Step Review 3: GI, Repro Flashcards
Describe the rotation of the midgut in development
270 degree counterclockwise around SMA
What GI development defect is associated with Down Syndrome? Radiographic finding?
Duodenal atresia, double bubble finding
Olive mass in epigastric region? Associated with exposure to what antibiotics?
Hypertrophic pyloric stenosis, Macrolides
What ligament contains the portal triad?
The hepatoduodenal ligament
What ligament contains the splenic artery and vein?
Splenorenal ligament
What layers are Meissners and Myenteric plexus in? Function?
Meissner: Submucosa, secretes fluid
Myenteric: Muscularis, motility
How deep do ulers and erosions penetrate?
Ulcers into submucosa and inner or outer muscular layer while erosions are confined to the mucosa
Where do you find peyer patches?
Ileum
Are there villi in the colon? Crypts?
Crypts are present but no villi
What portion of the duodenum is compressed in SMA syndrome?
Transverse (3rd portion)
Vertebral levels of Celiac trunk, SMA, and IMA
T12, L1, L3
What are the three branches of the celiac trunk?
Common hepatic, left gastric and splenic
Which rectal vessels are part of the portal circulation?
Superior only, middle and inferior are systemic
Lymphatic drainage above and below pectinate line? Cancers?
Above: Internal iliac nodes, adenocarcinoma
Below: superficial inguinal nodes, squamous cell
What hepatic cells store vitamin A when quiescent and produce ECM when stimulated? Where are they located?
Stellate (ito) cells in the space of Disse
Where is zone 1 in liver? What affects it?
Periportal: ingested toxins and viral hepatitis (also where hepatic artery comes in)
What affects zone 2 of the liver?
Yellow fever
Where is zone 3 of the liver? What affects it? What is important here?
Pericentral vein. 1st affected by ischemia, contains cytochrome p450 and is thus most sensitive to metabolic toxins and the site of alcoholic hepatitis
What is the portal triad? What zone is it in?
Bile duct, portal vein branch and hepatic artery branch. Zone 1
What is a classic cause of painless jaundice?
Tumor in the head of the pancreas (ex. ductal adenocarcinoma)
What is in the femoral sheath?
Femoral vein, artery and deep inguinal lymph nodes BUT NOT FEMORAL NERVE
Where does a femoral hernia occur compared to the nerve, artery, vein, etc.
Very medial (femoral ring)
What covers direct hernias? What is this derived from?
External spermatic fascia only. External oblique
Watery Diarrhea, low potassium and low stomach acid?
VIPoma
Where is ghrelin produced?
Stomach
What converts pepsinogen to pepsin?
Acid (H+)
Where in the stomach do you find G cells? Pareital and Chief cells?
Antrum, body (note: D cells are also in the antrum)
How does gastrin mainly cause acid secretion?
By its action on ECL cells which release histamine rather than its direct effect on parietal cells
Describe the concentration of bicarbonate in pancreatic secretions based on flow rate? Cl-?
High flow is high bicarbonate (makes sense because this is the job). Low flow is high Cl-
What converts trypsinogen to trypsin?
Enterokinase/enteropeptidase (brush border enzyme in duodenal and jejunal mucosa)
What specialized cells do you find in peter patches?
M cells which sample and present antigens to immune cells (submucosa of ileum)
Where do IgA secreting plasma cells of the GIT eventually reside?
Lamina propria in ileum (post stimulation that begins in Peyer patches)
What catalyzes rate limiting step of bile acid synthesis? What are bile acids conjugated to?
Cholesterol 7 alpha hydroxylase, glycine or taurine
What is an intermediate in heme conversion to bilirubin? What enzyme mediates this step?
Heme oxygenase catalyzes the formation of bilverdin from heme (green in bruises)
Enzyme that conjugates bilirubin?
UDG-glucuronsyl transferase
Most common salivary gland tumor? Most common malignant? Which one is a benign cystic tumor with germinal centers and often bilateral?
Pleomorphic adenoma: most common (pleomorphic)
Mucoepidermoid carcinoma: most common malignant
Warthin tumor: bilateral, smoking, germinal centers
Cause of eosinophilic esophagitis?
Food allergens–> dysphagia causing rings and linear furrows
Dysphagia, IDA and esophageal webs with glossitis too
Plummer-Vinson syndrome
How does scleroderma cause esophageal dysmotility?
Esophageal smooth muscle atrophy
What are curling and cushing ulcers?
Curling: burns–> hypovolemia–> mucosal ischemia
Cushing: brain injury–> inc. vagal stimulation–> inc. ACh–> increased H+ production
What prostaglandin is protective to the gastric mucosa?
PGE2
What area of the stomach does H. pylori preferentially affect?
Antrum
What do you suspect if you see gastric mucosa with hypertrophied rugae?
Menetrier disease. Gastric hyperplasia of mucosa causes excess mucus production with excess protein loss and parietal cell atrophy with decreased acid production
Where do you most often see gastric intestinal adenocarcinoma?
Lesser curvature
Grossly thickened and “leathery” stomach wall. What is this called?
Linitis plastica (diffus gastric cancer- signet ring cells)
What is a Sister Mary Joseph Nodule?
Subcutaneous periumbilical metastasis from gastric tumor (also famous is the virchow node)
Where is the virchow node?
Left supraclavicular node
If you suspect a malabsorption syndrome, where should you start the workup?
Screen for fecal fat (Sudan stain)
HLA for celiac? Antibody that you might not know?
HLA DQ2 and DQ8. Anti-endomysial
What do you see on histology with celiac?
Villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis
What area must be biopsied for celiac?
Duodenum
What does it mean with the D-xylose test if you see normal amounts in blood/urine? Low?
