Gastrointestinal

The functional unit of the liver is made up of hexagonally arranged lobules surrounding the central vein with portal triads on the edges (consisting of a portal vein, hepatic artery, bile ducts, as well as lymphatics).- Apical surface of hepatocytes faces bile canaliculi. Basolateral surface faces sinusoids.- Kupffer cells, which are specialized macrophages, are located in the sinusoids.- Hepatic stallate (Ito) cells in space of Disse store vitamin A (when quiescent) and produce extracellular matrix (when activated). Responsible for hepatic fibrosis. Zone I – periportal zone:- Affected 1st by viral hepatitis- Ingested toxins (eg, cocaine)Zone II – intermediate zone:- Yellow feverZone III – pericentral vein (centrilobular) zone:- Affected 1st by ischemia- High concentration of cytochrome P-450- Most sensitive to metabolic toxins (eg, ethanol, CCl4, halothane, rifampin)- Site of alcoholic hepatitis

Gallstones that reach the confluence of the common bile duct and pancreatic ducts at the ampulla of Vater can both block the common bile and pancreatic ducts (double duct sign), causing both cholangitis and pancreatitis, respectively. Tumors that arise in the head of pancreas (usually ductal adenocarcinoma) can cause obstruction of the common bile duct → enlarged gallbladder with painless jaundice (Courvoisier sign). Cholangiography shows filling defects in gallbladder and cystic duct.

Lateral to median: Nerve-Artery-Vein-Lymphatics Femoral triangle: Contains femoral nerve, artery, vein Femoral sheath: Fascial tube 3-4 cm below inguinal ligament. Contains femoral vein, artery, and canal (deep inguinal lymph nodes) but not femoral nerve.

↑ smooth muscle relaxation, including lower esophageal sphincter (LES). - Loss of NO secretion is implicated in ↑ LES tone of achalasia.

Unencapsulated lymphoid tissue found in lamina propria and submucosa of ileum. Contain specialized M cells that sample and present antigens to immune cells. - B cells stimulated in germinal centers of Peyer patches differentiate into IgA-secreting plasma cells, which ultimately reside in lamina propria. IgA receives protective secretory component and is then transported across the epithelium to the gut to deal with intraluminal antigen.

Composed of bile salts (bile acids conjugated to glycine or taurine, making them water soluble), phospholipids, cholesterol, bilirubin, water, and ions.- Cholesterol 7α-hydroxylase catalyzes rate-limiting step of bile acid synthesis. Functions:- Digestion and absorption of lipids and fat-soluble vitamins- Cholesterol excretion (body's 1° means of eliminating cholesterol)- Antimicrobial activity (via membrane disruption) ↓ absorption of enteric bile salts at distal ileum (as in short bowel syndrome, Crohn disease) prevents normal fat absorption. Calcium, which normally binds oxalate, binds fat instead, so free oxalate is absorbed by gut → ↑ frequency of calcium oxalate kidney stones.

Heme –heme oxygenase→ biliverdin.Biliverdin –biliverdin reductase→ unconjugated bilirubin. Unconjugated bilirubin is removed from blood by liver, conjugated with glucuronate, and excreted in bile. Indirect bilirubin – unconjugated, water insoluble.Direct bilirubin – conjugated with glucuronic acid, water soluble. Gut bacteria convert conjugated bilirubin to urobilinogen. - 80% of urobilinogen is excreted in feces as stercobilin (→ brown color of stool)- From the rest 20%, 10% is excreted in the urine as urobilin (→ yellow color) and 90% undergoes enterohepatic circulation.

Stone(s) in salivary gland duct. Can occur in 3 salivary glands (parotid, submandibular, sublingual). - Primarily in the submandibular gland (Wharton duct), especially single stones (~80% of cases).- Parotid gland (~20% of cases) Presentation:- Sudden, recurrent pre-/periprandial pain - Swelling in affected gland Caused by dehydration or trauma. Treat conservatively with NSAIDs, gland massage, warm compresses, sour candies (to promote salivary flow). Sialadenitis – inflammation of salivary gland due to obstruction, infection, or immune-mediated mechanisms.

