5/18/06

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Drugs for treating alcohol abuse

Disulfaram

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Antibiotics for use in GI

ampicillin, ciprofloxacin, doxycycline, erythromycin, metronidazile, trimethoprim-sulfa, vancomycin

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Antiinflammatories for use in GI

prednisone, sulfasalazine

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Anti-nausea drugs

Ondasetron, Prochlerperazine

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Drugs for treating colon cancer

5-fluorouracil, levamisol

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Drugs for treating Helicobacter pylori infection

Bismuth, clarithromycin, amoxicillin, tetracycline, metronidazole, omeprazole

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Laxatives

Docusate, Lactulose, Magnesium hydroxide

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Antidiarrheals

Loperamide

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Inhibitors of gastric secretion

Aluminum hydroxide, Atropine, Cimetidine, Magnesium hydroxide, Lansoprazole, Metoclopramide, Octreotide, Misoprostol, Omeprazole, Ranitidine, Sucraflate

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H2 Blockers

Cimetidine, Ranitidine, Fomatidine, Nizatidine; Uses = peptic ulcer, gastritis, mild esophageal reflux

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H2 Blocker MOA, Toxicity

Reversible block of histamine H2 receptors; (Toxicity = cimetidine inhibits P450, is antiandrogenic, and dec renal creatinine clearance); the others are ok)

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Proton pump inhibitors

Omeprazole, Lansoprazole; Uses = Peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome

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Proton pump inhibitors: MOA

irreversibly inhibits H+/K+ ATPase in stomach parietal cells

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Bismuth and Sucralate

Uses: increase ulcer healing

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Bismuth and Sucralate MOA

binds to ulcer base, provides physical protection and allows HCO3- secretion to reestablish pH gradient in mucus layer

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Misoprostol

Uses: prevents NSAID-induced peptic ulcers; maintains patent ductus arterisus; can induce labor

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Misoprostol: MOA and toxicity

PGE1 analog; increases production and secretion of gastric mucus barrier; (Toxicity = diarrhea; contraindicated in women of childbearing age d/t abortifactant potential)

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Infliximab

Uses: Crohn's disease, rheumatoid arthritis

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Infliximab: MOA, Toxicity

monoclonal Ab to TNF-a, proinflammatory cytokine; (toxicity = respiratory infxn, fever, hypotension)

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Sulfasalazine

uses: ulcerative colitis, Crohn's dz

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Sulfasalazine: MOA and Toxicity

combo of sulfapyridine (antibacterial) and mesalamine (anti-inflammatory); (toxicity = malaise, nausea, sulfonamide toxicity)

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Ondansetron

Uses: controls vomiting postoperatively and in pts on chemotherapy (you can gO ON DANCing)

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Ondansetron: MOA and Toxicity

5-HT3 antagonist; powerful central-acting antiemetic; (Toxicity = HA and constipation)

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Antacid overdose

affects absorption, bioavailability or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying

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Overdose on Aluminum hydroxide antacid

constipation ("minimum" amount of poo), hypophosphatemia, hypokalemia

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Overdose of magnesium hydroxide antacid

diarrhea (Mg = must go to bathroom), hypokalemia

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Overdose of Calcium carbonate antacid

hypercalcemia; increased rebound acid, hypokalemia

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The Boundaries of the Epiploic Foramen of Winslow (opening of lesser sac)

Hepatoduodenal ligament (anterior; containing common bile duct, common hepatic artery and portal vein); Caudate Lobe of Liver (superior); Duodenum (inferior), IVC (posterior)

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Foregut

esophagus --> common bile duct at 1st part of duodenum; pancreas is fused from dorsal/ventral buds; Blood = Celiac trunk; Nerves = vagal parasympathetics, thoracic n, splanchnic sympathetics

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Midgut

2nd part of duodenum --> splenic flexure of colon; Blood = superior mesenteric artery; Nerves = vagal parasympathetics; thoracic splanchnic sympathetics

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Hindgut

distal 1/3 of colon --> rectum & pectinate line; Blood = inferior mesenteric artery; Nerves = pelvic splanchnic (S2-S4) parasympathetics and lumbar splanchnic sympathetics

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Ectodermal derivatives in the GI system

Oropharynx (anterior 2/3 of tongue, lips, parotid gland, tooth enamel) and Anus, distal rectum (outward from pectinate line)

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Hormones of GI System

Nitrous oxide, Gastrin, CCK, Secretin, ACh (parasymp), VIP, NE (symp)

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Nitrous oxide in GI

causes smooth muscle relaxation of LES

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Gastrin in GI

secreted in response to gastric distention, vagal stimulation and AA entering the stomach; It causes gastric H+ secretion

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CCK (cholecystokinin) in GI

secreted in response to AA and FA entering duodenum; causes gallbladder contraction and pancreatic secretionof enzymes and HCO3-

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Secretin in GI

secreted in response to H+ and FAs entering duodenum; causes pancreatic secretion of HCO3- and inhibits gastric H+ secretion

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ACh parasympathetics in GI

increases saliva production; inc gastric H+ secretion, inc pancreatic enzyme and HCO3- secretion, causes gallbladder contraction; allows for gastric receptive relaxation; stimulates enteric plexuses for peristalsis; relaxes sphincters

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VIP (vasoactive intestinal peptide)

secreted by smooth muscle and nerves of intestines; relaxes intestinal smooth muscle, causes pancreatic HCO3- secretion and inhibits gastric H+ secretion

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Sympathetic NE in GI

increases production of saliva; decreases splanchnic blood flow in fight/flight response; decreases motility; constricts sphincters

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Presentation of congenital malformations of GI

all present during neonatal period EXCEPT meckel's diverticulum which can remain asymptomatic for life

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Hypertrophic pyloric stenosis

projectile vomiting, palpable knot in pyloric region

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Extrahepatic biliary atresia

dark urine, clay-colored stool, jaundice; incomplete recanalization of bile duct

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Annular pancreas

duodenal obstruction by a constrictive ring d/t abnormal fusion of ventral/dorsal pancreatic buds