Normal: pancreatic insufficiency
Low: mucosa defects or bacterial overgrowth
What does low fecal elastase indicate? What pH will you see?
Pancreatic insufficiency which will also cause a decrease in duodenal pH
Describe Topheryma whipplei
Intracellular gram (+) that will stain PAS positive
Crohn or UC?
1) Cobblestone mucosa
2) Transmural
3) Psuedopolyps
4) Lead pipe
5) Crypt abscesses
6) Kidney stones
1,2,6 are crohn
3-5 are UC
What type of diverticula are most in GIT? Why?
False, only mucosa and submucosa out pouch (lack or have attenuated muscular is externa)
Where is diverticulosis most commonly located?
Sigmoid colon
Muscle involved in Zenker?
Inferior pharyngeal constictor
What types of tissue may be in a Meckel diverticulum?
Pancreatic or gastric
What mutations are associated with Hirschsprung disease? Increased risk for it with what?
RET, Down syndrome
Fibrous bands in midgut leading to obstruction?
Malrotation
Where do you see volvulus in infants? Elderly?
Midgut, sigmoid
Currant jelly stools?
Intussusception or acute mesenteric ischemia
Two possible lead points that can cause intussusception?
1) Virus–> peyer patch hypertrophy
2) Meckel diverticulum
What is angiodysplasia?
Tortuous dilation of vessels in GIT leads to hematochezia. Most often in cecum, terminal ileum or ascending colon
When should you pick hyper plastic polyp as an answer?
Basically never. They are small and non-neoplastic
Two syndromes with hamartomatous polyps?
PJ and juvenile polyposis
Pathway for adenomatous polyps? How do they present?
AK53 pathway (Chromosomal instability pathway-CIN) and although usually asymptomatic may present with occult bleeding
Saw tooth pattern of crypt, premalignant polyps. How do they arise?
Serrated polyps via CpG hypermethylation path with microsatellite instability and BRAF mutations
Genetics and chromosome with FAP? Which side do these carcinomas typically present on if it progresses that far?
APC tumor suppressor on c5, AD, left side
What do you suspect if you see supernumerary teeth?
Gardner: FAP +osteomas and congenital hypertrophy of retinal pigment epithelium
Turcot syndrome
FAP + malignant CNS tumor
What is the heritability of any polyp syndrome?
AD
Cancer risk with PJ? Lynch (HNPCC)?
Breast/GI for PJ
Endometrial, ovarian and skin with lynch
What are the genetics associated with Lynch syndrome?
AD mutation of mismatch repeater genes with subsequent microsatellite instability (right sided)
What part of the GIT is ALWAYS involved with Lynch syndrome? Are there polyps?
Proximal colon, NOOOOO (HNPCC)
Describe, in short, right vs. left sided colorectal cancer presentation?
Right side bleeds, left side obstructs
What type of endocarditis should be suspected with CRC?
Steptococcus bovis
Tumor marker for CRC?
CEA
Name the two pathways to CRC. What syndromes/problems are associated with each?
CIN (AK-53): FAP, sporadic (this is APC)
MSI: Lynch syndrome and some sporadic via serrated polyp pathway
What cells cause fibrosis in cirrhosis? What cells are in the nodules?
Stellate cells, hepatocytes
Whats free points you should always look for when given liver function test markers?
AST>ALT think alcohol
Why is gamma glutamyl transpeptidase better than ALP?
ALP can also increase with bone activity
What happens to platelets with liver disease?
Decrease due to decreased thrombopoietin and liver sequestration
What type of liver change is seen with Reye syndrome? Pathogenesis?
Microvesicular fatty change caused by decrease in beta oxidation by reversible inhibition of mitochondrial enzymes
What is a mallory body?
Associated with alcoholic liver disease and an intracytoplasmic eosinophilic inclusion of damaged keratin filaments.
Where do you see sclerosis in alcoholic cirrhosis?
Zone 3 (Peri hepatic vein)
What most likely leads to non-alcoholic fatty liver disease? How do you distinguish it from alcoholic liver disease?
Metabolic syndrome/ obesity, ALT will be> AST
Treatment for hepatic encephalopathy? What is fidaxomycin?
Lactulose (turns NH3 to NH4) and rifaximin or neomycin. Fidaxomycin is for C. diff.
Tumor marker for hepatocellular carcinoma?
AFP
What is a common benign liver tumor that you see blood on histology? What should you not do?
Cavernous hemangioma: do not biopsy due to risk of hemorhage
Liver tumor that is related to OCPs or steroid use
Hepatic adenoma
Tumor associated with arsenic and vinyl chloride exposure.
Angiosarcoma
Do you see JVD in Budd-Chiari syndrome? What should you immediately associate?
No, Polycythemia vera
Why do newborns get jaundice? Where can it cause problems?
Immature UDP-glucuronsyltransferase leads to unconjugated hyperbilirubinemia that can build up in the brain and cause kernicterus (specifically basal ganglia)
Does UV radiation on neonates conjugate bilirubin?
No
Inheritance of all of the hyperblirubinemia, wilsons disease and hemochromatosis?
AR
Specific finding in dubin johnson syndrome?
Black liver (conjugated bilirubin)
Which type of Crigler-Najjar might be survived? What helps it?
Type II, phenobarbital because it increases liver enzyme synthesis
Chromosome and defect in Wilson disease? What is a very close mutation disease?
Copper transporting ATPase (ATP7B gene on c13), Menkes disease
What are the levels of ceruloplasmin and urine copper in wilson disease? Where does it accumulate in the eyes?
Decreased ceruloplasmin, increased urine copper. Cornea
Mutation and chromosome for hemochromatosis?
HFE gene on c6 (C282Y>H63D)
Common cause of death with hemochromatosis?
HCC
Immediate association with light colored stool?
