GI

Question 1

Midgut development

Answer 1

6th week: midgut herniates through umbilical ring

10th week: returns to abdominal cavity, rotates around SMA

Question 2

Apple peel atresia

Answer 2

Vascular accident in utero:

• Intestinal atresia distal to duodenum–> bilous vomit
• SMA obstruction–> blind end to proximal jejunem, absence of part of small bowel and mesentary
• Terminal ileum distal to atresia spirals around ileocolic vessel

Question 3

Hepatoduodenal ligament

Answer 3

Connects liver to duodenum

Contains:
- Portal triad= hepatic artery, portal vein, common bile duct

• *Pringle maneuver= compress ligament between thumb and forefinger to control bleeding
• Connects greater and lesser sacs

Question 4

Gastrohepatic ligament

Answer 4

Connects: Liver to lesser curvature of stomach

Contains: Gastric arteries

Question 5

Gastrocolic ligament

Answer 5

Connects: greater curvature and transverse colon

Contains: gastroepiploic arteries (some L also contained in gastrosplenic ligament)

Question 6

Plexi in digestive tract

Answer 6

Submucosa (internal)= Meissner’s plexus
- Controls secretory activity

Muscularis externa: Auerbach’s plexus= myenteric nerve plexus
- Controls inner circular and outer longitudinal muscle layers of muscularis externa

Question 7

Hindgut supply/innervation

Answer 7

Artery= IMA

Parasympathetic innervation= Pelvic (vs Vagus for mid and foregut)

Vertebral level= L3

Structures:
- Distal 1/3 of transverse colon to upper portion of rectum

Question 8

Pectinate (dentate) line in rectum

Answer 8

Formed by endoderm (hindgut) meeting ectoderm

Above:

• Internal hemorrhoids (supplied by superior rectal (portal) and middle/inferior rectal (IVC))
• Visceral innervation: non-painful hemorrhoids
• Arterial supply= IMA (superior rectal artery)
• Adenocarcinoma
• Drains to deep lymph nodes

Below:

• External hemorrhoids (painful)
• Venous: Inferior rectal–> internal pudendal–> internal iliac–> IVC
• Arterial= internal pudendal (inferior rectal artery)
• Squamous cell carcinoma
• Drains to superficial inguinal nodes

Question 9

Hepatic zones

Answer 9

Zone 1= first affected by viral hepatitis

Zone 3= portal vein/hepatic artery—> venous drainage to hepatic vain

• Affected first by ischemia
• Contains P450 system
• Sensitive to toxic injury
• EtOH hepatitis

Question 10

Direct hernia

Answer 10

Thru Hesselbach’s triangle:

- Between inferior epigastric vessels (lateral) and medial umbilical ligament (medial)

Question 11

Hiatal hernia

Answer 11

Sliding= most common
- GE junction displaced (above diaphragm)

Paraesophageal=

• Normal GE junction
• Fundus of stomach protrudes into thorax

Question 12

Gastrin

Answer 12

Source:
- G-cells in antrum of stomach

1. Stimulates ECL (enterochromaffin-like cells) to secrete histamine–> stimulates parietal-cell acid secretion
2. Stimulates Parietal cell acid release

Stimulated by vagus nerve via GRP (vs Ach to parietal cells)

• Increased in Zollinger-Ellison syndrome
• Increased by chronic PPI use
• Stimulated by Phe, Tryptophan
• Gastrinoma: can lead to jejunal ulcers, diarrhea, abdominal pain

Question 13

CCK

Answer 13

Source: I cells in duodenum, jejunem

• increase pancreatic secretion (all types), gallbladder contractions (emptying), relax sphincter of Oddi
• Decrease gastric emptying

Question 14

Secretin

Answer 14

Source: S cells in duodenum

• Increases pancreatic bicarb secretion, bile secretion
• Decreases gastric acid secretions
• • both allow pancreatic enzymes to function

Stimulated by fatty acids in duodenum

Question 15

Somatostatin

Answer 15

Source: D cells in pancreatic islets, gastric mucosa

BLOCKS all the things! (stimulated by acid, blocked by vagal stimulation)
- Anti-growth hormone effects

Question 16

Glucose-dependent insulinotropic peptide (GIP)

Answer 16

Source: K cells in duodenum

• decrease H+ secretion
• Increase insulin release (endocrine!)
• • Oral glucose used more rapidly than equivalent by IV due to GIP secretion

Question 17

Vasoactive intestinal polypeptide (VIP)