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Meckel's diverticulum

persistant remnant of vitelline duct; outpouching (true diverticulum) of ileum; ulcers/bleeds; 50% contain gastric or pancreatic tissue

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Rule of 2s for meckel's diverticulum

2ft from ileocecal junction, 2 inches long, 2% of population, 2 types of ectopic tissue

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Malrotation of midgut

a/w Volvulus (twisting of intestine & obstruction); normal rotation = 270*; cecum and appendix lie in upper abdomen

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Intestinal stenosis or atresia (ex: Duodenal atresia)

a/w Down's syndrome and "double bubble" sign on xray; failure of recanalization; may cause FTT

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Hirschsprung's Disease (congenital or toxic megacolon)

failure of neural crest cells to migrate to colon; no peristalsis; bowel movement precipitated on digital exam

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Anal agenesis

no opening d/t improper formation of urorectal septum; may cause fistulas into bladder, vagina or urethra

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Esophagus composition

upper 1/3 = skeletal m; middle = skeletal/smooth m; lower 1/3 = smooth m;

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Achalasia

LES cannot relax = dysmotility in esophagus and food doesn't enter stomach (progressive dysphasia); "bird beak" appearance on barium swallow xray; 2* may occur from Chagas Disease; a/w inc risk of esophageal carcinoma

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Gastric secretion phases

Cephalic (sight, smell, taste, thought ); Gastric (entry of food into stomach); Intestinal (food entering duodenum sends feedback for gastrin secretion)

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HCL

secreted by parietal cells in fundus; stimulated by GASTRIN, HISTAMINE, VAGAL STIMULATION

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Inhibition of gastric HCL secretion

Omeprazole (PPI), Cimetidine (H2 blocker), chyme in small intestine via GIP (gastric inhib peptide) and Secretin

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Intrinsic factor

secreted by parietal cells of fundus; binds to vitamin B12 (extrinsic factor); the complex is absorbe din terminal ileum

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Pepsinogen

secreted by chief cells in stomach; it is converted to pepsin by low pH to DIGEST PROTEINS

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Gastrin

secreted by G cells of antrum and pylorus; Stimulates release of HCL from parietal cells

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Somatostatin

secreted by many cells in GI tract; has global INHIBITORY EFFECT

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Motilin

stimulates migrating motor comlexes during inter-digestive periods to flush undigested food thru GI

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Sialolithiasis

blockage of salivary gland; acute pain; usus submandibular gland or Stenson's duct of parotid; induce passage of stone w/salivation (ex: suck on lemon)

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Pleomorphic adenoma

mc salivary gland tumor; a/w radiation exposure; benign recurring mixed cell tumor of parotid; facial nerve injury; 20-40yo women

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Most common benign tumor of stomach

leiomyoma

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Esophageal variceal bleeding

a/w portal HTN (caput medusa, ascites); hemetemesis, Tx = vasopressin; do endoscopy to r/o ulcers

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Boerhaave's syndrome

complete rupture of esophagus d/t severe retching; presents as left pneumothroax; predisposition related to GERD

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Mallory-Weiss syndrome

laceration of gastroesophageal junction d/t severe retching in ALCOHOLICS

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Acute gastritis

"coffee-ground" vomitus; a/w NSAIDs, smoking, alcohol, Curling (burn) or Cushing (brain) ulcer; erosive, necrotic hemorrhage (seen in nasogastric tube)

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Chronic gastritis: Type A

fundal; autoimmune; a/w pernicious anemia; non-erosive mucosal inflammation and atropy; risk for carcinoma

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Chronic gastritis: Type B

antral; H. pylori; non-erosive mucosal inflammation and atropy; risk for carcinoma

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Gastric ulcers

70% d/t H. pylori; also a/w bile, aspirin or NSAIDs; Post-prandial bleeding and perforation; Pain with food; NOT precancerous

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Dumping syndrome

post-vagotomy; quick passage of hypertonic food into small intestine causing distention d/t osmotic flow into lumen; N/D, palpitations, sweating, lightheaded, reactive hypoglycemia; can be prevented by eating small meals and liquids separately

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Oral cancer

a/w smoking, chew, alcohol; SSC usu involving tongue; leukoplakia is a precursur lesion

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Esophageal adenocarcinoma

d/t Barrett's esophagus (GERD complication); Columnar metaplasia of esophageal squamous epithelium in distal 1/3 of esophagus; whites

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absorption in the stomach

very little water and ethanol

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absorption in the ileum

most nutrients are absorbed prior to arrival; this is a reserve for absorption if needed in a healthy person; BILE SALTS and B12 are specifically absorbed here

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absorption in the colon

there is a fixed daily capacity for H2O absorption; when it is exceted it is excreted

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Hiatal hernia

sliding form if GEJ is most common; a/w smoking, obesity, retrosternal pain (worse supine); can cause GERD

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Duodenal ulcers

90% a/w H. pylori, hypersecretion of acid, NSAIDs, ZE syndrome; coffee ground vomitus; Smooth Border w/Clean Base; black stool; Pain relieved with food; NOT precancerous

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Treatment of H. pylori

triple therapy: PPI (omeprazole) and 2 of the following Abx (clarithromycin, amoxicillin, metronidazole)

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Ischemic bowel disease

atherosclerosis of celiac artery or mesenteric artery; watershed areas at splenic flexure or rectosigmoid junction

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Diverticulitis

outpouching of colon; fecalith; usu Sigmoid colon; FALSE diverticula (pockets of mucosa and submucosa herniated thru mucosal layer)

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Appendicitis

obstruction (fecalith or lymphoid hyperplasia); periumbilical pain that moves to McBurney's point in LRQ once parietal peritoneum gets irritated; psoas or obturator sign; DDx in females = ectopic pregnancy, ovarian torsion, ruptured cyst, PID

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Small bowel obstruction versus large bowel obstruction

d/t adhesions versus the result of neoplasms

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Ileus

common cause of temporary small bowel paralysis that occurs post-operatively

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Adenocarcinoma of colon and rectum

d/t chronic inflammatory bowel dz, diet, age, familial polyposis; increased CEA (assessment not dx); Restrosigmoid tumors = annular/obstructive; Right sided = blood in stool; 3rd mc cause of cancer death (after lung, breast/prostate)