Biliary tract disease
Which biliary tract disease is intrahepatic only? Which is extra hepatic too?
PSC is both, PBC is in
Anti-mitochondrial antibody?
PBC
Onion skin bile duct fibrosis?
PSC
What does PSC increase risk for? Classic association and marker?
Increased risk for cholangiocarcinoma and gallbladder cancer. Associated with UC and p-anca
Relationship of bile salts and gallstones?
Decreased bile salts increases risk of stones
Is serum amylase or lipase more specific for pancreatitis?
Lipase (amylase is in mouth too)
What lines the cyst with pancreatitis?
Granulation tissue, not epithelium
Where does pancreatic adenocarcinoma arise from? Tumor marker? Odd risk factor?
Pancreatic ducts, CA 19-9, tobacco use
What cancer is associated with migratory thrombophlebitis?
Trosseau syndrome, pancreatic adenocarcinoma
What happens to blood pH when the stomach secretes acid?
It increases (HCO3 that was formed with the H+ is pushed into blood)
What kind of electrolyte disturbance can be caused by all antacids?
Hypokalemia
How does sucralfate work?
Binds to ulcer base providing physical protection and allowing bicarbonate secretion to reestablish pH gradient in mucus layer
What is misoprostol?
PGE1 analog. Increases gastric protection (don’t use in pregnant women, can cause abortion)
What is sulfasalazine?
Combo of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory) that is activated by colonic bacteria. Used for UC and the colitis component of Crohn disease
Odansetron mechanism and use? (SE?)
5-HT3 antagonist that decreases vagal stimulation (may prolong QT interval)
Metoclopramide MOA?
D2 antagonist that increases resting tone, contractility, LES tone and motility (don’t use in obstructed patients or Parkinsons)
Orlistat MOA?
Inhibits gastric and pan creating lipase leading to decreased breakdown and absorption of dietary fats
What is Ursodiol?
Nontoxic bile acid that increases bile secretion and decreases cholesterol secretion and reabsorption
Recurrent aphthous ulcers, genital ulcers, and uveitis. Pathology?
Behcet syndrome, which is due to immune complex vasculitis involving small vessels
Most common location for oral cavity SCC? Major risk factors?
Floor of mouth. Tobacco and alcohol
White patch on lateral tongue that cannot be scraped away. Pre-malignant?
Oral hairy leukoplakia, not pre-malignant rather it is EBV induced squamous cell hyperplasia
Salivary gland tumor composed of stromal (e.g. cartilage) and epithelial tissue. Major fact relevant to treatment?
Pleomorphic adenoma, high rate of recurrence due to incomplete resection (small islands penetrate through the capsule)
Parotid gland tumor that resembles lymph tissue (lymphocytes and germinal centers)
Warthin tumor
What part of the esophageal wall is involved in esophageal web?
Mucosa only
Painful hematemesis? Painless?
Painful: Mallory-Weiss
Painless: Esophageal varicies
Most common esophageal cancer worldwide?
Squamous cell carcinoma
When does esophageal cancer present?
Late thus poor prognosis
Where is lymph node spread from esophagus in:
upper 1/3
middle 1/3
lower 1/3
upper 1/3: cervical nodes
middle 1/3: mediastinal or tracheobronchial nodes
lower 1/3: celiac or gastric nodes
What is the pathogenesis of a cushing ulcer?
Increased ICP causes increased vagus stimulation and acid secretion
Where do you find parietal cells?
Body and fundus of stomach
HSR type in pernicious anemia?
HSR type IV (t-cells)
What layer of lymph tissues is only present in inflammation? Tumor that does this?
Marginal zone, MALToma
How to tell difference in benign peptic ulcers and malignant ulcers
Malignant are large and irregular with heaped up margins as opposed to sharply demarcated benign ulcers
What blood type increases risk for gastric carcinoma?
Type A
What do the intestinal and diffuse types of gastric carcinoma physically look like?
Intestinal: ulcer
Diffuse: thickened gastric wall (linitis plastica)
What vasculitis might affect the SMA?
PAN
Where is lactase found?
Brush border of enterocytes
What type of HSR is celiac?
Type IV
What cancers could celiac potentially cause late in the course?
Small bowel carcinoma and T-Cell Lymphoma (EATL)
Apparent celiac that responds to antibiotics? Where is it probably located?
Tropical sprue. Not duodenum like celiac but jejunum and ileum
Classic site of whipple disease? Pathogenesis?
Small bowel lamina propria. Bacteria builds up in lysosomes of macrophages, macrophages accumulate and compress lacteals, chylomicrons cannot be transferred from enterocytes to lymphatics
Low VLDL and LDL with malabsorption?
Possibly abetalipoproteinemia (AR deficiency of B-48 and B-100 with malabsorption due to defective chylomicron formation)
Why is carcinoid syndrome heart effect limited to right side?
MAO in lungs metabolize serotonin to 5-HIAA
Does smoking increase UC risk? What about Crohn?
Protects against UC, Increases Crohn risk
Is Crohn or UC more likely to cause bloody diarrhea?
UC
What type of biopsy is useful in diagnosing Hirschsprung disease?
Rectal suction biopsy
What provides the weak point in the colonic wall to allow diverticula to form?
Where vasa recta traverse muscularis propria
Where does angiodysplasia classically arise?
Right colon (think of it as the result of high pressure in right colon as diverticulosis is to the left colon)
Most common site of ischemic colitis?
Splenic flexure
Mouth and GI bleeds? Inheritance?
Hereditary hemorrhagic telangiectasia (AD)
Why might aspirin help prevention of colonic carcinoma?
At the same point as P53 on the AK53 progression there is an increase in COX expression that is needed as well. Aspirin prevents this and impedes progression
Which colorectal carcinoma syndrome do you associate with ovarian/endometrial cancer? Breast?
