic torticollis
-blepharospasm, writer’s cramp

Chorea: Huntington disease

Hemiballism: contralateral injury in or near the subthalamic nucleus

Aflatoxins are categorized as A1, B2, G1, and G2, with aflatoxin B1 the most
common and most toxic.
-High levels of dietary aflatoxin exposure is associated with a G:C — T:A
transversion in codon 249 of the p53 gene a mutation thought to greatly
increase the risk of developing hepatocellular carcinoma
http://www.pathology.med.ohio-stat.../Images/10534/PAXIT025.JPG

Kawasaki disease= vasculitis of medium-sized arteries that affects very young

children (12-24 months of age). The most serious complication =coronary artery
involvement leading to the development of coronary artery aneurysms.
Symptoms of Kawasaki disease include:

1. Fever 2. Bilateral conjunctivitis 3. Lymphadenopathy 4. Cutaneous

involvement:
1. Oropharyngeal: Erythema of the palatine mucosa, fissured erythematous lips,
“strawberry” tongue
2. Peripheral extremities: Edema of hands and feet, erythema of palms and
soles, desquamation of the fingertips (periungual)
3. Generalized rash: Polymorphous (usually urticarial) erythematous rash
beginning on the extremities and moving to the trunk (centri petal spread)

There are two types of membranoproliferative glomerulonephritis.

- Type I = with upper respiratory tract infections and causes a nephrotic
sediment
- Type II = also called "dense deposit disease"= nephritic sediment.
-Both are caused by immune complex deposition in the glomerular basement
membrane.
Gastric adenocarcinoma:
- Intestinal type forms a solid mass that projects into the stomach lumen and is
composed of glandular-forming cuboidal or columnar cells.
- Diffuse carcinoma (linitis plastica) infiltrates the stomach wall and displays a
signet-ring pattern on light microscopy.
http://web2.iadfw.net/uthman/specimens/images/gastcarc_enface.jpg

http://www.pathologyatlas.ro/patho..._diffuse_type_mucinous.jpg

Von Willebrand disease (vWF deficiency)

= impairments of platelet function and coagulation pathway abnormalities.
= prolonged bleeding time and decreased platelet aggregation in response to
ristocetin
-the ristocetin aggregation test is used to measure vWF-dependent platelet
aggregation. Ristocetin activates Gp Ib-IX receptors on platelets and makes
them available for vWF binding. When the vWF level is decreased, there is poor
platelet aggregation in the presence of ristocetin.
=abnormal menstrual bleeding/Bleeding of the gums/Bruising/Nose bleeds/Skin
rash
=more common and milder than hemophilia
-definitive diagnosis of von Willebrand disease = measuring the levels of
different fractions of vWF factor.
-Rx= desmopressin (DDAVP)I which stimulates vWF release from endothelium.
Blood products containing vWF are used in severe forms of von Willebrand
disease.

Hereditary deficiency of GP lIb-Illa receptors=Glanzmann thrombasthenia

= mucocutaneous bleeding and increased bleeding time. Platelet aggregation in
response to ristocetin is normal, but is decreased with addition of ADP.

Deficiency of thromboxane A2= with aspirin treatment, due to irreversible

inactivation of COX in platelets.
= decreased platelet adhesion and aggregation
- The ristocetin aggregation test is normal.

Primary ciliary dyskinesia

=autosomal recessive mutation in the microtubule-associated protein dynein,
can cause Kartagener’s syndrome in about 50% of patients (variable
penetrance). Kartagener’s syndrome is characterized by male infertility, situs
inversus, recurrent sinusitis, and bronchiectasis.

Most cases of hypertrophic cardiomyopathy

= mutations in the genes encoding cardiac sarcomere proteins

Burkitt lymphoma
=“starry sky” appearance due to the presence of macrophages and
apoptotic bodies in a sea of medium-sized lymphocytes. The rates of mitosis and
apoptosis in the cancerous tissue are high. Almost all cases of Burkitt lymphoma
are associated with translocations of the C-MYC gene on chromosome 8, usually
onto the Ig heavy chain region of chromosome 14 [t(8:14)].
- very aggressive, responds well to intensive, short-term, high-dose
chemotherapy
-endemic (African type) Burkitt lymphoma: jaw involvement; asso/w EBV
infection

http://www.pathguy.com/lectures/l3.jpg

Holoprosencephaly = from failure of forebrain cleavage into cerebral

hemispheres= congenital malformation, a primary abnormality in a development
process.
-Amniotic band syndrome = disruption (secondary destruction of a previously
well-formed tissue or organ).
-Congenital hip dislocation, clubbed feet and flat facies (Potter syndrome) are
deformations (secondary to extrinsic compression).
- Potter syndrome = a sequence.
http://www.amnioticbandsyndrome.com/handcloseup.jpg

Autosomal Recessive (infantile) Polycystic Kidney Disease (ARPKD) manifests in

infants. Most of these patients die shortly after birth or during the first years of
their lives.
ADPKD = the most frequent genetic cause of renal failure in adults, accounting
for 10% of patients on dialysis in the United States = autosomal dominant.

Trinucleotide repeat mutations

= three-nucleotide sequence is abnormally repeated. Such mutations cause
fragile X syndrome, myotonic dystrophy, and Huntington disease.

Mitochondrial disease:
Myoclonic epilepsy with ragged red fibers syndrome, Kearns-Sayre syndrome ,
Leber’s hereditary optic neuropathy
= bright red irregular (moth eaten) subsarcolemmal depositions with Gomori
trichrome on frozen sections
http://webeye.ophth.uiowa.edu/eyef...ggedredfibers_03252005.jpg

Thromboangiitis obliterans (Buerger’s disease)

= vasculitis of medium and small-sized arteries, principally the tibial and radial
arteries.
= acute and chronic inflammation of the arterial walls, often with thrombosis of
the lumen, which can undergo organization and recanalization. This segmental
thrombosing vasculitis often extends into contiguous veins and nerves (a feature
rarely seen in other types of vasculitis). The inflammatory process may
eventually encase all three structures (arteries, veins, and nerves) in fibrous
tissue.
- Onion-like concentric thickening of arteriolar walls = malignant hypertension
-Granulomatous inflammation of the media= temporal (giant cell) arteritis
- Transmural inflammation of the arterial wall + fibrinoid necrosis = polyarteritis
nodosa.
- Lipid-filled intimal plaques that bulge into the arterial lumen= atherosclerosis.

DIC :
=bleeding +PT and PTT are prolonged +Low fibrinogen and increased FDP
TTP/HUS:
-no bleeding, normal fibrinogen, PT, PTT

Keloids
=excessive collagen formation during tissue repair in susceptible individuals.
=soft or firm nodules that grow beyond the borders of the wounds within which
they form with claw-like extensions onto normal tissue.
= large collagen bundles lying in parallel with one another and excess cellular
connective tissue.
- Unlike keloids, hypertrophic scars are limited to the area of the wound and may
regress spontaneously though this is uncommon.

Wound healing= three phases:

1. The inflammatory phase consists of movement of neutrophils (within first 24
hours) and macrophages (2-3 days) to the damaged area and phagocytosis of
necrotic debris and bacterial contaminants.
2. The proliferative phase begins 3-5 days after the injury. Fibroblasts and
endothelial vascular cells proliferate to form connective tissue and blood vessels
(neovascularization) respectively. During this phase, granulation tissue looks
pink, friable and edematous.
3. The maturation phase is characterized by fibrosis (scar formation) and starts
during the second week after the injury. During this phase active fibroblasts
synthesize collagen elastin and other components of the connective tissue
matrix. By 6-8 weeks initial scar formation is complete and the wound reaches
30-40% of normal tensile strength during this time. Maturation of the scar
continues for the next several months with a slowly progressive increase in
tensile strength occurring over that span of time.

Subungual splinter hemorrhages: splinter- or flame-shaped hemorrhagic streaks

in the nailbed that appear as a consequence of microemboli. Infectious
endocarditis (IE) is the usual source of such microemboli.
Janeway lesions (small, erythematous or hemorrhagic macular, nontender
lesions on the palms and soles) are a sign of microembolism as well.

Complete mole
=46 XX or XY (paternal origin), 15% risk of malignant trophoblastic disease;
bunch of grapes appearance; the uterus is enlarged out of proportion to the
gestational age. There may be pre-eclampsia, hyperthyroidism and theca-lutein
cysts as well.
Partial mole
=69 XXX or XXY, normal villi and fetal tissue are also present; low risk of
malignancy

Malignant mesothelioma
= rare neoplasm that arises from the pleura or peritoneum
= strongly associated with asbestos exposure
- Hemorrhagic pleural effusions and pleural thickening are characteristic.
-Electron microscopy is the gold standard for diagnosis, revealing tumor cells
with numerous, long, slender microvilli and abundant tonofilaments.
http://health.act.gov.au/gfx/pubs/-1843038135_r0.jpg

http://www.mesothelioma-asbestos-l...formation/images/meso9.jpg

Bronchioloalveolar carcinoma
= is a variant of adenocarcinoma. It almost always arises at the periphery of the
lung and has a characteristic distribution along the alveolar septa without
vascular and lymphatic spread. On chest x-ray it appears as a peripheral mass or
as an area of pneumonia-like consolidation.
http://www.brown.edu/Courses/Digit...emic_path/pulmonary/L4.jpg

Small cell carcinoma

= usually arises from the major bronchi. On chest imaging it is seen as a hilar
mass. Neuroendocrine markers such as chromogranin and synaptophysin are
usually positive.
http://farm4.static.flickr.com/3146/2921388243_e748573afe.jpg

Squamous cell carcinoma also arises from the major bronchi. Imaging will show
a hilar mass. Histologically, it is characterized by keratinization and intercellular
bridges. This tumor can sometimes present as a cavitary lung lesion.
http://www.pathologyatlas.ro/patho..._carcinoma_skin_detail.jpg

The major clinical manifestations of factor V Leiden

= deep vein thrombosis (DVT), cerebral vein thrombosis, and recurrent
pregnancy loss.
-Factor V Leiden is the most common cause of inherited thrombophilia, with the
heterozygote prevalence of this genetic mutation ranging from 1-9% in
Caucasian populations worldwide. Heterozygote carriers of factor V Leiden have
five to ten times the risk of developing a thrombosis, while homozygote carriers
of factor V Leiden have fifth to one hundred times the risk of developing a
thrombosis.
-Because factor Va is a cofactor in the conversion of prothrombin to thrombin,
persistently circulating factor Va Leiden results in increased thrombin production

Renal artery stenosis (RAS)

=is most often caused by atherosclerotic plaques at the junction of the aorta and
the renal artery
-On light microscopy of the smaller kidney, tubular atrophy with decreased
tubular epithelial size, tubuloclerosis, patchy inflammation, and fibrosis of the
interstitium and glomerular atrophy would be seen.
- renal blood flow is normally 3-5 times greater than that of blood flow in other
organs. When renal perfusion pressure decreases to 70-85 mm Hg for any
reason renin-secreting cells of the juxtaglomerular apparatus are stimulated to
convert angiotensinogen to angiotensin l, which is then converted to angiotensin
II. Angiotensin II is a potent vasoconstrictor and also releases aldosterone. This
vasoconstriction is necessary to maintain glomerular filtration. The
vasoconstriction that occurs causes hypertension.
- proceed cautiously with ACE inhibitors when RAS is present because elevated
levels of angiotensin II are necessary to maintain glomerular filtration in these
patients, and a sudden decrease in renal function may develop.
http://www.ajronline.org/content/v...ge/09_07_2426_14_cmyk.jpeg

Antiphospholipid antibody syndrome

= common immune cause of hypercoagulability.
=the presence of antiphospholipid antibodies (lupus anticoagulant and/or
anticardiolipin antibodies) plus one or more of the following: venous
thromboembolism, arterial thromboembolism, or frequent fetal loss.
- patients with antiphospholipid antibody syndrome typically have a prolonged
baseline aPTT. Lupus anticoagulants are the most common cause of aPTT
prolongation.

Paraneoplastic syndrome of hypercoagulability

= in some patients with cancer, especially patients with adenocarcinomas of the
pancreas, colon, or lung. The mechanism of cancer-induced hypercoagulability is
thought to involve release of procoagulant tumor products. Vascular stasis due
to obstruction of blood flow by the tumor, patient immobility, hepatic
involvement and dysfunction, sepsis, and advanced age may also contribute to
the tendency toward thrombosis in cancer patients. None of these
mechanisms/factors directly promotes activated protein C resistance in the aPTT
coagulation test.

A bluish neoplasm occurring underneath the nail bed

= may be either a glomus tumor (glomangioma) or a subungual melanoma. Both
are rare diagnoses.
-A glomangioma is a tumor of the modified smooth muscle cells of a glomus
body. Glomus bodies are numerous small, encapsulated neurovascular organs
found in the dermis of the nail bed, the pads of the fingers and toes, and the
ears. Each glomus body is composed of an afferent arteriole connected to a
richly innervated, muscular arteriovenous anastomosis, which is then connected
to an efferent vein. Modified smooth muscle cells are arranged in layers around
these vascular channels. The role of the glomus body is to shunt blood away
from the skin surface in cold temperatures in order to prevent heat loss, and to
direct blood flow to the skin surface in hot environments to facilitate the
dissipation of heat.
http://www.davidlnelson.md/images/Glomus_2.jpg
Lymphangiomas
= occur subepidermally, in the head, neck, and axilla. They consist of networks
of endothelium-lined lymph spaces. Because they do not contain pigmented cells
or red blood cells, lymphangiomas would be unlikely to have a bluish
appearance.

Colonic diverticula
= usually develop due to increased intraluminal pressure and are composed of
mucosa and submucosa.
- The most common site is the sigmoid colon. Diverticula may be asymptomatic
or may manifest with painless rectal bleeding or acute diverticulitis. Chronic
constipation is a risk factor for this condition.

Traction diverticula
= occur due to inflammation and subsequent scarring and are true by structure
(consist of mucosa, submucosa and muscular layer). Example of traction
diverticula are midesophageal diverticula, which occur due to mediastinal
lymphadenitis and periesophageal scarring.

Meckel diverticulum
= an example of both a true and congenital diverticulum. It results from an
abnormality that occurs during fetal development and it consists of all layers of
the intestinal wall.

Familial hypocalciuric hypercalcemia

= autosomal disorder caused by a defective calcium-sensing receptor on the
parathyroid cells. The defective receptor does not allow PTH to be appropriately
suppressed by an increase in serum calcium level. In familial hypocalciuric
hypercalcemia, mild to moderate hypercalcemia is accompanied by normal to
high serum PTH levels. These patients have excellent long-term prognoses.
Urinary calcium excretion is the key feature that differentiates the familial
disease from hyperparathyroidism, as both conditions have elevated calcium and
PTH levels.
HCTZ
- cause hypercalcemia (and hypocalciuria) increasing the distal tubular
reabsorption of filtered calcium. The increased serum calcium levels usually
suppress PTH.

Small cell carcinoma

=the most aggressive type of lung cancer. Most patients have distant
metastases at the time of diagnosis. Surgery is usually not a treatment option,
even when the disease is localized. This tumor is sensitive to chemotherapy and
radiation.
-average lifespan following diagnosis is less than one year

Lambert-Eaton myasthenic syndrome

= paraneoplastic disorder, most commonly associated with small cell lung cancer
that clinically resembles myasthenia gravis.
=poor signal transmission at the neuromuscular junction.
-Antibodies to voltage-gated presynaptic calcium channels are found in these
patients.
-weakness improves during the day and with exercise
-nerve stimulation studies = incremental response
-no improvement after tensilon test

Varicella-zoster virus (VZV)

= enveloped double-stranded DNA virus
-Weakening of cellular immunity leads to reactivation of the virus that manifests
as herpes zoster (shingles).
= painful vesicular rash in a dermatomal distribution
-Light microscopy of a sample from a vesicle base reveals intranuclear inclusions
in keratinocytes and multinucleated giant cells (positive Tzanck smear). Skin
biopsy would show acantholysis (loss of intercellular connections) of
keratinocytes and intraepidermal vesicles. Dermal inflammatory infiltration and
leukocytoclastic vasculitis may be present.
http://www.lmp.ualberta.ca/resourc...ages/Images-T/000p028w.jpg
http://tray.dermatology.uiowa.edu/DPT/Hist/Tzanck01.jpg

Guillain-Barre syndrome
=acute demyelinating disease with an immune-mediated pathogenesis.
-Antibodies against infectious antigens are thought to cross-react with the myelin
of the spinal roots and peripheral nerves.
-On light microscopy, segmental demyelination of peripheral nerves is seen.
Demyelination is accompanied by an “endoneural inflammatory infiltrate”
consisting of lymphocytes and macrophages.
Demyelination causes ascending flaccid paralysis and areflexia. Paralysis of
respiratory muscles may occur, as can paralysis of cranial nerves, such as CN VII
(Bell’s palsy).
-CSF =increased protein with normal or only slightly elevated cell count
(albumino-cytologic dissociation).

Diabetic microangiopathy
=Hyalinization of nerve arterioles
= narrowing of the arterial lumen and ischemic nerve injury.
- Another contributing factor of diabetic neuropathy= accumulation of sorbitol
and fructose in nerve axons.
http://diabetesinfodesk.com/wp-con.../diabetic-neuropathy-1.jpg

Polymyositis
= “Endomysial” inflammatory infiltration
=bilateral, symmetric weakness of proximal muscles. Reflexes are normal, as
polymyositis involves the muscles, rather than nerves.
http://www.bcm.edu/neurology/images/nmus16.jpg

Giant cell (temporal) arteritis

=the most common form of systemic vasculitis in adults
=Granulomatous inflammation of the media with fragmentation of the internal
elastic lamina of branches of the carotid artery
= patients older than 50: headache, facial pain, jaw claudication, and vision loss,
and elevation of the erythrocyte sed rate
- because of the segmental nature of the disease, biopsy may not show
inflammation
-prevent blindness by prompt initiation of prednisone therapy; physicians may
wait to obtain ESR, but should not wait for biopsy results before starting high-
dose prednisone

Growth factors
= stimulate cell proliferation by altering the expression of certain genes in the
nucleus. After the growth factor binds its cell membrane receptor, signal
transduction systems transfer the signal to the nucleus. Examples of signal
transduction systems include:
1. MAP-kinase pathway
2. Phosphoinositide-3-kinase pathway
3. Inositol-lipid pathway
4. cAMP pathway
5. JAK/STAT pathway

MAP-kinase pathway :
http://www.brc.riken.go.jp/lab/dna/en/GENESETBANK/mapk_ras.png
http://www.youtube.com/watch?v=bYioSvT33cA
Growth factor binding to the receptor tyrosine kinase leads to auto
phosphorylation of the receptor. Phosphotyrosine produced in this reaction
interacts with a number of proteins (such as 3H2-domain proteins and SOS
protein), leading to Ras activation. Ras is a G-protein that exists in active and
inactive forms. Inactive Ras contains GDPI while the active form is bound to GTP.
Activated Ras transmits the signal to MAP (mitogen-activated protein) kinase,
which enters the nucleus to influence gene transcription.
The Ras protein exists in a balance between its active and inactive forms.
Inactive (GDP-containing) Ras is activated by a signal from the receptor tyrosine
kinase. Active (GTP-containing) Ras is inactivated by GAP (GTPase-activating
protein), which induces the hydrolysis of GTP into GDP. Mutation of Ras can lead
to an inability to split GTP; the resultant permanently activated Ras stimulates
cell proliferation and can lead to cancer.
http://www.scripps.edu/news/sr/sr2007/images/Sun.MB.Fig1.jpg

http://www.nature.com/onc/journal/v26/n22/images/1210394f1.jpg

http://oregonstate.edu/instruction/bb450/stryer/ch15/Slide60.jpg

Hepatic steatosis
= nonspecific condition = triglyceride accumulation within the hepatocellular
cytoplasm
=decrease in free fatty acid oxidation secondary to excess NADH production by
the two major alcohol metabolism enzymes, alcohol dehydrogenase and
aldehyde dehydrogenase. Additional pathogenetic factors include impaired
lipoprotein assembly and secretion and an increase in peripheral fat catabolism.
-The alteration of the hepatic NAD/NADH ratio in alcoholics induces fatty liver
through inhibition of gluconeogenesis and fatty acid oxidation.
-fatty tissue = cytoplasmic vacuoles because the lipid is dissolved during
histologic processing. In frozen sections, lipids can be demonstrated by staining
with oil red O or sudan black.
http://www.science.psu.edu/alert/i...vener_GCN2_OilRedLiver.jpg

Polycystic ovarian syndrome

1. Menstrual irregularity (most often oligomenorrhea) and infertility, due to
anovulation.
2. Hormonal dysregulation (progesterone deficiency, acyclic estrogen production,
and elevated LH ). An increased LH/FHS ratio (>3) is characteristic;abnormally
high levels of unopposed estrogen on the endometrium = long-term risk of
endometrial hyperplasia and endometrial adenocarcinoma.
3. Increased insulin resistance leads to obesity. Patients with PCOS have a
higher risk of developing type 2 DM
4. Hirsutism and acne due to increased androgen levels.
5. Changes of lipid metabolism= increased risk for atherosclerosis and CAD
6. Abdominal U/S =bilateral ovarian enlargement. Histologic = multiple enlarged,
sclerotic, cystic follicles.
http://www.learningradiology.com/c...ftheweekpix2006/cow190.jpg

http://www.youtube.com/watch?v=cUQNoAK9OUs&feature=channel

Hemolytic-uremic syndrome (HUS)

=common cause of acute renal failure in children. It is associated with shiga
toxin-producing organisms like E. coli 0157:H7 and Shigella dysenteriae.
= triad of acute renal failure, microangiopathic hemolytic anemia, and
thrombocytopenia.

Henoch-Schonlein purpura (HSP)

= systemic hypersensitivity (leukocytoclastic) vasculitis that can be induced by
numerous bacterial and viral pathogens as well as a number of medications. It is
caused by immune complex (classically IgA) deposition in affected tissues.
=palpable purpura on the buttocks and lower extremities, abdominal pain,
arthralgias and acute glomerulonephritis
http://www.residentandstaff.com/co...06/11/img/RSP200611f21.jpg

Xanthomas
= suggestive of hyperlipidemia, especially when present in conjunction with a
family history of early cardiac death.
-yellow nodules composed of lipid-laden histiocytes in the dermis
-eruptive xanthomas =yellow papules that abruptly appear when plasma
triglycerides and lipids increase
-tuberous and tendinous xanthomas often present on Achilles tendons and the
extensor tendons of the fingers
- plane xanthomas =linear lesions in skin folds that are strongly associated with
prima biliary cirrhosis
- xanthelasma =soft eyelid or periorbital plaques with no associated lipid
abnormalities in 50% of affected individuals
Histologically xanthomas = benign macrophages packed with finely vacuolated,
“foamy” cytoplasm. This cytoplasm contains high levels of cholesterol,
phospholipids, and triglycerides. The lipid-laden macrophages are frequently also
enclosed by inflammatory cells and fibrotic stroma. With xanthelasmas, the small
aggregates of dermal foam cells are present without any surrounding
inflammation or fibrosis.
http://www.hepatonet.com/img/imagenes8.jpg

Renal cell carcinoma

= large cells with clear cytoplasm and eccentric nuclei. The cytoplasm appears
clear due to the high lipid content of the tumor. For the same reason, this
neoplasm is often golden-yellow on macroscopic examination. The classic triad of
hematuria, flank pain and palpable mass occurs in a minority of patients. Non-
specific symptoms and paraneoplastic syndromes are common; erythrocytosis
can occur, due to secretion of erythropoietin-like substance, and hypercalcemia
is common as well, due to synthesis of PTH-related peptide.
-The lung= most common site for metastasis.

http://www.webpathology.com/slides...idney_RCC_Chromophobe4.jpg
http://renis.registry.cz/res/image/renal-cell-ca-nephrectomy.jpg

Infectious mononucleosis
=Fever, pharyngitis, lymphadenopathy, hepatosplenomegaly, atypical
lymphocytosis, and a positive heterophile antibody reaction
=most commonly caused by EBV. EBV infection is also associated with an
increased incidence of Burkitt’s lymphoma and nasopharyngeal carcinoma.
= classic atypical lymphocytes on the peripheral smear. The abundant cytoplasm
and lack of bizarre nuclear changes (e.g. multiple nucleoli) in these cells
distinguishes them from the immature blast forms found in various hematologic
malignancies.
http://mmserver.cjp.com/images/image/0147056.jpg
http://www.microscopyu.com/galleri...ges/mononucleosis40x02.jpg

Cytomegalovirus (CMV) infection

- can cause a mononucleosis-like syndrome in immunocompetent patients. CMV
can also cause retinitis in immunocompromised (especially HIV+) patients. CMV
infection is sometimes associated with the presence of atypical lymphocytes but
these cells are less prominent than in EBV infection.
http://www.asm.org/Division/c/photo/cmv1.jpg
Dilated cardiomyopathy (DCM)
= dilatation of all four chambers of the heart, systolic dysfunction and
myocardial failure.
-Both primary (idiopathic) and secondary (e.g. due to exogenous cardiotoxic
agents) DCM may exist in the absence of coronary artery disease.
http://www.daviddarling.info/images/cardiomyopathy.gif

Acute myocardial infarction

-changes on light microscopy are usually not apparent until 4 hours after the
onset of severe ischemia. Although a variable waviness of myofibrils at border of
the infarct (due to myofibril relaxation) might be observed before this more
definite signs of early coagulative necrosis such as cytoplasmic eosinophilia and
nuclear pyknosis take at least 4 hours to develop.
Temporal sequence of the major histologic changes:

0-4 hrs :minimal change

4-12 hrs: early coagulation necrosis, edema, hemorrhage wavy fibers
12-24 hrs: coagulation and marginal contraction band necrosis
1 to 5 days:coagulation necrosis and neutrophilic infiltrate
5 to 10 days: macrophage phagocytosis of dead cells
10 to 14 days:granulation tissue and neovascularization
2 weeks to 2 months:collagen deposition / scar formation

http://www.microscopyu.com/galleri...myocardialinfarct20x02.jpg
http://www.microscopyu.com/galleri...myocardialinfarct10x03.jpg

Toxic megacolon
= complication of ulcerative colitis. Abdominal pain and distention, along with
fever, diarrhea, and signs of shock are typical. Plain abdominal X-ray should be
used for diagnosis. Barium contrast studies and colonoscopy are contraindicated
due to risk of perforation.
-Complete cessation of neuromuscular activity in the intestinal wall is the first
step in the pathogenesis of toxic megacolon. Rapid colonic distention ensues,
which thins the intestinal wall, making it prone to rupture. On light microscopy,
segmental necrosis may be seen. Perforation is a life-threatening complication of
megacolon, with a mortality rate > 50%.
http://www.ajronline.org/cgi/content-nw/full/188/6/1604/FIG21
- If improvement does not follow within 24-48 hours surgery should be
considered (total colectomy with ileostomy).
Congenital syndromes that cause QT prolongation:
- Jervell and Lange-Nielsen syndrome (autosomal recessive, with neurosensory
deafness) and the more common Romano-Ward syndrome (autosomal dominant,
no deafness). Both may predispose to torsades de pointes at a young age,
causing syncopal episodes and possible sudden cardiac death.
= from mutations in a K channel protein that contributes to the delayed rectifier
current K of the cardiac action potential;These changes disrupt the flow of
potassium ions in the inner ear and in cardiac muscle, leading to the hearing loss
and irregular heart rhythm

Arrhythmogenic right ventricular cardiomyopathy (ARVC)

=progressive fibrofatty replacement of the right ventricular myocardium of
uncertain pathogenesis.
-no QT prolongation
=Mutations of a calcium-binding sarcoplasmic reticulum protein

Bacterial endocarditis (BE)

- Microemboli from endocardial vegetations in BE can produce systemic
thromboembolic events in the brain, kidneys, myocardium, and other tissues.
Janeway lesions — small, erythematous or hemorrhagic, macular, nontender
lesions on the palms and soles — are an example of this process.
-In order to decrease GFR by5O%, 75% of all renal glomeruli would have to be
affected.
-Acute, diffuse, proliferative glomerulonephritis secondary to circulating immune
complexes may complicate BE and can result in acute renal insufficiency.
-while endotoxin production can cause acute tubular necrosis as part of sepsis, it
is unlikely to cause glomerulonephritis.

Gilbert syndrome
= familial disorder of bilirubin glucuronidation that typically presents with mild
unconjugated hyper bilirubinemia thought to be provoked by one of the classic
triggers.
-unconjugated hyperbilirubinemia persists with repeat testing, but liver function
tests, CBC, blood smear, and reticulocyte count are normal.

Hepatitis B virus infection

= associated with a serum-sickness like syndrome in the prodromal
period:experiencing malaise, fever, skin rash pruritus, lymphadenopathy, and
joint pain. Anorexia nausea jaundice, and right upper quadrant pain may ensue.
-significant elevations in ALT and AST (with ALT> AST) followed by rises in
bilirubin and alkaline phosphatase.
http://medsci.indiana.edu/c602web/602/C602web/liver/slide132.htm
http://www.egyhep.com/ctrls/atlas/Images/153.jpg
http://www.pathology.med.umich.edu...onlab/Acutehep-diffuse.jpg
http://www.pathology.med.umich.edu/greensonlab/Lyticdeath.jpg

Hashimoto’s thyroiditis
=symptoms of hypothyroidism; a diffusely enlarged thyroid gland; and very high
titers of anti-thyroid peroxidase antibody.
- the thyroid has intense mononuclear infiltration consisting of lymphocytes and
plasma cells. There are several germinal centers also present. The thyroid
follicular epithelial cells undergo a metaplastic change, leading to the formation
of large oxyphilic cells with granular cytoplasm, called “Hurthle cells.”
-diagnosis of Hashimoto’s thyroiditis= clinical examination, presence of
hypothyroidism (elevated TSH and low T4/T3) and elevated antithyroid
peroxidase antibody.
- A biopsy is typically not required. Occasionally, the thyroid gland is nodular on
examination. The presence of thyroid nodules may be an indication for fine-
needle aspiration biopsy to rule out malignancy.
http://library.med.utah.edu/WebPath/ENDOHTML/ENDO018.html

de Quervain’s thyroiditis=granulomatous thyroiditis=subacute thyroiditis

=Mixed, cellular infiltration with occasional multinuclear giant cells
-The original insult to the thyroid may be a viral infection.
=symptoms of thyrotoxicosis and a painful, tender thyroid gland. After a brief
thyrotoxic phase, patients often develop transient hypothyroidism. Eventually,
patients afflicted with subacute thyroiditis usually attain euthyroidism.
http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)71550-
9

Riedel’s thyroiditis
= extensive fibrosis of the thyroid gland extending into the surrounding
structures. A hard, fixed thyroid gland can simulate a malignancy. A large
proportion of patients with Riedel thyroiditis have positive antithyroid peroxidase
antibody titers, suggesting an autoimmunity role in the development of
Riedel’s thyroiditis.
http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)71551-
0
Psammoma bodies
= typical of papillary thyroid cancer. Another characteristic feature of papillary
thyroid cancer is the ground-glass nucleus with intranuclear grooving. The tall
cell variant of papillary thyroid cancer is characterized by follicular hyperplasia,
lined by tall epithelial cells. This variant of papillary thyroid cancer is seen in
older individuals and carries a relatively worse prognosis when compared to well-
differentiated papillary thyroid cancer.
http://www.hmc.org.qa/hmc/qmj/images/813%20Fig%201.jpg
http://www.hakeem-sy.com/main/files/pasomma.jpg

Schistocytes (helmet cells)

= fragmented erythrocytes.
-They occur in microangiopathic hemolytic anemias (DIC, HUS, UP) and due to
RBC destruction by prosthetic cardiac valves.
-Hemolytic anemias = decreased serum haptoglobin level as well as an increased
LDH and bilirubin.
-Intravascular erythrocyte destruction results in hemoglobinemia and
hemoglobinuria as well as increased LDH.
-Haptoglobin is a serum protein that binds free hemoglobin and promotes its
excretion by the reticuloendothelial system. In intravascular hemolysis, the
amount of free hemoglobin in the serum exceeds the binding capacity of
haptoglobin thereby decreasing the level of haptoglobin
http://www.som.tulane.edu/classwar...normalRBC/AbnormalRBC.html

Megaloblastic anemia
= hypersegmented neutrophils (> 5 nuclear lobes) and enlarged ovoid
erythrocytes (oval macrocytes).
http://home.kku.ac.th/acamed/kanchana/p27.jpg

Erythroid precursors
- in organs such as the liver and spleen is indicative of extramedullary
hematopoiesis, a condition characterized by erythropoietin-stimulated, and
hyperplastic marrow cell invasion of extramedullary organs. Extramedullary
hematopoiesis is most frequently caused by severe chronic hemolytic anemias,
such as β-thalassemia.
http://pathology.class.kmu.edu.tw/ch10/Slide98.htm
Pulmonary abscesses
= local suppurative collections within lung parenchyma
-if the abscess cavity communicates with an air passage, the semiliquid exudate
within will partially drain creating an air-containing cavity that can be identified
on chest radiograph.
= secondary to the release of lysosomal enzymes by neutrophils and
macrophages.
http://radiology.med.miami.edu/x40.xml

IEN- y production
= responsible for phagolysosome formation, inducible nitric oxide synthase
release, and the development of granulomas and caseous necrosis.

Follicular adenomas
= benign thyroid tumors that can be very difficult to distinguish from well
differentiated FTC. To be called FTC the lesion must show capsular and vascular
invasion.

FTC
= the second most common thyroid cancer. Histologically, FTC may be well-
differentiated, simulating normal thyroid morphology, or less well-differentiated
consisting of sheets of follicular cells or large cells with eosinophilic cytoplasm
(Hurthle cells). FTC and PTC are differentiated based on the presence of ground
glass nuclei and psammoma bodies in PTC. FTC is distinguished from benign
follicular adenomas by its capsular and vascular invasion.
http://www.pathologystudent.com/?tag=follicular-thyroid-carcinoma

Anaplastic thyroid carcinoma

= very aggressive tumor with a poor prognosis. The 1-2 year mortality
approaches 100% given the tendency of this tumor to invade nearby structures
and metastasize to distant sites.
= large pleomorphic cells and large multinucleated osteoclast-like cells.
Occasionally small cells mixed with spindle cells are seen as well.
-no psammoma bodies and no ground glass nuclei of PTC
http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)71562-
5

Lung cancer
1. Small cell (oat cell) carcinoma= aggressive behavior=rapid growth, early local
and distant spread, and poor prognosis =treated with chemotherapy and
radiation.
-central; asso/w Lambert-Eaton Sd, SIADH, Cushing sd
2. Non-small cell carcinoma is far more common = adenocarcinoma, squamous
cell carcinoma, and large cell carcinoma.
- Adenocarcinoma=peripheral =MC subtype of non-small cell carcinoma. It is
also the MC subtype in women and non-smokers; asso/w clubbing and
hypertrophic osteoarthropathy
= tumor cells that form glandular or papilla structures.
http://www.lmp.ualberta.ca/resourc...ages/Images-A/000p032y.jpg

-squamous cell ca = central, cavitation is common; asso/w hypercalcemia

http://www.lmp.ualberta.ca/resourc...ages/Images-S/000p026k.jpg
http://www.lmp.ualberta.ca/resourc...ages/Images-S/000p026r.jpg

-large cell ca = peripheral, asso/v gynecomastia, galactorrhea

http://www.lmp.ualberta.ca/resourc...es/Images-K,L/000p045b.jpg

-squamous cell carcinoma and small cell carcinoma have a strong association
with smoking.

Warfarin-induced skin necrosis

= in patients with a protein C or S deficiency who are started on warfarin.
Protein C is natural anticoagulant (as is protein S). Following the initiation of
warfarin, a rapid drop in factor VII and protein C levels occurs. If a protein C
deficiency is present, the transient procoagulant/anticoagulant imbalance is
further exaggerated, causing a relative hypercoagulable state with thrombotic
occlusion of the microvasculature and skin necrosis.
Treatment= discontinuing warfarin and administering fresh frozen plasma to
replenish protein C content.
http://upload.wikimedia.org/wikipe...-induced_skin_necrosis.jpg

Mitral valve prolapse (MVP)

= defects in mitral valve connective tissue proteins which predispose to
myxomatous degeneration and stretching of the valve leaflets by chronic
hemodynamic stress.
- mitral incompetence = due to elongation and redundancy of the valve leaflets
and possibly also the chordae tendineae, impairing proper coaptation of the
valve margins during systole. Under these circumstances an increase in left
ventricular end diastolic volume (EDV) could facilitate proper closure of the
otherwise oversized mitral valve leaflets. Thus, the patient most likely has mitral
valve prolapse (MVP) at low LV volumes but fewer prolapses as LV EDV is
increased.
-MVP is thought to be caused by subtle defects in connective tissue proteins that
predispose connective tissues rich in microfibrils and elastin (such as cardiac
valves) to damage by chronic hemodynamic stress. Marfan and Ehlers-Danlos
syndromes are examples of connective tissue disorders promoting MVP.
-Histologically= attenuation of the fibrosa layer of the valve and thickening of
the spongiosa layer by deposition of mucoid (myxomatous) material. The
chordae tendineae may have an attenuated collagenous structure and may be
elongated.
= A mid-systolic click followed by a systolic murmur
http://www.medskool.net/images/cir...ral%20valve%20prolapse.jpg
http://www.wilkes.med.ucla.edu/Systolic.htm

Aortic stenosis
Severe aortic stenosis = exertional syncope, angina and dyspnea (SAD). In AS, a
systolic ejection murmur is heard at the right second intercostal space (aortic
area) and may radiate to the carotids.
-MCC= Senile calcific aortic valve degeneration
- Senile calcific aortic valve degeneration usually becomes clinically apparent in
the 7th decade of life, whereas the AS associated with congenitally bicuspid
aortic valves tends to present by the 6th decade.
- Rheumatic aortic heart disease usually produces combined AS and aortic
regurgitation. Aortic valve infective endocarditis tends to cause aortic
regurgitation.
http://www.blaufuss.org/tutorial/index2.html

Hepatic angiosarcoma
=exposure to carcinogens such as arsenic, thorotrast, and polyvinyl chloride.
Tumor cells express CD 31, an endothelial cell marker.
=cells that express CD 31, which is PECAM (platelet endothelial cell adhesion
molecule)

Extrahepatic biliary atresia

= a congenital obstruction of extrahepatic bile ducts. By the 3rd week of life
there is total obstruction. Affected children will have the characteristic cholestatic
picture of acholic (light) stools and dark urine. On physical examination there is
a firm, enlarged liver. Laboratory findings =increased levels of direct bilirubin,
alkaline phosphatase, and gamma-glutamyl transferase.
Liver biopsy is usually diagnostic, showing:
1. Marked intrahepatic bile ductule proliferation
2. Portal tract edema and fibrosis
3. Parenchymal cholestasis
If biliary drainage is not restored surgically, bile stasis will cause development of
biliary cirrhosis by 6 months of life.
http://library.med.utah.edu/WebPath/jpeg4/LIVER049.jpg
http://img.medscape.com/pi/emed/ck...ogy/336139-406335-9293.jpg

Gilbert syndrome
=famlial disorder of bilirubin glucuronidation. Reduced production of UDP-
glucuronyl transferases causes a mild unconjugated hyperbilirubinemia during
times of stress (fasting, illness). These patients do not develop liver disease.

α1-antitrypsin deficiency
= oval-to-round intracytoplasmic hepatocyte inclusions that appear eosinophilic
on H&E stain and are strongly PAS positive.

Subacute granulomatous thyroiditis

= de Quervain’s thyroiditis = granulomatous thyroiditis, possibly caused by a
viral infection. The patient has had a recent illness, possibly viral, and also has
various features of thyro toxicosis tenderness over the thyroid gland, increased
ESR, and a markedly reduced radioactive iodine uptake.
-Thyrotoxicosis in subacute thyroiditis= by release of stored thyroid hormones
secondary to thyroid inflammation; subacute thyroiditis does not cause excessive
production of thyroid hormone which is why iodine uptake is decreased.
-The involvement of thyroid gland in subacute thyroiditis can be patchy. Initial
neutrophil infiltration predominance is followed by infiltration of lymphocytes,
histiocytes, and multinucleated giant cells. The thyroid follicles become
disrupted, and multinucleated giant cells surround the fragmented colloid. The
thyrotoxic phase is followed by a hypothyroid phase for few months. Most
patients eventually recover without any residual thyroid dysfunction. An
antithyroid peroxidase antibody titer is not elevated in these patients. Most
patients respond to non-steroidal anti- inflammatory drugs for thyroid pain and
inflammation.

Chronic lymphocytic thyroiditis=Hashimoto’s thyroiditis

=Diffuse mononuclear infiltration with formation of germinal centers is a very
characteristic feature
- The infiltrate consists of lymphocytes and plasma cells.
-Patients with Hashimoto’s thyroiditis present with thyroid enlargement
(goiter) and/or hypothyroidism. Usually, the presentation of Hashimoto’s
thyroiditis is chronic, with symptoms gradually worsening over several weeks or
months.
- Can be differentiated from other thyroid dysfunction by the following: a
relatively normal erythrocyte sedimentation rate, features of hypothyroidism, a
nontender thyroid gland with a rubbery texture, and high titers of antithyroid
peroxidase autoantibody.

Cerebral amyloid angiopathy

= β-amyloid is deposited into the arterial wall, resulting in weakening of the wall
and predisposition to rupture.
-is associated with advanced age and is not related to systemic amyloidosis.
-Recurrent hemorrhagic stroke is the most common presentation of cerebral
amyloid angiopathy. Unlike cerebral hemorrhages caused by hypertension
amyloid-associated strokes are less severe. They are usually located in the
cerebral hemispheres (lobar strokes) and involve smaller areas of brain
parenchyma. Conversely hypertensive hemorrhagic strokes are larger and tend
to involve the basal ganglia.
http://medirec.ncvc.go.jp/cgi-bin/...NAME=S2004081257570005.jpg
http://www.med.uc.edu/neurorad/webpage/cya.html

Hypoxic encephalopathy
= from global interruption of the cerebral blood supply. “Watershed
infarcts” wedge-shaped areas of necrosis on the border of distribution
between the anterior and medial cerebral arteries are common sequelae.
http://www.radiologyassistant.nl/en/484b8328cb6b2#p484bc1fd1c74d
http://www.radpod.org/wp-content/uploads/2007/07/internal-wsi.jpg
http://missinglink.ucsf.edu/lm/ids...epWatershedInfarct1_21.jpg

Charcot-Bouchard aneurysms
= small in size (<1 mm in diameter) and occur in patients with longstanding
hypertension. They are found in the arterioles that supply the basal ganglia,
internal capsule, and deep white matter.
- can rupture and cause intracerebral hemorrhage.
http://www.uwo.ca/pathol/cases/Neuro/neuro53.jpg

Barrett esophagus
=metaplasia = replacement of squamous cells by intestinal- type columnar cells
= believed to be a compensatory reaction as intestinal epithelium is resistant to
acid. (Chronic gastroesophageal reflux disease)
=is a pre-malignant condition that increases the risk of adenocarcinoma of the
esophagus by 30-40 times. Adenocarcinomas develop through the progression
from intestinal metaplastic epithelium to dysplasia to malignancy.
http://pathology2.jhu.edu/beWeb/images/beprog.gif

Old cerebral infarct = liquefactive necrosis

- Interruption of blood supply to an area of the brain (by thrombosis or
embolism) induces irreversible ischemic changes in the neurons. Release of
lysosomal enzymes from these ischemic neurons results in degradation of the
tissue in the ischemic region . Phagocytic cells migrate into the area and remove
the necrotic tissue leaving a cavity, and astrocytes proliferate around the
necrotic area with the formation of a scar (gliosis). Complete digestion of
necrotic tissue with the formation of a cavity is known as liquefactive necrosis.
Liquefactive necrosis is characteristic for hypoxic injury to the CNS. This
predilection for liquefactive necrosis is thought to be associated with large
amounts of lipids and lysosomal enzymes in the nervous cells.
http://203.131.209.130/neurosurger...troke/mca-o-infarct03a.jpg

Caseous necrosis
=Granulomatous reactions, Mycobacterial infections
-cheesy appearance and is surrounded by histiocytes and multinucleated giant
cells.
-Non caseous granulomatous inflammation occurs in sarcoidosis.
http://library.med.utah.edu/WebPath/jpeg1/LUNG031.jpg

Coagulative necrosis = most commonly seen type of necrosis.

= relative preservation of the architecture of the necrotic tissue.
http://pathology.class.kmu.edu.tw/ch14/Slide114.htm

Creutzfeldt-Jakob disease
=a rare disorder that can be sporadic or infectious. Most of the transmitted cases
are iatrogenic, seen in patients that received contaminated corneal transplants,
implantable electrodes or preparation of growth hormone.
-CJD is included in a group of rare prion diseases. Kuru (a type of transmissible
spongiform encephalopathy in cannibals of New Guinea that eat infected human
brain) and fatal familial insomnia are the other examples of prion disorders that
affect humans. All prion diseases have a number of common features:
1. They are associated with an abnormal prion protein (PrP). This protein is
normally present in host neurons. A change in its secondary structure renders it
resistant to enzymatic digestion by proteases and leads to its accumulation.
2. These diseases have long incubation periods. However they are rapidly
progressive after the onset of clinical symptoms.
3. Characteristic morphologic changes in brain are described as spongiform
encephalopathy. Vacuoles form in the cytoplasm of the neutrophils and neurons.
As the disease progresses, the vacuolated areas transform into cysts. No
inflammatory changes are present.
4. There is no treatment for prion diseases. These conditions are invariably fatal.

http://graphics8.nytimes.com/image...8/01/health/adam/17146.jpg

Progressive multifocal leukoencephalopathy

= usually seen in immunocompromised (HIVI lymphoma or leukemia) patients.
=caused by JC polyoma virus. Patches of demyelination due to the preferential
infection of oligodendrocytes is the primary pathologic effect.
http://pathmicro.med.sc.edu/mhunt/pml2.jpg
http://kobiljak.msu.edu/WebGraphics/Pathgraph/31957.jpg

Subacute sclerosing panencephalitis

= progressive dementia, spasticity and seizures.
=linked to an abnormal measles virus that persists in the CNS of these patients
for years after recovery from measles infection. Microscopic examination shows
myelin degeneration and viral inclusions.
http://www.cdc.gov/ncidod/eid/vol6no4/bonthius1G.htm

Gallstones
= aggregation of bile constituents and are categorized as cholesterol stones,
pigment stones, or mixed stones.
-Pigment stones are most common in rural Asian populations (accounting for
only 10-25% of gallstones in the United States), with an increased incidence in
women and the elderly. Black pigment stones form within the gallbladder when
increased unconjugated bilirubin precipitates in bile as calcium bilirubinate.
Elevated levels of circulating unconjugated bilirubin are primarily associated with
chronic intravascular hemolysis (eg, sickle cell anemia, β-thalassemia, and
hereditary spherocytosis). Grossly, black pigment stones are usually present in
significant numbers and are small, spiculated, and crumbly. Because these
stones contain high amounts of calcium carbonates and phosphates, 5O-75% of
them are radioopaque and will appear on x-ray.
http://1.bp.blogspot.com/_0yn9eo5n...LU/xdFxVJWAWwI/s320/04.JPG
http://knol.google.com/k/-/-/qjyFwIjC/PyLeBQ/pigment%20stone.jpg

Normal pressure hydrocephalus

= decreased absorption of CSF leads to increased CSF volume, which is
accommodated by ventricular enlargement. Expanded ventriculi place traction on
cortical efferent and afferent fibers (corona radiata). This traction disrupts the
periventricular pathways that transmit impulses from the cortex to the sacral
micturition center.
-Later in the disease process, lack of inhibition from the cerebral cortex leads to
frequent and uncontrolled micturition, or urge incontinence. The bladder fills with
urine and empties reflexively when full. The patient has no sensation of bladder
fullness and no control over bladder function. Voluntary relaxation of the urethral
sphincter remains intact.
=triad of ataxic gain and urinary incontinence, then dementia. These symptoms
are explained by distortion of periventricular white matter.
http://www.thebarrow.org/stellent/...ts/webcontent/bqjpg141.jpg

Micturition reflex is regulated by the following centers:

1. Sacral micturition center— located in S2-S4 level and responsible for bladder
contraction. Parasympathetic fibers travel from S2-S4 ventral white matter
within pelvic nerves and stimulate cholinergic receptors in the bladder wall.
2. Pontine micturition center— located in the pontine reticular formation. It
coordinates relaxation of external urethral sphincter with bladder contraction
during voiding.
3. Cerebral cortex — inhibits sacral micturition center.

Myotonic dystrophy
=autosomal-dominant disorder
=caused by an increased number of trinucleotide repeats on myotonia-protein
kinase gene. Sustained muscle contraction (myotonia), along with weakness and
atrophy, is common. Cataracts are seen in almost all patients. Frontal balding
and gonadal atrophy are other common features.
-Myotonic muscular dystrophy is the second most common inherited muscle
disorder (Duchenne muscle dystrophy is the most common).
- The number of repeats increases with subsequent generation, causing
increasingly severe disease in each generation (anticipation).
-Age of presentation varies from early childhood to late adulthood.
-On light microscopy, atrophy of muscle fibers is prominent. Unlike Duchenne
muscular dystrophy, necrosis of muscle fibers and fibrofatty replacement are not
common in myotonic dystrophy.
-DM1=DMPK (Dystrophia myotonica protein kinase) gene on chromosome 19
-DM2=Znf9 (Zinc finger 9) gene on chromosome 3
-congenital myotonic dystrophy= noted at birth. The signs and symptoms
include generalized weakness, weak muscle tone (hypotonia), club foot,
breathing problems, developmental delays, and intellectual disability.

Vitamin B12 deficiency

= may occur due to low dietary intake of this vitamin, the presence of antibodies
against intrinsic factor (pernicious anemia), or malabsorption. The Schilling test
helps differentiate between these causes. The patient is first given a dose of
radiolabeled oral vitamin B12 and an intramuscular injection of unlabeled
Vitamin B12. The urinary excretion of radioactive B12 is then measured. Normal
urinary excretion of radiolabeled vitamin B12 suggests normal absorption, and
B12 deficiency in this setting is most likely due to poor intake of Vitamin B12 in
the diet . Diminished urinary excretion of radiolabeled vitamin B12 is a sign of
impaired intestinal absorption. To differentiate between pernicious anemia and
malabsorption, the next dose of radiolabeled B12 is given with intrinsic factor.
Normal excretion after the addition of intrinsic factor is diagnostic of pernicious
anemia. Low excretion of B12 after administration of intrinsic factor rules out
pernicious anemia and suggests a malabsorption syndrome such as pancreatic
insufficiency, bacterial overgrowth, or short gut syndrome.
- Pernicious anemia is associated with atrophic gastritis and the presence of
antibodies against gastric parietal cells and intrinsic factor. Administration of
vitamin B12 without intrinsic factor will show low urinary radioactive B12
excretion on the Schilling test.

Pituitary tumors
- Compression of the optic chiasm by suprasellar extension of pituitary tumors
causes the characteristic bitemporal hemianopsia. Headache is likely caused by
an increase in intracranial pressure, caused by mass effect of the tumor.
-Pituitary tumors typically arise from one of the five major cell types of the
anterior pituitary gland. Approximately 60% of pituitary tumors are prolactin-
secreting adenomas. Prolactin is a 199 amino acid peptide hormone secreted
from lactotrophs of the pituitary gland. The primary physiologic action of
prolactin is preparation of the breasts for milk production/lactation in the
postpartum period. Prolactinomas stimulate inappropriate milk production in non
postpartum females (galactorrhea). Prolactin also suppresses gonadotrophin-
releasing hormone (GnRH) production from the hypothalamus which causes
decreased libido, amenorrhea, and infertility. Pituitary tumors can grow beyond
the limits of the sella turcica, causing compression and erosion of surrounding
structures. If the pituitary tumor grows superiorly it erodes the optic chiasm;
laterally it invades the cavernous sinus; inferiorly, it grows into the sphenoid
sinus. A growing pituitary tumor can also compress normal pituitary cells causing
hypopituitarism.

- Somatotroph adenomas= increase growth hormone production= acromegaly in

adults and gigantism in children.
- Corticotroph adenomas produce adrenocortical-stimulating hormone (ACTH)
which causes Cushing’s disease.
- Thyrotroph adenomas produce thyroid-stimulating hormone (TSH) leading to
thyrotoxicosis. Thyrotroph adenomas are very uncommon.
- Gonadotroph adenomas usually do not produce intact follicle-stimulating
hormone (ESH) or luteinizing hormone (LH). These tumors typically over produce
alpha subunits of these glycoprotein hormones and present with mass effects
and hypogonadism. Most nonsecretory adenomas arise from the gonadotrophs.
These tumors tend to grow slowly.

Hypertrophic cardiomyopathy (HCM)

= myocyte hypertrophy (relatively large transverse diameter of myocytes) and
haphazardly arranged myocytes and myocyte bundles. In addition, the
interstitial spaces are particularly prominent, which may represent fibrosis
- In most cases HCM is the result of mutations in the genes coding for cardiac
sarcomere proteins, such as components of the thick or thin filaments (most
commonly beta-myosin heavy chain). Approximately 5O% of cases HCM are
familial; inheritance is autosomal dominant with variable expression.
http://eurheartj.oxfordjournals.or...images/medium/coverfig.gif
http://gilead.org.il/hcm/sarcomere.jpg

Dilated cardiomyopathy (DCM)

-Toxic agents like alcohol, cocaine, iron (in hemochromatosis), or doxorubicin
may cause dilated cardiomyopathy which may occasionally progress to sudden
cardiac death. The histologic changes seen in DCM are non-specific, potentially
including interstitial fibrosis and variable myocyte hypertrophy or thinning.

