Female repro

Anatomy
- Vulva = external genitalia, labia majora/minor, clitoris (corpora cavernosa)
- Vagina = muscular (middle) and inner mucous (stratified squamous) layers
o Kept moist by Bartholin/lesser vestibular glands, transudate, desquamations,
cervical mucus, UGT fluids, leukocytes
o Sexual stimulation/estrogen increase vaginal fluid
o Upper 1/3 formed by Mullerian duct, lower 2/3 from urogenital sinus
(sinovaginal bulbs -> vaginal plate -> canalization -> hymen perforation)
- Cervix = internal/external os, transformation zone (squamocolumnar junction)
o SCJ near ectocervix before puberty, in the ectocervix during reproductive age and
recedes into endocervix post menopause
o Formed from Mullerian duct
o Culdocentesis done through posterior fornix -> pouch of Douglas
- Uterus = myogenic, supports growing embryo, triple layered myometrium, anteverted
and anteflexed
o Supported primarily by pelvic diaphragm + perineal body, secondarily by the
transverse cervical/cardinal + uterosacral + pubocervical ligaments
o Formed from Mullerian duct
- Fallopian tubes = site of sperm capacitation and oocyte fertilization (ampulla), conduit
(ciliated cells) and nutrition (peg cells) for oocyte/sperm/zygote
o Ampullary region highly invaginated while isthmus and intramural region are
progressively smoother
o Formed from Mullerian duct
- Ovaries = site of oogenesis and ovulation
o Hilar cells = in fetal and post-pubescent ovary -> secrete androgens
o Oocyte = surrounded by single layer of cuboidal granulosa cells (primary follicle)
-> granulosa cells divide into multiple layers with a zona pellucida in between the
oocyte and the granulosa layer -> stromal cells differentiate into theca
interna/externa cells -> antrum forms with the oocyte surrounded by the corona
radiata (secondary oocyte)
- Blood supply = ovarian artery (abdominal aorta), uterine + vaginal + internal pudendal
arteries (internal iliac)
o Ureters pass beneath uterine artery
- Lymphatic drainage = superficial structures to superficial inguinal nodes, deep structures
to internal iliac, ovaries to paraaortic
- Innervation
o Parasympathetic = pelvic splanchnic nerves (S2-4)
o Sympathetic = sacral splanchnic nerves (sympathetic trunk)
o Pudendal nerve = superficial structures (S2-4)
Physiology
Hormones - pulsatile release regulates menstrual/ovarian cycle
- GnRH (hypothalamus) -> causes release of FSH/LH
- FSH/LH (anterior pituitary) -> causes release of estrogen/progesterone
o FSH increases LH sensitivity in granulosa cells
o Puberty = decreased negative feedback on FSH/LH release + increased gonadal
sensitivity
o Menopause = oocyte depletion -> estrogen depletion -> continuous high FSH/LH
▪ Lack of estrogen -> osteoporosis, hypercholestermia, hot flashes,
urogenital atrophy, etc.
- Estrogen (ovaries) -> estradiol is main estrogen (benzene ring)
o Promotes acidification of vagina (pH < 4.5) -> lactobacillus thrives (lactic acid) ->
suppression of pathogens
▪ Decrease in lactobacillus -> pH > 4.5 -> vaginosis/vaginitis -> SCFAs
(pro-inflammatory)
o Promotes uterine contraction, increases ciliated cells in fallopian tube, ductal and
endometrial growth, increases progesterone receptor expression, relaxes pelvic
ligaments, increased cholesterol uptake (progesterone synthesis), genitalia
enlargement, prolactin secretion
o Binds to sex-hormone binding globulin with high specificity/affinity, albumin with
low specificity/affinity but high capacity -> binds to intracellular receptors
- Progesterone (ovaries)
o Promotes uterine relaxation (decreased oxytocin sensitivity), increases peg cells
in fallopian tubes, breast tissue/alveoli growth, increases body temp by 0.5oC,
decreases estrogen receptors and aromatase
o Binds to corticosteroid binding globulin with high specificity/affinity, albumin
with low specificity/affinity but high capacity -> binds to intracellular receptors
- Oxytocin (posterior pituitary)
o Promotes uterine contraction, milk ejection
- hCG (trophoblasts)
o Maintains corpus luteum -> secretion of progesterone and estrogen
o Testosterone production in male testes
- hCS (placenta)
o Mammary gland development, decreases maternal insulin sensitivity (glucose
sparing for fetus), increases maternal lipolysis
- Relaxin (corpus luteum and placenta)
o Increased CO/renal blood flow/arterial compliance, relaxes pelvic ligaments
- Prolactin (anterior pituitary)
o Stimulates breast alveolar growth, milk production
o Estrogen induces synthesis/secretion, dopamine inhibits release
 o Increased CO/renal blood flow/arterial compliance, relaxes pelvic liga
- Prolactin (anterior pituitary)
o Stimulates breast alveolar growth, milk production
o Estrogen induces synthesis/secretion, dopamine inhibits release
Menstrual cycle – between 23 and 35 days
- Menstruation = decline in progesterone (25th day) -> endometrial shedding
o Fibrinolysin prevents clotting and prostaglandins induce contractions
- Proliferation = increase in estrogen -> endometrial proliferation (stratum functionalis) +
spinal artery extension + thin/stringy cervical mucus (sperm motility)
- Secretory = increase in progesterone -> endometrial secretion + thick cervical mucus
plug (blocks sperm movement)
Ovarian cycle
- Follicular = increase in FSH causes follicles to develop
o Primordial follicle -AMH/activin sensitive-> primary follicle -FSH sensitive->
secondary follicle -FSH dependent-> tertiary follicle
▪ Primary follicle arrested in prophase I -> LH causes cGMP/cAMP depletion
causing meiosis II -> sec. follicle arrested in metaphase II until fertilization
▪ Single oocyte produces 1 mature ovum + 2 polar bodies

▪ AMH suppresses recruitment of primordial follicles -> maintains pool of

egg -> used to measure ovarian reserve
o FSH decreases because of inhibin (granulosa cells) + increased estrogen ->
follicular atresia
- Ovulation = estrogens increases causes positive feedback and LH surge -> progesterone +
prostaglandin spike + angiogenic spike -> collagenases (weakened follicular wall) +
hyperemia (follicular swelling) -> rupture of tertiary follicle
o Fertile period is 6 days before and 3 days after ovulation
- Luteal = LH induces corpus luteum production of progesterone to transform
endometrium into secretory state (decidualization, Arias-Stella reaction/hob nail
change) -> consistently lasts 12-16 days
o Theca lutein cells produce androgens (StAR, 17a-hydroxylase) that are sent to
granulosa lutein cells and converted to estrogen (aromatase)
o Absence of fertilization = no hCG -> corpus luteum becomes corpus albicans
Fertilization & Implantation & Embryonic development
- Acrosome reaction releases hyaluronidase -> sperm penetrates zona pellucida -> sperm
fuses with egg -> Ca release -> cortical reaction -> ZIP release -> zona pellucidum
hardening + detachment of other sperm blocking polyspermy -> completion of meiosis II
- Zygote undergoes mitosis -> blastocyst implants into uterus after 5 days -> inner cell
mass forms embryo and outer cell mass forms trophoblasts/placenta
o Synctitiotrophoblasts secrete hCG to maintain corpus luteum for estrogen and
progesterone secretion for first trimester until placenta takes over
- Synctitiotrophoblasts invade the endometrium/decidua -> formation of lacunae and
intervillous space -> development of utero-placental circulation -> invasion of spiral
arteries by cytotrophoblasts
Pregnancy and lactation
- Placenta = provides nutrients and O2 and removes waste and CO2 for the fetus
- Pituitary enlarges -> increased TSH, ACTH, PTH
 - Labor = uterus become more excitable -> cervical stretch from fetal head causes oxytocin
and prostaglandin release + downregulation of progesterone receptors + increased
estrogen -> uterine contraction
- Lactation = prolactin stimulates milk production -> nipple stimulation causes release of
oxytocin and milk ejection
o Lactogenic effect inhibited by estrogen and progesterone -> post-partum
decrease in estrogen/progesterone allows for milk production
- Prenatal visits = monthly until week 28 -> biweekly from week 29-36 -> weekly from
week 36 onwards
o History and physical exam updated 3 times -> once in 2nd trimester, once in early
3rd trimester, once in late 3rd trimester
- Blood changes = decrease in protein C/S + antithrombin -> prone to thromboembolism
- Changes prior to labor = increased CRH (estrogen, PG synthesis) + estrogen (gap
junctions, oxytocin/PG receptors), decreased progesterone
- Stages of labor
o Stage 1 = initial latent phase -> active phase (up to 10 cm dilated, cervix effaced,
1 minute contractions every 3-5 minutes)
o Stage 2 = crowning of head -> delivery of baby
o Stage 3 = delivery of placenta
Fetal physiology
- Blood flow = half goes to placenta, half to fetus (majority to the head)
o Maternal O2 transfer to fetus -> fetal Hb (2a2y chains) has higher O2 affinity,
double Bohr effect
- Changes after birth
o Loss of placenta -> increase in systemic TPR -> increased aortic, left atrial and
ventricular pressure -> closure of foramen ovale
▪ Patent foramen ovale remains closed due to greater pressure in left
atrium as compared to right atrium
o Expansion of lungs -> decrease in pulmonary resistance -> decreased right
atrial/ventricular pressure + atrophy
▪ Gas exchange established by -> lung fluid clearance + spontaneous
breathing + opening of alveoli + closure of right-left shunt + decreased
pulmonary resistance
▪ Transient tachypnea due to poor lung fluid resorption (C-section delivery)

▪ Lack of surfactant (<25 weeks) -> infant respiratory distress

o Closure of ductus areteriosus due to lack of vasodilator PGE2 (no placenta) +
increased vasoconstrictor bradykinin (lungs) -> undergoes fibrosis
▪ PDA due to increased PGE2 in vessel wall -> treated with indomethacin
o Closure of ductus venosus -> increased blood flow through fetal liver
o Transient hypoproteinemia edema/jaundice due to deficient liver function
 o Transient hypoglycemia especially in children born to diabetic mothers
o Physiologic anemia due to drop in erythropoietin in response to increase in PaO2
o Non-shivering thermogenesis by burning brown fat (thermogenin) to regulate
body temperature
o Passive immunity from mother for 6 months

Pathology
Newborn disorders
- Periods of infancy
o Perinatal = 28th week of gestation – 7th day post-natal
o Neonatal = 1-28 days post-natal
▪ Very early = first 24hrs

▪ Early = first 7 days

▪ Late = 7-28 days

o Infancy = 1st year post-natal
- Infant mortality = mainly due to prematurity, low birth weight & congenital anomalies
o Highest risk during the first 24hrs
- High risk pregnancy = family history, genetics, polyhydramnios, oligohydramnios, etc.
- High risk infants = placental abnormalities, meconium staining, pre/post-term, etc.
- Clinical manifestations = central cyanosis, pallor, hypotension, seizures, lethargy, fever,
jaundice, vomiting, etc.
- Disorders
o Prematurity = < 37 weeks gestational age
▪ Risks factors = chorioamnionitis, maternal diabetes, extremes of age, etc.

▪ Complications = IRDS, apnea, hearing impairment, feeding intolerance,

retinitis, sepsis, PDA, etc.
▪ Management = respiratory support, thermoregulation, diet, weighing
o Perinatal asphyxia = decreased O2 to brain and organs
▪ Can cause hypoxic ischemic encephalopathy -> lethargy, seizures,
hypotonia, stupor, coma
● Management = stabilize cardiopulmonary function by maintaining
temperature (prevent hypothermia by controlled rewarming)
o Neonatal sepsis = bacterial infection
▪ Early onset = premature membrane rupture, GBS vaginal colonization,
chorioamnionitis
 ▪ Late onset = acquired from environment (staph, E. coli, listeria, etc.) ->
prolonged catheter use, contaminated catheters, exposure to resistant
bacteria, prolonged hospitalization
o Neonatal jaundice = physiological, self-limiting, may require phototherapy
Congenital anomalies
- Uterine hypoplasia/agenesis = developmental failure of Mullerian duct
- Unicornate uterus = failure of one of the Mullerian ducts to form
- Didelphys uterus = lack of fusion of Mullerian ducts -> 2x separate uterine horns +
cervices + vaginas (upper 1/3)
- Bicornuate uterus = partial fusion of Mullerian ducts
- Septate uterus = failure of Mullerian septal resorption
- Arcuate uterus = partial Mullerian septal resorption -> indentation into uterus at fundus
o Can carry normal pregnancy
- T-shaped uterus = due to DES (anti-miscarriage drug)
o Can cause vaginal clear cell carcinoma
- Vaginal atresia = failure of vaginal plate canalization
- Imperforate hymen = blood accumulates in FGT after menarche
- Gartner duct cyst = Wolffian duct remnant -> cyst in lateral vaginal wall
- Hydatid of Morgagni = Wolffian duct remnant -> cyst in fimbriae of fallopian tubes
Gynecological infections
- Vaginitis = inflammation of vagina
o Gardnerella vaginalis = fishy grayish discharge, occurs at pH > 4.5 pH, clue cells
▪ Complications = preterm births, increased risk of infection (STIs)
o Candidiasis = itching, white curd like discharge, dyspareunia, pain on urination,
occurs at normal pH (4-4.5), pseudo hyphae
▪ Risk factors = obesity, immunosuppression, diabetes, antibiotics
o Trichomoniasis = green-yellow foul smelling discharge, pruritis and pain, occurs
at pH > 4.5 pH, dyspareunia, strawberry cervix, pear-shaped flagellated parasites
▪ Risk factors = multiple sexual partners (STI), no protection