Ovarian/endometrial: HNPCC
Breast: PJ
Which side of tumor do you see HNPCC on?
Right, polyps are in the left
Gene leading to appendages in wrong places? Gene for proper organization along dorsal-ventral axis?
Homeobox, Wnt-7
When does the blastocyst implant? What happens?
Day 6, hCG secretion begins
What week starts the fetal heartbeat? What else happens this week?
4, the limbs begin to develop
Disruption vs deformation vs malformation
Disruption: secondary breakdown of previously normal tissue
Deformation: extrinsic disruption that occurs after embryonic period
Malformation: Intrinsic disruption that occurs in embryonic period (week 3-8)
Teratogenic agents that cause:
Absence of digits
Limb defects
Caudal regression syndrome
Alkylating agents, thaldiomide, maternal diabetes
Mechanism of fetal alcohol syndrome?
Failure of cell migration
Type of twins formed most often? When does the split occur?
Monochorionic diamnionic (4-8 days with the morula)
What if twinning happens after blastocyst stage?
Monochorionic, mono amniotic with the possibility of being conjoined if also after the embryonic disc is formed
What does the syncytiotrophoblast do?
Secretes/synthesizes hormones such as hCG which stimulates the corpus luteum to secrete progesterone during first trimester
What is the outer layer of chorionic villi? Why does this make sense?
Synctiotrophoblast- these cells lack MHC-I which decreases the chance of them being attacked by the maternal immune system
Where do the umbilical arteries arise?
Fetal internal iliac arteries
What are the umbilical arteries and veins derived from? What else is derived from this?
Allantois, urachus- duct between fetal bladder and umbilicus
Duct involved if urine is coming from umbilicus? What if it is meconium?
Uracus
Vitelline (omphalo-mesenteric duct)
What do the left and right recurrent laryngeal nerves wrap around?
Left: Ligamentum arteriosum/ aortic arch
Right: subclavian artery
What does the 1st pharyngeal cleft form? 2-4?
1st: external auditory meatus
2-4: temporary cervical sinuses which are obliterated by proliferation of 2nd arch mesenchyme
If you see an immobile (upon swallowing) mass on lateral neck, what is it?
Persistent cervical sinus
Which arch develops into the: Malleus, incus, stapes? Stylopharyngeus? Artenyoids? Which intrinsic laryngeal muscle does the 6th arch not do?
Malleus and incus: 1
Stapes: 2
Artenyoids: 4,6
Cricothyroid
What nerves are associated with the 4th and 6th pharyngeal arches?
4th: superior laryngeal nerve (CN X)
6th: recurrent laryngeal nerve (CN X)
What nerve does the anterior belly of the digastric? Posterior?
Anterior is CN V, Posterior is CN 7
Heart defects associated with DiGeorge syndrome?
Conotruncal defects TOF, PTA
What causes cleft lip? Cleft palate?
Failure of fusion of the maxillary and medial nasal processes (formation of the primary palate)
-Failure of fusion of the two lateral palatine shelves
Other names for the mesonephric and paramesonephric ducts?
Mesonephric= wolffian Paramesonephric= Mullerian
What does the SRY gene mediate?
Y-chromosome gene that mediates testicular development.
What causes the paramesonephric duct to not develop in males? Internal genitalia development? External?
1) Sertoli cell–> mullerian inhibitory factor
2) internal–> testosterone
3) external–> DHT from 5 alpha reductase on testosterone
What forms the upper and lower portions of the vagina?
Upper: paramesonephric duct
Lower: urogenital sinus
What can cause amenorrhea in females with fully developed secondary sexual characteristics?
Mullerian agenesis (ovaries are still fully functional)
What would cause a XY fetus to develop both male and female internal genitalia with male external genitalia?
Absence of sertoli cells or MIF in XY fetus (mullerian duct is not suppressed, but testosterone still present)
What do the urogenital folds on an undifferentiated fetus develop into in male and female?
Male: ventral shaft of penis
Female: labia minora
What does the urogenital sinus develop into in male and female?
Male: bulbourethral glands and prostate gland
Female: Greater vestibular glands and urethral and paraurethral glands
Is hypo or epi spadias more common? What is associated with the less common one?
Hypospadias is more common and epispadias is associated with exstrophy of the bladder
What causes hypospadias? Epispadias?
Hypo: failure of the urethral folds to fuse
Epi: faulty positioning of the genital tubercle
What does the gubernaculum do in male and female after descent of testes and ovaries?
Male: anchors testes within scrotum
Female: ovarian ligament + round ligament of uterus
Which side of the scrotum is more likely to develop varicocele?
Left, gonadal vein here drains into renal vein rather than straight into IVC. Renal vein could be compromised or just the turbulence around the turn causing fluid back up into the testes
What lymph nodes do the ovaries/testes drain to?
Para-aortic lymph nodes
Where does the scrotum drain to? Glans penis?
Scrotum- superficial inguinal lymph nodes
Penis: deep inguinal
Which ovarian ligament contains the ovarian vessels? (2 names)
Infundibulopelvic ligament or suspensory ligament
Which ovarian ligament travels through the inguinal canal?
The round ligament goes through the round inguinal canal
Where does the ovarian ligament attach to the uterus?
Lateral uterus. Ovarian Ligament Latches to Lateral uterus
Normal position of the uterus?
Anteverted and anteflexed
What is the epithelium transition at the transformation zone?
From stratified squamous of the vagina and ectocervix to simple columnar epithelium
What type of epithelium lines the ovary?
Simple cuboidal
Urine leak into retropubic space? What about beneath fascia of buck/superficial perineal space?
1) Posterior (membranous) urethra injury
2) Anterior (straddle injury)
What nerve is responsible for emission in the male sexual response? Ejaculation?