Sickle cell trait (Hb AS)

= hemoglobin composed of 35 to 40% hemoglobin S (Hb S); they are generally
protected from sickle cell crises aplastic crises and sequestration crises by the
presence of> 50% normal hemoglobin (Hb A).
-Patients with sickle cell trait are usually asymptomatic, although they may
develop hematuria and a limited ability to concentrate urine. A high incidence of
UTI and splenic infarction at high altitude has also been reported.
-In contrast, patients with homozygous SS have severe disease with >80 % Hb
S.
-although homozygotes for the sickle cell trait are often very ill, heterozygotes
enjoy relative protection from Plasmodium falciparum (malaria). The exact
mechanism is not known: proposed mechanisms include increased sickling of
parasitized sickle-cell trait red blood cells and accelerated removal of these cells
by the splenic monocyte macrophage system.
-Peripheral smears are usually normal in sickle cell trait patients; irreversibly
sickled cells are not seen. Furthermore, red cell indices and red cell morphology
are normal; the reticulate count is not elevated. However, the sickling test will
be positive (RBCs will sickle when sodium metabisulfite is added). Increased
MCHC, which represents intracellular dehydration, is seen only with homozygous
SS (i.e. full-blown sickle cell anemia). It is unlikely that patients will develop
painful crises as they are protected by the 60% Hb A (normal hemoglobin).
Generally, patients with sickle cell trait are asymptomatic, except perhaps for
hematuria.
http://www.nj.gov/health/fhs/sicklecell/images/inheritance.gif

Adenomatous polyps
= dysplastic mucosa and are considered premalignant. They tend to develop in
people older than 50 years old as a result of APC gene mutation. Stepwise
progression to adenocarcinoma may follow. This progression includes a series of
other gene mutations, such as R-ras, p53 and DCC. This accumulation of gene
mutations is called the “adenoma-to-carcinoma sequence”.
-The best prevention of malignant transformation of adenomatous polyps =
regular screening and timely excision of adenomas. Recent studies, however,
have shown increased activity of enzyme cyclooxygenase-2 (COX-2) in some
colon adenocarcinomas and in inherited polyposes syndromes. Patients taking
NSAIDs regularly have been shown to have a lower incidence of adenomas
compared to the general population, perhaps because of the COX-2 inhibitory
effect of NSAIDs.
http://upload.wikimedia.org/wikipe...mons/4/44/Colon_cancer.jpg
http://radiology.rsna.org/cgi/content-nw/full/244/2/471/F2C

Hepatocellular carcinoma
- In the integrative phase of hepatitis B infection, HBV DNA is incorporated into
the host genome of those hepatocytes that survived the immune response.
Infectivity ceases and liver damage tapers off when the host’s antiviral
antibodies appear and viral replication stops. The risk of hepatocellular
carcinoma, however, remains elevated because of the HBV DNA that has been
integrated into the host genome. This integration of HBV DNA into the host
genome is thought to have multiple implications. First, it causes chronic liver cell
injury and regenerative hyperplasia, increasing the number of hepatocytes
susceptible to genetic mutations. Second HBV encodes for HBx protein, a
substance that disrupts growth control of infected cells by activating multiple
growth-promoting genes. HBx protein also binds to p53 apparently impeding its
growth-suppressing activities.
http://pathmicro.med.sc.edu/virol/hep-bstruct.gif
http://www.ncbi.nlm.nih.gov/ICTVdb/WIntkey/Images/em_hepad.gif
http://www.pathguy.com/lectures/hepatocellular_carcinoma.jpg

Celiac sprue (gluten-sensitive enteropathy)

=caused by hypersensitivity to gluten, a protein found in wheat, barley, and rye.

-Common symptoms = those of malabsorption: diarrhea, steatorrhea, flatulence,

and symptoms of nutrient deficiencies.
-diagnosed by small bowel biopsy = flattening of the mucosa, atrophy of villi,
and chronic inflammation of the lamina propria. These changes are most
commonly seen in the duodenum and proximal jejunum, where the
concentration of gluten is the highest. Histologic changes and clinical symptoms
will disappear after a period of gluten- free diet if celiac disease is present.
-Anti-gliadin, anti-reticulin, and anti-endomysial antibodies are found in patients
with celiac sprue.
http://www.aafp.org/afp/20071215/afp20071215p1795-u3.jpg

Paroxysmal nocturnal hemoglobinuria (PNH)

- Ironically PNH is neither paroxysmal, nor nocturnal. This misnomer originated
because the primary clinical manifestation of PNH is dark-colored urine
(hemoglobinuria from hemolysis) in the morning. It was once believed that the
complement that hemolyses red blood cell membranes was activated by sleep-
associated acidosis. We now know that hemolysis only appears to be
nocturnal/paroxysmal because urine collects and concentrates overnight causing
a dramatic color change in the morning—hemolysis in PNH has been
demonstrated to occur all throughout the day.
- PNH is a condition in which there is mutation of the PIG-A gene that codes for
the glycosylphosphatidylinositols (OPI) anchor. The OPI anchor is necessary for
the attachment of CD55 and CD59, which are cell-surface proteins that help
inactivate complement. Without CD59 and CD55, complement stays activated
and hemolysis of the cell results . Patients with PNH, therefore commonly
develop thrombosis: recurrent venous thrombosis is common, including Budd-
Chiari syndrome, and thrombosis the commonest cause of death in these
patients. Since PNH is a stem cell disorder, it is often associated with
pancytopenia, as well.
Know that the deficiency of CD 55 and CD 59 proteins is diagnostic of PNH and
that this deficiency disallows the inactivation of complement.
http://www.alxn.com/images/diag_comp_activation.gif
http://www.pnhsource.eu/styles/images/sidebar.eu.jpg

Gallbladder hypomotility
- Risk factors= pregnancy, rapid weight loss, prolonged use of total parenteral
nutrition or octreotide, and high spinal cord injuries.
-One of the more frequent consequences of gallbladder hypomotility is the
formation of biliary sludge, which results from bile precipitation. Biliary sludge
typically contains cholesterol monohydrate crystals, calcium bilirubinate, and
mucus and is a known precursor to stone formation. Complications such as acute
cholecystitis occur in up to 2O% of patients with biliary sludge.
http://gallstoneflush.com/images/biliary%20tract.JPG

Crohn’s disease
=abdominal pain and diarrhea in a 20-30 year old patient. Weight loss,
fatigability, low grade fever, and aphthous ulcers of the oral mucosa are also
common.
- Crohn’s disease causes transmural inflammation of any area of the
gastrointestinal tract
-Transmural inflammation explains the two most common complications of
Crohn’s disease: strictures, and fistulas. Chronic inflammation causes edema
and fibrosis leading to narrowing of the intestinal lumen (strictures).
Inflammation and necrosis of the intestinal wall causes ulcer formation. Ulcers
can penetrate the entire thickness of the affected intestinal wall, leading to the
formation of a fistula. Remember, in ulcerative colitis, only the mucosa and
submucosa are inflamed, so strictures and fistulas are not common.
- Toxic megacolon is a potentially life-threatening complication of both
Crohn’s disease and ulcerative colitis. It occurs due to neuromuscular
degeneration of the intestinal wall and its rapid dilatation. Abdominal pain and
distention are common symptoms. Toxic megacolon is associated with bowel
perforation.
http://www.medgadget.com/archives/img/crohn.jpg
http://www.proctosite.com/newslett...onteudo/Crohn_surgical.jpg
http://www.diagnosticimaging.com/i...id=1384330&t=1236110195004
http://www.learningradiology.com/a...g%20Sign/stringcorrect.htm
http://www.pathology.pitt.edu/lectures/gi/s-int-b/16.htm

Ischemic colitis
= Low perfusion to the bowel can cause ischemia and necrosis of the intestinal
wall. Any area of the bowel maybe affected; however the splenic flexure and
distal sigmoid colon are the most susceptible.
-The splenic flexure is a “border” area between the distribution of the
superior mesenteric (SMA) and inferior mesenteric (IMA) arteries. The distal
sigmoid colon lies between the areas supplied by IMA and hypogastric arteries.
Hence ischemia affects these areas first and is called “watershed
infarction.”
-Clinically=abdominal pain and bloody diarrhea.
The cecum, hepatic flexure, ascending colon and most of the transverse colon
are supplied by branches of the superior mesenteric artery (SMA). Mesenteric
ischemia can occur in any of these areas although ischemia there occurs less
frequently than in “watershed areas.”
http://www.gastro.com/Gastro/images/ischemic_colitis1_img.jpg

Cushing syndrome
The overnight dexamethasone suppression test is commonly used in the workup
of Cushing syndrome. In normal individuals, administration of this potent
glucocorticoid causes suppression of ACTH and cortisol production. However,
patients with endogenous Cushing syndrome do not show complete suppression
of cortisol and ACTH production. If the a.m. cortisol level is moderately
suppressed (i.e. to a level <5O% of baseline) in the setting of elevated baseline
ACTH levels then the cause of the Cushing syndrome is likely a pituitary
adenoma. If the baseline ACTH is high, and there is little/no suppression of
cortisol release on the overnight dexamethasone suppression test, then the
cause of the Cushing syndrome is likely ectopic ACTH production. If there is low
baseline ACTH and little/no cortisol suppression with the overnight
dexamethasone test, the Cushing syndrome likely stems from some primary
adrenal process.
- In normal individuals, serum cortisol levels drop significantly in the evening
hours as a function of normal circadian rhythm. In endogenous Cushing
syndrome, however, this normal circadian rhythm is lost, and there is no
decrease in evening cortisol levels. Thus, measuring cortisol at 8 a.m. alone is
not a very sensitive or specific screening test for Cushing syndrome.

Helicobacter pylori infection

-the rapid urease test is able to make a relatively quick diagnosis from tissue
samples.
- a sample from the gastric mucosa is added to a solution containing a pH
indicator and urea
-H. pylori produces large amounts of extracellular urease enzyme, hence the use
of a urea solution in this test. Urease converts urea to carbon dioxide and
ammonia, causing a pH increase and resultant color change of the phenol red pH
indicator. An alkaline (pink) color persisting more than five minutes is considered
a positive test for H. pylori. Although the pink color typically develops within 30
minutes when H. pylori is present, the sample should be observed for 24 hours
before being considered negative.
http://bioweb.uwlax.edu/bio203/s20...pylori%20scott%20smith.gif
http://www.clinicalcorrelations.or...loads/2008/06/h-pylori.jpg

Cystinuria
= from a defect in the renal proximal tubules, which causes decreased
reabsorption of the amino acid cystine. The increased cystine excretion can
precipitate stone formation. The cystine transporter also contributes to the
reabsorption of other dibasic amino acids (arginine, ornithine, and lysine).
Increased excretion of these amino acids does not result in stone formation,
however, as these are relatively soluble.
-Patients with cystinuria experience recurrent kidney stones, beginning at a
young age.
-Hexagonal cystine crystals on urinalysis are pathognomonic. These crystals are
relatively radiopaque due to the density of sulfur-containing compounds. They
form in acidic urine (pH < 6).
-The detection of cystine in urine is important not only for establishing a
diagnosis, but also for monitoring treatment effects and for predicting the rate of
stone formation.
-The sodium cyanide-nitroprusside test detects sulfhydryl groups, and is a rapid
qualitative determinant of the presence of urine cystine. The cyanide added to
the urine converts cystine to cysteine. The nitroprusside then binds cysteine,
causing a purple discoloration in 2-10 minutes.
-Treatment of cystinuria = hydration and alkalinization of urine.
http://www.thiola.com/gfx/stones/MS/27_cystine_crystals.jpg

Actinic keratoses (AK)

= erythematous papules with a central scale due to hyperkeratosis.
- A “sandpaper-like” texture on palpation of the affected areas= typical
- The lesions are small and flat at first but may enlarge and become elevated.
Usually their size does not exceed 10 mm in diameter. Hyperkeratosis in such
lesions may become prominent and turn into “cutaneous horns”.
-Actinic keratoses develop in genetically predisposed individuals 40-60 years of
age under the influence of excessive sun exposure. The most commonly affected
areas are the face, ears, scalp and the dorsa of the arms and hands, but any
other chronically sun-exposed site (legs, back, upper chest) can be involved.
-On light microscopy, affected areas show acanthosis (thickening of the
epidermis) parakeratosis (retention of nuclei in the stratum corneum),
dyskeratosis (abnormal keratinization), and hyperkeratosis (thickening of
stratum corneum). Keratinocytes display various degrees of atypia. Mitoses and
an inflammatory infiltrate are present. Actinic keratosis is regarded as either a
premalignant condition or a carcinoma in situ, but less than 1% of AKs will
evolve into frank squamous cell carcinoma.

http://www.scopnetwork.org/images/actinic_keratosis_th.GIF
http://www.visualdxhealth.com/imag...larKeratosis_51744_med.jpg

Pityriasis rosea
= pink or brown scaly plaque with central clearing and a collarette of scale
(herald patch) on the trunk neck or extremities. It is followed by development of
maculopapular rash classically in a “Christmas tree” pattern along the skin
tension lines.
http://www.visualdxhealth.com/imag...tyriasisRosea_42641_lg.jpg

Seborrheic keratoses
= in elderly individuals and presents with “stuck-on” deeply pigmented or
flesh- colored lesions with velvety or “greasy” surface.
http://rad.usuhs.mil/derm/lecture_notes/Images/sebK2.JPG

Sheehan’s syndrome
High estrogen levels during pregnancy stimulate growth of the pituitary, causing
it to both enlarge and become more vascular. If significant hypotension occurs
while the pituitary is still enlarged (the most common cause is postpartum
hemorrhage) ischemic necrosis of the pituitary occurs. A deficiency of multiple
pituitary hormones (panhypopituitarism) follows this ischemia. Prolactin
deficiency is one sequelae of the necrosis, which has important symptomatic and
diagnostic significance. As prolactin is responsible for milk secretion from the
breast, its deficiency leads to failure to lactate. Patients suffering from Sheehan
syndrome also commonly have hypothyroidism and hypercortisolism.

Autoimmune hypophysitis
= sometimes seen during late pregnancy or the early postpartum period. Both
the anterior and posterior pituitary become inflamed. The presentation is acute
with headaches, visual field defects and cortisol deficiency. For unknown reasons
cortisol deficiency develops more commonly than other hormonal deficiencies.
Hypophysitis differs from Sheehan syndrome in the presence of visual field
deficits and the acuity of presentation.

Pituitary apoplexy
= hemorrhage into a preexisting pituitary adenoma. It is a medical emergency.
The patient usually presents with acute, severe headache, ophthalmoplegia, and
altered sensorium. A high index of suspicion is required. The patients require
urgent neurosurgical consultation and stress doses of glucocorticoids.
http://radiographics.rsna.org/cgi/content-nw/full/27/1/95/F8

Abdominal aortic aneurysm (AAA)

- The major cause of AAA is atherosclerosis. Atherosclerotic atheromas can
sufficiently progress enough to weaken the underlying media of the aortic wall.
Intimal (fatty) streaks, the earliest lesion of atherosclerosis, are composed of
intimal lipid-filled foam cells, which are derived from macrophages and smooth
muscle cells that have engulfed lipoproteins, predominantly LDL. These
complexes then insudate into the intima through an injured leaky endothelium.
- An intimal tear is thought to be the process that initiates formation of a
dissecting aortic aneurysm. An aortic dissection generally results in severe chest
and/or back pain, which may extend as the dissection progresses distally. A
palpable abdominal mass need not be present, since the dissecting intramural
hematoma is often contained within an intact adventitial layer of the aorta.
Aortic dissections can rupture and are therefore considered medical
emergencies.
-Perivascular fibrosis—more specifically, dense periaortic fibrosis with an
inflammatory reaction— characterizes an unusual variant of AAA. The
inflammatory reaction is known to be rich in lymphocytes, plasma cells,
macrophages, and often giant cells, although the cause of such inflammatory
AAAs is uncertain. Nonetheless, the major cause of AAA is atherosclerosis.
http://www.cvtsa.com/MediaServer/MediaItems/MediaItem_237.jpg

Vasa vasorum obliteration

- vasa vasorum endarteritis in the thoracic aorta—is thought to be the
mechanism by which syphilis produces thoracic aortic aneurysms. Currently,
syphilis rarely progresses to this stage in the United States.

Adenocarcinoma at the head of the pancreas

=The palpable but non-tender gallbladder (Courvoisier sign), weight loss, and
obstructive jaundice (associated with pruritus, dark urine, and pale stools)=
common bile duct compression signs
- Cancers of the body and tail of the pancreas usually do not become
symptomatic until they invade the splanchnic plexus and cause midepigastric
abdominal pain. Because pancreatic cancer is a malignancy that manifests late
most tumors are unresectable at the time of diagnosis.
-The following are risk factors for this malignancy:
1. Age: The highest incidence is in the 65-75 age groups.
2. Smoking is the most important environmental risk factor for pancreatic
cancer. It doubles the risk.
3. Diabetes mellitus: The risk of pancreatic cancer increases with the duration of
diabetes.
4. Chronic pancreatitis: The risk of pancreatic cancer increases with the duration
of the disease. The risk is highest after 20 years of chronic pancreatitis.
5. Genetics: Hereditary pancreatitis, MEN syndromes, HNPCC (hereditary non-
polyposis colon cancer) and familial adenomatous polyposis syndromes can all be
associated with an increased risk of pancreatic cancer.
-Alcohol consumption increases the risk of the malignant tumors of the head,
neck, esophagus and liver. It is not a risk factor for pancreatic cancer.
http://www.meddean.luc.edu/LUMEN/m...chanisms/pancreas_mass.htm

TB
- a lower lobe lung lesion (Ghon focus) accompanied by ipsilateral hilar
adenopathy is described as a Ghon complex. The Ghon complex occurs during
initial infection with M. tuberculosis.
-M. tuberculosis is passed from person to person through the transmission of
aerosolized airway secretions. These droplets are of varying sizes: larger
droplets make contact with the tracheal and bronchial epithelium and are
typically removed by mucociliary motion, while smaller droplets are carried to
the alveoli and can establish infection. Most droplets of infectious size carry
approximately five organisms. Pulmonary tuberculosis infection is first
established after the gravi-assisted entry of small, organism-laden droplets into
the lower lung fields. The mycobacteria are phagocytosed by alveolar
macrophages, and the sulfatide virulence factor expressed by M. tuberculosis
allows for intracellular bacterial proliferation. While nestled within these
macrophages, M. tuberculosis enters the lymphatic circulation. Eventually, it can
seed organs throughout the body.
The immune reaction to M. tuberculosis is TH1 cell-mediated, resulting in
caseating necrosis where the organisms are present. The caseating granulomas
consist of T lymphocytes, epithelioid activated macrophages, Langhans giant
cells (with a horseshoe-shaped arrangement of nuclei), and proliferating
fibroblasts that actively synthesize collagen. The net result of this response is a
“walling off” of the organisms within a fibrous capsule. Although eliminated
in 95% of cases, dormant M. tuberculosis bacilli are still present within the larger
granulomas of many patients, able to later cause secondary tuberculosis during
periods of immunosuppression.
- Secondary M. tuberculosis infection occurs when patients who have been
primarily infected incompletely eliminate the M. tuberculosis bacilli within Ghon
foci or extrapulmonary sites. The organisms that remain then mobilize from
these foci during periods of immunosuppression to cause active disease. Patients
who take chronic corticosteroids, anti-TNF agents (eg, infliximab or etanercept),
calcineurin inhibitors (eg, cyclosporine), or who are HIV positive are at increased
risk for reactivation tuberculosis. In the lung, the typical pathologic finding
associated with secondary infection is an apical cavitary lesion.
- Hematogenous dissemination of M. tuberculosis is associated with
extrapulmonary tuberculosis. Classic locations of extrapulmonary tuberculosis
include the basal meninges (tuberculous meningitis), the lumbar spine (Pott
disease), the psoas muscle (psoas abscess), and serous membranes such as the
pericardium and pleura. The most extreme case of extra pulmonary tuberculosis
is miliary tuberculosis. In this condition the M. tuberculosis organisms spread
widely through out the body in small, scattered, seed-like foci of infection.
http://granuloma.homestead.com/files/tb_gross_lung26.jpg
http://granuloma.homestead.com/files/tb_gross_lung50.jpg
http://tbfreeindia.com/xar.jpg
http://www.ewashtenaw.org/governme...c_health/phcontent/xray_tb
http://brighamrad.harvard.edu/fireCases/images/41/cxr.gif

Acute myelogenous leukemia

- In acute promyelocytic leukemia (APL)I type M3 of acute myelogenous
leukemia in the FAB classification system, white blood cells produce an aberrant
protein with an affinity for retinoic acid. APL results from that (15;17) mutation
where by the gene for the retinoic acid receptor alpha (RARa) is transferred from
chromosome l7 to chromosome 15 where it fuses with the promyelocytic
leukemia (PML) gene, resulting in the formation of new gene called PML/RARα.
Normally the retinoic acid receptor plays a role in the proper differentiation of
myeloid precursors. (The receptor interacts with retinoic acid to effect
transcription of genes required for maturation.) However, the (15; 17) mutation
produces an abnormal retinoic acid receptor that is unable to signal for the
differentiation of myeloid precursors.
-Treatment with all-trans-retinoic acid (ATRA) stimulates differentiation of
myeloblasts into mature granulocytes and induces remission in about 90% of
patients with acute promyelocytic leukemia.
http://www.wadsworth.org/chemheme/heme/microscope/auerrod.htm
http://renalfellow.blogspot.com/2008/10/atra-syndrome.html
http://www.healthsystem.virginia.e...ukemia-m2-100x-website.jpg

Acute lymphocytic leukemia

= predominantly affects children. Blast cells positive for the CD1O antigen
(CALLA) suggest a good prognosis.
http://rebeccanelson.com/leukemia/all.html

Chronic lymphocytic leukemia

= is frequently seen in elderly patients. It presents with lymphadenopathy,
hepatosplenomegaly and anemia, and has an indolent course. Neoplastic cells
resemble mature B-lymphocytes.
http://www.wadsworth.org/chemheme/heme/microscope/cll.htm
Chronic myeloid leukemia
- myeloid precursors in different stages of differentiation proliferate. This disease
is caused by at (9; 22) translocation that forms the bcr-abl fusion gene which
codes for an abnormal tyrosine kinase.
http://www.pathologystudent.com/wp...9/04/cml-blood-better7.jpg

Gastrointestinal reflux disease (GERD)

= heartburn and regurgitation.
- However, patients can have “silent GERD,” which means they may have
symptoms like dysphagia, nocturnal cough, and sore throat even though they
don’t feel heartburn.
Gastroesophageal junction incompetence is the primary pathophysiologic
mechanism responsible for GERD. This incompetence is most commonly caused
by transient lower esophageal sphincter relaxations and a hypotensive lower
esophageal sphincter (LES). Acidic gastric contents reflux back into the
esophagus and irritate the esophageal mucosa, leading to an inflammatory
reaction and epithelial repair.
Macroscopically, mucosal erythema or edema in the distant esophagus is seen:
in severe cases, erosions or ulcerations may be seen. Basal zone hyperplasia,
elongation of lamina propria papillae, and inflammatory cells (eosinophils,
neutrophils and lymphocytes) are characteristic histologic findings

Pill-induced esophagitis
= commonly seen with tetracycline antibiotics, potassium chloride, and
bisphosphates

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

=X-linked disorder that affects mostly males, and is more common in patients of
African, Asian and Mediterranean descent.
-G6PD is an enzyme of the pentose phosphate pathway that in erythrocytes is
essential for maintaining adequate concentrations of NADPH. Insufficient NADPH
results in an inability to maintain glutathione in the reduced state. This increases
the vulnerability of erythrocytes to oxidative stress and manifests with hemolysis
induced by infection, drugs (e.g. Bactrim, dapsone, antimalarials, nitrofurantoin),
or other oxidants (e.g. fava beans).
-Hemolytic episodes= malaise and pallor, indirect bilirubinemia (jaundice),
hemoglobinemia and hemoglobinuria (dark-red urine). The level of serum
haptoglobin decreases and a reticulocytosis develops to compensate for the
increased destruction of RBC. Patients are generally asymptomatic between
episodes.
http://www.med.unc.edu/medicine/web/Smearreview/img024.jpg
http://www.diseaseaday.com/wp-cont.../g6pddeficiencyprocess.png

Hereditary spherocytosis
= autosomal dominant defect in RBC structural proteins (spectrin, ankyrin, or
protein 4.1) characterized by increased erythrocyte osmotic fragility and MCHC
(mean corpuscular hemoglobin concentration) increased above 36 g/dL.
http://www.indwes.edu/Faculty/bcup...s/Blood/spherocytes_nw.jpg

Measles virus
= helical, enveloped RNA virus, which is a member of Paramyxoviridae family.
Measles manifests with prodromal fever, cough coryza (runny nose),
conjunctivitis, and erythematous maculopapular rash.
- Complications include acute encephalitis, primary measles pneumonia, and
secondary bacterial infections (pneumonia and acute otitis). Most American
children are vaccinated against measles.
-Subacute sclerosing encephalitis is a rare complication of measles. It occurs in
children who appear to have recovered from measles infection several years
earlier. Scientists hypothesize that subacute sclerosing encephalitis is caused by
a certain type of measles virus that is missing an antigen (M protein). The
missing antigen causes failure of the measles virus to be cleared by the immune
system and allows its persistence in the CNS. This retained virus causes
inflammation, demyelination, and gliosis in many cerebral areas. Neurons and
glial cells display viral nuclear inclusions.
Affected children may have various neurological deficits and progressive
dementia. The disease is slowly progressive, but is fatal.
-High titer of antibodies to the measles is found in the serum and CSF of these
patients. In the CSF antibodies are found as oligoclonal bands of
immunoglobulins. Note that there are no antibodies to M. component of the
virus.
http://pathology.mc.duke.edu/neuro...ecture2/sspeinclusions.jpg

Chronic pancreatitis
=recurrent abdominal pain, hepatomegaly and pancreatic calcifications
- the most common cause= ethanol abuse. Alcohol-associated hepatic steatosis
is probably the cause of his hepatomegaly. The patient also has a megaloblastic
anemia which in alcoholics typically stems from folic acid deficiency.
-The underlying biochemical feature of megaloblastosis is a defect in DNA
synthesis. Folic acid is a single carbon donor required for the synthesis of purine
and pyrimidine bases. RNA and protein synthesis may continue relatively
unaltered, leading to a state of unbalanced cytoplasmic growth with impaired cell
division.
http://www.nature.com/modpathol/jo.../n8/fig_tab/3800613f1.html
http://www.pathguy.com/sol/13889.jpg

Colon cancer
= third most common malignancy in the United States (lung and breast cancers
occur more often). Its incidence increases with age, and it affects males and
females equally. A diet that is high in cholesterol and carbohydrates and low in
fiber increases the risk. Certain diseases (such as inflammatory bowel disease)
and genetic factors also play an important role in the development of this
malignancy.
-Most cases of sporadic colon adenocarcinoma arise from preexisting
adenomatous polyps. The transformation of normal mucosal cells into malignant
ones is caused by a series of gene mutations called the “adenoma-to-
carcinoma sequence” which includes the following steps:
1. Progression from normal mucose to a small polyp. The initial appearance of
small adenomatous polyps is attributed to the mutation of the APC tumor
suppressor gene. APC is located on chromosome 5, and its mutation leads to
uncontrolled cell proliferation.
2. Increase in the size of the polyps. Mutation of the K-ras protooncogene is
thought to facilitate this step. This mutation leads to the appearance a protein
that stimulates unregulated cell growth.
3. Malignant transformation of adenoma into carcinoma requires mutation of two
genes: p53 and DCC.
Sometimes called a “molecular policeman” p53 is an anti-oncogene. It
codes for protein p53, which triggers apoptosis of cells with damaged DNA.
Mutation of p53 allows cells with genomic errors to enter the cell cycle. This
mutation is considered the last “hit” in the adenoma-to-carcinoma
sequence.
http://img.medscape.com/pi/emed/ck...gery/188616-190486-676.jpg
http://radiographics.rsna.org/content/24/1/e18/F1.large.jpg

Sarcoidosis
= chest x-ray findings and elevated serum ACE level
- Sarcoidosis can cause arthralgias and skin changes occur in 30-50%. A variety
of skin lesions are possible, including subcutaneous nodules (erythema
nodosum), erythematous plaques, or macules that are slightly reddened and
scaling.
-Liver biopsy shows changes in up to 75% of cases. Scattered granulomas are
the most common liver pathology finding. Liver granulomas affect the portal
triads to a greater degree than the lobular parenchyma.
- The major cause of morbidity in sarcoidosis is pulmonary fibrosis, which can
progress to cor pulmonale.
http://www.aafp.org/afp/20020415/1581_f5.jpg
http://www.med.yale.edu/intmed/car...coidosis/graphics/rad1.gif
http://www.som.tulane.edu/classwar...8/Lung_Review/Lung-53.html

Lactase deficiency
=classified as congenital (rare) or acquired (common). The congenital variant is
a rare autosomal recessive condition caused by a gene near (but separate from)
the lactase gene. The acquired variant typically arises in certain races (eg,
Native Americans, African Americans) that cease producing lactase by mid-
childhood. Some individuals also appear to develop lactase deficiency secondary
to injury of the gastrointestinal mucosa.
-Light and electron microscopic examination of the bowel mucosa in lactase-
deficient patients has never demonstrated an identifiable abnormality, so normal
intestinal mucosa would be the expected finding in this patient population.
DIFF:
- Distended macrophages in the intestinal lamina propria= Wipple disease.
-Collections of neutrophils within the crypt lumina =ulcerative colitis.
-Intestinal inflammation with scattered noncaseating granulomas= Crohn
disease.
-Massive infiltration of the intestinal lamina propria with atypical lymphocytes =
gastrointestinal lymphomas.

Follicular lymphoma
= most common non-Hodgkin lymphoma in adults. It derives from follicular B-
cells and has an indolent clinical course marked by remissions and recurrences.
This condition most often presents with painless lymph node enlargement or
abdominal discomfort from an abdominal mass.
DIFF:
- Burkitt lymphoma is associated with EBV infection and is an aggressive tumor
(short doubling time) that is yew susceptible to chemotherapy.
-Diffuse large cell lymphoma is an aggressive non-Hodgkin lymphoma of B-cell
origin. It presents with a large lymph node or extranodal mass. The Waldeyer
ring (oropharyngeal lymphoid tissue) and GI tract are commonly involved.
-Mycosis fungoides is a cutaneous T-cell lymphoma. Proliferating CD4+
lymphocytes infiltrate the dermis and epidermis where they form Pautrier
microabscesses. This condition manifests with plaques that may be confused
with eczema or psoriasis. Generalized erythema, scaling and thickening of the
skin (erythroderma) may result
http://www.webpathology.com/image.asp?case=389&n=3
http://courseweb.edteched.uottawa....icular%20lymphoma%20lp.jpg

So:Follicular lymphoma is the most common non-Hodgkin lymphoma in adults. It

is of B-cell origin and presents with painless “waxing and waning”
lymphadenopathy. The cytogenetic change (14:18) is characteristic and results
in overexpression of the bcl-2 oncogene.

Carcinoid syndrome
- carcinoid heart disease= fibrous intimal thickening with endocardial plaques
limited to the right heart
- classically produces episodes of skin flushing, abdominal cramping, nausea,
vomiting, and diarrhea, and is thought to be due to production of serotonin,
kallikrein, bradykinin, histamine prostaglandins, and/or tachykinins by carcinoid
tumors. The degree of endocardial fibrosis seen in this syndrome correlates with
plasma levels of serotonin and urinary excretion of the serotonin metabolite 5-
hydroxyindoleacetic acid.
-This fibrosis is generally limited to the right heart because both serotonin and
bradykinin in the blood are inactivated distally by pulmonary vascular endothelial
monoamine oxidase. Pulmonic stenosis and restrictive cardiomyopathy may
ultimately result from this condition.
http://www.sandostatin.com/images/...eatment/gep_4.0_image1.gif

Night blindness
This patient describes symptoms consistent with decreased visual acuity and
tunnel vision in low ambient light. Tunnel vision predisposes to motor vehicle
accidents. Night blindness (nyctalopia) implies degeneration and/or functional
impairment of the retinal rods.
-Although the most common cause of night blindness is hereditary retinitis
pigmentosa, this patient has acquired nyctalopia, the differential diagnosis of
which includes:
1. Toxic retinopathy due to phenothiazines or chloroquine
2. Vitamin A deficiency
3. Congenital rubella, syphilis, or other infections
4. Diabetic retinopathy
This patient also has dry skin, which suggests vitamin A deficiency (from biliary
obstruction leading to cholestasis and fat soluble vitamin malabsorption)

Hemophilia A
= X-linked recessive disorder that develops due to mutations of the gene that
codes for factor VIII. If the concentration of this pro-coagulant is greater than
5% of normal then the bleeding disorder is mild.
-Symptoms= prolonged bleeding after tooth extractions and surgeries. Easy
bruising maybe seen, but no petechial lesions are present because petechiae are
characteristic of platelet disorders. Spontaneous bleeding into the joints
(hemarthrosis) is typical for hemophilia and may lead to inflammation and
deformity of affected joints.
- Factor VIII is synthesized by hepatocytes and stored in the endothelium of
blood vessels.
-Desmopressin acetate (DDAVP) stimulates release of factor VIII from
endothelial cells and can temporarily increase plasma factor VIII levels by two to
three-fold. DDAVP is used for the treatment of mild-to- moderate hemophilia A
and has no effect in hemophilia B, an X-linked recessive defect in factor IX.
Desmopressin is a synthetic analog of vasopressin (ADH) and is also used for
treatment of diabetes insipidus because it increases reabsorption of water in the
collecting tubules.

a1-antitrypsin deficiency
- Deficiency of a1-antitrypsin can cause panacinar emphysema (a form of
COPD), which usually affects the lower lung lobes most severely.
-A1-antitrypsin is the major serum inhibitor of neutrophil elastase. Panacinar
emphysema is thought to be caused by excess neutrophil elastase activity inside
alveoli. Lower lung fields maybe affected most severely because they receive
relatively greater perfusion, allowing a greater rate of neutrophil infiltration.
DIFF:
- Centriacinar emphysema =predominantly upper lung lobe distribution and a
strong association with smoking. Destructive proteases released by both
macrophages and neutrophils cause the acinar wall destruction in this type of
emphysema. The predilection of this type of emphysema for upper lung
segments may reflect the relatively low perfusion and therefore low presence of
serum α1-antitrypsin.
http://pathhsw5m54.ucsf.edu/case25/image253.html#answer
http://pathhsw5m54.ucsf.edu/case25/image253.html#answer2
http://pathhsw5m54.ucsf.edu/case25/image253.html#answer3

Cavernous hemangioma
= most common benign liver tumor typically presenting in adults aged 30-50
years. These benign tumors are thought to be congenital malformations that
enlarge by ectasia, not hyperplasia or hypertrophy.
-Hemangiomas may occur singly or in multiples and are well-circumscribed
masses of spongy consistency, typically measuring less than 5 cm in width.
-Microscopically, these tumors consist of cavernous, blood- filled vascular spaces
of variable size lined by a single epithelial layer. Collagenous scars or fibrous
nodules may be seen in association with thrombosis.
-Most patients are asymptomatic, although some will complain of abdominal pain
and right upper quadrant fullness. Prognosis is usually excellent, with surgical
resection an option for those patients who are symptomatic or who have
compression of adjacent structures.
http://www.learningradiology.com/a...iver/hemangiomacorrect.htm
http://www.pathology.vcu.edu/education/gi/lab3.j.html

Intussusception
= an invagination of a portion of the intestine into the lumen of the adjacent
intestinal segment (imagine a collapsed telescope). Intussusception leads to
impaired venous return from the invaginated segment of the bowel which can
cause ischemia and subsequent necrosis of the intestinal wall.
-The most typical location for intussusception is at the ileocolic junction. The size
differences in the adjacent segments of the intestine allow the small bowel to
invaginate into the cecum.
-Intussusception is most common in children younger than 2 years old. In this
age group, it often occurs without any structural cause (sometimes associated
with viral infection). In patients older than 2 years of age, a lead point, such as
Meckel diverticulum, foreign body, or intestinal tumor, should be sought.
-Clinical presentation is colicky, intermittent abdominal pain, nausea, vomiting,
and “currant jelly” stools (that contain blood and mucus). A tubular mass
may be palpable in the lower right abdominal quadrant. Barium enema is
diagnostic and may be therapeutic. If the intussusception does not resolve with
barium enema, surgical intervention is mandated.
http://surgery.med.umich.edu/pedia...mages/intussusception3.jpg

Chronic bronchitis
-The leading cause of chronic bronchitis is cigarette smoking. Chronic irritation
by other inhaled environmental substances, such as air pollutants and grain
cotton, or silica dusts may also be a contributing factor.
- Thickened bronchial walls, neutrophil infiltration, mucous gland enlargement
and patchy squamous metaplasia of the bronchial mucosa are features of chronic
bronchitis.
https://courses.stu.qmul.ac.uk/smd...sepics/images/broncrbr.jpg
DIFF:
- Chronic asthmatics with extrinsic allergic asthma =bronchial wall pathology
(remodeling) which includes thickening of the bronchial epithelium, basement
membrane, and bronchial walls as well as edema, inflammatory infiltrates
submucosal mucous gland enlargement, and bronchial smooth muscle
hypertrophy. However, the infiltrate will consist predominantly of eosinophils and
mast cells. Furthermore, while asthma can cause chronic bronchitis (e.g. chronic
asthmatic bronchitis, chronic eosinophilic bronchitis), cigarette smoking is a
much more common cause.

Comedocarcinoma (DCIS)Ductal carcinoma in situ

= precancerous breast lesion characterized by a malignant clonal cell
proliferation contained by the surrounding ductal basement membrane. The
(basal) myoepithelial layer of the duct is preserved and uninvolved. Usually only
a single ductal system appears to have DCIS. However, far more extensive DCIS
lesions can occur, with widespread involvement of the breast parenchyma
occasionally identified. In mammographically screened populations, DCIS now
represents 15-30% of all carcinomas and 5O% of mammogram-identified
carcinomas.
-Classically DCIS is divided into five different subtypes: comedocarcinoma, solid
cribriform, papillary, and micropapillary. Most cases have a mixture of patterns.
-Comedocarcinoma, = identified as solid sheets of pleomorphic, high-grade cells
with central necrosis. Chronic inflammation and periductal concentric fibrosis are
additional findings. As the malignant cell membranes become necrotic they
calcify, allowing mammographic detection of microcalcification clusters. If the
comedocarcinoma is extensive the lesion maybe palpable as a poorly defined
nodule.
http://www.lmp.ualberta.ca/resourc...ages/Images-C/000p039q.jpg
http://pathology.class.kmu.edu.tw/ch10/Slide86.htm

DIFF:
- Paget disease of the nipple= rare form of breast cancer in which malignant
cells spread from superficial DCIS into nipple skin without having crossed the
basement membrane. Physical examination reveals unilateral erythema and
scale crust around the nipple.
http://radiographics.rsna.org/cont.../suppl_1/S65/F32.large.jpg

- Medullary carcinoma = by solid sheets of vesicular pleomorphic, mitotically

active cells with a significant lymphoplasmacytic infiltrate around and within the
tumor and a pushing noninfiltrating border.
http://www.breastdiseases.com/slides/invsl25.htm

- Sclerosing adenosis=central acinar compression and distortion (by surrounding

fibrotic tissue) and peripheral ductal dilation. Sclerosing adenosis is a common
finding in fibrocystic change.

- Mammary duct ectasia= ductal dilation, inspissated breast secretions and

chronic granulomatous inflammation in the periductal and interstitial areas.

- Phyllodes tumors= similar to fibroadenomas but have increased cytological

atypia and stromal cellularity and overgrowth. The resultant architecture is
described as “leaflike.”
http://wpcontent.answers.com/wikip...190px-Phyllodes_tumour.jpg

Wernicke encephalopathy
=Confusion, ataxia and ophthalmoplegia f
= occurs in the setting of chronic thiamine deficiency (usually due chronic
alcoholism or severe malnutrition). In alcoholics, thiamine tends to be deficient
because of liver dysfunction among other things. Because thiamine is a cofactor
of the enzymes responsible for glucose metabolism, infusion of glucose will
exacerbate the pre-existing thiamine deficiency, often precipitating Wernicke
encephalopathy.
-Damage to mamillary bodies (foci of hemorrhage and necrosis) is characteristic
of Wernicke encephalopathy.
The clinical presentation of thiamine-deficient (Wernicke) encephalopathy:
1. Hallmark ocular findings include horizontal nystagmus, bilateral abducens
palsy, and complete ophthalmoplegia. Ocular irregularities are the first to
respond to thiamine infusion.
2. Ataxia is a manifestation of cerebellar damage (degeneration of all layers of
the cortex). Damage can be irreversible.
3. Confusion, apathy, inattentiveness, and disorientation indicate the
development of encephalopathy.
Always give thiamine supplementation with glucose in patients suspected of
having thiamine deficiency (patients who abuse alcohol and patients with a poor
diet).

Rejection reactions
-The severity of the rejection depends on the degree of difference between the
donor and recipient MHC (major histocompatibility complex) antigens.
1. Hyperacute rejection
= occurs within minutes of transplantation. Preformed antibodies are the cause.
There is graft blood vessel spasm and resultant ischemia. For this reason,
hyperacute rejection is sometimes called “white graft” reaction.
Hyperacute rejection is rare.
2. Acute rejection occurs 1-2 weeks after receiving a transplant. It represents
the recipient’s reaction to the HLA antigens of the graft. This is a cell-
mediated immune response. CD8 I-cells play a central role. Acute rejection
causes vascular damage. On light microscopy perivascular and peribronchial
lymphocytic infiltrates are seen. In lung transplant patients, acute rejection
manifests with dyspnea, dry cough, and low-grade fever.Pulmonary and
bronchial vessels are the main targets of acute rejection. Perivascular infiltration
with lymphocytes, macrophages and plasma cells is characteristic. There may be
perihilar and lower lobe opacities on chest x-ray. Immunosuppressants can
successfully treat acute rejection.
3. Chronic rejection occurs months or years following transplantation. It is the
major cause of mortality in lung transplant patients. Chronic rejection causes
inflammation of the small bronchioles, a process called bronchiolitis obliterans.
Inflammation and fibrosis of the bronchiolar walls lead to narrowing and
obstruction of the affected bronchioli. Clinically bronchiolitis obliterans presents
with dyspnea, non-productive cough and wheezing. Alveolar walls and pleura are
not affected in chronic rejection.

Atrophic gastritis
-can result in profound hypochlorhydria, inadequate intrinsic factor production,
vitamin B12 deficiency, megaloblastic anemia, and elevated serum gastrin and
methylmalonic acid (MMA) levels.
- Once vitamin B12 replacement therapy is initiated in an individual with atrophic
gastritis, the reticulocyte count increases dramatically. Hemoglobin and RBC
count levels gradually rise while the methilmalonic acid level decreases.
- Vitamin B12 deficiency is associated with increased serum levels of
methylmalonic acid and homocysteine. The levels of these substances should
gradually fall in accordance with effective vitamin B12 replacement.

Crohn’s disease
Complications:
1. Intestinal: fistulas, strictures, abscesses perianal disease, increased risk of
adenocarcinoma.
2. Skin: erythema nodosum, pyoderma gangrenosum.
3. Joints: arthritis, ankylosing spondylitis.
4. Eyes: iritis ,uveitis, episcleritis.
5. Malabsorption: oxalate kidney stones, anemia, hypoproteinemia, B12 and
folate deficiencies, and gallstones.
6. Liver: primary sclerosing cholangitis, increased risk of cholangiocarcinoma.
Crohn’s disease may involve any area of the gastrointestinal tract. The
terminal ileum, however, is commonly involved. Normally bile acids which are
necessary for the absorption of fat and other nutrients are reabsorbed in the
terminal ileum, “recycled” in the liver, and then reused in the absorptive
process. When the wall of the terminal ileum is inflamed, most bile acids are lost
with feces. Loss of bile acids cause impaired fat absorption. The excess lipids in
the bowel lumen bind calcium ions, and this complex is excreted with feces.
In the healthy bowel, dietary calcium binds dietary oxalate, enabling oxalate
excretion. In Crohn’s disease calcium binds instead to lipids making it
unavailable for oxalate binding. As a result oxalate is absorbed and forms urinary
stones.
http://www.worldofstock.com/slides/PHE1608.jpg
DIFF:
- Increased intestinal calcium absorption= in sarcoidosis and certain lymphomas.
It is caused by excess synthesis of 25-dihydroxy vitamin D, leading to
hypercalcemia.
-Struvite stones (not oxalate) are associated with chronic urinary tract infection.
http://www.calculilab.com/art/pix/struvite.jpg

Chronic mesenteric ischemia

=most often caused by atherosclerotic narrowing of the celiac trunk SMA and
IMA. This triad of symptoms characterizes the disease:
1. Epigastric or periumbilical abdominal pain occurs 30-60 min after food intake.
Atherosclerotic arteries are not able to dilate in response to increased blood flow
requirements during the digestion and absorption of food.
2. Weight loss is common; many patients avoid the pain associated with eating.
Patients report severe pain; but the physician examination will usually appear
benign.
-On light microscopy hypoperfused areas of intestine show mucosal atrophy and
loss of villi. Atherosclerotic plaques are found in the intestinal vessels.
-Correctly diagnosing chronic mesenteric ischemia is difficult. Angiography is the
gold standard but this method is invasive and expensive. Mesenteric duplex
ultrasonography is a non-invasive alternative in assessing intestinal blood

Fibroadenoma
=the most common benign tumor of the breast typically arising in young adult
women in their twenties or thirties. As well-demarcated spherical nodules
ranging in size , fibroadenomas can occur in both breasts. Fibroadenomas may
increase in size during the luteal phase of the menstrual cycle or during
lactation.
-In younger women= freely movable, palpable mass; in older women, the tumor
generally is identified as a mammographic density.
-Histologically = a cellular, often myxoid stroma that encircles epithelium-lined
glandular and cystic spaces. The epithelium of a fibroadenoma can be
compressed by the surrounding stroma. As women age, this epithelium atrophies
and the stroma becomes more hyalinized.
http://www.hopkinsbreastcenter.org/pathology/benign/1r.jpg

DIFF
intraductal papilloma
http://www.hopkinsbreastcenter.org/pathology/benign/1u.jpg
fat necrosis with microcalcifications
http://www.hopkinsbreastcenter.org/pathology/benign/1k.jpg
Medullary carcinoma=solid sheets of vesicular pleomorphic, mitotically active
cells with a significant lymphoplasmacytic infiltrate around and within the tumor
and a pushing noninfiltrating border.
http://www.breastpathology.info/Special%20Types.html#Inv Medullary Like Ca
Rapidly progressive (crescentic) glomerulonephritis (RPGN)
=Crescent formation on light microscopy
= a syndrome of severe glomerular injury that rapidly progresses to renal failure
within weeks to months of its onset. PRGN can be caused by a number of
different diseases.
-RPGN is divided into 3 types based on immunologic findings:
1.Type 1 RPGN is characterized by anti-glomerular basement membrane (anti-
GBM) antibodies. Linear GBM deposits of lgG and C3 are found on
immunofluorescence. Anti-GBM antibodies cross-react with pulmonary alveolar
basement membranes, producing pulmonary hemorrhages (hemoptysis). Type 1
RPGN is found in association with Goodpasture syndrome (anti-GBM disease).
2.Type 2 RPGN is immune-complex mediated. There is a “lumpy bumpy”
granular pattern of staining on immunofluorescence microscopy. Type 2 RPGN
can be a complication of poststreptococcal glomerulonephritis, SLE, IgA
nephropathy, or Henoch-Schonlein purpura.
3.Type 3 RPGN is called “pauci immune” because there are no
immunoglobulin or complement deposits on the basement membrane. Most
patients with type 3 RPGN have ANCA (anti-neutrophil cytoplasmic antibodies) in
their serum. This condition is often associated with Wegener’s
granulomatosis, but can also be idiopathic.

http://www.medic.usm.my/~pathology/KIDNEY.HTM

DIFF
- Decreased serum C3 level = seen with poststreptococcal glomerulonephritis
and with dense-deposit disease (type II MPGN). The cause is activation of the
alternative complement pathway so Cl and C4 levels are normal.
-Decreased serum C4 level=seen in hereditary angioedema. Here, the classical
pathway is activated secondary to a lack of C1 esterase inhibitor, which permits
unopposed breakdown of C4 by Cl esterase.

Congestive heart failure (CHF)

- Possible causes of CHF=diffuse ischemic heart disease or dilated
cardiomyopathy (DCM). DCM is the most common form of cardiomyopathy. It
may be idiopathic or a consequence of viral myocarditis ,cardiotoxic substances
such as alcohol, the peripartum state or genetic mitochondrial or cytoskeletal
defects. DCM is characterized by ventricular dilatation contractile dysfunction and
oftentimes symptoms and signs of CHF (as is chronic ischemic heart disease).
=abnormal decrease in myocardial contractility.
http://www.bmb.leeds.ac.uk/illingworth/myopath/postmort.jpg
Pick’s disease
=rare cause of dementia that is characterized by the destruction of frontal lobes.
- The important structures of the frontal lobe include the motor cortex,
Broca’s speech area, frontal eye fields and the prefrontal cortex. Lesions of
the prefrontal cortex cause inappropriate behavior impaired judgment and lost
problem solving skills. Incontinence and gait disturbances may be seen.
- In evaluating a patient Pick’s disease should be differentiated from the
more common Alzheimer disease.
Pick's disease:
-pronounced atrophy of frontal and temporal lobes
-neuronal loss in frontotemporal lobes; Pick bodies (cytoplasmic inclusions of
microtubule-associated protein tau)
-urinary incontinence
-unknown genetic basis
-most cases are sporadic
-behavioral: apathy, socially inappropriate behavior,disinhibition, speech
difficulties, such as dysarthria, aphasia, and echolalia.
http://neuropathology.neoucom.edu/chapter9/images9/9-9.jpg
http://www.ftdrg.org/wp-content/uploads/pick-bodies2.jpg

DIFF
-hippocampus damage = inability to form new memories (anterograde amnesia).
In Alzheimer disease, the hippocampus is one of the first regions to suffer
damage.
-subthalamic nucleus damage = hemiballism (involuntary flinging movements of
extremities contralateral to the lesion); is a part of the basal ganglia system. It
utilizes the neurotransmitter glutamate and sends axons to the globus pallidus.
-inferior parietal lobule of the dominant hemisphere damage = Gerstmann’s
syndrome—right left confusion ,dysgraphia, dyslexia, and dyscalculia. Damage
of the inferior parietal lobule of the non-dominant hemisphere causes apraxia
and contralateral hemi neglect.

Renal cell carcinoma

=most common renal neoplasm, accounting for about 70% of all kidney tumors.
-originates from the epithelium of the proximal renal tubules.
-typically affects patients who are 60 to 70 years old. Risk factors include
smoking and obesity.
- On gross examination, this tumor appears as a golden yellow mass.
- Prominent vascularity is evident. The tumor cells are cuboidal to polygonal in
shape, with clear abundant cytoplasm and eccentric nuclei. These cells have this
appearance because they are packed with glycogen and lipids. The tumor cells
show little polymorphism (the cells are similar in shape and size) and the nuclei
are small (suggesting that the tumor is well-differentiated).
http://www.med.niigata-u.ac.jp/npa...ages/Slides/RCC/1RCC_L.gif
DIFF
-Renal oncocytomas =very rare tumors that originate from collecting duct cells.
Oncocytes are large, well-differentiated neoplastic cells that contain numerous
mitochondria.
http://www.lmp.ualberta.ca/resourc...ages/Images-R/000p0115.jpg

Patent ductus arteriosus (PDA)

- Normally, the ductus arteriosus closes during first 15 hours of life. In neonates
prostaglandins (PGE1) can help to maintain a PDA and indomethacin and
ibuprofen (NSAIDS) can help to close the PDA by inhibiting PGE synthesis.
-Delayed closure of the ductus arteriosus is associated with prematurity,
perinatal distress, congenital rubella and fetal alcohol syndrome. Physical
examination = continuous “machinery” murmur, heard best at the left
upper sternal border.
-The ductus arteriosus is a remnant of the 6th aortic arch that connects the
aorta and left pulmonary artery, allowing already-oxygenated blood from the
mother to bypass the fetal lungs. After birth, a PDA allows blood from the
systemic circulation to flow to the pulmonary circulation (left-to-right shunt),
resulting in excessive pulmonary blood flow. If the blood flow though the PDA is
small, the infant is asymptomatic. With a large shunt dyspnea, cyanosis and
frequent respiratory infections may occur over time.
http://www.healthofchildren.com/im...ch_0001_0003_0_img0204.jpg

Hydrocephalus - three groups:

1. increased CSF production is a rare cause of hydrocephalus. Excessive CSF
may be produced by choroid plexus papillomas.
2. Abnormal CSF circulation is the most common cause of hydrocephalus.
Obstruction is located in either the ventricles or arachnoid villi.
3. Disorders of cerebrospinal fluid absorption are rare.
-In true hydrocephalus, the increase in CSF volume and pressure cause
ventricular enlargement.
- In diseases associated with cerebral atrophy (Alzheimer, Pick disease, etc.),
however, ventricular enlargement occurs secondary to atrophy of the brain. Such
compensatory ventricular expansion is called “hydrocephalus ex vacuo.”
Although the distended ventriculi produce a CT image similar to true
hydrocephalus, CSF pressure is not increased. Cortical atrophy is a common
sequelae of advanced HIV infection.
http://wpcontent.answers.com/wikip...n/9/98/Schiavo_catscan.jpg
Pseudotumor cerebri (idiopathic intracranial hypertension)
=elevated intracranial pressure with normal CSF content and normal neuro-
imaging. This disorder classically occurs in young, obese women and manifests
as headache and papilledema; possible sequelae include optic nerve atrophy and
blindness.

Lissencephaly (agyria)
= a congenital absence of gyri. This condition is accompanied by severe mental
retardation. On both gross exam and imaging studies, the brain surface has a
smooth appearance.
http://www.mcl.tulane.edu/classwar...ology/68_Lissencephaly.jpg

Lipoprotein lipase deficiency

Dietary lipids are transported to the peripheral tissues as chylomicrons, at which
point they are hydrolyzed by lipoprotein lipase, releasing triglycerides.
Lipoprotein lipase deficiency is a rare disorder that results in increased
concentrations of serum chylomicrons. The body is unable to clear dietary lipid
loads due to the defective hydrolysis of triglycerides in chylomicrons.
=in childhood:marked hyperlipidemia, pancreatitis (abdominal pain) lipemia
retinalis, eruptive skin xanthomas and hepatosplenomegaly.
- The risk of pancreatitis is significantly increased with serum triglyceride
concentrations above 1000 mg/dL.
-In normal individuals heparin releases endothelium-bound lipases, encouraging
the clearance of triglycerides from the circulation. In patients with lipoprotein
lipase deficiency, heparin-induced lipoprotein lipase activity is significantly
reduced.

Defects in the LDL receptor

- LDL is composed predominantly of cholesterol. The main mechanism by which
LDL is cleared from the circulation is by “receptor-mediated uptake” by the
liver. Defects in the LDL receptor lead to hypercholesterolemia.
- Individuals heterozygous for the defective LDL receptor gene have an LDL
receptor density of about 50% normal. Serum LDL in these individuals ranges
from 200-400 mg/dL. Individuals homozygous for the defect have LDL receptor
activity that is less than 2% of normal, with dramatically elevated of LDL
concentrations.
-Patients with hypercholesterolemia are at high risk for accelerated coronary
artery disease. Those with the homozygous defect may present at a very young
age. (In contrast, patients with lipoprotein lipase deficiency are not usually at
increased risk for premature coronary artery disease making chest pain an
unlikely presentation ).
- Clinically patients with defective LDL receptors have tubular xanthomas, which
are nodular lipid deposits in the tendons (most often seen in the Achilles and
elbow tendons). Tubular xanthomas are the hallmark of familial
hypercholesterolemia. Some patients also have xanthelasma and arcus cornea.
http://www.cytochemistry.net/Cell-biology/medical/end4.jpg

Systemic lupus erythematosus (SLE).

