FAGI2

• Acute Gastritis (Erosive:
• 1. Disruption of mucosal barrier → inflammation. BCan be caused by stress, NSAIDs (↓ PGE2 →↓ gastric mucosa production), alcohol, uremiaburns (Curling’s ulcer—↓ plasma volume →sloughing of gastric mucosa), and brain injury (Cushing’s ulcer— ↑ vagal stimulation →↑ ACh →↑ H+ production).
• 2. Burned by the Curling iron.Always Cushion the brain. Especially common amongalcoholics and patients taking daily NSAIDs (e.g., patients with rheumatoidarthritis).

• Chronic Gastritis (nonerosive):
• 1. Type A (fundus/body):
• Autoimmune disorder characterized by Autoantibodies to parietal cells, pernicious Anemia, and Achlorhydria (4 A's). Associated withother autoimmune disorders.

Mnemonic: AB pairing—perniciousAnemia affects gastricBody.

• 2. Tupe B (Antrum):
• Most common type. Caused by H. pylori infection.↑ risk of MALT lymphoma.

Mnemonic: AB Pairing: H. pylori Bacterium affects Antrum.

Gastric hypertrophy with protein loss, parietal cell atrophy, and ↑ mucous cells. Precancerous. Rugae of stomach are so hypertrophied that they look like brain gyri.

• Gastric Ulcer:
• Pain can be Greater with meals—weight loss. Often occurs in older patients.H. pylori infection in 70%; chronic NSAID use also implicated.Due to ↓ mucosal protection against gastric acid.

• Duodenal Ulcer:
• Pain Decreases with meals—weight gain. Almost 100% have H. pylori infection.Due to ↑ gastric acid secretion (e.g., Zollinger-Ellison syndrome) or ↓ mucosal protection. Hypertrophy of Brunner’s glands.Tend to have clean, “punched-out” margins unlike the raised/irregular margins of carcinoma. Potential complications include bleeding, penetration into pancreas, perforation, and obstruction (not intrinsically precancerous).

• Possible Etiology:
• C: Disordered response to intestinal bacteria.
• U: Autoimmune.

• Location:
• C: Any portion of the GI tract, usually the terminal ileum and colon. Skip lesions, rectal sparing.
• U: Colitis = colon inflammation. Continuous colonic lesions, always with rectal involvement.

• Gross morphology:
• C: Transmural inflammation. Cobblestone mucosa, creeping fat,bowel wall thickening (“string signon barium swallow x-ray), linear hulcers, fissures, fistulas.
• U: Mucosal and submucosal inflammationonly. Friable mucosal pseudopolyps w freely hanging mesentery. Loss of haustra → “lead pipe” appearance on imaging.

• Microscopic morphology:
• C: Noncaseating granulomas and lymphoid aggregates.
• U: Crypt abscesses and ulcers, bleeding, granulomas.

• Complications:
• C: Strictures, fistulas, perianal disease, Mmalabsorption, nutritional depletion.
• U: Malnutrition, toxic megacolon, colorectalcarcinoma.

• Intestinal Manifestation:
• C: Diarrhea that may or may not be bloody.
• U: Bloody diarrhea.

• Extraintestinal Manifestations:
• C: Migratory polyarthritis, erythema nodosum, ankylosing spondylitis, cuveitis, immunologic disorders.
• U: Pyoderma gangrenosum, 1° sclerosing cholangitis.

• Treatment:
• C: Corticosteroids, infliximab.
• U: ASA preparations (sulfasalazine), infliximab, colectomy.

Recurrent abdominal pain associated with ≥ 2 of the following:

• 1. Pain improves with defecation
• 2. Change in stool frequency
• 3. Change in appearance of stool

No structural abnormalities. May present with diarrhea, constipation, or alternating. Pathophysiology is multifaceted. Treat symptoms.

All age groups; most common indication for emergent abdominal surgery in children

• Kids- lymphoid hyperplasia after viral infection.
• Adults- Obstruction, fecalith

.Initial diffuse periumbilical pain →localized pain at McBurney’s point (1⁄3 the distance from iliac crest to umbilicus). Nausea, fever; may perforate →peritonitis.