▪ Complications = vertical transmission, infertility, acute PID

o Atrophic = post-menopausal -> dryness, dyspareunia, etc.
- HSV1/2 = infects lower FGT -> vesicular painful red ulcers, tender inguinal lymphedema,
painful urination, self-limiting, dormant in sacral ganglia -> reactivated by stress
o Diagnosis = tzank smear -> giant multinucleated cells + Cowdry A bodies
- Molluscum contagiosum = on trunk/legs/arms in children, genitals/lower abdomen in
adults -> pearly umbilicated papules
o Diagnosis = Molluscum bodies (intracytoplasmic)
- PID = upper FGT infection caused by N. Gonorrhea or chlamydia -> abdominal pain,
cervical motion tenderness -> can cause infertility/ectopic pregnancy (fallopian tube
scarring), intestinal obstruction (adhesions)
Vulvar diseases
- Bartholin cysts = at 4 & 8 o’clock -> can be due to infection or duct obstruction -> drain
- Inflammatory dermatoses = dermatitis (type 4 HSR), psoriasis, lichen planus
- Lichen sclerosis & atriphicus = atrophy + hyperkeratosis in elderly -> white areas
- Lichen simplex chronicus = due to rubbing/scratching -> squamous hyperplasia,
hyperkeratosis, acanthosis, etc.
- Condyloma accuminata = leukoplakic verrucous lesions due to HPV 16/18, can be warty
(cauliflower) or coalescing (Bowenoid) -> diagnosed by koliocytes
- VIN/vulvar squamous ca
o Basaloid/warty type = classic VIN -> preceded by HPV 16/18 in reproductive age
women -> nuclear atypia, mitotic bodies, severe dysplasia
o Keratinizing type = differentiated VIN -> preceded by lichen sclerosis/squamous
hyperplasia in elderly women
o Invasive SCC -> can invade inguinal and paraaortic nodes -> lungs
- Accessory breast tissue = extension of milk lines, expands during pregnancy
- Papillary hidradenoma = benign circumscribed apocrine tumor
- Extramammary Paget disease = pruritic red crusty area on labia majora in elderly
women, Paget cells (clear cells infiltrating epidermis) -> cytokeratin/PAS positive
- Malignant melanoma = pigmented lesion on vulva -> cytokeratin/PAS negative
Vaginal diseases
- Vaginal adenosis = persistence of glandular tissue in vagina due to taking DES -> red area
within white squamous mucosa -> can cause clear cell carcinoma (teenagers)
- Vaginal intraepithelial neoplasia = usually due to HPV 16
- Embryonal rhabdomyosarcoma = sarcoma botryoides -> rhabdomyoblasts
(cross-striations) in children < 5 years
Cervical diseases
- Chronic cervicitis = inflammation of cervix due to chlamydia (follicular lymphocytic
infiltrate), gonococcus (creamy purulent discharge), HSV (vesicular), etc.
- Nabothian cysts = mucus filled cysts due to blocked glands
- Endocervical polyp = may cause spotting
- Microglandular hyperplasia = polypoid lesion of mucin glands -> progesterone OCP
- CIN = infection of basal cells by HPV 16/18 of squamocolumnar junction -> koilocytosis
o HPV produces E6 (p53 degradation) and E7 (Rb degradation -> high p16)
o Risk factors = early sex, multiple partners, immunosuppression
o Can progress to cervical cancer -> post-coital bleeding, ulcerations, keratin pearls
Uterine disease
- Dysfunctional uterine bleeding = bleeding with no uterine lesion
o Anovulatory cycle -> prolonged estrogen exposure -> unsustainable endometrial
proliferation -> stromal breakdown and hemorrhage
o Luteal phase defect -> irregular ripening (low progesterone due to early corpus
luteum degeneration) or irregular shedding (persistence of corpus luteum)
- Endometritis = inflammation of endometrium
 o Acute = bacterial infection post-delivery (GBS, staph, strep, etc.), retained
gestational tissue
o Chronic = due to PID, retained gestational tissue, IUD (actinomyces sulfur
granules), TB (granulomas), etc. -> plasma cell infiltrate
- Endometriosis = endometrial tissue outside of uterus -> infertility (tubal scarring),
anovulation, dysmenorrhea (estrogen producing tissue), dyspareunia, pain, constipation,
chocolate cysts (ovary), powder burns (bowel), etc.
o Adenomyosis = endometrial tissue in myometrium -> uniformly enlarged uterus,
menorrhagia
- Endometrial polyp = women >40 years, endometrial hyperplasia in the fundus due to
tamoxifen
- Endometrial hyperplasia = due to prolonged estrogen exposure (anovulation, obesity,
PCOS, granulosa tumor, estrogen replacement) -> increased gland to stroma ratio
o Non-atypical/simple = resembles proliferative endometrium (tubular glands)
o Atypical/complex = irregular tortuous crowded glands, nuclear atypia -> high
cancer risk (PTEN mutated)
- Endometrial adenocarcinoma = presents as postmenopausal bleeding
o Type I (endometroid) = estrogen related + PTEN mutation (Cowdens) + mismatch
repair mutation (Lynch) -> in 55-65 year old obese women with
diabetes/hypertension
o Type II (serous) = p53 mutation -> in 65-75 year old women, lymphatic spread
- Malignant mixed Mullerian tumor = malignant adenocarcinoma AND sarcoma -> due to
pelvic irradiation
- Endometrial stromal neoplasms
o Adenosarcoma = malignant stroma + benign glands
o Stromal nodule = benign
o Stromal sarcoma = spindle cells, invades myometrium and spreads via lymphatics
- Myometrial neoplasms
o Leiomyoma = multiple benign monoclonal fibroids in reproductive age women ->
bleeding (iron deficiency), infertility, pain, urinary retention/frequency,
constipation -> estrogen sensitive
o Leiomyosarcoma = necrotic/hemorrhagic tumor in women 40-60 years -> atypia,
spindle cells, mitotic bodies
Fallopian tube diseases
- Salpingitis = tubal inflammation -> usually due to PID -> adhesions, infertility, ectopic
pregnancy, hydrosalpinx
- Adenomatoid tumor = benign, usually asymptomatic
- Adenocarcinoma = BRCA1/2 + p53 mutation -> usually papillary serous carcinoma
Ovarian diseases
- Follicular cyst = no LH surge -> follicle doesn’t rupture -> benign and resorbed
- Corpus luteum cyst = failure/delayed degeneration -> continued progesterone secretion
-> increased body temp + enlarged ovaries
- Theca lutein cyst = due to elevated hCG (choriocarcinoma, hydatidiform mole)
- Ovarian torsion = sudden unilateral pain in younger women
- Polycystic ovarian syndrome = hypersecretion of LH (LH:FSH >2) in obese women of
reproductive age -> hirsutism (excess androgens), dysmenorrhea, pelvic pain,
anovulation, enlarged ovaries, multiple cysts under the surface of both ovaries, insulin
resistance -> increased risk of endometrial hyperplasia/cancer
- Stromal hyperthecosis = luteinized thecal cells in postmenopausal women -> bilateral
uniform enlargement of ovaries, virilization
- Ovarian cancer = due to prolonged estrogen exposure (anovulation, obesity, PCOS, early
menarche, late menopause, etc.) + family history + BRCA1/2 + Lynch -> present late with
abdominal pain, ascites, GU/GI symptoms, vaginal bleeding, CA-125 maker
o Surface epithelial tumors
▪ Serous tumors = cystadenoma, borderline or adenocarcinoma ->
BRCA1/2, KRAS, mutations -> bilateral solitary tumors lined by single layer
of columnar cells, psammoma bodies (adenocarcinoma) -> spreads to
peritoneum
▪ Mucinous tumors = cystadenoma, adenocarcinoma -> KRAS mutation ->
unilateral multiloculated tumors filled with mucus ->
▪ Endometroid tumors = due to endometriosis -> PTEN/RAS mutations
o Sex cord tumors
▪ Granulosa tumor = postmenopausal women with FOXL2 mutation -> solid
yellow tumor that produces estrogen, Call-Exner bodies, coffee bean
nucleus
▪ Fibroma = white unilateral tumor made of fibroblasts in menopausal
women
● Meigs syndrome = fibroma + right hydrothorax + ascites
● Gorlin syndrome = fibroma + basal cell carcinoma +
medulloblastoma + PTCH mutation
▪ Thecoma = unilateral luteinized thecal yellow tumor secreting estrogen
● Fibrothecoma = mixture of fibroma and thecoma -> produces
estrogen -> differentiate with granulosa tumors via reticulin stain
▪ Sertoli-Leydig tumor = DICER1 mutation -> secretes androgens ->
virilization, hirsutism
▪ Hilus/Leydig cell tumor = secretes androgens -> virilization, crystalloids of
Reinke
o Germ cell tumors – occurs in < 25 years
▪ Teratoma = filled with hair, teeth, etc.
 ● Struma ovarii = monodermal teratoma producing T4 ->
hyperthyroidism
▪ Dysgerminoma = unilateral, radiosensitive, fried-egg appearance

▪ Yolk sac tumor = produces a-fetoprotein/a1-antitrypsin -> Schiller-Duval

bodies (glomerulus like)
o Metastatic carcinoma
▪ Pseudomyxoma peritonei/krukenburg tumor = metastases from
appendix or stomach -> bilateral involvement of ovaries, mucinous ascites
Diseases of pregnancy
- Ectopic pregnancy = bleeding and pain 2 months after last menstrual period
o Tubal pregnancy = usually due to PID -> hematosalpinx, rupture, etc.
o Ovarian pregnancy = due to failure of ovum to rupture
o Abdominal pregnancy = failure of ovum to enter fimbriae
o Diagnosis = pregnancy test -> serum hCG -> transvaginal ultrasound -> serum
progesterone -> laparoscopy
- Spontaneous abortion = loss of pregnancy before 20 weeks -> due to chromosomal
anomalies, defects in uterus, infection, endocrine dysfunction, vascular disorders
- Placental abnormalities = twin placentation, twin-twin transfusion syndrome
(monochorionic placenta), accessory lobe, bilobed, knotted (fatal), nuchal/prolapsed
cord (fetal asphyxiation)
- Implantation abnormalities
o Placenta previa = low lying, partially or fully covering the os -> painless
intrapartum bleeding
o Placenta accreta = attached to myometrium in areas of scarring -> postpartum
bleeding, uterine rupture
o Abruptio placenta = premature separation -> retroplacental hemorrhage ->
painful bleeding
- Chorioamnionitis = ascending infection (GBS, E. Coli, etc.) -> neutrophilic infiltrate
- Chronic villitis = transplacental infection (ToRCHeS)
- Preeclampsia = failure of trophoblasts to invade spiral arteries -> placental ischemia ->
reduced NO release -> hypertension + proteinuria/end organ dysfunction after 20 weeks
o Can cause HELLP syndrome, DIC, kidney damage
▪ Decrease in PGI2 leads to DIC
o Eclampsia = preeclampsia + seizures/hyperreflexia
- Hydatidiform mole = occurs in teenagers and postmenopausal women -> hCG secretion
-> enlarged uterus, theca lutein cysts, vaginal bleeding, thyrotoxicosis, hyperemesis,
snowstorm ultrasound, miscarriage -> can invade myometrium & cause uterine rupture
o Complete = empty ovum fertilized by 2 sperm (diploid) -> no fetus, grape like
clusters, swollen villi -> can cause choriocarcinoma
o Incomplete = ovum fertilized by 2 sperm (triploid) -> fetus, normal and swollen
villi, p57 positive
 - Choriocarcinoma = neoplastic trophoblasts -> marked increased in hCG -> bloody brown
spotting -> metastases to lungs
- Placental site trophoblast tumor = trophoblast invade myometrium -> increase hCG/HPL
- Gestational hyperthyroidism = transient thyrotoxicosis in beginning of 2nd trimester due
excessive stimulation of thyroid by hCG -> increased risk of preeclampsia and CHF
o Treated with propylthiouracil in 1st trimester then methimazole onwards
- Caesarian delivery = required in abnormal placentation, uterine scar, deformities,
previous C-section, congenital anomalies, abnormal umbilical cord, failed vaginal
delivery
Breast diseases
- Supernumerary nipple = remnant of milk line
- Accessory breast tissue = breast tissue extending into axilla
- Congenital nipple inversion = failure of eversion during development -> if acquired, can
be sign of carcinoma
- Acute mastitis = staph/strep infection during breastfeeding -> pain, erythema, fever,
neutrophilic infiltrate
- Periductal mastitis = vitA deficiency (smokers) -> squamous metaplasia -> keratin plug ->
subareolar abscess
- Duct ectasia = thick white discharge in multiparous postmenopausal women -> ducts can
rupture and cause granulomatous inflammation and fibrosis
- Fat necrosis = trauma/surgery -> liquefactive necrosis of adipocytes -> oil cysts,
granulomas, calcification
- Lymphocytic mastopathy = autoimmune disorder, common in DM I and Hashimoto
patients -> lymphocytic infiltrate
- Granulomatous mastitis = seen in Wegner granulomatosis, sarcoidosis, TB, fungal
infection, ruptured implant
- Non-proliferative breast changes = lumpy-bumpy breast in 20-50 year old -> cysts,
apocrine metaplasia, fibrosis, adenosis
- Proliferative breast changes without atypia = epithelial hyperplasia (both luminal and
myoepithelial proliferation), sclerosing adenosis (stromal fibrosis + acini hyperplasia +
microcalcifications), intraductal papilloma (bloody nipple discharge), sclerosing lesion
(radial scar)
- Proliferative breast changes with atypia = atypical ductal hyperplasia (calcification) and
atypical lobar hyperplasia (acinar cells) -> regularly spaced
- Fibroadenoma = freely moveable solitary encapsulated benign tumor in women <30
years -> intracanalicular fibroadenoma compresses ducts
- Phyllodes tumor = leaf-like tumor in women between 40-50 years
- Breast cancer = risk factors -> postmenopausal, early menarche/late menopause,
nulliparity or late first birth, family history, obesity, history of previous breast cancer,
BRCA1/2 + tp53 + CHECK2 + HER2 -> metastases to axillary lymph nodes then lungs ->
worse prognosis when cancer cells are found in circulation/bone marrow or if cancer is
estrogen/progesterone receptor negative or p53/HER2 mutations
o Ductal carcinoma in situ = microcalcifications -> comedocarcinoma (cheesy
necrotic material), micropapillary (no fibrous core)
 ▪ Paget’s diseases = DCIS extension into nipple/areola -> crusted red lesion
with underlying mass, Paget cells (PAS+)
o Lobular carcinoma in situ = bilateral, loss of E-cadherin, cells filling and
expanding the acini
o Invasive ductal carcinoma = palpable mass, fixed, dimpling, retracted nipple, firm
gritty tumor, lymph node metastases
o Invasive lobular carcinoma = bilateral, loss of E-cardherin, Indian file
arrangement of cells
o Tubular carcinoma = glands without myoepithelial cells
o Medullary carcinoma = soft fleshy tumor, lymphocyte infiltrate, BRCA1 mutation
o Colloid mucinous tumor = soft circumscribed mass filled with mucus in elderly
women
o Inflammatory carcinoma = dermal lymphatics filled with malignant cells -> blocks
drainage -> peau d’orange
- Male breast
o Gynecomastia = enlargement of breast -> steroids, Leydig cell tumor, Kleinfelder
syndrome
o Invasive duct carcinoma = seen in elderly with Klinefelter of BRCA2
Repro
Anatomy
- Penis = corpus spongiosum, 2x corpus cavernosum, tunica albuginea, Bucks fascia,
foreskin, frenulum
o Supplied by internal pudendal artery
o Drained by deep dorsal veins -> prostatic venous plexus -> vertebral plexus
- Testes = tunica vaginalis/albuginea/vasculosa ->
o Epididymis -> ductus deferens + seminal vesicles -> ejaculatory ducts -> prostatic
urethra
o Supplied by testicular arteries (aorta)
o Drained by testicular veins (right to IVC, left to left renal vein)
- Prostate = transitional zone (BPH), peripheral zone (cancer), central zone (ejaculatory
ducts), corpora amylacea, papillary infoldings
- Lymphatic drainage
o Superficial structures = penis, scrotum, anus -> superficial inguinal nodes
o Deep structures = prostate, vas deferens, seminal vesicles, bladder -> internal
iliac nodes
o Testes -> para-aortic nodes
- Nerve supply
o Superficial structures by internal pudendal nerve (S2-4)
o Deep structures by PANS pelvic splanchnic (S2-4)
Physiology
- TDF/SRY -> determines male sex -> differentiation into Sertoli and Leydig cells
- Hormones
o LH -> Leydig cells -> testosterone (StAR enzyme + cholesterol)
o FSH -> Sertoli cells -> AMH + inhibin -> degenerate Mullerian ducts, nurse
spermatogonia
▪ Inhibin used to determine spermatogenesis and male infertility
o Testosterone = development of fetal male characteristics, puberty, bone/muscle
growth, spermatogenesis (stimulates Sertoli cells), growth of larynx (voice
deepening), pubic/facial hair, libido
▪ DHT (5a-reductase) = differentiation of penis/scrotum/prostate, male
pattern baldness, growth of prostate
- Spermatogenesis = primordial germ cells migrate to testes in utero -> puberty (increase
in testosterone) -> type A spermatogonia divide by mitosis to form more type A
spermatogonia and type B spermatogonia in seminiferous tubules -> type B
spermatogonia differentiate to 1st spermatocytes which undergo meiosis I to form 2nd
spermatocytes -> 2nd spermatocytes undergo meiosis II to form spermatids (haploid) ->
maturation into spermatozoa
o Blood testes barrier = tight junctions between Sertoli cells maintains
environment for spermatogenesis -> disruption leads to sterility (Abs against
sperm)
 o Spermatozoa = head (DNA + hyaluronidase), midpiece (mitochondria), tail
(microtubules)
- Sexual act
o Erection = PANS -> cGMP -> NO -> relaxation
o Emission/ejaculation = SANS -> contraction of vas deferens, seminal vesicles,
prostate + rhythmic contractions
▪ Seminal fluid = 10% testes (sperm, acidic) + 30% prostate (clotting
factors, alkaline) + 60% seminal vesicles (seminal fluid, fructose,
fibrinogen, acidic) -> vasectomy removes testes contribution
- Capacitation = uterine/tubal fluids increase sperm activity (Ca influx) -> movement
towards ampulla -> acrosome reaction -> penetration of corona radiata/zona pellucida
-> fertilization
- Fertility management
o Definitions
▪ Fecundability = probability to conceive in one cycle