Answer 17

Source: parasympathetic ganglia in sphincters, gallbladder, small intestine

• Moves things along in GI system
• Increases intestinal water, electrolyte secretion
• Relaxes smooth m., sphincters

Stimulated by distention, vagal stimulation
- Inhibited by adrenergic input

• • VIPoma= non-alpha, non-beta islet cell pancreatic tumor
• -> watery diarrhea, hypokalemia, metabolic acidosis (and achlorhydria)
• • Treatment= somatostatin

Question 18

Motilin

Answer 18

Source: small intestine

Produces MMCs (increased in fasting state)

** Erythromycin= motilin receptor agonist–> stimulates intestinal peristalsis

Question 19

Saliva

Answer 19

Parotid gland (IX)
Submandibular and sublingual gland (VII)
- Stimulated by sympathetic and parasympathetic activity
- Amylase–> hydrolyzes alpha1,4 linkages–> disaccharides (maltose, alpha-limit dextrins)
- HCO3- –> bacterial acid
- Lipase (also pancreatic)–> digest medium chain triglycerides—> monoglycerides

Hypotonic d/t reabsorption of ions (CFTR protein) but at high flow is isotonic due to decreased time for reabsorption

Question 20

Chief cells

Answer 20

Located in stomach

• Secrete pepsinogen
• Converted from pepsinogen–> pepsin by stomach acid
• -> cleaves polypeptides at aromatic aa sites

Question 21

Brunner’s glands

Answer 21

Duodenal submucosa

Secrete alkaline mucous

Hypertrophied in peptic ulcer disease

Question 22

Trypsinogen

Answer 22

Converted to trypsin (from zymogen)

• Enterokinase/enteropeptidase (duodenal mucosa enzyme) cleaves trypsin
• Activated trypsin cleaves more trypsinogen (positive feedback)
• • Inhibited by serum alpha-1-antitrypsin and BPTI (basic-pancreatic trypsin inhibitor)
• • Alcoholic pancreatitis= damage to acinar cell–> abnormal trypsin activation
• • Hereditary pancreatitis= mutation in trypsinogen–> not inhibited by BPTI

Question 23

Amylase

Answer 23

Salivary amylase: starts digestion
- Hydrolyzes alpha-1,4 linkages to yield disaccharides (maltose, alpha-limit dextrans)

Pancreatic amylase:
- Hydrolyzes starch in duodenum: oligosaccharides and disaccharides

Question 24

Oligosaccharide hydrolases

Answer 24

Brush border of intestine: rate-limiting step in carb digestion–> monosaccharides from oligo/di-saccharides

• • Only monosaccharides can be absorbed
• SGLT1 (Na+-dependent): glucose, galactose
• GLUT-5: facilitated diffusion of fructose
• Transport sugar to blood via GLUT-2

**D-xylose absorption test= distinguish GI mucosal damage from other malabsorption problems

Question 25

Bile

Answer 25

- Bile salts: bile acid conjugated to glycine, taurine - Phospholipids - Cholesterol - Bilirubin (conjugated heme and glucuronic acid via UDP glucuronosyl transferase) - Water and ions ** Cholesterol 7-alpha hydroxylase catalyzes rate-limiting step Functions: 1. Digest/absorb lipids/fat-soluble vitamins 2. Cholesterol excretion 3. Antimicrobial: membrane destruction via emulsification of gram-negative outer membranes * * Enterococci + Strep bovis can grow in bile

Question 26

Cimetidine Ranitidine Famotidine Nizatidine

Answer 26

H2-blockers (reversible)--> decreased parietal cell H+ secretion due to decreased histamine stimulation Tox: - Cimetidine= potent inhibitor of P450; antiandrogenic (prolactin--> gynecomastia, impotence, decreased libido); can cross BBB (confusion, dizziness, h/a) and placenta - Rantidine + Cimetidine--> decreased renal creatinine excretion

Question 27

Omeprazole, -prazole

Answer 27

Proton pump inhibitors MOA: irreversible inhibtion of H+/K+ ATPase in stomach parietal cells Use: ulcers, reflux, Zollinger-Ellison Tox: increased risk of C. diff (decreased aciditiy), pneumonia - Hip fractures, decreased Mg+2 with long-term use

Question 28

Bismuth, sucraflate

Answer 28

Bind ulcer base: physical protection - Allow HCO3- secretion to reestablish pH gradient in mucosa Use: Ulcer healing, traveler's diarrhea