Associated with caustic ingestion and acid reflux.

Dilated submucosal veins in lower 1/3 of esophagus 2° to portal hypertension. Common in cirrhotics, may be source of life-threatening hematemesis.

Associated with reflux, infection in immunocompromised (Candida: white pseudomembrane; HSV-1: punched-out ulcers; CMV: linear ulcers), caustic ingestion, or pill esophagitis (eg, bisphosphonates, tetracycline, NSAIDs, iron, and potassium chloride).

Esophageal smooth muscle atrophy → ↓ LES pressure and dysmotility → acid reflux and dysphagia → stricture, Barrett esophagus, and aspiration.  Part of CREST syndrome.

Due to chronic pancreatitis, cystic fibrosis, obstructing cancer. - Causes malabsorption of fat and fat-soluble vitamins (A, D, E, K) as well as vitamin B12. ↓ duodenal pH (bicarbonate) and fecal elastase.

Similar findings as celiac sprue (affects small bowel), but responds to antibiotics.- Cause is unknown, but seen in residents of or recent visitors to tropics. ↓ mucosal absorption affecting duodenum and jejunum but can involve ileum with time.  - Associated with megaloblastic anemia due to folate deficiency and, later, B12 deficiency.- Fecal fat 10-40 g/d (normal <5 g/d) Treatment: Tetracycline in combination with folic acid for 3-6 months

Fibrous band of scar tissue; commonly forms after surgery. Most common cause of small bowel obstruction. Demonstrated by multiple dilated small bowel loops on x-ray.

Also known as 1° bacterial peritonitis.Bacterial infection of ascitic fluid in the absence of other intra-abdominal causes (which would otherwise lead to secondary bacterial peritonitis). Etiology:- Common in patients with cirrhosis and ascites.- Common in patients receiving peritoneal dialysis.- Bacterial species: aerobic gram ⊝ organisms (eg, E coli, Klebsiella) or less commonly gram ⊕ streptococcus. Presentation:- Often asymptomatic- Fevers, chills, abdominal pain, tense abdominal wall, ileus, worsening encephalopathy. Diagnosis: Paracentesis with ascitic fluid absolute neutrophil count (ANC) > 250 cells/mm3. Empiric first-line treatment is 3rd generation cephalosporin (eg, cefotaxime).

Presence of gallstone(s) in common bile duct. - Colicky, epigastric pain- Nausea, vomiting- Extrahepatic cholestasis→ obstructive jaundince, pale stool, dark urine→ pruritus - Often leads to elevated ALP, GGT, direct bilirubin and AST/ALT

Calcified and fibrotic gallbladder due to chronic cholecystitis.- Usually found incidentally on imaging. Pathogenesis is due to dystrophic intramural deposition of calcium salts in the set of chornic inflammation. Gross findings: bluish, brittle, thickened gallbladder wall with a "crunchy" texture.Microscopic findings: calcified plaques within the muscularis or spotty calcification in the mucosa. - Treatment: prophylactic cholecystectomy due to high rates of gallbladder cancer (mostly adenocarcinoma).

Infection of biliary tree Etiology:- Obstruction (eg, biliary lithiasis, stenosis, malignancy) that leads to stasis/bacterial overgrowth.- May follow cholecystitis - Ascending infection after manipulation of the bile tract (eg, papillotomy, stent-placement, post-ERCP) Charcot triad of cholangitis:- RUQ pain- Fever- Jaundice Reynolds pentad is Charcot triad plus altered mental status and shock (hypotension). Associated with ↑ mortality.