▪ Fecundity = probability of live birth in one cycle

▪ Infertility = failure to conceive within 12 months of regular unprotected

sex -> primary (never had kids) or secondary (had at least one kid before)
● Within 6 months for women >35 years
▪ Sterility = intrinsic inability to attain pregnancy
o Fertility awareness method of contraception
▪ Calendar method = fertile period is calculated by subtracting 18 days
from shortest menstrual cycle and subtracting 11 days from the longest
menstrual cycle over at least 6 months of tracking
▪ Basal body temperature method = body temp rises 0.5oF-1oF during
ovulation -> no intercourse from end of menstruation till 3 days after rise
in temp
▪ Cervical mucus method = fertile period between first sign of mucus until 4
days after the peak day (last day of wetness)
o Tubal ligation Pomeroy = elevation of tubal segment -> suture tied -> loop
excised with a 1-2cm gap remaining
Pathology
Penile disorders
- Penile agenesis = developmental failure of genital tubercle -> aphalia + undescended
testes + normal scrotum
- Chordee = upward/downward curvature of the penis, resistant to straightening
o Peyronie’s disease = curvature due to injury
- Hypospadias = urethral opening on ventral surface of penis -> associated with chordee
 - Epispadias = urethral opening on dorsal surface of penis
- Phimosis = cannot retract prepuce -> risk of penile carcinoma
o Paraphimosis = phimotic prepuce forcible retracted -> constriction/edema of
glans -> gangrene
- Balanoposthitis = infection of glans/prepuce
- Penile fracture = break in tunica albuginea related to sexual activity
- Bowens disease = solitary white patch on shaft or scrotum, >35 years, HPV infection
(koilocytosis), risk of cancer
o Erythroplasia of Queyret = type of Bowens -> red velvety patch on glans
- Bowenoid papulosis = multiple plaques in sexually active adults -> no risk of cancer
- Squamous cell carcinoma = can be papillary/cauliflower or flat/thick/ulcerated
o Predisposing factors = Bowens/Erythroplasia of Queyret, HPV 16/18 (condyloma
acuminata), lack of circumcision
Testicular disorders
- Cryptorchidism = undescended testes -> failure of AMH -> risk of seminoma and
infertility (dilated seminiferous tubules, thick basement membrane) -> orchiopexy repair
- Testicular atrophy = seen in alcoholism, hypopituitarism, atherosclerosis, chemo,
mumps, cryptorchidism, Klinefelter’s (47, XXY)
- Orchitis = <35 years (chlamydia, gonococcus) >35years (E. Coli, pseudomonas) -> sudden
pain/swelling, normal cremasteric reflex
o Granulomatous orchitis = painless mass occurring in middle age
- Epididymitis = <35 years (chlamydia, gonococcus) >35years (E. Coli, pseudomonas) ->
gradual pain/swelling, relief on testicular elevation (Prehn test)
- Testicular torsion = blocked venous drainage -> hemorrhagic infarct -> sudden onset of
pain/swelling, nausea, abnormal cremasteric reflex, pain on testicular elevation
- Hydrocele = accumulation of fluid in tunica vaginalis -> diagnosed via transillumination
o Chylocele = elephantiasis = due to nematodes (W. bancrofti, B. malayi, B. timori)
- Varicocele = increased pressure in left testicular vein that drains into left renal vein
(renal cancer) -> bag of worms, can cause infertility due the increased heat
- Germ cell tumors = PLAP+, painless -> metastasis to lungs
o Choriocarcinoma = hCG secreting hemorrhagic small nodular tumor -> lethal
o Teratoma = seen in infants/children -> tumor from multiple germ cell layers
(teeth, skin, glands, etc.)
o Yolk sac tumors = seen in infants/children -> a-fetoprotein yellow tumors,
Schiller-Duval bodies (glomerular like)
o Embryonal carcinoma = seen in ages 20-30 -> hCG + a-fetoprotein secreting
hemorrhagic tumors
o Seminoma = seen in ages 30-50 with cryptorchidism -> radiosensitive,
homogenous mass, fried-egg appearance
- Sex cord tumors
o Leydig cell tumors = seen in ages 20-60 -> excess estrogen (gynecomastia), excess
androgens (precocious puberty), crystalloids of Reinke
o Sertoli-Leydig tumors = small nodules, hormonally silent
 - Testicular lymphoma = seen in men over 60 years -> monotonous lymphocytic infiltrate
Prostatic disorders
- Prostatitis = painful inflammation of prostate, leukocytic secretions
o Acute = associated with UTIs (E. coli) -> fever, chills, dysuria
o Chronic = abacterial or ureaplasm/chlamydia -> low back pain, dysuria, etc. ->
prostatic discharge with lymphocytes
- BPH = firm/rubbery multiple non-tender nodules in transitional zone (periurethral) ->
stomal and glandular hyperplasia due to DHT (worsens with age) with 2 layers of cells ->
urinary hesitancy, incomplete emptying, increased frequency, nocturia, poor stream
o Complications = bladder infections, bladder hypertrophy, bilateral
hydronephrosis, kidney stones, hematuria, bladder atony
o Diagnosis = urine culture and analysis are mandatory, PSA recommended
o Treatment = a1 blockers (tamsulosin), 5a-reductase inhibitors (finasteride)

(BPH) (adenocarcinoma)
- Prostatic adenocarcinoma = fixed hard nodules in peripheral zone occurring in older age
-> altered CYP450 C17/5a-reductase type II genes -> crowded back to back glands with a
single layer of cells, PSA/acid phosphatase+ -> dysuria, hematuria, etc.
o Complications = lymphatic and hematogenous (to bone) spread
Sexually transmitted diseases
- Syphilis = 1o painless chancre -> 2o palmar rash + condyloma latum -> 3o neurosyphilis
(tabes dorsalis) + aortitis (tree barking) + gummas (plasma cell granulomas)
- H. ducreyi = painful chancroid -> school of fish/train track appearance on gram stain
- Gonococcus = creamy purulent discharge -> can cause PID/infertility/ectopic pregnancy
-> dissemination in MAC deficiency -> can cause neonatal conjunctivitis and blindness
- Chlamydia = obligate intracellular bacteria -> follicular inflammation
o L1-3 -> painless papule that progresses to painful inguinal lymphadenopathy
o A-C -> causes Reiters syndrome (conjunctivitis + urethritis + reactive arthritis),
especially in HLA-B27 patients
o D-K -> causes urethritis/cervicitis (also caused by ureaplasma and mycoplasma)
- Klebsiella = causes granuloma inguinale -> painless papular lesion that ulcerates +
lymphadenopathy (elephantitis) -> Donovan bodies on gram stain (coccobacilli in
macrophages)

Pharmacology
Estrogens, progestins & infertility drugs
- Estrogens = estrone (natural), mestranol (synthetic), diethylstilboestrol (nonsteroidal)
o Therapeutic uses = primary female hypogonadism, osteoporosis (blocks
osteoclastic activity), menstrual abnormalities, prostatic tumors (androgen
dependent), hirsutism, intractable dysmenorrhea, PCOS, acne
▪ Menopausal hormone therapy -> improve lipid profile, decrease hot
flashes, decreased risk of CVD
● Paroxetine (SSRI) can be used for hot flashes
o ADR = increased risk of endometrial hyperplasia/cancer, breast cancer,
thromboembolism, nausea, high BP, MI, migraine, edema, post-menopausal
bleeding, clear cell carcinoma (DES)
▪ Concomitant progestin increases breast cancer risk and decreases
endometrial cancer risk
- Progestins = norethindrone (androgenic), megestrol, drosiprenone (less androgenic)
o Therapeutic uses = contraception, menopausal hormone therapy (with estrogen),
endometrial hyperplasia/cancer (blocks estrogen), stimulate appetite, prevent
recurrent miscarriages
o ADR = poor lipid profile, headache, depression, osteoporosis/hirsutism (estrogen
block), weight gain, decreased libido, acne
- Clomiphene = estrogen partial agonist -> decreases negative feedback on hypothalamus
& pituitary -> increased ovulation
o Therapeutic uses = fertility pill for men and women (also PCOS)
o ADR = hot flashes, nausea, visual disturbances, multiparity, ovarian
hyperstimulation syndrome
- Fulvestrant = estrogen antagonist
o Therapeutic uses = tamoxifen/aromatase inhibitor resistant breast cancer (with
endometrial risk)
o ADR = hot flashes, GI symptoms, headache, back pain
- SERM = Tamoxifen, raloxifene
o Therapeutic uses = breast cancer, decrease LDL, osteoporosis
o ADR = increased risk of endometrial hyperplasia/cancer (tamoxifen),
thrombus/DVT (raloxifene), decreased efficacy with CYP3A4 (amiodarone,
verapamil, cyclosporine) and CYP2D6 (fluoxetine) inhibitors, hot flashes, nausea,
cataract, bone pain, hypercalcemia
- Trastuzumab = HER2 receptor monoclonal Ab -> HER2+ breast cancer
- Aromatase inhibitors = anastrozole, testolactone, exemestane
o Therapeutic uses = estrogen dependent breast cancer, endometriosis, precocious
puberty
o ADR = hot flashes, nausea, fatigue, acne, osteoporosis
- GnRH analog = gonadorelin, leuprolide
o Therapeutic uses
 ▪ Sustained release -> decreases FSH/LF release -> preoperative treatment
before leiomyoma resection, prostate cancer (initial flare up then DHT
depletion), endometriosis, precocious puberty, breast cancer,
▪ Pulsatile release -> increases FSH/LH release -> male/female infertility
o ADR = headache, ovarian cysts, osteoporosis, depression, decreased libido,
menopausal symptoms/gynecomastia (continuous use)
- GnRH receptor antagonist = ganirelix -> decrease FSH/LH release
o Therapeutic uses = controlled ovarian stimulation in fertility treatments,
advanced prostate cancer
o ADR = weight gain, hot flushes, nausea, headache
- Gonadotropin analogs = recombinant LH/FSH
o Therapeutic uses = induce ovulation/controlled ovarian stimulation in fertility
treatments, cryptorchidism, male infertility
o ADR = ovarian hyperstimulation syndrome, multiparity, gynecomastia, headache,
depression
- Bromocriptine = D1 agonist -> prolactinoma
Contraceptives
- Combined pills = estrogen + progesterone -> suppresses ovulation + decrease sperm/ova
transport
o Therapeutic uses = contraception, reduced risk of endometrial/ovarian cancer,
decreased premenstrual symptoms
o Mild ADR = nausea, headache, increased appetite, weight gain, decreased libido,
increased temperature
o Moderate ADR = vertigo, cramps, insulin resistance, hirsutism, amennorhea
o Severe ADR = thrombus, hepatic adenoma, jaundice, cervical/breast cancer
o Interactions = Decreased effectiveness with enzyme inducers or antibiotics
- Mini pills = progesterone only -> decreased GnRH/LH -> suppresses ovulation + thickens
cervical mucus -> useful in comorbid situations (smokers, HTN, hepatic disease, etc.)
- Injectable contraceptives = progesterone -> reduces menstrual blood loss + decreased
risk of endometrial cancer -> can cause irregular bleeding, anovulation, osteoporosis,
weight gain, breast cancer
- Emergency contraceptive pills = progestin OR estrogen + progestin (Yupze method) ->
used within 72hrs -> inhibit ovulation + decreased receptivity of tubes/endometrium +
altered cervical mucus -> can cause vomiting
o Ulipristal = progesterone receptor modulator -> can be used within 120hrs
- Mifepristone = progesterone/glucocorticoid receptor antagonist -> deprives uterus of
progesterone + luteolytic effect -> medically induced abortifacient within 49 days
o Given with misoprostol (PGE1) -> uterine contractions + cervical ripening -> also
used to treat stomach ulcers
▪ Dinoprostone (PGE2) can also be used
o ADR = uterine bleeding, incomplete abortion, cramps, septic shock
 - Methotrexate = terminate ectopic pregnancy within 6 weeks
Androgens, anabolic steroids and drugs for erectile dysfunction
- Androgens = testosterone, 17a-alkylated androgens (oxandrolone, danazol, etc.)
o Therapeutic uses = hypogonadism, testosterone deficiency, anemia (stimulates
erythropoietin), anabolic effects in osteoporosis/burns/AIDS, menopausal
symptoms, increase muscle mass (anabolic steroids)
▪ Danazol -> C1-esterase inhibitor -> androgenic and antiestrogenic -> used
for endometriosis, hereditary angioneurotic edema, fibrocystic breast
o ADR = hirsutism/dysmenorrhea in women, precocious puberty/short stature in
kids, priapism/impotence/gynecomastia/prostate hyperplasia in men,
aggressiveness, dyslipidemia, edema, hepatic dysfunction
▪ Not give to patients who are pregnant or have prostate/bleeding disorder
- Ketoconazole = inhibits steroid synthesis -> increases estradiol : testosterone ratio ->
used in precocious puberty/hirsutism in PCOS -> can cause gynecomastia
- 5a-reducates inhibitors = finasteride, abiraterone
o Therapeutic uses = BPH, baldness, hirsutism
o ADR = decreased libido, erectile dysfunction, gynecomastia
- Androgen receptor inhibitors = flutamide, enzalutamide
o Therapeutic uses = metastatic prostate cancer (+ GnRH analog)
o ADR = gynecomastia, diarrhea, hepatotoxicity, chest pain
- Cyproterone = antiandrogen -> used for hirsutism, excessive male sex drive
- Spironolactone = competes with DHT at androgen receptors -> used for hirsutism -> can
cause gynecomastia, dysmenorrhea, hyperkalemia
- PDE5 inhibitors = sildenafil, tadalafil -> increase cGMP -> smooth muscle relaxation
o Therapeutic uses = erectile dysfunction
o ADR = hypotension with nitrates, headache, flushing, disturbed color vision