Question 29

Misoprostol

Answer 29

PGE1 analog: increases production and secretion of gastric mucous, decreased acid production Use: prevent NSAID-induced peptic ulcers - Maintain PDA - Induces labor (but don't use in pregnant women before this!--> abortifactant) Tox: diarrhea

Question 30

Octreotide

Answer 30

Somatostatin analog Use: variceal bleeds, VIPoma, carcinoid tumors Tox: nausea, cramps, steatorrhea

Question 31

Antacids

Answer 31

Can affect absorption, bioavailability, urinary excretion of other drugs: alters gastric, urinary pH, delays gastric emptying ALL cause hypokalemia Overuse: - Aluminum hydroxide--> constipation, hypophosphatemia, muscle weakness, osteodystrophy, seizures - Magnesium hydroxide: diarrhea, hyporeflexia, hypotension, cardiac arrest - Calcium carbonate: hypercalcemia, rebound acid increase (can also chelate and decrease effectiveness of other drugs, like tetracycline)

Question 32

Brunner's glands

Answer 32

Submucosal glands in Duodenum

Question 33

Peyer's patches

Answer 33

Lymphoid nodules in lamina propria/submucosa of Ileum

Question 34

Vitamin/mineral absorption

Answer 34

Iron= Fe+2 in duodenum Folate+ Fats= jejunem B12 + bile acids= ileum

Question 35

ECL cells

Answer 35

Enterochromaffin-Like Cells 1. Vagal stimulation (+Phe, Tryptophan) to G cells--> gastrin released into circulation 2. Parietal cell direct stimulation (CCKb receptor) and ECL stimulation 3. ECL cells--> histamine--> H2 receptor on parietal cell--> acid

Question 36

Gastric parietal cell

Answer 36

Directly stimulated by: 1. Gastrin (via vagus stimulation of G cell)--> CCKb receptor - Activates Gq--> IP3 2. Vagal stimulation--> M3 receptor - Activates Gq--> IP3 3. Histamine (via ECL cell)--> H2 receptor - Activates cAMP production Inhibited by: 1. Prostaglandins/misoprostol - Gi--> inhibition of cAMP 2. Somatostatin - Gi--> inhibition of cAMP Lumen side: Cl- channel and H+/K+ ATPase (proton pump)

Question 37

Pancreatic secretions

Answer 37

Isotonic fluid (same K+/Na+ as serum) - Low flow--> increased Cl- (pumped out) - High flow--> increased HCO3- (stomach emptying acidic contents into duodenum offset by bicarb)

Question 38

Unconjugated bilirubin

Answer 38

Indirect bilirubin= 0.8 of bilirubin (vs 0.2 direct) - Breakdown product of heme - Elevated--> black pigment gallstones due to hemolysis Bacteria contain beta-glucuronidase--> breaks down conjugated--> unconjugated bilirubin - Brown pigment stones

Question 39

Conjugated bilirubin

Answer 39

Direct bilirubin (water soluble) - Unconjugated bilirubin taken up from bloodstream (bound to albumin)- passive - Converted to conjugated by UDP glucuronosyl-transferase

Question 40

Urobilinogen

Answer 40

Liver-excreted direct bilirubin converted by gut bacteria to urobilinogen - 80% excreted in feces - 20% moves to either: enterohepatic circulation (90%), or kidney (10%- yellow color to urine)

Question 41

Osmotic laxatives

Answer 41

Magnesium hydroxide, magnesium citrate, polyethylene glycol, lactulose - Osmotic: draw water into colon Treatment for constipation

Question 42

Infliximab

Answer 42

Monoclonal ab to TNF-alpha Use: crohn's, UC, RA Tox: infection (reactivate latent TB), fever, hypotension

Question 43

Sulfasalazine

Answer 43

Sulfapyridine (antibacterial) and 5-ASA (antiinflammatory) - Activated by colonic bacteria Use: UC, Crohn's, mild RA Tox: malaise, nausea, sulfonamide toxicity, reversible oligospermia

Question 44

Ondansetron

Answer 44

5-HT3 antagonist; acts on CTZ trigger zone in dorsal medulla (antiemetic) Use: post-op N/V, chemotherapy Tox: H/A, constipation

Question 45

Metoclopramide

Answer 45

D2 receptor antagonist (increases resting tone, contractility, LES tone, motility) - No influence on colon transport time Use: - Diabetic, post-op gastroparesis - Antiemetic Tox: - Increased parkinson effects (contraindicated in Parkinson's disease) - Restlessness, drowsiness, fatigue, depression, Nausea, diarrhea - Drug interaction with digoxin and diabetic patients - Contraindicated in small bowel obstruction

