Step 1 - GI 4

denniskwinn's version from 2015-04-25 16:01


Question Answer
H2 blockersCimetidine, ranitidine, famotidine, nizatidine.
H2 blocker mechanismreversible block of histamine H2 receptor - reduce H+ secretion by parietal cells
H2 blocker clinical usePeptic ulcer, gastritis, mild esophageal reflux
H2 blocker toxicityCimetidine is a potent inhibitor of P-45 0; it also has antiandrogenic effects (prolactin release, gynecomastia, impotence ↓ libido in males); can cross blood-brain barrier (confusion, diZZIness, headaches) and placenta. Both cimetidine and ranitidine ↓ renal excretion of creatinine. Other H2 blockers are relatively free of these effects.
Proton pump inhibitorsOmeprazole, Lansoprazole
Proton pump inhibitor mechanismirreversible inhibit H+/H+ ATPase in stomach parietal cells
Proton pump inhibitor clinical usePeptic ulcer, gastritis, Esophageal refluse, Z-E syndrome
Bismuth, sucralafe mechanismBind to ulcer base, providing physical protection, and allow HCO3 secretion to reestablish pH gradient in the mucous layer.
Bismuth, sucralafe clinical use↑ ulcer healing, traveler’s diarrhea
Triple therapy for H. Pylori ulcersMetronidazole, Amoxicillin, Bismuth
Misoprostol mechanismA PGE1 analog. ↑ production and secretion of gastric mucous barrier, ↓ acidProduction
Misoprostol clinical usePrevention of NSA1D-induced peptic ulcers; maintenance of a patent ductus arteriosus. - Also used to induce labor
Misoprostol toxicityDiarrhea, contraindicated in women of childbearing potential (abortifacient)
Muscarinic antagonistsPirezipine, propantheline
Muscarinic antagonist mechanismBlock M1 receptors on ECL cells (↓ histamine secretion) and M3 receptors on parietal cells (↓H+ secretion)
Muscarinic antagonist clinical usePeptic ulcer (rarely used)
Muscarinic antagonist toxicityTachycardia, dry mouth, difficulty focusing eyes
Antacid overuse problems1. Aluminum hydroxide: constipation and hypophosphatemia; proximal muscle weakness, osteodystrophy, seizures 2. Magnesium hydroxide: diarrhea, hyporeflexia, hypotension, cardiac arrest 3. Calcium carbonate: hypercalcemia, rebound acid ↑ - All can cause hypokalemia
Antacid useCan affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying
Infliximab mechanismA monoclonal antibody to TNF, proinflammatory cytokine
Infliximab clinical useCrohn’s disease, rheumatoid arthritis
Infliximab toxicityRespiratory infection (including reactivation of latent TB), fever, hypotension
Sulfasalazine mechanism A combination of sulapyridine (antibacterial) adn 5-aminosalicylic acid (anti-inflammatory). Activated by colonic bacteria
Sulfasalazine clinical useUlcerative colitis, Crohn’s disease
Sulfasalazine toxicity Malaise, nausea, sulfonamide toxicity, reversible oligospermia
Ondansetron mechanism5-HT3 antagonist - powerful central acting antiemetic
Ondansetron clinical useControl vomiting postoperatively and in patients undergoing cancer chemotherapy
Ondansetron toxicityHeadache, constipation
Metoclopramide mechanismD2 receptor antagonist, increases resting tone, contractility, LES tone, motility, Does not influence colon transport time
Metoclopramide clinical useDiabetic and post surgery gastroparesis (delayed gastric emptying)
Metoclopraminde Toxicityincreased parkinsoniian effects - restlessness, drowsiness, fatigue, depression, nausea, diarrhea. Drug interaction with digoxin and diabetic agents. Contraindicated in patient with small bowel obstruction