GIT
Anatomy
- Foregut = esophagus till 2nd part of duodenum -> supplied by celiac artery, greater
splanchnic nerve (SANS T5-T9), Vagus nerve (PANS)
o Esophagus = cervical/thoracic/abdominal constrictions, lower part drained by left
gastric (varices in portal hypertension)
▪ Portal vein formed by splenic and superior mesenteric veins
● Portocaval shunts = left gastric + esophageal veins (drains to
azygos), superior + inferior rectal veins (drains to internal iliac),
paraumbilical veins (drains to femoral/axillary veins)
o Stomach = fundus, body, pylorus, angula incisura, greater/lesser omentum
▪ Foramen of Winslow = opens into lesser sac -> hepatoduodenal ligament
anteriorly, IVS posteriorly, caudate lobe superiorly, duodenum inferiorly
 o Small intestine = duodenum (intraperitoneal bulb, pancreatic ducts), jejunum
(ligament of Trietz), ileum (ileocecal valve)
- Midgut = 3rd part of duodenum till proximal 2/3 transverse colon -> supplied by SMA,
lesser splanchnic nerve (SANS T10-T11), Vagus (PANS)
o Large intestine = retroperitoneal ascending/descending colon, intraperitoneal
appendix
- Hindgut = distal 1/3 transverse colon till rectum -> supplied by IMA, lumbar splanchnic
nerve (SANS L1-L3), pelvic splanchnic nerve (PANS S2-S4)
o Pectinate line
▪ Above supplied by IMA (superior rectal artery), drains into portal system,
internal smooth muscle anal sphincter (ANS innervation), lymph to
internal iliac nodes
▪ Below supplied by internal iliac (middle/inferior rectal arteries), drains
into caval system, external skeletal muscle anal sphincter (somatic
innervation), lymph to superficial inguinal nodes
- Pelvis
o Pelvic diaphragm = levator ani [puborectalis + pubococcygeus + iliococcygeus] +
coccygeus
o Somatic innervation supplied by pudendal nerve (Alcock’s canal) that branches
into inferior rectal and perineal nerve
o Autonomic innervation by inferior hypogastric plexus = PANS pelvic splanchnic
(S2-S4) + SANS sacral splanchnic (T12-L2) -> all smooth muscle and glands
Physiology
- Functions = movement, secretion, digestion (duodenum), absorption (jejunum),
circulation into blood
o Segmentation = mixing of chyme with digestive juices in duodenum
o Peristalsis = movement of chyme through the GI tract
- Functional anatomy
o Epithelial cells = secretion/absorption
o Muscularis mucosa = surface area change to enhance secretion/absorption
▪ Villi prone to damage due to countercurrent blood flow
o Sphincters = controlled movement of food
o Circular/longitudinal muscle = decrease diameter/length of segment -> smooth
muscle cells act as a functional syncytium due to gap junctions
▪ Interstitial cells of Cajal -> generate slow waves via Ca and K ion channels
-> spike potentials cause contractions -> contraction are proportional to
rate of APs
▪ Stretch, ACh (ENS and PANS) and GI hormones cause depolarization ->
more APs
 ▪ NE (SANS) causes hyperpolarization -> less APs
o Submucosal plexus = enteric nervous system -> integrate/coordinate GI activities
Hormones
- Gastrin = G cells -> gastric acid secretion, increased gastric motility
- CCK = I cells -> gallbladder contraction (bile), pancreatic enzyme secretion, delays gastric
emptying, stimulates PYY, inhibits ghrelin (food intake regulation), pancreatic growth
- Secretin = S cells -> released in response to low pH in duodenum -> bicarbonate
secretion, inhibit gastric acid
- GIP = K cells -> released in response to lipids -> inhibits gastric acid secretion, stimulates
insulin release
- Motilin = motilin cells -> interdigestive GI motility -> also activated by erythromycin
- Ghrelin = GH release, gastric emptying, increases hunger, decreases fat use
o High ghrelin in Prader-Willi syndrome
- PYY/GLP1 = inhibits upper GI motility, histamine/gastric acid release -> ileal brake ->
inhibitory feedback due to undigested nutrients to slow digestion -> optimize nutrient
digestion and absorption
GI innervation
- Extrinsic
o PANS = excitatory -> through Vagus and pelvic splanchnic nerves -> synapse on
the ENS (preganglionic)
o SANS = inhibitory -> synapse on ENS (postganglionic) AND directly on sphincters,
vessels, mucosa -> tonic sphincter constriction
▪ Autoregulatory escape = SANS vasoconstriction compensated due to local
vasodilating metabolites leading to absorptive hyperemia (NO, adenosine,
CO2, etc.)
- Intrinsic = ENS -> local reflexes
o Myenteric/Auerbach plexus = motility of GI smooth muscle -> tonic (sphincters)
AND phasic (peristalsis, segmentation)
o Submucosal/Meissner plexus = secretion, blood flow, infolding to enhance
absorption
- Reflexes
o Local = controlled by ENS
o Prevertebral = GI to sympathetic chain and back -> gastrocolic reflex,
enterogastric reflex, colonoileal reflex
o Long = vagovagal reflexes, defecation reflex
Food propulsion
- Swallowing
o Oral phase = voluntary -> triggers swallowing reflex
o Pharyngeal phase = inhibition of respiration
o Esophageal phase = primary peristalsis AND secondary peristalsis (leftover food
or reflux from stomach into esophagus) -> triggers receptive relaxation
 ▪ Receptive relaxation = relaxation of LES/stomach to accommodate
incoming food after swallowing
▪ Adaptive relaxation = relaxation of stomach in the presence of chyme
● Vagotomy inhibits reflex -> increased gastric tone
▪ Feedback relaxation = relaxation of stomach in response to chyme in
duodenum
- Gastric motility = leading contraction (closure of pyloric orifice) -> trailing contraction
(retropulsion and trituration)
o Increased motility/emptying = PANS, distension of stomach (increased volume),
liquid meal, gastrin (antral pump activity)
o Decreased motility/emptying = distension of duodenum, hypertonic fatty acidic
chyme in duodenum, SANS, CCK, diabetic neuropathy
- Small intestinal motility
o Increased motility = PANS, gastrin, CCK, prostaglandins, serotonin
o Decreased motility = glucagon, secretin
o Migrating motility complex = contractions from stomach to ileum in between
meals -> controlled by ENS and motilin -> clears debris and bile, prevents
bacterial overgrowth -> terminated upon food ingestion
o Peristaltic rush = defense mechanism to rapidly clear undesirable contents
- Large intestinal motility = mixing movements, haustral migration, mass propulsive
movements
- Defecation = movement of fecal material to rectum -> defecation reflex -> relaxation of
external anal sphincter/puborectalis + contraction of abs/diaphragm + relaxation of
internal anal sphincter

GI secretions = for digestion (enzymes) or protection (mucus)

- Saliva = stimulated by PANS AND transiently from SANS mainly from the parotid (serous)
-> initially isotonic (acinar) that is modified in the ducts and secreted hypotonic via
myoepithelial ejection
o Serous = watery, amylase
o Mucous = thick, mucin
- Gastric secretion – high in H/K/Cl, low in Na
o HCl/IF = parietal cells -> activates pepsinogen, increases B12 absorption
▪ Alkaline tide = exchange of bicarbonate into blood for Cl into gastric
secretion -> increase venous blood pH
▪ Stimulated by Vagus, gastrin (also stimulated by Vagus) and histamine
(ECL cells)
▪ Inhibited by low gastric pH, somatostatin and prostaglandins
● NSAIDs inhibit prostaglandins -> ulcers
 o Pepsinogen = chief cells -> breaks down proteins
▪ Stimulated by secretin, Vagus, gastrin, CCK
o Mucus/bicarbonate/trefoil peptides = surface mucous cells -> protects stomach
- Pancreatic secretion – isotonic secretion with higher bicarbonate and lower Cl -> mainly
Na and bicarbonate at high secretion
o Lipase/amylase/protease = active enzymes and zymogens (prevents
autodigestion)
▪ Enterostatin cleaves trypsinogen which in turn activates other proteases

▪ Stimulated by CCK and ACh (PANS, ENS) in response to macronutrients in

duodenum -> vagotomy decreases pancreatic secretions by 60%
o Bicarbonate = neutralizes gastric acid
▪ Stimulated by secretin in response to decrease pH in duodenum
- Bile = liquefaction/alkalinisation of chyme, micelle formation (fat emulsification),
regulation of plasma cholesterol, excretion of heme degradation products ->
concentrated in the gallbladder
o Stimulated by CCK (contraction of gallbladder + relaxation of sphincter of Oddi) in
response to peptides/fats in duodenum as well as secretin and Vagus
o Recirculation = recycled back to liver via Na/bile cotransporter in terminal ileum
▪ Ileal resection -> no recycled bile -> poor fat absorption -> steatorrhea
Digestion of macronutrients – digestion via hydrolysis
- Sites of digestion = luminal (secreted enzymes), membrane (brush border enzymes),
intracellular (cytoplasmic enzymes, lysosomes)
- Carbs = a-amylase breaks a-1,4 glycosidic bonds (pancreatic amylase > salivary amylase)
-> brush border enzymes further break down disaccharides -> monosaccharides
absorbed (primary glucose)
o Glucose/galactose enter enterocytes via SGLT1, fructose via GLUT5 -> leave
enterocytes via GLUT2
- Proteins = gastric acid denatures proteins + activates pepsinogen -> cleavage into smaller
peptides -> single AAs cleaved off of oligopeptides by exopeptidases -> further hydrolysis
by bush border enzymes
o Free AAs enter enterocytes via Na/AA cotransport while oligopeptides enter
quicker via H/peptide cotransport (PEPT1)
▪ Defective AA absorption often asymptomatic due to oligopeptide
absorption via PEPT1
- Lipids = lingual/gastric lipase + decreased gastric emptying via CCK allows for fat
breakdown -> pancreatic enzymes (lipase, cholesterol ester hydrolase, phospholipase
A2) break down lipids + bile emulsifies lipids in micelles -> micelles enter blood via
lymph (thoracic duct) -> absorbed via protein dependent and protein independent
mechanisms
 o SCFA are produced via fermentation -> absorbed in colon -> stimulated colonic
blood flow, fluid/electrolyte absorption
Pathophysiology
Congenital anomalies
- Esophageal atresia = regurgitation/suffocation soon after birth -> associated with
VACTERL syndrome
o Proximal blind ended pouch + distal tracheoesophageal fistula is most common
- Congenital diaphragmatic hernia = defect mainly in posterolateral (Bochdalek) or
parasternal (Morgagni) diaphragm -> pulmonary hypoplasia/hypertension
- Gastroschisis = herniation of abdominal contents without a membranous sac through
abdominal wall
- Omphalocele = herniation of abdominal contents with a membranous sac through
abdominal wall
- Ectopia = gastric tissue (mainly upper 1/3 of esophagus), pancreatic tissue (mainly
stomach)
- Meckel diverticulum = failed involution of vitelline duct (true diverticulum) -> contains
ectopic gastric/pancreatic tissue -> infant with painless red brick stool
- Pyloric stenosis = hypertrophic pyloric sphincter -> non-bilious vomit, epigastric mass ->
use contrast ultrasound
- Duodenal atresia = failure of duodenal recanalization -> bilious vomit, double-bubble
sign, no meconium -> non-contrast ultrasound
- Hirschsprung disease = congenital megacolon due to lack of ganglion cells
o Acquired megacolon = Chagas (true megacolon), neoplasms, toxicity
Esophageal disorders
- Stenosis = can be congenital but more commonly due to inflammation -> use endoscopy
- Mucosal webs = circumferential protrusions -> use endoscopy
o Paterson Brown-Kelly/Plummer-Vinson syndrome = upper mucosal web + iron
deficiency anemia + glossitis + cheilosis
o Schatzki rings = thicker in patients >40 years
- Jackhammer esophagus = nutcracker, lack of coordination
- Diffuse esophageal spasm = uncoordinated contractions -> chest pain (angina like),
corkscrew esophagus
- Achalasia = incomplete LES relaxation + increased LES tone + esophageal aperistalsis due
to loss of inhibitory neurons and ganglionic cells -> dysphagia (more for liquids), chest
pain, birds beak -> manometry, barium meal
- Dysphagia = seen in myasthenia gravis, dermatomyositis, polymyositis, scleroderma
- Hernias = hiatal/sliding (bell shaped, seen in reflux), rolling/paraesophageal (greater
curvature of stomach enters thorax)
- Diverticula = Zenker’s (false, above UES -> halitosis), traction (true, mid-esophageal),
epiphrenic (false, above LES)
- Esophagitis = can be due to alcohol, corrosives, smoking, viruses, fungi -> can cause
peptic stricture
 o Viral = HSV (multinucleated giant cells, small mid-esophageal ulcers) or CMV
(owl’s eye, diarrhea, abdominal pain, immunocompromised, large ulcers) or HIV
(diffuse inflammation and ulceration)
o Fungal = candida -> pseudohyphae, no fever, esophageal stasis
- GERD = decreased LES tone + increased abdominal pressure -> reflux of gastric acid and
bile in patients >40 years -> heart burn, dysphagia, regurgitation, eosinophils,
circumferential inflammation, basal zone hyperplasia -> 24hr pH monitoring
o Treatment = lifestyle modification + antacids + H2 blockers -> PPI -> promotility
drugs -> surgery
o Eosinophilic esophagitis = mutated eotaxin genes -> failure of PPI, no reflux

- Mallory-Weiss syndrome = longitudinal tears at gastroesophageal junction due to

excessive vomiting/retching (bulimia, alcohol) -> can rupture (Booerhave’s syndrome),
associated with hiatal hernia
- Esophageal varices = dilated inferior esophageal veins due to increase portal
hypertension (liver cirrhosis) -> can rupture (fatal)
- Barrett’s esophagus = intestinal metaplasia of any length seen in endoscopy ->
complication of GERD seen in 40-60 years old patients -> risk of adenocarcinoma
- Benign tumors = leiomyoma (most common), fibroma, lipoma
- Squamous cell carcinoma = more common in black males with high alcohol/tobacco
consumption or taking nitrites or have tylosis (TEC mutation) primarily in the upper 2/3
of the esophagus -> dysphagia, sudden weight loss, hoarseness, blood loss
o Also seen with p53, E-cadherin, SOX2, NOTCH1 mutation
- Adenocarcinoma = arises from chronic GERD/Barrett’s esophagus -> sudden weight loss,
dysphagia, hematemesis -> treated with EMR
Upper GI disorders
- Peptic ulcer disease = loss of mucous barrier or over secretion of gastric acid
o H. pylori produce urease -> alkalizes stomach + inhibits somatostatin
o Gastric ulcer = usually on near incisura on the lesser curvature
o Duodenal ulcer = anteriorly will perforate into greater sac, posteriorly will erode
gastroduodenal artery (hemorrhage)
- Zollinger Ellison syndrome = gastrin secreting tumor in pancreas immune to negative
feedback -> increased gastric acid production + decreased pancreatic lipase -> ulcers,
steatorrhea
- Cystic fibrosis = mutated CFTR gene -> defective Cl channels -> thick mucus, organ
damage, malabsorption, steatorrhea
- Lactase deficiency = bloating, gas, diarrhea due to lactose digestion by gut bacteria ->
common in Asians, Natives, blacks, Mediterranean’s
- Gastritis = progressive mucosal damage/atrophy -> gastric ulcer, achlorhydria (no HCl),
pernicious anemia (lack of IF -> no B12 absorption)
GI
Physiology
Intestinal secretion and absorption
- Intestinal secretion
o Bicarbonate = from Brunner’s glands/enterocytes in duodenum/ileum/colon ->
protection against acidity
o NaCl = from enterocytes of crypts throughout small intestine
▪ Cl secretion coupled to Na and water
● CFTR = Cl channel -> defective in cystic fibrosis -> thick clogging
mucus + decreased pancreatic enzymes
- Colonic secretion = mucin + K + bicarbonate -> transport stimulated by aldosterone
o K secretion into colon -> Na/K + Na/K/2Cl pumps K into cells -> passive secretion
via K channels -> stimulated by aldosterone
o Diarrhea causes acidosis/hypokalemia (loss of bicarbonate/K), vomiting causes
alkalosis (loss of HCl)
- Absorption
o Na = enters enterocyte via passive diffusion (colon) + Na/glucose/AA cotransport
+ Na/Cl cotransport + Na/H exchange -> enters blood via Na/K pump
▪ Na channels in colon are stimulated by aldosterone
o Cl = enters enterocyte via passive diffusion + Na/Cl cotransport + Cl/bicarbonate
exchange
o K = enters enterocyte via passive diffusion (small intestine) + K/H exchange
(colon)
o Ca = requires 1-25vitD
o Fe = absorbed in ferrous form (Fe2+) primarily in duodenum/proximal jejunum->
stored as ferritin (liver) or hemosiderin
▪ Deficiency = impaired erythropoiesis + microcytic anemia
o Vitamins = water soluble primarily absorbed in duodenum/jejunum, fat soluble
require micelles
▪ Folate = absorbed in jejunum