Differential: diverticulitis (elderly), ectopic pregnancy (use β-hCG to rule out).

• Diverticulum:
• 1. Blind pouch protruding from the alimentary tract that communicates with the lumen of the gut. Most wdiverticula (esophagus, stomach, duodenum, colon) are acquired and are termed “false” in that pthey lack or have an attenuated muscularis externa. mMost often in sigmoid colon.

2. “True” diverticulum—all 3 gut wall layers outpouch.“False” diverticulum or pseudodiverticulum—only mucosa and submucosa outpouch. Occur especiallywhere vasa recta perforatemuscularis externa.

• Diverticulosis:
• 1. Many diverticula. Common (in ~50% of people > 60years). Caused by ↑ intraluminal pressure and wfocal weakness in colonic wall. Associated with plow-fiber diets. Most often in sigmoid colon.

2. Often asymptomatic or associated with vague discomfort and/or painless rectal bleeding.

• Diverticulitis:
• 1. Inflammation of diverticula classically causing LLQ pain, fever, leukocytosis. May perforate→peritonitis, abscess formation, or bowel stenosis c(see Image 32). Give antibiotics.

2. May cause bright red rectal bleeding. May also cause colovesical fistula (fistula with bladder) →pneumaturia.Sometimes called “left-sided appendicitis” due to clinical presentation.

False diverticulum. Herniation of mucosal tissue at junction of pharynx and esophagus. Presenting symptoms: halitosis (due to trapped food particles), dysphagia, obstruction.

Congenital megacolon characterized by lack of Tganglion cells/enteric nervous plexuses (Auerbach’s and Meissner’s plexuses) in segment on intestinal Rbiopsy. Due to failure of neural crest cell migration.

Presents as chronic constipation early in life. Dilated portion of the colon proximal to the aganglionic segment, resulting in a “transition zone.” Involves rectum. Usually failure to pass meconium.

Think of a giant spring that has sprung in the colon. Risk ↑ with Down syndrome.

• Duodenal atresia:
• Causes early bilious vomiting with proximal stomach distention (“double bubble”) due to failure of recanalization of small bowel. Associated with Down syndrome.

• Meconium ileus:
• In cystic fibrosis, meconium plug obstructs intestine, preventing stool passage at birth.

• Necrotizing Enterocolitis:
• Necrosis of intestinal mucosa and possible perforation. Colon is usually involved, but can involve entire GI tract. In neonates, more common in preemies (↓ immunity).

• Ischemic colitis:
• Reduction in intestinal blood causes ischemia. Pain after eating → weight loss.Commonly occurs at splenic flexure and distal colon. Typically affects elderly.

• Adhesion:
• Acute bowel obstruction, commonly from a recent surgery. Can have well-demarcated necrotic zones.

• Angiodysplasia:
• Tortuous dilation of vessels → bleeding. Most often found in cecum, terminal ileum, and ascending colon. More common in older patients. Confirmed by angiography.

Masses protruding into gut lumen → sawtooth appearance. 90% are non-neoplastic. Often rectosigmoid.

Adenomatous polyps are precancerous. Malignant risk is associated with ↑ size,villous histology, ↑ epithelial dysplasia (see Image 31). Precursor to colorectal cancer (CRC). The more villous the polyp, the more likely it is to be malignant (VILLous = VILLainOUS).

• Hyperplastic:
• Most common non-neoplastic polyp in colon (> 50% found in rectosigmoid colon).

• Juvenile:
• Mostly sporadic lesions in children < 5 years of age. 80% in rectum. If single, no malignant potential.
• Juvenile polyposis syndrome—multiple juvenile polyps in GI tract, ↑ risk of adenocarcinoma.

• Peutz Jeghers:
• Single polyps are not malignant.
• Peutz-Jeghers syndrome—autosomal-dominant syndrome featuring multiple nonmalignant hamartomas throughout GI tract, along with hyperpigmented mouth,lips, hands, genitalia. Associated with ↑ risk of CRC and other visceral malignancies.