= chronic autoimmune disorder, affects mostly women of childbearing age. Black
women have a higher risk of developing SLE than Caucasian and Asian women.
-Hematologic abnormalities are common in patients with SLE. They occur due to
formation of antibodies against blood cells and represent a form of type II
hypersensitivity reaction.
-Anemia in SLE is caused by autoimmune hemolysis, and develops due to
formation of warm lgG antibodies to RBCs. It is characterized by spherocytosis, a
positive direct Coombs test, and extravascular hemolysis.
-The pathogenesis of SLE-associated thrombocytopenia is identical to that of
ITP; antibodies against platelets are formed causing destruction of platelets.
-Neutropenia due to antibody-mediated destruction of WBCs also occurs, but this
is less common.

B-cell neoplasm follicular lymphoma

-The characteristic cytogenetic abnormality associated with follicular lymphoma
is a translocation of the bcl-2 oncogene from chromosome 18 to the lg heavy
chain locus on chromosome 14 [t(14:18)].
-Juxtaposition of the bcl-2 gene with the lg heavy chain region results in
overexpression of the Bcl-2 protein product. Bcl-2 protein inhibits apoptosis of
tumor cells, thereby facilitating neoplastic growth.
http://medicineworld.org/images/ne...gs/follicular-lymphoma.jpg

DIFF:
-Burkitt lymphomas= translocations of the C-MYC gene on chromosome 8,
usually onto the Ig heavy chain region of chromosome 14 [t(8:14)].
Histologically, Burkitt lymphoma shows a diffuse population of medium-sized
lymphocytes with a ‘starry sky appearance due to the high proliferation index
and high rate of apoptosis.
http://courseweb.edteched.uottawa....%20images/Burkitt%20lp.jpg
- The t(9;22) BCR-ABL rearrangement is found in CML
- Overexpression of the N-MYC proto-oncogene is common in neuroblastoma and
small cell carcinoma of the lung.
Adrenal crisis
-Cushing syndrome = glucocorticoid excess. Exogenous administration of supra
physiological doses of glucocorticoid can produce clinical features
indistinguishable from endogenous Cushing syndrome. Cushing syndrome
resulting from exogenous administration of glucocorticoids can lead to
suppression of the entire hypothalamic-pituita-adrenal axis. Thus, these patients
have low endogenous CRH, ACTH and cortisol production. Suppression of CRH
and ACTH causes atrophy of the bilateral adrenal cortices. HPA axis suppression
is more likely to occur with long-term use of exogenous glucocorticoids (i.e.
more than three weeks duration). Sudden cessation of glucocorticoids after
prolonged use can cause adrenocortical insufficiency and adrenal crisis.
DIFF
- With an adrenocortical adenoma, there is autonomous production of cortisol by
the affected adrenal gland. This causes pituitary ACTH secretion to be
suppressed, resulting in atrophy of the contralateral adrenal gland.

Carcinoid tumor
=uniformity in shape and size of the cells that comprise the nests and glands
-Tumor cells have an eosinophilic cytoplasm and oval-to- round nuclei.
-Carcinoid tumors are easily recognizable, as there is minimal to no variation in
shape and size of tumor cells. Glands, nests, rows, or sheets may be formed.
-On electron microscopy, multiple dense-core granules are seen in the
cytoplasm. These granules contain secretory products of the tumor cells.
-Carcinoids can produce a number of hormone-like substances (such as insulin
and gastrin) and vasoactive peptides (serotonin, bradykinin, and many others).
-Intestinal carcinoids are malignant transformations of enterochromaffin
(endocrine) cells of the intestinal mucosa. These cells are a part of the APUD-
system (Amine Precursor Uptake and Decarboxilation). APUD or
enterochromaffin cells are found in many organs and tissues, where they secrete
a number of hormone-like substances that play an important role in regulating
organ function.
-The most common location of intestinal carcinoids is the appendix. They also
frequently occur in the ileum and rectum.
http://pathhsw5m54.ucsf.edu/case7/image76.html

Dermatitis herpetiformis
= erythematous, pruritic papules, vesicles, and bullae that appear bilaterally and
symmetrically on the extensor surfaces, elbows, knees, upper back, and
buttocks. The term “herpetiformis” is applied because this distinctive
vesicular grouping looks quite similar to the lesional clustering seen in
herpesvirus infections. Men are more frequently affected than women, with the
age of onset peaking in the third and fourth decades.
= strongly associated with celiac disease, and both the enteropathy and
dermatitis tend to improve with a gluten-free diet.
-pathogenesis =formation of IgA and IgG antibodies against gliadin (a protein
unique to the gluten portion of wheat). These antibodies appear to cause clinical
disease by cross-reacting with reticulin, a protein found in the anchoring fibrils of
the epidermal basement membrane.
-Histologically, = microabscesses containing fibrin and neutrophils at the dermal
papillae tips. The overlying basal cells become vacuolated, and blisters begin to
form at the tips of involved papillae. Older lesions may also demonstrate an
eosinophilic infiltration.
http://graphics8.nytimes.com/image...08/01/health/adam/2791.jpg

Lichen planus
= the “5 Ps”: polygonal, planar, pruritic, purplish plaques on the wrists,
hands, trunk, and legs. A finely reticulated scale termed “Wickham’s
striae” may be present on the plaque surface.
http://www.aafp.org/afp/20000601/3319_f2.jpg

Crohn’s disease
=non-caseating granuloma, a classical histologic finding
= abdominal pain and bloody diarrhea.
Light microscopy findings in Crohn’s disease are characteristic:
1. Chronic inflammation involves the entire thickness of intestinal wall
(transmural inflammation).
2. Non-caseating granulomas may be present in all tissue layers.
3. Mucosal ulceration: long linear ulcers with spared intervening mucosa lead to
a cobblestone appearance.
-On macroscopic examination, involved segments of the intestine are thick and
edematous. Diseased and healthy areas of the mucosa are sharply demarcated
(skip lesions formed by normal mucosa are characteristic of Crohn’s disease.)

Inflammation of the intestinal wall almost universally leads to the narrowing of

that intestinal segment. On contrast barium study, the “string sign” or
narrowed segments of bowel, will be present. Strictures that commonly occur in
Crohn’s disease may lead to symptoms of chronic intestinal obstruction.
Another complication is fistula formation between two adjacent loops of intestine
or between the intestine and other organs such as the bladder or vagina.
http://www.nature.com/nri/journal/v3/n7/images/nri1132-i1.gif
http://www.pathguy.com/sol/10190.jpg
Poststreptococcal glomerulonephritis (PSGN)
=inflammatory reaction involves all glomeruli in both kidneys. The kidneys are
enlarged and swollen, with multiple surface punctuate hemorrhages.
-On light microscopy, all glomeruli are enlarged and hypercellular due to
leukocyte infiltration and proliferation of endothelial and mesangial cells. On
electron microscopy, electron-dense deposits (“humps”) on the epithelial
side of the basement membrane are seen.
-Immunofluorescence reveals coarse granular deposits of lgG and C3 that have a
characteristic “lumpy-bumpy” appearance.
http://www.pathologyatlas.ro/patho...ive_glomerulonephritis.jpg
http://anatpat.unicamp.br/erim.html#micro

Goodpasture syndrome (anti-GBM disease)

= Linear lgG and C3 deposits on immunofluorescence microscopy
-. There is crescent formation on light microscopy. Renal involvement is often
accompanied by pulmonary symptoms.
=Glomerular basement membrane (GBM) disruptions and fibrin deposition on
electron microscopy . The GBM breaks are due to fibrinoid necrosis of the
glomeruli. There is typically crescent formation on light microscopy, but
crescents may not be detectable in early disease. An important contributor to
crescent formation is fibrin escape into Bowman’s space.
http://www.idac.tohoku.ac.jp/en/or...immunology/image/Exp-4.jpg
http://www.bio.davidson.edu/course...rter/restricted/Cresgn.jpg

Membranous glomerulopathy
=Uniform, diffuse thickening of glomerular capillary walls on light microscopy
= one of the most common causes of nephrotic syndrome in adults. Clinical
manifestations of nephrotic syndrome include generalized edema, marked
proteinuria (>3.5 g/day), hypoalbuminemia, hyperlipidemia and lipiduria.
http://www.pathologypics.com/PictView.aspx?ID=465

Henoch-Schonlein purpura (HSP)

= the most common small vessel vasculitis in children. This disease classically
affects boys 2-10 years old, and is often preceded by viral or streptococcal upper
respiratory infections.
-Symptoms of HSP generally develop a few weeks after the associated illness
resolves. It is hypothesized that antigen from the infection stimulates production
of IgA antibodies and that IgA-containing immune complexes then deposit on
vessel walls, inducing an inflammatory reaction. HSP is therefore an IgA-
mediated leukocytoclastic (hypersensitivity) vasculitis.
The effects of this vasculitis
1. Gastrointestinal tract: Intermittent severe abdominal pain is common in HSP.
Vasculitis within the GI tract may result in upper and lower GI bleeding
(hematemesis and bloody diarrhea, respectively) as well as bowel wall edema.
Patients with HSP also have an increased risk of intussusception.
2. Kidneys: Renal involvement in HSP is identical to that seen in IgA
nephropathy (Berger disease), a condition characterized by IgA leukocytoclastic
vasculitis limited to the kidney. Both diseases cause mesangial proliferation and
crescent formation.
3. Skin: HSP classically causes “palpable purpura” on the buttocks and
lower extremities. These lesions may begin as urticarial papules or plaques and
subsequently evolve into purpura. The cutaneous findings in HSP result from
leuko cytoclasis of cutaneous vessels.
4. Joints: Self-limited migratory arthralgias and arthritis are most commonly
seen in the large joints of the lower extremities (ankle and knee joints) possibly
because of their dependent nature.
http://www.hdcn.com/symp/lund/jtimg26.jpg

Inflammatory breast cancer

=Peau d’orange= the presence of pitting edema in subcutaneous breast
tissue accompanied by skin thickening around exaggerated hair follicles.
- This malignancy causes lymphatic obstruction and tissue swelling when
collections of neoplastic cells plug the dermal lymphatic channels. Commonly,
women with inflammatory breast cancer present with breast tenderness skin
discoloration (ranging from pale pink to deep red brown to purple), and a rapidly
progressive underlying mass.
http://content.revolutionhealth.co...popup-ans7_breast_rash.jpg

Lipofuscin
=An insoluble pigment composed of lipid polymers and protein-complexed
phospholipids,
= a sign of “wear and tear” or aging. This yellow-brown, finely granular
perinuclear pigment is the product of free radical injury and lipid peroxidation. It
is commonly seen in the heart and liver of aging or cachectic, malnourished
patients.
http://www.jonbarron.org/images/lipofuscin.gif
http://www.technion.ac.il/~mdcours...ac%20Muscle-Lipofuscin.jpg
Anthracosis
= coal dust that is taken up by macrophages within the lung parenchyma
http://146.201.250.180/staticgalle...logy/anthracosis20x04.html

Childhood brain tumors:

1. Pilocytic astrocytomas are the most common. They are low-grade neoplasms
that arise from astrocytes. The cerebellum is the most common location of
pilocytic astrocytomas. On macroscopic examination, the neoplasm is cystic with
a tumor nodule protruding from the wall. This nodule is the active part of the
tumor. On imaging studies, a pilocytic astrocytoma appears as a mass with both
solid and cystic components. On microscopic examination pilocytic astrocytes
and Rosenthal fibers are seen. This tumor has a relatively good prognosis.
http://1.bp.blogspot.com/_oAQI4j4B...I/s320/sag%2Bcontr%2B1.jpg
http://www.surgicalpathologyatlas....sort=0&s=20080802174937135
2. Medulloblastomas are the second most common brain tumors of childhood.
They are located only in the cerebellum (most commonly, in the vermis).
Medulloblastomas are solid, and are composed of sheets of small blue cells with
hyperchromatic nuclei and scant cytoplasm. This tumor is highly malignant and
carries a bad prognosis. Clinical presentation is severe headache and cerebellar
dysfunction.
http://neurosurgery.seattlechildre...ts/images/tumors_large.jpg
3. Ependymomas are the third most common brain tumor in children. They arise
from the ependymal lining of the ventricle and can obstruct the flow of CSE.
Clinically they present with hydrocephalus. On microscopic examination, tumor
cells form gland-like structures called “rosettes.”
http://www.bccancer.bc.ca/NR/rdonl...157/pseudorosettesX100.jpg

Glioblastoma multiforme (GBM)

= tumor that arises from astrocytes and is the most common primary cerebral
neoplasm in adults. It is typically located within the hemispheres (in the frontal
or temporal lobe or near the basal ganglia).
http://radiographics.rsna.org/cgi/content-nw/full/27/2/525/F24C
http://upload.wikimedia.org/wikipe...sagittal_with_contrast.jpg

Oligodendrogliomas
=in patients of 40-50 years old. Their most common location is the white matter
of the frontal lobe. On gross examination they oligodendrogliomas present as
well-circumscribed gray masses. Calcifications may be visible; areas of necrosis
and hemorrhages are not common.
http://www.molecular-cancer.com/co...7/1/41/figure/F7?highres=y

Tumors that stain positive for keratin

= carcinomas, mesotheliomas, thymomas, various sarcomas, trophoblastic
tumors, and desmoplastic small round cell tumors.

Sickle cell anemia

- symptoms of “acute chest syndrome” (ACS), which is vaso-occlusive
crisis localized to the pulmonary vasculature that can occur in patients with
sickle cell anemia. ACS is commonly precipitated by pulmonary infection.
-In patients with homozygous hemoglobin S disease vaso-occlusive crises can
also cause splenic infarctions. Repeated infarctions overtime produce a spleen
that is shrunken, discolored, and fibrotic. By the time they reach adulthood,
most patients with sickle cell anemia have undergone “autosplenectomy”
as a result of these infarcts and are left with only a small, scarred splenic
remnant. The spleen may demonstrate brownish discoloration (hemosiderosis)
due to extensive ingestion of sickled RBCs by splenic macrophages
(extravascular hemolysis).
http://www.flickr.com/photos/14309782@N04/1607988490

Colon adenocarcinomas
-most develop from preexisting adenomatous polyps (adenomas).
-Colon adenomas usually occur in patients in 50-60 years old and are considered
premalignant. It is hypothesized that 10 years on average, is required for
malignant transformation of adenoma. Early detection and excision of
adenomatous polyps is therefore, an effective prophylaxis for colon
adenocarcinoma.
The malignant potential of adenomatous polyps is determined by the following:
1. Size of the polyp: <1cm — unlikely to undergo malignant transformation;
>4cm —4O% risk of malignancy.
2. Histologic appearance: villous adenomas are more prone to be malignant than
tubular adenomas.
3. Degree of dysplasia.
The transformation of normal mucosal cells into malignant ones is caused by a
series of gene mutations called the “adenoma-to-carcinoma sequence.”
This sequence includes the following steps:
1. Progression from normal mucosa to a small polyp. The initial appearance of
small adenomatous polyps is attributed to mutation of the APC tumor suppressor
gene.
2. Increase in the size of the polyps. Mutation of K-ras protooncogene is thought
to facilitate this step by leading to uncontrolled cell proliferation.
3. Malignant transformation of adenoma into carcinoma requires mutation of two
genes: p53 and DCC.
Increase in the size of adenomatous polyps (and, therefore, increase in their
malignant potential) is attributed to K-ras protooncogene mutation. This gene
normally encodes for a protein that regulates cell cycle by stimulating and
inhibiting it as necessary. Mutation of K-ras causes it to become the oncogene K-
ras, which encodes for a protein that has lost its ability to inhibit the cell cycle,
but can still stimulate it. Thus, unregulated cell proliferation ensues.
http://www.geocities.com/HotSpring.../7780/images/villaden.html
http://www.ajronline.org/cgi/content-nw/full/189/1/35/FIG12

Rapidly progressive glomerulonephritis (RPGN).

=a syndrome of severe renal injury that may be the result of a number of
disease processes. RPGN usually leads to rapid (within weeks to months) and
irreversible loss of renal function.
-The crescents =proliferated glomerular parietal cells, monocytes and
macrophages that have migrated into Bowman’s space, as well as abundant
fibrin between the cellular layers of the crescents. Fibrin escape into
Bowman’s space is an important contributor to crescent formation. As the
disease progresses, crescents become sclerotic and obliterate Bowman’s
space, thus impeding glomerular function.
-C3 and lgG are deposited along the glomerular basement membrane in patients
with type 1 RPGN (Goodpasture syndrome). In Goodpasture syndrome
immunofluorescence microscopy shows linear deposits of these complexes. C4
deposition is usually not found.
http://www.pathologyatlas.ro/patho..._glomerulonephritis_02.jpg

Pathogenesis of Crohn’s disease

- Increased activity of TH-1 helper cells increases production of IL-2, interferon-
y, and TNF causing subsequent intestinal injury.
-Non-caseating granulomas= characteristic of Crohn’s disease.
http://www.pathology.vcu.edu/education/gi/lab2.g.html
DIFF:
- TH-2 cells = involved in the pathogenesis of ulcerative colitis. They produce IL-
4, IL-5, IL-6, and IL-10, which might damage mucosal cells of the intestine.

Left recurrent laryngeal nerve impingement (Ortner syndrome)

-In rare instances, it may be compressed to the point of neurapraxia (failure of
nerve conduction due to blunt injury) by enlargement of the left atrium and/or
other structures in the vicinity of its course as it loops behind the ligamentum
arteriosum, underneath and around the aortic arch, and back up alongside the
trachea to the larynx.
-Mitral stenosis can cause left atrial dilatation sufficient to impinge on the left
recurrent laryngeal nerve
-The recurrent laryngeal nerves innervate all of the intrinsic muscles of the
larynx except the cricothyroid muscle. Paresis of vocal cord muscles innervated
by left recurrent laryngeal nerve can cause hoarseness.
http://www.drguide.mohp.gov.eg/New...-Learning/Cases/Case31.asp

Multiple sclerosis
= optic neuritis( pain with ocular movements and decreased vision) + Intention
tremor (sign of cerebellar dysfunction)
=Waxing and waning neurological deficits in a 20-30 year old patient are
suggestive of this disorder.
-The etiology of multiple sclerosis remains unknown. Currently, it is considered
an autoimmune disease, with viral and environmental factors also playing a role
in its pathogenesis. The autoimmune character of this disorder is supported by
the following features:
1. There is an elevated immunoglobulin G (lgG) level in the cerebrospinal fluid
(CSF). It is seen as an oligoclonal band on electrophoresis and suggests an
activation of B cells in multiple sclerosis.
2. The incidence of multiple sclerosis is increased in people with certain HLA
types.
3. Immunomodulatory agents, such as interferon beta, have a positive impact on
multiple sclerosis. Its mechanism is counteraction of the inflammatory action of
immune cells.
http://images.quickblogcast.com/80...tiple_sclerosis_MRI__2.gif

Goodpasture syndrome
= anti-glomerular basement membrane (anti-GBM) disease
=linear deposits of immunoglobulin along the glomerular basement membrane .
-These deposits are composed of lgG and C3. Anti-GBM antibodies target the α3
chain of collagen type IV, a component of the glomerular basement membrane.
The resultant renal injury is a type 1 RPGN. The presence of crescents in the
damaged glomeruli on light microscopy is diagnostic of RPGN.
Anti-GBM antibodies cross-react with the pulmonary alveolar basement
membrane, causing pulmonary hemorrhages. The combination of renal failure
with pulmonary hemorrhage (hemoptysis) is the typical clinical presentation of
anti-GBM disease.
http://www.pathguy.com/sol/16843.jpg
http://www.pathologyatlas.ro/patho...tic_glomerulonephritis.jpg
http://www.dokkyomed.ac.jp/dep-k/c...litis/vas-html/vas-63.html
DIFF:
-Basement membrane splitting is seen on electron microscopy in Alport
syndrome and membranoproliferative glomerulonephritis (MPGN) type 1. In
Alport syndrome, symptoms of nephritis are accompanied by deafness and
various ocular manifestations. In MPGN there are granular deposits on
immunofluorescence. On light microscopy, the glomeruli of MPGN have a lobular
appearance with proliferating mesangial cells and increased mesangial matrix.
http://www.gamewood.net/rnet/renalpath/tut41.jpg
http://www.uncnephropathology.org/jennette/mpgn_i/tut42.jpg
-Uniform, diffuse capillary wall thickening on light microscopy is a sign of
membranous glomerulopathy. The typical presentation is nephrotic syndrome:
generalized edema, marked proteinuria (>3.5 g/day), hypoalbuminemia,
hyperlipidemia and lipiduria. Immunofluorescence demonstrates granular
deposits of lgG and C3 along the glomerular basement membrane.
http://www.unckidneycenter.org/images/Membranous_capwalls.jpg
- In focal segmental glomerulosclerosis (FSGS) IgM and C3 deposits are found in
the sclerotic areas of the glomeruli on immunofluorescence. Linear deposition of
immunoglobulins is not typically found.
http://www.gamewood.net/rnet/renalpath/t9.jpg

Cholelithiasis
-Estrogenic influence facilitates the biosynthesis of cholesterol by increasing
hepatic HMG-CoA reductase activity. As the water-insoluble cholesterol is
secreted in bile, it is rendered soluble in small amounts by detergent-like bile
salts and phosphatidylcholine. Suppression of cholesterol 7α-hydroxylase
activity (as accomplished through medications such as clofibrate) reduces the
solubilization of cholesterol into bile acids, resulting in excess cholesterol
secretion in bile. When the gallbladder is hypomotile or there is more cholesterol
than bile salts, the cholesterol precipitates into insoluble crystals that eventually
form to make gallstones. Cholesterol and mixed stones together comprise 80%
of all gallstones in the Western population.
-numerous risk factors for the formation of cholesterol gallstones: Caucasian
race; obesity or rapid weight loss; female sex hormones or usage of oral
contraceptive pills; glucose intolerance; hypomotility of the gall bladder (which is
associated with pregnancy, advanced age, fasting hypertriglyceridemia, and
prolonged total parenteral nutrition); malabsorption of bile acids as would occur
secondary to ileal disease or resection; and pharmacotherapy with clofibrate,
octreotide, or ceftriaxone.
-Asymptomatic patients do not require intervention, but symptomatic
cholelithiasis is usually treated with laparoscopic cholecystectomy.
http://path.upmc.edu/cases/case23/images/gross1.jpg
http://www.telepathology.com/cases/gall1a.htm
Infant of diabetic mother
- Macrosomia is the classic “defect” this term describes a large infant
(larger than 4.0 kg by conservative measures). If blood glucose is poorly
controlled with diet and activity, insulin treatment is generally started. High
glucose levels in the mother enter fetal circulation, causing high blood glucose
levels to be present in the fetus. The fetus responds to this elevated blood
glucose by increasing insulin. Obviously, the amount of insulin generated by
these fetuses is more than normal, and beta cell hyperplasia results. Once free
from the mother, the neonate continues to over-produce insulin
(hyperinsulinemia), which can cause the neonate to experience severe
hypoglycemia. High insulin levels are also responsible for the increased fat
deposition and enhanced fetal growth that results in macrosomia.
- Other birth defects in children whose mother’s had uncontrolled diabetes
during pregnancy = caudal regression syndrome, neural tube defects, ventricular
septal defect, transposition of blood vessels, rectal atresia, and renal agenesis.
- Maternal insulin cannot be transferred to fetus because it is catabolized during
transfer across the placenta

Superior vena cava syndrome

=impaired venous return from the upper body. The superior vena cava provides
the venous drainage of head, neck, upper trunk and upper extremities.
-The superior vena cava is a 6-8 cm long vein that drains into the right atrium. It
is located in the medial mediastinum and is surrounded by the sternum, trachea,
right bronchus aorta, and pulmonary artery. It is located in close proximity to
the perihilar and paratracheal lymph nodes. This vein has thin walls and is easily
compressed by mediastinal masses.
-Bronchogenic carcinoma is the most common cause of superior vena cava
syndrome.
-Non-Hodgkin lymphomas are the second most common cause.
-Patients with SVC syndrome complain of dyspnea, cough, and swelling of the
face, neck and upper extremities. Headaches, dizziness and visual disturbances
may occur due to elevated intracranial pressure. Dilated collateral veins may be
seen in the upper torso.
http://img.medscape.com/pi/emed/ck...gy/1048885-1094030-708.jpg
http://img.medscape.com/pi/emed/ck...y/1017692-1017949-3209.jpg

Superior sulcus tumor (or Pancoast tumor)

= arises at the lung apex and may cause shoulder pain due compression of the
brachial plexus. Involvement of the cervical sympathetic ganglia leads to
Horner’s syndrome (ptosis, miosis and anhydrosis).
http://www.mevis-research.de/~hhj/Lunge/imabc/BCWandTH_52.JPG
Colorectal tumor staging
-The degree of tumor differentiation (from well- differentiated to anaplastic) is
referred to as the grade.
-Tumor stage is the most important criteria for determining prognosis.
-If the tumor is confined to the mucosa (stage A), the patient has 90%+ chance
of 5-year survival. If it involves the muscular layer, 5-year survival rate is 70-
80%. Lymph node involvement (stage C) and distant metastasis (stage D) have
poor prognosis.
http://www.sgpgi.ac.in/path/seminars/Image5.gif
Prognosis of colorectal adenocarcinoma is directly related to the stage of the
tumor (not to the grade!).

Pyelonephritis
= fever, chills, nausea, vomiting, flank/abdominal pain, and costovertebral angle
(CVA) tenderness. Urine sediment microscopy reveals WBCs, WBC casts, and
bacteria.
-WBC casts = pathognomonic
-.WBC casts are also seen with acute interstitial nephritis, but clinical
presentation is different in that patients have only a low-grade fever and do not
experience painful urination.
-Sterile pyuria (WBCs, but no bacteria) is seen in a small number of patients
with acute pyelonephritis, but can also be seen with non-gonococcal urethritis
caused by Chlamydia and Ureaplasma.
http://www.med.osaka-u.ac.jp/pub/hp-lab/www/atlas/EWBCCAST.html
http://www.pathologyatlas.ro/patho...cute_pyelonephritis_01.jpg

Von Hippel—Lindau disease

=rare autosomal dominant condition characterized by the presence of capillary
hemangioblastomas in the retina and/or cerebellum, as well as congenital cysts
and/or neoplasms in the kidney, liver, and pancreas.
-Patients are also at increased risk for renal cell carcinoma, which can be
bilateral.
http://hmg.oxfordjournals.org/cont...images/large/DDE08901.jpeg

Von Recklinghausen’s disease or neuro fibromatosis type (NF1)

= inherited peripheral nervous system tumor syndrome.
- Patients develop neurofibromas, optic nerve gliomas, Lisch nodules (pigmented
nodules of the iris), and café au lait spots (hyperpigmented cutaneous
macules).
http://www.nfmidatlantic.org/images/Resources/nf1bodyImage.jpg

Neurofibromatosis type 2
=autosomal dominant =bilateral cranial nerve VIII schwannomas and multiple
meningiomas.
http://www.nfcalifornia.org/uploads/images/NF2Body.jpg
http://jnnp.bmj.com/content/vol75/...ages/large/np53603.f1.jpeg

Sturge-Weber syndrome (encephalotrigeminal angiomatosis)

= rare congenital neurocutaneous disorder characterized by the presence of
cutaneous facial angiomas as well as leptomeningeal angiomas. Skin
involvement typically overlies the ophthalmic (V1) and maxillary (V2)
distributions of the trigeminal nerve.
-This condition is associated with mental retardation, seizures, hemiplegia, and
skull radiopacities. Skull radiographs may show characteristic “tram-track”
calcifications.
http://rad.usuhs.mil/rad/home/cases/sw_dis.html
http://radiology.rsna.org/content/231/2/515.figures-only

Tuberous sclerosis (TS)

-may cause kidney, liver, and pancreatic cysts
- central nervous system (CNS) involvement manifests as cortical and
subependymal hamartomas.
= autosomal dominant syndrome
- is also characterized by cutaneous angiofibromas (adenoma sebaceum),
visceral cysts, and a variety of other hamartomas, as well as renal
angiomyolipomas and cardiac rhabdomyomas. Clinically, seizures are a major
complication.
http://www.uwo.ca/cns/resident/piclib.html
http://www.uwo.ca/cns/resident/poc...tures/tuberousclinical.jpg

Osler-Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia)

= the autosomal dominant inheritance of congenital telangiectasias. Rupture of
these telangiectasias may cause epistaxis, gastrointestinal bleeding, or
hematuria.
http://img.medscape.com/pi/emed/ck...y/1048885-1086114-1749.jpg
Psoriasis
= a common chronic inflammatory skin disorder characterized by sharply
demarcated salmon-colored plaques covered with a loosely adherent, silvery
scale. The most common areas of skin eruption include the elbows, knees,
gluteal cleft, lumbosacral area, glans penis, and scalp.
-Nail changes occur in 30% of afflicted individuals and entail a yellow-brown
discoloration with associated pitting, thickening, or crumbling.
- The psoriatic arthritis ranges from mild to severe and has the potential to
cause marked deformities in the joints, as seen with rheumatoid arthritis.
http://www.myfootshop.com/images/medical/ortho/psoriatic_mod.jpg
http://attra.registry.cz/res/image.../psoriaticka-artritida.jpg
http://www.medem.com/medem/images/...lev20_psoriasis_jpp_01.jpg

Brain herniation
http://missinglink.ucsf.edu/lm/int..._Images/HerniationBlum.jpg
The cranial vault is limited by the rigid cranial bones and is divided into
compartments by the dural folds (falx cerebri and tentorium cerebelli). There is
not room for brain expansion in an event of brain edema, tumor or hemorrhage.
As a result portions of the brain may protrude through the openings in the falx
cerebri tentorium cerebelli or through the foramen magnum. This process is
called herniation.
-Transtentorial (uncal) herniation occurs when the medial temporal lobe (uncus)
herniates through the gap between the crus cerebri and the tentorium.
http://missinglink.ucsf.edu/lm/ids...iation/UncalHerniation.htm
http://missinglink.ucsf.edu/lm/ids...rniation/PCAInfarction.htm
http://www.urmc.rochester.edu/neuroslides/slide056.html
- In sub falcine herniation the cingulate gyrus herniates under the falx cerebri.
http://missinglink.ucsf.edu/lm/int...n/SubfalcineHerniation.htm
-In tonsillar herniation, the cerebellar tonsils displace through the foramen
magnum and compress the medulla.
http://www.cerebrospinalfluidresea...m/content/2/1/11/figure/F1
-The most common cause of transtentorial herniation is an ipsilateral mass lesion
such as a brain tumor subdural or epidural hematoma. This mass causes an
increase in supratentorial pressure on the side of the lesion and forces the ipsi
lateral parahippocampal uncus through the tentorial incisure. As a result, the
following structures may become compressed:
1. Ipsilateral oculomotor nerve (CN III) compression leads to a fixed and dilated
pupil on the side of compression. Paralysis of oculomotor muscles occurs later,
and leads to ptosis and “down-and-out” gaze.
2. Ipsilateral posterior cerebral artery (PCA) compression leads to contralateral
homonymous hemianopsia.
3. Compression of the contralateral cerebral peduncle against the tentorium may
occur. The damage to the contralateral corticospinal tract leads to ipsilateral
hemiparesis.
4. Brainstem hemorrhages (Duret hemorrhages) may occur in the pons and
midbrain due to stretching and rupture of the basilar artery. This is usuallyfatal.
None of the other cranial nerves become compressed due to uncal herniation.
http://www.binglixue.com/image/images/cns/CNS060.jpg

Normal aging of the heart

- Aging is associated with a decrease in left ventricular chamber size particularly
in the apex to base dimension. This chamber length decrease causes the basal
ventricular septum to bulge into the left ventricular outflow tract (sigmoid
septum). Atrophy of cardiac myocytes results in increased interstitial connective
tissue and, in some cases, the deposition of amyloid. Finally, there is a
progressive accumulation of cytoplasmic granules containing brownish lipofuscin
pigment (the result of indigestible byproducts of subcellular membrane lipid
peroxidation).

Hypertrophic cardiomyopathy (idiopathic hypertrophic subaortic stenosis)

=asymmetric septal hypertrophy.
-There is disproportionate thickening of the ventricular septum compared to the
free wall of the left ventricle and the septal muscle bulges into the left
ventricular outflow tract. Although left ventricular cavity size is reduced, there is
an associated thickening and biconvex shape of the interventricular septum. On
histologic exam, there is extreme hypertrophy, as well as disarray and branching
of myocytes.
http://www.nature.com/nature/journ...68/fig_tab/415227a_F3.html
http://eurheartj.oxfordjournals.or...images/medium/coverfig.gif

Acute rheumatic carditis

- biopsy =a circumscribed interstitial collection of mononuclear inflammatory
cells, including some large histiocytes and a prominent binuclear histiocyte (in
the path of the black arrow). These interstitial myocardial granulomas (Aschoff
bodies) are typically found in acute rheumatic carditis. The plump macrophages
with abundant cytoplasm and central, round to ovoid nuclei with central, slender
chromatin ribbons are called Anitschkow cells (“caterpillar cells”). When
the larger macrophages become multinucleated they are referred to as Aschoff
giant cells. This inflammatory focus maybe surrounded by some lymphocytes
and occasional plasma cells.
-During acute rheumatic fever (ARE), diffuse inflammation and Aschoff bodies
may be found in any of the three layers of the heart. Aschoff bodies are later
replaced by fibrous scar. ARE is typically preceded by an episode of group A
streptococcal pharyngitis 10 days to 6 weeks prior.
http://www.med.cmu.ac.th/student/patho/Lertlakana/040.html
http://www.med.cmu.ac.th/student/patho/Lertlakana/041.html
http://www.med.cmu.ac.th/student/patho/Lertlakana/042.html

Chagas disease
-Recent travel to Latin America (particularly South America and Brazil)
= caused by the intracellular protozoan parasite Trypanosoma cruzi. Chagas
disease can result in a myocarditis characterized histologically by distension of
individual myofibers with intracellular trypanosomes.
http://www.brown.edu/Courses/Digit...dio/myocarditis-chaga.html

Viral myocarditis
http://www.brown.edu/Courses/Digit...ocarditis-lymphocytic.html

Diphtheritic myocarditis
- A child who has not been immunized against diphtheria is susceptible to
diphtheritic myocarditis. However, this condition results from a circulating toxin
produced by a primary focus of infection in the upper aerodigestive tract
(tonsillopharyngitis). Moreover, in diphtheritic myocarditis, there is a
pleomorphic interstitial infiltrate of macrophages.

Subarachnoid hemorrhage (SAH)

=a life-threatening condition.
= due to rupture of saccular (berry) aneurysm or arteriovenous malformation.
SAH manifests with the abrupt onset of severe headache, sometimes described
as a ‘thunderclap headache.” Confusion, fever, and nuchal rigidity may also
be present. CT scan without contrast reveals blood in the subarachnoid space
(between the arachnoid and pia mater).
-If the patient survives initial subarachnoid hemorrhage, a number of
complications may occur. More than half of patients develop secondary arterial
vasospasm. This vasospasm occurs in the vessels surrounding the ruptured
aneurysm. Secondary vasospasm causes cerebral ischemia, which presents as
new-onset confusion and/or focal neurological deficit 4-12 days after the initial
insult. The mechanism of vasospasm is related to impaired brain autoregulation.
CT scan may fail to show vasospasm, so transcranial color Doppler is needed.
- Nimodipine, a selective calcium channel blocker, is often prescribed to prevent
this vasospasm.
http://uwmedicine.washington.edu/N...SubarachnoidHemorrhage.jpg
http://www.daviddarling.info/images/aneurysms.jpg
Endocardial cushion defects
A congenital defect in the lower part of the interatrial septum is most likely the
result of failure of the endocardial cushions of the atrioventricular canal to fuse
completely during embryonic development, resulting in an ostium primum atrial
septal defect (ASD). These patients usually also have a cleft in the anterior
leaflet of the mitral valve as well as in the septal leaflet of the tricuspid valve,
causing regurgitation through the AV valves. These endocardial cushion defects
are commonly associated with Down syndrome.
http://www.chelationtherapyonline....ticles/images/asd-prim.jpg

DiGeorge syndrome
= thymic aplasia and failure of parathyroid formation as a result of defective
embryonic development of the third and fourth pharyngeal pouches.
=hypocalcemic tetany and recurrent viral and fungal infections secondary to T-
cell deficiency.
-The dominant cardiac defects in this syndrome are tetralogy of Fallot and aortic
arch anomalies. Chromosome 22q11.2 deletion is found in 90% of cases.

Friedreich’s ataxia
= spinocerebellar degeneration with predominantly spinal ataxia. There is initial
loss of sensory (including proprioceptive) neurons in the dorsal root ganglia, with
accompanying gait ataxia. This autosomal recessive condition may be associated
with hypertrophic cardiomyopathy. This disease is the result of mutations in
frataxin, a mitochondrial protein important in iron homeostasis and respiratory
function.
http://www.brown.edu/Courses/Digit...interstitial-fibrosis.html

Major associations:
1. Down syndrome: endocardial cushion defects (ostium primum ASDI
regurgitant AV valves)
2. DiGeorge syndrome: tetralogy of Fallot and aortic arch anomalies
3. Friedreich’s ataxia: hypertrophic cardiomyopathy
4. Marfan syndrome: cystic medial necrosis of the aorta
5. Tuberous sclerosis: valvular obstruction due to cardiac rhabdomyomas
6. Turner’s syndrome: coarctation of the aorta
Cell injury
-vacuoles and phospholipid-containing amorphous densities within mitochondria
= signifies irreversible injury, and implies a permanent inability to generate
further ATP via oxidative phosphorylation. When the mitochondria are injured
irreversibly, the cell cannot recover. Simple mitochondrial swelling may be
associated with reversible cellular injury, however.
-Myofibril relaxation=an early sign of reversible injury in cardiac myocytes, which
occurs within the first 30 minutes of severe ischemia. Myofibril relaxation
corresponds with intracellular ATP depletion and lactate accumulation due to
anaerobic glycolysis during this period.
-Disaggregation of polysomes= the dissociation of rRNA from mRNA in reversible
ischemic/hypoxic injury. Depletion of intracellular ATP is thought to promote the
dissolution of polysomes into monosomes as well as the detachment of
ribosomes from the rough endoplasmic reticulum. Disaggregation of polysomes
results in impaired protein synthesis.
-Disaggregation of granular and fibrillar elements of the nucleus= reversible cell
injury. Another common nuclear change associated with reversible cell injury is
clumping of nuclear chromatin, perhaps secondary to a decrease in intracellular
pH.
-Triglyceride droplet accumulation= characteristic of reversible cell injury,
especially in hepatocytes, and also in striated muscle cells and renal cells. This
fatty change may result from the decreased synthesis of intracellular proteins
that occurs with cell injury. In the hepatocyte, decreased production of lipid
acceptor proteins prevents the normal incorporation of triglycerides into
lipoproteins. Since triglycerides cannot be rapidly exported from the cell in the
form of lipoproteins, they accumulate intracellularly.
-Glycogen loss=early and reversible cellular response to injury. As a result of
lowered mitochondrial ATP production, ATP must be supplied to the cell via
anaerobic glycolysis of glucose derived from the cell’s glycogen stores.
Myocardial glycogen stores may be completely depleted within 30 minutes of the
onset of severe ischemia.

Anaplastic tumors:
1. Loss of cell polarity and normal tissue architecture, with cells coalescing into
sheets or islands in a disorganized, infiltrative fashion
2. Significant variation in shape and size of cells (cellular pleomorphism)
3. Deep staining of nuclei (hyperchromatism) and significant variation in shape
and size of nuclei (nuclear pleomorphism)
4. Larger nuclei than those found in normal cells of the same tissue (high
nucleus-to-cytoplasm ratio)
5. Numerous often abnormal mitoses
6. Giant multinucleated tumor cells
The appearance of giant multinucleated cells in a muscle tumor would therefore
suggest anaplasia.
Vitiligo
= partial or complete loss of epidermal melanocytes. Age of onset varies, but
most afflicted individuals will have developed lesions by the second or third
decade of life.
- can affect all races, but it is particularly striking in darkly pigmented
individuals. Vitiligo typically erupts on the face, extremities, axillae, umbilicus,
groin, genitalia, and over hard bony surfaces (eg, knees). Clinically, the lesions
are flat, well-circumscribed macules and patches of absent pigment, varying in
size from a few to several centimeters.
-Histologic= loss of melanocytes and a complete absence of melanin pigment.
-The pathogenesis of vitiligo remains unclear. Proposed mechanisms encompass
autoimmune activity, neurohumoral toxicity specific for melanocytes, and
melanocytic self-destruction secondary to toxic intermediate exposure during
melanin synthesis. Most of the available data supports an autoimmune causality
for vitiligo. Not only have circulating melanocyte antibodies been identified in this
population but there is a significant correlation between vitiligo and autoimmune
disorders (eg, type I diabetes mellitus, pernicious anemia, Addison disease,
autoimmune hepatitis, Graves disease, autoimmune thyroiditis).
http://www.eregimens.com/images/regimens/Vitiligo.JPG
DIFF:
-albinism=absent or defective tyrosinase.
-Postinflammatory hypopigmentation=redistribution of existing melanin within
the skin. This finding may also be associated with reduced transfer of melanin to
keratinocytes.

Ulcerative colitis :
1. The rectum is always involved; involvement of other areas of the intestine is
variable.
2. Inflammation is limited to the mucosa and submucosa only.
3. Mucosal damage is continuous. There are no areas of normal mucosa between
the affected segments.
4. Bloody diarrhea with or without abdominal pain, is the hallmark of ulcerative
colitis. (In Crohn’s disease there may also be bloody diarrhea, but abdominal
pain is virtually always present.)
Complications:
-toxic megacolon ; adenocarcinoma of the colon.
http://www.virtualmedicalcentre.co...s/650_Ulcerative_Colon.JPG

Temporal arteritis
= inflammatory condition that affects the walls of medium-sized and large
arteries.
-granulomas are seen in the media of the arteries, consisting of mononuclear
infiltrates and multinucleated giant cells. Due to the characteristic histologic
features, this condition is also called giant cell vasculitis.
-The changes in the arteries are segmental: abnormal areas are interspersed by
segments of normal-appearing arterial wall. Affected segments cause narrowing
of the vessel with a decrease in blood supply to the perfused areas.
-The median age of onset of the temporal arteritis is 65 years.
-Commonly reported symptoms include:
1. Headache: Focal pain over the temple and tenderness on palpation .
Sometimes patients have scalp tenderness with hair combing; pain, nodularity,
and thickening found on palpation of the temporal area.
2. Craniofacial pain syndromes: Jaw claudication, tongue claudication, and facial
pain may occur. This tends to appear during mastication when the blood supply
to the corresponding areas does not increase normally due to the narrowing of
the arterial lumens.
3. Polymyalgia rheumatica occurs in more then half of patients with temporal
arteritis. It is characterized by neck, torso, shoulder and pelvic girdle pain and
morning stiffness. Fatigue, fever and weight loss may also occur.
4. Sudden vision loss is a dreaded complication of temporal arteritis. It may be
transient or may result in permanent blindness.
http://www.pathguy.com/lectures/temporal.gif
http://www.pathology.washington.ed...ry/jpgs575/spd/img0020.jpg

Poststreptococcal glomerulonephritis (PSGN).

= hematuria, proteinuria and urine RBC casts are present in a patient with
hypercellular glomeruli on light microscopy
-Lab findings : elevated titers of anti streptococcal antibodies (anti-Streptolysin
0, anti-DNAse B, anti-cationic proteinase), and low C3 concentration.
- Whereas C3 levels are decreased in almost all patients with PSGN (suggesting
activation of the alternative complement pathway), C4 levels are usually normal.
In some patients, however, C4 levels are slightly low (suggesting the possibility
of classical pathway activation as well).
-Cryoglobulins may be present in serum.
-On light microscopy, =enlarged hypercellular glomeruli . The hypercellularity,
which involves all lobules of all glomeruli is the result of leukocyte infiltration and
endothelial and mesangial cell proliferation. Electron microscopy typically shows
electron-dense deposits (“humps”) on the epithelial side of the basement
membrane. These deposits are composed of immune complexes. On
immunofluorescent microscopy, there are coarse granular deposits of lgG and C3
with the characteristic “starry sky” appearance.
http://www.nature.com/ki/journal/v54/n67s/fig_tab/4490515f1.html

Rickets
= Defective mineralization of the matrix occurs in growing bones causing weight-
bearing bones to bow laterally (genu varus), bony prominence at the
costochondral junction (rachitic rosary), indentations in the lower ribs
(Harrison’s sulci), softening of the skull (craniotabes), hypocalcemia,
hypophosphatemia, hypertonia, and growth retardation.
- Histologically vitamin D deficiency is characterized by an increase in
unmineralized osteoid and widening between osteoid seams. The latter can be
measured by bone histomorphometry and by double tetracycline labeling.
-Vitamin D deficiencies can be from poor sunlight exposure, an inadequate diet
or defective absorption of vitamin D
http://familydoctor.org/online/etc...000/902.Par.0001.Image.gif
http://www.wellesley.edu/Chemistry/chem227/lipids/ricketslegs.jpg

Hyperparathyroidism
- increases osteoclastic activation resulting in increased bone resorption;
however the bone resorption in hyperparathyroidism mainly involves cortical
bones. Increased resorption of cortical bones results in subperiosteal thinning, a
characteristic feature of hyperparathyroidism.
http://www.rad.washington.edu/stat...ubperiostealResorption.jpg

Paget’s disease
= seen in elderly patients and involves only focal points of the skeleton.
-The disease process starts as marked, local osteoclastic activation followed by
increased osteoblastic activity. The net result is the focal formation of abnormal
bone. New collagen is laid down in a haphazard manner compared to the linear
manner found in normal bones. The end product is a mosaic of lamellar bone;
irregular sections of lamellar bone are linked by areas of previous bone
resorption known as “cement lines.”
http://www.mikety.net/Answers/pagets.html
http://www.med.wayne.edu/diagradiology/TF/MS/MS05.jpg

Hemosiderin
-Golden yellow or brownish cytoplasmic granules may be either lipofuscin or
hemosiderin. The Prussian blue stain, which detects intracellular iron, can
differentiate the two. In the Prussian blue histochemical reaction, colorless
potassium ferrocyanide is converted by iron to blue-black ferric ferrocyanide.
-When there is increased intravascular pressures in the pulmonary capillary bed,
iron-containing proteins and erythrocytes are extravasated into the alveoli. After
leaking from congested capillaries, these iron-containing macromolecules are
phagocytosed by macrophages and converted to hemosiderin. Hemosiderin-
containing alveolar macrophages (also known as siderophages, or “heart
failure cells”) indicate that episodes of pulmonary congestion and edema
associated with chronic left-sided heart failure occurred previously.
http://www.pathguy.com/lectures/heart_failure_cells.jpg
http://www.biomedcentral.com/1471-2407/6/87/figure/F3

Eczematous dermatitis
= erythematous, papulovesicular, weeping, encrusted lesions that may evolve
into thickened, scaly plaques. While still “wet” these lesions are prone to
bacterial superinfection and can develop a yellow crust.
-The conditions included under the heading of eczematous dermatitis can be
separated into five distinct categories: allergic contact dermatitis; atopic
dermatitis; drug-related eczematous dermatitis; photo-eczematous dermatitis;
and primary irritant dermatitis.
-Allergic contact dermatitis arises when antigens at the epidermal surface are
selected by Langerhans cells and carried into draining lymph nodes where they
are presented by these Langerhans cells to naive CD4 T cells. The T cells are
activated and migrate to the skin, where they incite an inflammatory response
within 24 hours of antigen re-exposure. Cutaneous delayed hypersensitivity in
the form of spongiotic dermatitis is the end result.
-Histologically, acute eczematous dermatitis is characterized by an epidermal
accumulation of edematous fluid in the intercellular spaces (spongiosis). The
intercellular bridges become more distinctive in an edematous background and
the epidermis is often described as appearing “spongy.” Eventually, the
edema can become so marked as to form intraepidermal vesicles by tearing the
desmosomes apart. A superficial perivascular infiltrate of lymphocytes and
eosinophils may also be seen. When present this infiltrate typically extends to
include the deeper vessels, especially if systemic antigen exposure (eg, to drugs)
has occurred. Should the dermatitis be secondary to contact with a surface
antigen, then the inflammation is usually restricted to the superficial dermis.
http://missinglink.ucsf.edu/lm/Der...s/spongiosis_mid_power.jpg
http://www.rch.org.au/emplibrary/rchcpg/eczema_erythema2.jpg

Acanthosis
= increase in thickness of the stratum spinosum (the prickle cell layer). This
layer is situated between the granular cell layer and the basal layer of the
epidermis. Psoriasis is commonly associated with acanthosis.
http://missinglink.ucsf.edu/lm/Der...ages/Acanthosis_2x-201.jpg
http://www.thejcdp.com/issue009/case09/diagnos3.htm
Dyskeratosis
= abnormal, premature keratinization of individual keratinocytes. The
dyskeratotic cells are strongly eosinophilic and may have a small, basophilic
nuclear remnant. Dyskeratosis can be found in diseases such as squamous cell
carcinoma.
http://dermatology.cdlib.org/1502/case_presentations/darier/3.jpg

Hyper parakeratosis
=retention of nuclei in the stratum corneum, which signals incomplete
keratinization. This finding is normal on mucous membranes, but suggests
abnormality (eg, actinic keratosis) in other areas.
http://missinglink.ucsf.edu/lm/Der...ic_keratosis_low_power.jpg

Hypergranulosis
=excessive granulation in the stratum granulosum of the epidermis and is seen
in conditions such as lichen planus.
http://www.geocities.com/sampurnaroy2001/lp1.jpg
http://library.med.utah.edu/kw/derm/mml/24830096.jpg

Tissue Necrosis
= cell death that occurs in living tissue after exogenous injury. Unlike apoptosis,
where individual cells die in isolation, necrosis is associated with the death of a
large number of cells. Enzymes released from these cells injure the surrounding
tissue leading to necrosis of cells not affected by the initial stimulus.
-Tissue necrosis can occur in a number of distinct morphologic patterns:
1. Coagulative necrosis is the most common variant. It is characterized by
relative preservation of cell outlines in the necrotic tissue. Most exogenous
injuries, including a brown recluse spider bite , are associated with coagulative
necrosis. Organ ischemia (especially in myocardium or kidney) is the classic
example of coagulative necrosis. Cell cytoplasm becomes eosinophilic due to
protein denaturation. The nucleus shrinks and there is chromatin clumping
(pyknosis), fragmentation (karyorrhexis) and, eventually lysis.
2. Liquefactive necrosis usually occurs in the CNSI in sites of ischemic strokes.
Necrotic cells undergo fragmentation and are phagocytized by macrophages with
the formation of a cystic cavity.
3. Fat necrosis is seen in acute pancreatitis. Pancreatic enzymes, including
lipases, digest the parenchyma with formation of fatty acids. Saponification
(soap formation) occurs when fatty acids combine with calcium.
4. Caseous necrosis occurs in tuberculosis. Necrotic tissue has a “cheesy”
appearance and consists of fragmented cells and acellular material.

Li-Fraumeni syndrome
=genetically predisposed to the early development of cancer. The syndrome is
the result of a mutation in the p53 gene. Inheritance is autosomal dominant.
-The p53 gene codes for the p53 protein, which plays an essential role in
maintaining the integrity of the human genome. Normally, p53 causes cells with
mutant DNA to arrest in the G1/S stage of the cell cycle until the damage is
repaired. Cells with irreversible DNA damage are not allowed to divide and
proceed instead to apoptosis. Mutations of p53 can be acquired during one’s
lifetime, and are seen in the majority of sporadic human cancers.
- Patients with Li-Fraumeni syndrome inherit one mutated allele of p53; somatic
mutation of the second allele is needed for tumor development. These patients
develop malignant tumors at a young age (<45 years old). Patients often have a
family history of multiple cancers in individuals less than 45-years-old. The most
common malignancies in Li-Fraumeni syndrome are tumors of the breast, brain,
and adrenal cortex, as well as sarcomas and leukemias.
http://p53.free.fr/Database/p53_cancer/image_cancer/lfs1.jpg
DIFF:
-Mutation of the Rb tumor suppressor gene =development of retinoblastomas
and osteosarcomas.
- Mutation of the BRCA-1 tumor suppressor gene=risk for breast and ovarian
cancers.
-Mutation of NF2= risk for developing neurofibromatosis type 2. Patients present
with bilateral acoustic neuromas (schwannomas of the cerebellopontine angle).
Symptoms include bilateral hearing loss vertigo and tinnitus.
-The APO (adenomatous polyposis coli) gene mutation is found in patients with
familial polyposis syndromes, sporadic colon cancer and melanomas. This gene is
responsible for maintaining low levels of β-catenin (which is oncogenic) and for
intercellular adhesion.

Carcinoid syndrome
-The vasoactive substances secreted by tumors in extra-intestinal locations are
not filtered by the liver
-If a carcinoid tumor is confined to the intestine, its secretory products are
metabolized by the liver, so patients do not develop clinical manifestations. If
however, the tumor metastasizes to the liver (or is present in an extra-intestinal
site, such as the lung), the liver does not metabolize the vasoactive secretory
products and carcinoid syndrome ensues.
Dubin-Johnson syndrome
= a defect in the hepatic excretion of bilirubin glucuronides across the canalicular
membrane. Individuals with this rare, benign condition have predominantly
conjugated chronic hyperbilirubinemia that is not associated with hemolysis.
-Grossly, the liver is strikingly black. Histological features are normal, though a
dense pigment composed of epinephrine metabolites within the lysosomes can
be seen.
-Clinically icterus is evident, though the physical examination is typically
otherwise normal. Most patients are asymptomatic, with some complaining of
nonspecific issues (eg, fatigue, abdominal pain, weakness). The icterus may be
so mild as to only become evident in the context of a trigger such as illness,
pregnancy, or oral contraceptive usage. Routine laboratory testing is
unremarkable, including the complete blood count and liver function profile.
-Serum bilirubin levels usually range from 2-5 mg/dL but can also be normal or
extremely elevated (20-25 mg/dL).
-For the diagnosis of Dubin-Johnson syndrome to be made, conjugated
hyperbilirubinemia with a direct bilirubin fraction of at least 50% and an
otherwise normal liver function profile must be present. Confirmation can be
obtained by evaluating the urinary coproporphyrin for unusually high levels of
coproporphyrin I. Because this condition is benign, no treatment is necessary
and the prognosis is excellent.
http://www.meddean.luc.edu/lumen/MedEd/orfpath/images/11-1-1.jpg
DIFF:
Impaired bilirubin conjugation is seen in conditions such as Crigler-Najjar
syndrome and Gilbert syndrome, not Dubin-Johnson syndrome.