Emission: sympathetic (hypogastric)
Ejaculation: visceral and Somatic (pudendal)
Where do you find spermatogonia?
Lining the seminiferous tubules
Name three important products of sertoli cells
Inhibin B (inhibits FSH), Androgen binding protein (maintain local levels of testosterone for sperm production), Produce MIF (important in development)
Are leydig cells temperature sensitive?
No
What type of estrogen comes from ovary, placenta, and fat? Relative potency?
Estradiol (ovary)> estrone (fat)> estriol (placenta)
What does estrogen do to the levels of progesterone receptors? What does progesterone do to the level of estrogen receptors?
Estrogen increases progesterone receptors
Progesterone decreases estrogen receptors
Why do you not lactate during pregnancy?
Progesterone inhibits prolactin, when progesterone falls after delivery–> prolactin is disinhibited
What and when are the two arrest phases in oogenesis?
1) prophase I until ovulation
2) metaphase II until fertilization (an egg MET a sperm)
Transient mid cycle ovulatory pain classically associated with peritoneal irritation
Mittelschmerz
What causes the LH surge to kick off ovulation?
An estrogen surge
How long is the luteal phase? How long is the follicular phase?
The luteal phase is 14 days, the follicular phase is classically 14 but can be variable in length
In the menstrual cycle, when is LH concentration higher than FSH?
Only right around ovulation
What is dysmenorrhea often associated with?
Endometriosis
Where does fertilization most often occur?
Upper end of fallopian tube (ampulla)
When is hCG detectable in blood? Urine?
Blood: 1 week after conception
Urine: 2 weeks after conception
Difference in gestational age vs. embryonic age?
Gestational: from last menstrual period
Embryonic: calculated from conception date (subtract 2 weeks from gestational)
Why do you see anemia in pregnancy? Hypercoagulability?
Anemia- relative increase in plasma to RBC concentration
Hypercoag.- To decrease blood loss at delivery
Which hormone does not continually increase through pregnancy?
hCG (it peaks at 8-10 weeks)
How doe hCG work?
Just assume always that hCG gets the job done by acting like LH (this is how it maintains the corpus luteum and thus progesterone concentration for pregnancy)
What are the hCG levels in the three major trisomies? What can high levels of hCG cause and why?
Inc. in Down, Decreased in patau and edwards
Identical alpha subunit to TSH and thus can cause hyperthyroidism (symptoms in pregnancy perhaps)
What does apgar stand for? What number?
Appearance (blue or pink) Pulse (>100) Grimace Activity Respiration (crying)
Which pro-milk hormone provides protection against pregnancy?
Prolactin (decreases GnRH)
What vitamin must be supplemented to exclusively breastfed infants?
Vitamin D
What future benefits might a mother get out of breast feeding?
Decreased risk of breast and ovarian cancer due to decreased estrogen exposure
What hormone level is specific for menopause?
Very increased FSH (no estrogen feedback)
What androgen is secreted from the adrenals?
Androstenedione
What causes differentiation of the prostate?
DHT
Which is mature: spermatogonium of spermatozoon
zoon is zooming to egg
What gonadotropin levels will you see in Klinefelter disorder? Why?
Increased LH and FSH. FSH up due to dysgenesis of seminiferous tubules and thus decreased inhibin B. LH up due to abnormal leydig cell functions
Renal defect associated with turner syndrome?
Horseshoe kidney
What is a non meiotic cause of turner syndrome?
Mosaicism from mitotic error causing some normal cells and some of the turner syndrome genotype
Very tall male with learning disability and severe acne may have what genetic disorder?
Double Y male
Incomplete puberty and lack of smell?
Kallmann syndrome. Hypogonadotropic hypogonadism due to decreased GnRH cells and messed up formation of the olfactory bulb
What are the common karyotypes of complete and partial moles?
Complete: 46 XX or XY (usually from an enucleated egg+ single sperm that duplicates paternal DNA)
Partial: 69 XXX, XXY or XYY from 2 sperm + 1 egg
Clusters of grapes or snowstorm on fetal ultrasound?
Complete mole
No chorionic villi are present.
Choriocarcinoma (like mole, proliferation of trophoblastic tissue)
Where might choriocarcinoma spread and how?
Hematogenously to the lungs
Painless vs painful bleeding in third trimester
Painless: Placenta previa
Painful: placental abruption
Membrane rupture, painless vaginal bleeding and fetal bradycardia
Vasa previa
Difference in gestational hypertension and preeclampsia? Preeclampsia to eclampsia?
Preeclampsia is new-onset HTN with proteinuria or end organ dysfunction
Eclampsia is preeclampsia plus seizures
What causes preeclampsia?
Abnormal placental spiral arteries–> endothelial dysfunction–> vasoconstriction–> ischemia
Why would you give IV magnesium sulfate to a pregnant woman?
To prevent seizures
Pregnant lady with schistocytes and high ALT, AST
HELLP: Hemolysis, Elevated Liver enzymes, Low Platelets
How do you treat Eclampsia or HELLP syndrome?
Immediate delivery is important
Incidence of gynecologic tumors in US? Worldwide?
US: Endometrial> ovarian> cervical
Cervical is most worldwide (HPV screening)
In utero exposure leading to vaginal clear cell carcinoma
DES
Most common cause of vaginal SCC?
Cervical SCC, primary vaginal carcinoma is rare
How does HPV cause CIN and cancer?
E6- inhibits p53
E7- inhibits RB
Risk factors for cervical dysplasia (4). Which is biggest?
1) Multiple sexual partners (#1)
2) Smoking
3) Starting sexual intercourse at young age
4) HIV infection
Signs of menopause before 40?