Question 46

Whipple's disease

Answer 46

Tropheryma Whipplei infection - Foamy PAS-positive macrophages in intestinal lamina propria, mesenteric nodes Presentation: - Cardiac, arthralgias, neurologic symptoms - Older men - Malabsorption

Question 47

Abetalipoproteinemia

Answer 47

Decreased synthesis of ApoB - -> inability to generate chylomicrons in intestine - -> decreased cholesterol, VLDL in bloodstream - -> fat accumulation in enterocytes Early childhood presentation: malabsorption, neurologic disease

Question 48

Intestinal stomach cancer

Answer 48

Associated with: - H. pylori infection - Dietary nitrosamines (smoked food) - Chlorhydria - Chronic gastritis - Type A blood Seen on lesser curvature: ulcer with raised margins Signs: - Virchow's node (L supraclavicular) - Sister Mary Joseph nodule (subcutaneous periumbilical mets)

Question 49

Diffuse stomach cancer

Answer 49

NOT associated with H. pylori Histo: - Signet ring cells (mucin pushes nucleus to periphery) - Stomach wall= thickened, leathery (linitis plastica) Signs: - Virchow's node (L supraclavicular) - Sister Mary Joseph nodule (subcutaneous periumbilical mets) - Krukenberg's tumor= bilateral mets to ovaries (abundant mucus, signet ring cells)

Question 50

H. pylori therapy

Answer 50

Triple: PPI, Clarithromycin, Metronidazole/amoxicillin Quad: PPI, bismuth subsalicylate, metronidazole, tetracycline

Question 51

Ulcer vs erosion

Answer 51

Ulcer= penetrates into (not thru) submucosa Erosion= does not extend thru muscularis mucosa - Acute erosions= NSAID, surgical stress, Cushing/Curling, smoking EtOH

Question 52

Ulcer complications

Answer 52

Hemorrhage: - Gastric, duodenal (posterior > anterior) - Ruptured gastric ulcer= lesser curvature (bleed from L gastric artery) - Posterior duodenal ulcer--> gastroduodenal artery Ulcer: Duodenal (anterior > posterior)