▪ B12 = binds IF in small intestine -> absorbed in distal ileum

● Ileal/gastric resection -> B12 deficiency (long lag time due to liver
stores) -> tested via Schilling test
Liver
- Blood flow = receives blood from portal circulation (abdominal organs) + oxygenated
blood from hepatic artery -> all blood returns to heart via hepatic veins and IVC
o High blood flow and low vascular resistance
- Functions
o Blood reservoir -> ability to expand -> provides extra blood in hypovolemia
 o Blood cleansing -> sinuses lined by Kupffer cells (macrophages) clean blood of
pathogens
o Carb metabolism -> glycogen storage + fructose/galactose conversion to glucose
+ gluconeogenesis + forming carb intermediates for synthesis
o Fat metabolism = B-oxidation + fat/cholesterol/lipoprotein synthesis
o Protein metabolism = deamination/transamination + urea formation + plasma
protein synthesis
o Vitamins/minerals = storage of vitamins A/D/B12, iron (ferritin)
o Coagulation factors = synthesis of fibrinogen, prothrombin, factor VII/IX/X, etc.
o Excretion = removal of drugs, hormones, etc. into bile
- Regulation of liver mass = hepatocytes are quiescent but can regenerate after
uncomplicated tissue loss
o Cirrhosis = chronic alcoholism or fat accumulation or infection -> inflammation ->
destruction of parenchymal cells -> hepatosteatosis -> fibrosis (non-reversible)
▪ Non-alcoholic fatty liver disease seen in obesity and type II diabetes
Clinical genetics
- Nucleosome = 8 histones (rich in arginine/lysine) + 146 base pairs
o H1 -> chromosome compaction
o Methylation decreases transcriptions, acetylation increases transcription
▪ Lyonization = X-inactivation -> Xist gene make ssRNA -> methylation of X
chromosome into heterochromatin
● Manifesting heterozygote = female presenting with X-linked
recessive disease due to skewed lyonization
- DNA replication = helicase unwinds DNA -> single strand binding proteins prevent
reannealing -> primases form RNA primer -> DNA polymerase attaches to primer and
replicates DNA -> DNA ligase connects Okazaki fragments -> topoisomerase relieves
supercoils
o Fluoroquinolones inhibits topoisomerase II (DNA gyrase)
- Nucleotide excision repair = endonuclease recognizes and removes pyrimidine dimers
(UV radiation) -> DNA polymerase fills in replacement segment
o Mutated endonuclease -> xeroderma pigmentosa
- DNA mismatch repair = MUT1/2 recognizes mismatch and repairs segment
o Mutation -> Lynch syndrome/HNPCC
- Ribosomes = 30S for initiation, 50S for elongation
- RNA
o rRNA = most abundant, resistant to RNAase
o microRNA = regulation of gene expression
o snRNP = RNA splicing -> splice donor site (5’) and acceptor site (3’)
Pathology
Stomach disorders
- Acute gastritis = mucosal inflammation -> pain worsened by meals, nausea, vomiting ->
associated with NSAIDs, alcohol, bile, stress -> can cause erosion, ulceration,
hematemesis, melena, etc.
o Acute erosive hemorrhagic gastritis -> reddish mucosa, hematemesis -> mainly
due to NSAIDs and alcohol
- Stress related disorders = stress/curling/Cushing ulcers -> decreased blood flow due to
vasoconstriction -> small rounded ulcers
- Chronic gastritis
o H. pylori -> increased gastric acid secretion in antrum (decreased gastrin) ->
neutrophil infiltrate, germinal centers -> can cause ulcers/gastric ca/MALToma
▪ Virulence factors = urease, CagA (cancer risk), VacA (ulcers)

▪ Diagnosis = serology (IgG), urease breath test, stool antigens, biopsy (gold
standard) -> test in gastritis/ulcers -> treat if infected
o Autoimmune = Abs against parietal cells -> decreased pepsinogen/HCl + G cell
hyperplasia (increased gastrin) + B12 deficiency + achlorhydria -> diffuse atrophic
gastritis (fundus, body) + WBC infiltrate + intestinal metaplasia -> can cause
pernicious anemia, adenocarcinoma, carcinoid tumor
▪ B12 deficiency = diarrhea, peripheral neuropathy, Romberg sign,
personality changes
- Uncommon gastritis
o Reactive = foveolar hyperplasia, gastric antral vascular ectasia (watermelon
stomach, eosinophilic round thrombus) -> caused by NSAIDs, reflux, surgery, etc.

o
o Eosinophilic = eosinophil infiltrate in antrum/pylorus -> allergic reaction (IgE)
o Lymphocytic = CD8 T lymphocytic infiltrate in entire stomach
o Granulomatous = seen in Crohn’s, sarcoidosis, TB, fungi, CMV, H. pylori
- Peptic ulcer disease = seen in H. pylori, NSAIDs, smoking, alcohol, stress, etc. -> chronic
punched out ulcer with clean base extending into submucosa due to increased acidity or
 failure of protective mucus + epigastric pain -> can cause bleeding (most common upper
GI bleeding), perforation and obstruction
o Gastric ulcer = usually in lesser curvature near angularis incisura, pain worsened
by meal -> nausea, weight loss
▪ Type I (body of stomach), type II (gastric + duodenal ulcer), type III
(pre-pyloric area), type IV (cardia of stomach)
o Duodenal ulcer = more common, usually in 1st part of duodenum, pain relieved
by meal and worsens after several hours -> weight gain, interrupts sleep
- Gastric outlet obstruction = seen in ulcers (chronic scarring) & malignancy in adults,
pyloric stenosis in children -> diagnosed via barium swallow
- Menetrier disease = foveolar epithelial hyperplasia (large rugae, corkscrew glands) due
to overexpression of TGFa -> epigastric pain, nausea/vomiting, weight loss,
hypoproteinemia -> risk of adenocarcinoma
o Transient in children post infection
- Zollinger-Ellison syndrome = ectopic malignant gastrinoma -> increased gastrin -> G cell
hyperplasia -> multiple peptic ulcers in unusual locations, diarrhea, gastric cobble
stoning -> in patients with recurrent PUD, H. pylori negative, no NSAID usage, MEN I
o Use secretin challenge test -> no decrease in gastrin
- Gastric tumors
o Polyps = nodules due to hyperplasia, inflammation, ectopia, neoplasm
▪ Inflammatory polyps -> chronic gastritis (H. pylori) in patients 50-60 years,
can be malignant
▪ Fundic gland polyps -> females with FAP or using PPIs
o Gastric adenoma = solitary mass in antrum seen in 50-60 years old males with
metaplasia/atrophy/FAP
o Gastric adenocarcinoma = seen in males >50 years usually in antrum/pylorus and
confined to mucosa/submucosa (early -> 90% survival) -> asymptomatic until late
symptoms -> epigastric pain, weight loss, iron deficiency anemia, Krukenburg
tumor (metastasis to ovary), Virchow’s node (supraclavicular), Sister Mary Joseph
nodes (periumbilical) -> resect with a 5cm surgical margin
▪ Intestinal type = in distal stomach of males -> exophytic (cauliflower like),
glandular cells, preceded by dysplasia -> hematogenous spread
▪ Diffuse type = in females -> flat linitis plastica (leather bottle) + signet
ring cells, small cobblestone stomach -> lymphatic spread
▪ Risk factors = mainly H. pylori, also poor diet (smoked foods, excess Na),
Menetrier disease, polyps, atrophic gastritis, anemia, CDH1 mutation
o Gastrointestinal stromal tumor = solitary mesenchymal tumor seen in >60 years
or children -> spindle cells made of interstitial cells of Cajal, C-kit/PDGFA/DOG1
mutations
 o Metastatic tumors = from breast (CK20/CDX2-), lung (CK7+), melanoma
(SB100/HMB45+)
o Gastric lymphoma = at sites of chronic inflammation (H. pylori) + t(11:18) ->
lymphoepithelial lesion
▪ Usually marginal zone B-cell lymphoma -> diffuse large B-cell lymphoma

Small intestine
- Intestinal obstruction = most common in small bowel -> caused by adhesions (adults,
most common), volvulus, intussusception (ileocolic junction in children, rota virus,
currant jelly stool, bullseye pattern on CT) -> increased ticking bowel sounds
(borborygmus), bilious vomiting, colicky pain, step-ladder appearance (x-ray), distension
o Physiologic obstruction seen in paralytic ileus (postop, infection, drugs, etc.)
o Large bowel obstruction -> feculent vomiting -> children with Hirschsprung’s
- Ischemic bowel disease = major artery impairment -> mainly in watershed areas (splenic
flexure) -> can be acute (mucosal -> strictures) or transmural (infarction -> gangrene) ->
colicky pain, bloody vomiting/diarrhea, decreased bowel sounds
o Occlusive type = thrombus/embolism, atherosclerosis, mechanical
o Nonocclusive type = vasoconstriction, hypotension, dehydration, etc.
- Angiodysplasia = dilations of veins near cecum -> lower intestinal painless bleeding
- Malabsorption = usually due to pancreatic insufficiency
o Celiac sprue = Abs against gliadin/transglutaminase -> loss of villi -> anemia,
weight loss, dermatitis herpetiformis (posterior forearms), IgA deficiency ->
patients with prior adenovirus infection, HLA-DQ2, other autoimmune disorders
o Tropic sprue = post diarrheal enteric infection -> atrophy usually in distal ileum
(B12 deficiency -> megaloblastic anemia)
o Abetalipoproteinemia = MTP mutation -> decreased apoprotein B48/B100 ->
decreased chylomicrons/VLDL -> decreased fat/vitamin ADEK uptake -> failure to
thrive, steatorrhea
- Infective enterocolitis
o Cholera = gram- comma shaped -> rice water fishy smelling diarrhea,
dehydration, hypotension, shock
▪ V. parahaemolyticus -> seafood associated gastroenteritis
o Campylobacter = from chicken -> travellers’ diarrhea, reactive arthritis (HLA-B27),
erythema nodosum, Guillain Barre
o Shigella = daycares, travellers, nursing homes -> bloody diarrhea, reactive
arthritis, HUS
o Yersinia = appendiceal pain, erythema nodosum, reactive arthritis
 o E. coli = gram- rod -> travellers diarrhea
▪ EHEC (O:157:H7) -> bloody diarrhea, HUS
o C. perferinges = spore forming gram+ rod -> food poisoning (heat labile
enterotoxin) from meats -> can cause enteritis necroticans
o Whipples disease = seen in white males with arthritis -> macrophages with PAS+
rods -> steatorrhea, weight loss, lymphadenopathy
o C. difficile = causes pseudomembranous colitis after antibiotic use -> fever,
diarrhea
o Viral gastroenteritis = norovirus (adults), rotavirus (children)
o Parasitic enterocolitis = ascaris (eggs in stool), strongyloides (penetrate through
skin -> autoinfection), necator/ancylostoma (iron deficiency anemia), enterobius
(perianal itchiness), trichuriasis (vitA deficiency in children, rectal prolapse),
Schistosoma (granuloma, bloody diarrhea, portal/pulmonary hypertension),
amoebiasis (flask shape ulcer, RBC in trophozoites), giardia (drinking stream
water, steatorrhea, pear shaped trophozoite), trichinella (undercooked pork,
larvae in muscle), cryptosporidium (acid fast oocysts in stool, effect ileocolic
area), D. latum (raw fish, B12 deficiency, proglottids in stool), Echinococcus
(hyatid cysts in brain/liver), hymenolepsis (autoinfection), T. saginata/solium
(beef/pork, abdominal pain, obstruction, neurocysticercosis)
- Diarrhea = decreased stool consistency or increased stool volume/frequency
o Osmotic = due to nutrient malabsorption (lactase deficiency)
o Secretory = due to increased endogenous secretion (cholera toxin ADP
ribosylates Gs -> increase cAMP)
o Inflammatory = destruction of epithelium (EHEC, salmonella, etc.)
o Motility = accelerated transit time (thyrotoxicosis)
- Intestinal lymphomas
o Burkitt’s lymphoma = terminal ileum of children with prior EBV infection
o Mediterranean lymphoma = IgA deficiency
o Diffuse large B-cell lymphoma = in adults and children -> mucosal nodules, thick
intestinal wall, ulcerations, etc.
o Enteropathy type T cell lymphoma = seen in refractory celiac disease
Large intestine
- Irritable bowel syndrome = more common in neurotic females, idiopathic -> alternating
mucous diarrhea and constipation, bloating, abdominal pain relieved by defecation
- Crohn disease = NOD2 mutation, ASCA abs, young and old females (bimodal) ->
transmural inflammation primarily in terminal ileum, fissures/fistulas, non-caseating
granulomas, skip lesions, creeping fat, string sign (x-ray), ulcers (aphthous ->
longitudinal), watery or bloody diarrhea, weight loss, pernicious anemia, strictures, joint
pain -> increased risk of intestinal cancer
 <-CD|UC->
- Ulcerative colitis = pANCA, young females -> continuous mucosal inflammation involving
distal colon (rectum always involved), loss of haustra (smooth colon), bloody mucoid
diarrhea, normal bowel thickness, pseudopolyps, broad based ulcers, crypt abscesses ->
increased risk of colon cancer, bile duct cancer, primary sclerosing cholangitis, toxic
megacolon (gangrene), polyarthritis, pyoderma gangrenosum
- Intermediate colitis = overlap between Crohn and UC
- Colitis associated neoplasia = long term IBD complication -> monitor after 8 years OR at
time of diagnosis if associated with primary sclerosing cholangitis
- Diversion colitis = complication of intestinal resection -> follicular lymphoid hyperplasia
- Microscopic colitis = chronic watery diarrhea with normal mucosa and weight
o Collagenous type = in middle aged females -> thick subepithelial collagen layer
o Lymphocytic type = in celiac disease -> intraepithelial lymphocytes
- Diverticulosis = low fibre/high fat diet -> mucosal herniation through muscularis (false
diverticula) -> fever, abdominal pain, painless rectal bleeding -> can form abscesses,
fistulas, or rupture and cause peritonitis/sepsis/obstruction -> contrast CT for diagnosis
- Melanosis coli = seen in laxative abuse -> pigmented colon -> PAS/lipofuscin+
- Volvulus = sudden abdominal pain and distention, obstipation -> usually occurs at
sigmoid colon
- Colorectal cancer = seen in old African Americans with high fat diet or IBD or genetic
predisposition (familial polyposis) -> usually asymptomatic but can have alternating
constipation and diarrhea -> segmental resection or total resection (familial polyposis)
or chemotherapy (late stages) -> CEA can be used to monitor treatment
Appendix
- Acute appendicitis = occurs in ages 10-30 years -> luminal obstruction (fecalith,
lymphoid hyperplasia, worms) -> stasis + bacterial proliferation -> inflammation +
increased pressure + distension + neutrophil infiltrate -> ischemia -> necrosis/gangrene
-> fever, anorexia, nausea, pain starts as periumbilical then shifts to RLQ -> can rupture
leading to peritonitis -> won’t fill on barium enema
- Mucocele = dilated mucus filled appendix due to luminal blockage or mucinous tumors
- Neoplasms
o Mucinous cystadenocarcinoma = can cause pseudomyxoma peritonei ->
peritoneal spread causing mucinous ascites -> right hemicolectomy
o Carcinoid = most common, serotonin secreting yellow tumor -> can cause
obstruction, intussusception, carcinoid syndrome -> appendectomy (only tip
effected) OR right hemicolectomy (base or lymph involvement)
 ▪ Neuroendocrine cells = neural crest origin, small/round/blue cells, salt &
pepper pattern, synaptophysin & chromogranin+ -> makes serotonin
▪ Carcinoid syndrome = flushing, sweating, diarrhea, bronchospasm -> rare
in appendiceal carcinoid tumor (serotonin metabolized by liver)