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Carcinoid tumor

arises from neuroendocrine cells and release histamine, serotonin, prostaglandins; Inc 5-HIAA in urine; flushing of face, hypotension; most commonly in appendix (also ileum, rectum, bronchus); tryptophan deficiency = niacin deficiency = Pallagra

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Diverticulosis

mc cause of bleeding from lower GI; can be differentiated from diverticulitis based on present of blood

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Osmotic diarrhea

non-absorbed solutes inc intraluminal oncotic pressure, causing an outpouring of water

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Secretory diarrhea

active ion secretion causes obligatory water loss

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Exudative diarrhea

sloughing of colonic mucosa d/t inflammation and necrosis, usu d/t infxn

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How many bugs required for diarrhea? Salmonella versus Shigella

100,000 versus 100

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Vibrio cholerae exotoxin

activates adenylate cyclase in crypt cells; an inc in cAMP activates Cl-secretory channels and Na and Water enter lumen causing osmotic diarrhea

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Shigella

shiga-toxin; bloody diarrhea w/fever up to 2wks; Tx = bismuth, ampicillin; Dx = fecal leukocytes and stool culture

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Salmonella

bloody diarrhea; Tx = supportive only, no opiates; a/w eggs or poultry; Dx = stool culture; immunocomp more susceptible

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Campylobacter jejuni

bloody diarrhea for up to 4wks; Tx = supportive or erythromycin after 7days; #1 cause of food-borne diarrhea in US (meat); a/w Guillain-Barre

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Vibrio cholerae

Watery (rice-water) diarrhea; vomiting, dehydration in 12-48hrs; d/t Toxin; Tx = supportive, no opiates

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Clostridium difficile

Watery diarrhea; Pseudomembranous colitis; Tx = metronidazole, oral Vancomycin; d/t exotoxin A, B

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Enterotoxigenic E. coli

Watery traveler's diarrhea for 3-6days; Tx = Bismuth, TMP-sulfa, Doxycycline, Ciprofloxacin (use Abx to reduce duration to 1-2days)

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Entrohemorrhagic E. coli

Bloody diarrhea d/t Shiga toxin from O157:H7 strain; Tx = supportive; a/w uncooked hamburger; Dx = culture stool

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Yersinia enterocolitica

Bloody diarrhea; Tx = supportive, no opiates; a/w food contaminated by animal feces (indistinguishable from Salmonella or Shigella)

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Rotavirus

Severe dehydrating diarrhea; vomiting; low fever; Tx = supportive only; mcc of diarrhea in INFANTS in winter (fecal oral)

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Normwalk virus

mild diarrhea; Tx = supportive; affects older kids/adults; epidemics in 3rd world (fecal oral)

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Entamoeba histolytica

phagocytoses RBCs, resistant to acid & excysts in cecum causing FLASK shaped ULCERS & Bloody diarrhea; can enter portal v. & abscess R lobe of liver, R diaphragm, lungs, brain; Tx = Metronidazole; d/t ingestion of viable cysts via fecal-oral

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Giardia lamblia

Watery, foul-smelling diarrhea for wks - months; Tx = metronidazole; Fecal-oral often transmitted via camping; the trophozoite is pair-shaped w/4 flagella and 2 nuclei resembling eyes

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Cryptosporidium

Watery diarrhea w/ large fluid loss (worse in immunocompromised); Tx = supportive;

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Inflammatory bowel diseases

Crohn's and Ulcerative colitis; d/t activation of immune system and release of cytokines/inflammatory mediators

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Crohn's disease

diarrhea, malabsorption, obstruction; "mouth to anus;" full thickness inflammation; GRANULOMAS, Cobblestone; SKIPPED areas; FISTULAS;

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Ulcerative colitis

bloody, mucus diarrhea; wt loss, toxic megacolon; COLON and RECTUM only; Mucosal inflammation, CRYPT abscess; pseudopolyps; BIG INC risk of CANCER

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Associated systemic manifestations of inflammatory bowel disease

arthritis, eye lesions, erythema nodosum, pyoderma gangrenosum, (sclerosing cholangitis = ulcerative only)

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Medical Treatment of Inflammatory Bowel Disease

Sulfasalazine, Steroids, Metronidazole

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Abetalipoproteinemia

AR; lack of ApoB; defective chylomicron assembly = enterocytes congested w/lipid; Acanthocytes ("burr" cells) in blood; NO CHYLOMICRONS, VLDL or LDL in blood;

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Celiac disease (non-tropical sprue)

Gluten sensitivity; foul, pale poo; BLUNTED intestinal VILLI; a/w HLA-B8 and DQW2; predisposition to Tcell lymphoma, GI and breast cancer

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Disaccharidase deficiency

enzyme deficiency; bacterial digestion of unabsorbed disaccharide; diarrhea, bloating; most commonly lactase deficiency

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Tropical sprue

affects small intestine; may cause vitamin deficiencies and megaloblastic anemia; possibly infectious

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Whipple's disease

systemic dz d/t Tropheryma whippelii (found in MQs); older white males w/diarrhea, wt loss, lymphadenopathy, hyperpigmentation

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Bacterial overgrowth malabsorption syndrome of small intestine

usu d/t stasis, raised pH, impaired immunity or CLINDAMYCIN therapy; causes inflammatory infiltrate in bowel wall; Tx = Abx

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Tubular adenoma

most common benign GI polyps; usu multiple and pedunculated

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Tubulovillous adenoma

GI polyps with a risk of malignancy; shares features of both tubular and villous adenomas

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Villous adenomas

highly MALIGNANT GI polyps; "sessile" tumors; finger-like projections

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Familial adenomatous polyposis

AD; 100s of polyps in colon; 100% chance of malignancy

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Turcot's syndrome

AD polyposis; w/ CNS TUMORS; 100% chance of malignancy

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Gardner's syndrome

AD polyposis; a/w soft tissue and BONE TUMORS; 100% chance of malignancy

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Peutz-Jeghers syndrome

AD polyposis; benign hamartomatous polyps is small intestine; HYPERPIGMENTED mouth, hands, genitalia; tumors in uterus, breast, ovaries, lung, stomach, pancreas; NO malignant potential