Premature ovarian failure
Abnormal vaginal bleeding that is often postcoital?
Possible cervical dysplasia or carcinoma in situ
Main thing to remember about PCOS?
LH:FSH ratio increases
Diabetes, hirsutism, acne, obesity?
PCOS
Treatment for PCOS?
Clomiphene, ketoconazole, spironolactone
What risk increases with PCOS?
Endometrial cancer secondary to unopposed estrogen from repeated anovulatory cycles?
Why do follicles not mature well in PCOS?
Increased LH causes peripheral conversion to estrogen which causes feedback inhibition of FSH in the pituitary
Most common ovarian mass in young women?
Follicular cyst
Most common group of ovarian neoplasms? Most common of this group?
Epithelial- most often serous cytadenocarcinoma
What polyp syndrome increases ovarian cancer risk?
Lynch syndrome
Pelvic pain, dysmenorrhea, dyspareunia and symptoms that vary with menstrual cycle
Endometrioma
What type of ovarian tumor can cause hyperthyroidism directly?
Mature cystic teratoma with thyroid tissue (struma ovarii)
Coffee bean nuclei on H & E?
Brenner tumor
Ascites and hydrothorax can be combined with what ovarian neoplasm to form a common syndrome? Name?
Meigs syndrome- ovarian fibroma, ascites, hydrothorax
Abnormal uterine bleeding in a postmenopausal woman ovarian neoplasm? Why?
Thecoma- produces estrogen and thus can cause bleeding
Three types of ovarian neoplasms?
Surface epithelium, germ cells, or sex cord stromal tissue
Call exner bodies ovarian tumor? Type?
Granulosa cell tumor- most common malignant stromal tumor
Psammoma bodies in ovarian tumor?
Serous cystadenocarcinoma
If you see an accumulation of mucinous material on the ovary what should you check?
Appendix! Mucinous cystadenocarcinoma
What makes a teratoma immature in a female? Is it malignant?
Presence of fetal tissue or neuroectoderm. Yes, it is malignant unlike the mature form
Fried egg cells in ovarian tumor. Tumor markers?
Dysgerminoma, LDH and hCG
Glomeruli-like structures in ovarian tumor? Marker?
Schiller-Duval bodies in yolk sac tumor, AFP
Signet cell adenocarcinoma that metastasizes? Where is it from?
Krukenberg tumor most often from stomach
Uniformly enlarged, soft uterus. What causes it?
Adenomyosis- caused by extension of endometrial tissue into uterine myometrium
Most common tumor in females?
Leiomyoma (fibroid)
Endometrial tumor that is estrogen sensitive?
Leiomyoma
Endometrial condition causing postmenopausal vaginal bleeding? Major risk factor for progression to carcinoma?
Endometrial hyperplasia (nuclear atypia is a greater risk factor than complex architecture)
Small, well-defined breast mass that increases in size and tenderness with increased estrogen
Fibroadenoma
Increased acini and stromal fibrosis in breast with calcification? Does it increase cancer risk?
Sclerosing adenosis, does increase cancer risk (1.5-2x)
Most common cause of nipple discharge?
Intraductal papilloma
Eczematous patches on nipple? Association?
Paget disease: intraepithelial adenocarcinoma cells
UNDERLYING DCIS
Carcinoma of the breast that forms linear cell formulations? How?
ILC: invasive lobular carcinoma due to decreased E-cadherin expression
Abnormal curvature of penis due to fibrous plaque within tunica albuginea?
Peyronie disease
Leukoplakia on penile shaft? Erythroplakia of glans?
Leuko: Bowen disease
Erythro: Queyrat
Two associations with SCC of the penis?
HPV, lack of circumcision
Testicular mass that increases with standing and regresses with sitting and does not transilluminate
Varicocele
Fried egg appearance testicular tumor? Marker?
Seminoma, increased placental ALP
Most common testicular tumor in boys less than 3 years old?
Yolk sac tumor (endodermal sinus tumor)
Is a mature teratoma benign in men? how do you tell?
Not necessarily. May be malignant in adult males, benign in children
Testicular tumor with Reinke crystals?
Leydig cell tumor (testosterone)
Most common testicular cancer in older men?
Lymphoma
What is the cause of BPH?
HYPERPLASIA not hypertrophy of periurethral lobes of prostate (lateral and middle lobes)
Treatments for BPH?
Finasteride, alpha 1 antagonists like terazosin and tamsulosin), tadalafil
MOA of clomiphene
Blocks estrogen negative feedback at the hypothalamus
What is leuprolide?
GnRH analog
Actions of tamoxifen and raloxifene?
Tamoxifen: agonist at bone and uterus, antagonist at breast
Raloxifene: agonist at bone, antagonist at breast and uterus
Any drug that ends with gestural or norethindrone
Progestins
Can estrogen or progesterone stop bleeding after birth?
Progesterone
How does combined contraception stop pregnancy?
Inhibit LH and FSH via feedback and thus prevent estrogen surge. No ovulation= no pregnancy chance
What are two major contraindications of OCPs?
Smoking and increased risk of CV disease
How does a copper IUD work?
Produces local inflammatory reaction toxic to sperm and ova
What is danazol?
Partial agonist at androgen receptors
What do testosterone and methyl testosterone do to lipid levels?
Increased LDL and decreased HDL
Flutamide MOA?
Comeptitive inhibition at androgen receptors
What do ketoconazole and spironolactone inhibit? When might you use them?
Ketoconazole: 17-20 desmolase
Spironolactone: 17 alpha hydroxylase and 17,20 desmolase
Both used in PCOS to reduce androgenic sx
Why is tamsulosin used in BPH?
Specific alpha 1 antagonist for alpha 1A,D receptors on prostate vs alpha 1B receptors in vasculature
Which PDE-5 inhibitor can be used for BPH?