Question 53

Infectious diarrhea: microbe inoculum

Answer 53

``` Lowest: - Giardia (few) - Entamoeba, Campylobacter jejuni, Shigella (~200) - Clostridium perfringens (~500) - Vibrio parahaemolyticus (~10^6) - Salmonella (10^7) - ETEC (10^9) Highest ```

Question 54

Meckel's diverticulum

Answer 54

Five 2's: 2 inches long, 2 feet from ileocecal valve, 2% population, 2 years, 2 types of epithelia True diverticulum - Persistance of vitelline duct - May contain ectopic gastric/pancreatic mucosa (secrete acid) Symptoms: - melena (young children) - RLQ pain - Intususception - Volvulus - Terminal ileum obstruction Diagnosis: Pertechnetate study for ectopic uptake

Question 55

Angiodysplasia

Answer 55

tortuous dilation of vessels--> hematochezia - Cecum, terminal ileum, ascending colon Seen in elderly - Confirm with angiography

Question 56

Adenomatous polyp

Answer 56

Precancerous (precursor to CRC) - Malignancy associated with size, histology, dysplasia of epithelium Symptoms: - Asymptomatic - Lower GI bleed - Partial obstruction - Mucous secretory diarrhea

Question 57

Hyperplastic polyp

Answer 57

Non-neoplastic | - 50% in rectosigmoid colon

Question 58

Juvenile polyposis

Answer 58

Sporadic lesions in children < 5 years (80% in rectum) - NOT malignant if SINGLE Juvenile polyposis syndrome= multiple juvenile polyps in GI tract--> increased risk of adenocarcinoma

Question 59

Peutz-Jeghers

Answer 59

Single polyp= not malignant Peutz-Jeghers= AD syndrome, multiple nonmalignant hamartomas (can bleed, cause intussiception) - Hyperpigmented mouth, LIPS, hands, genitalia Mutation in serine/threonine kinase 11 (STK11) on Chromosome 19 - Increased risk of CRC, other malignancies

Question 60

Familial adenomatous polyposis (FAP)

Answer 60

AD mutation of APC on chromosome 5q - 2 hit hypothesis - 100% progress to CRC - 1000s of polyps, pancolonic, always in rectum Gardner's= FAP + osseous, soft tissue tumors, congenital hypertrophy of retinal pigment epithelium Turcot's syndrome= FAP + malignant CNS tumor

Question 61

Hereditary nonpolyposis coloretal cancer (HNPCC/ Lynch syndrome)

Answer 61

AD mutation in MSH2 (DNA mismatch repair gene) - 80% progress to CRC - ALWAYS in proximal colon

Question 62

Site of colorectal cencer

Answer 62

Rectosigmoid > Ascending > Descending - Ascending= exophytic mass, iron deficiency anemia, weight loss (right colon has larger diameter- less likely to see obstruction) - Descending= infiltrating mass, partial obstruction, colicky pain, hematochezia ** Rare presentation with strep bovis CEA good for monitoring recurrence (not good screening test)

Question 63

APC/beta-catenin (chormosomal instability pathway of CRC

Answer 63

Normal colon--> Loss of APC--> At-risk colon - APC maintains low beta-catenin (oncogenic), and intracellular adhesion - Decreased intracellular adhesion, increased proliferation (seen in all sporadic, most familial CRC) - See tubulovillous adenomatous polyps Loss of k-RAS--> Adenoma - Unregulated intracellular signal transduction - See increased size in polyps Loss of p53--> Carcinoma - loss required for tumorigensis

Question 64

Carcinoid tumor

Answer 64

MUST metastasize outside GI system to observe effects of 5-HT production (serotonin) - Wheezing, R-sided heart murmurs, diarrhea, flushing Originates as neuroendocrine cell "dense core bodies" (EM) in appendix, ileum, rectum Tx: - Resection - Octreotide - Somatostatin

Question 65

Hepatic encephalopathy

Answer 65

Glutamate released by neurons--> astrocytes--> convert to glutamine Neurons take glutamine: - Recycle to glutamate--> neurotransmitters - Convert to alpha-ketoglutarate--> TCA Encephalopathy= Ammonia toxicity--> depletion of glutamate and alpha-ketoglutarate--> excess glutamine - Glutamine= hyperosmolarity in neuron cell, mitochondrial dysfunction (no Alpha-ketoglutarate)--> astrocyte swelling

Question 66

Liver markers of pathology

Answer 66

AST, ALT: - Viral hep ALT > AST - Alcoholic hep AST > ALT Alk Phos: obstructive liver disease (HCC), bone disease, bile duct disease Gamma-glutamyl transpeptidase (GGT): measure if LFTs increased to rule out bone disease

Question 67

Reye's syndrome

Answer 67

Aspirin + viral infection Symptoms: - Mitochondrial abnormalities (decreased beta-oxidation d/t reversible inhibition of enxyme) - Hypoglycemia - fatty liver (microvesicular fatty change) - Vomiting, hepatomegaly, coma ONLY use aspirin in children with Kawasaki's disease

Question 68

Hepatocellular carcinoma

Answer 68

Due to: - Hep B, Hep C - Wilson's - Hemochromatosis (HLA-A3) - Alpha-1-antitrypsin - Alcoholic cirrhosis - Carcinogens (alflatoxin B1 from aspergillus--> p53 mutations (G:C--> T:A))

Question 69

Angiosarcoma

Answer 69

Malignant tumor of endothelial origin | - Associated with arsenic, polyvinyl chloride exposure

Question 70

Crigler-Najjar syndrome

Answer 70

Absent UDP-glucouronyl transferase - Early in life: patients die early Findings: - jaundice, kernicterus (bilirubin in brain) - Increased unconjugated bilirubin Tx: plasmapheresis, phototherapy - Type 2 respods to phenobarbital (increases liver enzyme synthesis)

Question 71

Dubin Johnson/Rotor syndrome

Answer 71

Conjugated hyperbilirubinemia (defective liver secretion - Benign - Black liver in Dubin-Johnson

Question 72

Gallstone ileus

Answer 72

Fistula between gallbladder and small intestine (large gallstone) - Air in biliary tree - Gallstone obstructing ileocecal valve Women, 70+ years - Symptoms= crampy abdominal pain, vomiting, abdominal distention, hard mass at ileocecal valve

Question 73

Pancreatic adenocarcinoma

Answer 73

CA-19-9 tumor marker (CEA less specific) Presents: - Abdominal pain to back - Weight loss * *Trousseau's syndrome**= migratory thrombophlebitis; redness, tenderness on palpation of extremities (CANCER) - -> hypercoagulability due to adenocarcinoma (pancreas, colon, lung)--> thromboplastin-like substance production

Question 74

Glucagonoma

Answer 74

Gluconeogenesis, lipolysis (weight loss) | Necrolytic migratory erythema, erythematous rash of groin