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Familial nonpolyposis syndrome

AD polyposis; Defective DNA repair causing proximal colonic lesions; 50% chance of malignancy

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Portal triad

branch of hepatic artery, branch of hepatic duct, branch of portal vein

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Portal lobule

connects three hepatocytes via their central veins

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Portal acinus

connects 2 hepatocytes via their central veins and portal triads

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Source of unconjugated jaundice

Gilbert's syndrome, Crigler-Najjar syndrome, Physiologic jaundice of newborn and Hepatitis

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Sources of conjugated jaundice

Dubin-Johnson syndrome, Obstruction of common bile duct; Hepatitis

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Glycolysis pathway

activated as food is absorbed; energy is stored as glycogen in liver

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Glycogenolysis

provides food for teh periods btw regular meals

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Gluconeogenesis

after 30hrs of fasting, all glycogen is depleted and this pathway becomes the only source of blood glucose

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Description of Glycolysis

glucose is broken down to form pyruvate and energy is released; requires 2 ATPs (gluco/hexokinase and phosphofructokinase-1)

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Rate limiting step in glycolysis

enzyme in glycolysis; Phosphofructokinase-1 (PFK1); requires ATP, (+) AMP, F2,6BP; (-)ATP, citrate

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Glucokinase (liver only) and Hexokinase (entire body)

enzyme in glycolysis; requires ATP; (-) G6P

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Pyruvate Kinase

enzyme in glycolysis; PRODUCES ATP; (+) F1,6BP; (-) alanine, phosphorylation, ATP

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Pyruvate dehydrogenase

glycolysis enzyme; (+) pyruvate, insulin, ADP; (-) NADH, acetyl-CoA, phosphorylation

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Description of Gluconeogenesis

glucose is formed after 4-6hrs of fasting; key enzymes include: Pyruvate carboxylase, Phosphoenolpyruvate carboxykinase; Fructose-1-6-bisphosphatase, Glucose-6-phosphatase

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Pyruvate carboxylase

gluconeogenesis enzyme; requires BIOTIN, CO2 and ATP; (+) acetyl-CoA

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Phosphoenolpyruvate carboxykinase (PEPCK)

gluconeogenesis enzyme; REQUIRES GTP; (+) cortisol, glucagon

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Fructose1,6bisphosphatase

gluconeogensis enzyme; (+) glucagon; (-) AMP, F2,6BP

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Glucose-6-phosphatase

gluconeogenesis enzyme; (+) glucagon

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Description of Glycogenolysis

Glucose is produced from glycogen stores after 2-3 hours of fasting; key enzymes include: Glycogen phosphorylase and phosphoglucomutase

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Glycogen phosphorylase

glycogenolysis enzyme; (+) AMP, phosphorylation

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Phosphoglucomutase

glycogenolysis enzyme; converts G1P to G6P

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Gaucher's disease

defective GLUCOCEREBROSIDASE; accumulate glucocerebroside; hepatosplenomegaly, bone erosion, "Gaucher's cells" w/wrinkled paper appearance in liver, spleen, bone marrow

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Niemann-Pick Disease

defective SPHINGOMYELINASE; "Foamy Histiocytes" in liver, spleen, nodes, skin; hepatosplenomegaly, anemia, Neuro deterioration

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von Gierke's Disease

defective Glucose-6-Phosphatase (part of GNG); accumulate glycogen in liver/kidney; Hepatomegaly, HYPOGLYCEMIA

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Cori's Disease

defective DEBRANCHING enzyme; accumulate glycogen in liver/striated muscle; Hepatomegaly, HYPOGLYCEMIA, Can't Grow

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Pompe's Disease

defective a-1,4-glucosidase (lysosomal enzyme); accumulate glycogen in liver an striated muscle; CARDIOMEGALY; death d/t heart failure b/f 3yo

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Galactosemia

defective Galactose-1-phosphate uridyl transferase; Accumulate galactose-1-phosphate in many tissues; CATARACTS, Cirrhosis, MR, FTT

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PKU

defective Phenylalanine hydroxylase; accumulate Phenylalanine; MR, cerebral myelin degeneration

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Maple Syrup Urine Disease

defective Branched chain a-ketoacid DH; cannot mebatolize Leu, Iso, Val; Neurologic sx; high mortality

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McArdle's Disease

a glycogen storage dz like von Gierke's, Pompe's and Cori's, but has no GI manifestations; it is a deficiency of muscle glycogen phosphorylation w/accumulation of glycogen in skeletal muscle

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Viral hepatitis

can lead to DIRECT hyperbilirubinemia, elevated LFTs, icterus, hepatomegaly, but NOT ascites; it ranges from multifocal hepatocellular necrosis w/Councilman bodies (HAV, HBV) to Ballooning degeneration (HBV, HCV) to Piecemeal necrosis (HCV)

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Hepatitis A

ssRNA; fecal oral; IgM anti-HAV; mild self-limiting; vaccine available; 14 day incubation

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Hepatitis B

**dsDNA**; sexual and blood transmission; Dx = HBsAg, anti-HBsAg, IgM anti-HBcAg; moderate; carrier, chronic (1-2%), cancerous states; vaccine and immune globulin available; Dane particle; has Reverse Transcriptase; 2-3 month incubation

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HBeAg

correlated with viral infectivity

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anti-HBsAg

indicative of recovery and immunity

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IgM anti-HBcAg

asks as marker for hepatitis infection during window period

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Hepatitis C

ssRNA; blood and sexual transmission; most frequent cause of transfusion-mediated hepatitis; Dx = anti-HCV; carrier, chronic (80-90%), cancerous states; no Tx or prophylaxis

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Hepatitis D

incomplete RNA, requires coinfection with HBV for replication; sexual and blood transmisson; Dx = anti-delta Ag; Severe dz; carrier states, no cancer; Tx = HBV immune globulin + vaccine

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Hepatitis E

ssRNA; fecal-oral; no diagnostic test; mild dz; no carrier, chronic, cancer state or treatement; problem in 3rd world