Peritoneum
- Peritonitis = caused by visceral perforation (PPUD) -> invasion of bacteria (E. coli,
Bacteroides, step, c. difficile) -> sudden abdominal pain, board like abdomen -> can lead
to sepsis and death
o Spontaneous bacterial peritonitis = in adults with cirrhosis, portal HTN, ascites
o Chemical peritonitis = due to bile, HCl, hemorrhage, etc.
o Diagnosis = upright CXR (pneumoperitoneum), always biopsy gastric perforation
o Treatment = bilateral truncal/selective/highly selective vagotomy
- Peritoneal tumors = mesenteric/omental cysts, mesothelioma (asbestos), primary
peritoneal carcinoma, metastatic carcinoma (from ovaries, stomach, pancreas)
- Bezoar = concretion of partially digested foreign materials -> trichobezoar (hair),
phytobezoar (vegetable), etc.
Pharmacology
Peptic diseases drugs -> STOP NSAIDs
Acid secretion reduction
- PPIs = omeprazole -> prodrug (thiophilic sulfonamide = active form) -> irreversibly
inhibits H/K pump -> stops acid secretion
o Uses = GERD, PUD, ZES, gastrinoma, NSAID ulcers
o ADR = rebound acid hypersecretion, hypochlorhydria (atrophic gastritis), B12
deficiency, inhibits CYP2C10 (blocks clopidogrel activation), hypomagnesia,
pneumonia, C. difficile colitis
- H2 blockers = cimetidine -> block H2 receptors on parietal cells -> decreased cAMP and
acid secretion
o Uses = nocturnal acid secretion, PUD, GERD, ZES, stress ulcers
o ADR = rebound acid hypersecretion, tolerance, thrombocytopenia +
antiandrogenic effects (gynecomastia, galactorrhea, etc.) + inhibits CYP450
(increases warfarin, phenytoin, etc.)
▪ Famotidine has no antiandrogenic effects, nizatidine excreted by kidney
- Antimuscarinics = propantheline/dicyclomine/scopolamine -> decreased effect of
gastrin/ACh/histamine to stimulate gastric acid secretion -> rarely used in PUD/ZES
because of antimuscarinic effects (dry mouth, blurred vision, urinary retention)
Acid neutralizers
- Antacids = fast acting for acute gastritis pain relief -> can cause acid rebound,
hypokalemia, chelates drugs (tetracyclines, fluoroquinolones, etc.)
o Aluminum hydroxide + magnesium hydroxide = combined to neutralize their
ADRs (constipation + diarrhea)
o Calcium carbonate = causes constipation, milk alkali syndrome
o Sodium bicarbonate = can cause belching and flatulence
Cytoprotective agents
- Misoprostol = PGE1 analog -> stimulates mucus/bicarbonate secretion -> prevent NSAID
induced ulcers -> causes cramps/abortion
- Sucralfate/Bismuth = forms gel like coat on ulcer + stimulates PGE2 synthesis (mucus +
bicarbonate)
H. pylori treatment
- Triple therapy = PPI + amoxicillin + clarithromycin
o BMT regimen = bismuth + metronidazole + tetracycline
- Quadruple therapy = PPI + bismuth + metronidazole + tetracycline
Antiemetics & Prokinetics
- 5HT3 antagonist = ondansetron -> blocks peripheral (stomach) and central (CTZ, nucleus
solitarius) stimulation for vomiting
o Uses = chemo/post radiation/postop nausea and vomiting, traveller diarrhea
▪ Alosetron can be used for diarrheal IBS in women
o ADR = constipation, ischemic colitis (alosetron in men), headache, QT
prolongation, serotonin syndrome
- Metoclopramide = D2 antagonist + 5HT4 agonist (ACh release) + 5HT3 antagonist ->
increased LES tone + increase gastric emptying + blocks central vomiting stimulus (CTZ)
o Uses = nausea/vomiting, intractable hiccup, GERD, diabetic gastroparesis
o ADR = extrapyramidal effects (tardive dyskinesia), hyperprolactinemia
▪ Domperidone = D2 antagonist that has less extrapyramidal effects but is
cardiotoxic
- Antimuscarinics = scopolamine -> blocks muscarinic receptors in vestibular system ->
used for motion sickness
- H1 antihistamines = diphenhydramine -> anticholinergic + antihistaminic + sedative ->
used for motion sickness
 - Erythromycin = stimulates motilin receptors
- Cannabinoids = dronabinol/nabilone -> inhibits GABA -> used for chemo
nausea/vomiting + appetite stimulant
- Substance P/NK1 antagonists = aprepitant -> prevents acute/delayed chemo
nausea/vomiting -> causes constipation/fatigue
Laxatives
- Bulk forming = bran, psyllium, methylcellulose -> retain water in intestines -> increase
stool mass -> used for chronic constipation
o ADR = bloating, flatulence
▪ Laxative abuse syndrome = flaring, hypokalemia, malabsorption,
dehydration
- Stool softeners = docusate, mineral oil, glycerin -> incorporates water/fat into stool ->
used in hemorrhoids, fecal impaction, constipation
o ADR = lipid pneumonitis (aspiration), impaired vitamin ADEK absorption
- Osmotic laxatives = stimulates colonic secretion
o Magnesium preparations = osmotic solutes (attracts water) + stimulate CCK
(increased secretions + motility) -> can cause renal insufficiency (hypermagnesia)
o Lactulose = degraded by colonic bacteria into osmotic solutes (attracts water) ->
used in hepatic encephalopathy (ammonia trapping by reducing colon pH)
o Polyethylene glycol = unabsorbable osmotic sugar -> produces watery stool ->
used for complete colonic cleansing/whole bowel irrigation, chronic constipation
- Stimulant laxatives = castor oil/senna/bisacodyl -> irritants (stimulate peristalsis) +
decrease water absorption -> can cause atonic colon (abuse), melanosis coli (senna)
- Methylnaltrexone bromide/alvimopam = block peripheral opioid receptors without
effecting analgesic effects in CNS -> used in postoperative ileus

IBS drugs
- Chloride secretion activators = lubiprostone (PGE2) & linaclotide (CFTR) -> used in
constipation dominant IBS
- Alosteron = 5HT3 antagonist -> used for diarrheal IBS in women -> causes ischemic colitis
in men
Antidiarrheals
- Oral rehydration therapy = glucose + sodium + potassium + citrate + zinc sulfate
- Antibiotics = ONLY used if there is abdominal pain/bloody stool/fever for >7 days
o NOT USED with EHEC -> precipitates HUS
o Rifaximin (RNA polymerase inhibitor) -> used for non-invasive E. coli (travellers
diarrhea), hepatic encephalopathy, diarrheal IBS
o Oral vancomycin used for C. difficile colitis
- Antimotility agents = loperamide/diphenoxylate -> inhibit ACh release -> decrease
peristalsis + secretion -> used for acute diarrhea -> can cause toxic megacolon/HUS
- Octreotide = somatostatin analogue -> inhibits hormone/pancreatic/intestinal secretion
+ decreased motility/gallbladder contraction/splanchnic blood flow -> used for carcinoid
 tumors (reduces flushing/diarrhea), acromegaly, variceal bleeding, diarrhea, acute
pancreatitis, portal hypertension
IBD drugs
- Mesalamine = treatment of choice for ulcerative colitis -> maintenance and acute attack
- Glucocorticoids = used to manage acute flare ups -> must be tapered off
- Immunosuppressants = azathioprine/mercaptopurine/methotrexate -> used in IBD
maintenance of remission
- Biological agents = infliximab (anti-TNFa), natalizumab (anti-a4 integrin subunit) -> last
line of treatment before surgery
GI
Physiology
Hepatobiliary secretions
- Secretory = bile acids + bicarbonate + phospholipids
o Bile concentrated in the gallbladder
o Bile flow = depends on secretion pressure + gallbladder compliance + spincter of
Oddi resistance + CCK secretion
- Excretory = cholesterol + bile pigments + lipophilic drugs/metabolites + xenobiotics
- Enterohepatic circulation = bile secreted -> 95% of bile resorbed in terminal ileum and
recirculated to live via portal vein + 5% of bile is excreted in feces
o Ileal resection -> leads to bilious/choleretic diarrhea (small resection) or fatty
diarrhea/steatorrhea (large resection)
- Bilirubin metabolism = Hb broken down by macrophages in RES (spleen) ->
unconjugated bilirubin transported to liver via albumin -> liver conjugates bilirubin ->
excreted in feces (urobilin) or urine (urobilinogen)
o Unconjugated bilirubin = insoluble, toxic, tightly bound to albumin, not excreted
in urine
o Conjugated bilirubin = soluble, non-toxic, loosely bound to albumin, freely
excreted in urine
Pathophysiology
GIT pathology
- Internal hemorrhoids = dilated superior hemorrhoidal veins (above pectinate) -> bright
red painless bleeding seen in constipation, pregnancy, obesity, portal hypertension
- External hemorrhoids = dilated inferior hemorrhoidal veins (below pectinate) -> painful
bleeding -> can led to painful thrombosis
- Benign polyps = pedunculated (attached via stalk) or sessile (broad base)
o Hyperplastic -> small sessile piles of goblet cells in left colon of elderly
o Hamartomas -> cell proliferation due to genetic mutation
▪ Cowdens syndrome = AD PTEN mutation -> macrocephaly,
trichilemmoma, breast/thyroid follicular/endometrial carcinoma
▪ Cronkhite-Canada syndrome = non-hereditary in >50 year olds
▪ Juvenile polyps = SMAD4/BMPR mutation -> many large polyps in
children <5 years with rectal bleeding -> increased risk of cancer
▪ Peutz-Jeghers syndrome = STK11/LKB1 mutation -> multiple large
pedunculated polyps in small intestine + hyperpigmentation in mouth,
palms, genitalia, perianal -> increased risk of cancer
o Inflammatory -> due to chronic injury and healing -> solitary rectal ulcer in
anterior rectal wall + rectal bleeding + mucus discharge
- Neoplastic polyps = pedunculated (attached via stalk) or sessile (broad base)
o Adenomatous (tubular, villous, tubulovillous) -> precursor to adenocarcinoma ->
surveillance colonoscopy by 50 years (40 years if family history)
▪ Multiple large villous polyps with high dysplasia = higher cancer risk
o Serrated sessile adenoma -> BRAF mutation with MSA -> large polyps in right
colon with NO dysplasia
 o Traditional serrated adenoma -> small pedunculated polyps on left side
o Serrated polyposis syndrome = at least 5 polyps >10mm OR polyps + family
member with SPS OR >20 polyps of any size -> increased risk of colorectal cancer
- Familial syndromes
o Familial adenomatous polyposis = 1000s of precancerous colorectal polyps ->
prophylactic colectomy (patients with APC mutation)
▪ Gardner’s syndrome = AD disease -> FAP + osteomas + desmoid tumors +
epidermal cysts + duodenal/thyroid cancer -> risk of colon cancer
▪ Turcot’s syndrome = AR disease -> FAP + CNS tumors
o Lynch syndrome = mismatch repair defect -> fewer polys in right colon
- Large bowel malignancies
o Colorectal adenocarcinoma = in patients >50 years with previous cancer, UC,
Crohn, Lynch, HPS, pelvic radiation -> iron deficiency, metastases to liver -> CEA
for postop monitoring
▪ APC/B-catenin pathway -> most common -> left colon, change bowel
movements (diarrhea, melena), annular tumor (obstruction)
▪ MSI/mismatch repair pathway -> right colon, polypoid, exophytic, bulky
tumor that tend to bleed
▪ KRAS pathway -> CpG methylation
o Squamous cell carcinoma = poor prognosis tumors
o Carcinoid tumor = rare, solitary yellowish mass -> carcinoid syndrome if
metastasizes to liver
o Lymphoma = primary lymphoma in cecum or rectum
▪ Lymphoid polys -> benign smooth soft polyps in rectum
o GIST = less common in large bowel as compared to stomach
o Leiomyoma/leiomyosarcoma = arise mainly in rectum/sigmoid colon
- Anal malignancies
o Squamous cell carcinoma = most common malignancy -> HPV 16/18 infection ->
bleeding, pain, pruritis, verrucous appearance with keratin pearls
Hepatic injury
- Degeneration/intracellular accumulation = steatosis (fatty yellow liver, lipid vacuoles),
feathery degeneration (bile stained swollen hepatocytes), ballooning degeneration,
Mallory Denk bodies (hyaline membranes), bile duct stasis, pigment/mineral
accumulation (hereditary hemochromatosis/iron deposition), councilman body
 - Cell death = apoptosis (TNFa, FAS/FASL, BAX) or necrosis (alcohol, viral hepatitis, ROS)
- Inflammation
o Acute -> seen in alcoholic injury -> PMNs, Mallory Denk bodies, necrosis
o Chronic -> lymphocytes
- Regeneration = ability to fully regenerate after injury
- Fibrosis = irreversible -> leads to cirrhosis
o Cardiac cirrhosis = congestive hepatopathy due to right sided heart failure ->
bridging fibrosis with lobular reorganization (portal triad at center of lobule)
- Hepatic failure = caused by chronic liver diseases, drug injury, viral hepatitis,
mushrooms, alcohol, Reye syndrome, etc. -> hyperbilirubinemia, hypoalbuminemia,
hyperammonemia, portal hypertension, GI distress, jaundice, hepatic encephalopathy,
hyperestrogenemia, coagulopathy, hepatorenal syndrome, etc.
o Acute -> hepatic encephalopathy develops within 6 months
o Fulminant -> hepatic encephalopathy develops within 2 weeks of jaundice
o Chronic -> hepatitis lasting longer than 6 months -> cirrhosis
▪ Acute on chronic -> acute failure due to hypotension superimposed on
chronic failure
- Cirrhosis = micronodular or macronodular irreversible end stage of chronic liver diseases
-> bridging fibrosis (type I/III collagen deposition) + regenerative nodules + architectural
disruption of entire liver

- Portal hypertension = can be due to thrombus/portal vein narrowing (pre-hepatic) or

right sided heart failure/constrictive pericarditis/hepatic outflow obstruction/cirrhosis
(hepatic) -> ascites, portocaval shunts, congestive splenomegaly, hepatic
encephalopathy, hepatorenal syndrome
o Ascites = collection of fluid in peritoneal cavity
o Portocaval shunts = can lead to hemorrhoids, varices, caput medusa
o Hepatorenal syndrome = increased endothelin due to lack of liver metabolism ->
renal hypoperfusion -> RAAS activation -> cirrhosis + ascites + renal failure +
tubular bile casts
o Hepatic encephalopathy = hyperammonemia -> cerebral edema + asterixis +
hyperreflexia
Viral hepatitis -> acute infection (apoptosis, ballooning degeneration -> can cause fulminant
hepatitis) and/or chronic infection (lymphocytic infiltrate, bridging necrosis, fibrosis)
- HepA/E = fecal-oral transmission (contaminated food/water), never chronic, seen in
travellers, lifelong immunity, commonly asymptomatic
o HepE diagnosis = exclusion of HepA as there is no serological test
 - HepB = resilient virus (lasts 7 days exposed), infection through blood/mucosal contact,
more likely to be chronic in infants -> can cause fulminant/interface hepatitis, ground
glass hepatocytes -> associated with polyarteritis nodosa/hepatocellular carcinoma
- HepD = requires HepB infection to replicate -> coinfection (recoverable) or
superinfection (HepB carrier -> chronic disease)-> ALWAYS symptomatic
- HepC = transmitted via blood (mainly IVDU), causes chronic infection, high mutation
(lacks 3’-5’ exonuclease) -> can cause hepatocellular carcinoma

Other liver infections -> usually secondary involvement of liver

- Malaria = plasmodium infection via Anopheles mosquito -> sporozoites replicate in and
burst hepatocytes to infect RBCs as merozoites -> hepatosplenomegaly with splenic
fibrosis and hemozoin stained Kupffer cells
- Leishmaniasis = transmitted via sand fly (L. Donovani) -> amastigotes infect macrophages
-> fever, hepatosplenomegaly, pancytopenia, weight loss, skin hyperpigmentation, liver
fibrosis
- Tapeworms = egg ingestion of T. solium (cysticercosis) or Echinococcus (hyatid cysts)
- Schistosomiasis = S. mansoni/japonicum cause liver granulomas + clay pipe fibrosis +
destroy portal veins (portal hypertension), S. haematobium causes bladder
granulomatosis
- Liver flukes = Fasciola/Clonorchis -> embed in liver then move to bile ducts -> periportal
fibrosis, cholestasis, cholangiocarcinoma
- Fungal = due to candidemia in patients with undergoing chemotherapy -> abscesses
Other liver disorders
- Autoimmune hepatitis = chronic hepatitis in HLA-B8 women with elevated IgG + other
autoantibodies/autoimmune diseases and NO viral markers
- a1-antitrypsin deficiency = low neutrophil elastase/cathepsin B/proteinase 3 ->
emphysema + liver diseases -> round inclusions in hepatocytes