Acute or chronic inflammation of gallbladder. Calculous cholecystitis – most common type; due to gallstone impaction in the cytic duct resulting in inflammation and gallbladder wall thickening; can produce 2° infection.- Commonly: E coli, Klebsiella, EnterobacterAcalculous cholecystitis – due to gallbladder stasis, hypoperfusion, or infection (CMV); seen in critically ill patients. Presentation:- RUQ pain: More severe and prolonged (>6 hours) than in cholelithiasis, worse after meals, may radiate to right shoulder (due to irritation of phrenic nerve).- Guarding- Murphy sign: inspiratory arrest on RUQ palpation due to pain. - ↑ ALP if bile duct becomes involved (eg, ascending cholangitis) Diagnosis: - Ultrasound or cholescintigraphy (HIDA scan). Failure to visualize gallbladder on HIDA scan suggests obstruction.- Wall thickening >4 mm- Double wall sign Gallstone ileus – fistula between gallbladder and GI tract → stone enters GI lumen → obstructs at ileocecal valve; can see air in biliary tree (pneumobilia). Treatment: Piperacillin-tazobactam, ampicillin, meropenem (life-threatening cases); alternatively 3rd generation cephalosporin + metronidazole

Foregut – esophagus to upper duodenumMidgut – lower duodenum to proximal 2/3 of transverse colonHindgut – distal 1/3 of transverse colon to anal canal above pectinate line Midgut development:- 6th week – physiologic midgut herniates through umbilical ring- 10th week – returns to abdominal cavity + rotates around superior mesenteric artery (SMA), total 270° counterclockwise

Developmental defects due to failure of rostral fold closure (eg, sternal defects [ectopia cordis]), lateral fold closure (eg, omphalocele, gastroschisis), or caudal fold closure (eg, bladder exstrophy) Gastroschisis:- Extrusion of abdominal contents through abdominal folds (typically right of umbilicus)- Not covered by peritoneum or amnion- Not associated with chromosome abnormalities Omphalocele:- Failure of lateral walls to migrate at umbilical ring → persistent midline herniation of abdominal contents into umbilical cord- Surrounded by peritoneum (light gray shiny sac)- Associated with congenital abnormalities (eg, trisomies 13 and 18, Beckwith-Wiedemann syndrome) and other structural abnormalities (eg, cardiac, GU, neural tube) Congenital umbilical hernia: Failure of umbilical ring to close after physiologic herniation of the intestines. Soft, nontender bulge at umbilicus. Protrudes with increased abdominal pressure. Typically reducible. Small defects usually close spontaneously.

Presents with bilious vomiting and abdominal distension within first 1-2 days of life. Duodenal atresia – failure to recanalize at 8-10 weeks of gestation. Associated with "double bubble" (dilated stomach, proximal duodenum) on x-ray. Associated with Down syndrome. Jejunal and ileal atresia – mesenteric vessel occlusion → ischemic necrosis → segmental resorption (bowel discontinuity or "apple peel").- Risk factor: Vasoconstrictive drugs during pregnancy (eg, cocaine MDMA)

Pancreas – derived from foregut. Ventral pancreatic buds contribute to uncinate process and main pancreatic duct. The dorsal pancreatic bud alone becomes the body, tail, isthmus, and accessory pancreatic duct. Both the ventral and dorsal buds contribute to pancreatic head. Annular pancreas – abnormal rotation of ventral pancreatic bud forms a ring of pancreatic tissue → encircles 2nd part of duodenum; may cause duodenal narrowing and vomiting. Pancreas divisum – ventral and dorsal parts fail to fuse at 8 weeks. Common anomaly, mostly asymptomatic, but may cause chronic abdominal pain and/or pancreatitis. Spleen – arises in mesentery of stomach (hence is mesodermal) but has foregut supply (celiac trunk → splenic artery).