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Cirrhosis

liver dz characterized by fibrosis and disorganization of lobular and vascular structures d/t destruction and regeneration of hepatocytes; often leads to portal HTN

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Chronic alcoholic cirrhosis

MICRONODULAR FATTY liver; dec estrogen metabolism, dec coag factors; Jaundice, bleeding, gynecomastia, edema, ASTERIXIS (flappy hands); portal HTN, encephalopathy; MCC of cirrhosis in USA

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Wilson's Disease and cirrhosis

Decreases CERULOPLASMIN; copper deposits (liver, basal ganglia = EPS), Kayser-Fleischer rings on cornea; AR disease

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Hemochromatosis and cirrhosis

Familial; inc total Fe and dec TIBC; inc Ferritin; inc transferrin saturation; IRON DEPOSITS (liver), DM, skin pigmentation, cardiomyopathy; "Bronze Diabetes" w/inc risk of hepatocellular carcinoma

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Primary Biliary Cirrhosis

AUTOIMMUNE; Anti-mitochondrial Abs; Jaundice, pruritis, hypercholesterolemia; women, middle aged

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Posthepatic Cirrhosis

Chronic active hepatitis d/t HBV or HCV; Jaundice, pruritis; most likely cause of cirrhosis to lead to hepatocellular carcinoma

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a-1-antitrypsin deficiency and cirrhosis

AR; decreased inactivation of elastase; Jaundice, PANACINAR EMPHYSEMA, Pancreatic manifestations; More severe in homozygote (PiZZ)

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Congestive heart failure and cirrhosis

Passive congestion; "NUTMEG LIVER;" most often d/t Right heart failure

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Three major collateral circulation pathways utilized in cirrhosis pts

Esophageal varices, Hemorrhoids, Caput medusae

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Esophageal varices pathway

left gastric --> esophageal plexus --> azygous --> SVC

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Hemorrhoidal blood pathway

inferior mesenteric --> superior rectal --> inferior rectal --> IVC

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Caput medusa blood pathway

Ligamentum teres --> superficial abdominals --> SVC or IVC

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Hepatobiliary diseases

variable in presentation and etiology; cholelithiasis is common and curable w/surgery whereas hepatocellular carcinoma is much less common and usu fatal

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Cholelithiais

gallstones; fat, fertile female >40; Steatorrhea, N/V; bile duct obstruction, jaundice, possible cholangitis/cholecystitis; malignancy; +Murphy's sign; Large stones = cholesterol; Pigment stones = hemolytic anemia or excess bilirubin; MOST = Mixed stones

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Pigment gallstones (cholethiasis) occurring in kids

may be a/w congenital hemoglobinopathy (ex: sickle cell or thalassemia)

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Hepatocellular Adenoma (hepatoma)

Benign; 20-30yo F on OCPs; incidental finding d/t pain or bleed; 10% malignant; Tx = stop OCP use

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Adenocarcinoma of Gallbladder

d/t Gallstones; Obstructive jaundice and enlarged gallbladder; "Courvoisier's Law" = obstruction of common bile duct enlarges gallbladder while obstructing stones do not (d/t scarring of gallbladder)

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Most common source of hepatic malignancy

metastasis

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Hepatocellular Carcinoma

d/t cirrhosis, HBV or HCV, Aflatoxin B (peanut carcinogen); Inc AFP, Jaundice, Abdonimal distention, Ascites; Hematogenous spread

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Hematogenously spreading carcinomas

Hepatocellular and Renal cell

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Most common cause of pancreatic pathology in US?

alcohol

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Acute Pancreatitis

d/t gallstones (obstructing Ampulla of Vater) OR Alcohol abuse; Midepigastric pain radiating to back; Inc SERUM AMYLASE and lipase; hemorrhage may cause Cullen's or Grey Turner's black and blue sign; hypocalcemia; Autodigestion of pancreas

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Chronic Pancreatitis

d/t ALCOHOLISM in adults; CF in kids; Inc SERUM AMYLASE and lipase; Pancreatic CALCIFICATIONS; epigastric pain, Steatorrhea; IRREVERSIBLE, organ atrophy or pseudocyst

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Adenocarcinoma of Exocrine Pancreas

more common in smokers; invasive; "Trousseau's Syndrome" = migratory thrombophlebitis; radiating abd pain, obstructive jaundice; elevated CEA; poor Px, 50% head of pancreas; black males w/DM >60yo

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Insulinoma (endocrine pancreas)

b cell origin; "Whipple's Triad" = Hypoglycemia, CNS dysfxn, reversal w/Glucose; most common islet cell tumor

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Gastrinoma (Zollinger-Ellison Syndrome)

Gastrin-secreting tumor (islet cell origin); causes recurrent peptic ulcers; part of MEN1

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Presence of C-peptide in blood

helps distinguish endogenous insulin secretions (as in insulinoma) from exogenous insulin administration (as seen in Munchausen's syndrome)

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MEN1 (aka Wermer's syndrome) involves:

neoplasia or hyperplasia of pancreas, the parathyroid and the pituitary

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Layers of digestive tract

mesentery, serosa (support), "M"yenteric/Auerbach's plexus, outer longitudinal &inner circular muscles ("M"otility), submucosa (support) & "S"ubmucosal/Meissner's plexus (secretions); muscularis mucosae (motility), lamina propria (support), villi (inc SA)

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Myenteric plexus

coordinates motility along entire gut wall; aka Auerbach's; contains cell bodies of parasymp terminal effector neurons; btw inner (circular) and outer (longitudinal) layers of smooth muscle of GI wall

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Submucosal plexus

regulates local secretions, blood flow and absorption; aka Meissner's plexus; contains cell bodies of parasymp terminal effector neurons; located btw mucosa and inner (circular) layer of smooth muscle of GI wall

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Brunner's glands

secrete alkaline mucus; located in submucosa of DUODENUM (the only GI submucosal glands); duodenal ulcers cause hypertrophy of these glands

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Sinusoids of liver

irregular capillaries w/round pores; no basement membrane; allows macromolecules of plasma full access to surface of liver cells thru space of Disse