(a1-antitrpsin) (acetaminophen toxicity)

- Drug induced liver injury = can be direct injury, toxic conversion of xenobiotics or hapten
injury that is predictable (acetaminophen) or unpredictable (aspirin, halothane, etc.) ->
hepatocyte necrosis, cholestasis, livery dysfunction
o Acute acetaminophen toxicity = zone 3 necrosis with no infiltrate
- Alcoholic liver disease = depends on gender (females have lower alcohol dehydrogenase
activity) + amount of alcohol consumed -> steatosis (chronic drinking) OR alcohol
hepatitis (binge drinking) -> hepatomegaly, jaundice/ascites/hepatic encephalopathy
(fatty liver), fever/leukocytosis (alcohol hepatitis), macrocytic anemia, increased
GGT/AST/ALT (AST:ALT >2)
o Alcohol toxicity = NAHD trapping -> increase lipogenesis + decreased glutathione
(oxidative stress) + CYP450 induction (ROS) + iron mobilization + lipid
peroxidation + MDA formation (carcinogenic, immunogenic, CVD) +
mitochondrial injury
o Non-alcoholic fatty liver = diagnosis of exclusion -> seen in obese patients with
abnormal lipid profile and diabetes and no alcohol history, AST:ALT <1

- Hemochromatosis = TFR2/HJV/HFE mutation -> decreased hepcidin (cannot detect iron

levels) -> increase iron absorption -> iron deposition in liver (hemosiderin in Kupffer
cells), pancreas, heart, pituitary
o Primary hemochromatosis = effects males >40 years -> hepatomegaly, skin
pigmentation, type I diabetes, cardiac dysfunction, arthritis, cirrhosis, pancreatic
fibrosis, elevated iron/transferrin/ferritin
o Acquired hemochromatosis = excessive iron intake/blood transfusions
- Wilsons disease = ATP7B mutation -> loss of Cu transport -> Cu accumulation in liver,
eye, brain -> cirrhosis, neuropsychiatric symptoms (movement disorders + depression),
Kayser-Fleischer rings, elevated transaminases, increased urine/liver Cu, decreased
ceruloplasmin, rhodamine+
- Menke’s = ATP7A mutation -> copper deficiency -> early death
- Neonatal hepatitis = due to bile duct obstruction, infection, toxicities,
genetic/metabolic/endocrine disorders -> lobular disarray, giant cell hepatocytes,
cholestasis, leukocytosis, extramedullary hematopoiesis
- Intrahepatic biliary diseases
o Primary biliary cirrhosis = bile duct granulomatous destruction in middle-aged
women -> cirrhosis, pruritis, late jaundice, leukocytosis, anti-mitochondrial Abs
o Secondary biliary cirrhosis = prolonged biliary obstruction due to stone (adults)
or biliary atresia (children) -> cholestasis, biliary inflammation, cirrhosis ->
greenish nodular liver
o Primary sclerosing cholangitis = occurs in men with IBD (UC) -> inflammation
and obliterative fibrosis of bile ducts -> onion skin periportal tract, pipe stem
fibrosis -> risk of cholangiocarcionoma

- Bile duct anomalies

o Von Meyenberg complex = benign tumor -> dilated bile ducts in hyalinized
fibrous stroma
o Polycystic kidney disease = associated with ADPKD
- Circulatory disorders
o Impaired blood flow into liver -> hepatic artery/portal vein occlusion -> liver
infarct
o Impaired blood flow through liver -> passive congestion + centrilobular necrosis +
peliosis hepatis -> chronic passive congestion (nutmeg liver)
o Impaired blood flow out of liver (Budd Chiari syndrome) -> hepatic vein
thrombosis -> icterus + ascites + hepatosplenomegaly + ankle edema +
ulcerations + prominent collateral beins + hepatic blood retention + chronic
hepatic congestion
▪ Also seen in pregnancy, OCP use, polycythemia vera, paroxysmal
nocturnal hemoglobinuria, intraabdominal cancers
- Liver disorders of pregnancy = HELLP syndrome, preeclampsia (HTN), eclampsia (HTN +
seizures), acute fatty liver, intrahepatic cholestasis
 - Neoplasia
o Focal nodular hyperplasia = benign asymptomatic well circumscribed nodule with
stellate fibrous core, small bile ducts and vessels in females
o Nodular regenerative hyperplasia = diffuse nodules -> associated with portal
hypertension and renal transplant
o Hepatic adenoma = benign neoplasm derived from hepatocytes with not portal
tracts -> associated with prolonged OCP use
o
Jaundice
- Unconjugated hyperbilirubinemia = jaundice due to overproduction/impaired liver
uptake (prehaptic) or defective conjugation (hepatic)
o Hemolytic anemia -> increased RBC degradation -> increased bilirubin
o Criggler Najjar I -> complete lack of glucuronosyltransferase activity (UGT1A1) ->
normal liver, colorless bile, death from kernicterus within 18 months
o Criggler Najjar II -> reduced glucuronosyltransferase activity -> mild jaundice
corrected with phototherapy + low does phenobarbital
o Gilberts -> mutation in promoter region of UGT1A1 gene -> jaundice precipitated
by stress and resolved spontaneously
- Conjugated hyperbilirubinemia = jaundice due to membrane transport disorder
(hepatic) or obstruction (post hepatic)
o Dubin Johnson -> failed transport of conjugated bilirubin out of hepatocyte due
to MDR2 mutation -> recurrent jaundice, black liver (epinephrine metabolite
pigmentation)
o Rotor -> defective uptake/excretion of bilirubin pigments -> normal liver with
jaundice
o Liver/biliary tract obstruction
- Neonatal jaundice = glucuronidase in breast milk deconjugates bilirubin causing
transient jaundice
- Cholestasis = due to liver dysfunction or intrahepatic/extrahepatic biliary obstruction ->
pruritis, jaundice, xanthoma, dark urine, pale stool -> elevated alkaline phosphatase,
conjugated bilirubin, cholesterol, feathery degeneration, bile stasis
o Intrahepatic biliary obstruction
▪ Benign recurrent intrahepatic cholestasis -> ATP8B1 mutation -> normal
liver with life-long intermittent attacks, low GGT
▪ Progressive familial intrahepatic cholestasis 1 -> ATP8B1 mutation ->
severe pruritis + liver failure in early childhood, low GGT
▪ PFIC 2 -> ABCB11 mutation -> severe cholestasis + pruritis + growth
failure + cirrhosis in childhood, high GGT
▪ PFIC 3 -> ABCB4 mutation -> increased GGT
▪ Primary hepatolithiasis -> calcium bilirubinate stones due to recurrent
ascending cholangitis -> can cause biliary neoplasia
o Extrahepatic biliary obstruction
▪ Stones, tumors, etc.
▪ Biliary atresia/choledochal cysts in children
Gallbladder disorders
- Congenital anomalies = agenesis, duplication, bilobed, aberrant location, congenital
diverticula, biliary atresia, folded fundus (most common), choledochal cyst (cystic
dilatation in children <10 years)
o Biliary atresia -> bile duct proliferation, cirrhosis, bile plugs, green liver -> normal
birth weight, death within 2 years
- Cholelithiasis = gallbladder stones in obese/estrogenic female Native Americans with
ABCG8 gene mutation -> colicky pain, worse with fatty foods -> can lead to empyema,
gallstone ileus, etc.
o Cholesterol stones = supersaturation + hypomotility + nucleation + accretion (due
to increased mucus) -> yellow stones
▪ Directly related to [cholesterol] and inversely related to [bile salt/lecithin]
o Pigment stones = black stones due to bilirubin accumulation (hemolysis) or
brown stones due to infections
- Cholesterolosis = lipid accumulation in macrophages (foam cells) -> strawberry
gallbladder
- Acute cholecystitis = due to cystic duct (stone) obstruction -> Murphy’s sign, epigastric
constant pain, fever, leukocytosis, fibrinous/suppurative exudate ->
o Acute acalculous cholecystitis -> due to bile stasis/ischemia
o Chronic cholecystitis = repeated acute cholecystitis attacks -> Rokitansky-Aschoff
sinuses (epithelial outpouchings), xanthogranulomatous cholecystitis, follicular
cholecystitis, porcelain gallbladder
- Choledocholithiasis = biliary tree obstruction -> obstructive jaundice, dilated hepatic bile
ducts -> can lead to ascending cholangitis (intrabiliary infection)
- Cholangitis = choledocholithiasis + infection -> Charcot’s triad (fever/leukocytosis + RUQ
pain + jaundice)
- Neoplasia
o Adenomyomatous hyperplasia, adenomyoma, andenomyomatosis
o Extrahepatic cholangiocarcinoma = seen in patients with chronic inflammation
(primary sclerosing cholangitis), cholestasis, choledochal cysts, Clonorchis
infection
o Gallbladder carcinoma = in females with gallstones -> can be infiltrating or
exophytic adenocarcinoma
Exocrine pancreatic disorders
- Congenital anomalies
o Agenesis
o Pancreas divisum = duct of Wirsung and Santorini don’t fuse -> poor drainage ->
pancreatitis
o Annular pancreas = pancreatic tissue encircling 2nd part of duodenum ->
duodenal obstruction
o Ectopic pancreas = most commonly in stomach or duodenum -> pain, bleeding,
mistake for tumor
- Pancreatitis = injury causing autodigestion of pancreas by its own enzymes ->
permanent loss of pancreatic function
 o Acute = reversible damage -> inappropriate release of pancreatic enzymes due to
obstruction (gallstones) or acinar cell injury (alcohol) or defective intracellular
transport (intracellular activation of enzymes) -> stabbing abdominal pain
radiating to back, fever/chills -> focal areas of fat necrosis, hyperglycemia,
increase pancreatic enzymes, hypocalcaemia, periumbilical/flank hemorrhage
(Cullen/Grey-Turner sign) -> use ultrasound if stones are suspected, if not then
contrast CT then MRI
▪ Acute necrotizing pancreatitis = acinar necrosis + hemorrhage -> black
hemorrhagic tissue and yellowish chalky fat necrotic tissue
▪ BISAP parameters = ≥3 of the following for severe acute pancreatitis ->
BUN >25mg/dL + GCS <15 (mental status) + SIRS (systemic inflammation)
+ >60 years + pleural effusion
o Hereditary = recurrent attacks of severe acute pancreatitis from childhood due to
increased activity of trypsin -> PRSS1 (gain of function) or CFTR/SPINK1 (loss of
function) mutations
o Chronic = prolong inflammation leading to exocrine/endocrine pancreatic
destruction and fibrosis (TGFB/PDGF) in middle aged males (alcohol abuse) or
children (CF) -> abdominal pain precipitated by alcohol/eating/opiates, diabetes
(endocrine insufficiency), steatorrhea, malabsorption, weight loss, calcifications
o Autoimmune = IgG4 secreting plasma cells in pancreas -> painless jaundice, mass
mimicking pancreatic adenocarcinoma -> respond to steroids
- Non-neoplastic cysts
o Congenital = unilocular, thin wall, associated with ADPKD)
o Pseudocyst = solitary collection of necrotic material with no epithelial lining in
chronic alcoholic pancreatitis
- Neoplastic cysts
o Serous cystadenoma = benign multiple clear fluid filled cysts in elderly women
with VHL mutation in tail of pancreas
o Mucinous cystic neoplasm = precancerous large cystic cavities filled with mucin
in tail of pancreas with ovarian like stroma, KRAS/p53/RNF43 mutation
o Intraductal papillary mucinous neoplasm = precancerous mucin producing cyst in
men with GNAS/KRAS mutation in head of pancreas
o Solid pseudopapillary neoplasm = malignant large circumscribed cysts in young
women with CTNNB1/B-catenin mutation, non-cohesive cells surrounding blood
vessels
- Infiltrating ductal adenocarcinoma = seen in smoking diabetic patients >50 years with
high fat diets -> abdominal pain, weight loss, DVT, jaundice (tumor in head of pancreas)
- Acinar cell carcinoma = malignant AFP secreting epithelial tumor forming pancreatic
enzyme granules in elderly -> lipase hypersecretion syndrome -> metastatic fat necrosis,
polyarthralgia, thrombotic endocarditis
- Pancreatoblastoma = AFP secreting neoplasm in children with squamous islands mixed
with acinar cells
Pharmacology
Viral hepatitis drugs
Hepatitis B
- IFNa = degrades viral mRNA
o Uses = HBV, HCV, HDV, HPV, CML, Kaposi’s sarcoma, etc.
o ADR = flu like symptoms, neuropsychiatric reactions (suicidal ideation and
depression), myelosuppression, neuro/cardio/nephrotoxic, HSR, infertility,
exacerbates autoimmune disorders and liver diseases -> not given to
immunosuppressed/pregos
- HBV polymerase inhibitors = tenofovir, lamivudine, emtricitabine, adefovir, entecavir
o Entecavir = guanosine analog -> inhibits all three functions of HBV DNA
polymerase -> used in chronic HBV infection -> can cause lactic acidosis
o Tenofovir = used in chronic HBV infection -> can cause proximal renal
tubulopathy (loss of calcium -> osteomalacia)
o Lamivudine = can develop tolerance, can cause rebound hepatitis
o Telbivudine = thymidine analog -> can cause myopathy, GI distress, peripheral
neuropathy, lactic acidosis, fatty large liver
o Adefovir = used for liver cirrhosis -> can cause nephrotoxicity
Hepatitis C
- Direct viral inhibitors = used for chronic HepC infection
o NS3/NS4A inhibitors = pratiprevir -> inhibit viral protease from polyprotein
cleavage -> metabolized by CYP3A -> can cause pruritis, nausea, fatigue, anemia
o NS5A inhibtors = daclatasvir -> inhibits viral assembly
o NS5B inhibitors = sofosbuvir -> inhibit viral RNA polymerase
- Ribavirin = combined with protease inhibitors (pratiprevir) and RNA polymerase
inhibitors (sofosbuvir) and INFa to treat HepC
o Uses = HepC, RSV, lassa fever
o ADR = hemolytic anemia, teratogenic