GI Hormones


GastrinG cells (antrum of stomach)↑ gastric H+ secretion, ↑ growth of gastric mucosa, ↑ gastric motility↑ by stomach distention, amino acids, peptides, vagal stimulation, ↓ by stomach pH < 1.5↑↑ in Zollinger-Ellison syndrome. Phenylalanine and tryptophan are potent stimulators. Main way that it increases H+ is by effecting ECL cells that release histamine which effect parietal
CholecystokininI cells (duodenum, jejunum)↑pancreatic secretion, ↑ gallbladder contraction, ↓gastric emptying ↑ by fatty acids, amino acidsIn cholelithiasis, pain worsens after fatty food ingestion due to increase
SecretinS cells (duodenum) ↑pancreatic HC03 secretion, ↓ gastric acid secretion, ↑bile secretion↑ by acid, fatty acids in lumen of duodenum↑ HCO3 neutralized gastric acid in duodenum, allowing pancreatic enzymes to function
SomatostatinD cells (pancreatic islets, GI mucosa↓gastric acid and pepsinogen secretion, ↓ pancreatic and small intestine fluid secretion, ↓ gallbladder contraction, ↓insulin and glucagon release↑ by acid, ↓ by vagal stimulationInhibitory hormone, Antigrowth hormone effects (digestion and absorption of substances needed for growth). Used to treat VIPoma and carcinoid tumor.
Glucose-dependent insulinotropic peptide (GIP)K cells (duodenum, jejunum)Exocrine: ↓ gastric H+ secretion Endocrine: ↑ insulin release↑by fatty acids, amino acids, oral glucose An oral glucose load is used more rapidly than the equivalent given by IV.
Vasoactive intestinal polypeptide (VIP)Parasympathetic ganglia in sphincters, gallbladder, small intestine↑intestinal water and electrolyte secretion, ↑ relaxation of intestinalsmooth muscle and sphincters↑by distention and vagal stimulation, ↓ by adrenergic inputVIPoma - non alpha, non beta islet cell pancreatic tumor that secretes VIP - copious diarrhea
Nitric oxide↑ smooth muscle relaxation, including lower esophageal sphincterLoss of NO secretion is implicated in lower tone of achalasia
MotilinSmall intestineProduces migrating motor complexes (MMCs)↑ in fasting state
GhrelinP/D1 cells (stomach)↑ GH, ACTH, cortisol and prolactin secretion↑ before meals, ↓ after mealsregulates hunger, meal initiation, lost following gastric bypass surgery, associated with hyperphagia in prader-willi


Biliary tract disease
DiseasePathophysiology/pathologyPresentationLabsAdditional information
Secondary biliary cirrhosisExtrahepatic biliary obstruction (gallstone biliary structure, chronic pancreatitis, carcinoma of the pancreatic head → ↑ pressure in intrahepatic ducts → injury/fibrosis and bile stasisPruritis, jaundice, dark urine, light stools, hepatosplenomegaly↑ conjugated bilirubin, ↑ cholesterol, ↑ alkaline phosphataseComplicated by ascending cholangitis and hypergammaglobulinemia
Primary biliary cirrhosisautoimmune reaction → lymphocytic infiltrate + granulomas, ↑ serum mitochondrial antibodyPruritis, jaundice, dark urine, light stools, hepatosplenomegaly↑ conjugated bilirubin, ↑ cholesterol, ↑ alkaline phosphatase ↑ serum mitochondrial antibodies - associated with other autoimmune conditions (e.g. CREST, RA, celiac disease)
CholangitisPruritis, jaundice, dark urine, light stools, hepatosplenomegaly↑ conjugated bilirubin, ↑ cholesterol, ↑ alkaline phosphataseHypergammaglobulinemia (IgM). Associated with ulcerative colitis. Can lead to secondary biliary cirrhosis


DiseasePossible etiologyLocationGross morphologyMicroscopic morphologyComplicationsIntestinal manifestationsExtraintestinal manifestationsTreatment
Crohn’s diseaseDisordered response to intestinal bacteriaAny portion of GI tract, usually in terminal ileum and colon - skip lesions, rectal sparingTransmural inflammation. Cobblestone mucosa, creeping fat, bowel wall thickening (“string sign” on barium swallow), linear ulcers, fissures, fistulasNoncaseating granulomas and lymphoid aggregatesStrictures, fistulas, perianal disease, malabsorption, nutritional depletionDiarrhea that may or may not be bloodMigratory polyarthritis, erythema, nodosum, ankylosing spondylitis, uveitis, immunologic disorderscorticosteroids, infliximab
Ulcerative colitisAutoimmuneColon inflammation, continuous colon lesions always with rectal involvementMucosal and submucosal inflammation only, friable mucosal pseudopolyps with freely hanging mesentery. Loss of haustra→”lead pipe” appearance on imagingcrypt abscesses and ulcers, bleeding, no granulomasmalnutrition, toxic megacolon, colorectal carcinomabloody diarrheapyoderma gangrenosum, primary sclerosing cholangitisASA preparations (sulfasalazine), infliximab, colectomy


GI secretory productssourceActionRegulationNotes
Intrinsic factorParietal cells (stomach)Vitamin B12 binding protein (required for B12 uptake in terminal ileum) Autoimmune destruction of parietal cells→ chronic gastritis and pernicious anemia
Gastric acidParietal cells (stomach)↓ stomach pH↑ by histamine, ACh, gastrin . . ↓ by somatostatin, GIP, prostaglandin, secretingastrinoma = gastrin secreting tumor that causes continuous high levels of acid secretion and ulcers
PepsinChief cells (stomach)Protein digestion↑ by vagal stimulation, local acidInactive pepsinogen→pepsin by H+
HCO3-Mucosal cells (stomach, duodenum, salivary glands, pancreas) and Brunner’sNeutralizes acid↑ pancreatic and biliary secretion with secretinHCO3 is trapped in mucus that covers the gastric epithelium