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Peyer's patch

unencapsulated lymphoid tissue in lamina propria and submucosa of SMALL INTESTINE; M cells make antigen; Stimulated B cells differentiate into IgA-secreting plasma cells

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IgA

produced by plasma cells in Peyer's patches of small intestin; it is transported across epithelium to gut to deal with intraluminal antigens

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Structures perforating diaphragm: I 8 10 EGgs at 12

I = IVC at 8th vertebra; EG = esophagus at 10th; A = aorta, azygous, T = thoracic duct all at 12th vertebra

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Abdominal layers

peritoneum, extraperitoneal tissue, transversalis fascia, transversus abdominus, internal oblique, external oblique, quadratus lumborum, latissimus dorsi, psoas erector spinae; rectus abdominus and sheath; IVC, aorta, sympathetic trunk, superficial fascia

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Lymph drainage of everything besides right arm and right half of head

thoracic duct

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Stomach's main blood supply

celiac trunk as L gastric artery; the R gastric artery branches off of celiac trunk's hepatic artery; R gastroepiploic artery comes from gastroduodenal; L gastroepiploic from splenic artery

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Retroperitoneal structures

2nd, 3rd, 4th part of duodenum; descending and ascending colon; kidneys and ureters; pancreas (except tail); aorta; IVC; adrenal glands and rectum

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Pectinate line

where hindgut meets ectoderm

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Internal versus External hemorrhoid innervation

visceral (painless) versus somatic (painful)

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Above pectinate line

internal hemorrhoids; adenocarcinoma; Visceral innervation; Superior rectal artery (branch of IMA); Venous drainage to superior rectal v --> inferior mesenteric vein --> PORTAL SYSTEM

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Below pectinate line

external hemorrhoids (painful); Squamous cell carcinoma; Somatic innervation; Inferior Rectal Artery (from internal pudendal a); Venous drainage = Inferior rectal v --> Internal Pudendal v --> Internal iliac v --> IVC

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Abdominal Hernias: MDs don't LIe

Medial to inferior epigastric artery = Direct hernia; Lateral to inferior epigastric artery = Indirect hernia

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Direct Hernia

protrudes thru Inguinal (Hesselbach's) triangle; Medial to inferior epigastric artery; Thru EXTERNAL inguinal ring ONLY; usu older men

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Indirect Hernia (IN)

INternal (deep) inguinal ring and external inguinal ring and INto the SCROTUM; enters internal ring LATERAL to inferior epigastric artery; occurs in INfants owing to failure of processus vaginalus to close; most common inguinal hernias

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Hasselbach's inguinal triangle

inferior epigastric artery, lateral border of rectus abdominus, inguinal ligament

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Free edge of lesser omentum contains

common bile duct, hepatic artery and portal vein

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most common primary site of oral (excluding lower lip) squamous cell carcinoma

floor of mouth (> tip of tongue, hard palate, base of tongue); usu a/w alcohol, tobacco use, HPV-16

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What are the 2 most common causes for bloody stools?

Angiodysplasia (cecum w/cystic spases d/t inc wall tension) AND Diverticulosis

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What is the most common site for GI cancer, polyps (into lumen) and diverticuli (out of lumen)?

Sigmoid colon

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mc complication of diverticuli?

diverticulosis; "L-sided appendicitis" in an old person; fistulas can cause "Colovesicle" w/air in urine stream; can rupture causing peritonitis

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Crohn's disease

80% terminal ileum, anus; fistulas, segmental, transmural inflammation, colicky pain in YOUNG person d/t narrow lumen, cobblestone, non-caseating GRANULOMAS, ulcers, dilated proximal bowel, string sign, mouth to anus

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Ulcerative colitis

RECTUM (lower bowel only), bloody diarrhea, non-segmenta, mucosa/submucosa only, PANCLOLITIS = greatest risk for cancer; Pseudopolyps (remnants of mucosa btw ulcers); HLA-B27; Sclerosing Cholangitis/cholangiocarcinoma

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Intussusception

telescoping of a bowel segment into a distal segment; can compromise blood supply

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Volvulus

a twisting of a portion of bowel around its mesentery; can lead to obstruction

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Stomach cancer is almost always...and spreads to...and is a/w...and is given this term when diffusely infiltrative

adenocarcinoma; Supraclavicular node (Virchow's node) and Ovary (Krukenberg's tumor); dietary nitrosamines, achlorhydria, chronic gastritis; linitis plastica

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Colonic polyps are most commonly...

benign hyperplastic hamartomas in the sigmoid colon

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Tubular adenoma colonic polyps

look like strawberry on a stalk; they are precancerous; if >2cm they are more likely to become malignant;

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Juvenile polyp

a hamartoma located in rectum (can come out of butt)

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Internal hemorrhoid in adult

prolapse, not painful, coats stool with blood

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External hemorrhoid

painful, thrombosed

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Villous adenoma colonic polyp

most malignant polyp (50% progress to cancer); found in rectum/sigmoid colon; MUCUS is seen on stool

🗑

Familial polyposis

>100 polyps; AD; APC suppressor gene (ras and p53 also involved); 100% chance of cancer, must prophylactically remove bowel; expressed in adult life

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Peutz-Jeghers polyposis

benign; not a risk for cancer; hyperpigmented mouth, hands, genitalia

🗑

Turcot's syndrome has colonic polyps and

Brain tumors; malignancy approaches 100%; AD

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Gardner's syndrome has colonic polyps and

bone and soft tissue tumors; malignancy approaches 100%; AD

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Left sided colon cancer causes...

obstruction (smaller lumen) w/alternating diarrhea and constipation; the cancer is typically annular

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Right sided colon cancer causes...

bleeds; the larger diameter allows polyps to grow; pt can have Fe deficiency

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CEA is a tumor marker in colon cancer that is primarily used to...

follow recurrence; pts should eat fiber to decrease lithocolic acid

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Appendicitis in kids is a/w

viral infections (measles, adenovirus) causing hyperplasia of lymphoid tissue

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Appendicitis in adults is a/w

fecoliths (similar to diverticulitis); causes ischemia, E.coli and inflammation

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Bilirubin metabolism; the majority (99%) of bilirubin is in the _ form

unconjugated form d/t destruction of old RBCs; it binds albumin and goes to liver