Pharmacology of alcohol
- EtOH = oxidize in liver by alcohol dehydrogenase (less enzyme activity in women) via
zero order kinetics OR microsomal enzymes -> acetaldehyde further oxidized by to
acetate acetaldehyde dehydrogenase -> acetate is converted to acetyl CoA via acetyl CoA
synthetase -> NADH trapping -> lactic acidosis + hypoglycemia + fatty liver change
o Acute alcohol consumption -> CNS depression (enhances GABA + inhibits
NMDA/Ca channels), sedation, anxiolytic, euphoria, increased endorphins,
analgesia, peripheral vasodilation, diuretic, increases appetite, stimulates sexual
desire but decreases performance, emesis, tocolytic, hyperuricemia, etc.
o Uses = fever, rubefacients, antiseptic, methanol/ethylene glycol poisoning,
trigeminal neuralgia
o Drug interactions = potentiate benzos (respiratory depression) and
antihistamines (extreme sedation)
- Treatment for acute alcoholism = prevent respiratory depression + aspiration vomitus ->
maintain ABC, gastric lavage, treat hypoglycemia/ketoacidosis (glucose + thiamine),
correct electrolyte imbalances
- Treatment for alcohol withdrawal = cravings, nausea, delirium tremens, diaphoresis,
tachycardia, seizures -> treated with long + short acting benzos (diazepam, lorazepam,
etc.) that are eventually tapered (can also add haloperidol/olanzapine for hallucinations)
- Alcohol dependence treatment
o Disulfiram = inhibits acetylaldahyde dehydrogenase -> causes extreme
discomfort when drinking (nausea, headache, flushing, tachycardia, emesis,
diaphoresis, hypotension)
▪ Griseofulvin/metronidazole have disulfiram like reactions
o Naltrexone = opioid antagonist -> can cause hepatotoxicity if combined with
disulfiram
o Acamprosate = NMDA inhibitor and GABA activator -> reduces relapses
- Ethylene glycol/methanol poisoning = metabolites can cause oxalate stones and renal
damage, malaise, vomiting, acidosis, snowstorm blindness -> stabilization + fomepizole
(alcohol dehydrogenase inhibitor) + EtOH (higher affinity to alcohol dehydrogenase)
correcting acidosis
Pediatrics
Clinical genetics
- Nucleosome = 8 histones (rich in arginine/lysine) + 146 base pairs
o H1 -> chromosome compaction
o Methylation decreases transcriptions, acetylation increases transcription
▪ Lyonization = X-inactivation -> Xist gene make ssRNA -> methylation of X
chromosome into heterochromatin
● Manifesting heterozygote = female presenting with X-linked
recessive disease due to skewed lyonization
- DNA replication = helicase unwinds DNA -> single strand binding proteins prevent
reannealing -> primases form RNA primer -> DNA polymerase attaches to primer and
replicates DNA -> DNA ligase connects Okazaki fragments -> topoisomerase relieves
supercoils
o Fluoroquinolones inhibits topoisomerase II (DNA gyrase)
- Nucleotide excision repair = endonuclease recognizes and removes pyrimidine dimers
(UV radiation) -> DNA polymerase fills in replacement segment
o Mutated endonuclease -> xeroderma pigmentosa
- DNA mismatch repair = MUT1/2 recognizes mismatch and repairs segment
o Mutation -> Lynch syndrome/HNPCC
- Ribosomes = 30S for initiation (blocked by aminoglycosides, tetracyclines), 50S for
elongation (blocked by clindamycin, macrolides, chloramphenicol)
o Diphtheria toxin blocks EF2 (blocks elongation/translocation)
- DNA mutations = missense (sickle cell), nonsense (hemophilia), deletion causing
frameshift (Duchenne MD), deletion with no frameshift (cystic fibrosis)
- RNA
o rRNA = most abundant, resistant to RNAase
o microRNA = regulation of gene expression
o snRNP = RNA splicing -> splice donor site (5’) and acceptor site (3’)
o mRNA = RNA polymerase reads template strand in 3’-5’ & synthesizes in 5’-3’
▪ a-amanitin inhibits RNA polymerase II

▪ Mutation at promoter = decreased transcription

▪ Mutation at splice site = abnormal mRNA -> B-thalassemia (also caused

by point mutation in promoter), Gaucher’s, Tay-Sachs
- Oncogenic reciprocal translocations
o t(9:22) = Philadelphia chromosome -> CML
o t(15:17) = retinoid receptor -> AML
o t(14:18) = bcl2 -> follicular lymphoma
o t(8:14) = cMyc -> Burkitt’s lymphoma
o t(11:14) = cyclinD -> mantle cell lymphoma
Genetic disorders
 - Trisomy 21 = mental retardation, short stature, epicanthal folds, simian palmar crease,
depressed nasal bridge, Brushfield eye spots, etc. -> increased risk of septal defects, ALL,
Alzheimer’s, duodenal atresia -> amniocentesis shows increased hCG + inhibin A,
decreased unconjugated estriol + aFP
o Meiotic nondisjunction = nondisjunction mainly in anaphase I (2x trisomy + 2x
monosomy), also anaphase II (1x trisomy + 1x monosomy + 2x diploid) due to
increased maternal age -> 47, XX/XY +21
▪ Nondisjunction also causes Patau, + Edwards, Turners, Klinefelter’s
o Robertsonian translocation = loss of p arms of acrocentric chromosomes 14 and
21 leading to fusion of the q arms in parent that is passed on to child -> seen in
younger mothers with prior miscarriages -> 46 XX/XY, -14, +t(14;21)
o Genetic mosaicism = presence of 2+ cell lines in some of the cell lines within an
individual
- Fragile X syndrome = X-linked dominant increase in CGG repeats in 5’ UTR causing
hypermethylation of FMR1 gene -> mental retardation, long face, large ears, prominent
jaw, macroorchidism, joint hypermobility, autistic features, hand flapping, tantrums, etc.
o Anticipation = pattern of inheritance where subsequent generations develop
diseases earlier and/or more severely due to increased
▪ Also seen in Huntington’s (AD CAG repeats), myotonic dystrophy (AD CTG
repeats), Fredrich ataxia (AR GAA repeats)
- Osteogenesis imperfecta = loss of function mutation in COL1A -> reduction in type I
collagen -> brittle bones, fractures, hearing loss, blue sclera, etc.
o Locus heterogeneity = mutations at different locations can cause same disease
phenotype -> chromosome 7 or 17 mutations can cause osteogenesis imperfecta
o Penetrance = number of individuals with the genotype expressing the phenotype
o Expressivity = same mutation giving rise to variable phenotypical expression
- PKU = AR mutation of phenylalanine hydroxylase -> buildup of phenyl ketones ->
intellectual disability, musty odor, hypopigmentation -> tyrosine becomes essential AA
- Lieber hereditary optic neuropathy = mutation in mitochondrial DNA (maternal
inheritance) -> painless progressive bilateral loss of vision in young males -> associated
with ataxia, dysarthria
o Heteroplasmy = variable expressivity in mitochondrial diseases
Congenital GI disorders
- Esophageal atresia = failure of recanalization -> associated with trachea-esophageal
fistulas, polyhydramnios, VATER/VACTERL
- Esophageal stenosis = usually mid-esophagus due to muscular hypertrophy of failure of
recanalization
- Achalasia = autoimmune destruction ganglion cells in Auerbach’s plexus -> stenosed LES
(birds beak), dysphagia, heartburn, etc.
- Pyloric stenosis = muscularis hypertrophy/hyperplasia -> most common cause of GOO in
infants -> olive mass, visible peristalsis, non-bilious projectile vomiting after 1-2 months
 o GOO also caused by gastric volvulus (180-degree stomach rotation), gastric antral
webs, gastric duplication cysts (pancreatic tissue in greater curvature)
- Duodenal atresia = failure of recanalization -> double bubble sign, bilious vomiting ->
associated with Downs
o Also seen with annular pancreas (failure of ventral/dorsal pancreatic bud fusion)
- Biliary atresia = obliteration of ducts leasing to bile obstruction -> jaundice, dark urine,
pale stool -> associated with situs inversus, spleen/heart/vessel anomalies
- Omphalocele = persistence of physiologic hernia -> viscera covered by a sac, increase
aFP -> associated with trisomy 13/18
- Vitelline duct anomalies = umbilical-fecal fistula, Meckel diverticulum (persistent
vitelline duct), raspberry tumor (umbilical vitelline protrusion), enterocystoma
- Midgut rotation anomalies = nonrotation (left sided colon), malrotation (susceptible to
volvulus), reversed rotation (retro duodenal transverse colon)
- Intestinal atresia/stenosis = failure of recanalization or ischemia -> apple peel/Christmas
tree/corkscrew deformities
- Hirschsprung disease = failure of neural crest migration -> constipation, bilious vomiting
3-4 hours after eating, abdominal distension, proximal colonic dilatation
- Imperforate anus = too much mesoderm
- Anal atresia/fistula = too little mesoderm
Pediatric disorders
- Congenital anomalies = most common cause of death <1 year
o Types
▪ Malformations = intrinsic abnormality -> anencephaly

▪ Disruptions = extrinsic destruction of normal tissue -> amniotic bands

▪ Deformations = extrinsic compression -> structural anomalies (club feet)

▪ Sequences = single event causing cascade of anomalies -> Potter

sequence for oligohydramnios (pulmonary hypoplasia, limb contractures)
▪ Syndromes = inexplicable combination of anomalies
o Causes = genetics and/or environmental insults, especially during organogenesis
(week 3-9)
▪ Karyotypic aberrations = usually result in miscarriage -> can also result in
trisomy or monosomy
▪ Single gene mutations = mutation in SHH (holoprosencephaly), HOXGL13
(poly/syndactyly), PAX2 (renal coloboma syndrome), PAX6 (aniridia),
PAX3 (Waardenburg syndrome)
▪ Viral infection = rubella (cataracts, heart defects, deafness, mental
retardation), CMV (microcephaly, deafness, hepatosplenomegaly)
 ▪ Drugs/chemicals = retinoic acid, thalidomide (phocomelia), folate
antagonists, smoking, alcohol (microcephaly, ASD, flat nasal bridge, etc.)
▪ Radiation = can cause microcephaly, blindness, spina bifida, etc.

▪ Maternal diabetes = causes hyperinsulinemia in infant -> large baby with

organomegaly -> associated with heart/neural tube defects
- Prematurity = birth before 37 weeks -> 2nd leading cause of death <1 year
o Risk factors = preterm premature rupture of placental membranes (smokers with
vaginal bleeding or prior preterm ruptures), intrauterine infection (GBS),
structural abnormalities (fibroids, placenta previa/abruptio), multiparity (twins),
immaturity of fetal organs
- Fetal growth restriction = caused intrinsically by chromosomal abnormalities/TORCHES
infection (symmetric growth restriction), placentally by placenta previa/infection/etc.
(brain sparing asymmetric growth), maternally by eclampsia/alcohol/smoking
- Neonatal respiratory distress syndrome = decreased surfactant due to lung immaturity in
preterm infants born via C-section to diabetic mothers -> lung collapse -> hyaline
membrane disease (alternating atelectasis and alveolar dilation, eosinophilia, hyaline
membranes, ground glass CXR) -> increased risk of PDA, germinal matrix/intraventricular
hemorrhage, necrotizing enterocolitis (fever, bloody stool, vascular collapse, sepsis)
o O2 therapy can cause retinopathy/retrolental fibroplasia (rebound hypoxia
increasing VEGF) and bronchopulmonary dysplasia
- Fetal hydrops = accumulation of fluid in fetus leading to death
o Immune hydrops = due to Rh incompatibility (Rh- mother, Rh+ fetus -> treat with
anti-IgD) or ABO incompatibility (preformed anti-A/B blood group IgG, also
causes neonatal hemolytic anemia)
o Nonimmune hydrops = fetal cardiac failure, chromosomal anomalies (Turners,
trisomy 18/21), anemia (a-thalassemia), viral infection (parvovirus B19, CMV)
- SIDS = unexplained death usually occurs between 2-4 months at home during the night
due to delayed arousal of cardiorespiratory center -> petechia on thymus, pericardium,
pleura + pulmonary edema + infection/congenital anomaly/child abuse/genetic defects
seen in autopsies
o Risk factors = intrapartum smoking, prior SIDS death, sleeping prone on a soft
surface in a hot environment in the same bed as parents
- Benign tumors
o Hemangioma = most common tumor -> port-wine stain -> associated with VHL
and familial CNS cavernous hemangiomas
o Lymphangioma = cystic/cavernous spaces seen in Turners -> D2-40+
o Congenital infantile fibrosarcoma = t(12;15)(p13;q25) -> ETV6-NTRK3 fusion
o Teratoma = sacrococcygeal tumor that is usually mature but can also be
immature or malignant
- Malignant tumors = usually mesenchymal (blastomas -> small round blue cells)
 o Neuroblastoma = most common extracranial solid tumor (usually in adrenal
gland) -> nMyc amplification, NSE+, Homer-Right pseudorosettes, increased
VMA/HMA in urine, blueberry muffin baby -> can become ganglioneuroma

o Ewing sarcoma = t(11;22), CD99+

o Rhabdomyosarcoma = t(2;13), myogenin+
o Burkitt lymphoma = t(8;14), CD19/20+ (B cell)
o Retinoblastoma = Rb mutation on chromosome 13
o Medulloblastoma = chromosome 17 mutation, GFAP+, synaptophysin+
o Wilms tumor = most common primary renal tumor occurring between 2-5 years,
generally not syndromic, preceded by nephrogenic rests (embryonic cells) ->
abdominal mass/pain, hematuria, hypertension, pulmonary metastasis
▪ WAGR syndrome = 11p13 deletion (WT1, PAX6) -> Wilms tumor, aniridia,
genital anomalies, mental retardation
▪ Denys Drash syndrome = missense WT1 mutation -> Wilms tumor,
gonadal dysgenesis, nephropathy
▪ Beckwith Weideman syndrome = 11p15.5 deletion (WT2) -> Wilms tumor,
organomegaly, omphalocele, adrenal cytomegaly
Common pediatric diseases
- Conjunctivitis = usually viral but can be bacterial (contagious -> treatment needed)
- Strabismus = causes amblyopia (decreased visual acuity) due to misaligned eyes
(imbalanced EOMs) -> can cause blindness if one eye is consistently not used
- Hernias and hydroceles = inguinal hernia exam for every male child
- Skin lesions = can be erythematous (red), macular/patchy (flat), papule/nodular (raised
and solid), plaque (raised and flat), cystic/vesicular/bullous/pustule, wheal (elevated
itchy plaque), have skin turgor (dehydration), excoriation (from scratching),
abrasion/scrape, cut/laceration, petechiae, ecchymosis/contusion/bruising, scars
o Exanthem = widespread rash in children due to drugs, toxins, infections (roseola,
measles, rubella, parvovirus), autoimmune diseases, etc.
o Enanthem = rash/lesions occurring on mucous membranes (Kolpik spots due to
measles)
o Atopic dermatitis = chronic itchiness and maculopapular lesions
o Seborrheic dermatitis = yellow flaky scales on scalp
o Fungal infections = ring worm, tinea versicolor
o Impetigo = GAS infection
 - MSK disorders = scoliosis, genu varum (bow legs), genu valgus (knocked knee)
- Acute otitis media = negative middle ear pressure due to URI (especially otitis media
with effusion) or improperly functioning Eustachian tube -> Eustachian tube opens ->
microbial invasion -> fever, otalgia, hearing loss, ear stuffiness
o Diagnosis = pneumatic otoscopy or tympanocentesis
o Treatment = observation if non-severe/unilateral/>24 months old, antibiotics if
severe/bilateral/<6 months old -> tympanocentesis or myringotomy if severe or
chronic
- Acute tonsillopharyngitis = usually viral infection -> sore throat with associated
conjunctivitis, cough, diarrhea, etc.
o GAS pharyngitis -> enlarged tonsils with exudates, pharyngeal erythema, tender
cervical lymphadenopathy, soft-palate petechia -> can cause peritonsillar
abscesses (foul breath, unilateral bulge, hot-potato voice), rheumatic fever, PSGN
-> rapid strep test (anti ASO/DNAseB Abs) -> antibiotics, tonsillectomy if chronic
- UTIs = cystitis (lower UTI) or pyelonephritis (upper UTI) usually do to ascending colonic
bacterial infection -> fever, vomiting, dysuria, flank pain (pyelonephritis) -> can cause
dehydration, hypertension, impaired renal function, renal scarring -> urine analysis
(pyuria/bacteria) + urine culture (uropathogenic colonies) -> antibiotics + pain relief
- Acute diarrhea = usually due to rotavirus infection -> oral rehydration therapy
Autism spectrum disorder
Disease Symptoms Other
Autism Persistent deficits in social communication and Significant impairment,
interaction -> social-emotional reciprocity, present during early
developing and maintaining relationships, development, not better
non-verbal communication explained by another
Restrictive/repetitive patterns in ≥ 2 of the diseases
following -> repetitive movements, insistence on
routines, fixated interests, hypo/hyperreactivity
to sensory input
Autistic disorder = most common -> major delays in language, poor social interactions,
impaired mental abilities
Asperger’s disorder = high functioning autism -> poor social interactions + repetitive and/or
restrictive behaviours, no delay in language but pedantic speech (situationally inappropriate),
uncoordinated, cannot relate to others, average or above average intelligence, obscure
interests,
Pervasive developmental disorder (NOS) = mild autistic symptoms, no delays in language or
intellectual abilities
Childhood disintegrative disorder = significant regression in functioning following at least 2
years of normal functioning
Rett’s Syndrome = X-linked dominant (only in females), autistic features, hand wringing,
screaming fits, seizures, language regression