Tadalafil
What is minoxidil?
Direct arteriolar vasodilator used for androgenetic alopecia and severe refractory hypertension
Unilateral, painful cystic lesion at the lower vestibule adjacent to the vaginal canal
Bartholin cyst
What causes condyloma latum? Accuminatum?
Latum: secondary syphilis
Accuminatum: HPV 6 and 11 (more common)
White vulvar patch with parchment-like skin. Risk for cancer down the road?
Lichen sclerosis, yes a slightly increased risk of SCC
Leukoplakia with leathery, thick vulvar skin. Risk of cancer down the road?
Lichen simplex chronicus, no increased risk of SCC
What is the major cause of non-HPV related vulvar carcinoma? Age group?
Lichen sclerosis, old (>70) chronic inflammation takes a long time to cause cancer
Erythematous, pruritic and ulcerated vulvar skin with malignant epithelial cells in the epidermis.
Extramammary Paget disease (not associated with carcinoma like the form in the breast)
How do you differentiate Melanoma from Paget disease of the vulva with PAS, keratin and S100
Paget: PAS and keratin positive, S100 negative
Melanoma: S100 positive, PAS and keratin negative
What forms the upper 2/3 and lower 1/3 of the vagina?
Upper: Mullerian ducts
Lower: urogenital sinus
What is adenosis? What increases the risk of it?
Focal persistence of columnar epithelium (from mullerian duct) in the upper vagina. Increased risk with DES in utero
Grape-like mass protruding from vagina or penis of a child? What is it called?
Embryonal rhabdomyosarcoma (sarcoma Botryoides)
Where does the lower 1/3 of the vagina drain to (LN), upper 2/3?
Lower 1/3–> inguinal nodes
Upper 1/3–> iliac nodes
How does RB work?
RB holds E2F which is needed for cell cycle progression. When RB is phosphorylated by CDKs it releases E2F and the cell cycle may proceed
Is CIN irreversible?
No, it may reverse- it is dysplasia. However, the higher grade of CIN, the less likely this is
What type of vaginal bleeding is a big hint for cervical carcinoma?
Postcoital vaginal bleeding
What are two secondary risk factors to cervical carcinoma besides HPV?
Immunodeficiency, and SMOKING
What is a common cause of death in advanced cervical carcinoma? Is it metastasis?
Hydronephrosis with post renal failure due to invasion through the anterior uterine wall into the bladder. This is not metastasis but local invasion
What follow an abnormal pap smear?
Confirmatory colposcopy and biopsy
What are the two major limitations of the Pap smear?
1) inadequate sampling of T-zone (false negative)
2) Doesn’t detect adenocarcinoma since it doesn’t arise via the CIN sequence
Why do we need pap smears if there is a vaccine for HPV?
The vaccine only covers 6, 11, 16 and 18 types, and these are not all of them
What is asherman syndrome?
Secondary amenorrhea due to loss of basalis (regenerative endometrium layer) and scarring. It is caused by overaggressive dilation and curettage
What happens in anovulatory cycles. Why does bleeding eventually occur?
Results in estrogen-driven proliferative phase without a progesterone-driven secretory phase. Eventually the glands break down and shed due to overgrowth compared to the blood supply
What do you suspect if you see plasma cells in the endometrium?
Chronic endometritis (plasma cells are necessary for the diagnosis given that lymphocytes are normally in the endometrium)
What drug may cause endometrial polyps?
Tamoxifen (no surprise here)
What is a major effect of endometriosis?
Infertility
What is adenomyosis?
Involvement of the uterine myometrium with endometriosis
What benign condition classically presents as postmenopausal uterine bleeding? What is the biggest predictor for it progressing to carcinoma?
Endometrial hyperplasia. Cellular atypia
What are the two pathways that endometrial carcinoma may arise?
1) Hyperplasia leads to carcinoma (endometroid histology, risk is increased estrogen exposure)
2) Sporadic arises in elderly and usually has serous or papillary-serous histology with psammoma body formation and p53 mutations (aggressive)
Most common outcome of leiomyomas?
Asymptomatic but can cause bleeding and infertility
Do leiomyomas progress to leiomyosarcoma?
NOOOO! Leiomyosarcoma arises de novo
What is the gross presentation of leiomyosarcoma?
Single lesion with areas of necrosis and hemorrhage
LH:FSH ratio >2
PCOS
Obese woman with infertility, oligomenorrhea and hirsutism. May develop type II DM 10-15 years later.
PCOS
What are serous and mucinous cells in regard to ovarian epithelium?
Serous: line fallopian tube
Mucinous: line the endocervix
What type of ovarian cancer do BRCA1 mutation carriers have a greater risk for? What other mutation can do this?
Serous carcinoma of the ovary and fallopian tube. Lynch syndrome
What type of ovarian tumor is most associated with endometriosis?
Clear cell carcinoma (also endometroid tumors to a lesser extent)
Which type of tumor specifically carries the worst prognosis of female genital tract tumors, why?
Surface epithelial carcinoma because it is often discovered late
What is CA-125 good for monitoring?
Surface epithelial ovarian carcinomas
Name the types of germ cell tumors of the ovary
Cystic teratoma, embryonal carcinoma, dysgerminoma, choriocarcinoma, endodermal sinus tumor (yolk sac)
What indicates malignancy in a female teratoma?
Immature tissue (usually neural) or somatic malignancy within the teratoma
Fried egg cell tumor in women (clear cytoplasm and central nuclei)
Dysgerminoma (seminoma is male counterpart)
Most common germ cell tumor in children? Marker? Histology?
Yolk sac tumor. AFP. Schiller-Duval bodies
What proliferates in choriocarcinoma?