Pernicious anemia
= immune-mediated destruction of gastric mucosa. Over time, this damage
results in chronic atrophic gastritis, a condition characterized by:
1)loss of the intrinsic factor- secreting parietal cells in the upper glandular layer;
2) marked lymphocytic and plasma cell infiltration;
3) megaloblastic changes in mucosal cells. Once the number of parietal cells has
been sufficiently depleted and the stores of vitamin B12 are exhausted,
pernicious anemia classically manifests with symptoms such as fatigue and
paresthesias.
http://faculty.une.edu/com/abell/histo/fundiglandw.jpg
http://www.mfi.ku.dk/ppaulev/chapter22/images/22-9.jpg
http://www.cytochemistry.net/microanatomy/digestive/stomach.htm
-the parietal cells subject to pernicious anemia-induced atrophy are the oxyntic
(pale pink), round platelike cells in the periphery of upper-layer glands. These
cells secrete hydrochloric acid and intrinsic factor
Epidural hematoma=due to tear of the middle meningeal artery. It is often
associated with temporal bone fracture, and is located between the bone and
dura mater. Clinical presentation is characterized by a “lucid interval”,
followed by loss of consciousness.
Subdural hematoma=between the dura mater and arachnoid, and is caused by
tearing of the bridging cortical veins.
Subarachnoid hemorrhage=between the arachnoid and pia mater. It most often
occurs due to rupture of berry aneurysms or arteriovenous malformations of the
posterior communicating, anterior communicating or middle cerebral arteries.
http://neuropathology.neoucom.edu/chapter4/images4/4-2L.JPG
http://neuropathology.neoucom.edu/chapter4/images4/4-3L.JPG
http://www.strokecenter.org/patien...ah_coronal_berry_2_500.jpg

M. tuberculosis infection
= granulomatous inflammation with caseous necrosis. Caseous necrosis occurs
through an incompletely understood mechanism, but is believed to be largely
due to a T lymphocyte-mediated delayed type hypersensitivity reaction elicited
by M. tuberculosis. This hypersensitivity reaction stems from the TH1
lymphocyte stimulation of both macrophages and CD8+ cytotoxic T lymphocytes.
Ultimately, the macrophages undergo epithelioid and Langhans giant cell
transformation and fibroblasts are activated.
-Delayed-type hypersensitivity plays an important role in the host defense
against M. tuberculosis infection. Although the associated tissue damage is an
unpleasant consequence, this immune response is essential in containing the
organism and preventing disseminated infection.
- The tissue destruction caused by M. tuberculosis infection is the direct result of
host immune activation and inflammation through a type IV delayed-type
hypersensitivity reaction. The characteristic pathologic lesion consists of
granulomatous inflammation and caseous necrosis.

Reactive arthritis
= a spondyloarthropathy that tends to affect HLA-B27 positive individuals
following infections with Campylobacter, Shigella, Salmonella Yersinia,
Chlamydia, or Bartonella. It typically presents as an asymmetric arthritis of the
large joints.
-Joint aspirates are always sterile (hence it is a reactive not infectious arthritis).
Reactive arthritis may be part of Reiter’s syndrome, an HLA-B27
spondyloarthropathy involving the triad of reactive arthritis, conjunctivitis and
urethritis typically in the setting of Chlamydial infections.
MEN type 1 syndrome
= hyperparathyroidism, pituitary tumor, and pancreatic tumor. Hypercalcemia
from hyperparathyroidism is the most common manifestation of MEN type 1 and
is caused by parathyroid chief cell hyperplasia. About 70% of patients with MEN
type I have endocrine pancreatic tumors that usually secrete gastrin, leading to
refractory peptic ulceration and diarrhea (Zollinger-Ellison syndrome). Rarely,
endocrine tumors of the pancreas in MEN type 1 secrete other hormones such as
insulin, which causes hypoglycemia; or vasoactive intestinal polypeptide, which
causes massive diarrhea. The production of other pancreatic endocrine hormones
is very rare. Pituitary tumors are present in 50% of patients with MEN type 1.
Large pituitary tumors with suprasellar extensions are likely to cause visual
disturbances (usually bitemporal hemianopsia).
DIFF:
-The mucosal neuromas, thyroid nodule, and Marfanoid habitus of this man
indicate MEN type 2B. (Although pheochromocytomas are also a feature of MEN
2B, not all features have to be present to suggest a MEN syndrome.) Even
without the mucosal neuromas, one would suspect a MEN syndrome as about
20% of medullary thyroid cancers are familial. Episodic secretion of
catecholamines by pheochromocytomas causes episodic increases in blood
pressure, flushing, diaphoresis, and headaches. All patients with medullary
thyroid cancer should be screened for pheochromocytoma by clinical and
biochemical assessment.

Right-sided endocarditis
= commonly occurs in IV drug users and is typically caused by S. aureus. In
patients other than IV drug abusers, dissemination of S. aureus occurs from a
primary disease process such as surgical I & D of an abscess or from infected IV
catheters such as central lines, and it moves by hematogenous spread to the
endocardium. S. aureus settles on the valve leaflets because of the turbulence of
the blood flow at these sites. S. aureus has the ability to cause perforations in
the heart valves, rupture the chordae tendineae, and send septic emboli to the
lung (in the case of right heart endocarditis) and to the brain and systemic
circulation (in the case of left heart endocarditis).

Streptococcus bovis
= part of the normal flora of the colon, and bacteremia or endocarditis caused by
S. bovis is associated with colonic cancer in approximately 25% of cases.
Culture-negative endocarditis
-special serologies and cultures need to be sent for organisms that do not grow
in standard blood culture. These organisms include, but are not limited to,
Bartonella, Coxiella, Mycoplasma, Histoplasma, Chlamydia and the HACEK
organisms (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella and
Kingella).
http://faculty.matcmadison.edu/mlj...it1Review/endocarditis.jpg

Subarachnoid hemorrhage (SAH)

=abrupt onset of a severe headache often described by patients as “the
worst headache of my life.” Fever and nuchal rigidity may also be present.
Usually, focal neurological deficits are not present.
-Saccular (berry) aneurysms are the most common cause of SAH. These
aneurysms usually occur at the circle of Willis, with the anterior communicating
artery being the most common site. Berry aneurysms are associated with Marfan
syndrome Ehlers-Danlos syndrome, and adult polycystic kidney disease.
Arteriovenous malformation also predisposes certain individuals to subarachnoid
hemorrhage.
-In SAH blood accumulates between the arachnoid and pia mater. CT scan
without contrast is diagnostic. Lumbar puncture reveals gross blood or
xanthochromia .

Cerebral amyloid angiopathy

= occurs in elderly patients. It may be asymptomatic or may lead to recurrent
intracerebral hemorrhage. These bleeds usually affect small areas of the cerebral
hemisphere and present with headache and focal neurologic deficits (paresis,
sensory loss etc).
http://wiki.cns.org/wiki/images/a/a8/CAA1.gif

Acute pancreatitis
-Gallstones and alcoholism are the most common causes of acute pancreatitis.
-Gallstones typically affect middle-aged and older patients unless there is a
predisposing condition (e.g. young patients with sickle cell disease are at
increased risk for bilirubin gallstones). l
Lss common causes of acute pancreatitis
1. A recent ERCP (endoscopic retrograde cholangiopancreatography) procedure
is the third most common cause of acute pancreatitis
2. Drugs (e.g. azathioprine, sulfasalazine, furosemide, valproic acid)
3. Infections (mumps, measles EBV, VZV, Coxsackie virus, Mycoplasma
pneumoniae, and Mycobacterium tuberculosis)
4. Hypertriglyceridemia
5. Structural abnormalities of the pancreatic duct (strictures, cancer, pancreas
divisum) or of the ampullary region (choledochal cyst stenosis of sphincter of
Oddi)
6. Surgery (particularly of the stomach and biliary tract, also after coronary
artery bypass grafting)
7. Hypercalcemia
-High levels of triglycerides lead to increased production of free fatty acids.
Normally fatty acids exist in serum bound to albumin. If serum triglyceride levels
are higher than 1000 mg/dL, the concentration of free fatty acids exceeds the
binding capacity of albumin and leads to direct injury to acinar cells and
pancreatic capillaries. Thus, hypertriglyceridemia causes acute pancreatitis via
direct tissue toxicity.

Pericarditis (post MI)

=sharp and pleuritic nature of this patient’s new pain suggests pericardial
involvement. The exacerbation with swallowing indicates that the posterior
pericardium may be involved, and the radiation into the neck suggests
involvement of the inferior pericardium, which is adjacent to phrenic nerve
afferents supplying the diaphragm.
-A fibrinous or serofibrinous early-on set pericarditis develops in about 10-20%
of patients between days 2 and 4 following a transmural myocardial infarction.
This pericarditis is a reaction to the transmural necrosis. The inflammation
affects the adjacent visceral and parietal pericardium; in other words, the
inflammation is usually localized to the region of the pericardium overlying the
necrotic myocardial segment. This type of early post-MI pericarditis is generally
short-lived and disappears with 1 to 3 days of aspirin therapy.
http://www.pathologyatlas.ro/patho...fibrinous_pericarditis.jpg
http://www.uptodate.com/online/con...geKey=card_pix/normal3.htm

Dressler’s syndrome
=late-onset post-myocardial infarction pericarditis
=typically begins one week to a few months after a myocardial infarction in
fewer than 4% of patients. Typical features include fever, pleuritis, leukocytosis,
pericardial friction rub, and chest radiograph evidence of new pericardial or
pleural effusions.
-Dressler’s syndrome is thought to be an autoimmune polyserositis provoked
by antigens exposed or created by infarction of the cardiac muscle. Thus, the
pericardium is usually diffusely inflamed. Other serosal surfaces including the
lung pleura may be involved. Dressler’s syndrome generally responds to
aspirin, NSAIDS, and/or glucocorticoids.
http://www.learningradiology.com/a...drome/dresslerscorrect.htm

Normal pressure hydrocephalus (NPH)

=Gait abnormality and urinary incontinence are the first symptoms ;left
untreated, progressive dementia and emotional blunting will occur.
- The order of symptoms are important in distinguishing NPH from Alzheimer and
other dementing diseases. Additionally, CT scan will show symmetrically-
enlarged ventriculi.
-occurs in elderly patients.
-Pathophysiology and etiology are debated, but most agree that a gradual
decline in the reabsorptive capacity of the arachnoid villi, with slow accumulation
of CSF, is the root of the problem. Pressure remains normal in NPH because
gradual ventricular distention accommodates the CSF increase. Distended
ventriculi distort the surrounding white matter that carries cortical afferent and
efferent fibers (corona radiata). Ataxic gait and urinary incontinence occur due to
traction of the sacral motor fibers that innervate the legs and the bladder.
Distention of the periventricular limbic system leads to progressive dementia and
emotional blunting. Note that no permanent damage to the brain structures
occurs; therefore symptoms of NPH, including dementia, are sometimes reversed
by lowering the CSF volume.
http://www.thebarrow.org/stellent/...ts/webcontent/bqjpg141.jpg

Syringomyelia
=classic presentation of disproportionate loss of pain and temperature sensation.
In syringomyelia, cerebrospinal fluid-filled cavities (called “syrinx”) form,
usually in the cervical region of the spinal cord. These cavities enlarge over time
and destroy adjacent portions of the spinal cord. The areas commonly damaged
in this condition are the ventral white commissure and the ventral horn.
-The ventral white commissure is the area of decussation of the fibers of the
lateral spinothalamic tract. This tract transmits pain and temperature sensation
from receptors to the somatosensory cortex. Its first-order neurons are located
in the dorsal root ganglia and the second-order neurons are found in the dorsal
horn. The axons of the second- order neurons decussate in the ventral white
commissure and ascend in the contralateral lateral funiculus. Third order neurons
are located in the ventral posterolateral nucleus of the thalamus. Fourth-order
neurons are found in the primary somatosensory cortex in the parietal lobe.
-Destruction of the ventral white commissure leads to loss of pain and
temperature sensation in the arms and hands bilaterally. Touch, vibration and
position senses are preserved in syringomyelia.
-LMN lesions of syringomyelia are characterized by areflexia, flaccid paralysis,
fasciculations and atrophy of the intrinsic muscles of the hands.
http://webhome.idirect.com/~braino...devpath_14_spinalcord.html
http://www.asap.org/images/abnormal_50.jpg
Prinzmetal’s (variant) angina
=Episodic and transient anginal chest pain, occurring during the nighttime hours
and accompanied by temporary ST- segment elevations on Holter monitoring;
generally occurs at rest.
-The coronary artery vasospasm may occur near sites of atherosclerosis, and can
result in transient transmural ischemia with ST-segment elevations on ECG. -The
ergonovine test is the most sensitive provocative diagnostic test for coronary
vasospasm. Ergonovine is an ergot alkaloid that constricts vascular smooth
muscle by stimulating both alpha-adrenergic and serotonergic receptors. In
patients with hypercontractile coronary artery segments (as in Prinzmetal’s
angina), low doses of ergonovine induce coronary spasm, chest pain, and ST-
segment elevation.
-Nitrates are used to treat attacks in patients with Prinzmetal’s angina.
-Calcium channel blockers are used to treat and prevent attacks in patients with
Prinzmetal’s angina.

Aplastic anemia,
=pancytopenia, very low reticulocyte count, and lack of splenomegaly. The
differential diagnosis for pancytopenia without splenomegaly includes: severe
vitamin B12 and folic acid deficiency anemia, aleukemic leukemia, and
myelodysplastic syndrome.
-Bone marrow examination can distinguish a myeloproliferative disease with
increased bone marrow cellularity from aplastic anemia, where the bone marrow
is markedly hypocellular.
-In aplastic anemia, bone marrow hematopoietic elements are replaced by fat
cells and fibrous stroma. Bone marrow aspiration typically produces a “dry
tap.” The absence of splenomegaly is key in diagnosing aplastic anemia; a
patient with pancytopenia and splenomegaly is very unlikely to have this
condition.

Medullary thyroid cancers

= tumors of parafollicular calcitonin-secreting C-cells. 80% of medullary thyroid
cancers are sporadic and 20% are familial (as in the MEN type 2 syndrome).
-Germline mutations of the RET proto-oncogene are present in more than 95%
of patients with familial medullary thyroid cancer. The RET proto-oncogene codes
for a membrane-bound tyrosine kinase receptor involved in cell cycle regulation.
RET proto-oncogene mutations are also commonly found in sporadic medullary
thyroid cancers.
-Inactivating mutations of p53 are fairly common in anaplastic thyroid cancer
http://library.med.utah.edu/WebPath/ENDOHTML/ENDO028.html
Fibromyalgia
= chronic disorder characterized by widespread musculoskeletal pain in
association with stiffness, paresthesias, poor sleep and emotional disturbances.
Muscle pain and stiffness are more severe in the morning and are often
exacerbated by exercise.
-A characteristic physical examination finding is the presence of multiple
symmetrically distributed tender spots over the patients muscles joints and
tendons such as over the spine of the scapula the lateral epicondyle and the
medial fat pad of the knee
- Tenderness in eleven of eighteen predetermined painful points is required for a
diagnosis of fibromyalgia.
-Fibromyalgia affects women much more often than men, and commonly
manifests between 20 and 50 years of age. The precise etiology of fibromyalgia
is still unknown but it is presently postulated to be produced by a genetic
predisposition to heightened pain sensitivity or pain misperception that results
following a stressor such as an infection.

Polymyalgia rheumatica
- affects patients over 50 years old with morning stiffness of muscles of the
neck, shoulder and pelvic girdle. Weight loss, fever and an increased ESIR are
characteristic. Polymyalgia rheumatica occurs in approximately half of patients
with temporal arteritis.

Atherosclerosis
-fatty streaks = the earliest lesions in the progression to atherosclerosis.
-Fatty streaks are composed of intimal lipid-filled foam cells, derived from
macrophages and smooth muscle cells (SMC) that have engulfed lipoprotein
(predominantly LDL) which has entered the intima through an injured leaky
endothelium. The foamy appearance is due to intracellular lipid-containing
phagolysosomes.
-Fatty streaks begin as multiple yellow spots approximately 1 mm in diameter
which join to form streaks approximately 1 cm long. They may contain a few
lymphocytes, but foam cells are the predominant constituents. Because fatty
streaks are not significantly raised they do not disturb normal blood flow. They
can be seen in the aortas of children less than 1 year old and are present in the
aortas of all children over 10. Whereas some fatty streaks may be precursors of
atheromatous plaques not all tally streaks progress to these more advanced
atherosclerotic plaques.
http://www.ma.ic.ac.uk/~ajm8/BioFl...ictures/70fatty_streak.jpg
Hereditary breast cancer
=associated with mutation of BRCA-1 and BRCA-2. These are tumor suppressor
genes that function in gene repair and regulation of the cell cycle. Mutation of
these genes increases the risk of breast and ovarian cancer.
-BRCA mutations are inherited as an autosomal dominant trait. The BRCA-1 gene
is located on chromosome 17 and is a tumor suppressor gene. It codes the
protein that acts to control the cell cycle and plays a role in gene repair and
transcription. Women who carry BRCA-1 mutation have 70-80% lifetime risk for
development the breast cancer. Their risk of ovarian cancer is also increased by
40% compared to the general population.

Adrenal crisis
=The presence of shock in combination with hyponatremia, hyperkalemia, and
hypoglycemia
- fever, vomiting, nuchal rigidity and petechial rash = clinical signs strongly
suggestive of meningococcal meningitis. The association of Neisseria meningitidis
septicemia with adrenal hemorrhage is called Waterhouse-Friderichsen
syndrome. Although Waterhouse-Friderichsen syndrome can occur at any age, it
is more commonly seen in children.

Spherocytosis.
=Hereditary spherocytosis is (usually) an autosomal dominant condition that
results from red cell cytoskeleton abnormalities—most commonly, spectrin
deficiency. The definitive test for spherocytosis is a positive osmotic fragility test.

=anemia, an elevated LDH, and indirect bilirubinemia, suggesting hemolytic

anemia. The lysing of blood cells when incubated in hypotonic saline describes a
positive osmotic fragility test
-Pigmented gallstones are a complication of any hemolytic anemia. In chronic
hemolysis, the increased bilirubin from lysed red blood cells precipitates as
calcium bilirubinate, forming pigmented stones in gallbladder. “Mature”
pigmented gallstones are a mixture of calcium bilirubinate, bilirubin polymers,
and calcium salts.
http://www.unm.edu/~mpachman/Blood/spherocytosis.jpg
Multiple myeloma
=when an elderly patient presents with the following combination of findings:
1. Easy fatigability (due to anemia)
2. Constipation (due to hypercalcemia)
3. Bone pain, most commonly in the back and ribs (due to production of
osteoclast activating factor by myeloma cells and subsequent bone lysis)
4. Renal failure
-A number of factors contribute to renal failure in multiple myeloma:
hypercalcemia, hyperuricemia, infiltration of the kidney by myeloma cells, AL
amyloidosis, and frequent infection. The role of these factors in MM-associated
renal disease varies from patient to patient. Light chain deposition disease,
however, is always present in multiple myeloma.
- In small amounts, Bence Jones proteins (light chains) are filtered by the
glomerulus, and then reabsorbed in tubules. When levels exceed the
reabsorptive capacity of tubules however, these light chains precipitate with
Tamm Horsfall protein and form casts. These casts compress tubular epithelium,
obstruct tubular lumens, and thus impede renal function. Bence Jones proteins
are also directly toxic to tubular epithelial cells, causing atrophy. On light
microscopy, numerous, large, glassy, eosinophilic casts are seen in tubular
lumens.
http://library.med.utah.edu/WebPath/HEMEHTML/HEME070.html
http://granuloma.homestead.com/myeloma_kidney_YR1432-01.jpg

Small cell carcinomas

- show evidence of neuroendocrine differentiation. These tumors stain for
neuroendocrine markers, such as neuron-specific enolase, chromogranin, and
synaptophysin. Some small cell carcinomas express neurofilaments.
-Neurosecretory granules can be identified in the cytoplasm of the tumor cells on
electron microscopy. The fact that small cell carcinomas frequently synthesize
hormone-like substances also suggests a neuroendocrine derivation.
-Small cell carcinoma of the lung (also called oat cell carcinoma) is the most
aggressive type of lung cancer. It is characterized by rapid local invasion and
distant spread. Most patients have distant metastases at the time of diagnosis.
Although small cell carcinoma is sensitive to chemotherapy and radiation, the 5-
year survival rate of these patients is very low.
http://library.med.utah.edu/WebPath/LUNGHTML/LUNG074.html
http://library.med.utah.edu/WebPath/LUNGHTML/LUNG075.html
DIFF:
-Expression of ECE-receptors, mucin and surfactant-associated proteins is seen
in non-small cell carcinomas.
-Vimentin is an intermediate filament found within cells of mesenchymal origin.
It is used in diagnosing sarcomas.
-Leukocyte common antigen (LCA or CD 45) = for differentiating malignant
lymphomas from poorly differentiated neoplasms of other types.
Glucagonomas
=rare pancreatic tumors that characteristically present with necrolytic migratory
erythema, an elevated erythematous rash typically affecting the groin area.
-Other clinical features of glucagonomas include: hyperglycemia, stomatitis,
cheilosis, and abdominal pain. Diagnosis is made by the measurement of serum
glucagon levels.
-Glucagon is a hormone secreted by the alpha-cells of the pancreatic islets of
Langerhans. The three other types of pancreatic endocrine cells in the islets
include: insulin-secreting beta-cells, somatostatin-secreting delta-cells, and
pancreatic polypeptide-secreting PP-cells.
http://imaging.cmpmedica.com/consu...2007/0711ConPEGlucagoA.jpg
http://www.scielo.br/img/revistas/clin/v63n2/a16fig06.jpg

Pancreatic VIPoma
= intractable diarrhea, metabolic acidosis, and hypokalemia. Additionally, these
patients are usually hypotensive secondary to both dehydration as well as the
vasodilatory effects of VIP.
http://www.surgicalroundsonline.co.../2007-09/2007-09_01-04.jpg

Somatostatinoma
=a rare tumor of the pancreatic delta-cells
= abdominal pain, gallbladder stones, constipation, and steatorrhea. These
manifestations are due to somatostatins inhibition of the secretion of insulin,
glucagon, gastrin, cholecystokinin, and secretin, as well as its inhibition of
gastrointestinal motility.

Ectopic ACTH production

= present with rapid-onset hyperpigmentation, proximal muscle weakness,
hypokalemia, hyperglycemia, and markedly elevated levels of serum ACTH.

Juvenile pilocytic astrocytomas

= usually arise in the cerebellum, brainstem, hypothalamic region, or optic
pathways. Microscopically pilocytic astrocytomas are well-differentiated
neoplasms comprised of spindle cells with hair-like glial processes that are
associated with microcysts. These cells are mixed with Rosenthal fibers and
granular eosinophilic bodies.
http://www.uhrad.com/mriarc/mri052.htm
http://www.pedsoncologyeducation.com/images/jpabiphasicx50.jpg

Medulloblastoma (primitive neuroectodermal tumor, or PNET)

= the second most common posterior fossa tumor in children. On microscopic
examination, cells are small and poorly differentiated, with scant cytoplasm and
little stroma. A high mitotic index is common. Classic Homer-Wright rosettes can
be seen in one fifth of cases.
http://moon.ouhsc.edu/kfung/IACP-O...Q-Text/N1-TU-01-17-Ans.htm

Ependymomas
= account for 10% of posterior fossa tumors in children.
- Intracranial lesions usually occur infratentorial, arising from the roof of the
fourth ventricle in children, while spinal ependymomas typically occur in adults.
-Histologically, ependymal pseudorosettes with glial fibrillary acidic protein
(GFAP)—positive processes tapering toward blood vessels characterize
ependymomas.
http://library.med.utah.edu/WebPath/CNSHTML/CNS122.html
http://library.med.utah.edu/WebPath/CNSHTML/CNS121.html

Glioblastoma multiforme
=occur most often in the subcortical white matter of the cerebral hemispheres.
When a tumor in the frontal cortex spreads across the corpus callosum into the
contralateral hemisphere, it creates the appearance of a bilateral symmetrical
lesion, hence the term “butterfly glioma.” GBMs are composed of poorly-
differentiated often pleomorphic astrocytic cells with marked nuclear atypia and
brisk mitotic activity. Necrosis is an essential diagnostic feature, and prominent
microvascular proliferation is common.
http://library.med.utah.edu/WebPath/CNSHTML/CNS139.html

Neuroblastomas
= the most common extracranial solid tumors occurring in children.
-Undifferentiated neuroblastomas are small, round, blue-cell tumors. A neuritic
process, also called neuropil, is a pathognomonic feature of neuroblastoma cells.
NSEI chromogranin, synaptophysin, and S-100 immunohistochemical stains are
usually positive. More than 90% of patients have elevated urinary levels of
homovanillic acid (HVA) and/or vanillylmandelic acid (VMA). The most important
biologic marker is MYCN (N-MYC) of chromosome 2.
http://surgery.med.umich.edu/pedia..._images/neuroblastoma1.jpg

Huntington disease
=Involuntary choreiform movements, dementia, and behavioral abnormalities
= a progressive neurodegenerative disorder with symptom onset usually at 35-
45 years old: average lifespan after diagnosis is about 15-20 years.
- Loss of neurons in the caudate nucleus and putamen is characteristic.
-loss of GABA, Acetylcholine and substance P in the striatum (caudate nucleus
and putamen)
-molecular = NMDA (N-Methyl-D-aspartate) receptors bind glutamate and cause
neuronal death (NMDA-associated toxicity)
-Huntington disease is inherited as an autosomal dominant trait with 100%
penetrance. History of the disease in a first-degree relative is important for
diagnosis.
- Early signs and symptoms of Huntington's disease often include:
Personality changes, such as irritability, anger, depression or a loss of interest;
Decreased cognitive abilities, such as difficulty making decisions, learning new
information, answering questions and remembering important information;
Mild balance problems
- Young people who develop Huntington's disease may have signs and symptoms
that mimic Parkinson's disease:
Muscle rigidity,Tremors, Slow movements, Clumsiness
http://www.stanford.edu/group/pand...folding/pics/HD_effect.gif

Mallory-Weiss syndrome
=Longitudinal mucosal tears at the esophagogastric-squamocolumnar junction
-Most commonly these tears occur secondary to rapid increase of intraabdominal
and intraluminal gastric pressure, as when happens during retching and
vomiting. Other precipitating factors include coughing, hiccupping, other
repeated abdominal straining, and abdominal trauma. Additionally hiatal hernias
are found in about half of patients with Mallory-Weiss syndrome and are
considered a strong predisposing factor. Mallory-Weiss syndrome is very
commonly associated with alcoholism.
-Mallory-Weiss tears can be asymptomatic or can lead to gastrointestinal
hemorrhage that manifests as hematemesis. About 10% of all upper
gastrointestinal bleeds are from Mallory-Weiss syndrome. The intensity of
hemorrhage and amount of blood loss varies widely according to the length and
depth of the tears, but is almost never life-threatening.
http://www.pathology.pitt.edu/lectures/gi/esoph-a/10.htm
DM
-Myocardial infarction is the most common cause of death in patients with
diabetes.
-diabetes is the strongest risk factor for coronary heart disease. Approximately
40-50% of patients with diabetes mellitus die secondary to coronary artery
disease. For a person with diabetes the risk of dying from ischemic heart disease
exceeds the risk of dying from any of the other causes listed. Even in the
absence of other major risk factors for ischemic heart disease—hypertension
hypercholesterolemia, and smoking—the relative risk of ischemic heart disease
in diabetes is elevated.

Lung abscesses
Patients experiencing decreased consciousness (e.g. patients with a seizure
disorder) may aspirate oropharyngeal contents, causing a lung abscess. On chest
x-ray, a lung abscess appears as a cavitary lesion with an air-fluid level.
-Peptostreptococcus and Fusobacterium species are components of the normal
mouth flora.
- Lung abscesses arising as a complication of aspiration typically contain mixed
flora, often including these two species. Lung abscesses cause fever, weight loss,
cough and foul-smelling sputum. There may also be anorexia, malaise, chest
pain and clubbing.
-Lung abscesses may develop by the following mechanisms:
1. Aspiration of oropharyngeal contents is the most common cause. These
abscesses often contain Fusobacterium, Peptostreptococcus and Bacteroides
species. Risk factors include all conditions associated with loss of consciousness,
such as alcoholism, seizure disorders, prolonged anesthesia, and severe
neurologic diseases. Aspiration-associated abscesses are found in the dependent
parts of the right lung.
2. Lung abscesses may also occur as a complication of bacterial pneumonia.
Predisposing factors include immunosuppression, old age and underlying chronic
disease. Necrotizing pneumonias are usually nosocomial, caused by S. aureus, E.
coli, K. pneumoniae or S. pneumoniae type 3.
3. In patients with septicemia or infectious endocarditis, there may be
hematogenous spread of infection to the lung. Lung abscesses that develop in
this manner are oftentimes multiple. The most common causative agents are
Staphylococcus and Streptococcus species. E. coli and fungi may also be
implicated.
http://www.cvmbs.colostate.edu/ilm...pulmonary%20abscesses2.JPG
http://www.szote.u-szeged.hu/radio/mellk1/amelk5a.htm

Brain tumors in adults

-In adults, brain tumors are most commonly metastases from other cancers
especially those of the lung, breast, kidney, and skin (melanoma). On
macroscopic examination, brain metastases appear as multiple well-
circumscribed masses at the junction of gray and white matter. Brain metastases
are usually multiple.
- The following types of primary brain tumors listed in order of frequency, are
the most common in adults:
1. Glioblastoma multiforme (GBM) is a tumor that arises from astrocytes and is
the most common primary cerebral neoplasm in adults. It is typically located
within the hemispheres (in the frontal or temporal lobe or near the basal
ganglia). GBMs may become significantly large and may cross the midline. On
macroscopic examination GBMs are soft and poorly defined with areas of
necrosis and hemorrhage. GBMs are highly- malignant tumors with a very poor
prognosis: most patients die less than a year after diagnosis.
http://library.med.utah.edu/WebPath/CNSHTML/CNS136.html
2. Meningiomas are derived from arachnoid cells and are the second most
common brain neoplasm in adults. Meningiomas are benign and well
circumscribed. They are located on the brain surface, where they are attached to
dura. Meningiomas can be found over the lateral and parasagittal brain
convexities falx cerebri, sphenoidal ridge and olfactory groove.
http://library.med.utah.edu/WebPath/CNSHTML/CNS114.html
3. Acoustic neuromas are a special type of schwannoma that arise from Schwann
cells of CN VIII; acoustic neuromas are found at the cerebropontine angle.
http://www.ent.uci.edu/images/acoustic_neuroma_copy.jpg
-oligodendrogliomas present as well-circumscribed gray masses. Calcifications
may be visible; areas of necrosis and hemorrhages are not common.
http://www.medi-fax.com/atlas/brai...igodendroglioma/case2.html

Metalloproteinases
- are Zn-containing enzymes that degrade extracelluar matrix. They participate
in the normal tissue remodeling and in tumor invasion through the basement
membrane and connective tissue.
- Penetration of the basement membrane distinguishes an invasive tumor from
carcinoma in situ. This process includes the following steps:
1. Detachment of tumor cells from surrounding ceils occurs due to decreased
expression of cell adhesion molecules in most tumors itis determined by down-
regulation of the adhesion molecules E-cadherins.
2. Detached tumor cells have the ability to adhere to basement membranes.
Neoplastic cells may acquire this ability due to increased expression of laminin
and other adhesion molecules.
3. Invasion of the basement membrane occurs due to secretion of proteolytic
enzymes by the tumor ceils. A number of enzyme metalloproteinases play an
active role in this process. Another important enzyme is the cathepsin D
protease.
-Metalloproteinases degrade components of the extracelluar matrix and
basement membrane, composed primarily of laminin and collagens IV and VII.
These enzymes participate in a number of physiologic processes, such as tissue
remodeling and embryogenesis.
http://php.med.unsw.edu.au/cellbiology/images/4/4a/Cadherin2.gif

Retinopathy of prematurity
-Respiratory distress in a premature neonate is most commonly due to
pulmonary surfactant deficiency resulting in hyaline membrane disease.
-Treatment involves administration of supplemental oxygen at high
concentrations, nasal continuous positive airway pressure, and/or mechanical
ventilation with intratracheal surfactant. One potential adverse effect of oxygen
therapy is retinal damage.
-Temporary local hyperoxia in the retina is thought to induce changes that cause
up-regulation of proangiogenic factors such as vascular endothelial growth factor
(VEGE) upon return to room air ventilation. Retinal vessel proliferation
(neovascularization) and possible retinal detachment with blindness may result.
This complication of neonatal respiratory distress syndrome is referred to as
retinopathy of prematurity or retrolental fibroplasia.
http://www.sciencedaily.com/images/2007/06/070624141851-large.jpg

Cystic medial degeneration

=Myxomatous changes in the media of large arteries
- Medial degeneration is characterized by the fragmentation of elastic tissue and
by separation of the elastic and fibromuscular components of the tunica media
by small, cleft-like spaces. These spaces become filled with amorphous
extracellular matrix, and the normal elastic tissue is lost. Such medial
degeneration is the frequent histopathological abnormality found in association
with aortic dissections (dissecting hematomas) in humans. Aortic dissection can
occur in inherited connective tissue disorders, especially in Marfan syndrome.
Marfan syndrome is an autosomal-dominant defect in an extracellular
glycoprotein called fibrillin-1 that causes a specific body habitus (tall and thin
with spidery fingers) and an increased risk of aortic dissection. Fibrillin-1 is a
major component of extracellular matrix microfibrils, which form scaffolding for
elastic fibers. The weakness of the aortic media in Martan’s patients maybe
mimicked by anti nutritional feeding of experimental animals. Ingestion of β-
aminopropionitrile, a chemical found in certain kinds of sweet peas, causes
“angio lathyrism,” a change in the elasticity of the aorta. Note that aortic
dissection in humans can occur without any identifiable histopathological
abnormality of the aortic wall especially when hypertension is present.
http://pathologyoutlines.com/images/softtissue/02_08L.jpg
Pseudoaneurysm
= the entire wall of a blood vessel (usually arterial) ruptures. There is a breach
in the original continuity of the adventitia (or epicardium). The resulting
hematoma is then contained within a sac of the connective tissue surrounding
the original point of arterial wall rupture. Examples are leaks at the anastomosis
sites of vascular grafts and postinfarction myocardial ruptures that have been
contained by pericardial adhesions.
http://applications.spectrum-healt...types%20of%20aneurysms.gif

Giant cell arteritis (GCA) involves granulomatous inflammation of the media and
fragmentation of the internal elastic lamina, perhaps due to autoimmunity to
elastin.
http://www.djo.harvard.edu/files/5077_728.jpg

Primary spontaneous pneumothorax

= a pneumothorax in someone without pre-existing pulmonary disease and not
caused by trauma or barotrauma. Though the exact pathogenesis of this
condition is uncertain it is thought to result from rupture of apical subpleural
blebs. Blebs are continuous, distended airspaces that range in diameter from
<0.5 cm to more than 2.0 cm and sometimes form cyst- like sacs. Blebs may
spontaneously rupture usually while the patient is at rest causing a
pneumothorax. Tall thin males around the age of 20 are the most commonly
affected. There is also an association with smoking.

Panacinar emphysema
= occurs more commonly in the lower zones and anterior margins of the lung.
This condition is associated with a1-antitrypsin deficiency.
Centriacinar emphysema
-The emphysematous dilatation has a predominantly upper lung lobe distribution
but initially affects the respiratory bronchioles rather than the peripheral alveoli
and alveolar ducts. This type of emphysema is strongly linked to smoking.
http://www.geocities.com/drroy5/Emphysema1.JPG
Septic shock
=infection + the tetrad of hypotension, tachycardia, tachypnea, and markedly
elevated or decreased body temperature
- Early sepsis is characterized by increased cardiac output, peripheral
vasodilation, and warm extremities . When sepsis progresses, the stroke volume
decreases, cardiac output decreases, and distal hypoperfusion becomes evident.
In advanced septic shock, cool and clammy extremities, delayed capillary refill,
altered mental status, and decreased urine output are observed.
-The most important mediator of sepsis is tumor necrosis factor alpha (TNF-a),
an acute phase cytokine produced by activated macrophages. Other cytokines
responsible for inducing the systemic inflammatory response include IL-i and IL-
6.
DIFF:
-Leukotriene B4 is a metabolite of arachidonic acid. Its main function is to
stimulate neutrophil migration to the site of inflammation.
-IL-3 is a cytokine produced by activated I cells. It stimulates the growth and
differentiation of stem cells in the bone marrow.
-IL-4 is a cytokine produced by Th2 T-helper cells. It stimulates the growth of B
cells and increases the number of Th2 T-helper cells at the site of inflammation.
-IL-10 is an anti-inflammatory cytokine produced by macrophages and Th2 T-
helper cells. IL-10 limits the production of pro-inflammatory cytokines (eg,
gamma interferon IL-2, IL-3, TNF-a).
-Gamma interferon (INF-y) is produced by activated T cells and serves to recruit
leukocytes and activate phagocytosis.

Central retinal artery occlusion

=Acute and painless monocular vision loss
- The vision loss includes the entire visual field and is often permanent. Specific
funduscopic findings include a pale retina and a cherry- red macula. These
findings are explained by the fact that the macula has a separate blood supply
from the choroid artery, while the rest of retina is supplied by the central retinal
artery. These findings develop within an hour of the event.
-The central retinal artery is a branch of the ophthalmic artery, which arises from
the internal carotid artery. Embolism is the most common cause of central retinal
artery occlusion. Predisposing conditions include atrial fibrillation and carotid
artery stenosis.
http://www.residentandstaff.com/fi...s/2004RSPMay19_Figure1.gif
DIFF
-Amaurosis fugax
http://www.eyesite.ca/7modules/Module7/jpg/Mod7_08.jpg
-hypertensive retinopathy
http://www-clinpharm.medschl.cam.a...mages/HT_retinopathy_4.jpg
-diabetic retinopathy
http://www.topnews.in/health/files/diabetic-retinopathy.jpg
-“pie in the sky” visual defect
http://www2.kumc.edu/coa/Education...gy/images/TemporalLobe.gif

Benign prostatic hyperplasia

- leads to intermittent bladder outlet obstruction and overflow incontinence.
- Early symptoms of BPH include frequency, urgency nocturia, hesitancy, and
weak urinary stream. As the prostate enlarges further and the bladder outlet
obstruction worsens, patients experience a sensation of incomplete bladder
emptying. This usually signifies urinary retention. Overflow incontinence is the
next clinical stage.
-Urinary retention results in increased pressure in the urinary tract and resultant
reflux nephropathy. Ultimately, hydronephrosis and renal interstitial atrophy and
scarring ensue. The condition should be promptly treated as prolonged
obstruction can cause permanent damage and chronic renal failure.

Hereditary Hemochromatosis
= there is a defect in the intestinal absorption of dietary iron that results in the
storage of 0.5-1.0 grams of iron (primarily in the parenchymal organs) each
year. The disease is typically silent in early adulthood, manifesting only once at
least 20 grams of iron have been accumulated.
- After the age of 40, men can present with signs and symptoms typical of
hemochromatosis (eg, abdominal pain, skin pigmentation, hepatomegaly,
deranged glucose homeostasis, cardiac dysfunction, atypical arthritis,
hypogonadism).
-Women tend to present significantly later secondary to the protective effects of
blood (iron) loss during menses or pregnancy. After entering menopause,
however, women begin to accumulate iron at a faster rate and may become
symptomatic. Therefore, if a woman had a particularly heavy menstrual flow, she
would not have accumulated significant quantities of iron until after menopause.
http://www.pathguy.com/lectures/iron_overload.jpg
http://upload.wikimedia.org/wikipe...ver_iron_prussian_blue.jpg

Lymphangiosarcoma
-Persistent lymphedema (with chronic dilatation of lymphatic channels)
predisposes patients to the development of lymphangiosarcoma, a rare
malignant neoplasm of the endothelial lining of lymphatic channels. A typical
clinical scenario would be the appearance of lymphangiosarcoma approximately
10 years following radical mastectomy for breast cancer.
http://www.dermis.net/bilder/CD036/550px/img0076.jpg

Cavernous hemangiomas
=benign neoplasms of small blood vessel endothelial cells.
http://www.microscopyu.com/galleri...rnoushemangioma10x01_b.jpg

Pyogenic granuloma
=a polypoid form of capillary hemangioma. Pyogenic granulomas often grow
rapidly, as exophytic red nodules attached by a stalk to the gingival or oral
mucosa or skin. Pyogenic granulomas bleed easily, and may be ulcerated. One-
third of these lesions develop following local trauma. Histologically, these lesions
resemble hypertrophic granulation tissue.
http://www.skinsight.com/images/dx...enicGranuloma_35737_lg.jpg

Cystic hygroma
=cavernous lymphangioma consisting of a network of endothelium-lined lymph
spaces beneath the epidermis. Cystic hygromas differ from cavernous
hemangiomas only by the absence of luminal blood cells. Cystic hygromas
typically occur in children, and tend to affect the neck or axilla. Cystic hygromas
are associated with Turner’s syndrome.
http://www.pathology.washington.ed...ry/jpgs575/spd/img0041.jpg
http://www.iame.com/learning/olig/olig_fig9.html

Port-wine stain (nevus flammeus)

= a birthmark consisting of malformed, dilated blood vessels in the superficial
dermis. Clinically, these lesions present as dark red or purple patches, typically
involving the face or limbs. Port-wine stains are permanent lesions present from
birth.
http://imaging.cmpmedica.com/consu...3/2004/w_0406conpcport.jpg
Kaposi’s sarcoma
= a hyperplasia or neoplasm of spindle-shaped cells with markers of both
smooth muscle and vascular endothelial lineage. It is associated with HIV
infection and other immunocompromised states
http://depts.washington.edu/hivaids/images/derm/derm_c3_q01.jpg

Liver hemangiosarcoma
= rare malignant vascular endothelial cell neoplasm associated with such
carcinogens as arsenic (exposure to pesticides), thorotrast (a former radioactive
contrast medium), and polyvinyl chloride (a plastic widely used in industry).
http://www.pathguy.com/sol/10863.jpg

Fat embolism syndrome.

=respiratory distress, a non-focal neurologic disturbance, and chest lesions
consistent with thrombocytopenia after suffering multiple long bone fractures
- The fat embolism syndrome is a condition affecting less than 10% of patients
with severe skeletal injuries, and is characterized by pulmonary insufficiency,
diffuse neurological impairment, thrombocytopenia, and anemia. Fat globules
dislodged from bone marrow enter the marrow vascular sinusoids and then
occlude pulmonary microvessels, impairing gas exchange. Microvascular
occlusion in the cerebral white matter, brain stem, and spinal cord causes the
neurologic manifestations.
The pulmonary and CNS microvascular and parenchymal dysfunction may be
promoted by:
1. release of mediators from platelets which adhere to and coat the fat emboli (a
phenomenon also resulting in thrombocytopenia), and
2. systemic activation of lipoprotein lipase and intravascular release of toxic
levels of oleic acid
-The anemia is thought to be due to increased RBC aggregation and destruction,
as well as possible pulmonary hemorrhage.
Spontaneous intracranial hemorrhage (SICH)
-The most common causes of SICH in young adults are arteriovenous
malformations, ruptured cerebral aneurysms, or abuse of sympathomimetic
drugs such as cocaine.
- Berry aneurysms are particularly prone to rupture when associated with
coarctation, because of hypertension in branches of the aortic arch proximal to
the coarct. Subarachnoid hemorrhage is the result.
- Patients with adult-type coarctation of the aorta commonly die of hypertension-
associated complications, including left ventricular failure, ruptured dissecting
aortic aneurysm, and intracranial hemorrhage.
http://www.neurosurgery.ufl.edu/pa...-aneurysm-common-sites.jpg

Hypertrophic cardiomyopathy (HCM)

= asymmetric ventricular septal hypertrophy and variable dynamic left
ventricular outflow tract obstruction which may produce a systolic ejection
murmur.
- Decreases in the LV end diastolic volume increase the obstruction causing the
murmur of HCM to be enhanced. Actions like standing suddenly from the supine
position and the Valsalva maneuver decrease venous return and thus accentuate
the murmur.
- Squatting, sitting, or lying supine increase venous return thereby increasing
right and left ventricular preload.
-Sustained (isometric) handgrip increases the systemic vascular resistance and
thus reduces the gradient across the LV outflow tract.
-Passive leg raising augments venous return thereby increasing right and left
ventricular preload.
-Phenylephrine (a selective al agonist) increases systemic vascular resistance
and thus reduces the gradient across the LV out flow tract.

Differential cyanosis
= cyanosis of the lower extremities but not of the upper body. Differential
cyanosis is the result of reduced arterial oxygen saturation in the distal aorta
compared to that in the aorta proximal to the takeoff of the left subclavian
artery. The most likely cause is right-to-left shunting of blood flow through a
patent ductus arteriosus (PDA) into the junction between the aortic arch and the
descending aorta. Although PDAs initially involve left-to-right shunting, overtime
the resultant pulmonary hypertension can cause pulmonary vascular sclerosis,
increased pulmonary vascular resistance, and reversal of shunt flow across the
ductus.
- The infantile, preductal form of coarctation of the aorta is generally associated
with a PDA. The PDA causes shunting to the aorta distal to the point of aortic
constriction, causing cyanosis restricted to the lower body. However these
patients generally develop congestive heart failure and are unlikely to survive
beyond infancy without surgical correction.
-The adult form of COA represents a lesser degree of aortic constriction and is
not associated with a right-to-left shunt, since the PDA is closed. Adult-type COA
can limit lower extremity exercise tolerance but does not commonly cause
cyanosis.
DIFF:
-Atrial and ventricular septal defects initially present with left-to-right
intracardiac shunting and are therefore not associated with cyanosis at birth. If
arterial oxygen desaturation develops later in life because of shunt reversal
(Eisenmenger syndrome), the resulting cyanosis affects the upper and lower
body equally.
http://www.mfi.ku.dk/ppaulev/chapter12/images/12-7.jpg

Whipple disease
The periodic acid- Schiff (PAS) reaction is used in histochemical staining because
the periodic acid oxidizes carbon- carbon bonds, forming aldehydes that produce
a brilliant magenta color upon reacting with the fuchsin-sulfurous acid. As a
result the PAS stain is particularly effective at highlighting polysaccharides of the
fungal cell wall mucosubstance secreted by epithelia, and basement membranes.
Diastase can be used in conjunction with PAS to demonstrate glycogen, which is
found in skin, liver, parathyroid, and skeletal/cardiac muscle. The diastase works
by digesting glycogen to form maltose and glucose, two sugars that are easily
washed from sections during processing (therefore giving a negative reaction).
-The glycoprotein present in the cell walls of the gram-positive actinomycete
Tropheryma whippelii appears magenta with PAS and is diastase-resistant, which
makes this stain an excellent choice when microscopically evaluating small bowel
mucosa for Whipple disease.
http://www.uptodate.com/online/con...AS%20positive%20macrophage

Dermatitis herpetiformis
= groups of small vesicles that occur on extensor surfaces. Knees, elbows,
buttocks, and back are the most typical locations for the rash. The eruptions are
symmetrically distributed and extremely pruritic.
-Dermatitis herpetiformis is an autoimmune disorder associated with celiac
disease (gluten-sensitive enteropathy). Skin biopsy will show neutrophils and
fibrin at the tips of dermal papilla, forming, and microabscesses.
-Immunofluorescence reveals IgA deposits also present in the tips of dermal
papillae.
-Twenty to thirty percent of patients with dermatitis herpetiformis also have
diarrhea, steatorrhea, or other symptoms of malabsorption. On endoscopy,
almost all patients with dermatitis herpetiformis have villous atrophy, which is
typical for celiac disease.
Symptoms of both dermatitis herpetiformis and celiac sprue diminish or resolve
completely on a gluten-free diet. Wheat, rye, and barley do contain gluten, while
oats and rice do not.
http://www.pathology.vcu.edu/education/gi/lab2.c.html

Abetalipoproteinemia
=an inherited inability to form chylomicrons. This disease manifests during the
first year of life with malabsorption, failure to thrive, progressive ataxia, and
abnormal red blood cells (acanthocytes).
http://www.pathguy.com/sol/13871.jpg

Crohn’s disease
=associated with skin manifestations, such as erythema nodosum (tender
subcutaneous nodules) and pyoderma gangrenosum (deep ulcers with violaceous
borders)
http://www.med-ed.virginia.edu/cou.../images/medium/fm00060.jpg

Abnormal bleeding in uremia

=is due to a qualitative platelet disorder with normal platelet count, PT and PTT.
Bleeding time however, is generally very prolonged in patients with uremia,
signifying a major defect in platelet function, which improves after dialysis. A
number of dialyzable platelet-inhibitory factors have been shown to inhibit
platelet function.
http://www.microscopyu.com/galleri...es/burrcelluremia40x04.jpg

Squamous cell carcinoma of the esophagus

= solid nests of neoplastic squamous cells with abundant eosinophilic cytoplasm
and distinct borders. Areas of keratinization (keratin pearls) are easily noticed.
Keratin pearls are a sign that the tumor hasn’t yet lost the properties of an
original tissue—in other words, it is a well-differentiated tumor. -In poorly-
differentiated squamous cell carcinoma, there is usually no keratinization, cells
vary in size and shape, and cells have large darkly-staining nuclei. Numerous
mitotic figures might be seen.
- The most important risk factors are alcohol and tobacco use. Plummer-Vinson
syndrome, achalasia and corrosive strictures of esophagus are other risk factors
-Most squamous cell carcinomas of the esophagus occur in male patients older
than 50 years old. Presentation includes progressive dysphagia, first for solids,
then for both solids and liquids. Significant weight loss is common.
http://www.gastrointestinalatlas.c...ncer/esophagus_cancer.html
http://library.med.utah.edu/WebPath/GIHTML/GI014.html

Benign tumors of esophagus

= quite rare and slow growing. The most common of them is leiomyoma. On
light microscopy leiomyomas consists of fascicles of spindled cells with variable
amount of fibrosis.

Cystic fibrosis
=Recurrent pulmonary infections and malabsorption in a Caucasian child
=autosomal recessive disorder of exocrine secretion. In CE, the cystic fibrosis
transmembrane conductance regulator (CFTR) is non-functional. This membrane
protein is normally responsible for transporting chloride ions across mucosal
epithelial cell membranes. When the CFTR gene is mutated transport of chloride
and water from the cells is suppressed, leading to the secretion of viscous
mucus. There is stasis and accumulation of these viscous secretions in tissues.
-The most pronounced changes in cystic fibrosis are seen in the respiratory tract
and pancreas. The male reproductive system, liver and salivary glands may also
be involved.
-Characteristic findings include:
1. Increased viscosity of bronchial secretions leads to impaired mucociliary
clearance of bacteria. Repeated pulmonary infections particularly with
Pseudonomas aeruginosa, are characteristic. Mucus plugging of bronchi causes
dilatation and bronchiectasis.
2. Viscous pancreatic secretions are not transported to the intestinal lumen and
instead accumulate in pancreatic ducts. Pancreatic insufficiency causes the
symptoms of malabsorption (steatorrhea and poor weight gain). Pancreatic
secretions form mucous plugs that with time totally obstruct the ductal lumina,
leading to fibrosis of pancreatic tissue.
3. Decreased secretion of water by the intestinal epithelium may cause intestinal
obstruction. Neonates with cystic fibrosis may develop meconium ileus.
-Mucous plugging can also be seen in biliary ducts (with development of biliary
cirrhosis) vas deferens (causing male infertility), and salivary gland ducts. Upper
respiratory tract symptoms include bilateral sinusitis and nasal polyps.
http://www.pathguy.com/sol/26249.jpg
B12 deficiency
-Vitamin B12 and folic acid deficiencies cause similar hematological pictures.
However, neurological dysfunction is only seen in patients with vitamin B12
deficiency. This is because B12 deficiency also causes axonal demyelination and
degeneration. In late disease, the neurological dysfunction may be irreversible.
-The main sites of neurological involvement include the peripheral nerves, spinal
cord (posterior and lateral columns), and the cerebrum. Decreased vibratory and
position sense are early signs of vitamin B12 deficiency. Patients experience
ataxia and recurrent falls because of compromised proprioception. Importantly,
neurologic abnormalities can occur in vitamin B12 deficiency in the absence of
frank anemia. Treating megaloblastic anemia due to vitamin B12 deficiency with
folate alone could worsen the neurological dysfunction.
-An RBC mean corpuscular volume (MCV) of more than 100 fL is suggestive of
megaloblastic anemia. However RBC macrocytosis can also occur in liver disease,
hypothyroidism, and alcoholic liver disease.
-MCVs greater than 110 fL are typically seen only with vitamin B12 and folic acid
anemias. On peripheral blood smear there is macrocytosis , hypersegmented
neutrophils, and large bizarrely shaped platelets. The presence of even a single
neutrophil with more than 6 lobes should raise the suspicion of megaloblastic
anemia.
The medications listed in the other answer choices are not used for the
treatment of megaloblastic anemia.
http://www.vitaminsdiary.com/UserF...e/megaloblastic-anemia.gif

Poststreptococcal glomerulonephritis
The classic presentation = a 6 to 10-year-old child developing malaise, fever,
nausea and cola-colored urine 2-3 weeks after recovering from a streptococcal
skin or throat infection. Dysmorphic red cells, RBC casts, and mild proteinuria
(<1 g/day) are present in urine. Periorbital and facial edema and hypertension
are also usually detected.
-Therapy includes loop diuretics and vasodilators to relieve the edema and
hypertension.
-Age is the most important prognostic factor in patients with poststreptococcal
glomerulonephritis. 95% of children recover completely with conservative
therapy, 1-2% develops chronic glomerulonephritis, and less than 1% progress
to RPGN.
-The prognosis in adults is not as good. Only 60% of sporadic cases in adults will
resolve completely; the rest will develop chronic glomerulonephritis or RPGN.
Colon adenocarcinomas
- Left-sided colon cancers tend to infiltrate the intestinal wall and encircle the
lumen; hence they present with symptoms of partial intestinal obstruction.
Change in the stool caliber, constipation, cramping abdominal pain, abdominal
distention, nausea, and vomiting occur.
-Right-sided colon cancers usually grow as exophytic masses. Patients generally
do not develop intestinal obstruction because the right-sided colon has a larger
caliber than the left. Right-sided colon cancers usually present with
manifestations of iron deficiency anemia (fatigue and pallor) due to the ongoing
blood loss. Non-specific symptoms such as anorexia, malaise and weight loss
also occur.

Anorexia nervosa
= is an eating disorder characterized by an intense fear of eating significant loss
of bodyweight(to less than 85% of expected weight or BMI less than 17.5
kg/m2), inaccurate perception of ones own body shape and size, and
amenorrhea.
-The amenorrhea results from loss of pulsatile GnRH release from the
hypothalamus, which occurs when the level of body fat falls below a certain
critical level. Loss of this cyclic gonadotropin release leads to a decrease in LH
and ESH secretion from the pituitary, which in turn causes circulating estrogen
levels to be low. Administration of pulsatile GnRH in individuals with anorexia
nervosa allows for the normalization of estrogen levels and subsequent
ovulation.
-Amenorrhea also often occurs in serious athletes with very low body fat (e.g.
long distance runners, ballet dancers) as well as in individuals with prolonged
cachectic illnesses, via the same mechanism. If left untreated, the low estrogen
levels in these amenorrheic individuals could lead to osteoporosis.
- Patients with anorexia nervosa can develop the abnormality of thyroid
functioning termed “sick euthyroid syndrome” orl owT3 syndrome. Early in
the course of anorexia T3 levels are low and T4 and TSH levels are normal.
However, in prolonged severe disease, both T3 and T4 levels are low.

Aortic dissection
= widened descending thoracic aorta with a “double barrel.” An apparent
tissue septum divides the lumen of the aorta. The “septum” is actually the
normal wall of the descending aorta, which is now medially flanked by a second
cavity. This apparent second cavity is really an intramural hematoma. Aortic
dissections give rise to these hematomas as more and more blood creeps behind
the medial wall. An intimal tear is thought to be the primary event in the process
that leads to aortic dissection.
-The dissection can extend both proximally toward the heart and
distally—sometimes it runs all the way to the iliac and femoral arteries!
-Hypertension is the single most important risk factor for the development of
intimal tears leading to aortic dissections. Cystic medial degeneration (which
may be seen in Marfan syndrome) also predisposes patients to aortic dissections,
but is relatively infrequent.
http://www.ispub.com/ispub/ijem/vo...l_features/aortic-fig1.jpg

Membranous glomerulopathy= “spike and dome” appearance

= the second most common cause of nephrotic syndrome in adults. (The most
common cause is focal segmental glomerulosclerosis.) Up to 85% of cases are
idiopathic. The remainder occur secondary to the following:
*Systemic diseases - diabetes mellitus, solid tumors (lung and colon), and
immunologic disorders (such as SLE)
*Certain drugs - gold, penicillamine, and NSAIDs
*Infections - hepatitis B, hepatitis C, malaria, and syphilis
- The microscopic findings : uniform, diffuse thickening of the glomerular
capillary wall on light microscopy. Electron microscopy reveals that this
thickening is caused by irregular, dense deposits laid between the basement
membrane and the epithelial cells. These protrusions resemble “spikes”
when stained with silver. Immunofluorescence microscopy reveals that these
granular deposits contain immunoglobulins (IgG) and C3.
http://library.med.utah.edu/WebPath/RENAHTML/RENAL088.html
http://library.med.utah.edu/WebPath/RENAHTML/RENAL089.html

Berger disease
= painless hematuria in children and young adults a few days after upper
respiratory infection. IgA deposits in the mesangium are found on
immunofluorescence.
http://www.kidneypathology.com/Im%...IgA/IgA.mesangial.IFw..jpg

Minimal change disease

=the most common cause of nephrotic syndrome in children. No abnormalities
are found on light or immunofluorescent microscopy. On electron microscopy,
effacement of the foot processes of podocytes are seen.
http://pathcuric1.swmed.edu/PathDemo/kid1/kid170.htm
Peptic ulcer disease (PUD)
= most commonly occurs due to infection with Helicobacter pylori. Peptic ulcer
disease encompasses both gastric and duodenal ulcers.
-symptoms of a duodenal ulcer—pain a few hours after eating that resolves
with antacid. Symptoms of a duodenal ulcer occur when acid is secreted without
a food buffer. Gastric emptying occurs usually 2-3 hours after a meal, but food-
stimulated acid secretion continues for 3-5 hours. Thus, the pain associated with
a duodenal ulcer typically happens 2-4 hours after a meal or with an empty
stomach. Most patients also complain of pain between 11 PM and 2 AM because
maximal circadian acid secretion occurs then.
-On the other hand, pain associated with gastric ulcers occur immediately after
meals and responds poorly to antacids.
-Duodenal ulcers affect 10-15% of the population, and manifest in young and
middle-aged people. Gastric ulcers tend to occur later in life (average age of
patients is 50-60 years old). Gastric ulcers are usually located within the body of
the stomach at the lesser curvature and affect about 1% of the population.
-The most common site for duodenal ulcers is the first portion of the duodenum
(within 3 cm of the pylorus). This area is called the duodenal bulb and is exposed
to the most gastric acid.
http://www.szote.u-szeged.hu/radio/nyelocs/anyel11c.htm

Friedreich ataxia
=autosomal recessive disorder. It is caused by the mutation of a gene on
chromosome 9 that codes for the protein “frataxin" which is essential for
normal mitochondrial function. An increased number of trinucleotide repeats is
present in the mutated gene, causing diminished levels of frataxin in patients
with Friedreich ataxia. The disease occurs only if the both alleles of the gene are
abnormal.
-Friedreich ataxia causes degeneration of neural tracts and peripheral nerves.
-The following sites of involvement are characteristic:
1. Ascending and descending spinocerebellar tract degeneration causes gait
ataxia.
2. Degeneration of the dorsal columns and dorsal root ganglia causes loss of
position and vibration sensation.
3. Kyphoscoliosis and foot abnormalities (pes cavus) are characteristic skeletal
deformities.
4. Heart involvement includes hypertrophic cardiomyopathy and congestive heart
failure.
5. Diabetes mellitus develops in about 10% of patients with Friedreich ataxia.
http://www.nature.com/nrn/journal/v5/n8/fig_tab/nrn1474_F1.html
Adult respiratory distress syndrome (ARDS)
=progressive hypoxemia refractory to oxygen therapy, decreasing lung
compliance, interstitial edema progressing to diffuse alveolar infiltrates, and
absence of cardiogenic pulmonary edema (normal pulmonary capillary wedge
pressure) in most cases.
-In ARDS, diffuse injury to the pulmonary microvascular endothelium and/or the
alveolar epithelium results in a leaky alveolocapillary membrane. In the acute
stage, the lungs are heavy, red, and boggy. The interstitial and intra-alveolar
edema, inflammation, and fibrin deposition cause the alveoli to become lined
with waxy hyaline membranes. These membranes consist of fibrin exudate and
plasma protein-rich edema fluid mixed with the cytoplasmic and lipid remnants
of necrotic epithelial cells. These membranes are morphologically similar to those
seen in hyaline membrane disease of newborns.
-Acute necrotizing pancreatitis is a major risk factor for progression to adult
respiratory distress syndrome
http://www.histopathology-india.net/ARDS1.JPG

Frank intraalveolar hemorrhage

= could impair gas exchange and cause dyspnea if widespread but would also
tend to produce hemoptysis as a clinical sign. Widespread intraalveolar
hemorrhage may occur in pulmonary hemorrhage syndromes, including
Goodpasture syndrome, Wegener granulomatosis, and lupus erythematosus.
http://www.som.tulane.edu/classwar...8/Lung_Review/Lung-51.html

CREST syndrome
=Calcinosis, Raynaud syndrome, esophageal dysmotility, Sclerodactyly, and
Telangiectasia . It is a systemic sclerosis variant that mostly involves skin of the
face and fingers.
-The pathogenesis of systemic sclerosis is unknown, although immunologic
hyperreactivity is suspected. An unknown antigen is thought to stimulate
accumulation of CD4 lymphocytes in skin and other tissues. CD4 lymphocytes
secrete biologically-active substances and stimulate fibroblasts to produce
collagen. Excessive tissue fibrosis ensues and is the hallmark of systemic
sclerosis.
-Esophageal dysmotility is a result of atrophy and fibrous replacement of
esophageal muscles. The esophageal body and the LES become atonic and
dilated, resulting in severe reflux.
-The main symptoms of esophageal dysmotility in CREST syndrome are
heartburn, regurgitation, and dysphagia. Barium esophagram shows a dilated
esophagus and absent peristalsis. These patients are at risk of development of
Barrett esophagus and subsequent esophageal adenocarcinoma.
http://www.radiology.co.uk/srs-x/cases/081/d.htm

Achalasia
= increase in resting lower esophageal sphincter tone and diminished LES
relaxation during meals. Barium swallow reveals a distended esophageal body
and narrowed LES (“bird’s beak”).
https://www.hon.ch/OESO/books/Vol_...rticles/Images/1324-74.jpg

Hiatal hernia
-An abnormal location of the gastroesophageal junction describes a sliding hiatal
hernia. In this condition, the gastroesophageal junction along with a portion of
the stomach moves up through the esophageal hiatus. These patients are prone
to GERD.
http://www.learningradiology.com/a...tzkis%20Ring/hhcorrect.htm

Diffuse esophageal spasm (DES)

=Periodic non-peristaltic esophageal muscle contractions
- Clinical manifestations are dysphagia and chest pain. Barium esophagogram
will reveal the characteristic “corkscrew esophagus.”
http://myweb.lsbu.ac.uk/dirt/museum/margaret/718-741-1641420.jpg

Precocious puberty
=Growth of facial and pubic hair along with enlarged genitalia in a boy younger
than 9 years old
- For girls = an appearance of secondary sexual characteristics before age 7.
-A number of diseases can cause precocious puberty including congenital adrenal
hyperplasia, and ovarian and adrenal tumors. The association of precocious
puberty with a neurologic abnormality (such as paralysis of upward gaze)
suggests a hormone-secreting brain tumor. Such neurologic abnormalities are
caused by mass effect.
-Paralysis of upward gaze is called Parinaud syndrome (or dorsal midbrain
syndrome). This neurological finding is consistent with a tumor of the pineal
region. Germinomas are the most common tumor of the pineal gland.
Germinomas are malignant tumors thought to originate from embryonic germ
cells. These germ cell neoplasms have identical counterparts that occur in the
gonads and mediastinum. Germinomas are found in children and adolescents,
and show a strong male predominance.
-The following combination of symptoms are associated with pineal germinomas:

1. Precocious puberty may occur in males and is caused by beta-hCG production.

2. Aqueductal compression by the tumor may lead to obstructive hydrocephalus.

3. Parinaud syndrome includes paralysis of upward gaze and of
convergence—these symptoms occur due to compression of the tectal area of
the midbrain.
http://radiopaedia.org/cases/pineal-germinoma

"Locked-in” syndrome
=Pontine hemorrhage or tumor (spastic quadriplegia and paralysis of most
cranial nerves).
http://rad.usuhs.edu/medpix/parent...r&imageid=30646&pt_id=9764

Lesions of the medulla

=can cause lateral and medial medullary syndromes.
-Lateral medullary syndrome (Wallenberg) leads to contralateral loss of pain and
temperature sensation along with ipsilateral paralysis of CN V, IX, X, and Xl.
http://www.neuropat.dote.hu/wallenb/wallenb.htm
-Medial medullary syndrome causes contralateral spastic paralysis and ipsilateral
flaccid paralysis of the tongue (CN XII).
http://medinfo.ufl.edu/year2/neuro/review/images/fig09.jpg

Achnodroplastic dwarfism
=disproportionately short stature (short upper and lower extremities compared
to the axial skeleton) and some cranial abnormalities.
- The most common defect in achondroplasia is the mutation of the
“fibroblast growth factor receptor-3” at the epiphyseal growth plate.
-Long bones have a wide epiphysis at each end and narrower, tubular diaphysis
in the middle. Young bone has several layers; in order, from middle to end, they
are diaphysis metaphysis epiphyseal cartilage, and epiphysis.
-Expansion of the epiphyseal cartilage, also called the “growth plate” is
responsible for linear growth. This growth is regulated by a number of factors
including hormones and cytokines. The major factors are growth hormone IGF-1,
insulin, thyroid hormone, sex steroids and fibroblast growth factor. If fibroblast
growth factor receptor-3 has an activating mutation, growth is inhibited at the
epiphyseal growth plate ultimately resulting in short, thick tubular long bones in
the appendicular (limb) skeleton. Axial (spine) length is usually normal.
http://www.moondragon.org/obgyn/gr...hondroplasiacomparison.jpg
DIFF:
-Hypothalamic and pituitary lesions cause short stature by decreasing the growth
hormone / insulin like growth factor-1 (IGF-1) pathway. Short stature in growth
hormone / IGF-1 deficiency is proportional; that is the axial and appendicular
skeleton are proportionate.

Colonic polyps
- types of non-neoplastic polyps:
1. Hyperplastic polyps are composed of well-differentiated mucosal cells that
form glands and crypts.
http://kathrin.unibas.ch/polyp/bilder/gross/p011-01.jpg
2. Hamartomatous polyps consist of mucosal glands, smooth muscle and
connective tissue. They may occur sporadically or in Peutz-Jeghers syndrome or
juvenile polyposis.
http://www.nature.com/modpathol/jo.../n4/fig_tab/3880773f4.html
3. Inflammatory polyps are seen in ulcerative colitis and Crohn disease. They are
composed of regenerating intestinal mucosa.
4. Lymphoid polyps are found in children. They consist of intestinal mucosa
infiltrated with lymphocytes.
http://www.ispub.com/ispub/ijpa/vo..._report/polyposis-fig1.jpg
-Unlike non-neoplastic polyps, adenomatous polyps contain dysplastic mucosal
cells and can transform into adenocarcinoma. The following criteria determine
the malignant potential of adenomatous polyps:
1. Degree of dysplasia.
2. Histologic pattern: villous adenomas are more likely to undergo malignant
transformation than tubular adenomas.
3. Size: adenomas >4 cm have 40% risk of becoming malignant; those <1 cm
are most likely benign.
http://www.pathologyatlas.ro/patho...dunculated_polyp_colon.jpg

Metaplasia
= adaptive change that occurs in response to chronic epithelial irritation.
-Smoking induces squamous bronchial metaplasia, while long-standing reflux
results in columnar metaplasia of the distal esophagus (Barrett’s esophagus).
Both these conditions increase the risk of malignancy and are therefore referred
to as premalignant.
- . This change of cell types is called metaplasia and is initially adaptive.
Squamous epithelial cells are more resistant to irritation than columnar cells and
are more likely to survive in the bronchial lining of a chronic smoker. The
squamous epithelium, however, does not have cilia and goblet cells, and is
unable to provide mucociliary clearance. Metaplastic epithelia can progress to
dysplasia (low-grade atypical cells confined to the epithelium) and is therefore a
risk factor for carcinoma (high-grade atypia with or without invasion beyond the
epithelial space). Squamous bronchial metaplasia is reversible and may resolve
upon discontinuation of smoking.
http://www.lmp.ualberta.ca/resourc...ages/Images-S/000p027y.jpg

Apoptosis involves the following steps:

1. Initiation: Apoptosis is triggered by different stimuli and can occur through
either the intrinsic mitochondria mediated pathway or the extrinsic, receptor-
initiated pathway. Cells damaged by ultraviolet light, heat, hypoxia, toxins, or
radiation display intrinsic apoptotic signals (eg, phosphatidylserine or
thrombospondin) on their plasma membranes. Extrinsic apoptosis, in contrast, is
induced by the tumor necrosis factor (TNF) when bound to tumor necrosis factor
receptor (TNFR1) or the Fas ligand when bound to cell surface receptor Fas.
2. Control: Intrinsic apoptosis is mediated by a group of bcl-2 proteins. Some of
the components of this system are pro-apoptotic (eg, Bak, Bax, and Bim
proteins) while others are anti-apoptotic (eg, Bcl-x and Bcl-2 proteins). Apoptotic
signals tip the balance between these two forces resulting in changes of the
inner mitochondrial membrane. These changes are responsible for the formation
of the mitochondrial permeability transition (MPT) and the release of cytochrome
c and other pro-apoptotic proteins into the cytoplasm, which then activate
caspases. In extrinsic apoptosis, the binding of the death ligand and the death
receptor allows for pro-caspase molecules to be brought into close proximity.
3. Destruction: Both the intrinsic and extrinsic pathways converge at this step
resulting in caspase activation. Caspases are proteolytic enzymes that destroy
cell components. They contain cysteine and are able to cleave aspartic acid
residues (cysteine-aspartic-acid-proteases). The eleven caspases that have been
identified are classified as either initiator or effector caspases. Initiator caspases
activate the effector caspases, which then cleave the cellular proteins.
http://www.new-science-press.com/i...-cellcycle-10-14-10_29.jpg
http://www.bio.davidson.edu/Course...wails/apoptoticpathway.gif

Protein kinase A
= a component of the cAMP-associated signaling system. The binding of a ligand
to S-protein-linked receptor results in adenylyl cyclase activation and the release
of cAMP. Elevated levels of cAMP activate protein kinase A.
http://employees.csbsju.edu/hjakub...1/signaltrans/sigtrans.gif

Shaken baby syndrome

=the combination of subdural hematoma with bilateral retinal hemorrhages in an
infant. Any suspicion of child abuse should be reported to state protective
agencies.
- The injuries produced by severe shaking are due in part to the unique anatomic
features of the head of a young child. Infants have larger heads, larger
subarachnoid spaces, higher brain water content, and decreased cervical muscle
tone compared to adults. Shaking leads to movement of the immature brain in
relation to the skull, and subsequent tearing of the bridging veins, resulting in a
subdural hematoma. Retinal hemorrhages occur due to rupture of congested
retinal veins.
Other types of trauma suggestive of child abuse include bruises, burns and
fractures. Bruises and lacerations in the different stages of healing may indicate
repeated abuse. Burns to the genitals buttocks, or perineum may be indicative of
forced immersion burns. Spiral fractures, as well as multiple fractures in different
stages of healing, are also typical.
http://www.medscape.com/content/20...53/art-adnc478153.fig2.jpg

Sistemic embolism
-Because of his high blood supply the kidneys are more likely than other organs
to suffer embolic infarctions.
-Another distinctive feature of the renal circulation is the small number of
collaterals between the segmental renal arteries. This “end-organ” blood
supply means that interruptions of blood flow lead to the formation of
coagulative infarcts. Macroscopically, these appear as pale wedges (base facing
cortex, apex pointing to medulla). A thin rim of subcortical tissue maybe
preserved, as it derives its blood supply from the renal capsule.
-a stroke and renal infarction suffered simultaneously most likely resulted from
systemic emboli. Most often, these emboli arise from the left atrium or left
ventricle. Emboli can form adjacent to a necrotic ventricular wall following an
acute Ml or in the resultant ventricular aneurysm weeks later. Other common
causes of systemic embolism include atrial fibrillation, aortic aneurysm, and
infective endocarditis.
http://library.med.utah.edu/WebPath/RENAHTML/RENAL011.html

Acute interstitial nephritis

= a hyper sensitivity reaction that occurs 1-2 weeks after starting a new
medication. Fever, rash, oliguria, eosinophilia and eosinophiluria are common
manifestations.
http://cnserver0.nkf.med.ualberta....rier/Vol1/Fig.%209-17a.jpg
Malignant melanoma
= an increasingly common neoplasm that typically arises in the skin, although it
has also been identified in the eye, esophagus, meninges and on mucosal
surfaces. Sunlight exposure appears to be an important factor in the
pathogenesis of skin malignant melanoma, as are hereditary factors and a
history of pre-existent dysplastic nevus in the same location.
-Light-skinned individuals are more likely than dark-skinned individuals to
develop malignant melanoma.
-Clinically these lesions are either asymptomatic or pruritic. Most melanomas are
greater than 1 cm in diameter and have demonstrated change in color size, or
shape. Marked variability of pigmentation may occur, with shades of black brown
red navy blue and/or gray present. The borders are frequently irregular and
notched.
- Histologically the melanoma cells congregate in poorly formed nests and are
large with irregular nuclei, clumped chromatin and prominent nucleoli.
-The risk of metastasis is based on the growth phase of the tumor. Those
melanomas in the radial growth phase remain superficial and extend horizontally
within the epidermis and superficial dermis with no risk of metastasis. In
contrast melanomas in the vertical growth phase contain atypical, immature cells
that travel downward into the deeper dermal layers increasing the risk of
metastasis. Measurement of the depth of invasion (Breslow thickness) is the
most important prognostic indicator for patients with malignant melanoma.
http://www.howtogetridofmoles.net/Malignant_Melanoma.jpg

Chronic Constrictive pericarditis

- Tuberculous caseous pericarditis is the common cause. In normal individuals
the jugular venous pressure decreases with inspiration. In patients with chronic
constrictive pericarditis, however, Kussmaul’s sign, a paradoxical rise in the
height of the jugular venous pressure during inspiration, is evident. This occurs
because of the increase in venous return that occurs with inspiration and the
restriction of right heart filling that occurs in chronic constrictive pericarditis.
- Chronic constrictive pericarditis results in replacement of the normal pericardial
space by a thick fibrous shell which can cause heart failure by restricting
ventricular filling
- The pericardial knock occurs earlier in diastole than an S3 gallop.
http://www.som.tulane.edu/classwar...cPath/GR_Heart/Heart3.html

Nephrotic syndrome
= clinically characterized by facial edema combined with massive proteinuria.
-The most common cause of nephrotic syndrome in children between 2 and 8
years old is minimal change disease (MCD), also called as lipoid nephrosis. This
disease may be associated with respiratory infections, immunization, or with
atopic disorders.
- An important feature of this condition is its rapid response to corticosteroid
therapy.
-The long-term prognosis for these patients is excellent: renal function remains
good. Although nephrotic syndrome may recur, it usually resolves before
puberty.
-Light microscopy in MCD shows normal glomeruli. Immunofluorescence
microscopy doesn’t reveal any immunoglobulin or complement deposits.
-Electron microscopy, however, shows diffuse effacement of the foot processes
of podocytes with a morphologically-normal glomerular basement membrane.
The “fusion” of foot processes is the only pathological finding in MCD: renal
function, and light microscopy remain unchanged. The pathology of MCD is
completely reversible after steroid therapy.
http://www.pathology.vcu.edu/education/em/case11.html

Iron deficiency anemia

-the following sequence of changes can be tracked with laboratory testing:
1. Decreased bone marrow iron stores (ferritin and hemosiderin)
2. Decreased serum ferritin
3. Increased serum total iron binding capacity (TIBC), reflecting increased serum
transferrin
4. Decreased serum iron concentration
5. Decreased blood hemoglobin
6. Appearance of microcytic, hypochromic red blood cells
-Ferritin is the cellular iron storage protein, and serum ferritin is an excellent
marker of iron stores. Serum ferritin is decreased in cases of iron deficiency and
elevated in cases of iron overload.
-Transferrin transports iron through the plasma. In individuals with normal iron
levels, approximately one-third of the circulating transferrin is saturated with
iron. Hepatic synthesis of transferrin is markedly increased in states of iron
deficiency. When the supply of iron is decreased, the transferrin saturation
drops. Likewise, when the supply of iron is increased, the transferrin saturation
rises.
-This patient would be expected to have low serum ferritin, high circulating
transferrin, low (microcytic) MCV, normal folate levels, and no hypersegmented
neutrophils.
- Anemia in a woman of childbearing age is most commonly caused by iron
deficiency secondary to menstrual blood loss
http://www.pathguy.com/lectures/low_iron.jpg

Hereditary non-polyposis colon cancer (HNPCC) or Lynch syndrome

= autosomally-dominant genetic predisposition to colon cancer. In patients with
this syndrome, colon cancer occurs at a young age (<50 years old). Family
history reveals high incidence of colon and other cancers in first- degree
relatives.
-Unlike sporadic colon cancer, HNPCC does not involve mutations of proto-
oncogenes or anti-oncogenes. Instead there is an inherited mutation in one of
the four genes responsible for DNA mismatch repair. The products of these
genes “proofread” DNA during replication.
- Patients with HNPCC inherit a mutation in one allele of the gene: and mutation
of the second allele occurs during adult life. When two dysfunctional copies are
present, malignancies develop readily.
- Two-thirds of colon cancers in those with HNPCC occur in the right side of the
colon, whereas in the general population colon cancer occurs more frequently on
the left side of the colon.
-genetic basis = mutations of DNA mismatch repair genes: MLH1, MSH2, MSH6
and PMS2; Germline mutations in MLH1 and MSH2 account for 90% of Lynch
syndrome, while mutations in MSH6 and
PMS2 are responsible for approximately 10%.
- There are two types of Lynch syndrome. Lynch I is characterized by a family
predisposition to colon adenocarcinoma. Lynch syndrome type II causes
predisposition to colon cancer (with features common to Lynch I) and increased
incidence of extraintestinal cancers. Endometrial and ovarian carcinoma, cancers
of the stomach, pancreas, and urothelial tract (among many others) may occur.

Amyotrophic lateral sclerosis (ALS) = Lou Gehrig's disease

= the most common motor neuron disease. Combined upper motor neuron
(UMN) and lower motor neuron (LMN) lesions are characteristic: damage to
motor neurons of the anterior horns (LMN lesion) and demyelination of the
corticospinal tracts (UNM lesion) are present. The result is denervation atrophy
of the muscles (amyotrophy).
-The disease manifests in middle-aged people and has a progressive course.
Most patients die within 5 years of diagnosis. Respiratory complications (such as
aspiration pneumonia) are the most common cause of death.
- Symptoms of lower motor neuron degeneration include muscle weakness and
atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under
the skin (fasciculations).
- Symptoms of upper motor neuron involvement include tight and stiff muscles
(spasticity) and exaggerated reflexes (hyperreflexia) including an overactive gag
reflex
- About 5 to 10 percent of all ALS cases are inherited; About 20 % of all familial
cases result from a specific genetic defect that leads to mutation of the enzyme
superoxide dismutase 1 (SOD1).
- Riluzole is believed to reduce damage to motor neurons by decreasing the
release of glutamate. Clinical trials with ALS patients showed that riluzole
prolongs survival by several months, mainly in those with difficulty swallowing.
Vitamin B12 deficiency
- Vitamin B12 is important in DNA synthesis; therefore hematological
manifestations of B12 deficiency are megaloblastic anemia and pancytopenia.
-Vitamin B12 (deoxyadenosyl cobalamin) also serves as a cofactor for
methylmalonyl CoA mutase. (This enzyme catalyzes the conversion of
methylmalonyl CoA into succinyl CoA. Succinyl CoA is the final product of fatty
acid oxidation that enters citric acid cycle. Deficiency of B12 leads to an
accumulation of methylmalonic acid)
-Elevated levels of methylmalonic acid result in myelin synthesis abnormalities.
- Neurological damage associated with B12 deficiency includes subacute,
combined degeneration of the posterior and lateral spinal columns. Axonal
degeneration of peripheral nerves is also seen. Loss of position and vibration
sensation, ataxia, and spastic paresis result. Increased serum levels of
methylmalonic acid are diagnostic of vitamin B12 deficiency.
http://products.mercola.com/Images...in-b12-spray/chart-b12.JPG

Transketolase
= an enzyme of the hexose monophosphate pathway. It utilizes thiamine
(vitamin B1) as a coenzyme. Levels of RBC transketolase are decreased in
thiamine deficiency; they increase after thiamin supplementation.
http://pubs.niaaa.nih.gov/publicat...rh27-2/IMAGES/Page137b.gif

Diabetes mononeuropathy
- DM causes a number of complications, with neuropathy being very common.
Diabetics most commonly have (symmetric) peripheral neuropathy
mononeuropathy and autonomic neuropathy. Mononeuropathies are divided into
cranial and somatic—among cranial nerves CN III is affected the most often.
-In diabetes oculomotor nerve (CN III) neuropathy is ischemic. Somatic and
parasympathetic fibers of CN IIIhave separate blood supplies. For this reason,
diabetic CN III neuropathy affects only somatic fibers leaving parasympathetic
fibers intact. Symptoms are ptosis and a “down and out” gaze.
Accommodation and the pupil’s response to light remain intact. (Alternatively
if nerve compression causes CN Ill neuropathy both somatic and
parasympathetic fibers will be affected. Patients will have ptosis a “down and
out” gaze a fixed, dilated pupil and no accommodation reflex.)
-CNIII (oculomotor nerve) has the following functions:
1. Its somatic component innervates the inferior superior, and medial rectus
interior oblique and levator palpebrae muscles. Ptosis occurs due to paralysis of
the levator palpebrae; whereas the unopposed action of the lateral rectus (CN
VI) and superior oblique (CN IV) muscles lead to a “down and out” gaze.
2. Parasympathetic fibers of CN III innervate the sphincter of the iris and the
ciliary muscle. Paralysis of parasympathetic fibers causes a fixed dilated pupil
and loss of accommodation
DIFF:
- CN III neuropathy due to nerve compression: Causes include transtentorial
(uncal) herniation or aneurysm of the posterior communicating artery. Both
somatic and parasympathetic fibers of CN III are equally affected in this
condition.
http://ww2.lafayette.edu/~dearworj...ages/humanCranialNerve.jpg

Pulmonary hypertension
-Primary pulmonary hypertension is often familial, inherited as an autosomal
dominant trait.
The following mechanisms can lead to the development of pulmonary
hypertension:
1. Any pulmonary disease that causes hypoxemia can cause pulmonary
hypertension. Hypoxemia induces a number of changes in the endothelium of the
pulmonary artery that lead to increased vascular resistance. COPD is the most
common cause of this hypoxic vasoconstriction of the pulmonary artery.
2. Any decompensated cardiac disorder produces volume overload. An increased
volume of blood in the left atrium causes a compensatory increase in pulmonary
artery pressure. Disorders of the left ventricle (MI) valvular heart disease, and
CHF can produce pulmonary artery hypertension.
3. Idiopathic dysfunction of the endothelium causes primary pulmonary
hypertension (PPH). Increased thickness of the vascular wall (due to impaired
apoptosis) and decreased production of prostacyclin and NO are considered the
main pathogenetic factors of this disease.
-Pulmonary hypertension leads to right ventricular hypertrophy. Because the
compensatory capability of the right ventricular wall is low, right ventricular
failure (cor pulmonale) develops, producing dyspnea on exertion, chest pain and
distended neck veins. Increased pulmonary artery pressure causes an
accentuated pulmonary component of the second heart sound (P2) as well as
paradoxical splitting of S2. Additional physical examination findings may include
a holosystolic tricuspid insufficiency murmur that is accentuated with inspiration,
hepatomegaly, and peripheral edema.

Gallstone ileus
= rare type of mechanical bowel obstruction caused when a large gallstone
(usually greater than 2.5 cm in diameter) erodes into the intestinal lumen
through a cholecystenteric fistula. As the gallstone travels down the intestinal
passage, it intermittently obstructs the lumen, causing waxing and waning of
symptoms. Eventually, the gallstone may come to rest in the ileum, which has
the smallest lumen of the intestinal tract.
-Most patients with gallstone ileus are female and over 70 years old. The classic
clinical presentation includes crampy abdominal pain, vomiting, and abdominal
distention.
-Abdominal radiographs tend to demonstrate an intestinal gas pattern that is
consistent with intestinal obstruction, and pneumobilia (air in the biliary tree) is
evident in roughly half of these patients.
-Ultrasound is used to confirm cholelithiasis and can occasionally identify the
fistula.
-Removing the stone can be accomplished through a small enterotomy, with
bowel resection typically unnecessary.
http://nypemergency.org/radiology/...h:+Radiology&type1=2Select

Left pleural effusion

= suggestive of a wide range of conditions, with pancreatitis and esophageal
rupture two of the more likely gastrointestinal causes in the differential.

Curling ulcers
=Ulcers arising in the proximal duodenum in association with severe trauma or
burns
- Events that trigger such stress include shock, extensive burns, sepsis, severe
trauma, and intracranial injury or surgery.
- Ulcers arising in the esophagus, stomach, or duodenum in patients with high
intracranial pressure are particularly prone to perforation and are called Cushing
ulcers. Cushing ulcers are likely induced by direct stimulation of the vagus nerve
by increased intracranial pressure, thereby resulting in hypersecretion of gastric
acid. Once the causative stressors are resolved, healing with full re-epithelization
of the gastric mucosa occurs within days to weeks.

Chronic antral-predominant gastritis

= suggestive of Helicobacter pylori infection. This form of gastritis is associated
with increased acid production and an elevated risk of duodenal ulcer formation.

Granulomatous gastritis
= idiopathic, benign condition characterized by intramucosal epithelioid
granulomas that cause narrowing of the antrum secondary to transmural
inflammation.
http://www.geocities.com/drroy2005/gragas3.JPG

Gastric adenocarcinoma
- occurs in two forms: the intestinal and diffuse sub-types, with the former
arising from precursor lesions.
-The intestinal sub-type is characterized by intestinal glands that are similar in
appearance to those of colonic adenocarcinoma.
-The diffuse sub-type is classically characterized by signet-ring cells.
-Chronic gastritis, Barrett esophagus, Helicobacter pylori infection, frequent
nitrate consumption, diet lacking in fresh fruit and vegetables, and cigarette
smoking are some of the risk factors for developing this neoplasm.
http://www.microscopyu.com/galleri...arcinomaofstomach20x03.jpg

Lymphadenopathy
- can represent inflammatory changes within the lymph node (reactive
hyperplasia) or malignant transformation.
- Reactive hyperplasia is a broad term that encompasses all benign, reversible
enlargement of the lymphoid tissue secondary to antigenic stimulus. The nodal
response to antigenic stimuli is highly variable and can be classified as follicular
hyperplasia, sinus hyperplasia, or diffuse hyperplasia. Follicular hyperplasia
occurs when the follicles increase in size and number, whereas sinus hyperplasia
occurs when the sinuses enlarge and fill with histiocytes. Diffuse hyperplasia is
observed when the nodal architecture is diffusely effaced by sheets of
lymphocytes, immunoblasts, and macrophages.
-When malignant transformation occurs (as in lymphomas), the normal lymph
node architecture is distorted or effaced by the proliferation of malignant
lymphoid cells. This effacement of nodal architecture may be follicular or diffuse.
-Reactive lymphoid hyperplasia is polyclonal in that it consists of a proliferation
of many different cell types within the lymph node. Malignant transformation in
contrast, is monoclonal in that it results from the proliferation of one cell line.
-Evaluation for monoclonality of the lymphocyte population is important when
lymphoma is suspected. The clonality of a T cell population is assessed by
molecular methods that examine the rearrangement of T-cell receptor (TCR)
genes. If a single allele for the V region of the T-cell receptor predominates in a
lymphocytic population, monoclonal proliferation is suspected. The same
principle applies when assessing B-cell clonality. Clonal rearrangement of the
genes for immunoglobulin heavy chains is suggestive of a B cell lymphoma.
http://medsci.indiana.edu/c602web/602/C602web/lymphnd/slide84.htm
Hepatic abscess
=The presence of a fluid-filled cavity in the liver in conjunction with fevers, chills,
and right upper abdominal pain
- In developed countries, hepatic abscesses are relatively uncommon and are
usually secondary to bacterial infection. The bacterial organisms responsible for
hepatic abscess typically reach the liver through one of five routes: portal vein,
arterial supply, ascending biliary tract infection, direct invasion from an adjacent
source, or a penetrating injury.
- Staphylococcus aureus can cause hepatic abscess through hematogenous
seeding of the liver. Enteric bacteria can cause hepatic abscess by ascending the
biliary tract or directly invading from an adjacent area.
-In contrast, developing countries have a relatively high incidence of hepatic
abscesses secondary to parasitic infections (eq, amebic or echinococcal).
http://www.nzma.org.nz/journal/119-1231/1906/content01.jpg

Porcelain gallbladder
= a term used to describe the bluish, brittle, calcium-laden gallbladder wall that
can develop in some patients with chronic cholecystitis.
-The porcelain gallbladder is typically diagnosed on radiograph, sometimes
incidentally, by a rim of calcium deposits that outline the gallbladder. The
pathogenesis of the condition remains unclear, but it is thought that calcium
salts are deposited intramurally secondary to either chronic irritation from
gallstones or as a component of the natural progression of chronic inflammation.
-Although patients are often asymptomatic, some may present with right upper
quadrant pain or with a firm, nontender mass in the right upper quadrant.
Cholecystectomy is recommended for those with porcelain gallbladders because
11-33% of this patient population will eventually develop gallbladder carcinoma.
http://lh6.ggpht.com/_dcyYRih3ez8/...njuRS9Ar0/Porcelain+GB.jpg

Bronchioloalveolar carcinoma
=a subtype of lung adenocarcinoma (sometimes regarded as a separate entity).
-is uncommon, representing less than 10% of all lung cancers. The tumor arises
from the alveolar epithelium and is located at the periphery of the lung. On
microscopic examination, the tumor is usually well-differentiated, composed of
tall columnar cells that line the alveolar septa without evidence of vascular or
stromal invasion. Imaging shows a pneumonia-like consolidation.
http://www.brown.edu/Courses/Digit...nary/badenocarcinoma1.html

Pulmonary Hamartomas (=pulmonary chondroma)

= the most common benign lung tumors. Hamartomas are usually asymptomatic
and detected incidentally on chest x-ray as a peripheral “coin lesion" with
“popcorn calcifications.” Histological examination reveals areas of mature
hyaline cartilage mixed with connective tissue, smooth muscle and fat.
http://library.med.utah.edu/WebPath/LUNGHTML/LUNG076.html
Kidney stones
- Idiopathic hypercalciuria is the most common cause of calcium kidney stone
disease. This condition is characterized by normal serum calcium levels with high
levels of calcium excreted in the urine. Other causes of calcium nephrolithiasis
include hyperoxaluria, hyperuricosuria, low urinary volume, and hypocitraturia.
- Hyperoxaluria can result from a diet high in oxalate (found in foods like
chocolate, nuts, and spinach). Low calcium diets can also cause hyperoxaluria,
because when there is less calcium available to bind oxalate in the gut, there is
more oxalate available for absorption and subsequent renal excretion. This
situation also occurs in Crohn’s disease and other syndromes of intestinal
malabsorption.
- Hyperuricemia and hyperuricosuria typically affect patients with
myeloproliferative disorders or who are undergoing chemotherapy for
malignancies (tumor lysis syndrome). Gout, Lesch-Nyhan syndrome, high purine
diets and high alcohol intake can also be associated with increases in serum uric
acid concentration. Hyperuricosuria stimulates calcium oxalate stone formation.
Uric acid stones can be formed as well.

Wegener granulomatosis
= “necrotizing granulomatous vasculitis” with a characteristic triad of
findings.
1. Pulmonary symptoms, such as cough and/or hemoptysis, are caused by focal
necrotizing granulomas in the lungs. These granulomas sometimes coalesce into
nodules or undergo cavitation.
2. Involvement of the upper respiratory tract (ear, nose, sinuses throat).
Symptoms of chronic sinusitis and mucosal ulceration of the nasopharynx result
from the development of mucosal granulomas that later ulcerate.
3. Renal disease is most often in the form of rapidly progressive (crescentic)
glomerulonephritis (RPGN).
-The RPGN that is associated with Wegener granulomatosis is classified as type
3, or pauci-immune. A high serum level of c-ANCA is diagnostic, and there are
specific microscopic findings. Although crescent formation is obvious on light
microscopy, there are no immunoglobulins or complement deposits found by
immunofluorescent studies as in other types of RPGN such as RPGN type 1 (anti-
GBM disease or Goodpasture syndrome) and RPGN type 2 (immune complex-
mediated disease).
http://www.ndt-educational.org/ferrarioanca.asp
http://www.pathguy.com/sol/24847.jpg
Scurvy
- In the United States, vitamin C deficiency (scurvy) is most often seen in
severely malnourished individuals (the homeless, alcoholics, drug users). Vitamin
C is necessary for the hydroxylation of the proline and lysine residues of pro-
collagen. This reaction is executed by prolyl and lysyl hydroxylases, with vitamin
C serving as a reducing agent. Hydroxyproline and hydroxylysine are essential
for cross-linking collagen molecules. In scurvy, collagen cross- linking is
compromised, thus greatly reducing its strength.
-The symptoms of vitamin C deficiency are the result of decreased connective
tissue strength. The capillary walls are especially fragile, causing easy bruising
and a propensity to bleed. Perifollicular petechial hemorrhages and ecchymoses
of the skin and mucosa also occur. These patients also suffer gum disease (gum
swelling, loosening of the teeth and periodontal infection) and poor wound
healing.
-Vitamin C deficiency is even more severe in children. Here, hemorrhages may
cause subperiosteal and joint hematomas.
DIFF:
- Thiamine (vitamin B1) serves as a coenzyme in decarboxylation reactions. It is
necessary for the conversions of pyruvate to acetyl CoA and of alpha-
ketoglutarate to succinyl CoA in the citric acid cycle. Vitamin B1 deficiency can
cause peripheral neuropathy (dry beriberi) and high-output heart failure (wet
beriberi).
-Vitamin B6 (pyridoxine) serves as a cofactor in many reactions that involve
amino acids (such as transamination, decarboxylation and deamination).
Pyridoxine deficiency manifests with seborrheic dermatitis, glossitis, and
peripheral neuropathy.
-Vitamin B12 is necessary for the synthesis of methionine as well as for the
synthesis of succinyl CoA from methylmalonyl CoA. Deficiency of vitamin B12
causes megaloblastic anemia and subacute combined degeneration of spinal
cord.

Bladder carcinomas
- arise from the transitional epithelium lining the bladder. In most cases, the
neoplastic cells resemble those of normal bladder epithelium. These tumors are
called urothelial (or transitional cell) carcinomas. Urothelial carcinomas compose
90% of malignant bladder neoplasms. Squamous cell carcinomas and
adenocarcinomas of the bladder are rare.
-The classic presentation of bladder carcinoma is painless gross hematuria. The
tumor most often grows as a papillary or sessile mass and is easily diagnosed on
cystoscopy. Less often, the growth pattern may be flat or nodular. Staging of
this type of tumor depends on the degree of its invasion into the bladder wall
and adjacent tissues. Carcinoma in situ is confined to the epithelium, whereas
tumor penetration through the mucosa and into the lamina propria and deeper
layers signifies invasiveness. The tumor stage is the most important factor
determining prognosis.
- The size of the bladder carcinoma is not reflected in its stage. A bigger tumor
confined to the epithelium has a better prognosis than a smaller tumor that
involves deeper layers of the bladder wall.
http://atlasgeneticsoncology.org/Tumors/blad5001.html

Adult respiratory distress syndrome (ARDS)

-sepsis is a major risk factor.
-One of the minor diagnostic criteria for ARDS is absence of cardiogenic
pulmonary edema which means that the pulmonary capillary wedge pressure is
usually normal. An elevated wedge pressure would be more suggestive of a
cardiogenic (hemodynamic) cause of pulmonary edema, such as pulmonary
venous hypertension.
-ARDS is characterized by diffuse injury to the pulmonary microvascular
endothelium and/or alveolar epithelium, resulting in increased pulmonary
capillary permeability and a leaky alveolocapillary membrane. The interstitial and
intra-alveolar edema, inflammation, and hyaline membrane formation cause lung
compliance to decrease, the work of breathing to increase, and the oxygen
diffusion capacity of the lung to decrease. More severe involvement and/or
atelectasis of regional alveoli can cause V/Q mismatch (decreased ventilation
with maintained perfusion).

Age-related changes
-Accommodation (near reflex)= a change in the optical power of the eye in order
to maintain an image focused on the retina. When the eye focuses on a near
object, for example while reading, contraction of the ciliary muscle causes
relaxation of the zonular fibers allowing the lens to relax and assume a more
convex shape. When looking at the distant object, the ciliary muscle relaxes and
the lens flattens due to outward radial tension exerted by zonular fibers.
-With age the stroma of the lens undergoes sclerosis leading to decreased lens
elasticity. This factor, along with changes in lens curvature and diminished
strength of the ciliary muscle leads to presbyopia (inability of lens to focus on
near objects). It is not a pathologic process; it is an age-related condition that
occurs in most people beginning at approximately 40-50 years of age.
-Presbyopia manifests with difficulty reading fine print, eye stain after reading,
and the need to hold objects further from the eye in order to see them clearly. In
myopic (near-sighted) individuals, however, age-related presbyopia may lead to
improvement in distant vision
-skin rhytids (wrinkles) are clearly age-related ,both chronological aging and
photoaging resulting from the harmful effects of UV light contribute to their
development. Morphologically, aging skin is characterized by a decreased
number of fibroblasts, decreased collagen and elastin synthesis, increased
collagen and elastin breakdown, and abnormal organization of collagen and
elastin fibers.
http://www.nei.nih.gov/healthyeyes/eye_images/Presbyopia.gif

Tabes dorsalis
=a form of neurosyphilis that involves the dorsal columns and dorsal roots of the
spinal cord. Although syphilis is not common in the United States any more, this
infection may still be found in immigrants and in HI V-positive patients.
-The pathophysiology of tabes dorsalis :
1. Involvement of the dorsal column causes loss of positional and vibratory
sensation. Patients display ataxia and a wide-based gait. Affected patients may
compensate for poor balance with visual clues, but cannot maintain balance with
their eyes closed (positive Romberg sign).
2. Involvement of the dorsal sensory roots leads to the loss of pain sensation
and areflexia.
3. Argyll Robertson pupil occurs due to the involvement of periaqueductal gray
matter of the midbrain. The pupil fails to constrict in response to light but
constricts normally in response to accommodation. Older texts may refer to this
phenomenon (albeit pejoratively) as “whore’s pupils” because both
Argyll Robertson pupils and sex-workers can be said to accommodate, but not
react.

Progressive multifocal leukoencephalopathy (PML).

= Infection with JC virus (polyomavirus)
- This infection usually occurs in severely immunocompromised patients, such as
those who suffer from AIDS, lymphoma, or leukemia. PML causes progressive
dementia and various neurologic deficits.
http://pathmicro.med.sc.edu/mhunt/pml2.jpg
http://pathmicro.med.sc.edu/mhunt/pml.jpg

Cherry hemangiomas
=small, vascular, bright-red papular lesions
= the most common benign vascular tumors in adults. Cherry hemangiomas
appear during the third or forth decade of life. They do not regress
spontaneously, and their number often increases with age which is why they are
also referred to as senile hemangiomas. Cherry hemangiomas, also referred to
as cherry angiomas, are always cutaneous and are not found on the mucosa or
deep tissues. Histologically they appear as sharply circumscribed areas of
congested capillaries and post-capillary venules in the papillary dermis
http://medsapiens.com/wp-content/u...ell-de-morgan-angiomas.jpg
DIFF:
-Strawberry (infantile) hemangiomas appear during the first weeks of life,
initially grow rapidly, and then frequently regress spontaneously by 5-8 years of
age. They are bright red when near the epidermis and more violaceous when
deeper
http://www.skinsight.com/images/dx...ileHemangioma_3670_med.jpg
- Spider angiomas consist of a bright red central papule surrounded by several
outwardly radiating vessels. They occur due to dilatation of a central arteriole
and its superficial capillary network and are estrogen- dependent.
- Cavernous hemangiomas consist of dilated vascular spaces with thin-walled
endothelial cells. They present as soft blue compressible masses up to a few
centimeters in size. They may appear on the skin mucosa, deep tissues and
viscera; when they appear on the skin they are most frequently based in the
dermis. They are less likely to regress spontaneously than capillary
hemangiomas. Cavernous hemangiomas of the brain and viscera are associated
with von Hippel-Lindau disease.

Alcoholic pancreatitis
= epigastric calcifications and history of alcoholism
- Although the pathophysiologic mechanism is not well-defined, it is thought that
alcohol-related chronic pancreatitis may develop secondary to alcohol-induced
protein precipitation within the pancreatic ducts. These proteins form ductal
plugs which may calcify, forming calculi consisting in part of calcium carbonate.
Ductal obstruction by such concretions may cause exocrine insufficiency due to
atrophy of the pancreatic acinar cells and pancreatic fibrosis.
-Pancreatic exocrine insufficiency (failure to secrete adequate amylases,
proteases and lipases) leads to malabsorption with consequent
diarrhea/steatorrhea. Weight loss and bulky, frothy stools are typical clinical
findings.
http://www.pathology.vcu.edu/education/gi/images/2.1a.b.jpg

Short bowel syndrome

= can result from extensive surgical small bowel resection. The decreased small
intestinal surface area available for absorption causes impaired reabsorption of
fluid and electrolytes. The excessive delivery of intestinal fluid and osmotically
active solutes to the colon can produce diarrhea.
http://www.scielo.br/img/fbpe/rhc/v54n1/a07f01.gif

Primary biliary cirrhosis (PBC)

= chronic liver disease characterized by autoimmune destruction of the
intrahepatic bile ducts and cholestasis. The condition presents most commonly in
middle-aged women and is insidious in onset. Pruritus is usually the first
symptom and may be very severe especially at night. Fatigue is also often
reported. Physical findings typically include hepatosplenomegaly and evidence of
cholestasis (eg, xanthelasma, pale stool). As the disease progresses jaundice,
steatorrhea, portal hypertension, and osteopenia may develop.
-Histologic findings of PBC include the destruction of interlobular bile ducts by
granulomatous inflammation (“florid duct lesion”) and a heavy portal tract
infiltrate of macrophages, lymphocytes, plasma cells, and eosinophils.
http://granuloma.homestead.com/biliary_cirrhosis4_S91-11804.jpg

Crohn’s disease
- Normally, the mucosa of the terminal ileum plays an important role in
“recycling” bile acids that are necessary for the absorption of fat. Bile acids
are produced in the liver, excreted with bile, and then reach the terminal ileum.
There they form micelles with fat droplets, are reabsorbed, and return to the
liver to start a new cycle. When the mucosa of terminal ileum is inflamed (as in
Crohn’s disease), bile acids are not reabsorbed, becoming lost with feces. As
a result, a lesser amount of bile acid is present in bile, and the ratio of
cholesterol/bile acids increases. Cholesterol precipitates in bile of the gallbladder
and forms gallstones.

Wilson’s disease
= an autosomal recessive disorder characterized by toxic accumulation of copper
within organ tissues (especially the liver, brain, and eye).
-Normally, approximately 60% of ingested copper (0.6-3.0 mg/day) is absorbed
in the stomach and duodenum, loosely bound to circulating albumin and then
transported to the liver. Within the liver, copper is incorporated into an α2-
globulin to form ceruloplasmin. The ceruloplasmin is then resecreted into
plasma, where it accounts for 90-95% of circulating copper. Normal total body
copper is estimated at 50-150 mg.
-Senescent ceruloplasmin and the remainder of ingested, unabsorbed copper are
secreted into bile and excreted in stool, which is the primary route for copper
elimination. Renal losses represent only 5-15% of daily copper excretion.
http://www.kellogg.umich.edu/theey...nital/wilsons-disease.html

Varicose veins
= dilated superficial veins
= associated skin changes consistent with stasis dermatitis. Normally, venous
blood flows from superficial veins through perforating veins into the deep veins
of the extremities. Blood from the deep veins travels upward and eventually
drains into the inferior vena cava. Valves are located in the superficial
perforating and deep veins to prevent backward flow from deep to superficial
veins. When these valves are incompetent, retrograde flow into the superficial
veins occurs. Increased pressure in the superficial veins causes them to dilate
and normal venous out flow from the tissues becomes restricted.
-Incompetence of venous valves is the main mechanism for development of
varicose veins. It may occur after deep venous thrombosis (DVT), in pregnancy,
or by genetic predisposition.
http://wirawanady.files.wordpress.com/2007/11/varicose.jpg

Acute dissecting aortic aneurysm

- Such dissections are likely initiated by an intimal tear.
-The origins of these tears are usually 10 cm or less downstream from the aortic
valve (type A dissection). The tears are usually oblique or transverse and about
1 to 5 cm in length. The dissection can extend through the media both
proximally and distally. It is not unheard of for a tear to extend all of the way to
the iliac and femoral arteries.
-Major arterial branches from the aorta can be compressed by the dissecting
intramural hematoma. This arterial branch blockade accounts for the differing
blood pressures in the right versus the left arm of this patient. The reduced
right-arm blood pressure suggests compromise of the proximal brachiocephalic
trunk.
- Severe retrosternal pain radiating to the mid—upper back is characteristic of
an aortic dissection. Back pain may indicate extension of a type A dissection into
the descending thoracic aorta, or a type B dissection. The level of back pain may
descend as the dissection progresses distally. Hypertension often primarily
promotes aortic dissections.
http://heart.chungbuk.ac.kr/slide/lecimage/aortic_ds_ytjin_02.gif
http://www.health-res.com/EX/07-28...rtic%2520dissection_lg.gif
http://home.earthlink.net/~radiologist/tf/060302.htm

Medial calcification (Monckeberg’s medial calcific sclerosis, medial calcinosis)

= a form of arteriosclerosis characterized by calcific deposits in muscular
arteries. These lesions generally occur in people older than 50 and are not
clinically significant. The etiology of these calcifications is not well understood.
http://www.pathology.vcu.edu/education/cardio/lab1.d.html
Pseudogout (or calcium pyrophosphate deposition disease CPPD)
= results from the accumulation of calcium pyrophosphate crystals in the
synovial fluid. Patients present with an acute mono- or oligoarticular arthritis
characterized by pain joint swelling erythema and warmth. Pseudogout and gout
can be difficult to distinguish clinically. The knee joint is involved in more than
50% of cases of pseudogout, whereas the first metatarsophalangeal joint is more
frequently involved in gout.
-In pseudogout, synovial fluid analysis reveals increased white blood cells with a
neutrophilic predominance. The presence of rhomboid-shaped calcium
pyrophosphate crystals is diagnostic. These crystals are positively birefringent
under polarized light meaning that the color pattern is the opposite of that seen
in gout. Pseudogout crystals are blue when aligned parallel to the slow ray of the
compensator and yellow when aligned perpendicularly.
http://img.medscape.com/pi/emed/ck...logy/336139-388348-510.jpg
http://www.e-radiography.net/radiology/djd/CPPD3.jpg
http://img.medscape.com/pi/emed/ck...ogy/329097-330936-4264.jpg

Calcific tendonitis
- results from the deposition of calcium hydroxyapatite crystals in periarticular
soft tissues (especially tendons). The rotator cuff tendons are most commonly
affected.
http://www.shoulderdoc.co.uk/img/s.../calcific_deposit_xray.jpg

Hepatitis B virus infection

Can produce one of three syndromes:
-acute hepatitis with complete resolution
-chronic hepatitis (with or without cirrhosis and the attendant increased risk of
hepatocellular carcinoma);
-or fulminant hepatitis with massive liver necrosis. By far the most common
outcome in HBV-infected adults (>95%) is acute hepatitis with mild or subclinical
symptoms that eventually completely resolve.
Fulminant hepatitis occurs in< 1% of patients who develop acute hepatitis.
Only 4-5% of patients with hepatitis B virus infection will go onto develop chronic
hepatitis. Of those 50- 80% will remain stable with no evidence of cirrhosis.
Approximately 20-50% of patients with chronic hepatitis B infection will also
eventually develop cirrhosis.
Hepatocellular carcinoma arises in 10% of patients with chronic hepatitis and
cirrhosis.
Iron-deficient individuals
- on replacement therapy should experience hemoglobin level increases of
approximately 2 g/dL per week for the first three weeks. This increase in
hemoglobin results from enhanced erythropoiesis and the accelerated release of
both mature red blood cells and reticulocytes into the blood stream.
-The reticulocyte is an immature RBC that is slightly larger and bluer than a
mature RBC. It lacks a cell nucleus but retains a basophilic, reticular (mesh-like)
network of residual ribosomal RNA. The ribosomal RNA appears blue
microscopically after the application of the Wright-Giemsa stain.
After spending a day or so in the bloodstream, the reticulocytes are transformed
into mature red blood cells that have a lifespan of approximately 120 days.
http://www.healthsystem.virginia.e...tic-cells/Reticulocyte.cfm

Traumatic hemolysis
= Red blood cell fragments, burr cells and helmet cells
=can result from either microangiopathic hemolytic anemia or mechanical
damage (e.g. prosthetic valve).
-Prosthetic valves produce excessive shear and turbulence in the cardiac
circulation, causing mechanical trauma to the RBCs.
-Burr cells are erythrocytes with short, evenly-spaced projections. They can
occur as an artifact or in association with uremia, pyruvate kinase deficiency,
microangiopathic hemolytic anemia, or mechanical damage.
http://www.brown.edu/Courses/Digit...emic_path/heme/helmet.html

Viral meningitis
-The typical “viral pattern” of CSF includes lymphocytic pleocytosis, normal
glucose, and elevated protein. A few RBCs may also be present in the CSF due to
hemorrhagic destruction of the temporal lobes.
http://www.healthhype.com/wp-conte...ges/ViralMeningitis450.jpg

Atheroembolic renal disease

=A patient with signs of renal failure and toe gangrene or livedo reticularis
following an invasive vascular procedure
- Light microscopy shows cholesterol emboli obstructing renal arterioles.
-During the procedure, cholesterol-containing debris gets pushed from larger
arteries and lodges in smaller vessels, causing ischemia of the corresponding
organs and tissues. The kidneys are frequently involved. Oliguria, azotemia and
other features of renal failure develop a few days to weeks after the procedure.
There may also be evidence of extra-renal embolization, including livedo
reticularis, cholesterol emboli on retinal examination, and skin infarcts.
-Renal biopsy shows needle-shaped cholesterol crystals that partially or
completely obstruct renal arterioles.
-Most of the patients that sustain atherosclerotic damage to the renal arteries
are elderly, with multiple atherosclerosis-related comorbidities. Many never
recover normal renal function.
http://renalfellow.blogspot.com/20...embolic-renal-disease.html

ADPKD (autosomal dominant polycystic kidney disease)

- The classic presentation is a patient in his 40s or 50s with a family history of
renal disease who presents with flank pain, hematuria and hypertension.
= Cystic dilatation of the collecting ducts
http://library.med.utah.edu/WebPath/RENAHTML/RENAL049.html

Inflammatory bowel disease

= appears to be inherited as a complex, multi genic disorder rather than in the
standard Mendelian manner. Candidate genes include HLA associations (eg, HLA-
DR1//DQw5 in Crohn’s disease or HLA-DR2 in ulcerative colitis) and a gene
termed NOD2 which stands for nucleotide-binding oligomerization domain.
-Expressed in both epithelial cells and leukocytes, the NOD2 protein appears to
act as an intracellular microbial receptor that triggers the NF-KB pathway. NF-KB
is a transcription factor responsible for cytokine production in the immune
response to infectious pathogens. It has been proposed that the NOD2 mutation
linked with Crohn’s disease reduces the activity of the NF-KB protein thereby
allowing the inflammation-inducing intracellular microbes to persist.

Sarcoidosis
= inflammatory disease of unknown etiology that leads to development of non-
caseating granulomas in many organs and tissues. In sarcoidosis, noncaseating
granulomas consist of aggregates of epithelioid cells (activated macrophages)
and multinucleated giant cells consistent with chronic granulomatous
inflammation.
-The typical patient with sarcoidosis is a young black woman with non-specific
complaints of fever malaise and weight loss. Lung involvement is present in the
majority of patients, and manifests clinically with cough, dyspnea and chest pain.
Skin involvement is varied in presentation ranging from macules to plaques to
erythema nodosum (painful shin nodules).
-Chest X-ray is essential for diagnosis. In stage I of sarcoidosis, it classically
reveals bilateral hilar lymphadenopathy. Stage II is characterized by bilateral
hilar lymphadenopathy along with pulmonary infiltrates commonly in the upper
lobes. Progression of the disease leads to disappearance of hilar
lymphadenopathy, and the chest X-ray in stage Ill disease shows lung infiltrates
only, while stage IV is characterized by lung fibrosis.
http://radiopaedia.org/cases/sarcoidosis-2
http://www.brown.edu/Courses/Digit...ath/lymph/sarcoidosis.html

Dermatomyositis
= autoimmune disorder that presents with proximal muscle weakness and skin
involvement including a violaceous discoloration of the upper eyelids (heliotrope
rash), and a raised, violaceous, scaling eruption on the knuckles (Gottron’s
sign). CPK levels are typically elevated.
http://www.pathguy.com/sol/14338.jpg
http://dermatology.cdlib.org/1502/reviews/photoessay/16.jpg

Gallstones
= cholesterol stones, pigment stones, or mixed stones.
- Pigment stones are most common in rural Asian populations (accounting for
only 10-25% of gallstones in the United States), with an increased incidence in
women and the elderly.
-Brown pigment stones typically arise secondary to infection of the biliary tract,
which results in the release of β- glucuronidase by injured hepatocytes and
bacteria. The presence of this enzyme contributes to the hydrolysis of bilirubin
glucuronides and increases the amount of unconjugated bilirubin in bile.
Therefore, biliary infection with Escherichia coil, Ascaris lumbricoides, or the liver
fluke Opisthorchis sinensis significantly elevates the risk of developing brown
pigment stones.
-Grossly, brown pigment stones are soft laminated, and greasy. Because these
stones contain large amounts of calcium soaps, cholesterol, and mucin
glycoprotein, they are radiolucent and do not appear on x-ray.
http://members.fortunecity.com/dan...d/gallbladder/07bb0440.gif
http://millenniumdogs.net/vermi/diplostomatidae/sinensis.jpg
Retinoblastoma
=the most common ocular tumor of childhood. It usually presents with a white
pupillary reflex (leukocoria) in children less than 5 years old. About 6O% of
retinoblastomas are sporadic (usually unilateral), while 4O% are familial
(bilateral).
- Children with sporadic retinoblastoma are not at risk for other malignancies,
while patients with familial retinoblastoma often develop other tumors usually
sarcomas, later in life. Among these secondary malignancies osteosarcoma
occurs most often.
-Familial retinoblastoma occurs due to a germline mutation that affects the Rb
tumor suppressor gene on chromosome 13. All cells in the body of an affected
individual carry this mutation. As there are two alleles of Rb gene (one from each
parent), the malignancy does not occur while the second allele is functional. A
somatic (occurs in the retinal cells only) second mutation acquired early in life is
the “second hit” that leads to malignancy. The cell with two inactivated Rb
genes becomes the source of the malignant tumor. Sporadic retinoblastomas
occur due to two acquired somatic mutations that affect retinal cells only.
The Rb gene is a tumor suppressor; the corresponding protein exists in an active
and inactive state. The active (dephosphorylated) Rb protein does not allow the
cell to proceed from G1 to the S stage of the cell cycle. When the cell is
stimulated by a growth factor the Rb protein is phosphorylated and converted
into the inactive state. Inactivation of the Rb protein permits cell division. Cells
with two inactive Rb genes divide uncontrollably and give rise to malignancy.
http://www.mun.ca/biology/desmid/b...L2060/BIOL2060-19/1938.jpg
http://219.221.200.61/ywwy/zbsw(E)/pic/ech12-21.jpg
http://www.ukoptometry.co.uk/wp-co...ploads/retinoblastoma2.jpg

Hypertrophic cardiomyopathy (HCM)

- The autopsy finding of asymmetric hypertrophy of the interventricular septum
confirms the diagnosis. Most cases of HCM are familial. The transmission is
autosomal dominant with variable expression.
- Almost all cases of HCM are thought to be due to mutations in cardiac
sarcomere proteins. Specifically, these are predominantly single point missense
mutations in the genes for beta-myosin heavy chain [MHC] (35-50%), myosin-
binding protein C (15-25%), cardiac troponin T (15-20%), or tropomyosin
(<5%). These mutations cause myofibril and myocyte structural abnormalities
and possible deficiencies in force generation.
http://pawpeds.com/pawacademy/health/mybpc3/figure1.jpg

Dilated cardiomyopathy
- Approximately 1/3 of case are genetic. The majority of these cases are due to
autosomal dominant mutations of cardiac myocyte cytoskeletal proteins
(dystrophin) or mitochondrial enzymes.
http://jennyndesign.com/DMD/physiology5.html

Tetralogy of Fallot
=recurrent cyanotic spells that he counteracts by squatting.
- TOF accounts for approximately 10% of congenital heart disease and is the
most common cyanotic heart disease seen in children after infancy. It is
characterized by pulmonic stenosis, a ventricular septal defect (VSD), right
ventricular hypertrophy (RVH), and an overriding aorta (which straddles the
VSD).
- The major physiological problem in cyanotic TOF is stenosis of the pulmonary
out flow tract due to asymmetric division of the embryonic truncus arteriosus.
The result is right-to-left intracardiac shunting.
-Cyanotic spells occur when there are episodic decreases in lung blood flow due
to increased right-to-left shunting. Squatting increases total systemic vascular
resistance (SVR) thereby raising mean arterial pressure. If the ductus arteriosus
is patent, this increases pulmonary blood flow via the ductus (compensatory left-
to-right shunt). Any decrease in the ratio of total pulmonary vascular resistance
to SVR decreases right-to-left shunting.
http://www.mfi.ku.dk/ppaulev/chapter12/images/12-7.jpg

Dermatomyositis
=autoimmune disorder that combines inflammatory myopathy and cutaneous
involvement.
-Cutaneous manifestations of dermatomyositis include Gottron papules and a
heliotrope rash.
- Gottron papules= red or violaceous flat-topped papules with a light scale that
appear over bony prominences. Their most common locations are
metacarpophalangeal, proximal and distal interphalangeal joints.
-The heliotrope rash presents as an erythematous or violaceous edematous
eruption on the upper eyelids and periorbital skin. Both Gottron papules and the
heliotrope rash are specific for dermatomyositis.
-The myopathy of dermatomyositis manifests with proximal muscle weakness;
patients have difficulty climbing stairs, rising from the sitting position and
combing their hair. The CK level is characteristically elevated in myositis. Positive
ANA (antinuclear antibodies) is typical for dermatomyositis but nonspecific. Anti-
Jo1 antibodies are specific.
-Patients that develop dermatomyositis after 50 years old have increased risk of
an underlying malignancy as the occult cause.
http://www.nlm.nih.gov/medlineplus...ges/ency/fullsize/2402.jpg
http://dermatology.cdlib.org/1502/reviews/photoessay/2.jpg
Granulosa-theca cell tumors
= comprise approximately 5% of all ovarian tumors, and are primarily identified
in postmenopausal women.
-Derived from the ovarian stroma, these tumors fall under the broad category of
sex cord stromal tumors. Typically granulosa-theca cell tumors are unilateral and
variable in size, with the lipid content (and therefore the hormonal activity)
indicated by the yellow cut surface. Granulosa-theca cell tumors tend to contain
a predominance of granulosa cells and a scattering of theca cells. Because the
granulosa and theca cells secrete estrogen variants, these tumors have a
feminizing effect. If large quantities of estrogen are released, precocious sexual
development can occur in prepubertal girls. Older women may develop
fibrocystic change of the breast, endometrial hyperplasia, or endometrial
carcinoma.
- Rarely granulosa cell tumors will produce androgens and have a masculinizing
effect. This is not typical, however.
-Histologically granulosa cells are small cuboidal cells that grow in cords or
sheets. Small, gland-like structures that contain an acidophilic material may be
present; these are termed Call-Exner bodies, and are suggestive of immature
follicles. Thecoma cells present as clusters or sheets of cuboidal cells. Tumors
that primarily consist of thecoma cells are almost always benign.
http://www.pathology.med.ohio-stat.../Images/10532/PAXIT009.JPG
http://farm3.static.flickr.com/2400/1608008262_2963806ce3.jpg?v=0
DIFF:
- Alpha-fetoprotein is normally produced by the fetal liver and yolk sac, but can
also be used as a tumor marker in patients with hepatocellular carcinoma,
nonseminomatous testicular carcinomas, and ovarian carcinomas.
- Cancer antigen 125 (CA-125) is found in elevated amounts on the surface of
malignant ovarian epithelial cells in serous, endometrioid, and clear cell
carcinomas of the ovary. This glycoprotein is best used in monitoring therapeutic
response. CA-125 is not an appropriate screening tool for ovarian cancer
because it is highly nonspecific.

Ecchymosis
=cutaneous or subcutaneous collection of extravasated blood measuring at least
1 cm in diameter. Frequently ecchymoses arise superficially without a history of
noticeable trauma.
- Purpurae=cutaneous or subcutaneous collections of extravasated blood
measuring approximately 5 mm to 1 cm in diameter.
-Petechiae are cutaneous or subcutaneous collections of extravasated blood
measuring less than 5 mm in diameter (ranging from pinpoint to pinhead size).
Petechiae are asymptomatic, not palpable, and tend to appear in areas of
increased venous pressure, such as the feet and ankles.
- Lentigos are small tan or brown macules most often seen on the sun-exposed
skin of a middle-aged or elderly person (eg, face hands, arms).
- Telangiectasias= small focal permanent dilatations of superficial capillaries and
venules. Telangiectasias are usually found in the skin or mucous membranes and
will blanch under pressure because the red blood cells present are confined to
the vasculature.

Hemochromatosis
=autosomal recessive disease characterized by abnormally high iron
gastrointestinal absorption that causes an iron overload, primarily in
parenchymal organs such as the heart, pancreas, and liver. Common clinical
manifestations of hemochromatosis include liver disease with hepatomegaly,
abdominal pain, skin hyperpigmentation (particularly in sun-exposed areas),
diabetes mellitus secondary to pancreatic islet destruction, impotence,
arthropathy, and cardiac dysfunction and enlargement. The triad of skin
hyperpigmentation, diabetes mellitus, and pigment cirrhosis with hepatomegaly
is described as “bronze diabetes” and may not arise until late in the
disease course. Laboratory findings include mildly elevated liver function tests,
elevated plasma iron with more than 50% saturation of transferrin, and elevated
serum ferritin.

Budd-Chiari syndrome
= secondary to thrombotic occlusion of the hepatic veins and/or the intra- or
suprahepatic inferior vena cava. The venous occlusion causes the sinusoidal
pressure to increase, ultimately leading to portal hypertension, ascites,
hepatomegaly, and splenomegaly.

M. tuberculosis
= passed from person to person through the transmission of aerosolized airway
secretions. These droplets are of varying sizes; larger droplets make contact with
the tracheal and bronchial epithelium and are typically removed by mucociliary
motion, while smaller droplets are carried to the alveoli and can establish
infection. Most droplets of infectious size carry approximately five organisms.
Pulmonary tuberculosis infection is first established after the gravity assisted
entry of small, organism-laden droplets into the lower lung fields. The
mycobacteria are phagocytosed by alveolar macrophages, and the sulfatide
virulence factor expressed by M. tuberculosis allows for intracellular bacterial
proliferation. While nestled within these macrophages, M. tuberculosis enters the
lymphatic circulation. Eventually, it can seed organs throughout the body.
DIFF:
- Epithelioid transformation of macrophages can occur in a chronic granuloma
caused by infection with fungi or M. tuberculosis.
- Scattered caseous necrosis is a secondary immune response that occurs
because of TH1 T-lymphocyte activation of macrophages. The activated
macrophages and T-lymphocytes release chemotactic cytokines to attract other
leukocytes, which leads to an enhanced inflammatory response against the foci
of M. tuberculosis. The end result is local tissue necrosis and a collection of
macrophages, giant cells, and lymphocytes (as well as collagen- secreting
fibroblasts produced secondary to local cytokine secretion) that combine to form
caseating granulomas. Small foci of bacteria are destroyed by this process, while
the larger necrotic areas are simply “walled oft” and calcified. Such a
“walled off” area (Ghon focus) is a potential source of reactivated should
the patient later become immunosuppressed.
http://images.absoluteastronomy.co...images/g/gh/ghon_focus.gif
- Mounting response by B lymphocytes occurs after the antigen-presenting cells
stimulate specific T cells against M. tuberculosis. The T-cells then release
cytokines, leading to the activation of both macrophages (TH1 response, IFN-y
driven) and B-cells (TH2 response IL-4 driven). Activated B-lymphocytes
undergo class switching of their immunoglobulins from IgM to IgG and other
subsets. Unfortunately, immunoglobulins are rarely effective against M.
tuberculosis, as it is a facultative intracellular organism. The killing of M.
tuberculosis is therefore dependent on the cell-mediated TH1 response, because
immunoglobulins are unable to reach the organism while it resides within
macrophages.

Acute calculous cholecystitis

=acute inflammation of the gallbladder, initiated 90% of the time by obstruction
of the gallbladder neck or cystic duct. As the most common complication of
cholelithiasis, acute calculous cholecystitis typically results from chemical
irritation and inflammation caused by the presence of stones in the gallbladder.
The stones disrupt the protective mucus layer, leaving the epithelium exposed to
the detergent action of the bile salts. Prostaglandins released in the gall bladder
wall further incite inflammation of the mucosa and deeper tissues, and
gallbladder hypomotility ensues. The increasing distention and internal pressure
within the gallbladder eventually result in ischemia. Finally, bacteria invade the
injured and necrotic tissue, causing an infection.

Endometriosis
- The ovaries are the site most commonly affected. Ectopic endometrium
responds to hormonal influences in the same way as uterine endometrium. Thus,
during the woman’s menstrual period, bleeding and shedding of tissue
outside the uterus lead to the formation of blood collections. With time, the
blood undergoes hemolysis and induces an inflammatory response around the
ectopic endometrium. Local inflammation is followed by the formation of
adhesions and distortion of organ structure. In the ovaries the collections of old
blood may form endometriomas (chocolate cysts). Nodularity of the uterosacral
ligaments and fixed retroversion of the uterus are commonly found in patients
with endometriosis on vaginal examination.
-Shedding of the ectopic tissue causes pain during the menstrual period
(dysmenorrhea). Painful intercourse (dyspareunia) is related to retroversion of
the uterus and endometrial implants on the uterosacral ligaments. Painful
defecation (dyschezia) can also occur due to pelvic adhesions. Patients may have
difficulty conceiving because of adhesions involving the ovaries and fallopian
tubes. Ectopic endometrial tissue also secretes prostaglandins that interfere with
ovulation and tubal function. Many patients are diagnosed with endometriosis
while being evaluated for infertility.
http://www.swec.com.au/images/endometriosis_over_bladder.jpg

Strawberry (infantile) hemangioma

=a variant of a capillary hemangioma that is the most common benign vascular
tumor in children. Superficial infantile hemangiomas are bright-red compressible
plaques with sharply demarcated borders and are referred to as strawberry
hemangiomas. Deeper infantile hemangiomas have a duskier blue appearance.
Individual lesions can have superficial and deep components.
-Strawberry hemangiomas appear during the first days or weeks after birth and
grow rapidly during the first one to two years of life. The majority of these
tumors regress by five to eight years of age. Capillary hemangiomas can be also
found in deep tissues and the viscera, especially the liver. On microscopic
examination, capillary hemangiomas consist of thin-walled blood vessels with
narrow lumens filled with blood and separated by connective tissue. These
vessels are lined by endothelium that rapidly proliferates during the growth
phase of the tumor.
http://img.medscape.com/pi/emed/ck...gy/1048885-1083849-980.jpg

Ménière’s disease
= a disorder of the inner ear characterized by an increased volume of
endolymph, thought due to defective resorption of endolymph. The resultant
distention of the endolymphatic system causes damage to both the vestibular
and cochlear components of the inner ear. Ménière’s disease is
characterized by the triad of tinnitus, vertigo and sensorineural hearing loss.
1. Tinnitus refers to ringing in the affected ear, often accompanied by a feeling of
fullness.
2. Vertigo is the subjective sensation of motion in the absence of actual motion.
Vertigo is commonly associated with lightheadedness, nausea and sometimes
vomiting. Note that although dizziness and vertigo are often used
interchangeably, they are not synonyms. Dizziness is the sensation of
lightheadedness, whereas vertigo is the subjective sensation of movement of
one’s body or environment. Patients often describe feeling like the room is
spinning.
3. Hearing loss is sensorineural in Ménière’s disease. On physical
examination, the Rinne test will show air conduction superior to bone conduction
in the affected ear (normal pattern). The Weber test will reveal lateralization to
the healthy side.
DIFF:
- Labyrinthitis = inflammation of the vestibular labyrinth that causes acute-onset
vertigo, nausea and vomiting. A history of recurrent episodes would be unusual.
- Otosclerosis is an inherited condition with onset in middle-age. Patients present
with conductive hearing loss that occurs due to bony overgrowth of the footplate
of the stapes. Vertigo does not occur.

Hepatocellular carcinoma (HCC)

-Normally produced by the fetal liver and yolk sac during gestation, alpha-
fetoprotein (AFP) is a glycoprotein that is often elevated in patients with
hepatocellular carcinoma (HCC). This serum marker is not without clinical
limitations, as serum AFP levels do not correlate well with the size, stage, or
prognosis of HCC. Moreover, an elevated serum AFP is associated with numerous
other conditions, including pregnancy, tumors of gonadal origin, and chronic liver
disease (eg, viral hepatitis). The sensitivity of AFP in detecting HCC ranges from
41-65%, while its specificity ranges from 80-94%.
-Despite these limitations, AFP is a useful marker in the evaluation of cirrhotic
patients who are at increased risk for developing HCC. A rise in serum AFP to
levels exceeding 500 mcg/L (with the normal range typically 10-20 mcg/L) in a
high-risk patient is considered diagnostic of HCC. This neoplasm can also be
diagnosed in regularly monitored cirrhotic patients who experience a sudden
surge in AFP above their baselines.
http://odlarmed.com/wp-content/uploads/2009/01/s-212a.jpg
DIFF:
- Carcinoembryonic antigen (CEA) is a serum marker associated with colorectal
cancer
- CA-125 is a serum marker elevated in more than 80% of those women with
ovarian cancer. However, it is also elevated in patients with other malignancies
(endometrial, lung, breast, and pancreatic cancer) and in patients with various
benign conditions (such as endometriosis, cirrhosis, or pelvic inflammatory
disease). CA-125 is not an effective screening tool for ovarian cancer, as its
positive predictive value is only 3%.
- Acid phosphatase is a secondary prostate tumor marker antigen that is also
elevated in patients undergoing active osteoclast-initiated bone resorption.
Non-bacterial thrombotic endocarditis (NBTE)
=Small (1-5 mm), sterile, non-destructive fibrinous vegetations along the lines
of closure of cardiac valve cusps
- Histologically, these vegetations consist of bland thrombus without
accompanying inflammation or valvular damage. They are typically the result of
a hypercoagulable state, although they may also be caused by endothelial injury.
When caused by hypercoagulability, NBTE is most often related to some
underlying disease, such as a cancer. There is a particularly strong association of
NBTE with mucinous adenocarcinomas of the pancreas and adenocarcinomas of
the lung, which may relate to procoagulant effects of circulating mucin.
-NBTE associated with disseminated cancer is termed “marantic” (or
“marasmic”) endocarditis, derived from the term for cancer-related
wasting of body tissues (“marasmus”). By a similar mechanism, tumor-
associated release of procoagulants is thought responsible for the migratory
thrombophlebitis (Trousseau syndrome) sometimes seen in patients with
disseminated cancers.

Lambert-Eaton syndrome
=autoimmune paraneoplastic myasthenic syndrome that affects the presynaptic
calcium channels, resulting in decreased presynaptic acetylcholine release.
Lambert-Eaton syndrome is associated in most cases with oat cell carcinoma of
the lung.

Aplastic anemia
=The triad of low hemoglobin, thrombocytopenia, and absent hematopoietic cells
in the bone marrow
- A compensatory increase in circulating erythropoietin levels would be expected
in individuals with aplastic anemia and normal renal function.
- An increased reticulocyte index would be expected in a hemolytic or
hemorrhagic anemia, assuming normal bone marrow function. Reticulocyte count
is low in aplastic anemia because there are few progenitor cells in the marrow.

Sarcoidosis
-Dry cough, pulmonary infiltrates and hilar adenopathy can be found in a number
of lung diseases, including tuberculosis, sarcoidosis, endemic mycoses
(histoplasmosis, coccidioidomycosis), silicosis, and berylliosis, lymphoma, and
bronchogenic carcinoma. Transbronchial biopsy may be required to establish
and/or confirm the diagnosis. The biopsy specimen shows a central collection of
tightly clustered epithelioid macrophages surrounded by a rim of mononuclear
cells — a non-caseating granuloma.
-The combination of hilar adenopathy, pulmonary infiltrates, and noncaseating
granulomas in an African American female suggest a diagnosis of sarcoidosis.

Lead poisoning
-In the United States, lead poisoning (plumbism) is typically thought of as a
pediatric condition (usually the result of children ingesting lead-containing paint
chips).
-However, lead poisoning can occur in adults as well. Those affected are usually
miners or industrial workers (especially those who work in battery
manufacturing) who inhale particulate lead while working. Adults with lead
poisoning present with weakness, abdominal pain and constipation. In severe
cases there may be neurologic signs. On physical exam, patients may have blue
“lead lines” at the junction of the teeth and gingivae. The classic diagnostic
finding on peripheral blood smear is coarse basophilic stippling on a background
of hypochromic microcytic anemia. Basophilic stippling results from the abnormal
aggregation of ribosomes. The hypochromic microcytic anemia results from
inhibition of 6-ALA dehydratase and the resultant reduced incorporation of iron
into heme. The net effect of these defects is decreased hemoglobin synthesis.
http://www.healthsystem.virginia.e...D/Basophilic-stippling.cfm

Adult respiratory distress syndrome (ARDS)

- Sepsis and shock are two major risk factors for ARDS
- In 75% of cases ARDS arises within 24 hours of the precipitating cause. 95% of
cases arise within 72 hours. In ARDS, widespread injury to the pulmonary
microvascular endothelium and/or the alveolar epithelium causes the
alveolocapillary membrane to be leaky. In sepsis and/or shock, the pulmonary
capillary endothelial injury results from endotoxin-induced release of injurious
products from adherent leukocytes and/or ischemia-induced release of injurious
cytokines. This endothelial injury causes pulmonary interstitial and intra-alveolar
edema, inflammation, and alveolar hyaline membrane formation. In non-
cardiogenic pulmonary edema, the pulmonary capillary wedge pressure remains
within normal limits.

Matrix metalloproteinases
Secreted by several different cell types (eg, fibroblasts, macrophages,
neutrophils, synovial cells, some epithelial cells), matrix metalloproteinases
primarily function in the degradation of collagen and other proteins in the
extracellular matrix. MMP activity is important in wound healing, as it encourages
both myofibroblast accumulation at the wound edges and scar tissue remodeling.
The amassed myofibroblasts initiate wound contraction during healing by second
intention. Contractures may occur when unusually pronounced MMP activity
results in excessive wound contraction.
- The major determinant of whether or not a coronary artery plaque will cause
ischemic myocardial injury is the rate at which it occludes the involved artery. A
slowly developing occlusion would allow for formation of collaterals that could
prevent myocardial necrosis. A thin fibrous cap, a rich lipid core, and active
inflammation in the atheroma would all decrease plaque stability and thus
potentially promote rapid coronary occlusion via superimposed thrombosis if the
plaque were to rupture.
- Keloids are hypertrophic scars in which excessive collagenous scar tissue
deposited by fibroblasts permanently extends beyond the margins of the original
wound. Keloids are not known to be specifically related to excessive matrix
metalloproteinase or myofibroblast activity.

Coronary artery plaque

-A slowly developing occlusion would allow for formation of collaterals that could
prevent myocardial necrosis.
-A thin fibrous cap, a rich lipid core, and active inflammation in the atheroma
would all decrease plaque stability and thus potentially promote rapid coronary
occlusion via superimposed thrombosis if the plaque were to rupture.
http://www.ajmc.com/media/image/AJMC_07decDavidson_Fig_S260.gif

Eosinophilic neurons
- These “red neurons” are a sign of irreversible neuronal injury. Nissl
substance disappears, and the nucleus becomes pyknotic (small and deeply
basophilic). These damaged neurons subsequently undergo fragmentation and
will ultimately be phagocytized by macrophages.
http://missinglink.ucsf.edu/lm/int...to_Injury/InfarctIntro.htm
- 4-12 hours after the ischemic event: the earliest definitive microscopic signs of
irreversible ischemic injury in the infract are eosinophilic (red) neurons; distinct
intracellular features are lost (pyknotic nuclei, loss of Nissl substance)
- 24-72 h: necrosis and neutrophilic infiltration
- 3-5 day: macrophage infiltration and phagocytosis
- 1-2 weeks: reactive gliosis and vascular proliferation around the necrotic area
(macroscopic = liquefactive necrosis)
- > 2 weeks: glial scar (macroscopic = cystic area surrounded by gliosis)
- By 2-3 weeks, macrophages phagocytize the products of neuron and myelin
breakdown. Astrocytes proliferate around the area of necrosis (reactive
astrocytosis, or gliosis). New vessel formation peripheral to the necrotic area
may begin at this time.
-Several months or years after an infarct, the process of tissue destruction and
organization is complete. A cystic cavity replaces brain tissue in the ischemic
area. This cavity is surrounded by a wall formed by astrocyte processes (glial
scar) and new capillaries.

Chronic bronchitis
= caused by smoking and exacerbated periodically by superimposed bacterial
bronchitis.
- there is progressive thickening of the walls of the bronchi and bronchioles. The
severity of chronic bronchitis is largely dependent upon the extent to which the
luminal diameter of the bronchi and bronchioles is decreased. The major
contributor to this wall thickening is submucosal mucous gland enlargement
which can be quantified by the ratio of the thickness of the mucous gland layer
to the thickness of the wall between the epithelium and the cartilage (Reid
index). The Reid index is normally = 0.4. As chronic bronchitis progresses both
the total bronchial wall thickness and the Reid index increase. Thus the degree of
elevation of the Reid index correlates with the duration and severity of the
chronic bronchitis.
http://www.som.tulane.edu/classwar...8/Lung_Review/Lung-20.html
http://www.som.tulane.edu/classwar...8/Lung_Review/Lung-21.html

Central pontine myelinolysis

=Rapid correction of chronic hyponatremia= may lead to osmotic demyelination
of the axons in the central part of the pons.
- The typical clinical features include quadriplegia due to demyelination of the
corticospinal tracts and pseudobulbar palsy due to demyelination of the
corticobulbar tracts of CN IX, X and XI.
-Pseudobulbar palsy is characterized by head and neck muscle weakness,
dysphagia, and dysarthria. This palsy is called “pseudobulbar” because the
nuclei of corresponding cranial nerves remain intact. Bulbar palsy, to the
contrary, is caused by a pathologic process in the nuclei of these nerves.
http://www.dizziness-and-balance.c...ontine%20myelinolysis.html

“Blue sclera”
= presumes “osteogenesis imperfecta” until ruled out.
- Osteogenesis imperfecta is the heritable disorder resulting from quantitative or
qualitative abnormalities in type I collagen which results in abnormally weak
bones. Type I collagen is the predominant collagen in the bones but it is also
present in teeth ligaments, skin and sclera. Involvement of teeth leads to
malformed small teeth a condition called “dentinogenesis imperfecta.” The
sclera are often blue, and joints can have excessive laxity. Some patients are
also susceptible to bruises and hearing loss. The clinical phenotype of
osteogenesis imperfecta can vary from a mild asymptomatic defect to the lethal
form.
- Most patients with osteogenesis imperfecta have a mutation in the gene that
encodes type I bone collagen. In most subjects, osteogenesis imperfecta is
transmitted by autosomal dominant inheritance.
http://www.thachers.org/images/Ost...imperfecta_blue_sclera.JPG
http://www.thachers.org/images/Osteogenesis_imperfecta.JPG

Bitemporal hemianopsia
=Loss of peripheral vision
=caused by pressure on the central part of the optic chiasm. The most common
cause of bitemporal hemianopia is a pituitary tumor. Pituitary tumors can also
secrete hormones, causing endocrine disorders. A prolactin-secreting pituitary
adenoma is the most likely cause of both amenorrhea and visual defects.

“Pinealoma”
= a generic term for a tumor of the pineal region. Most often they are
germinomas. These tumors occur in children and cause obstructive
hydrocephalus, Parinaud syndrome, and precocious puberty.
http://www.eyecancer.com/ViewImage...a+bilateral+retinoblastoma

The ERB-B2gene (also called HER-2Neu)

= a member of the epidermal growth factor receptor family that is
overexpressed in 25-30% of breast cancers as well as in adenocarcinomas of the
ovary, stomach, lung, and salivary glands.
-The Erb-B2 protein is a transmembrane glycoprotein with tyrosine kinase
activity, and is present in minute amounts in normal breast and ovarian cells; is
often associated with aggressive tumors, and can be used to predict therapeutic
response to anti-HER-2 monoclonal antibody (trastuzumab). The overexpression
of this protein, however, is only weakly associated with a poor prognosis and is
not helpful in forecasting tumor response to broader chemotherapy.
-The other markers used to predict tumor response to treatment are the
estrogen and progesterone receptors (ER/PR). Their presence in tumor cells
positively correlates with response to anti-estrogen treatment (tamoxifen) or
chemotherapy.
DIFF:
- N-myc is a proto-oncogene located on chromosome 2 that is associated with
neuroblastomas and small cell carcinoma of the lung.
-The sis proto-oncogene encodes the platelet-derived growth factor.
Overexpression of this gene is seen in astrocytomas and osteosarcomas.
-The ras protein is a component of the MAP kinase-associated signaling pathway.
Mutated ras results in an increased cell response to growth factor stimulation.
This molecular abnormality has no bearing on breast cancer response to therapy.

-Bcl-2 encodes the group of proteins that inhibit apoptosis. Overexpression of

the Bcl-2 protein is observed in follicular lymphomas and facilitates neoplastic
cell survival.
http://www.nature.com/nature/journ.../images/387773ab.eps.2.gif
http://www.bio.miami.edu/~cmallery/150/gene/c7.19.12a.Ras.jpg

Echinococcus granulosus
=the most common cause of hydatid cysts in humans. Most cases occur either in
individuals from endemic regions (eg, Mediterranean countries, Middle East,
southern South America, Iceland, Austria, New Zealand, and southern Africa) or
in those people residing in the Southwest region of the United States with sheep
and dog exposure (two animals that participate in the tapeworm life cycle).
-The initial infection is always asymptomatic, with subsequent signs and
symptoms dependent upon the site of the cysts and their size. The liver is
affected in most patients, though other organs can be involved, including the
lung, muscle, or bone. Unilocular lesions are typical of E. granulosus, and
multilocular lesions are typical of E. multilocularis infection. Ultimately, patients
may experience hepatomegaly, right upper quadrant pain, nausea, and vomiting.

-When infection first occurs, the echinococcal larvae implant within the
capillaries, triggering an inflammatory reaction composed of monocytes and
eosinophils. Some larvae are destroyed by the host, but others encyst.
-Microscopic examination of hydatid cyst tissue demonstrates a characteristic
encapsulated and calcified cyst (“eggshell calcification”) that contains fluid
and budding cells that will eventually become daughter cysts. The outer cyst wall
is composed of many layers of delicate, gelatinous sheets surrounded by a thick
fibrous capsule.
-Both imaging (ultrasound, CT, or MRI) and serology testing can be used to
establish the diagnosis. Surgery and adjunctive chemotherapy with mebendazole
or albendazole is considered the treatment of choice for those symptomatic
patients with E. granulosus hydatid cysts. Aspiration is generally inadvisable, as
the spilling of cyst contents within the peritoneum can cause anaphylactic shock.

http://www.isradiology.org/tropica...hapter3/large3/03-119A.jpg
http://www.medicine.mcgill.ca/TROP...hology_platyhelminths3.jpg
http://www.radpod.org/2007/06/14/pulmonary-hydatid-cyst/
http://workforce.cup.edu/buckelew/...laris%20hydatid%20cyst.htm
http://www.pathconsultddx.com/imag...59867506708294/gr1-sml.jpg

Paraneoplastic syndromes
= non-metastatic systemic effects that accompany malignant disease. They are
often caused by substances produced from tumor cells
-For example, the rarely-occurring neurologic paraneoplastic syndromes have an
autoimmune etiology. Antibodies produced against tumor cells cross-react with
neurons and cause their degeneration. Paraneoplastic cerebellar degeneration
occurs predominantly in patients with cancer of the ovary, uterus, breast, and
small-cell carcinoma of the lung. Patients present with limb and truncal ataxia,
lack of coordination, dysarthria, and nystagmus. Other neurologic paraneoplastic
disorders are limbic encephalitis and sensors neuropathy.
- Some of the paraneoplastic syndromes do occur because of the production of
hormone-like substances from tumor cells. Examples of paraneoplastic
syndromes with an endocrine etiology are Cushing syndrome (due to secretion of
ACTH) and hypercalcemia (due to production of PTHrP).

Barrett esophagus
- People with a history of severe and longstanding reflux disease are most prone
to Barrett esophagus. When acidic gastric contents enter the esophagus, they
irritate the mucosa, causing inflammation and subsequent epithelial necrosis.
Sustained epithelial damage promotes the replacement of normal, stratified
squamous epithelium with intestinal—type columnar cells. This metaplasia is
hypothesized to be adaptive at first, as intestinal-type epithelium is more
resistant to acidic environment: however itis also a major risk factor for
esophageal adenocarcinoma.
-Patients with Barrett esophagus have a 30-40 times increased risk of developing
esophageal adenocarcinoma. This malignant cancer typically develops from the
metaplastic intestinal epithelium in the distal part of esophagus: it is clinically
silent until it obstructs the esophageal lumen. At this point, the cancer is usually
large: thus, it is very important to diagnose Barrett esophagus early. Regular
biopsies of the area should be performed to monitor for cellular dysplasia.
http://pathology2.jhu.edu/beWeb/images/newesphcan2.jpg
http://jcp.bmjjournals.com/content...ages/large/cp35337.f1.jpeg

Hepatic adenomas
= found predominantly in young and middle-aged women who have a lengthy
history of oral contraceptive usage. Hepatic adenomas are typically identified
when patients complain of abdominal pain in the epigastrium or right upper
quadrant, when imaging is obtained for unrelated issues, or when an individual
suddenly collapses because of rupture and intraabdominal bleeding. Serum AFP
levels are not elevated.
http://www.usapowerlifting.com/newsletter/07/photos/fig8.jpg

Arachidonic acid
http://www.fao.org/docrep/v4700e/V4700E0O.GIF
The most potent chemotactic eicosanoid is leukotriene B4
Other significant chemotactic agents include 5-HETE (the leukotriene precursor)
and complement component C5a.

Huntington disease
=neurodegenerative disorder inherited as an autosomal dominant trait. The
disease classically presents between 30 and 40 years of age with an insidious
onset of personality changes followed by physical symptoms. The patients may
demonstrate aggressiveness, flat affect, depression or anxiety, decreased
memory and concentration, and psychosis. The movement disorder presents
with purposeless choreiform movements of the extremities or, less commonly
bradykinesia.
-The characteristic abnormality seen in patients with Huntington disease is
bilateral atrophy of the caudate nucleus and putamen, which together form the
striatum. Caudate atrophy leads to the typical dilation of the frontal horns of the
lateral ventricles and microscopy of the atrophic areas reveals gliosis and
neuronal loss. Loss of GABA-containing neurons leads to decreased GABA in the
brain: this is the most characteristic biochemical feature of Huntington disease.
http://img.medscape.com/pi/emed/ck...gy/336139-416016-10513.jpg

Nitric oxide
=found in the cortex, hippocampus, hypothalamus, cerebellum and olfactory
system and is thought to participate in formation of new memories. It is a unique
neurotransmitter in that it freely diffuses across cell membranes and does not
need to interact with other neurons via a synapse.
http://cgmp.blauplanet.com/imag1/noeffect.gif
Colon cancer
- Serum carcinoembryonic antigen (CEA) levels are increased in 60-90% of
patients with colon cancer. CEA is a glycoprotein involved in cell adhesion. It is
produced in the embryonic pancreas, liver and intestine, and is also detected in
minute amounts in the serum of healthy adults. The CEA level cannot be used to
diagnose colon cancer because it is also increased in pancreatic, gastric and
breast malignancies, as well as in a number of benign diseases, such as
inflammatory bowel disease, cirrhosis and pancreatitis. Smokers have higher
CEA levels than non-smokers.
-Although not useful for diagnosis, a patient’s CEA level is a sensitive
indicator of colorectal cancer recurrence. It should be measured in colon cancer
patients perioperatively and in regular intervals after surgery. A rising CEA level
in such a patient is an indication to search for cancer recurrence/metastases
(with chest x-ray, abdominal CT scan colonoscopy, etc.).

Celiac disease (gluten-sensitive enteropathy)

= symptoms of malabsorption. Diarrhea steatorrhea, weight loss, and
deficiencies of vitamins and minerals occur. This disorder may manifest at an
early age or later in life and is caused by hypersensitivity to gluten, a component
of wheat and some other related grains.
- Celiac disease is diagnosed when flattening of the mucosa with loss of villi and
chronic inflammatory infiltration of the lamina propria is seen on small intestine
biopsy. The most pronounced changes are seen in the duodenum and proximal
ileum because the concentration of gluten is higher there.
-Celiac sprue is thought to occur by an immune-mediated mechanism in
genetically-susceptible individuals. Abnormal response to tissue
transglutaminase, an enzyme that participates in metabolism of gluten, is found.
Immunoglobulin A (IgA) antibodies to gliadin (a mixture of polypeptides
extracted from gluten) is a typical finding in these patients. Other antibodies
frequently found in patients with celiac disease are anti-endomysial and anti-
reticulin.
http://www.pathology.vcu.edu/education/gi/lab2.c.html

Small cell lung carcinoma

=also called undifferentiated or oat cell carcinoma. It comprises 10-20% of all
malignant lung tumors.
-Small cell lung carcinoma is strongly associated with smoking and is usually
centrally located. This tumor arises from the primitive cells of the basal layer of
the bronchial epithelium. On light microscopy itis composed of round or oval cells
with scant cytoplasm and large hyperchromatic nuclei. These cells may resemble
lymphocytes, but are smaller in size. Tumor cells can form sheets or clusters.
Abundant mitoses are usually seen.
-Small cell carcinomas can display varying degrees of neuroendocrine
differentiation. Immunohistochemical stains are frequently positive for
neuroendocrine markers, such as neuron specific enolase, chromogranin and
synaptophysin. On electron microscopy some of the cells are found to have
secretory granules in the cytoplasm.

Acute pyelonephritis.
=massive infiltration of the interstitium by polymorphonuclear leukocytes
(neutrophils), as well as a large number of neutrophils in the tubular lumina.
- In addition, tubular epithelial disruption may be seen, along with
microabscesses in the interstitium.
-Acute pyelonephritis is usually caused by gram-negative rods that ascend from
the bladder. Ureterovesical reflux is necessary in the pathogenesis of acute
pyelonephritis; without reflux, bacteria remain localized in the bladder and do
not reach ureters or renal tissue.
-Clinically, acute pyelonephritis manifests with flank and abdominal pain, fever,
shaking chills, nausea, and vomiting.
-Costovertebral angle (CVA) tenderness is commonly found on physical
examination. Urinalysis reveals pyuria (WBCs), VwBC casts bacteriuria, and often
hematuria.
http://www.pathologyatlas.ro/patho...cute_pyelonephritis_02.jpg

Hirschsprung disease
Submucosal (Meissner) and myenteric (Auerbach) autonomic plexi are absent in
the affected segment of the bowel in Hirschsprung disease. The submucosa of
the narrowed area is the most superficial layer where the absence of ganglion
cells can be seen.
- If a large area of the bowel is involved the disease will manifest during the first
few days of life with obstructive symptoms (failure to pass meconium, bilious
vomiting and abdominal distention). If only a short area is affected, the disease
may go undetected for months or years. In this case persistent constipation,
abdominal distention and failure to thrive are typical. Barium enema in such
patients shows narrowing in the rectosigmoid area. Proximal to the obstruction
the bowel is dilated and filled with feces.
Rectal biopsy is necessary for the diagnosis of Hirschsprung disease a condition
that results from the failure of neural crest cells to migrate to the intestinal wall.
Normally, these cells develop into ganglion cells of the submucosal (Meissner)
and myenteric (Auerbach) plexi of the bowel wall. Since those cells migrate
caudally, the rectum is always involved. The submucosa of rectum (the narrowed
segment) should be biopsied to demonstrate the absence of ganglionic cells.
Xanthoma
- Hyperlipidemia and/or dyslipidemia can result in xanthomas (including
xanthelasmas). Xanthelasmas are dermal accumulations of benign-appearing
macrophages with abundant finely vacuolated (foamy) cytoplasm, containing
cholesterol (free and esterified), phospholipids, and triglycerides. Due in part to
insulin resistance promoting increased VLDL production, diabetics may develop a
secondary Type IV or V hyperlipidemia (increased VLDL chylomicrons) and/or a
secondary diabetic dyslipidemia with elevated LDL cholesterol and low HDL
cholesterol. Thus, in order to determine the type of this patient’s lipid
disorder and to rule out underlying diabetes, her serum lipids and blood glucose
should be measured.

Multiple myeloma
=plasma cell neoplasm that occurs in patients 40 to 60 years of age. The
following symptoms are characteristic for this disease:
1. Normocytic and normochromic anemia develops due to bone marrow
infiltration and replacement by malignant plasma cells with resultant suppression
of normal hematopoiesis.
2. Secretion of IL-6 (osteoclast activating factor) by neoplastic cells activates
osteoclasts and leads to bone resorption with resultant osteopenia. Patients
present with bone pain pathologic fractures, and “punched-out” lytic
lesions on X-ray.
3. Hypercalcemia occurs due to increased bone destruction. It manifests with
fatigue, confusion, and constipation.
4. Production of monoclonal immunoglobulin by abnormal plasma cells impairs
the secretion of normal immunoglobulins, and leads to increased susceptibility to
infection. The presence of M protein (monoclonal immunoglobulin) in the serum
and monoclonal light chains (Bence-Jones protein) in the urine is characteristic
for multiple myeloma. Hyperimmunoglobulinemia also causes roleaux formation
on peripheral blood smear and an increased ESR.
5. AL amyloid forms due to accumulation of monoclonal immunoglobulin light
chains. It is seen as an eosinophilic extracellular deposit on H&E stain, and
shows “apple-green” birefringence with Congo red stain viewed under
polarized light. AL amyloidosis contributes into the development of renal failure
in multiple myeloma; amyloid id also characteristically deposited in the heart,
tongue and other muscles.
6. Renal failure develops due to infiltration of kidney by plasma cells, deposition
of amyloid, Bence-Jones casts in the tubules, hypercalcemia leading to
metastatic calcification and inflammation by macrophages and giant cells.
http://library.med.utah.edu/WebPath/HEMEHTML/HEME070.html
http://orthoinfo.aaos.org/figures/A00086F01.jpg
http://stanfordhospital.org/ImageG...t/amyloid/kidneyLargeA.jpg
Hepatocellular carcinoma
=A liver mass associated with an increased alpha-fetoprotein level
- Development of hepatocellular carcinoma is strongly associated with HBV
infection, and is often preceded by HBV-induced cirrhosis. Although the
pathogenesis of HBV-induced hepatocellular carcinoma is still unclear, the
integration of viral DNA into the cellular genome of the host is considered a
trigger of neoplastic changes. The viral protein HBV activates the synthesis of
insulin-like growth factor II and receptors for insulin-like growth factor I, thereby
stimulating cell proliferation. Another effect of HBV gene products is suppression
of the p53 tumor suppressor / cell cycle regulatory gene in host cells. It is also
believed that chronic inflammation and regeneration induced by HBV infection
facilitates accumulation of mutations in hepatocytes leading to carcinogenesis.
All these events result from integration of the viral genome into host cells.
- Other risk factors for hepatocellular carcinoma include HCV, alcoholic cirrhosis,
aflatoxins and hemochromatosis.

Poststreptococcal glomerulonephritis (PSGN)

= Abrupt onset of malaise, fever, cola-colored urine and facial edema 2-4 weeks
following a streptococcal infection of either the pharynx or skin in a 6 to 10-year-
old child
- Physical examination reveals facial and periorbital edema and mild to moderate
hypertension. Urine contains dysmorphic red cells RBC casts and some protein
(usually < 1 g/day). Elevations of creatinine and BUN may also be present.
-On light microscopy, the glomeruli are enlarged and hypercellular.
Immunofluorescence studies reveal granular deposits of IgG, IgM, and C3 along
the basement membrane and in the mesangium of glomeruli (“lumpy-
bumpy” appearance). On electron microscopy, there are electron-dense
deposits on the epithelial side on the basement membrane. These “humps”
are composed of immune complexes.
http://www.pathologyatlas.ro/patho..._glomerulonephritis_02.jpg
http://library.med.utah.edu/WebPath/RENAHTML/RENAL086.html
http://library.med.utah.edu/WebPath/RENAHTML/RENAL087.html

p53
= a tumor suppressor gene that controls cell division and apoptosis. It is
inactivated in many tumors.
- In normal individuals, p53 regulates cell proliferation. It acts during phase 01
of the cell cycle to detect abnormalities of the cellular genome. If there is
damaged DNA, p53 will prevent the cell from progressing to mitosis, causing the
cell to be arrested in the G1 phase. If the DNA can be repaired, the cell will
subsequently be allowed to divide, but if the damage is so severe that repair is
impossible the cell will proceed instead to apoptosis. p53 is nicknamed ‘the
molecular policeman” because of its important role in guarding the integrity of
genetic material.

Hemophilia
=X-linked recessive bleeding disorder that develops due to a decreased level of
factor VIII (hemophilia A) or factor IX (hemophilia B) in serum.
Factors VIII and IX are components of the intrinsic coagulation pathway. These
factors are necessary for activation of factor X: activated factor X (Xa), in turn
catalyzes the conversion of prothrombin (factor II) into thrombin. In the absence
of factors VIII or IX, activation of factor X and subsequent conversion of
prothrombin into thrombin does not occur. Administration of thrombin however
will make up for the deficiency and result in blood clotting.
- Coagulation studies in both types of hemophilia reveal a normal bleeding time
and platelet count, a normal PT and a prolonged PTT. The prothrombin time (PT)
tests the extrinsic clotting pathway and reflects the function of factors II, V, VII,
and X. The partial thromboplastin time (PTT) assesses the activity of factors II,
V, VIII, IX, X, Xl and XII the intrinsic clotting pathway . Diagnosis of hemophilia
A and B is made by measuring plasma levels of factors VIII and IX respectively.
http://www.moondragon.org/images2/mildhemophilia.jpg
http://intmedweb.wfubmc.edu/grand_...adindoc_files/image002.jpg

Protein C
= vitamin K dependent factor synthesized in the liver. It is a physiologic
anticoagulant that degrades factors Va and Vllla.
- Factor Xll (Hageman) is synthesized by the liver and is activated by endothelial
injury. It triggers the intrinsic coagulation pathway by activating factor Xl.

Type 2 diabetes mellitus

- Two cardinal defects involved in pathophysiology of type 2 diabetes mellitus
are insulin resistance and defective insulin secretion. Although still very
controversial, many researchers believe that insulin resistance is the primary
abnormality in type 2 diabetes mellitus.
- Early in the pathogenesis of type 2 diabetes glucose tolerance remains normal
because of a compensatory increase in insulin secretion from beta cells. This
compensatory insulin response from beta cell insulin ultimately fails, causing
poor glucose tolerance. A number of genetic and acquired factors are implicated
in the beta-cell dysregulation of type 2 diabetes. Islet associated polypeptide
(amylin, IAPP) is one factor thought to be responsible for this beta cell
dysfunction. IAPP is co-secreted with insulin from beta cells: IAPP is then
deposited in islet cells. Deposits of islet amyloid polypeptide are universally seen
in pancreatic islets of patients with type 2 diabetes mellitus. Islet associated
polypeptide was originally thought to be the causative agent in beta cell
apoptosis and defective insulin secretion. However this theory has been seriously
questioned by the normal glucose tolerance and normal insulin response of
transgenic mice that over-express human IAPP.
- Patients with type 2 diabetes retain at least some beta cell function but
patients with type 1 diabetes mellitus develop absolute deficiency of insulin
secondary to immune destruction of pancreatic beta cells. These patients need
insulin for survival.

Type 1 diabetes
= occurs when autoimmune response is triggered by an environmental insult in
genetically-susceptible individuals.
-Type 1 diabetes has a very strong genetic component. Twin studies have shown
a concordance rate of 50% in identical twins. Gene polymorphism within the
major histocompatibility complex contributes to disease in humans. HLA-DQ and
DR are the most important determinants of type 1 diabetes mellitus. In
Caucasians there is a strong association of DR3 and DR4 haplotypes with
diabetes mellitus. In the general population HLA-DR3 and DR4 are seen in
approximately 40% of subjects: however in patients with type 1 diabetes
mellitus HLA-DR3 and DR4 haplotypes are seen in more than 9O% of subjects.
Blood glucose starts to increase when lO% of beta cells remain. Antibodies
against islet antigens can be detected in serum of a large number of patients
with type 1 diabetes mellitus. Most researchers believe that these antibodies do
not cause beta cell destruction but are instead generated as a result of beta-cell
destruction by cellular immunity by T lymphocytes in particular. Infiltration of
islets by inflammatory cells is called insulitis.

Vitamin E
=primarily serves to protect fatty acids from oxidation. As a result, vitamin E
deficiency predisposes those cell membranes with high fatty acid content to
oxidative injury. The cells that are most susceptible to increased oxidation in
vitamin E deficiency are neurons with long axons (and therefore increased
surface area) and erythrocytes.
- Because pancreatic enzymes are necessary for the proper absorption of
nutrients in the gut, deficiencies of the fat-soluble vitamins A, D, E and K
frequently occur in patients afflicted with cystic fibrosis. The most common
clinical manifestations of vitamin E deficiency are neuromuscular disease (eg,
skeletal myopathy, spinocerebellar ataxia, pigmented retinopathy) and hemolytic
anemia. Involvement of the dorsal column in the spinal cord is associated with
the loss of proprioception and vibratory sense. Spinocerebellar tract involvement
causes ataxia.
Atherosclerotic plaques
= develop predominantly in large elastic arteries (e.g.. aorta, carotid, and iliac
arteries), and in large or medium-sized muscular arteries (e.g. coronary and
popliteal arteries). In humans, the abdominal aorta is the vessel most heavily
involved with lesions most prominent around the ostia of major arterial
branches. After the abdominal aorta, the next most heavily involved vessels are
(in decreasing order): the coronary arteries, the popliteal arteries the internal
carotids, and the circle of Willis. The upper limb arteries are usually spared. The
mesenteric and renal arteries tend to be spared except at their ostia (openings
from the aorta).
-Although the common carotid artery may be affected by atherosclerosis it is less
commonly involved than the abdominal aorta and other arteries. In the carotid
system, the region most prone to atherosclerosis is likely the carotid sinus at the
origin of the internal carotid artery.

Liver Metastases
=the most common malignant neoplasms of the adult liver and are twenty times
more common than hepatocellular carcinoma. The liver is the second most
common site of metastatic spread (after the lymph nodes) because of its large
size, dual blood supply, high perfusion rate, and the filtration function of Kupffer
cells.
-Patients with liver metastases typically have multiple nodules throughout the
liver that may replace more than 80% of hepatic parenchyma, with marked
hepatomegaly a common result. Frequently, the nodules outgrow their vascular
supply and become centrally necrotic and umbilicated. Even with significant
metastatic involvement, patients may have no clinical or laboratory signs
suggestive of hepatic insufficiency. Once the majority of the liver parenchyma is
destroyed or the major bile ducts become obstructed with tumor however,
patients tend to present with jaundice or abnormal hepatic enzymes.

Hepatic angiosarcomas
=associated with recent or remote exposure to vinyl chloride, arsenic, or
Thorotrast. This tumor is extremely aggressive and associated with a poor
prognosis, as most patients die within one year.
- Intrahepatic cholangiocarcinoma= a rare malignancy that arises from the intra-
and extrahepatic bile ducts. Grossly it appears as a treelike mass that grows
along the intrahepatic portal tract system, typically resulting in extensive
intrahepatic metastasis. Risk factors include primary sclerosing cholangitis,
congenital fibropolycystic diseases of the biliary system (eg, Caroli disease and
choledochal cysts), and a history of Thorotrast exposure. The prognosis is very
poor.
http://www.brown.edu/Courses/Digit...iary/cholangiosarcoma.html

Esophageal squamous cell carcinoma (SCC)

=demonstrates flattened polyhedral or ovoid epithelial cells with eosinophilic
cytoplasm keratin nests or “pearls” within or between cells, and
intercellular bridging. Large, hyperchromatic cells with bizarre nuclei and atypical
mitoses are commonly observed.
-The incidence of esophageal SCC is decreasing in the United States, with
middle-aged and older individuals of African or Asian heritage at greatest risk for
developing the disease. The most significant risk factors for the development of
SCC in the United States include cigarette smoking and alcohol intake. In Asia,
the chewing of betel nuts and the consumption of foods containing N-nitroso
compounds are commonly associated with the development of SCC.
-Esophageal squamous cell carcinoma typically presents with progressive solid
food dysphagia that may be accompanied by weight loss. Chronic
gastrointestinal blood loss is a frequent finding in this patient population and
may result in iron deficiency anemia.
http://www.pathology.med.ohio-stat.../Images/10533/PAXIT038.JPG
http://www.pathology.med.ohio-stat.../Images/10533/PAXIT002.JPG
DIFF:
-Heartburn and reflux esophagitis are associated with the development of
Barrett’s metaplasia and, eventually, esophageal adenocarcinoma.

Subacute, combined degeneration

-B12 deficiency occurs due to abnormal myelin synthesis. It leads to
degeneration of the following:
1. Dorsal columns of the spinal cord. Damage to these tracts leads to bilateral
loss of position and vibration sensation. Gait abnormalities are typical, especially
when the patients eyes are closed (sensory ataxia).
2. Lateral corticospinal tracts. Upper motor neuron signs: spastic paresis,
hyperreflexia, and pathologic reflexes (Babinski sign).
3. Axonal degeneration of peripheral nerves can cause numbness or
paresthesias.
The myelopathy associated with vitamin B12 deficiency is called subacute,
combined degeneration. “Combined” refers to the degeneration of both
ascending (dorsal columns) and descending (corticospinal tract) pathways.
http://www.urmc.rochester.edu/neuroslides/slide164.html
Anterior spinal artery syndrome
= a result of compression/occlusion of the artery that runs along the front of the
spinal cord. Compression may be from bone fragments or disc herniation.
-Patients with anterior spinal cord syndrome usually have complete loss of
strength below the level of injury with loss of pain and temperature sensation
but preserved vibratory senses.
http://www.anaesthesiauk.com/images/spinal-cord4.jpg
http://www.aan.com/globals/axon/assets/4817.gif

Adhesion molecules
= integrins,cadherins , selectins, and lg superfamily members. The integrins are
a family of transmembrane protein receptors that interact with the extracellular
matrix by binding to collagen, fibronectin, and laminin. Because integrins bind
ligands with relatively low affinity, cells are allowed some flexibility to explore
the surrounding environment without becoming affixed to one location or losing
an attachment altogether.
-Fibronectins are large glycoproteins produced by fibroblasts and some epithelial
cells. Fibronectin binds to integrins, matrix collagen, and glycosaminoglycans,
serving as a mediator of normal cell adhesion and migration.
http://bioweb.wku.edu/courses/Biol566/Images/Adherontypes.JPG

Heparan sulfate
= a proteoglycan component of the extra cellular matrix that is primarily
associated with reticular fibers and basal laminae. It contributes to vascular
endothelial cell attachment to the basement membrane
- Keratan sulfate is a galactose-containing glycosaminoglycan that may play a
role in maintaining type I collagen fibril organization in the cornea.

S phase
- The avid uptake of bromodeoxyuridine by the tumor reflects the high number
of tumor cells in S phase (preparing to divide) . A high proliferation rate suggests
a high tumor grade and, therefore a poor prognosis.
http://www.le.ac.uk/ge/genie/vgec/images/cellcycle.png
Hydatidiform moles
- characteristically have the macroscopic appearance of a “bunch of
grapes.” -Hydatidiform moles are the result of trophoblast proliferation.
Microscopic examination of a complete mole would reveal large villi with
decreased villous blood vessels and proliferation of the villous trophoblastic
lining. Fetal tissue is absent.
-A complete mole will cause vaginal bleeding during the first trimester of
pregnancy. The size of uterus may be out of proportion to the gestational age.
Some patients have severe nausea and vomiting as the result of increased hCG
secretion by the proliferating trophoblast. Excessive hCG also stimulates ovarian
growth and can cause the formation of theca-lutein cysts.
-In the majority of patients with a complete mole, evacuation leads to recovery.
In some, however, an invasive mole (penetrates the uterine wall) or
choriocarcinoma (malignancy of trophoblastic cells) may develop. An invasive
mole would consist of hydropic villi and proliferated trophoblast, while
choriocarcinoma would contain atypical cytotrophoblastic and
synticyotrophoblastic cells with foci of hemorrhage and necrosis. Invasive moles
and choriocarcinomas can be detected by serial measurements of hCG levels and
are treated with chemotherapy.
http://www.sswahs.nsw.gov.au/sswahs/sgog/assets/Mole.jpg
http://pathology.class.kmu.edu.tw/ch09/Slide77.htm

Urticaria, or “hives”
= common transient dermatologic disorder that arises secondary to the antigen-
induced degranulation of focal mast cells through IgE antibody sensitization.
Alternatively, an IgE-independent urticaria can also develop after exposure to
substances that directly stimulate mast cell degranulation (eg, opiates,
antibiotics and radiographic contrast media).
-Both degranulation pathways cause microvasculature hyperpermeability and the
formation of wheals that typically surface and resolve within hours with some
episodes persisting for days to months. The lesions may coalesce into larger
lesions that assume annular linear or acriform shapes.
-Histologically urticaria presents with subtle features. A mild superficial infiltrate
composed of mononuclear cells and occasional eosinophils is observed
immediately around dermal venules. Superficially, the collagen bundles are
parted by dermal edema and the lymphatic channels are dilated with excess
transudate. Epidermal changes are not identified.
http://strawberriesweb.com/urticaria.jpg

Hemochromatosis
- Caused by a mutation of the HFE gene on chromosome 6, hemochromatosis is
an autosomal recessive disease characterized by abnormally high iron
gastrointestinal absorption. The crucial site for HFE expression is the basolateral
surface of epithelial cells of the small intestine crypts, where it complexes with 2-
microglobulin and then binds to the transferrin receptor to facilitate endocytosis
of the transferrin/iron complex into cells. The iron is released once inside the cell
and added to the iron regulatory pool, which determines the intensity of apical
iron uptake expression. The crypt cells in individuals with hemochromatosis have
mutant HFE that is unable to detect circulating iron levels. As a result, there is
unregulated expression of the iron uptake proteins and an excessive amount of
iron is absorbed gastrointestinally. By middle adulthood, hemochromatosis
causes an iron overload, primarily in parenchymal organs such as the heart,
pancreas, and liver. Liver cirrhosis and hepatocellular carcinoma are two of the
more ominous potential complications of this disease.
http://www.pathologieutrecht.nl/im...r_with_hemochromatosis.gif

Abetalipoproteinemia
= normal intestinal mucosal structure and epithelial cells with clear (or foamy)
cytoplasm, which is more prominent on the tips of the villi. These changes occur
due to accumulation of lipids in the cells of intestinal absorptive epithelium.
-Apolipoprotein B (apoB) is a lipid transport protein that coats chylomicrons.
Impaired synthesis of apoB is present in abetalipoproteinemia, resulting in an
inability to transport lipids from the intestine. Excessive lipids are stored in the
intestinal epithelium cells, a characteristic “foamy” appearance to
cytoplasm. Serum levels of all lipids are decreased.
-Abetalipoproteinemia is an inborn metabolic error transmitted as autosomal
recessive trait. It manifests during the first year of life with symptoms of
malabsorption (abdominal distention, foul-smelling stool), neurologic deficiencies
(progressive ataxia), and retinitis pigmentosa.
http://www.eyepathologist.com/disease.asp?IDNUM=301210
http://www.hindawi.com/journals/cd...figures/723539.fig.003.jpg

Schwannomas
=tumors of the peripheral nervous system that arise from Schwann cells.
Microscopically they are composed of spindle cells, which are the elongated cells
with regular, oval nuclei.
-Schwannomas are biphasic: highly cellular areas (Antoni A pattern) are
intermixed with myxoid areas of low cellularity (Antoni B pattern). The cells in
the Antoni A areas may form “palisading” patterns (like a picket fence).
-Schwannomas are universally S100 positive. Another important S100-positive
tumor is the melanoma (both melanocytes and Schwann cells are derived from
neural crest cells).
-Schwann cells are to the peripheral nervous system, as oligodendrocytes are to
the CNS. Both protect and insulate axons, and both synthesize myelin. The
transition from oligodendrocytes to Schwann cells occurs within a few mm from
the surface of the brain and spinal cord. Schwannomas, therefore, may arise
within the cranial vault and spinal canal, despite belonging to the PNS.
-Cranial nerves are covered with Schwann cells, and are peripheral: thus
schwannomas can arise from any cranial nerve. The optic nerve (CN II) is an
important exception—it is covered by oligodendrocytes and cannot develop a
schwannoma. The most common site of intracranial schwannomas is the
cerebellopontine angle at CN VIII. Schwannomas in this particular location are
also called acoustic neuromas. They can cause tinnitus, vertigo, and
sensorineural hearing loss.
http://www.otopathology.com/acoustic.htm

Acute MI
Ten days following acute myocardial infarction, granulation tissue with
neovascularization begins to replace the zone of dead cardiac muscle. This
granulation tissue is most prominent on light microscopy at days 10-14 post-
infarction.
- Edema and punctate hemorrhages maybe detected in infarcted myocardium by
light microscopy from about 4 hours to 12 hours following myocardial infarction.
-Cytoplasmic hypereosinophilia is one of the earliest light microscopic signs of
coagulative necrosis of cardiac myocytes. It begins approximately 4 hours after
the onset of lethal ischemia. By post-infarction day 14, however, most of the
dead myocytes have been phagocytosed by macrophages.
-Approximately 24 hours after acute myocardial infarction neutrophilic infiltration
of the zone of dead myocardium begins. This acute inflammatory infiltrate then
becomes increasingly prominent, before receding around day5 to 7.
-Macrophage phagocytosis of infarcted myocardium begins at around 5 days
post-infarction, and is usually complete by day 10, when the accumulated
macrophages begin to be replaced by granulation tissue.
-Increased collagen deposition and decreased cellularity in the zone of infarcted
myocardium generally becomes evident beginning at 2 weeks post-infarction.
Fibrosis continues during weeks 2 to 8, resulting in a dense collagenous scar at
around two months post-infarction.
-Infarcted myocardium may appear normal under light microscopy until about 4
hours after the onset of lethal ischemia. After this period, light microscopic signs
of early coagulative necrosis appear.
http://ocw.tufts.edu/data/51/551163/551231_xlarge.jpg

Lipoprotein lipase deficiency

- causes impaired triglyceride clearance from the bloodstream. This enzyme is
synthesized by cells of adipose tissue (Uni loculated adipocytes), skeletal muscle,
and heart muscle. Recurrent bouts of acute pancreatitis, lipemia retinalis and
eruptive xanthomas are seen in these patients.
http://neuromedia.neurobio.ucla.ed...images/2_adipose_cells.gif
http://www.imsb.ethz.ch/researchgr...yte_Function/mat_Fig_1.jpg
Ethylene glycol
=is a widely-available substance found in automobile antifreeze, engine coolants
and hydraulic brake fluids. Ethylene glycol is rapidly absorbed from the GI tract
and metabolized to glycolic acid, which is toxic to renal tubules, and to oxalic
acid, which precipitates as calcium oxalate crystals in the renal tubules.
-Symptoms of acute renal failure (oliguria, anorexia, flank pain) are
characteristic of ethylene glycol poisoning and occur in 24-72 hours after the
ingestion. A high anion-gap metabolic acidosis and osmolar gap are typical.
Calcium oxalate crystals are detected by microscopy of the urine and are shaped
like folded envelopes. Although glomeruli appear normal signs of tubular
epithelial damage are clearly visible on light microscopy. This damage manifests
itself histologically as ballooning and vacuolar degeneration, predominantly in
the proximal convoluted tubules is seen on light microscopy.
http://www.nature.com/ki/journal/v...000107f1.html#figure-title
http://www.nature.com/ki/journal/v...5000107a.html#figure-title

Hereditary spherocytosis
1. Hereditary spherocytosis results from red cell cytoskeleton
abnormalities—the most common is a spectrin deficiency.
2. Hemolytic anemia, jaundice and splenomegaly are classic clinical
manifestations.
3. Diagnosis is made by peripheral smear and osmotic fragility testing.
- Spherocytosis also increases the risk of pigmented gallstones and aplastic crisis
(parvovirus B 19 infection).
- Spherocytes can be identified by the following criteria: they are approximately
two-thirds the diameter of normal RBCs; they are more densely hemoglobinated
at the periphery and they often lack a zone of central pallor. Spherocytes also
stain a deeper red than normal RBCs when viewed on Wright’s stain.
http://www.ezhemeonc.com/wp-conten...yte-100x-website-arrow.jpg

CREST syndrome
= a localized variant of scleroderma.
-An accentuated pulmonary component of the second heart sound suggests an
increase in pulmonary artery pressure, and pulmonary hypertension, in turn, has
caused cor pulmonale and symptoms of right-sided heart failure such as dyspnea
on exertion, lower extremity edema and hepatomegaly.
-Normal pulmonary function tests exclude chronic lung disease as the cause of
pulmonary hypertension, and the absence of a heart murmur on physical
examination makes valvular heart disease less likely.
-Both variants of scleroderma (systemic sclerosis and CREST syndrome) develop
due to increased deposition of collagen in tissues. It is thought to be triggered by
increased proliferation and accumulation of monoclonal T-cells in the affected
tissues that secrete a variety of cytokines, especially TGF-beta, that increase the
production of collagen and extracellular matrix proteins by fibroblasts. All tissues
can be affected, but the earliest damage is seen in small arterioles and
capillaries.
-Microvascular injury of pulmonary arterioles leads to narrowing of the lumen
and increased pressure in pulmonary circulation . Pulmonary hypertension is a
common complication of CREST syndrome. It leads to hypertrophy of the right
ventricle, with subsequent development of right-sided CHF.

Multiple sclerosis (MS)

=neurological deficits that cannot be explained by a single lesion.
- The hallmark of MS is demyelination of the axons, which can occur in any area
of white matter. Loss of myelin sheaths and depletion of oligodendrocytes is
seen within the plaques. Lipid laden macrophages containing the products of
myelin breakdown are also seen within plaques.
-MRI of the brain is diagnostic in most cases and typically shows demyelinating
plaques.
- CSF of these patients demonstrates increased concentration of gamma globulin
(lgG). It is found as an “oligoclonal band” on protein electrophoresis.
-Visual evoked potentials are used to assess conduction velocity, which slows in
MS due to demyelination of nerve fibers.
- Oligodendrocyte depletion is also seen in progressive multifocal
leukoencephalopathy.
https://hvelink.saintlukeshealthsy...ia/medical/hw/h9991221.jpg

Metastatic prostate cancer

- Back pain not relieved by rest or position change is a typical presentation for
neoplastic bone disease. The combination of symptoms of urinary urgency
nocturia, frequency, and hesitancy with constant back pain in an elderly man
together suggest prostate cancer.
- Metastatic prostate cancer has a strong predilection for bones (especially the
axial skeleton). Bone metastases in prostate cancer are blastic (sclerotic),
detected by radionuclide bone scanning.
-Prostate cancer is the most common type of malignancy in men. These
adenocarcinomas arise from the peripheral zone of the gland. The most common
presenting symptoms of prostate cancer are urinary frequency, hesitancy,
nocturia and hematuria. Because the tumor is located on the periphery of the
prostate, it is easily detected on digital rectal examination as an asymmetric
nodular enlargement of the prostate. Prostate cancer is associated with
increased level of prostate-specific antigen (PSA). In advanced disease, there
may be increased prostatic acid phosphatase (when the tumor penetrates the
capsule of prostate) and increased alkaline phosphatase (due to bone
metastases).
http://library.med.utah.edu/WebPath/MALEHTML/MALE074.html
http://library.med.utah.edu/WebPath/MALEHTML/MALE113.html
http://library.med.utah.edu/WebPath/MALEHTML/MALE114.html

Cardiac tamponade
-Clinically significant cardiac tamponade is associated with hemodynamic findings
such as pulsus paradoxus and arterial hypotension. Symptomatic cardiac
tamponade typically occurs when the pericardial pressure exceeds 10 mmHg.
This force is sufficient to cause collapse of the atria, which results in an increase
in systemic venous pressure, reduced ventricular preload, and eventually
decreased cardiac output.
-Death from cardiac tamponade occurs from cardiogenic shock, when cardiac
output becomes insufficient to provide the necessary oxygen to the patient’s
tissues.
-Pulsus paradoxus is an important clue to cardiac tamponade. Pulsus paradoxus
is an exaggeration of the normal physiologic decrease in blood pressure that
occurs during inspiration. It is defined as a drop in arterial blood pressure during
inspiration of over 10 mmHg (a decrease of less than 10 mmHg during
inspiration is physiologic). Pulsus paradoxus can be grossly diagnosed by
palpating the radial pulse and noting that it disappears during inspiration. A
more accurate means of diagnosis is done by blood pressure measurement with
a sphygmomanometer noting a decrease in arterial pressure greater than 10
mmHg during inspiration.
http://radiographics.rsna.org/content/27/6/1595/F5.large.jpg
DIFF:
- Pulsus alternans occurs in patients with left ventricular dysfunction. It is
defined as a beat to beat variation in the magnitude of the pulse pressure in the
presence of a regular cardiac rhythm.
- dicrotic pulse refers to a pulse with two distinct peaks, one during systole and
the other during diastole. It can be best palpated in the carotid arteries. This
finding typically occurs in patients with severe systolic dysfunction.
- Pulsus parvus et tardus refers to the pulse palpated in patients with aortic
stenosis. This pulse alteration literally refers to a pulse of low magnitude with a
delayed peak.
- A hyperkinetic pulse refers to the rapid ejection of a large stroke volume
against a decreased afterload. This can occur during fever or exercise in normal
subjects, or in patients with high-output conditions such as a PDA or an A-V
fistula

Hepatitis B virus infection

- two phases: the proliferative phase and the integrative phase.
-In the proliferative phase the entire virion and all related antigens of the
episomal HBV DNA are present. On the hepatocyte cell surface, viral HBsAg and
HBcAg are expressed in conjunction with the major histocompatibility complex
(MHC) class I molecules. This expression serves to activate the cytotoxic CD8+ T
lymphocytes, which respond by destroying the infected hepatocytes. Note that
the virion itself does not have a cytopathic effect.
-In the integrative phase, the HBV DNA is incorporated into the host genome of
those hepatocytes that survived the immune response. Infectivity ceases and
liver damage tapers of when the antiviral antibodies appear and viral replication
stops. The risk of hepatocellular carcinoma however remains elevated because of
the HBV DNA that has been integrated into the host genome.
http://depts.washington.edu/hepstudy/images/hepB/hbvdx1_d05.gif
http://tpis.upmc.com/TPIShome/chan...?url=/tpis/HB/H00030x.jsp?
http://www.philadelphia-reflections.com/images/hepB.jpg
- Host antibody HBsAb neutralizes HBV infectivity by binding to the viral surface
antigen HBsAg and preventing the antigen from interacting with hepatocyte
receptors.
- Antigen-antibody complexes cause some of the early symptoms of hepatitis B
virus infection (eg, arthralgias, arthritis, and urticaria) as well as some of the
chronic complications (eg, immune complex glomerulonephritis,
cryoglobulinemia, and vasculitis). These complexes are not responsible for
hepatocellular damage however.
-The pathogenesis of autoimmune hepatitis (not hepatitis B infection) involves
antigen mimicry with generation of self-antigen recognizing CD4 + T
lymphocytes that damage hepatocytes.

Liver infarction
- Infarcts in a normal liver are rare because it has a dual blood supply: the portal
vein and hepatic artery. Should the hepatic artery be occluded the portal venous
supply and retrograde arterial flow through accessory vessels is typically
sufficient to sustain the liver parenchyma. The notable exception is when a
transplanted liver undergoes hepatic artery thrombosis. In this case the liver can
develop biliary tree infarction and organ failure because the collateral blood
supply is severed during transplantation.
- Organ susceptibility to infarction after occlusion of a feeding artery is ranked
from greatest to least as follows: central nervous system, myocardium, kidney,
spleen, and liver. The presence of a dual or collateral blood supply (as seen in
the liver which is supplied by the hepatic artery and portal vein) enables organs
to tolerate arterial occlusion.

Ovarian cancer
-Epidemiological studies have linked ovarian cancer to conditions associated with
ovarian dysfunction such as infertility, nulliparity, miscarriages, and use of
clomiphene citrate to induce ovulation. Itis postulated that the risk of ovarian
cancer is increased in these conditions due to irregularities of reparative
processes on the ovarian surface (repeated aberrant repair is thought to induce
cellular dysplasia and neoplasia). Oral contraceptives reduce the risk of non-
hereditary ovarian cancer by decreasing the total number times a woman
ovulates in her lifetime. With fewer ovulatory cycles, there is less need for repair
at the ovarian surface. (It is unclear whether oral contraceptive pills reduce the
risk of hereditary ovarian cancer associated with the BRCA gene mutation.)
Multiparity and breast-feeding also decrease the risk of ovarian cancer.
-Mortality rates are higher for ovarian cancer than for endometrial or cervical
cancer. Because there is no effective screening method for ovarian cancer,
patients often present with advanced disease. Oftentimes, patients with
metastatic ovarian cancer have elevated circulating levels of CA-125. However,
CA-125 can also be elevated in number of other malignant conditions (e.g.
cancers of the endometrium, cervix, fallopian tube, lung and colon) as well as
non-malignant conditions making it a poor screening marker for ovarian cancer.
http://www.cancersafe.com/cancers/ovarian.asp

Rheumatic mitral valvular disease

=diffuse fibrous thickening, distortion of the mitral valve leaflets. There may also
be some commissural fusion at the leaflet edges and the mitral valve orifice
maybe somewhat stenotic. The relatively large surface area of the walls of the
left atrium is consistent with atrial dilatation. All of these findings are
characteristic of rheumatic mitral valvular disease.
-Fibrosis of the valve leaflets in chronic rheumatic heart disease following acute
rheumatic fever is the most common cause of mitral stenosis, accounting for up
to 99% of cases. Mitral stenosis can cause atrial enlargement, which may lead to
atrial mural thromboses. Thrombi dislodged from the wall of the left atrium may
later cause an embolic stroke, as likely occurred in this patient.
http://wpcontent.answers.com/wikip...athology_20G0013_lores.jpg
http://www.som.tulane.edu/classwar...cPath/GR_Heart/Heart7.html
http://www.som.tulane.edu/classwar...cPath/GR_Heart/Heart9.html

Degenerative calcific deposits

-most commonly develop in the mitral valve annulus in women over age 60 and
in individuals with a myxomatous floppy mitral valve or an elevated left
ventricular pressure.
- mitral annular calcification generally does not impair valve function.
http://www.learningradiology.com/c...eekpix2007-1/cow247arr.jpg

Pure red cell aplasia (PRCA)

=a rare form of marrow failure characterized by marked hypoplasia of marrow
erythroid elements in the selling of normal granulopoiesis and thrombopoiesis.
-PRCA can be idiopathic or due to a secondary process like a thymoma. The
association between thymomas and PRCA is well-documented. Removal of the
thymoma can cure the PRCA. Thus, all patients with PRCA should undergo a
chest CT scan. PRCA can also result from parvovirus B19 infection. This virus
preferentially attacks and destroys proerythroblasts. Recent parvovirus infection
can be confirmed via the detection of anti-B19 1gM antibodies in the serum.
http://www.wz16.net/Upload/Update/Info/2006330111442727.jpg

Subdural hematoma
= an accumulation of blood between the dura mater and arachnoid. The blood
comes from the bridging cortical veins which carry blood from the cortex to the
venous sinuses. They can rupture as a result of acceleration-deceleration injury.
As the hematoma expands, it raises the intracranial pressure and compresses
the brain.
-Venous bleeding is relatively slow which explains the gradual onset of
symptoms in subdural hematoma. Patients complain of gradually worsening
headache and display a slow decline in mental function. On CT scan, subdural
hematoma is seen as a crescent-shaped mass.
-Subdural hematoma often occurs in elderly individuals after a minor trauma.
This increased incidence is explained by age-related brain atrophy. As the
distance from the skull to the brain surface increases cortical bridging veins are
under more tension and rupture more easily. In elderly patients, subdural
bleeding is called a “great imitatorâ€ﾝ due to its subtle and variable
presentation. It may present as gait abnormalities, seizures, somnolence,
confusion and memory loss. These patients may go undiagnosed for weeks.
http://www.neurosurgery.com.sg/ima.../neurotrauma/LtSDHpre2.jpg

Rupture of lateral striate arteries

- The lateral striate arteries arise from the middle cerebral arteries. They are
also called the penetrating branches. These vessels supply the internal capsule
and the basal ganglia, and often rupture in hypertensive strokes.
http://commons.wikimedia.org/wiki/...ittal_view_description.JPG

Posterior communicating artery rupture

= the second most common site of rupture of berry aneurisms in the circle of
Willis (anterior communicating artery is the most common site). This results in
subarachnoid bleeding. It manifests with a severe headache that may be
described as “the worst headache of my life”. Fever and nuchal rigidity are
commonly present.
http://anatomy.med.umich.edu/atlas/n3a8p2.html

Cystinuria
=resulting from a defective transporter of dibasic amino acids is an autosomal
recessive disorder. The only clinical manifestation of this disorder is lifelong
recurrent urolithiasis. The classic clinical presentation is colicky flank pain and
hematuria, followed by the eventual passage of a stone.
- Cystine, ornithine, lysine and arginine are dibasic amino acids that share a
common transport mechanism in the kidney and intestinal lumen. In the gut
these amino acids are reabsorbed via a high affinity transporter on jejunal cells.
In the kidneys these substances are filtered at the glomerulus and reabsorbed by
a similar transmembrane channel on proximal tubular cells. Inherited defects of
this transport channel lead to defects in renal and intestinal reabsorption thus
causing these amino acids to be excreted in urine and feces.
-Ornithine, lysine, and arginine are soluble in urine; cystine however is relatively
insoluble at the physiologic urine pH of 5-7 (pKa = 8.3). Thus as the urine pH
increases so does cystine’s solubility. Risk factors for cystine precipitation
include: low urine pH, the presence of already formed cystine crystals, and urine
supersaturation.
http://www.medicine.uiowa.edu/cme/clia/images/testID20/UA067.jpg
http://img.medscape.com/pi/emed/ck...5-435576-435678-435819.jpg
- Mental retardation occurs in several inborn errors of amino acid metabolism
including phenylketonuria, homocystinuria and in some patients with maple
syrup urine disease. Mental retardation is not seen in cystinuria.

Asbestosis
=Localized pleural thickening with calcification particularly of the parietal pleura
of the posterolateral mid-lung zones and diaphragm. These calcified lesions are
referred to as pleural plaques.
-Lung injury due to asbestos inhalation predominantly affects the lower
pulmonary zones and manifests radiographically as linear interstitial densities in
the lower lobes. Small pleural effusions which are exudative and possibly blood
stained may occasionally be noted.
http://www.atsdr.cdc.gov/asbestos/....net_3q4959_Asbestosis.jpg
http://familyrights.us/vpap/asbestosis.jpg
DIFF:
- Unlike asbestosis, pulmonary silicosis is not strongly associated with pleural
plaques or effusions. Nodular densities and eggshell calcifications of the hilar
nodes are seen.
http://www.meddean.luc.edu/lumen/m...iseases/environmental4.htm
-Pulmonary berylliosis closely resembles sarcoidosis (nodular infiltrates, enlarged
lymph nodes, noncaseating granulomas) but is not strongly associated with
pleural plaques or effusions.
http://img.medscape.com/pi/emed/ck...logy/295571-296759-206.jpg
-The coal macules of coal worker’s pneumoconiosis are seen radiologically as
multiple discrete nodules (1- 4mm), most prominent in the upper lung zones.
Pleural plaques or effusions are not typical.
http://www.meddean.luc.edu/lumen/M...NAR/images/path3/sld19.jpg
- Hypersensitivity pneumonitis due to inhalation of organic dusts tends to result
in diffuse nodular interstitial infiltrates on chest x-ray. Pleural plaques or
effusions are not typical.
ALL
- bone marrow smear shows several lymphoblasts with a high nuclear-to-
cytoplasmic ratio, variably condensed nuclear chromatin, and prominent nucleoli.

-The differential diagnosis of this acute lymphoblastic leukemia (ALL) includes

precursor B-cell leukemia (precursor B-ALL) and precursor T-cell leukemia
(precursor T-ALL). Precursor B-ALL and precursor T-ALL can be distinguished
from each other only by immunophenotyping. Lymphoblasts in precursor B-ALL
are positive for TdT, CD1O, and almost always for CD19. In contrast,
lymphoblasts in precursor T-ALL are TdT positive and variably express CD1a and
the T cell markers CD2, CD3, CD4, CD5, CDT and CD8.
- ALL is primarily a disease of children (75% occurs in children under six years of
age). Most patients with precursor B- ALL present with evidence of bone marrow
failure: thrombocytopenia and/or anemia and/or neutropenia. The leukocyte
count may be normal, decreased or increased.
(Choice B) Precursor T-ALL accounts for about 15% of all childhood ALL and is
more common in adolescents than younger children. Patients typically present
with a high leukocyte count and often a large mediastinal mass. The
lymphoblasts in precursor T-ALL variably express CD1a and T-cell markers like
CD3, CD4, and CD8.
DIFF:
- Mature B-cell leukemia (or chronic lymphocytic leukemia/small lymphocytic
lymphoma, CLL/SLL) is a neoplasm of small, round, monomorphic B-lymphocytes
in the peripheral blood, bone marrow and lymph nodes. These neoplastic
lymphocytes express CD19 (B-cell marker) and coexpress CD5 (T-cell marker)
on their surface.
- Mature T-cell leukemia is a group of uncommon neoplasms that are derived
from mature or post-thymic T cells. Findings would include more mature
lymphocytes (not blasts) expressing T-cell markers.
http://www.meb.uni-bonn.de/cancer.gov/Media/CDR0000526538.jpg
http://www.healthsystem.virginia.e...ssIDB/Cell-Comparisons.cfm
http://www.healthsystem.virginia.e...rders/Leukemias/ALL-L1.cfm
http://www.wadsworth.org/chemheme/heme/microscope/all.htm
http://www.wadsworth.org/chemheme/heme/microscope/aml.htm
http://www.wadsworth.org/chemheme/heme/microscope/cgl.htm
http://www.wadsworth.org/chemheme/heme/microscope/cll.htm
http://www.healthsystem.virginia.e...ocytic-T-cell-leukemia.cfm

Reye syndrome
= hepatic failure and acute encephalopathy, and is most commonly associated
with the use of aspirin in patients 5-14 years old. The febrile illness that proceed
Reye’s syndrome is frequently an upper respiratory infection, influenza,
measles, varicella or another viral disease.
-The pathogenesis of this condition is still unclear, but it is hypothesized that
affected children have some inborn metabolic error that renders them sensitive
to the toxic effects of salicylates. It is especially pronounced in viral-infected
cells and causes mitochondrial dysfunction. The two components of Reye’s
syndrome include:
1. Hepatic dysfunction manifests with vomiting and hepatomegaly, but jaundice
is rare. Liver function tests reveal increased levels of ALT, AST, ammonia, and
bilirubin, and a prolonged PT and PTT. Light microscopy of a liver biopsy shows
microvesicular steatosis, the presence of small fat vacuoles in the cytoplasm of
hepatocytes . No necrosis or inflammation is present in the liver. Electron
microscopy findings include swelling, a decreased number of mitochondria and
glycogen depletion.
2. Encephalopathy of Reye syndrome is attributed to hepatic dysfunction and the
toxic effect of hyperammonemia on the CNS leading to cerebral edema.
To avoid the possibility of inducing Reye syndrome, aspirin should not be
administered to children under the age of sixteen except for very specific
circumstances where it is indicated for the treatment of a serious illness such as
in Kawasaki disease where salicylates are a mainstay of treatment.
http://www.pathguy.com/sol/40040.jpg

Gestational choriocarcinoma
= malignant tumor that arises from the trophoblast. It is most commonly
preceded by an evacuated hydatidiform mole. However this neoplasm can also
occur following abortion, normal pregnancy, or ectopic pregnancy.
-Clinically, the tumor causes abnormal vaginal bleeding, uterine enlargement,
and significantly increased chorionic gonadotropin levels. Choriocarcinoma is an
aggressive tumor that rapidly invades the uterine wall and metastasizes
hematogenously.
-The lungs are the most common site of distal spread. This tumor is highly
sensitive to chemotherapy.
-On macroscopic examination gestational choriocarcinoma is seen as a bulky
intrauterine mass that is usually soft and yellow-white, with extensive areas of
necrosis and hemorrhage.
-Histologically, it is composed of abnormal proliferations of both cyto
trophoblasts and syncytiotrophoblasts. No villi are present.
http://www.pathconsultddx.com/imag...59867506701565/gr2-sml.jpg
http://nursingcrib.com/wp-content/uploads/hydatidiformmole.jpg
DIFF:
- Endometrial adenocarcinoma consists of disorganized glands composed of
neoplastic columnar cells. This malignancy occurs in postmenopausal women and
presents with vaginal bleeding. Endometrial adenocarcinoma is not related to
pregnancy and patients do not have elevated b-hCG levels.
http://www.pathguy.com/~dlaporte/endo_ca.htm
- Carcinosarcomas (malignant mixed mullerian tumors) of the uterus are
composed of epithelial (endometrial-type glands) and mesenchymal
(sarcomatous) elements. These tumors are not associated with pregnancy and
do not cause b-hCG elevations.
http://en.wikipedia.org/wiki/File:Uterine_carcinosarcoma.jpg
- Malignant teratomas can contain tissue elements resembling immature
cartilage. These tumors can occur in the ovaries, but not in the uterus. Patients
present with abdominal pain and an ovarian mass. An ovarian teratoma would
not cause vaginal bleeding.
http://path.upmc.edu/cases/case52/images/gross4.jpg

Goodpasture syndrome
= caused by anti-glomerular basement membrane antibodies (anti-GBM
antibodies) that target the a3-chain of collagen type IV. (It is important to
remember that the GBM is composed of collagen type IV.) These patients
develop rapidly progressive glomerulonephritis (RPGN) that results in acute renal
failure with crescent formation on light microscopy. Crescents will have fibrin
deposition. Fluorescence microscopy shows “linear” lgG and C3 deposition.
Since this is a nephritic picture, there are red blood cell casts and mild
proteinuria (<1 g/day) on urinalysis, and the patient may become hypertensive.
These anti-GBM antibodies cross-react with other basement membranes,
especially those in the lung alveoli causing pulmonary hemorrhage (hemoptysis).

http://www.pathguy.com/sol/00049.jpg
http://www.pathologyatlas.ro/patho...tic_glomerulonephritis.jpg

Marfan syndrome
-upper body (head to pubis) is disproportionately short compared to leg length.
-spinal scoliosis and kyphosis (posterior convex angulation of the spine), long
extremities, and long tapering fingers
-Marfan syndrome is an autosomal dominant defect in the connective tissue
glycoprotein fibrillin-1 which causes abnormalities in the skeleton, eyes (lens
dislocation), and cardiovascular system. The cardiovascular lesions are the most
potentially life-threatening. The two most common cardiac abnormalities are
mitral valve prolapse and cystic medial degeneration of the aorta. Cystic medial
aortic degeneration may lead to aortic dilatation and dissection. Aortic dissection
is the cause of death in 30% to 45% of patients with Marfan syndrome, followed
by cardiac failure (which maybe secondary to mitral and/or aortic regurgitation).
The average age at death in Marfan syndrome is between 30 and 40 years.
http://www.medstudents.com.br/original/revisao/marfan/marfan2.jpg
http://www.scoliosisassociates.com.../our_unusualscoliosis7.jpg

Osteomyelitis
-The metaphyses of long bones are typically affected by hematogenous
osteomyelitis due to their rich vascularization and capillary fenestrae.
-Osteomyelitis is an infection of bone and bone marrow that occurs by:
1. Seeding of ischemic or infarcted bone, as occurs in sickle cell disease with
salmonella.
2. Hematogenous seeding of infection in normal bone, as occurs in children with
S. aureus, S. pyogenes and E. coil. This is also the mode by which M.
tuberculosis gains access to the bone and causes chronic osteomyelitis (Pott
Disease in the vertebrae).
3. Spread from a contiguous focus of infection, as occurs in Pseudomonas
aeruginosa osteomyelitis from an infected diabetic foot wound.
4. Direct infection of bone, as occurs in a compound fracture.
-Hematogenous osteomyelitis is predominantly a disease of male children. It is
initially an acute process, but without proper treatment it progresses to chronic
suppurative osteomyelitis where necrotic bone (sequestrum) serves as a
reservoir for infection and becomes covered by a poorly constructed shell of new
bone called the involucrum. Proper treatment includes antibiotic therapy and
debridement of necrotic bone. In the case of hematogenous osteomyelitis, the
proximal tibia, distal femur and proximal humerus are the most common bones
involved.
http://medical-dictionary.thefreed...orland&name=sequestrum.jpg
-The vertebral body is the most common location for hematogenous
osteomyelitis in the adult. This is also the location of Pott Disease, osteomyelitis
of the vertebral body caused by Mycobacterium tuberculosis.
-The long bone epiphysis is usually spared in osteomyelitis unless the acute
infection is not treated at which point the infection could spread into the joint
resulting in a pyogenic arthritis.
-The diaphysis can be involved in hematogenous osteomyelitis if the acute event
is not recognized and treated due to local bacterial invasion. The diaphysis is the
location of the bone marrow, and if infection gains access to this area of the
bone there will be resultant necrosis of a large portion of bone as well as a risk
of sepsis.
- Staphylococcus aureus and Streptococcus pyogenes (Group A Strep) are the
first and second most common causes of this disease, respectively, and
hematogenous osteomyelitis most frequently affects children and young adults.
-Pseudomonas aeruginosa frequently plays a role in osteomyelitis resulting from
chronic wounds such as in diabetics.

Avascular necrosis (osteonecrosis)

- occurs due to impaired blood supply to a segment of bone. The femoral head is
the most common location. Avascular necrosis of the femoral head is strongly
associated with the following conditions:
1. Sickle cell disease leads to avascular necrosis due to thrombotic occlusion of
arteries. Embolic occlusion (fat emboli, air emboli) can also cause avascular
necrosis.
2. Injury to the vessel wall (vasculitis) causes impaired blood supply to the
femoral head in systemic lupus erythematosus (SLE).
3. High-dose steroid therapy and alcoholism are also associated with avascular
necrosis of the femoral head
-Avascular necrosis of the femoral head presents with groin pain that is
exacerbated by weight bearing. Physical examination reveals painful and
restricted passive and active movement in the affected joint. There is no
swelling, erythema or temperature change to the affected area. MRI is the most
sensitive modality for diagnosing avascular necrosis.
http://www.xray2.20m.com/custom2.html
Hydronephrosis
-significantly enlarged kidney, with dilatation and deformation of the calices and
renal pelvis.
- On cut surface, this kidney would show marked atrophy and scarring of the
renal parenchyma and distortion of renal architecture. Light microscopy would
reveal interstitial fibrosis with patches of mononuclear infiltration and tubular
atrophy.
-Hydronephrosis is caused by prolonged urinary tract obstruction.
-Nephrolithiasis, tumor, anatomic abnormality, pregnancy, or functional
disorders (such as neurogenic bladder) are common causes. In older males,
benign prostatic hyperplasia is the most common cause of urinary obstruction.
The obstruction causes urinary stasis proximal to the blockage, with gradually
increasing urinary pressure and subsequent dilatation of ureters, urinary pelvis
and calices. When urinary pressure reaches a critical level, it overcomes renal
blood flow and disables glomerular filtration. Ischemia, nephron loss, and cortical
atrophy follow.
http://health.act.gov.au/gfx/pubs/-554515641_r0.jpg

Chronic myelogenous leukemia (CML)

-is associated with a specific cytogenetic abnormality. In this condition, the
classic and most common cause of disease is a translocation between
chromosome 9 and 22 in an immature myeloid precursor cell. The ABL oncogene
is transported from chromosome 9 to chromosome 22 where it is placed adjacent
to the BCR proto-oncogene. The new gene BCR-ABL codes for a protein with
tyrosine kinase activity. This protein stimulates proliferation of granulocytic
precursors and leads to development of CML. The chromosome that carries the
fusion gene BCR-¼BL is called the Philadelphia chromosome.
Imatinib (Gleevec) is a tyrosine kinase inhibitor specific for the BCR-ABL fusion
protein of CML. It competitively binds the ATP binding site of the ABL portion of
this protein thereby decreasing its activity.
http://www.nature.com/leu/journal/.../fig_tab/leu2008119f1.html

Sydenham chorea( hyperkinetic extrapyramidal movement disorder)

=purposeless extremity movements and restlessness
= the most common acquired chorea of childhood, and is the sole neurologic
manifestation of acute rheumatic fever. Sydenham chorea is thought to be a CNS
autoimmune reaction precipitated by a group A 3-hemolytic streptococcal sore
throat after a latency of 2-3 months. Anti-neuronal antibodies binding to the
caudate and subthalamic nuclei may be involved.
-Since Sydenham chorea is a manifestation of acute rheumatic fever, a patient
with this disorder would be at risk for chronic rheumatic heart disease, including
mitral and aortic valve involvement.
http://www.youtube.com/watch?v=VoHWsQWHbWQ&feature=related
http://www.pathology.vcu.edu/education/cardio/lab2.a.html
- Diagnosis of acute rheumatic fever requires either two major Jones criteria or
one major and two minor Jones criteria, with supporting evidence of an
antecedent group A streptococcal infection. The Jones criteria are:
Major Criteria: carditis, polyarthritis, chorea, erythema marginatum,
subcutaneous nodules
Minor Criteria: fever, arthralgia, elevated acute-phase reactants (erythrocyte
sedimentation rate or C-reactive protein), prolonged PR-interval
-Supporting evidence of an antecedent group A streptococcal infection may be a
positive throat culture or rapid antigen test or an elevated or rising streptococcal
antibody titer. As is evident from these criteria, renal failure is not part of the
acute rheumatic fever clinical syndrome.

Acute pancreatitis
- duct obstruction leads to stasis of pancreatic secretions and digestion of
adipose cells by lipase. This results in formation of fatty acids that bind calcium
ions and precipitate as insoluble calcium salts. The areas of focal necrosis and
calcium precipitation induce an inflammatory reaction. If the pathologic process
stops at this stage, benign acute interstitial pancreatitis develops. In this
subtype of acute pancreatitis, the pancreas looks edematous on macroscopic
examination. On light microscopy, interstitial edema, focal fat necrosis and
calcium deposits are seen. If the inflammatory process continues, blood flow to
the pancreatic acini is compromised as a result of the edema. Ischemia damages
the acinar cells and causes abnormal intracellular activation of trypsin. Trypsin
then activates other proteolytic enzymes, thus initiating autodigestion (autolysis)
of pancreatic tissue. Acute necrotic pancreatitis develops. Destruction of blood
vessel walls can cause hemorrhage into the necrotic areas. Macroscopically,
areas of white chalky fat necrosis are visible in the pancreatic tissue. They can
spread onto the mesentery, omentum and other parts of abdominal cavity. Black
areas of hemorrhage are also seen on gross examination.
http://www.wses.org.uk/foto/Acute%20Pancreatitis.jpg
DIFF:
- Intestinal perforation (due to ulcer, mesenteric ischemia, tumor or
inflammatory bowel disease) is characterized by the presence of a defect in the
intestinal wall along with signs of peritonitis.
- Bacterial peritonitis is characterized by a dull-appearing peritoneal surface with
areas of viscous white- yellow suppurative exudate.

Hemiballism
=Wild flinging movements of the extremities on one side of the body (arm
and/or leg)
- It occurs due to damage of the contralateral subthalamic nucleus—most
commonly from a lacunar stroke. Patients suffering lacunar strokes usually have
a long history of hypertension. The subthalamic nucleus is a component of the
basal ganglia. It is ventral to the thalamus and superior to the internal capsule.
http://homepages.inf.ed.ac.uk/anar...arch/anatomy/anatomy1.html
DIFF:
- Involvement of lentiform nucleus (globus pallidus and putamen) is
characteristic of Wilson disease (hepatolenticular degeneration). Manifestations
include wing-beating tremor, psychosis and cirrhosis. Kayser Fleischer rings are
seen in the cornea.
http://aids.hallym.ac.kr/d/kns/tutor/medical/ns10.jpg
- Damage to the substantia nigra occurs in Parkinson disease
- Atrophy of the caudate nucleus occurs in Huntington disease. Chorea,
dementia, and behavioral abnormalities are typical.
- Damage to the internal capsule occurs when perforating arteries are obstructed
(lacunar infarcts) and results in pure motor or pure sensory deficits.
http://neuropathology.neoucom.edu/...ebralinfarcts.html#lacunar
- Lesions of the thalamus can cause thalamic syndrome. This syndrome of post-
stroke pain occurs in about 2% of stroke victims and is often described as a
burning or stabbing sensation of one half of the body (contralateral to the
lesion).
http://www.thebrainwiki.com/uploads/Forebrain/thalamus.jpg

ATN
-Decreased renal blood flow triggers a chain of pathophysiologic changes in the
nephron that cause tubular epithelial necrosis and acute renal failure. The
initiating stage of ischemic ATN is usually unnoticed by clinicians as the
symptoms of the main disorder (hemorrhage, acute MI, sepsis etc) prevail.
- If significant tubular damage occurs the oliguric stage (maintenance stage)
follows in 24-36 hours. During this stage, urine output decreases, and metabolic
changes of acute renal failure manifest. The most significant of these changes
are detailed below:
1. Increased extracellular fluid volume can cause weight gain, edema, and
pulmonary vascular congestion.
2. Hyperkalemia is usually asymptomatic when serum K concentration is <6.0
mEq/L. Above this level, peaked T waves are apparent on ERG, and potentially-
fatal ventricular arrhythmias are possible.
3. Retention of both hydrogen and anions (sulfate, phosphate, and urate) will
lead to high anion gap metabolic acidosis.
4. Other electrolyte changes include a decreased concentration of sodium and
calcium and an increased level of phosphate and magnesium.
5. Urinalysis reveals pathognomonic muddy brown casts, low urinary osmolarity
(<350), high urinary sodium (>30), and high urinary fractional sodium excretion
(Fe Na >1).
-In spite of the seemingly-profound damage that occurs to nephrons in ATN
tubular epithelial cells have an excellent regenerative capacity. If the patient
survives the oliguric stage (by conservative management or dialysis) the
recovery stage will follow in 1-2 weeks. It manifests by vigorous diuresis
(sometimes >3 L/day). Because renal tubules cannot yet function fully
electrolyte balance is still altered. High-volume hypotonic urine causes sodium
retention and decreased concentrations of K, Mg, P04, and Ca. Hypokalemia is
one of the most serous complications of the recovery phase of ATN.
- During the recovery phase (polyuric phase) of ATN patients can become
dehydrated and can develop severe hypokalemia due to high-volume hypotonic
urine.

Clubbing
=Thickening of the distal portion of the distal phalanges
-This deformity of the fingers and fingernails is associated with a number of
chronic diseases causing hypoxia. On physical exam, the fingers will have a
“drumstick” appearance due to thickening of the distal phalanges.
Flattening of the nail folds and shininess of the nail and distal portion of the
finger will also be evident. Pressing on the nails reveals a spongy fluctuant
sensation of the nailbeds.
-Clubbing develops insidiously and is a sign of chronic hypoxic disease most
commonly. The pathophysiology of digital clubbing has yet to be completely
elucidated but it is thought to be caused by vasodilatation of the capillaries in the
distal phalangeal region leading to increased blood flow to the distal portion of
the finger, interstitial edema and increased growth of fibrovascular tissue. A
number of circulating vasodilators have also been implicated in the development
of clubbing. The following conditions commonly cause digital clubbing:
1. Lung diseases: lung cancer (especially large-cell carcinoma), tuberculosis,
cystic fibrosis bronchiectasis , pulmonary hypertension empyema and many
other chronic lung diseases associated with hypoxia.
2. Heart diseases: cyanotic congenital heart diseases (five T’s, especially
tetralogy of Fallot).
3. Other: Inflammatory bowel diseases (Crohn, ulcerative colitis)
hyperthyroidism, malabsorption.
http://inventorspot.com/files/images/finger%20clubbing2.jpg

Lung transplantation
- may be complicated by both acute and chronic rejection. Acute rejection can be
effectively treated with immunosuppressants. Chronic rejection, however, is a
major cause of morbidity and mortality among transplant patients. Chronic
rejection affects the small bronchioli producing the obstructive lung disease
known as bronchiolitis obliterans.
-The pathologic basis of this condition is lymphocytic inflammation and necrosis
of the bronchiolar walls. Early on, fibrinopurulent exudate and granulation tissue
are found in the lumen of the bronchioli. They are later replaced by connective
tissue. Scarring leads to progressive obliteration of small airway lumens.
- Ischemia-reperfusion injury (or reperfusion edema) is a form of noncardiogenic
pulmonary edema that can occur in the allograft due to surgical trauma, organ
ischemia, denervation, or interruption of lymphatic outflow. Reperfusion edema
is seen during the first few days following transplantation
- Acute rejection occurs within days to weeks of transplantation. There are
perivascular mononuclear infiltrates on histologic examination. The symptoms of
acute rejection include dry cough, dyspnea, and fever. Parenchymal infiltrates
are seen on chest x-ray.
- Infection is the leading cause of death in lung transplant recipients. CMV is the
most significant opportunistic infection in lung transplant recipients. Infected
cells have a characteristic intranuclear inclusion surrounded by a clear halo
(owl’s eye inclusion).

Congenital pyloric stenosis

=a relatively common disorder that is encountered primarily in male infants (at a
3:1 ratio) and characterized by a multifactorial pattern of inheritance.
- Infants typically present with recurrent projectile nonbilious vomiting, and
physical examination demonstrates visible peristalsis and the presence of an
olive-sized mass in the distal stomach or pyloric region. The mass is thought to
develop secondary to hypertrophy of the pyloric muscularis mucosae. The
narrowing of the pyloric channel is thought to be exacerbated by localized edema
and inflammation. The stenosis is relieved by surgical splitting of the muscle.
http://www.ultrasound-images.com/i...ic-pyloric-stenosis-1a.jpg
http://bms.brown.edu/pedisurg/imag...icStenosisUmbrellaSign.jpg
DIFF:
- Acquired pyloric stenosis occurs in adults and is associated with gastritis, peptic
ulcers in the pylorus, or a neoplastic process (eg, carcinoma of the pyloric region
or lymphoma). Neoplasm in this area would not be expected in an infant,
however.

Arnold-Chiari malformation
= congenital disease due to underdevelopment of the posterior fossa. The small
size of the fossa causes parts of the cerebellum and medulla to herniate through
the foramen magnum.
-There are two types of Arnold-Chiari malformations. In Arnold-Chiari
malformation type I, low-lying cerebellar tonsils extend below the foramen
magnum into the vertebral canal. It may be asymptomatic in infants, but in
adults manifests with headaches and cerebellar symptoms (such as ataxia).
-Arnold-Chiari malformation type II is more severe and becomes symptomatic in
the neonatal period. It is characterized by an abnormally formed cerebellum and
medulla. Both the cerebellar vermis and medulla extend downward through the
foramen magnum. Lumbar myelomeningocele and hydrocephalus (due to
aqueductal stenosis) are almost always present in these patients.
-Arnold-Chiari type II causes symptoms of compression of the medulla such as
difficulty swallowing, dysphonia, stridor, and apnea. Lumbar myelomeningocele
usually leads to leg paralysis. If untreated, hydrocephalus can cause mental
impairment.
http://www.spinabifidainfo.nl/CsfHead2.gif
http://www.medscape.com/content/20...14/art-jphc458614.fig2.gif
http://www.urmc.rochester.edu/neuroslides/slide169.html
Foramen ovale
- is patent in 20-30% of normal adults. Although it usually remains functionally
closed, any abnormality increasing right atrial pressure above left atrial pressure
can produce a right-to-left shunt across a patent foramen ovale.
- Hypoxemia and paradoxical embolization may result. A patent foramen ovale
should be suspected in any patient who has evidence of deep venous thrombosis
of the extremities and has developed a stroke.
http://www.guidetobelize.info/en/d...gtb-dive-foramen-ovale.gif

Endocardial cushion defect

=the result of failure of complete fusion of the endocardial cushions in the
atrioventricular canal during embryonic development.
-The result is usually a persistent atrioventricular (AV) canal, combined with a
continuous lower atrial and upper ventricular septal defect. Moreover, the atrial
and ventricular components of the septal defect are separated by abnormal AV
valves. Endocardial cushion defects are commonly associated with Down
syndrome.
http://www.fetal.com/FetalEcho/04%20Standard.html
http://www.nlm.nih.gov/medlineplus...es/ency/fullsize/22696.jpg

Persistent truncus arteriosus

-accounts for less than 1% of congenital heart defects. It results from incomplete
embryonic development of the aorticopulmonary septum, resulting a single great
vessel leaving the heart. The aorta pulmonary artery, and coronary vessels
originate from an ascending portion of this solitary vessel. In patients with
persistent truncus arteriosus, there is always an associated ventricular septal
defect. This defect causes cyanosis and, if not corrected, results in death due to
congestive heart failure within the first year of life. Obviously, then, this
condition would not normally be found in an adult.
http://www.rush.edu/rumc/images/ei_0427.gif
DIFF:
- The ductus arteriosus normally closes by the third month of life in response to
the high Pa02 of blood shunting from left to right through the ductus afterbirth.
Patency beyond one year of age is abnormal, even though individuals with a
patent ductus arteriosus may survive to middle age.
http://www.schneiderchildrenshospi...l_fixed/images/ei_0350.gif
Primary syphilis
= painless ulceration with raised, indurated borders known as a chancre. The
chancre develops at the site of inoculation of Treponema pallidum, most
commonly on the penis or vulva, one to three weeks after contact and resolves
in three to six weeks. The organism commonly disseminates systemically during
this primary stage.
-Secondary syphilis represents a bacteremic stage of infection and develops five
to ten weeks following resolution of the chancre. It presents with a diffuse
macular rash that include the palms and soles. Condylomata lata are large grey
wart-like growths that occur typically in the genital and perineal region; these
are another typical manifestation of secondary syphilis.
-Latent syphilis is an asymptomatic period divided into early latent (within a year
after resolution of symptoms of secondary syphilis) and late latent (more than a
year of asymptomatic state).
-Tertiary syphilis develops many years after infection in untreated individuals
and includes neurosyphilis, which may be asymptomatic or cause subacute
meningoencephalitis, tabes dorsalis or other neurologic sequelae. Tertiary
syphilis also causes ascending aortic aneurism and resultant aortic valve
insufficiency. Gummas are also characteristic of tertiary syphilis. Gummas are
white-gray granulomatous rubbery lesions that may ulcerate. They are most
commonly cutaneous but also appear in the subcutaneous tissue, bones, liver
and other organs.
http://pathmicro.med.sc.edu/fox/syph1.jpg

Human chorionic gonadotropin (hCG)

= a peptide hormone normally produced by the placenta, but also produced by
tumors such as teratomas, which are tumors often found in testes and ovaries
(Actually, it’s the beta-subunit of hCG that is a tumor marker.) The structure
of hCG is similar to TSH, LH, and FSH. Because of the structural similarities hCG
can bind to the TSH receptor, although with a much lower affinity than TSH. Very
high circulating levels of hCG then can stimulate the thyroid gland, producing
hyperthyroidism. hCG levels are increased in a small percentage of patients with
seminomas, as well.

Circulating alkaline phosphatase

- comes from bone, liver, gastrointestinal tract, and the placenta in gravid
women. Placenta-like alkaline phosphatase (PLAP) can be increased in testicular
germ cell tumors, but it is a nonspecific marker for testicular malignancies. PLAP
can be increased in other malignancies, including pancreatic, lung and colon
cancer.

LDH
= an enzyme involved in anaerobic glycolysis. LDH increase can occur in both
seminomatous and non-seminomatous tumors of the testes.

Synaptophysin
=a transmembrane glycoprotein found in the presynaptic vesicles of neurons,
neuroectodermal and neuroendocrine cells. Immunoreactivity of a CNS tumor for
synaptophysin indicates a neuronal origin . Such neoplasms are rare and
compose less than 1% of CNS tumors. The majority of primary CNS tumors in
adults are of glial origin, meningiomas and pituitary adenomas are the next most
common.
- Primary tumors in adults tend to be supratentorial while those in children tend
to lie below the tentorium. Metastatic disease to the CNS occurs more commonly
than primary CNS tumors.
-Unlike tumors of neuronal origin, gliomas are stain positively for glial fibrillary
acidic protein (GFAP). Immunoreactivity for GFAP is characteristic for
astrocytomas including glioblastoma multiforme, oligodendrogliomas,
ependymomas and peripheral neural sheath tumors.
http://missinglink.ucsf.edu/lm/ids...nation/Figures/MS_GFAP.jpg
- Cells of the arachnoid villi give rise to meningiomas, most of which are benign.
These tumors are diagnosed by imaging; they do not stain for GEAP or
synaptophysin.
- CNS tumors of neuronal origin frequently stain positively for synaptophysin on
immunohistology. Neoplasms of glial origin (astrocytomas, ependymomas, and
oligodendrogliomas) stain for GFAP.

Wallerian degeneration
-occurs in the segment of axon that has lost connection with the cell body. It
represents the degeneration of axon and myelin distal to a point of injury. First,
swelling and irregularity are noted in the distal segment of the axon. Within a
week the axon is destroyed and its fragments are digested by Schwann cells and
macrophages. Similar degenerative changes occur in the segment of axon that
lies proximal to the injury. Degeneration of the proximal segment extends to the
closest node of Ranvier.
-The changes seen in the neuronal body after the axon is severed are called
axonal reaction. The cell body shows signs of cellular edema. It becomes swollen
and rounded, with the nucleus displaced to the periphery. Nissl substance
becomes fine granular and dispersed through out the cytoplasm (central
chromatolysis). Axonal reaction becomes visible in 24-48 hours after the injury.
Maximal changes in the neuronal body occur approximately 12 days after the
injury. These changes reflect an increased synthesis of protein by the cells in
order to regenerate the severed axon.
DIFF:
- Transient but profound hypoxia, ischemia or toxic injury may lead to the loss of
neurons. Irreversible neuronal injury manifests with shrinkage of the neuronal
body, deep eosinophilia of the cytoplasm, pyknosis of the nucleus and loss of
Nissl substance.
- A decrease in the size and number of neurons is characteristic of compression
atrophy

Renal vein thrombosis

- Venous drainage from the left testis travels through the left testicular vein into
the left renal vein, and from there enters the inferior vena cava. In contrast the
right testicular vein empties directly into the inferior vena cava. This difference in
venous drainage gives diagnostic significance to left-sided varicocele, a condition
that often indicates an occlusion of the left renal vein by a malignant tumor or
thrombus.
-Membranous glomerulopathy is a common cause of nephrotic syndrome in
adults. Due to the increased permeability of the glomerular capillary wall in
nephrotic syndrome, many important substances are lost in the urine, causing a
number of varied complications. Loss of anticoagulant factors, especially
antithrombin Ill, is responsible for the thrombotic and thromboembolic
complications of nephrotic syndrome. Renal vein thrombosis can be a
manifestation of this hypercoagulable state. Patients present with sudden onset
abdominal or flank pain and gross hematuria. When renal vein thrombosis occurs
on the left side in male patients, the obstruction impedes venous flow from the
left testis, and left-sided varicocele appears.

Avitaminosis A
- Recurrent sinopulmonary infections and exocrine gland fibrotic atrophy in a
young Caucasian are suggestive of cystic fibrosis (CF). In the pancreas, severe
CF may cause total obstruction followed by complete fibrotic atrophy of the
exocrine glands. The resulting pancreatic insufficiency can cause a deficiency of
fat soluble vitamins. Avitaminosis A in particular may contribute to squamous
metaplasia of the epithelial lining of pancreatic exocrine ducts, which are already
injured and predisposed to squamous metaplasia by inspissated mucus. Normal
levels of vitamin A and its metabolite, retinoic acid, are required to maintain
orderly differentiation of specialized epithelia, including mucus- secreting
columnar epithelium. When a deficiency state exists, the epithelium undergoes
squamous metaplasia to a keratinizing epithelium.
- Vitamin A maintains orderly differentiation of specialized epithelia, including the
mucus-secreting columnar epithelia of the ocular conjunctiva, respiratory and
urinary tracts, and pancreatic and other exocrine ducts. Avitaminosis A can
cause squamous metaplasia of such epithelia to a keratinizing epithelium.
Seborrheic keratosis
=benign epidermal tumor that is commonly identified on the skin of middle-aged
or elderly individuals. Appearing most often on the trunk, extremities, head, or
neck, seborrheic keratosis presents as a tan to brown, round, flat, greasy, coin
like lesion ranging in size from a few millimeters to several centimeters. The
lesion has a velvety to granular texture and is classically described as having a
“stuck on” appearance.
http://missinglink.ucsf.edu/lm/Der...eborrheic_Keratosis-KK.jpg

Lichen planus
=characterized by the “5 Ps”: polygonal, planar, pruritic, purplish plaques
on the wrists hands, trunk, and legs. A finely reticulated scale termed
“Wickham’s striae” may be present on the plaque surface.
http://img.medscape.com/pi/emed/ck...122151-1123213-1123299.jpg

Idiopathic pulmonary fibrosis

=Insidious-onset progressive exertional dyspnea, pulmonary function tests
showing a restrictive profile and surgical biopsy showing extensive interstitial
fibrosis together with paraseptal and subpleural cystic airspace enlargement
(honeycomb lung)
http://ajrccm.atsjournals.org/cgi/content-nw/full/165/2/277/F3

Primary CNS lymphoma

=The most frequent CNS tumor in immunosuppressed patients
- is commonly associated with AIDS.
-Primary CNS lymphomas appear microscopically as dense, cellular aggregates of
uniform, atypical lymphoid cells. The majority of primary CNS lymphomas arise
from B-cells. Diffuse large B-cell lymphoma is the most common subtype. The
cells of CNS lymphomas are commonly positive for the B-cell markers CD2O and
CD79a.
-Primary CNS lymphomas are universally associated with the Epstein-Barr virus
(EBV). The clinical presentation is non-specific. Mental status changes, seizures,
or progressive focal neurologic deficits may occur. Most of CNS lymphomas are
high-grade and respond poorly to chemotherapy.
http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70476-
4
http://www.uhrad.com/mriarc/mri001.htm

Acute pyelonephritis
-Gram-negative rods such as E. coli ,Klebsiella, Proteus, and Enterococci are the
pathogenic bacteria that usually cause acute pyelonephritis. The distal urethra,
the introitus, and the vagina of healthy females are populated by non pathogenic
flora (lactobacilli, non-pathogenic staph and strep) that prevent colonization by
pathogenic strains. If this endogenous flora is suppressed (due to systemic
illness, antibiotic use, pregnancy, etc.), the distal urethra is colonized by
pathogenic gram-negative rods more easily. Pathogens present in the urethra
next encounter the bladder, which has several defenses against bacteria. The
bladder mucosa normally does not allow bacterial attachment; normal urine is
bactericidal due to high urea content and high osmolarity; and urine flow washes
the bacteria downstream. When these mechanisms are disrupted, or are
overcome by bacterial virulence factors, cystitis occurs.
-The normal vesicoureteral junction does not allow retrograde flow of urine. If
there is an anatomic abnormality of this area, or an increase in bladder pressure,
some urine returns to the ureter, bringing along any pathogens present in the
bladder (vesicoureteral reflux).
-Frequent bladder infections, may weaken the vesicoureteral junction and
facilitate reflux. Without vesicoureteral reflux, the ascent of pathogens to the
kidneys is impossible, and pyelonephritis does not occur.

Pituitary apoplexy
= acute bleeding in to a preexisting pituitary adenoma. Pituitary apoplexy is a
medical emergency; without treatment, prognosis is poor. Symptoms will be
bimodal; acute and chronic. The long-standing symptoms of a pituitary tumor
will be present for months as with this man’s headache and decreased libido;
accompanying these chronic symptoms will be an acute presentation, as with the
severe headache and visual disturbances in this patient.
-Signs of meningeal irritation can also be seen in pituitary apoplexy, mimicking a
subarachnoid hemorrhage. A careful physical exam can differentiate a
subarachnoid hemorrhage from a sellar mass with suprasellar extension
(pituitary tumor) by the presence of bitemporal hemianopsia, present only in the
latter. Patients suffering from pituitary apoplexy develop cardiovascular collapse
because ACTH deficiency leads to adrenocortical insufficiency. An urgent
neurosurgical consultation and treatment with glucocorticoids are required.

ALL
- Blast cells in the peripheral blood are strongly suggestive of leukemia. The
most common pediatric malignancy in children is acute lymphoblastic leukemia
(ALL). The neoplastic cells of ALL arise from lymphocytic precursors that are of
either pre-B or pre-T lineage.
-Clinical manifestations of ALL include fever, fatigue, pallor, petechiae, and
bleeding. Leukemic spread can cause lymphadenopathy, hepatosplenomegaly
and bone pain. T-cell ALL is more likely to present with a large anterior
mediastinal mass that can compress the great vessels, causing superior vena
cava syndrome. Mediastinal mass compression of the esophagus causes
dysphagia, while mass compression of the trachea leads to dyspnea and stridor.
Because pre-B and pre-T lymphoblasts can look identical in peripheral blood
-smear, immunohistochemical staining is used to differentiate the two cell
lineages. Both lineages express TdT (an antigen of lymphocyte precursors) on
their cell surfaces. Pre-B lymphoblasts are CD1O+, CD 19+. and CD2O+, while
pre-T lymphoblasts are CD2+, CD3+, CD4+, CD5+, CD 7+ and CD8+.
http://rebeccanelson.com/leukemia/all.html

Pulmonary embolus (PE)

-Lung scans display both the blood perfusion and the ventilation of each area of
the lung. A perfusion defect that is not anatomically matched by a ventilation
defect indicates that blood flow has been occluded to that segment of the lung.
(If there is a ventilation defect with the perfusion defect, lung collapse or
condensation is indicated.)
-Deep venous thrombosis (DVI) is the number one cause of PE, and in such
cases are better termed “pulmonary thromboembolism.” Many patients do
not realize they have a DVT until the clot migrates to the pulmonary vasculature,
resulting in acute symptoms like chest pain shortness of breath tachycardia,
tachypnea, and hypotension. Chest radiographs are often within normal limits.
Ventilation/perfusion scanning is usually the next step in evaluating these
patients, although lung scans can be negative despite the presence of a PE.
Angiography remains the gold standard in establishing the diagnosis of a PE, but
is often not performed because of cost and delay of treatment.
http://www.radpod.org/2006/12/07/saddle-pulmonary-embolus/

Dystrophic calcification
=hallmark of cell injury and death, occurring in all types of necrotic tissue —
including areas with fat necrosis.
-The most common sites of dystrophic calcification include aged or damaged
cardiac valves and atheromatous plaques.
-The process of calcification is defined in two stages: initiation (which transpires
within the mitochondria of dead or dying cells) and propagation (which can
eventually perforate the cell membrane from within). Grossly, dystrophic calcium
deposits are fine gritty white granules or clumps. On hematoxylin and eosin
staining, these deposits typically appear as dark purple, sharp-edged
aggregates. If the deposit develops lamellated outer layers, it is described as a
psammoma body.
http://www.medskool.net/images/circulatory/heart%20valve.jpg
http://upload.wikimedia.org/wikipe...hic_calcification,_H&E.jpg

Mitral valve thickening with vegetations

- includes infectious endocarditis, rheumatic valvulitis, Libman-Sacks
endocarditis associated with systemic lupus erythematosus (SLE) and non-
bacterial thrombotic endocarditis.
-Of these SLE is most likely to also affect the coronary arteries via arteritis
and/or thrombosis. In SLE thrombosis occurs due to the hypercoagulable
antiphospholipid antibody syndrome
-The verrucous endocarditis that occurs in up to 25% of patients with SLE
(Libman-Sacks endocarditis) produces small (1-4 mm in diameter) cardiac
valvular vegetations on either side of the valve consisting of sterile finely
granular fibrinous eosinophilic material. These vegetations may result from
immune complex deposition. The condition may progress to valve fibrosis
resulting in regurgitation or possibly stenosis.
http://www.pathguy.com/sol/06962.jpg
- SLE may cause an acute coronary syndrome at a young age even with
angiographically normal coronary arteries.

Cirrhosis
= diffuse hepatic fibrosis with replacement of the normal lobular architecture by
fibrous-lined parenchymal nodules (“nodular parenchymal regeneration”).
-Cirrhosis is considered micronodular if most nodules are 3 mm in diameter and
macronodular if most nodules are > 3 mm in diameter.
http://www.pathology.vcu.edu/education/gi/lab3.h.html
DIFF:
- Dilation of sinusoids and perivenular hemorrhage is associated with acute
venous outflow obstruction within the liver.
- Substance accumulation within hepatocytes occurs in conditions such as Dubin-
Johnson syndrome, in which the hepatocellular accumulation of coarse
pigmented granules causes the liver to appear black.
http://img.medscape.com/pi/emed/ck...ogy/169972-173517-3384.jpg
-Intrahepatic hydatid cysts with surrounding fibrous reaction can be seen in
patients with an Echinococcus infection.
http://radiographics.rsna.org/content/20/3/795/F8.large.jpg
-Granulomatous destruction of bile ducts is seen in patients with primary biliary
cirrhosis.

Pneumonias
- can be classified as one of three morphologic variants.
-Patchy inflammation of a number of lobules is characteristic of
bronchopneumonia.
-In interstitial pneumonia, the inflammatory infiltrate is confined to the alveolar
walls.
-When the inflammatory process involves an entire lung lobe, it is a lobar
pneumonia.
**Congestion (first 24 hr)is the first stage of lobar pneumonia. It is
characterized by pronounced dilatation of the alveolar capillaries. Some exudate
containing mostly bacteria may be present in the alveolar spaces.
**In the red hepatization stage (days 2-3) the intra-alveolar exudate consists of
RBCs, neutrophils and fibrin. The affected lobe is red, firm and airless.
** A lung lobe that is pale and firm macroscopically suggests the gray
hepatization phase (days 4-6). Microscopic examination of the exudates would
show neutrophils, fibrin and fragmented RBCs.
** Resolution is the last stage of lobar pneumonia. It is characterized by
resorption of the exudate and restoration of the pulmonary architecture.

Hemispheric stroke
- Hemiparesis, with more involvement of the arm than the leg, occurs due to the
occlusion of the middle cerebral artery (MCA). This artery supplies the face and
arm areas of the motor and sensory cortex, Broca’s and Wernicke’s
speech areas, and the frontal eye field. The MCA also gives rise to the small,
penetrating branches that perfuse the internal capsule and basal ganglia.
Along with hemiparesis, this patient has Broca’s (expressive) aphasia which
manifests with an inability to speak or write but preserved comprehension of the
spoken and written word. Broca’s area is located in the inferior frontal gyrus
in the dominant (left) hemisphere and is supplied by the left middle cerebral
artery. Contrary to popular belief the left hemisphere of the brain is most often
dominant in both right-handed and left-handed people.
http://commons.wikimedia.org/wiki/...A-Stroke-Brain-Humn-2A.jpg
http://img.medscape.com/pi/emed/ck...cine/756148-810904-783.jpg
DIFF:
- An infarct in the area of distribution of the left anterior cerebral artery leads to
right hemiplegia with lower extremities affected more than upper extremities.
Urinary incontinence and primitive reflexes (i.e. Moro, grasp tonic neck reflexes)
may also be present.
-Occlusion of the anterior inferior cerebellar artery causes lateral inferior pontine
syndrome. Contralateral loss of pain and temperature sensation is accompanied
by ipsilateral deficits of cranial nerves V and VIII, Horner’s syndrome, and
cerebellar symptoms.
- Occlusion of the posterior inferior cerebellar artery (PICA) leads to lateral
medullary (Wallenberg) syndrome. PICA occlusion is characterized by
contralateral loss of pain and temperature sensation, ipsilateral deficits of CN V,
VIII, IX. X, & Xl, and by Horner’s syndrome.
http://frontalcortex.com/?page=oll&topic=24&qid=1492

Lacunar infarcts
-The occlusion of distal, penetrating arterioles causes infarcts of only a few mm
in diameter, usually less than 15 mm. When these lesions resolve and become
cystic, they form small cavitary spaces called “lacunas” . Lacunar infarcts
occur because of hypertensive changes in the arterioles. These small,
penetrating branches supply the basal ganglia and deep white matter. The
leakage of plasma components through the endothelium and increased
production of extracellular matrix cause changes in the arteriolar wall. The end
process is called hyaline arteriolosclerosis, which causes narrowing of the vessel
lumen and possible occlusion.
-Lacunar infarction leads to characteristic clinical syndromes, depending on
exactly which portion of the brain is infarcted. Below, these specific syndromes
are listed with their anatomical counterparts.
1. Pure motor hemiparesis-- posterior limb of the internal capsule
2. Pure sensory stroke -- ventrolateral thalamus
3. ataxia-hemiplegia syndrome-- base of the pons
4. dysarthria-clumsy hand syndrome -- the base of the pons or the genu of the
internal capsule
http://anatomy.uams.edu/anatomyhtml/atlas_html/n1a5p7.html
- Hypoxic encephalopathy occurs due to abrupt cessation of cerebral blood flow,
as from cardiac arrest or shock. Pyramidal cells of hippocampus and Purkinje
cells of the cerebellum sustain ischemic damage first. Watershed infarcts occur
at the border of perfusion zones between the anterior and middle cerebral
arteries.
http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Images/N1-MS-01-16.gif
http://img.medscape.com/pi/emed/ck...y/336139-341971-2971tn.jpg

Varicose veins
=dilated, tortuous veins resulting from prolonged increases in intraluminal
pressure and from loss of vessel-wall tensile strength.
-The predominant location of varicosities are in superficial veins of the leg. Risk
factors are all related to a chronic increase in lower extremity venous pressure
and include long periods of standing age greater than 50, obesity, and multiple
pregnancies. Defective venous wall development may account for a familial
tendency. Varicose dilation of veins leads to incompetent venous valves, venous
stasis/congestion, edema, and an increased incidence of thrombosis.
-Complications result from the poor blood flow—painful thromboses, stasis
dermatitis, skin ulcerations, poorly healing wounds, and superficial infections
that may promote chronic varicose ulcers. Although deep venous thromboses
(DVTs) are the number one cause of pulmonary emboli varicose vein thromboses
are restricted to the superficial venous system; therefore thromboembolism is
very infrequent with varicose veins.
http://www.lonclin.co.uk/images/varicose%20veins%2018.jpg

Wernicke syndrome
=Confusion, ataxia, and ocular abnormalities
- These patients are likely to have an underlying chronic thiamine
deficiency—and because thiamine (B1) is used in the metabolism of simple
sugars, glucose infusion seriously exacerbates this pre-existing B1 deficiency.
Thiamine is essential for glucose utilization in the brain cells.
-Thiamine should be administered immediately when symptoms of Wernicke
encephalopathy manifest. Ocular motor signs (horizontal nystagmus, bilateral
abducens palsy) usually resolve completely within hours of thiamine
supplementation. Ataxia takes longer to resolve, and permanent gait
abnormalities may persist.
- In Wernicke syndrome ataxia is caused by damage to the cerebellar cortex and
vestibular nuclei. Unlike ophthalmopathy, ataxia takes longer to resolve. Some
patients may have permanent symptoms.
-Ophthalmopathy in Wernicke syndrome occurs due to damage to the nuclei of
CN Ill, IV and VI. These symptoms are rapidly reversible.
-Drowsiness and apathy are the early symptoms of Wernicke encephalopathy.
They resolve rapidly after thiamine administration.

Mental status changes (confusion) usually respond to treatment well. In a small

number of patients the improvement of mental status is followed by memory
abnormalities, a condition known as Korsakoff syndrome.
-Korsakoff syndrome is associated with the damage of the medial dorsal nucleus
of the thalamus. Damage to this nucleus causes memory loss and a fascinating
psychological phenomenon called “confabulation.” When patients with
Korsakoff syndrome unsure of a fact they fill in the memory gap with a
fabricated to that they themselves believe to be true. Korsakoff syndrome also
causes an inability to form new memories (anterograde amnesia). Memory and
learning impairment is usually permanent.
http://www.moondragon.org/health/graphics/beriberi1.jpg

Osteoporosis
=predominantly a disease of postmenopausal, white females. White females
have lower bone mass compared to black females. After menopause declining
estrogen levels accelerate the loss of bone mass mainly through a decrease in
osteoblastic activity and an increase in osteoclastic activity.
-The two major types of bone present in an adult skeleton are trabecular and
cortical. Trabecular bones are also called spongy or cancellous bones. Trabecular
bone composes only 15% of the total skeleton, by weight but trabecular bone is
metabolically more active because of its large surface area. Cortical bones (long
bones) contribute by serving as mechanical support and sites of muscle
attachment. Most of the appendicular skeleton (the limbs) is cortical bone.
Osteoporosis primarily involves trabecular, or spongy bone. The most prominent
changes in osteoporosis occur in dorsolumbar vertebral bodies as vertebrae are
predominantly trabecular. The neck of the femur consists of 50% of trabecular
and 50% of cortical bone. Osteoporotic fractures are most common at vertebral
bodies and second most common at the neck of the femur.
http://www.cdc.gov/nutrition/images/badbone.gif
DIFF:
- Increased deposition of unmineralized osteoid is very characteristic of vitamin
D deficiency. Vitamin D is important for the absorption of calcium and
phosphorus from the gastrointestinal tract and for bone mineralization.
- Hyperparathyroidism increases osteoclastic activity, which results in increased
bone resorption. Bone resorption in hyperparathyroidism primarily involves
cortical bones (bone loss in postmenopausal osteoporosis is trabecular).
Increased resorption of cortical bones results in subperiosteal thinning, a very
characteristic feature of hyperparathyroidism.
-Paget’s disease of the bone involves only focal areas of the skeleton. The
disease process starts as marked osteoclastic activation in particular locations
followed by increased osteoblastic activity. The net result is a focal formation of
abnormal bone. The new collagen is laid down in a haphazard manner in lieu of
the linear deposition in normal bones. The end product is a mosaic pattern of
lamellar bone where irregular sections of lamellar bone are linked by cement
lines. Cement lines represent previous areas of bone resorption.
-Histologically osteopetrosis is characterized by the persistence of primary,
unmineralized spongiosa in the medullary canals. In normal individuals the
primary spongiosa is replaced by bone marrow.

Ruptured left ventricular (LV) free wall

= a complication of transmural (ST elevation) myocardial infarction (Ml) that
generally occurs 3 to 7 days after the onset of total ischemia, when coagulative
necrosis neutrophil infiltration, and enzymatic lysis of connective tissue have
substantially weakened the infarcted myocardium (mean 4-5 days; range 1-10
days).
-Free wall rupture causes cardiac tamponade, which greatly limits ventricular
filling during diastole. As the pressure increases in the pericardial cavity, venous
return to the heart is reduced. This leads to profound systemic hypotension and
pulseless electrical activity. Failure to relieve the obstruction results in death.
-Clinically, these patients present with profound hypotension and shortness of
breath. On physical examination, the heart sounds are muffled and the jugular
venous pressure is elevated.
- the most common cause of death in a patient hospitalized for a Ml is ventricular
failure (cardiogenic shock), which accounts for 2/3 of in-hospital Ml deaths.
- The most frequent complication of fibrinolytic therapy for Ml is bleeding,
especially in patients receiving invasive procedures. Intracranial hemorrhage is a
serious bleeding complication. The frequency of early death (within the first 24
hours of an Ml) is actually increased by myocardial reperfusion via fibrinolytic
therapy, though there is a survival benefit overall. It is not clear whether this
early increased risk includes an increased risk of myocardial rupture.
- The risk factors for ventricular free-wall rupture following an Ml include: age
greater than 60, female gender, pre-existing hypertension, and absence of left
ventricular hypertrophy. Additionally, rupture is more likely to occur if this is the
patient’s first MI. Previous MIs may be protective because fibrosis tends to
decrease the probability of myocardial tearing.

NSAID-induced nephropathy, also called analgesic nephropathy

-pathogenesis is multifactorial. NSAIDs concentrate in the renal medulla,
allowing higher levels in the papillae than in the renal cortex. Decreased
prostaglandin synthesis also facilitates the constriction of medullar vasa recta
promoting ischemia. While the previous factors predispose to papillary necrosis,
NSAIDs also uncouple the oxidative phosphorylation in renal mitochondria, thus
causing direct cell damage.
-With prolonged NSAID use, the major pathophysiologic abnormality is chronic
interstitial nephritis. Patchy interstitial inflammation with subsequent fibrosis,
necrosis and scarring of papillae, distortion of caliceal architecture and tubular
atrophy are seen on light microscopy. Morphologic abnormalities in glomeruli and
vascular channels are often mild.
-Clinically, patients with chronic interstitial nephritis may show modest elevation
in serum creatinine, evidence of tubular dysfunction (polyuria, nocturia), or
Fanconi syndrome (aminoaciduria, glycosuria, hypophosphatemia,
hypouricemia). Proteinuria is usually mild often less than 1 gm/day. Papillary
necrosis may manifest with colicky flank pain, gross hematuria, and the passage
of tissue fragments in urine.
http://img.medscape.com/pi/emed/ck...y/336139-379762-6072tn.jpg

Sudden cardiac death (SCD)

- SCD is defined as cardiac arrest that begins within one hour of the precipitating
event and ultimately proves fatal. Approximately 80% of SCDs are due to
coronary artery disease (CAD). In the majority of CAD-related SCDI the
pathogenesis is acute plaque change producing acute myocardial ischemia.
Ischemia produces electrical instability in the heart and can generate a
potentially lethal arrhythmia. Ventricular fibrillation is usually the first arrhythmia
to appear as a result of acute myocardial ischemia, and is the most common
cause of lethal cardiac arrest in CAD-related SCD. Ventricular fibrillation is also
the most common cause of death from myocardial infarction in the pre-hospital
phase (i.e. prior to arrival in the emergency room).
-Ventricular tachycardia and ventricular fibrillation are the most lethal
arrhythmias in patients with acute Ml. Atrial flutter and atrial fibrillation are
arrhythmias that do not usually result in sudden cardiac death.
- Extensive myocardial infarction (Ml) may result in terminal ventricular failure.
However, death due to heart failure caused by an Ml usually does not occur
suddenly. Ventricular failure is the most common cause of death due to Ml during
the in-hospital phase.
- LV rupture generally does not occur until 3 to 7 days after the onset of
infarction. Similarly, death may result due to ventricular septal rupture but this
also does not occur until 3-7 days after the onset of infarction.
- Following a myocardial infarction (MI) there may be ventricular mural
thrombosis and cerebral thromboembolism. However it is unusual to have
significant mural thrombosis prior to 48 hours after the Ml.
Cardiogenic acute pulmonary edema
= increased filtration of plasma water and electrolytes into the lung interstitium
and alveoli. The fluid that accumulates is a transudate (an ultrafiltrate of plasma
caused by hemodynamic changes) rather than an exudate (an extravasation not
only of plasma water and small ions but also plasma protein components and
circulating leukocytes, as seen in inflammatory states).
DIFF:
- Focal necrosis of alveolar walls and intra-alveolar hemorrhages are more
typical of pulmonary hemorrhage syndromes such as Goodpasture syndrome and
vasculitis-associated hemorrhage (as seen in hypersensitivity angiitis Wegener
granulomatosis, and lupus erythematosus).
- Hemosiderin-containing macrophages in the alveoli (ie, siderophages, or
“heart failure cells”) are suggestive of prior episodes of pulmonary
congestion and edema that arose due to chronic left heart failure. When
erythrocytes extravasate into the alveoli due to the increased intravascular
pressures in the pulmonary capillary bed hemosiderin accumulates in alveolar
macrophages.
- Mononuclear interstitial pulmonary infiltrates are found in the early stages of
various interstitial lung diseases.
-The presence of numerous neutrophils in the alveolar fluid would be consistent
with an exudate, which occurs in the setting of an acute bacterial or aspiration
pneumonia.
-Fat-globule occlusion of pulmonary vasculature is an early histologic
manifestation of fat embolism syndrome which is not associated with myocardial
infarction but multiple fractures of the long bones pelvis or ribs.

Vitamin D
= normally produced endogenously via photoisomerization with casual exposure
to sunlight. It is also readily available via dietary consumption, being found in
fortified milk fatty fish, cod-liver oil, and eggs.
The metabolism of vitamin D is summarized as follows: 1) vitamin D is absorbed
in the gastrointestinal tract or synthesized from precursors in skin after sunlight
exposure; 2) the vitamin D is bound to a plasma D-binding protein and
transported to the liver; 3) once in the liver, conversion to 25-hydroxy vitamin
D, 25(OH)D (calcidiol) by 25- hydroxylase takes place; 4) the 25(OH) D is
converted to 25(OH)2D (calcitriol) by al-hydroxylase in the kidney. Calcitriol is
the most active form of vitamin D.
-Excessive vitamin D supplementation may result in hypercalcemia,
hypercalciuria, confusion, polyuria, polydipsia, anorexia, vomiting, muscle
weakness, and painful bone demineralization. Vitamin D intoxication usually
occurs in adults taking in excess of 60000 IU/day, with food faddists or those
who are taking vitamin D replacement therapy the most commonly affected.
Additionally, patients with granulomatous disorders (eg, sarcoidosis,
tuberculosis, Hodgkin’s disease, and non- Hodgkin’s lymphoma)
frequently develop hypercalcemia and hypercalciuria. It is thought that patients
with sarcoidosis experience increased intestinal calcium absorption and bone
resorption secondary to high serum calcitriol concentrations.
Herpetic encephalitis
- HSV-1 mostly affects teenagers and young adults and is the most common
cause of sporadic encephalitis. Encephalitis results from the reactivation of latent
virus “living” in the trigeminal ganglion and the virus spread along this
nerve into the cerebral vault. Temporal lobe involvement is characteristic of
HSV-1 encephalitis.
-The most common early symptoms of acute encephalitis are headache and
fever. Mental status changes (lethargy, confusion), cranial nerve deficits, and
seizures may follow. Specific symptoms of herpetic encephalitis are related to
HSV-1’s predilection for the temporal lobe including aphasia (damage of
speech areas), olfactory hallucinations (olfactory cortex involvement), and
personality changes (amygdala damage).
Macroscopic brain examination reveals edema and hemorrhagic necrosis of the
temporal lobes. Eosinophilic intranuclear inclusions (Cowdry type A) are present
in glial cells and neurons. Multinucleated giant cells may also be found.
-EEG can reveal focal temporal abnormalities. CT or MRI detect edema and
hemorrhage in the temporal lobe. CSE has a typical “viral pattern" with
lymphocytic pleocytosis, normal glucose, and elevated protein levels.
http://pathology.mc.duke.edu/neuropath/CNSlecture2/hsv.jpg
http://www.radpod.org/2007/03/24/herpes-simplex-encephalitis/

Hyaline arteriolosclerosis
=Homogeneous deposition of eosinophilic hyaline material in the intima and
media of small arteries and arterioles characterizes , which may result from
nonmalignant hypertension or diabetes. The underlying structure of the vessel
wall is maintained but the intima is thickened and the arterial lumen is narrowed.
The hyaline material is thought to result from leakage of plasma constituents
across the vascular endothelium, and from excessive extracellular matrix
production by smooth muscle cells (3MG). The 3MG may be stimulated by
chronic/repetitive endothelial injury caused by the hemodynamic stress of long-
standing hypertension or by the metabolic derangements of diabetes. In
diabetics, development of hyaline arteriolosclerosis is related not only to the
duration of the disease, but also to the degree of any concomitant hypertension.
http://lh5.ggpht.com/_czdfK6r5I8o/...tic+arteriolosclerosis.jpg
DIFF:
- Malignant hypertension produces hyperplastic arteriolosclerosis, which consists
of homogeneous onion- like, concentric thickening of the walls of arterioles. This
morphologic pattern results from laminated SMC and reduplicated basement
membranes.
http://doctorxdrive2.jeeran.com/images/0016.jpg

Cachexia
= a syndrome that encompasses anorexia, malaise, anemia, weight loss and
generalized wasting due to underlying systemic disease. Cachexia in the patient
described above is a manifestation of the lung neoplasm revealed on his chest X-
ray. Tumor necrosis factor-alpha is a cytokine that causes necrosis of some
tumors in vitro. In experimental animals it also produces symptoms of cachexia.
For this reason TNF-α is also called cachectin and is considered a main mediator
of paraneoplastic cachexia.
-TNF-α is produced by macrophages in response to infection as well as by some
neoplastic cells. Its role in cachexia is explained by its influence on
hypothalamus that leads to appetite suppression.
-In bacterial infections, TNF-α produces fever ,along with IL-1 mediates many
of the symptoms of septic shock and causes hepatic release of acute-phase
reactants such as C-reactive protein and fibrinogen.

Acute erosive gastritis

- can be caused by a number of factors such as NSAID use, smoking alcohol
acute stress or bacterial infection. Erosions are defined as mucosal defects that
do not penetrate the muscularis mucosa. Acute erosive gastritis can cause upper
GI hemorrhage.
- A gastric erosion is defined as a mucosal defect that does not penetrate the
muscularis mucosa. Erosions usually occur in the setting of acute erosive
gastritis, a condition that results from short-term, severe mucosal injury that
leads to inflammation and superficial mucosal destruction. A number of causative
agents can cause acute erosive gastritis. The use of NSAIDs, having surgery,
head trauma (Cushing ulcers), burns (Curling ulcers), smoking, and alcohol
consumption are the most common causes.

Portal vein thrombosis

-causes portal hypertension, splenomegaly, ascites and varicosities in portocaval
anastomoses. It does not cause histologic changes to the hepatic parenchyma.

Adult-type aortic coarctation

- can produce hypertension in the upper aortic circulation and simultaneously low
perfusion in the distal aorta supplying the legs. The likelihood of an adult-type 1
postductal coarctation is greatly increased by the finding of enlarged, palpable
intercostal vessels which indicate the development of a collateral arterial
circulation to the region of the aorta distal to the coarctation.
-On radiographic exam, patients with adult-type aortic coarctation often have
notching of the ribs as a result of the enlarged tortuous intercostal arteries.
- In adult-type aortic coarctation, the stenosis is post-ductal (in contrast to the
infantile form where the coarctation is generally preductal and fatal soon after
birth without surgical repair).
http://www.heartpearls.com/2009/05...rctation-of-the-aorta.html
A retained dead fetus in the uterus
= associated with disseminated intravascular coagulation (DIC) and progressive
hypofibrinogenemia. Monitoring of fibrinogen and platelet count is helpful in early
identification of the onset of DIC in high-risk patients. Know the findings of DIC:
Prolonged PTT and PT
Thrombocytopenia and microangiopathic hemolytic anemia
Low fibrinogen
Elevated fibrin split products (D-dimer)
Low factor V and VIII levels

-Sickle cell patients become functionally asplenic and thus are at an especially
increased risk for infection by encapsulated organisms (Hemophilus influenza
and pneumococcus).
-Salmonella is the most common cause of osteomyelitis in children with sickle
cell disease: staphylococcus aureus is the second most common cause in these
patients.

The hemochromatosis gene (HLA-H)

- On the short arm of chromosome 6 the hemochromatosis gene (called HFE)
encodes an HLA class I-like molecule that appears to affect iron absorption from
the gastrointestinal tract. Multiple mutations have been identified, with the most
common being a missense mutation that results in cysteine-to-tyrosine
substitution at amino acid 282 (mutation C282Y). In white populations of
northern European descent, the frequency of HFE is approximately 6% and the
homozygous frequency is approximately 0.45% (or 1 in 220). Hemochromatosis
is therefore one of the most common inherited diseases, as well as one of the
most common inborn defects in metabolism.

Undescended testes, cryptorchidism

- Embryologically, the testes originate within the abdomen, and then migrate to
the scrotal sac via the inguinal canal. The exact cause of cryptorchidism is poorly
understood in most cases. The undescended testes can lie anywhere along the
path from the abdomen to the scrotal sac. The failure to completely descend
may be unilateral or bilateral.
-The temperature inside the scrotal sac is lower than body temperature, creating
an ideal environment for the seminiferous tubules, which are very temperature-
sensitive and prone to heat-induced damage. If undescended testes are not
surgically moved to the scrotal sac the seminiferous tubules become atrophic
and hyalinized overtime, resulting in a low sperm count. Additionally, because
the seminiferous tubules are responsible for the secretion of inhibin, circulating
levels of inhibin decrease as the seminiferous tubules degenerate. FSH levels are
elevated due to loss of negative inhibition by inhibin. Unlike the seminiferous
tubules, the testosterone-producing Leydig cells are not very sensitive to
temperature. Thus, testosterone and LH levels are usually normal.
-Patients with cryptorchidism are at increased risk for testicular cancer,
especially when orchiopexy is not performed by age 2. Patients whose testes are
located intra-abdominally have a higher risk of malignancy compared with those
whose testes are located in the inguinal region.

Renal papillary necrosis

-The abrupt onset of gross hematuria in a patient with family histor of sickle cell
disease suggests renal papillary necrosis, which can be caused by a number of
systemic conditions associated with ischemia. The following conditions are most
strongly associated with papilla necrosis:
1. Sickle cell disease or trait: sickling causes obstruction of small kidney vessels
and predisposes to ischemia. This occurs most commonly in children and young
adults.
2. Analgesic nephropathy: phenacetin, the most nephrotoxic analgesic drug, has
been withdrawn from the U.S. market. Many of the other NSAIDs, however,
inhibit renal blood flow by decreasing prostaglandins synthesis. In patients
predisposed to renal hypoperfusion, certain analgesics can cause ischemia.
3. Diabetes mellitus: diabetic metabolic abnormalities, including non-enzymatic
glycosylation, cause changes in vascular walls, leading to compromised renal
vasculature.
4. Acute pyelonephritis and urinary tract obstruction :the edematous interstitium
of the pyelonephritic kidney compresses the medullary vasculature, thus
predisposing the patient to ischemia. Macroscopic pathological findings include
gray-white or yellow necrosis of the tips or distal two-thirds of renal pyramids.
Microscopically, the tissue shows coagulative infarct necrosis, with preserved
tubule outlines. After the acute phase, scars can be seen on the cortical surface
as fibrous depressions replace the inflammatory foci.
-Dark, rust-colored or bloody urine and acute, colicky flank pain are common
symptoms and are due to acute ureteral obstruction from sloughed papillae.
Patients with chronic papillary necrosis may remain asymptomatic until gross
hematuria or the passage of tissue fragments in urine occurs.
http://www.som.tulane.edu/classwar...Path/GR_Renal/Renal23.html
DIFF:
-Ischemic tubular necrosis presents with oliguria in hospitalized, severely ill
patients. Muddy-brown granular casts are pathognomonic.
-Hemolytic uremic syndrome (HUS) consists of the triad of microangiopathic
hemolytic anemia, thrombocytopenia, and acute renal failure.

Congenital bicuspid aortic valves

- occur in approximately 1 .4% of live births. The congenital bicuspid valve
accelerates the normal aging process, leading to premature calcific aortic
stenosis in the sixth and seventh decades. In patients without the defect, senile
calcific aortic stenosis typically comes to clinical attention in the eighth or ninth
decades.
http://my.clevelandclinic.org/Publ...d_aortic_valve_disease.jpg
- In early life, an isolated congenital bicuspid aortic valve usually remains
asymptomatic, without any hemodynamically significant degree of aortic out flow
tract obstruction or audible murmurs. This is in contrast to congenital aortic
stenosis, which occurs in approximately 0.04% of live births, and results from
more severe subvalvular, valvular, or supravalvular anatomic defects, and
usually produces a systolic murmur at birth.

Medulloblastomas
= part of a group called “primitive neuroectodermal tumors” (PNETs).
PNETs are composed of sheets of small cells with deeply basophilic nuclei and
scant cytoplasm (small, round, blue cells). Abundant mitoses are also seen.
-Medulloblastomas are undifferentiated and aggressive tumors.
The cerebellar vermis is the most common location of a medulloblastoma.
Symptoms include signs of increased intracranial pressure (morning headaches,
vomiting, and lethargy). Cerebellar dysfunction occurs as the tumor compresses
adjacent structures.
http://www.pathology.vcu.edu/WirSe...ents/image/090medblast.jpg
DIFF:
- Pilocytic astrocytoma is the most common brain neoplasm of childhood.
Although both pilocytic astrocytomas and medulloblastomas are often located in
the cerebellum, they can be differentiated by histology. On microscopic
examination of a pilocytic astrocytoma, pilocytic astrocytes and Rosenthal fibers
are seen. Pilocytic astrocytomas are low-grade tumors and have a better
prognosis than medulloblastomas.
http://wiki.cns.org/wiki/index.php/Pilocytic_Astrocytoma
http://moon.ouhsc.edu/kfung/jty1/C...m04Image/Com401-2-FR4b.gif
-Ependymomas are the third most common brain neoplasm found in children.
They arise in the walls of the ventriculi and can hamper CSF flow and cause
hydrocephalus. On microscopic examination, ependymal cells form gland-like
structures called “rosettes.”
http://www.mayoclinic.org/images/ependymomas-bdy.jpg
http://www.neuropathologyweb.org/chapter7/images7/7-16b.jpg

Whipple disease
=Caused by the gram-positive actinomycete Tropheryma whippelii, is a rare
systemic illness that involves the small intestine, joints, and central nervous
system. The actinomycete proliferates only within the macrophages of these
tissues, provoking no inflammatory response as a consequence.
-Classic histologic findings include small intestine mucosa containing enlarged,
foamy macrophages packed with both rod-shaped bacilli and PAS-positive,
diastase-resistant granules (which consist of lysosomes and partially digested
bacteria).
-Clinically Whipple disease is most commonly seen in middle-aged Caucasian
males, presenting as malabsorption with diarrhea and weight loss. Arthropathy,
polyarthritis, and psychiatric and cardiac abnormalities may also be observed.
Antibiotic therapy is usually successful in quickly resolving the illness.
http://www.ctisus.org/organsys/sma...astro_non_neo_smbowel.html
http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70921-
4

Anorexia nervosa
=distorted body image, restricted diet, exercise regimen, and physical exam
findings
- Physical examination findings in patients with anorexia often include dry skin,
lanugo (fine, pale, downy hair), and hypotension. As patients percentage of body
fat decreases to abnormally low levels, the normal cyclic LH surge is lost and
hypogonadotropic amenorrhea develops. Intense exercise regimens may
contribute to inadequate hypothalamic-pituitary gonadotropin secretion, which is
why thin female athletes (e.g. long distance runners) who are not anorexic also
sometimes develop amenorrhea.
-Anorexic females commonly have low levels of LH, FSH, estradiol, and estrone.
With successful treatment, patients with anorexia nervosa can resume menses
within 6 months of returning to 90% of their ideal bodyweight.

Helicobacter pylori-associated antral gastritis

-leads to a decrease in the number of somatostatin-producing antral cells.
Somatostatin is a hormone that inhibits gastrin release. In its absence, high
gastrin levels cause increased local release of histamine which stimulates the
gastric parietal cells to secrete increased levels of acid. The resulting very low pH
gastric fluid enters the duodenum, and if not adequately neutralized by local
bicarbonate production, causes duodenal ulceration.
-H. pylory live in the mucus layer overlying the epithelium of the gastric antrum
and fundus, as well as in any ectopic gastric tissue in the duodenum or
esophagus. H. pylory do not appear to invade these tissues and are susceptible
to gastric acidity. The organisms are protected by the mucus layer and their
urease production. H. pylory cause local inflammation of the gastric mucosa
which decreases the number of somatostatin-producing antral cells by an unclear
mechanism.
- Gastric adenocarcinoma and gastric lymphoma are associated with H. pylori
infection. The mechanism by which H. pylori leads to malignancy remains
unclear, though it has been hypothesized that immune activation or local
inflammation may play a role.
- H. pylori is associated with gastric as well as duodenal ulceration, but gastric
ulceration does not require increased acid secretion to occur. H. pylori associated
gastric ulceration results from its destruction of the local mucous layer as well as
from the local inflammatory response to these bacteria. Normal levels of gastric
acidity are sufficient to cause gastric ulceration when the mucosal layer is
degraded.

Cholesterol precipitation
-The two primary means by which we obtain cholesterol are: 1) dietary ingestion
of animal fat; and 2) hepatic synthesis, which is controlled by HMG-CoA
reductase.
-Once in the liver, the free cholesterol is converted into cholic and
chenodeoxycholic acids (bile acids) through a series of chemical reactions. These
bile acids are then conjugated to either glycine or taurine to create the bile salts
that are secreted into bile canaliculi. As more water-insoluble cholesterol is
secreted in bile, it is rendered soluble in small amounts by the detergent action
of the amphipathic (both hydrophobic and hydrophilic) bile salts and the
phospholipid phosphatidylcholine. When the gallbladder is hypomotile or there is
more cholesterol than bile salts, the cholesterol precipitates into insoluble
crystals that eventually form to make gallstones.
-To reduce the likelihood of cholesterol precipitation (and gallstone formation),
cholesterol quantities should be kept low and bile salt quantities kept high.

Acute interstitial nephritis

-Fever, rash, and oliguria one to three weeks after the initiation of treatment a
b-lactam antibiotic is highly suggestive of drug-induced acute interstitial
nephritis (AIN). NSAIDs, sulfonamides, rifampin, and diuretics are also cited
often.
-As the name of the condition implies, damage primarily involves the
interstitium, leaving the glomeruli intact. Interstitial edema and infiltration with
mononuclear cells (lymphocytes and macrophages) are typical. Plasma cells and
eosinophils are also commonly seen. Sometimes, the inflammatory cells may
infiltrate the tubular epithelium, which may cause tubulorrhexis and spillage of
tubular content into the interstitium. If the latter occurs, foreign-body
granulomas may be formed in the interstitium.
-Drug-induced hypersensitivity reactions are thought to be the cause of AIN.
Many patients have increased levels of eosinophils and IgE in serum: also,
granuloma formation may be observed. Therefore, IgE-mediated hypersensitivity
combined with cell-mediated reactions are thought to be involved in the
pathogenesis of AIN.
-Clinically, patients with AIN present with fever, maculopapular rash, and acute
renal failure. Peripheral eosinophilia and eosinophiluria (detected by Hansel or
Wright stain) are the most important clues. Symptoms almost always resolve
completely after cessation of the offending medication.
Guillain-Barre syndrome
=acute demyelinating disease occurs after infection, immunization, or allergic
reaction.
-It is hypothesized that in Guillain-Barre syndrome, some infectious agents
contain ganglioside-like substance in their lipopolysaccharide layer. Antibodies
formed against this substance cross-react with the ganglioside components of
myelin. Segmental demyelination and endoneural inflammatory infiltrate are
seen on light microscopy of the peripheral nerves.
-Guillain-Barre syndrome manifests with ascending muscle weakness that starts
after recovery of respiratory or gastrointestinal infection. It is strongly associated
with Campylobacter jejuni infection. Muscle weakness is accompanied by the
disappearance of deep tendon reflexes (areflexia). Paralysis may ascend to the
cranial nerves (especially CN VII ” Bell's" palsy). Paralysis of respiratory muscles
is fatal without supportive care.
DIFF:
- Werdnig-Hoffman syndrome results from anterior horn cell damage. Lower
motor neuron lesion signs are present: flaccid weakness, areflexia, muscle
atrophy, and fasciculation ('floppy child' syndrome).
- Eaton-Lambert syndrome clinically resembles myasthenia gravis. It is a
paraneoplastic syndrome associated with small cell carcinoma of the lung. Its
pathogenesis is explained by autoantibodies that react with presynaptic calcium
channels and hamper the release of acetylcholine
-Subacute, combined myelopathy occurs due to vitamin B12 deficiency. This
deficiency leads to degeneration of dorsal columns and lateral cerebrospinal
tracts. Loss of position and vibration sensation, spastic paresis, and ataxia are
typical.
- Beriberi (thiamine deficiency) can cause demyelination of peripheral nerves.
Unlike Guillain-Barre syndrome, no perineural inflammation is present.
Symptoms include muscle weakness and areflexia, associated with pain and
paresthesia. Involvement of the distal lower limb is characteristic.
-Duchenne muscular dystrophy is an X-linked muscular dystrophy that affects
male children. It is caused by a frame shift mutation of the dystrophin gene. Is
nota neurologic disease; pathology is at the level of the muscle.

Secondary (reactivation) tuberculosis

-occurs in patients who have been previously infected with tuberculosis. Primary
tuberculosis causes the formation of Ghon foci in the lower lung fields.
Reactivation tuberculosis occurs in immunosuppressed patients, and is
characterized by apical cavitary lesions and hemoptysis.
Urinary calculi
- Only uric acid stones are radiolucent (not seen on plain abdominal films). They
can be visualized instead by abdominal ultrasound or CT scan. Uric acid stones
occur in patients with gout myeloproliferative disorders, high protein diets low
fluid intake, or certain inborn errors of metabolism (e.g. Lesch-Nyhan
syndrome).
-Magnesium ammonium phosphate (struvite, or triple phosphate) calculi are
radiopaque. They form in alkaline environments (pH >7.4), and are usually
associated with urinary tract infections due to urease-forming organisms (such
as Proteus). Struvite stones can grow to be quite large filling the renal pelvis.
When these stones assume the shape of the renal pelvis they are called
staghorn calculi.
-Calcium oxalate and calcium phosphate stones are commonly grouped together
as calcium- containing calculi. These are the most common type of stone
accounting for 70-80% of all cases of nephrolithiasis. Calcium stones can form in
acidic urine (pH = 6) or neutral urine (pH = 7). They are radiopaque.
-Cystine stones are relatively radiopaque because they are composed of sulfur-
containing compounds. Cystine stones are found in cystinuria, an autosomal
recessive disorder characterized by a defect in the proximal tubule reabsorption
of cystine. An acidic pH is needed for the formation of these calculi.

Glioblastoma multiforme (GBM)

=the most common primary brain neoplasm in adults.
- Areas of necrosis and hemorrhage are seen on gross examination. On light
microscopy, 'pseudopalisading' tumor cells around areas of necrosis are
diagnostic.
http://frontalcortex.com/?page=oll&topic=24&qid=1113