Tumor of endocrine cells. Comprise 50% of small bowel tumors.

Most common site is in small intestine. “Dense core bodies” seen on EM. Often produce 5-HT, which can lead to carcinoid syndrome. Classic symptoms: wheezing, right-sided heart murmurs, diarrhea, flushing. If tumor is confined to GI system, no carcinoid syndrome isobserved, since liver metabolizes 5-HT. If tumor or metastases (usually to liver) exist outside GI system, carcinoid syndrome is observed. Thus, tumor location determineswhether or not the syndrome appears.

(Serum Enzyme: Then major Diagnostic use below)

• Aminotransferases (AST and ALT):
• Viral hepatitis (ALT > AST)
• Alcoholic hepatitis (AST > ALT)
• Myocardial infarction (AST)

• GGT (γ-glutamyl transpeptidase):
• Various liver diseases; ↑ withheavy alcohol consumption

• Alkaline phosphatase:
• Obstructive liver disease (hepatocellular carcinoma), bone disease, bile duct disease

• Amylase:
• Acute Pancreatitis, Mumps

• Lipase:
• Acute Pancreatitis

• Ceruloplasmin (↓) :
• Wilson's Disease

Rare, often fatal childhood hepatoencephalopathy. Findings: mitochondrial abnormalities, fatty liver (microvesicular fatty change), hypoglycemia, coma.Associated with viral infection (especially VZV and influenza B) that has been treatedwith salicylates. Mechanism: aspirin metabolites ↓β-oxidation by reversible inhibitionof mitochondrial enzyme. Aspirin is not recommended for children (useacetaminophen, with caution).

• Hepatic Steatosis:
• Short-term change with moderate alcohol intake.Macrovesicular fatty change that may be reversible with alcohol cessation (see Image 29).

• Alcoholic Hepatitis:
• Requires sustained, long-term consumption. YSwollen and necrotic hepatocytes with neutrophilic infiltration. Mallory bodies(intracytoplasmic eosinophilic inclusions)are present.

• Alcoholic Cirrhosis:
• Final and irreversible form. Micronodular, irregularly shrunken liver with “hobnail” appearance (see Image 30). Sclerosis around central vein (zone III). Has manifestations of chronic liver disease (e.g., jaundice, hypoalbuminemia).

You’re toASTed with alcoholic hepatitis: AST > ALT (ratio usually > 1.5).

Most common 1° malignant tumor of the liver in Cadults. ↑ incidence is associated with hepatitis hB and C, Wilson’s disease, hemochromatosis, dα1-antitrypsin deficiency, alcoholic cirrhosis, and carcinogens (e.g., aflatoxin in peanuts). tFindings: jaundice, tender hepatomegaly, ascites, polycythemia, and hypoglycemia.

Commonly spread by hematogenous dissemination.↑α-fetoprotein. May lead to Budd-Chiari syndrome.

Due to backup of blood into liver. Commonly caused by right-sided heart failure and Budd-Chiari syndrome. The liver appears mottled like a nutmeg. If the conditionpersists, centrilobular congestion and necrosis can result in cardiac cirrhosis.

Occlusion of IVC or hepatic veins with centrilobular congestion and necrosis, leading to congestive liver disease (hepatomegaly, ascites, abdominal pain, and eventual liver failure). May develop varices and have visible abdominal and back veins. Absence of JVD. Associated with polycythemia vera, pregnancy, and hepatocellular carcinoma.

Misfolded gene product protein accumulates in hepatocellular ER. ↓ elastic tissue in lungs → panacinar emphysema. PAS-positive globules in liver. Codominant trait.

At birth, immature UDP-glucuronyl transferase → unconjugatedhyperbilirubinemia → jaundice/kernicterus.

Treatment: phototherapy (converts UCB to water-soluble form).

Normally, liver cells convert unconjugated (indirect) bilirubin into conjugated (direct) bilirubin. Direct bilirubin is water soluble and can be excreted into urine and by the liver into bile to be converted by gut bacteria to urobilinogen (some of which is reabsorbed). Some urobilinogen is also formed directly from heme metabolism.