Syncytiontrophoblasts and cytotrophoblasts
Ovarian tumor with large primitive cells and aggressive/early metastasis?
Embryonal carcinoma
Reinke crystals in female? Male?
Sertoli-leydig tumor in both
Meigs syndrome?
Fibromas, pleural effusion and ascites
Drug that causes digit hypoplasia and cleft lip/palate in fetus?
Phenytoin
What type of necrosis do you see in preeclampsia?
Fibrinoid necrosis in placental vessels
Much larger uterus and higher B-hCG than expected for date of gestation.
Hydatidiform mole
Do choriocarcinomas respond well to chemo?
Yes only if the arise from the gestational pathway. If they arise from the germ cell pathway they do not
Necrotizing granulomatous inflammation of the inguinal lymphatics and lymph nodes
Lymphogranuloma venereum
Multiple reddish papules on penis. Does it progress?
Bowenoid papulosis, it is carcinoma in situ that does not progress to invasive carcinoma
Are leydig cells affected in orchitis?
No, they seemingly are never infected with anything (e.g. cryptorchidism)
What causes testicular torsion symptoms?
Vein (thin walled) is obstructed leading to congestion and hemorrhagic infarction
What is the state of the cremasteric reflex in testicular torsion?
Absent
Is it a patent tunica vaginalis that allows hydrocele?
No, processus vaginalis
What types of testicular tumors are there generally?
Germ cell and sex-cord stroma tumors
Do we biopsy testicular tumors?
No, risk of seeding scrotum. We just cut them out :/
What is the most common type of testicular tumors by far?
Germ cell
Homogenous mass with no hemorrhage or necrosis in testicle with large cells that have clear cytoplasm and central nuclei
Seminoma
What histology helps to distinguish an embryonal carcinoma in a male? Gross?
Hemorrhagic mass with necrosis with histology showing primitive cells that may PRODUCE GLANDS
What cell markers are with testicular embryonal carcinoma? What may chemo do?
AFP or B-hCG and chemo may result in differentiation into another type of germ cell tumor
What symptoms might choriocarcinoma present with due to its marker?
B-hCG may cause it to present with gynecomastia (similar to LH) or hyperthyroidism (similarity with TSH)
Is teratoma malignant in males?
Yes, after puberty it is malignant
What is the most common type of germ cell tumor in males?
Mixed… No clear boundaries
Reinke crystals in male?
Leydig cell tumor
Tender/boggy prostate on DRE?
Acute prostatitis (enterics in older males, ST bugs in younger)
Does BPH increase cancer risk?
No…
Whats the problem with finasteride tx for BPH?
Takes months to produce any results
What is the Gleason grading system for prostatic adenocarcinoma based on? How does it work?
Architecture alone, not nuclear atypia. Multiple areas of tumor are assessed and a score is assigned (1-5) for two distinct areas. Higher score is worse prognosis
Type of bone lesions with prostatic adenocarcinoma? How do we know it is happening?
OsteoBLASTIC (sclerotic). ALP rises
Where does the milk line run?
Axilla to vulva
How many layers of epithelium are there in breast lobules and ducts? Name them
2- myoepithelial cells, luminal cell layer (milk production)
Subareolar mass with nipple inflammation (not malignant). What is the pathology? Major association?
Periductal mastitis.
Usually seen in smokers since smoking causes a relative Vit. A deficiency. The specialized ductal epithelium (like many specialized epithelial surfaces) is highly dependent on vitamin A. This causes squamous metaplasia of the ducts producing duct blockage and inflammation.
Periareolar mass with green-brown nipple discharge? Cells on biopsy? Malignant?
Mammary duct ectasia. Not malignant. Plasma cells on biopsy
Among fibrocystic change, which cause increased cancer risk? Most? Cysts, ductal hyperplasia, atypical hyperplasia, apocrine metaplasia, sclerosing adenosis
5x risk: atypical hyperplasia
2x risk: ductal hyperplasia and sclerosing adenosis
No risk: Cysts, APOCRINE METAPLASIA
What body metaplasia carries no increased risk for carcinoma?
Apocrine metaplasia of the breat
Benign cause of bloody nipple discharge? How to discern from malignant?
Intraductal papilloma. This still has both epithelial layers while the carcinoma has no myoepithelial cell layer (also typically the carcinoma is in a postmenopausal woman)
Describe a phyllodes tumor of the breast
Leaf like projections with overgrowth of the fibrous component. Can be malignant, but is most often benign
Why does obesity increase risk for breast cancer?
Increased aromatase in adipose tissue increases estrogen exposure.
What cancer of the breast is often detected as calcification on mammography and does not cause a mass?
DCIS
Name two benign breast conditions associated with calcification.
Fat necrosis (trauma) and sclerosing adenosis
Breast carcinoma with large, high grade cells growing in sheets with lymphocytes and plasma cells. Association? Prognosis?
Medullary carcinoma (subtype of IDC) BRCA1 mutation, good prognosis
What two main cancers does BRCA1 mutation predispose to?
Medullary carcinoma in breast and serous carcinoma in ovary/fallopian tube
Type of invasive ductal carcinoma with poor prognosis?
Inflammatory carcinoma
What breast cancer may show signet ring morphology? What else is significant?
ILC (in line carcinoma due to decreased E-cadherin)
What are the most important and useful prognostic factors for breast cancer?
Important: metastasis (but most present before this)
Useful: Spread to axillary lymph nodes
Describe BRCA1 and 2 in regard to the chromosome and associated cancers
BRCA1: c17, breast and ovarian
BRCA2: c13 breast carcinoma in males
Two associations with male breast cancer? Subtype and location that are most common?
BRCA2 and Klinefelter syndrome
Invasive ductal carcinoma (male breast doesn’t really have lobules) and subareolar