Hirschsprung disesase:- Associated disorder: Down syndrome- Typical level of obstruction: Rectosigmoid- Meconium consistency: Normal- "Squirt sign": Positive Meconium ileus:- Associated disorder: Cystic fibrosis- Typical level of obstruction: Ileum- Meconium consistency: Inspissaed (thickened)- "Squirt sign": Negative

Vagus nerve → Ach → M3 receptor → Gq Vagus nerve → GRP → G cells → Gastrin → CCKB receptor → Gq Gastrin → ECL cells → Histamine → H2 receptor → Gs

Rare, benign liver tumor. - Often related to oral contraceptive or anabolic steroid use - May regress spontaneously or rupture (abdominal pain and shock). Histology: Enlarged hepatocytes, with small and regular nuclei, glycogen and lipid deposits.Ultrasound: Inhomogenous due to bleeding. More frequent in the right lobe.

Malignant tumor of endothelial origin. - Associated with exposure to arsenic (eg, exposure to pesticides), vinyl chloride (a plastic widely used in industry). - Immunohistochemical staining is positive for CD31, which is PECAM1 (functions in leukocyte migration through the endothelium)

- GI malignancies - Breast cancer - Lung cancer Hypodense on CT.

In cystic fibrosis, meconium plug obstructs intestine, preventing stool passage in the first 24-48 after birth. Clinical findings:- Bilious vomiting- Abdominal distension - Abdominal x-ray: dilated small-bowel loops, microcolon Treatment: Enema

Esophagus: Nonkeratinized stratified squamous epithelium. Stomach: Gastric glands. Duodenum: Villi and microvilli ↑ absorptive surface. Brunner glands (HCO3--secreting cells ob submucosa) and crypts of Lieberkühn (contain stem cells that replace enterocytes/goblet cells and Paneth cells that secrete defensins, lysozyme, and TNF). Jejunum: Plicae circulares (also present in distal duodenum) and crypts of Lieberkühn. Ileum: Peyer patches (lymphoid aggregates in lamina propria, submucosa), plicae circulares (proximal ileum), and crypts of Lieberkühn. Largest number of goblet cells in the small intestine. Colon: Crypts of Lieberkühn but no villi; abundant goblet cells.

Tear in the anal mucosa below the pectinate line. Etiology:- 90% located at the posterior commissure (6 o'clock in the lithotomy position), because this area is poorly perfused.- Chronic spasm/increased tone of the internal anal sphincter- Chronic constipation or diarrhea- Anal sex- Vaginal delivery- Secondary: previous anal surgery, Crohn disease Presentation:- Pain while pooping- Blood on toilet paper

Can cause diarrhea, steatorrhea, weight loss, weakness, vitamin and mineral deficiencies. Screen for fecal fat (eg, Sudan stain). - Celiac disease- Tropical sprue- Lactose intolerance- Pancreatic insufficiency- Whipple disease

Transmission: Sexual, parenteral (needlestick, blood products), perinatal Incubation period: 1-6 months Presentation:- Serum-sickness like syndrome: rash, polyarthritis, fever- Fatigue- Jaundice- RUQ pain- Chronic: cirrhosis, polyarthritis nodosa, membranous glomerulonephritis Histology: Councilman bodies, bridging necrosis Treatment: Tenofovir (NtRI), entecavir (NRTI), PEG-IGN-α

Hepatitis A:- Hepatocyte swelling- Monocyte infiltration- Councilman bodies Hepatitis B:- Granular eosinophilic "ground glass" appearance- Cytotoxic CD8+ T cells mediate damage Hepatitis C:- Lymphoid aggregates with focal areas of macrovesicular steatosis Hepatitis E:- Patchy necrosis

Etiology:- Halogenated inhalted anesthetics- Viral hepatitis - Rapid atrophy and shrunken liver on autopsy Presentation:- Fever, anorexia, nausea, myalgias, arthralgias, rash- Tender hepatomegaly, jaundice Lab:- Elevated aminotransfase levels- Prolonged prothrombin time (deficient VII production that has shortest half-life)- Leukocytosis- Eosinophilia- Normal albumin due to the long half-life of albumin (~20 days)