Inadequate hepatic copper excretion and failure copper to enter circulation as ceruloplasmin. ALeads to copper accumulation, especially in iliver, brain, cornea, kidneys, and joints.

• Characterized by: (ABCD)
• A. Asterixis
• B. Basal ganglia degeneration (parkinsonian symptoms)
• C. Ceruloplasmin ↓, Cirrhosis, Corneal deposits (Kayser-Fleischer rings—see Image 51), Copper accumulation, Carcinoma (hepatocellular), Choreiform movements
• D. Dementia
• And, Hemolytic anemia

Treat with penicillamine. Autosomal-recessive inheritance.

Hemosiderosis is the deposition of hemosiderin (iron); hemochromatosis is the disease caused by this iron deposition (see Image 28). Classic triad Tof micronodular Cirrhosis, Diabetes mellitus, eand skin pigmentation → “bronze” diabetes. Results in CHF and ↑ risk of hepatocellular Tcarcinoma. Disease may be 1° (autosomal recessive) or 2° to chronic transfusion therapy (e.g., β-thalassemia major). ↑ ferritin, ↑ iron, ↓ TIBC →↑ transferrin saturation.

Mnemonic: (HCCD) Hemochromatosis Can Cause Deposits: Hemochromatosis, Cirrhosis, CHF, Diabetes (bronze).

Total body iron may reach 50 g, enough to set off metal detectors at airports.

Treatment of hereditary hemochromatosis: repeated phlebotomy, deferoxamine.

Associated with HLA-A3.

Inflammation of gallbladder. Usually from gallstones; rarely ischemia or infectious (CMV). ↑ alkaline phosphatase if bile duct becomes involved (e.g., ascending cholangitis).

Cimetidine, Ranitidine, Famotidine, Nizatidine

• Mechanism:
• Reversible block of histamine H2 receptors →↓ H+secretion by parietal cells.

• Clinical Use:
• Peptic ulcer, gastritis, mild esophageal reflux.

• Toxicity:
• Cimetidine is a potent inhibitor of P-450; 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.

Mnemonic: Take H2 blockers before you DINE. Think “table for 2”to remember H2.

Omeprazole, Lansoprazole

• Mechanism:
• Irreversibly inhibit H+/K+-ATPase in stomach parietal cells.

• Clinical Use:
• Peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome.

• Mechanism:
• Bind to ulcer base, providing physical protectand allow HCO3– secretion to reestablish pgradient in the mucous layer.

• Clinical Use:
• ↑ ulcer healing, traveler’s diarrhea.

Triple therapy of H. pylori ulcers—Metronidazole, Amoxicillin (or Tetracycline),Bismuth.

Can also use PPI—Please MAkeTummy Better.

• Mechanism:
• A PGE1 analog. ↑ production and secretion of gastric mucous barrier, ↓ acidproduction.

• Clinical Use:
• Prevention of NSAID-induced peptic ulcers; maintenance of a patent ductus arteriosus. Also used to induce labor.

• Toxicity:
• Diarrhea. Contraindicated in women of childbearing potential (abortifacient).

Pirenzepine, propantheline.

• Mechanism:
• Block M1 receptors on ECL cells (↓ histamine secretion) and M3 receptors onparietal cells (↓ H+ secretion).

• Clinical Use:
• Peptic ulcer (rarely used).

• Toxicity:
• Tachycardia, dry mouth, difficulty focusing eyes.

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

• Overuse can also cause the following problems:
• 1. Aluminum hydroxide—constipation and Ahypophosphatemia; proximal muscle weakness, osteodystrophy, seizures
• 2. Magnesium hydroxide—diarrhea, hyporeflexia, hypotension, cardiac arrest
• 3. Calcium carbonate—hypercalcemia, Crebound acid ↑
• All can cause hypokalemia.

Mnemonics:

• Aluminimum amount of feces.
• Mg =Must go to the bathroom.

Calcium Carbonate Can chelate and ