PATOFISIOLOGI ENDOKRIN &

METABOLIK
Susiana Candrawati

A & P Review of Endocrine System

Mechanism of Hormone Action

Hormones play an important function in regulation & control of body functions &
metabolism
Hormones exert control that is slower acting but of longer duration than nerve impulses
Hormones secreted by endocrine glands go to a target organ
How do specific hormones know where to go?
Receptors in the cell are specific for certain hormones
Thus get lock & key effect
2 types of hormones
Protein derivative hormones (from amino acids or polypeptides)
water soluble, thus need plasma membrane receptor
then need second messenger for hormone to exert its action
this action occurs in the cytoplasm
Lipid derivative hormones (primarily steroids)
Fat soluble, thus pass right through the cell membrane
bind with receptor in the nucleus
this complex triggers DNA to make a specific protein

Regulation of Hormonal Secretion

The control of hormonal secretion is homeostatic feedback
Another name for this is: negative feedback

Remember negative feedback reverses the direction of change back to

physiologic normal
if hormone level too high----- the gland is shut down
if hormone level too low ------the gland is stimulated
Positive feedback augments the direction of change
if hormone level high ----- the gland is stimulated
if hormone level too low---- the gland is shut down, even further
Most endocrine diseases are centered around:
TOO MUCH = hypersecretion--- from glandular hyperplasia or a
functional tumor (adenoma or carcinoma)
TOO LITTLE = hyposecretion from glandular atrophy or a
destructive carcinoma

Prostaglandins
Written as PG; called tissue hormones
they are substances produced locally by specific tissues
they travel only short distances & thus have a localized effect
2 types: Inflammatory (bad) & non-inflammatory (housekeeping or good)
Prostaglandins & leukotrienes = usually enhance inflammation
Prostacyclins & thromboxanes = work in opposition to platelet aggregation

they are lipids called eicosanoids

The major eicosanoid fatty acid precursor = arachidonic acid
This is a essential fatty acid; thus from diet
Omega 3 fatty acids produce non-inflammatory PGs
Omega 6 fatty acids produce inflammatory PGs

their synthesis begins when a cell membrane is disrupted e.g. injury

the disrupted cell membrane releases certain lipids into the cytoplasm
that begins PG synthesis

Mech of action of PGs

COX = cyclooxygenase = enzyme that synthesizes prostaglandins
2 forms: COX-I & COX-II
COX-I = results in products (prostaglandins) that act on stomach,
platelets, & vascular endothelium (prostacyclins)
These prostaglandins are involved in homeostatic activities
Also called housekeeping activities
These include:
1. Maintaining GI mucosal barrier
2. Maintaining platelet function
(checks & balances via prostacyclin & thromboxane)
3. Maintaining vascular homeostasis
COX-II = results in products(prostaglandins) that are
inflammatory chemical mediators
Get organ smooth muscle contraction (constrict bronchi)
Vasodilation
Pain
Anti- prostaglandins (NSAIDs)
Non-selective NSAIDs inhibit COX I & COX II
Selective COX II agents exert their actions primarily on the inflammatory process (
they inhibit it)

Pituitary Gland
2 glands
Anterior pituitary
Adenohypophysis

Posterior pituitary
Neurohypophysis
Extension of
hypothalamus

Diseases of the Pituitary

General facts
Main cause of pituitary diseases = benign adenomas
Age: 30 50 years old
Symptoms fall into 2 main categories:
Pressure symptoms from glandular enlargement
Headache, seizures, drowsiness, visual defects
Hormonal effects
Usually stimulatory if functional tumor
May be inhibitory (non-functional with pressure necrosis)
Most common hormonally active adenomas = prolactinoma

Diseases of the Pituitary

TSH
hypersecretion = hyperthyroidism
hyposecretion = hypothyroisism

ACTH
hyposecretion = Addisons disease
hypersecretion = Cushings disease

FSH
hyposecretion
M = poor sperm production
F = low estrogen, amenorrhea
hypersecretion
F = menopause

LH
hyposecretion
F = no ovulation
M = low testosterone

MSH
hypersecretion = excess pigment

GH
hypersecretion
during growth = giantism
after growth = acromegaly
hyposecretion = dwarfism

PRL
hypersecretion = galactorrhea,
infertility
hyposecretion = poor milk production

ADH
Hypersecretion = SIADH
Syndrome of inappropriate ADH
secretion

hyposecretion = diabetes insipidus

Specific Pituitary Diseases

Giantism
If congenital may be accompanied by mental retardation &/or sexual retardation
If occurs after puberty ---- called acromegaly
Get enlarged hands & feet, protruding mandible
Etiology usually pituitary adenoma

Dwarfism
If congenital get mental retardation(+/-) & no secondary sexual characteristics
Tx = GH

Prolactinoma
Most common pituitary functional tumor
Get high prolactin levels
In women get galactorrhea, amenorrhea, infertility
In men get impotency, oligospermia, decrease libido

Diabetes Insipidus
Symptoms = polyuria & polydipsia
Get large amounts of dilute urine & dehydration
Etiol:
head injury or surgery = temporary condition
Nephrogenic tubular insensitivity to ADH = permanent condition
Tx = replacement therapy with ADH

SIADH
Get too much ADH secretion & get retention of fluid
Etiol :
Some cancers especially oat cell lung cancer (very common cancer)
Post op (temporary, only last 1 week)
Stress
Psychiatric diseases
Pathophysiology = hypoosolarity & hyponatremia
Symptoms related to low serum sodium
First = fatigue & weakness
Then G-I sx
Then twitchings, convulsions, & coma

Hypothalmus
Three things it does relating to the endocrine system
(1) it makes the posterior pituitary hormones
oxytocin (OT)
antidiuretic hormone (ADH)
* nb: diabetes insipidus & SIADH

(2) it controls the anterior pituitary by means of hormones it makes

This physiology used in pharmacology

Releasing Hormones
* exp = GnRH (gonadotropin releasing hormone)
Inhibiting Hormones
(3) It controls sympathetic output of adrenal medulla

Thyroid Gland
3 hormones
Thyroxine (T4) = more abundant than T3, but less potent
Triiodothyronine (T3) = more potent than T4
Calcitonin
Functions:
Thyroid hormones (T4 & T3) function = increase metabolic rate
Calcitonin
lowers serum calcium by preventing the bones from giving it up
works in harmony with the parathyroid & parathormone

 Disease states
Goiter may be euthyroid, hyper or hypo
hyperthyoidism
Graves disease = one specific type;autoimmune etiol;
get exophthalmos

hypothyroidism
cretinism = congenital type
myxedema = adult type;get edema of face & tongue
Hashimotos disease = autoimmune; chronic inflam.
produces fibrosis of thyroid

Thyroid cancer
Key cause = radiation exposure

Goiter
By definition just means thyroid enlargement
Pathophysiology = excess TSH
If have goiter, patient may be
Normothyroid
Hypothroid
Hyperthyroid

3 clinical types
Endemic goiter --- from lack of iodine in diet (hypothyroid)
See next slide

From goitrogens --- from drugs (e.g. lithium) & foods (e.g. cabbage)
These prevent T3 & T4 production

Toxic goiter --- hyperthyoidism

Note: if goiter present & patient hyperthyroid but not toxic ----think
of Graves disease

Endemic goiter; hypothyroidism

Hyperthyroidism
2 types: with exophthalmos & without exopthalmos
Graves disease
Autoimmune
Most common form of hyperthyroidism
Get goiter
Symptoms = motor running fast
Tachycardia, systolic hypertension, palpitations,
insomnia,
heat produces discomfort
Exophthalmos (+/-)
Complication = thyrotoxicosis or thyroid storm
Treatment
Radioactive iodine
Surgery
Antithyroid drugs

Hypothyroidism
Commonest problem of thyroid
3 forms
Hashimotos thyroiditis---- autoimmune
Myxedema --- adult severe hypothyroidism
Myxedema = nonpitting edema of puffy face & thick tongue
In early mild form --- symptoms subtle; hard to diagnose
Muscle weakness (hung-up reflex)
Mental apathy
Dry skin
Likes heat (always cold)

Cretinism ---- congenital

short stature, thick tongue, protruding abdomen, mental retardation
Lack of hair (axillary)

Parathyroid Glands

Normally 4 glands located on posterior surface of thyroid

may have up to 8 glands
produces hormone: Parathormone (PTH)
it increases calcium in blood by breaking down bone to release calcium
it works in conjunction & opposite calcitonin
Effects of parathormone:
3 key effects: 2 on bone & 1 on kidneys
1. Acutely --- breaks bone down & increases serum Ca++
2. Chronically --- get bone remodeling; i.e. bone is broken down &
reformed
3. In kidneys resorbs Ca++ & secretes phosphorus
Tissue effects of calcium:
Skeletal muscle ------- no effect
Cardiac muscle ------- low weakens contraction; high strengthens contraction
(arrhythmias)
Nerve conduction ----- low increases excitability (get twitching, spasm, tetany)
high decreases excitability

 Hyperparathyroidism = hypersecretion = hypercalcemia

symptoms = SOUP, cardiac irritibility, osteoporosis, skeletal muscle
weakness due to decrease excitability of nerves
Primary hyperparathyroidism
Etiology ---- adenoma
Secondary Hyperparathyroidism more common
Etiology = decrease serum calcium secondary to:
Renal disease

Hypoparathyroidism = hyposecretion = hypocalcemia

symptoms =
hyperexcitible neuromuscular system & get twitching, spasms, &
tetany
Skeletal muscle contraction power = same; no change
Cardiac muscle = weak contraction
Etiol
Metastatic cancer --- raises calcium in blood & thus shuts off gland
Immobility causes bone to release calcium

Pancreas
Pancreas is both endocrine & exocrine gland
exocrine = digestive enzymes secreted via duct into duodenum
endocrine located in Islets of Langerhans
Cells of the islets
alpha cells produce glucagon
it raises blood sugar by increasing liver
glycogenolysis
beta cells produce insulin & amylin
Insulin lowers blood sugar by escorting glucose into
the cells
Amylin contributes to postprandial glucose control
* slows gastric emptying
* regulates appetite centrally
* see comment on good health --- next slide

 Insulin
Anabolic hormone (a type of growth factor)

Promotes synthesis of proteins, nucleic acids, & fats

This occurs in liver, muscle, & adipose tissue
Permits primarily glucose & ,also, amino acids into the
cytosol
Certain cells do not need insulin to get their glucose supply
Brain
RBCs
G-I tract epithelial cells can absorb glucose from diet
Theory of good health, longevity, & prevention of aging diseases

Good health = slow rises & falls of insulin production

Bad health = peaks & valleys production of insulin
Glycemic index & food

Diabetes Mellitus
Def: a disease that involves an insulin deficit
Get hyperglycemia
Get lack of available glucose in cells for mitochondria to make ATP
Thus, mitochondria use fats to generate ATP
Side effect = ketone body formation

Pathophysiology (with associated symptoms/signs of the disease)

Hyperglycemia
Glucosuria
Polyuria
Polydipsia
Polyphagia
-- & then
Fat catabolism

2 types (90% = type II & 10% = type I)

Insulin Dependent Diabetes Mellitus(IDDM) = Type I
autoimmune; get decreased production of insulin
Non Insulin Dependent Diabetes Mellitus(NIDDM) = Type II
get cellular insensitivity to insulin
Current epidemic in USA ; incidence --- 10% of adults
Major risk factor = obesity
Alzheimers disease & insulin cellular insensitivity

Etiology = autoimmune process; ? triggered by an infection early in life

Complications ---- divided into acute & chronic
Acute complications
Diabetic Coma ---- lethargy, dry (dehydrated)
Insulin Shock ---- anxiety, sweating
Chronic complications
Vascular complications get macro & microangiopathy
Macroangiography

* MIs; CVAs, peripheral vascular disease

Microangiography
* Kidneys ---- ruins glomerular capillary basement membrane
*Eyes ------ get diabetic retinopathy which leads to blindness

Adrenal Cortex
Has 3 distinct layers or zones
from outside towards middle:

Zona Glomerulosa
secretes mineralcorticoids (Aldosterone)
Retain sodium (water follows sodium)
Usually gets rid of potassium & hydrogen

Zona Fasiculata
secretes glucocorticoids (Cortisol)
Secreted in response to stress
Causes gluconeogenesis & hyperglycemia
Causes protein catabolism
* thus, delays healing
Is anti-inflammatory
Maintains BP by sensitizing vessels to ANS

Zona Reticularis
secretes sex hormones (steroids)

Diseases of the Adrenal Cortex

even though there are 3 different classes of hormones, most diseases affect primarily
the glucocorticoids
Hypersecretion
Commonest problem = involves glucocorticoids; but some diseases may have a
combination of components

Of glucocorticoids = Cushing disease

Commonest etiology = pituitary adenoma secreting ACTH
Other etiol:
ectopic ACTH secreting tumor (oat cell lung cancer, etc)
*called paraneoplastic syndrome
Adrenal adenoma
Taking steroids (exogenous)
Of mineralcorticoids = hyperaldosteronism
Commonest etiol = adrenal adenoma
Note that 5-10% of people with hypertension have them
Of sex steroids = feminization or virilization
Clinical picture depends on sex
Commonest etiol = adenoma & associated with Cushing disease

Cushing Disease (MOODIAH)

Moon face
Obesity & edema from salt
&
water
retention
Osteoporosis
Diabetes
Infections
Atherosclerosis
Hypertension

Etiol
Pituitary adenoma
Adrenal adenoma
Ectopic paraneoplastic
syndrome
Iatrogenic
Only cause that
produces adrenal
atrophy & resultant
poor response to stress
see next slide

Etiol
Pituitary adenoma
Adrenal adenoma
Ectopic
paraneoplastic
syndrome
Iatrogenic
Only cause that
produces adrenal
atrophy &
resultant poor
response to
stress

 Hyposecretion
Usually affects both glucocorticoids & mineralocorticoids

Addison Disease = primary adrenal insufficiency

Commonest etiol = autoimmune destruction of adrenal cortex
Get increased levels of ACTH
In secondary hypocortisolism get low levels of ACTH
Commonest etiol = exogenous glucocorticoids
Diagnostic clinical difference:
Increase ACTH & Addison disease = skin pigmentation (bronze
color)
Decrease ACTH & Addison disease = no skin pigmentation
Clinical features
get hypotension, fatigue, weakness, & weight loss
* severe hypotension = shock = life threatening
get dehydration & hyperkalemia* (from lack of aldosterone)
get bronze skin color & pigmentation ( if increase of ACTH)
Vitiligo from autoimmune destruction of melanocytes

Adrenal Medulla

Works in conjunction with sympathetic nervous system

Involved in the stress response
Makes catecholamines
Key ones are norepinephrine (20%) &
epinephrine (80%)
Epinephrine is 10 times more potent in
producing direct metabolic effects
* note that norepinephrine is more
potent as neurotransmitter

Diseases of Adrenal Medulla

Pheochromocytoma

Benign tumor of adrenal medulla

Cells of medulla called pheochromocytes
Greek = dusky color
Secretes epinephrine
Get hypertension

Stress Response

Def: A systemic generalized response to a change (stressor) either internal or

external
Stressors:
Physical
Psychological
Real
Imagined
Anticipated
Stressors are normal component of life
Can be positive ---- stimulate growth & development
Can be negative ---- if severe and/or not properly dealt with

PATOPHYSIOLOGY OF
REPRODUCTIVE SYSTEM
Susiana Candrawati

Male Reproductive System

Anatomy
Gonads = Testes
Ductile system = epididymis, vas deferens,
ejaculatory duct, urethra
Supportive glands = seminal vesicles,
prostate, bulbourethral (Cowpers)
External genitals = scrotum, penis

 Testes
tunica vaginalis = parietal peritoneum that remains surrounding testis after
its descent
tunica albuginea = tough connective tissue membrane that surrounds testis
and enters the gland to form septa
seminiferous tubules = where sperm are developed; approx. 100 yards in in
testis; contain
Sertoli cells
Leydig cells

 Testes (cont)
Physiology
Spermatogenesis
mature sperm formed by process
of Meiosis
Key = getting mature
gamete with number of
chromosomes
mature sperm = head
(nucleus & acrosome), neck
(mitochondria), and tail
takes 60 days +/- to make a
sperm
primary spermatocyte, secondary
spermatocyte, spermatids, sperm

Testosterone Production
2 key functions
masculinization
anabolism

 Male Ductal System

Epididymis
storage tank for sperm
sperm get final maturation
Vas Deferens
becomes Ejaculatory Duct after it joins seminiferous tubule duct
Urethra

Accessory Glands
Seminal Vesicles
contributes 60% of semen
rich in fructose ; provides energy for the sperm
Prostate
contributes 30% of semen ; provides nutrients for the sperm; antibiotic
secretion
Bulbourethral Glands (Cowpers)
contribute 5-10% of semen ; provides lubrication & sterilization

External Genitalia
Penis
3 columns of erectile tissue
corpora cavernosa (2) & corpora spongiosum (1)
glans covered by foreskin (prepuce)
Scrotum
skin-covered (has hair follicles) pouch suspended from groin

 Hormones and male reproductive function

Female Reproductive
System
Anatomy
gonads = ovaries
ductal system = fallopian
tubes, uterus, vagina
accessory glands =
Bartholin's, breasts
external genitalia = clitoris,
labia majora & minora,
perineum

 Ovaries
contain gametes (oocytes) surrounded by
some cells (follicular cells)
these called Primary Follicles
each ovary has appox. 1 million
at birth
life cycle of oocyte after puberty: primary
oocyte, secondary oocyte, ovum
functions
gamete production
hormone production
Estrogen = causes feminization ;
from granulosa cells
Progesterone = prepares for
pregnancy ; from corpus luteum

 Female Ductal System

Fallopian Tubes
distal end = fimbria
Outer 1/3 = fertilization
Uterus
composed of fundus, body, & cervix
has myometrium & endometrium]
Vagina

Accessory Glands
Bartholins (greater vestibular)
exocrine gland
provides lubrication
Breasts
composed of glands & ducts surrounded by fat tissue

External Genitalia
clitoris, labia majora & minora (no hair follicles), vestibule, perineum

The Menstrual Cycle

begins after menarche ; ends
with menopause

4 basic parts:
Menses
Proliferative Phase
= first half of cycle
deals with
maturation of
follicle &
development of
more granulosa
cells thus
producing more
estrogen
Ovulation = usually
at midcycle
Secretory Phase =
second half of cycle
deals with
conversion of
ruptured follicle
to corpus
luteum
corpus luteum
produces
progesterone

 hormonal control
hypothalamus-------GnRH (gonadotropin
releasing hormone)
anterior pituitary---FSH (follicle
stimulating hormone)
LH
(luteinizing hormone)
Ovary --------------Estrogen
Progesterone

Male reproductive tract disorders

Disorders of testes & scrotum
Disorders of prostate
Disorders of the penis

Disorders of the Testes & Scrotum

Cryptorchidism
undescended testis
By age one, 80% are in scrotum
incidence: 3% of term babies; 20% of premies
increases the incidence of carcinoma (Seminoma)
treat early-------the longer you wait, the greater the chance of
decreased sperm & testosterone production

 Hydrocele
most common disease of testes
its fluid in cavity bound by the 2 layers of tunica vaginalis
this may communicate with peritoneal cavity via congenital patency of
process vaginalis
this may cause size to vary from time to time

 Infertility Problems
deals with decreased production and/or quality of sperm
2 distinct reasons
poor production in sperm development
One correctable cause = varicocele
blockage of ductile system
low count = oligospermia
zero count = azospermia

Varicocele
varicosities around the testis (usually left testis)
left spermatic vein into renal vein (10 cm higher
than insertion of right spermatic
vein into inferior vena cava)
usually begins at puberty
may be relieved by lying down

 Torsion of the testis

Etiol:
Spontaneous
Post trauma

Timing
Usually puberty

Path: necrosis & infarction

 Testicular Cancer
range from VERY aggressive to least aggressive
Germ cell tumors
Seminoma = least aggressive (most common)
Nonseminomas
* embryonal carcinoma
* teratomas
* choriocarcinoma = most aggressive
Non- germ cell tumors
May be hormonally active (secrete androgen or estrogen)
Exp: leydig cell, Sertoli cell
tumors of young men ( age 15 - 35)
diagnosis : tumors are solid masses - no transillumination
Usually unilateral
predisposing factors:
undescended testes
inguinal hernia during childhood
prior history of mumps orchitis
Note: in mumps orchitis, 50% of cases result in testicular atrophy
Cure rate = 95%

Prostate Diseases
Benign Prostatic
Hypertrophy (BPH)
enlargement of the
prostate common in older
men
Involves central area of
gland
complications include:
pyelonephritis
hydronephrosis
uremia

 Cancer
primarily occurs in men over age 50
third leading cause of cancer death
Involves periphery of gland
Usually begins as nodule on posterior surface of gland
Many are androgen dependent
If metastases, first usually to bone
diagnosis
DRE
2 serum markers
PSA (prostatic specific antigen)
Prostatic acid phosphatase
Ultrasound

Pathology of the Penis

Foreskin (prepuce)
phimosis
paraphimosis
redundant foreskin
Glans
Balantitis

 Carcinoma

Rare
Risk factors: HPV (now have vaccination)
First sign = usually leukoplakia
circumcision in child prevents it
adult circumcision does not prevent it

Impotency
approx. 50% of men age 40 - 70 have, at times, some degree or complete
impotency ( failure to get an erection)
sexual stimulation causes release of nitric acid from nerves in penis
an enzyme breaks down the product of nitric acid that causes the erection
this enzymes effect is loss of the erection
this is where Viagra works ; it prevents loss of the erection

Female reproductive tract

disorders
Structural abnormalities

Menstrual disorders
Endometriosis
Menopause

Infections
Tumors
Benign
Malignant

Breast
Pregnancy
STDs

Structural abnormalities
Pelvic relaxation disorders
Normal variations of uterine position
Uterine mobility is key to normalcy
Uterine prolapse
First, second, & third degrees
Cystocele
Rectocele

Normal variations of
uterine position
Uterine mobility
is key to
normalcy
midline
Anteverted &
anteflexed
Retroverted &
retroflexed

Uterine Prolapse
def = downward displacement of uterus
etiol = fascial tissue defect
First degree
Get vaginal shortening
Second degree
Cervix at introitus
Third degree
Vagina completely everted
Uterus hanging outside vagina

 Cystocele
downward displacement of bladder into vagina
Can get retention & frequent cystitis
urethra may or may not accompany it
called cysto-urethrocele
frequently get symptom of urinary stress
incontinence

Rectocele
displacement of rectum into vagina
Usually asymptomatic
If very large may get constipation & inability to
completely evacuate rectum
May get ulceration of vaginal wall
See picture

Menstrual Disorders
Dysmenorrhea
Primary dysmenorrhea = when no obvious pathology found
? Hormonal cause
prostaglandins
hormonal changes secondary to teenage ovulatory cycles
Secondary dysmenorrhea = when obvious pathology found as the cause

Amenorrhea
Primary Amenorrhea = never having a menstrual flow
Secondary Amenorrhea = having menstrual cycles & then they stop
causes = many !!!
Treatment directed at the underlying cause

 Dysfunctional Uterine Bleeding (DUB)

abnormal menstrual flow when no obvious cause is known
frequently thought to be secondary to some type of hormonal
imbalance, but specific diagnosis not necessary to have DUB

Types:

oligomenorrhea
polymenorrhea
menorrhagia
metrorrhagia
meno-metrorrhagia

Premenstrual Syndrome (PMS)

group of symptoms that occur in the womans secretory phase of cycle
Currently called : PMDD (premenstrual dysphoric disorder)
Def of dysphoria = excessive pain, anguish, & agitation

usually secondary to inappropriate ovulation

Key = too much estrogen & not enough progesterone in the
second half of the cycle

 Endometriosis
A condition when you get endometrial tissue located outside
its normal position, which is the inside lining of the uterus
symptoms depend on where the ectopic tissue is located
the tissue has function, i.e.
bleeds with menstruation
Sx : pain
Complications
Fibrosis
Scarring
Adhesions
Infertility
Dyspareunia

MENOPAUSE
Get cessation of menses & drop in estrogens which can cause:
general symptoms
irritability
short term memory loss
Insomnia
Vasomotor instability = hot flashes & night sweats
gynecological symptoms
vaginal dryness & dyspareunia
urinary stress incontinence
Cardiovascular problems
ASHD
coronary artery disease
strokes
Osteoporosis
Dx: High FSH; low estrogens

Infections of the Female Reproductive Tract

Vaginitis
3 types:
Yeast Vaginitis
caused by fungus from genus Candida or Monilia

Trichomonas
caused by a protozoa
may be sexually transmitted
Bacterial Vaginosis
caused by different bacterial overgrowth
used to be called non-specific vaginitis or Gardnella
Generally most cases of vaginitis are NOT sexually transmitted, but at
times they ALL may be sexually transmitted !!

 Pelvic Inflammatory Disease (PID)

usually acute, but may be chronic
may involve some or all of the pelvic organs
get tissue inflammatory reaction with
resultant symptoms
Key symptom = pelvic pain
Pain worsens with movement & sex
frequently secondary to untreated or
inadequately treated STD
Complications
Infertility (pyosalpinx)
Adhesions
Dysuria
Irregular vaginal bleeding

Note PID spread:

Vaginitis
Cervicitis
Endometritis
Oophoritis

 Toxic Shock Syndrome (TSS)

vaginal infection with systemic symptoms
caused by staphlococci toxin which comes from nidus of infected
tampon
prevention by proper tampon toilet
Symptoms begin immediately post menses

Bartholin cyst (Bartholinitis)

Etiol = pathogens that cause inflammation
Duct become obstructed
Get large pimple

Tumors of the Female Reproductive Tract

 Cervix
Benign
Cervical polyps

malignant
key ages: 20 - 40
pap smear
Etiol: HPV
Vaccine available

Uterus
benign
fibroids = commonest tumor of female repo. System
leiomyomas
only in premenopause
See next slide

malignant
? Estrogen related
Age: 50 70
Dx: pmb

Estimated that half the women get them

during the reproductive years
Clinically symptoms depend on size &
location
Submucous = bleeding
problems, infertility
Intramural = sx only if large
Subserous = pressure sx from
surrounding structures

 Ovary
Benign
Functional (commonest)
Follicular cyst
Corpus luteum cyst
Non-functional (benign germ cell)

(e.g. Teratoma)

Malignant
Factors that suppress ovulation decrease the risk
Avg age = 40
2 basic types
Epithelial (line ovary or follicles)
Germ cell aggressive
Mainly in children & adolescents
See next slide re:
Late diagnoses
seeding

Breast disorders
Fibrocystic breasts
Was called fibrocystic disease
lumpy breasts

Fibroadenoma
Benign
In young girls (age 15-25)
nontender

Intraductile papilloma
Get nipple discharge

Mammary duct ectasia

Get lumpiness beneath areola
Seen in
Postmenopausal
Pregnancy
Lactation
Get thick nipple discharge
Pathophysiology: ducts dilate & fill with cellular debris; get
inflammation

 Breast cancer

1 out of 8 women in USA

Most are intraductile carcinomas
50% in upper outer quadrant
Ca in situ = mammary dysplasia
Risk factors:
Family history
Menstrual history
Reproductive history

Pathology in Pregnancy
Morning Sickness
severe form = Hyperemesis Gravidarum

Spontaneous Abortion
3 Types : Complete, Incomplete, Missed

Ectopic Pregnancy
Toxemia of Pregnancy = syndrome of hypertension, proteinuria, &
edema
called Preeclampsia
If severe & accompanied by convulsions, called Eclampsia

Placental Problems
Placenta Praevia
Abruptio Placenta

Hydatidiform Mole = development abnormality of conception

may progress to Choriocarcinoma

 Preterm Birth
8% of all births in US
Preterm labor
Preterm PROM (premature rupture of membranes)
Responsible for half of all premie deliveries in US

Trauma during pregnancy

Complicates 1 out of 12 pregnancies in US
Watch for:
Uterine contractions
Uterine tenderness &/or irritability
Ruptured BOW
Nonreassuring FHR pattern
Vaginal bleeding

Maternal hemorrhage
Is the leading cause of maternal mortality
Hemorrhagic shock
Postpartum hemorrhage

Endometritis
Occurs in 1-3% of vaginal births
Occurs in 10-50% of cesarean sections

STDs
AIDS (Acquired Immunodeficiency Syndrome)
Def: progressive impairment of the immune system caused by the
immunodeficiency virus (HIV)
Attacks helper T lymphocytes

Initial infection similar to URI

Then latency
Then AIDS
Begins with generalized adenopathy, weight loss, fatigue, nt. Sweats,
and diarrhea
Get opportunistic infections:
PCP (pneumocystis carinii pneumonia) = caused by small
protozoa (? fungus) that can normally be found in lung tissue of
certain animals (dogs) and in humans
Toxoplasmosis = small protozoan that can infect many mammals
including cats and dogs
Herpes simplex
Herpes zoster (shingles)
TB

 AIDS (continued)
Get opportunistic cancers
Non-Hodgkins lymphoma
Kaposis sarcoma

HIV also has predilection to attack G-I cells & CNS cells
Get malabsorption, colitis, and proctitis
Dementia

Diagnosis
ELISA (enzyme-linked immunosorbent assay)
Western blot test

Treatment
AZT = reverse transcriptase inhibitors
Protease inhibitors
Fusion inhibitors

 Chlamydia
Most frequent bacterial STD
Known as the silent STD
Transmitted via oral, anal, or genital intercourse
Oral route can lead to conjunctivitis

If symptomatic, get urethritis

Incubation = 1-3 weeks

Gonorrhea

Bacterial
Incubation = 1-3 weeks (usually less than 1 week)
Very similar in signs & symptoms to chlamydia
Antibiotic resistance

Syphilis

Bacterial
Can get primary, secondary, and tertiary forms
New cases at an all time low
Primary = hard, painless chancre in 2-3 weeks ------------ see pictures
Secondary syphilis may appear 1-3 months later
Then latency for years & then possible tertiary syphilis

 Chancroid
Soft chancre (painful) with bubo(necrotizing ulceration &
lymphadenopathy) in 1 week
See pictures

Bacterial
Frequent in developing tropical countries
Increasing in urban USA

Genital Herpes
Type I & type II
Short incubation of 2-7 days
See pictures

Hepatitis B & C
Transmitted in body fluids

 Genital warts
Very contagious
First exposure incidence:
40% ---to--- 90%
Viral; HPV
120 different serotypes
A few cause dysplasia & neoplasia
Condylomata accuminatum
Benign growths
See picture
Prolonged incubation of 1-6 months
Most frequent STD
Estimated that 60% of sexually active young
women in USA have it
New vaccine available

Differences in clinical appearance among genital ulcers

PATOFISIOLOGI
MUSKULOSKELETAL
dr. Susiana Candrawati, Sp KO

JOINT

BONE

Metabolic Bone Dis

Osteoporosis

Osteomalacia

Paget Dis
Infection Bone Dis

Osteomyelitis

MUSKOSKELETAL

OA

Myositis

RA

Myopathy

GOUT

Definition
Osteoporosis density/mass of bone is
reduced

Normal Bone

Osteoporotic bone

 Porous bones
Bones have lost calcium and other
minerals
Bones are fragile
Bones fracture easily

Risk Factor
Female gender
Increasing age
Thin, small-boned - BMI < 19

Caucasian or Asian ethnicity

Family history of fractures or osteoporosis

Risk Factor
Abnormal menstrual history
Late menarche
Menstrual interruptions/irregularities

Early menopause (< age 45)

Have had an eating disorder or times of strict dieting

Risk Factor
Medical conditions
Bone fracture(s) after age 40
Rheumatoid arthritis
Thyroid disorder
Parathyroid disorder
Poorly controlled Type 1 diabetes
Lactose intolerance
Digestion disorders

Risk Factor
Lifestyle Risk Factors
Inactive lifestyle
Diet low in calcium*
Little sun exposure and diet low in vitamin D*
Consume few fruits and vegetables*
Drink excess alcohol (> 7 drinks/week)*
Current or former smoker
Consume large amounts of caffeine
* : untuk terapi diet susu dan produk olahannya

PathoPhysiology
an imbalance between bone resorption and
formation

estrogen deficiency
immobilization
metabolic acidosis
hyperparathyroidism
local inflammatory
diseases

TNF,
IL-1,
IL-6

OSTEOBLAST NUMBER &

ACTIVITY

MEDICAL OR MEDICATIONS

DIAGNOSTIC MEASUREMENTS
Radiography
signs of demineralization or

compression fractures

Bone densitometry
T score < - 2,5

Osteomalacia

Definition

is characterized by impaired mineralization of

bony matrix.

Calcium *
Phosphate, *
Vitamin D*
* untuk terapi diet

Symptom & Sign

generalized pain :
the pelvis, spine, ribs, or lower
extremities

skeletal deformities

Osteomyelitis

Definition
an acute or chronic inflammatory process
of the bone and its structures secondary
to infection with pyogenic organisms

 Hematogenous osteomyelitis
a remote source- blood

Direct or contiguous inoculation

osteomyelitis
direct contact of the tissue and bacteria
during trauma or surgery

Physical Finding

Fever
Edema
Warmth
Fluctuance
Tenderness to palpation
Reduction in the use of the extremity
Sinus tract drainage


Lab Studies:
The WBC elevated
A leftward shift - increased PMN

CRP elevated
ESR elevated
Culture or aspiration findings

Imaging Studies:
Radiography
MRI

Radionuclide bone scanning

CT scanning

Ultrasonography

Osteoarthritis

Arthritis affects many

older adults
Women

Men

53%

37%

What is Osteoarthritis?
Osteo (bone) + arthron (Gr. Joint) + itis
Osteoarthrosis ( osis Gr. Morbid
process)
Def.
a degenerative joint disease,
characterized by

 primarily in older persons,

erosion of the articular cartilage,
hypertrophy of bone at the margins
(i.e., osteophytes),

subchondral sclerosis, and

a range of biochemical and
morphologic alterations of the
synovial membrane and joint
capsule.

Risk factors

2 types :
cannot change and
you can change

Cannot change
Family history of
disease
Increasing age
Overuse of the joint
Major injury
Overweight
Muscle weakness

Diagnosing osteoarthritis

Medical history
Physical exam
X-ray
Other tests

Pathophysiology

Pathogenesis 3 stages:
Stage 1: Proteolytic
breakdown of the
cartilage matrix
occurs.

destroy
the
cartilage
matrix.

Metalloproteinases
(eg, collagenase,
stromelysin)

>
Production

Chondrocyte

protease inhibitors:
tissue inhibitors of
metallo-proteinases
(TIMP) 1 and 2


Stage 2:
the fibrillation and erosion of the cartilage surface-
release of proteoglycan and collagen fragments into
the synovial fluid.

 Stage 3:

Stage I

The
breakdown
products of
cartilage
Stage II

induce

chronic
inflammatory
response in
the synovium
Synovial
macrophage

Cytoken

IL-1
TNF-

metalloproteinases

Mol. Pro inflam.

NO

Rheumatoid Arthritis

Background
RA = a chronic syst. Inflam. Dis. of unknown cause
that primarily affects the peripheral joints in a
symmetric pattern.
Constitutional symptoms:
fatigue,
malaise, and
morning stiffness

Extra-articular:

skin,
heart,
lungs, and
eyes

The American College of

Rheumatology
1. Morning stiffness:

Occurs in and around the joints

2. Arthritis 3 or > joint areas:

At least 3 joint areas simultaneously + soft tissue

swelling or fluid (not bony overgrowth)

3. Arthritis of hand joints of at least one area

swollen in :

a wrist,
metacarpophalangeal (MCP),
proximal interphalangeal (PIP)

The American College of

Rheumatology
4. Symmetric arthritis with simultaneous
involvement of the same joint areas on

both sides of the body:

Bilateral involvement of PIPs, MCPs, and

MTPs is acceptable without absolute

symmetry.

The American College of

Rheumatology
5. Rheumatoid nodules<+>
6. Serum RF <+>

7. Radiographic changes typical of RA

RA - 4 of 7 criteria are present.

Etiology:
Genetic Susceptibility:
HLA DR4, or DR1 in 65% to 80% cases.

Microbial inciting agent:

Epstein-Barr virus, Borrelia & Mycoplasma

Autoimmunity:
IGM anti IgG RA Factor.
Helper T cell (CD4) against type II collagen &
cartilage glycoprotein-39

RA Is Characterised by Synovitis and

Joint Destruction
NORMAL

RA
Inflamed
synovial
membrane

Synovial
membrane

Major cell types:

T lymphocytes
macrophages

Pannus
Cartilage

Minor cell types:

fibroblasts
plasma cells
endothelium
dendritic cells

Synovial
fluid

Capsule

Cartilage thinning

Major cell type:

neutrophils

IL-1 Plays a Pivotal Role in the Inflammatory and Destructive

Processes of RA

IL-1

Activates
monocytes/ Induces fibroblast
proliferation
macrophages

Inflammation

Synovial pannus
formation

Activates
chondrocytes

Activates
osteoclasts

Cartilage
breakdown

Bone
resorption

Gouty Arthritis

Background
= disorder of uric acid

metabolism - :
recurrent episodes of
joint inflammation,
tissue deposition of
uric acid crystals, and
joint destruction if left
untreated.

GOUT OCCURS WHEN EXCESS URIC ACID ACCUMULATES IN THE

BLOOD, A CONDITION KNOWN AS HYPERURICEMIA *
* : TERAPI DIET
TO CRASH OUT OF SOLUTION AND FORM SMALL JAGGED CRYSTALS

THESE CRYSTALS ARE THEN

DEPOSITED IN/AROUND
VARIOUS JOINTS

MIOPATI

Miopathie

Inflamatory
Endocrine disorders
Electrolyte disorders
Metabolic myopathies
Drugs and toxin
Infections
Rhabdomyolisis

Differential Diagnosis

Pathophysiology
Inflamatory myopathy
Immune mediated triggered
Environmental Agents
Infectious: Coxsackie B1, HIV, HTLV-1, Hepatitis B,
Influenza, Echovirus, Adenovirus
Non infectious: statins, hydroxycholoquine, cochicine,
procainamide, phenytoin, ACE Inhibitors, D-penicillamine

Genetically predisposed
HLA A1, B8, DR3

Clinical Features of Dermatomyositis and Polymyositis

*Symmetrical proximal muscle weakness
Insidious onset with gradual worsening over months
Weakness of oralpharygeal muscles or striated muscle of upper one
third esophagus (poor prognosis)
Myalgia (25-50 %): can be confused with PMR
Neck flexors affected

Constitutional Symptoms
Morning stiffness, anorexia, weight loss, fatigue, fever (assoc with
anti-Jo1)

Joints
Arthralgia or symmetrical arthritis (rarely deforming erosive
arthropathy)

Clinical Features of Dermatomyositis and Polymyositis

Cardiac
Conduction defects, CHF, pericarditis, pulm HTN,
myocarditis

Kidneys
Rare: severe rhabdomyolysis with myoglobinuria (ATN)

Lungs

Interstitial lung disease10%

Dyspnea and nonproductive cough
Histopath: NSIP, UIP, BOOP, DAD
PFTs: restrictive pattern with markedly diminished
diffusing capacity (most sensitive)

 Skin:
Gottrons sign: symmetric, scaly, violaceous
erythematous eruption over extensor surfaces
of MCP and IP joints, elbows, knees (psoriasis)
Mechanic's Hands (PM):hyperkeratotic
eruptions over finger pads and lateral aspects
of fingers
Raynauds
Periorbital edema
Calcinosis (5% of DM)

 Labs
CK, LDH, aldolase, AST, ALT
Autoantibodies: ANA (myositis with overlap)
anti Jo-1 antibodyanti-histidyl-trna
synthetase: 20%, ILD, Raynauds, Mechanics
hands
Anti Mi 2 antibodyhelicase in transcriptional
activitation; associated with acute onset classic
DM
Anti PM-scl and Kuoverlap of myositis and
scleroderma

PATHOPHYSIOLOGY DIGESTIVUS
SYSTEM
Susiana Candrawati

Chronic Gastritis
The presence of chronic inflammatory changes
in the mucosa
Helicobacter pylori, HP
Mucosal atrophy
Epithelial metaplasia

Pathogenesis
The bacillus H. pylori.
Immunologic (autoimmune), in association with
pernicious anemia
Toxic, as with alcohol and cigarette smoking
Postsurgical, especially following antrectomy with
gastroenterostomy with reflux of bilious
duodenal secretions
Radiation
Miscellaneous-amyloidosis, graft-versus-host
disease, uremia

Peptic Ulcers
Peptic ulcers are chronic, most often
solitary,lesions that occur in any portion of the
gastrointestinal tract exposed to the aggressive
action of acid/peptic juices.
Duodenum, first portion
Stomach, usually antrum
Ulcers are defined histologically as a breach in the
mucosa of the alimentary tract that extends
through the muscularis mucosa into the
submucosa or deeper.

Pathogenesis
Imbalance between gastroduodenal mucosal
defense mechanisms and the damaging forces
H. pylori infection is a major factor in the
pathogenesis of peptic ulcer
Chronic use of NSAIDs
Cigarette smoking
Alcohol
Corticosteroids

 Two conditions are key for the development of

peptic ulcers
(1) H. pylori infection
(2) Mucosal exposure to gastric acid and
pepsin

NSAIDs are the major cause of peptic ulcer

disease in persons who do not have H. pylori
infection

Complications of Peptic Ulcers

Bleeding
Perforation
Obstruction from edema or scarring

Clinical Features
Epigastric gnawing, burning, or aching pain.
Iron-deficiency anemia, frank hemorrhage, or
perforation.
The pain tends to be worse at night and occurs
usually 1 to 3 hours after meals during the day
Nausea, vomiting, bloating, belching, and
significant weight loss
Treated by antibiotics active against H. pylori,
proton pump inhibitors, and hydrogen receptor
antagonists

Appendicitis
Is the most common acute abdominal
condition the surgeon is called on to treat.
Inflammation in the right lower quadrant
Adolescents and young adults
Acute Simple Appendicitis
Acute Suppurative Appendicitis
Acute Gangrenous Appendicitis

Complication
Rupture
Suppurative peritonitis
Pyelophlebitis with thrombosis of the portal
venous drainage
Chronic inflammation of the appendix
Cystic fibrosis

Clinical Features
(1) Pain, at first periumbilical but then localizing
to the right lower quadrant;
(2) Nausea and/or vomiting;
(3) Abdominal tenderness, particularly in the
region of the appendix;
(4) Mild fever;
(5) An elevation of the peripheral white blood
cell count up to 15,000 to 20,000 cell/L.

Viral Hepatitis
Infection of the liver caused by a group of viruses
having a particular affinity for the liver
Infectious mononucleosis (Epstein-Barr virus)
Cytomegalovirus
Yellow fever

Hepatotropic viruses cause overlapping patterns

of disease

Etiology
Hepatitis viruses A (HAV), B (HBV), C(HCV), D
(HDV), E (HEV), Hepatitis G virus (HGV)

Hepatitis A Virus
A benign, self-limited disease with an
incubation period of 2 to 6 weeks.
HAV occurs throughout the world and is
endemic in countries with substandard
hygiene and sanitation.
Blood-borne transmission of HAV occurs only
rarely.

Hepatitis B Virus
HBV can produce :
(1) Acute hepatitis with resolution
(2) Chronic hepatitis, which may evolve to
cirrhosis
(3) Fulminant hepatitis with massive liver necrosis
(4) The backdrop for hepatitis D virus infection
HBV also plays an important role in the
development of hepatocellular carcinoma.

Risk categories for HBV infection

Transfusion
Blood products
Dialysis
Needle-stick accidents among health care
workers
Intravenous drug abuse
Homosexual activity

Hepatitis C Virus
Hepatitis C virus (HCV) is a major cause of liver
disease worldwide.
The major routes of transmission are
inoculations and blood transfusions.
HCV could become the leading cause of
chronic liver disease in the Western world.
Cirrhosis may develop over 5 to 20 years after
acute infection.

Serologic Diagnosis
HCV RNA is detectable in blood for 1 to 3
weeks, coincident with elevations in serum
transaminases.
In patients with symptoms of chronic hepatitis,
HCV RNA testing must be performed to assess
viral replication and to confirm the diagnosis
of HCV infection.

Hepatitis D Virus
Causing infection only when it is encapsulated
by HBsAg

HDV is absolutely dependent on the genetic

information provided by HBV for
multiplication and causes hepatitis only in the
presence of HBV.

Serologic Diagnosis
HDV RNA is detectable in the blood and liver
just prior to and in the early days of acute
symptomatic disease.
Acute coinfection by HDV and HBV is best
indicated by detection of IgM against both
HDAg and HBcAg.

Hepatitis E Virus
An enterically transmitted, water-borne
infection that occurs primarily in young to
middle-aged adults.
In most cases, the disease is self-limiting.
HEV is not associated with chronic liver
disease or persistent viremia.
HEV RNA and HEV virions can be detected in
stool and liver.

General Aspects of Liver Disease

(1) Patterns of hepatic injury
(2) Hepatic failure and cirrhosis
(3) Jaundice and cholestasis

Patterns of Hepatic Injury

Degeneration and Intracellular Accumulation
Swelling of hepatocytes
Ballooning degeneration
Feathery degeneration
Steatosis

Patterns of Hepatic Injury

Inflammation
Influx of acute or chronic inflammatory cells
Regeneration
Hepatocellular proliferation is marked by
mitoses, thickening of the hepatocyte cords.
Fibrosis
In response to inflammation or direct toxic
insult to the liver.
Ductular reaction

Liver Cirrhosis
Among the top 10 causes of death in the
Western world.
Alcohol abuse
Viral hepatitis
Biliary disease
Iron overload

Pathogenesis
The most frequent are chronic hepatitis B and
C and chronic alcoholism.
Less frequent causes are autoimmune and
biliary diseases and metabolic conditions such
as hemochromatosis.
Types I and III collagen are deposited in the
lobule, creating delicate or broad septal tracts.

Hepatocellular death
Regeneration
Progressive fibrosis
Vascular changes

Clinical Features
Nonspecific clinical manifestations:
Anorexia, weight loss, weakness, osteoporosis, and,
in advanced disease, frank debilitation. Incipient or
overt hepatic failure
Gastrointestinal hemorrhage. Imbalances of
pulmonary blood flow
The ultimate mechanism of most cirrhotic deaths
(1) Progressive liver failure
(2) A complication related to portal hypertension
(3) The development of hepatocellular carcinoma

Portal Hypertension
Results from increased resistance to portal flow at
the level of the sinusoids and compression of
central veins.

Four major clinical consequences

Ascites
The formation of portosystemic venous shunts
Congestive splenomegaly
Hepatic encephalopathy

Ascites
Ascites refers to the collection of excess fluid
in the peritoneal cavity.
Clinically detectable 500ml
Cause massive abdominal distention
Influx of neutrophils suggests secondary
infection
Red cells point to possible disseminated intraabdominal cancer

Pathogenesis
Sinusoidal hypertension
Percolation of hepatic lymph into the
peritoneal cavity
Intestinal fluid leakage
Renal retention of sodium and water

 Seen here is "caput medusae" which consists

of dilated veins seen on the abdomen of a
patient with cirrhosis of the liver.

Jaundice and Cholestasis

Jaundice occurs when retention of bilirubin leads to
serum levels above 2.0 mg/dL.
Hepatitis and intra- or extra-hepatic obstruction of bile
flow are the most common causes of jaundice involving
the accumulation of conjugated bilirubin.
Hemolytic anemias are the most common causes of
jaundice involving the accumulation of unconjugated
bilirubin.
Cholestasis is the impairment of bile flow resulting in
the retention of bilirubin, bile acids, and cholesterol.
Serum alkaline phosphatase is usually elevated in
cholestatic conditions.

Hepatic Failure
As the end point of progressive damage to the
liver.
The result of sudden and massive destruction
of hepatic tissue.
Systemic infections
Electrolyte disturbances
Stress (major surgery, heart failure)
Gastrointestinal bleeding

The Causes of Hepatic Failure

Acute liver failure with massive hepatic
necrosis.
Chronic liver disease.
Hepatic dysfunction without overt necrosis

Clinical Features
Jaundice is an almost invariable finding.
Hypoalbuminemia, which predisposes to
peripheral edema.
Hyperammonemia is attributable to defective
hepatic urea cycle function.
Impaired estrogen metabolism and consequent
hyperestrogenemia are the putative causes of
palmar erythema and spider angiomas of the
skin.
In the male, hyperestrogenemia also leads to
hypogonadism and gynecomastia.

Hepatic Encephalopathy
A feared complication of acute and chronic liver failure.
Patients show a spectrum of disturbances in brain
function
Stupor, to deep coma and death.
Fluctuating neurologic signs include rigidity, hyperreflexia,
nonspecific electroencephalographic changes and
seizures.
Asterixis (also called flapping tremor).
Edema and an astrocytic reaction
An elevation in blood ammonia

Hepatorenal Syndrome
Appears in individuals with severe liver
disease, consists of the development of renal
failure without primary abnormalities of the
kidneys themselves.
The ability to concentrate urine is retained,
producing a hyperosmolar urine devoid of
proteins and abnormal sediment that is
surprisingly low in sodium.

The major clinical

consequences of portal
hypertension in the
setting of cirrhosis, shown
for the male.
In women, oligomenorrhea,
amenorrhea, and sterility
are
frequent,hypogonadism.

Summary of Cirrhosis
The three main characteristics of cirrhosis are
(1) bridging fibrous septa
(2) parenchymal nodules containing replicating hepatocytes
(3) disruption of the architecture of the entire liver.
The most frequent are chronic hepatitis B and C and chronic
alcoholism.
Morphologic features of advanced cirrhosis are similar, regardless of
the cause of the disease.
The main complications of cirrhosis
Decreased liver function
Portal hypertension
Increased risk of hepatocellular carcinoma

Pancreatitis
Pancreatitis encompasses a group of disorders
characterized by inflammation of the
pancreas.
Acute pancreatitis
Chronic pancreatitis

Pathogenesis
Pancreatic duct obstruction
Primary acinar cell injury
Defective intracellular transport of
proenzymes within acinar cells


Acute pancreatitis is characterized by inflammation and reversible
parenchymal damage with lesions ranging from focal edema and fat
necrosis to widespread parenchymal necrosis and hemorrhage; clinical
manifestations vary from mild abdominal pain to a rapidly fatal vascular
collapse.

Chronic pancreatitis is characterized by irreversible parenchymal damage

and scar formation; clinical manifestations include chronic malabsorption
(due to pancreatic exocrine insufficiency) and diabetes mellitus (due to
islet cell loss).Both entities share similar pathogenic mechanism, and
indeed recurrent acute pancreatitis can result in chronic pancreatitis.
Ductal obstruction and alcohol are the most common causes of both
forms.
Inappropriate activation of pancreatic digestive enzymes (due to
mutations in genes encoding trypsinogen or trypsin inhibitors) and
primary acinar injury (due to toxins, infections, ischemia, or trauma) also
cause pancreatitis.