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Liver conjugation depends on _ to become water soluble

CYP450; this is direct bilirubin; it shouldn't have access to bloodstream in liver; it travels to gallbladder --> common bile duct --> small intestine --> colonic bacteria

🗑

Colonic bacteria turns conjugated/direct bilirubin into...and then....which is oxidized into...

unconjugated bilirubin --> colorless urobilinogen --> urobilin (which colors stool; and some goes to kidney to color urine)

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Obstruction of the common bile duct will result in...

pale stool

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Jaundice d/t an excess of "unconjugated" bilirubin (~20% conjugated)

this is the result of hemolytic anemia (spherocytosis, sickle cell, ABO/Rh incompatability, enzymes)

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Jaundice d/t "mixed" bilirubin (20-50% conjugated)

this form is caused by Hepatitis; there is inflammation of the entire liver, so it doesn't want to take up the unconjugated form, yet necrosis of hepatocytes/damage to the bile ducts releases conjugated form

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Jaundice d/t "conjugated" bilirubin (>50% conjugated)

this form is d/t OBSTRUCTION; Intrahepatic cholestasis (blocked portal triads); Extrahepatic cholestasis (gallstone in common bile duct); Carcinoma of head of pancreas (complete bile duct obstruction); bile backs up into liver/blood = DARK PEE, LIGHT POO!

🗑

Gilbert's disease

2nd mc cause of jaundice; AR; UNCONJUGATED; pt can't take up conjugated bilirubin b/c low UDP-glucuronyl transferase; FASTING causes jaundice (get baseline bilirubin and it should double in 24hrs); benign condition

🗑

the most common cause of jaundice is...

Hepatitis A

🗑

Dubin-Johnson syndrome

can't get rid of CONJUGATED bilirubin; turns liver black; benign condition

🗑

Transaminases are a/w

liver cell necrosis; ALT is specific to liver, AST is mitochondrial, but present in muscle, RBCs and liver

🗑

When a pt has ALT > AST, what is the diagnosis?

Viral hepatitis

🗑

When a pt has AST > ALT, what is your differential?

cirrhosis, hepatitis, fatty change

🗑

What can an elevated GGT tell you?

there is obstruction of bile ducts; pt probably has damage d/t alcohol (enzyme located in smooth ER of hepatocytes)

🗑

What can an elevated AlkPhos tell you?

since it is present in bone, placenta and liver, you MUST see an elevated GGT to diagnose an OBSTRUCION of bile ducts

🗑

The severity of liver disease?

albumin will be low and PT will be prolonged b/c liver can no longer keep synthesize normal proteins

🗑

What does the presence of anti-mitochondrial antibody tell you?

the liver disease is a primary biliary cirrhosis

🗑

Elevated AFP in a liver patient is...

elevated in hepatocellular carcinoma

🗑

What markers are present in acute HBV infection?

s Ag, e Ag, HBV DNA, core IgM Ab

🗑

What is present in the window/recovery period in HBV infection?

core IgM Ab

🗑

What is present in a pt who has recovered from HBV?

core IgG and s Ag

🗑

What is present in a pt vaccinated against HBV?

surface Ab

🗑

What will be present in a chronic (>6mo) non-infective HBV patient?

core IgM Ab, surface Ag

🗑

What will be present in a chronic (>6mo) infective HBV pt?

surface Ag, e Ag, HBV DNA, core IgM Ab

🗑

What are the protective viral hepatitis antibodies?

anti-HAV IgG, surface Ab to HBV, anti-HEV Ab

🗑

A definitive host harbors what forms of a parasite?

sexually active ADULT worms that can lay eggs

🗑

An intermediate host harbors what forms of a parasite?

larval forms

🗑

Sheepherder's Hydatid disease is a/w

Echinoccus granulosus that resides in sheepdogs in the adult form; herder acquires eggs from petting dog and the larva infect human; ruptured cysts can cause anaphylactic shock

🗑

Tinea solium hydatid disease is a/w

pig tapeworms; the larvae exist in undercooked meat and are ingested by human definitive host; the host passes eggs to family members and the larvae then form cystocircosis that penetrate bowel, eye, brain, and can cause seizures

🗑

Nutmeg liver is a term that describes infarcts that occur in the...

posthepatic vasculature (ex: hepatic vein that drains liver); usu a/w RHF or Birth control pills

🗑

Budd Chiari Syndrome

occlusion of prehepatic (IVC) or posthepatic (hepatic vv) with centrilobular congestion/necrosis; can cause hepatomegaly, ascites, abd pain, liver failure; a/w POLYCYTHEMIA RUBRA, pregnancy, hepatocellular carcinoma

🗑

A thrombus in the portal vein will cause...

ascites d/t portal hypertension; not a nutmeg liver; these pts have varices, etc

🗑

What does alcoholism do to the liver?

causes reversible fatty change; elevates NADH, acetate and acetyl-CoA

🗑

Why would fatty change cause acidosis?

NADH (pyruvate --> lactate --> met acidosis/fasting hypoglycemia) AND acetyl-CoA (ketone bodies/acetoacetic acid inc anion gap acidosis & elevate TGs)

🗑

Alcoholic hepatitis

Mallory bodies; very bad; encephalopathy, PMN leukocytosis; AST>ALT; systemic; damage is d/t ptn-bound Acetaldehyde; ETO CELLS store vit A, but begin to form collagen ==> Fibrous tissue charachteristic of dz state

🗑

Cholestasis

Hi ALT/GGT; green liver, blocked common bile duct, backs conjugated bilirubin into liver & enters urine; NO UROBILINOGEN in urine, only CONJUGATED bilirubin = very YELLOW pee & LIGHT poo; hypercholesterolemia d/t back up & itchy skin d/t bile salt reflux

🗑

What is the most likely cholestasis d/t ulcerative colitis?

primary sclerosing cholangitis; it is the mcc of cholangiocarcinoma in US; a/w bloody diarrhea

🗑

What is the most common cause of cholangiocarcinoma in the 3rd world?

Clonorchis sinesis (chinese liver fluke)

🗑

50yo female, generalized itching, not jaundiced, very hight AlkPhos/GGT, large liver, normal bilirubin w/slightly elevated AST/ALT; what is it?

Primary Biliary Cirrhosis; run a test to detect anti-mitochondrial Ab; dz is d/t granulomatous autoimmune destruction of bile ducts in portal triads (takes yrs to decompensate & cause jaundice)

🗑

What do birth control pills and anabolic steroids have in common when it comes to liver disease?

they both can cause Intrahepatic Cholestasis AND Liver cell/hepatic Adenomas

🗑

Intrahepatic cholestasis

benign jaundice w/elevated AlkPhos/GGT in OCP/anabolic steroid user; mcc of jaundice in pregnancy d/t estrogen effect

🗑

Liver cell/hepatic Adenoma

serious emergency caused by steroid/OCP use; these are glandular masses that can rupture, cause intraperitoneal hemorrhage, hypotensive crises and death

🗑

What is the diagnosis: a diffusely pigmented adult with type I diabetes?

Hemochromatosis "bronze diabetes" d/t iron overload

🗑

Hemosiderosis

an acquired Fe overload d/t alcohol; can cause generalized bronzing of skin

🗑

Hemochromatosis

AR, hemosiderin deposition in liver (micronodular cirrhosis)/pancreas (fibrosis)/skin d/t OH-free radicals; HIGH risk for HEPATOCELLULAR carcinoma

🗑

What is the typical lab profile for Hemochromatosis pts? Tx?

Hi Fe, Hi Ferritin, Hi % saturation, Low Transferrin synthesis, Low TIBC; Tx = Phlebotomy or Deferoxamine

🗑

Associated conditions with hemochromatosis

Pancreatic malabsorption/type I diabetes; Skin stimulation of melanocytes/dark pigment; Joints get OA; Restrictive cardiomyopathy

🗑

Wilson's disease is a condition where

pt cannot get rid of copper d/t low levels of CIRULOPLASMIN (which normally binds 95% of Cu); so, total copper will be LOW and free copper will be HI; Keyser-Fleisher rings, hepatolenticular dz, movement disorder

🗑

How do you treat Wilson's Disease?

Penicillamine

🗑

Cirrhosis

never focal, always DIFFUSE; bumps = regenerative nodules (<3cm micro d/t etoh, >3 macro d/t infxn, drugs, risk for HEPATOCELLULAR carcinoma); Liver regenerates non-functional tissue which causes portal HTN

🗑

Signs of portal hypertension

pitting edema, varices, gynecomastia/impotence (can't metabolize estrogens); ascites w/spontaneous peritonitis (G- rods, E. coli in Adults, S. pneumoniae in Kids)

🗑

Portocaval shunt exists between...

splenic vein and left renal vein; may relieve portal HTN

🗑

When is enlarged breast tissue normal in males?

newborns, at puberty, old age

🗑

Hepatocellular carcinoma

most often develops on top of cirrhosis (Hemochromatosis or Hepatits B or C); nodularity, pale; Ectopic hormones, AFP tumor marker

🗑

What are the ectopic hormones produces in hepatocellular carcinoma? what is the tumor marker?

erythropoeitin (2* polycythemia) and insulin-like growth factor; AFP

🗑

What do you do with a pt who is getting worse, has wt loss and a hemorrhagic ascitic peritoneal tap?

run a AFP b/c pt probably has hepatocellular carcinoma

🗑

Pathogenesis of cholesterol gallstones

too much cholesterol too little bile salts (cirrhosis, crohn's, cholestyamine, obstruction) = yellow stone

🗑

25yo female with gallstones, normocytic anemia and splenomegaly, what does she have?

congenital spherocytosis; suprasaturated bilirubin forms BLACK Ca-bilirubinate stones

🗑

What is best screen for gallstones?

ultrasound

🗑

What is best screen to see pancreas?

🗑

Cystic fibrosis

Chrom 7 (3 nucleotide deletion causes Phe deficiency in CFTR and golgi can't modify it, so receptor is degraded) pt loses salt (sweat test), has diabetes type I d/t fibrosis of islets, and growth retardation

🗑

Why are CF secretions so thick?

CFTR should add salt back to the secretions to keep them viscous; deficiency sucks Na out and no Cl goes in

🗑

MCC of death in CF pts?

pseudomonas infxn

🗑

Are CF pts fertile?

0-5% of males, 30% females d/t thick cervical mucus

🗑

What are the 2 mcc of Acute pancreatitis

alcohol AND stone in pancreatic duct; presents as epigastric pain that radiates to back; bowel stops peristalsing at duodenum d/t inflammation (sentinal sign on xray w/air fluid level showing); enzymes autodigest pancreas

🗑

Pt has h/o acute pancreatitis, 10 days later a mass is felt; what do you order?

CT to see if a pseudocyst developed from the inflamed pancreas

🗑

Chronic pancreatitis

d/t alcohol; presence of dystrophic CALCIFICATIONS, RUQ pain, steatorrhea d/t malabsorption, no bile salt deficiency, hemorrhagic diasthesis d/t vit K deficiency from malabsorption

🗑

Where are the 2 most common locations for sentinal signs of inflammation on xray in a GI pt?

duodenum (d/t acute pancreatitis) and Appendicitis; both cause "localized ileus" when peristalsis stops

🗑

What are the 2 mcc of Carcinoma of the head of the pancreas

smoking AND chronic pancreatitis; causes PAINLESS JAUNDICE d/t conjugated bilirubin; LIGHT POO, palpable gallbladder (Courvassier's sign); "C-sign" on barium swallow in duodenum

🗑

Secondary biliary cirrhosis

d/t extrahepatic biliary obstruction; inc pressure in hepatic ducts causing injury/fibrosis; bacterial ascending cholangitis

🗑

Reye's syndrome

a/w use of aspirin to treat viral infxn (VZV or Hib); fatal childhood hepatoencephalopathy; fatty liver, hypoglycemia, coma

🗑

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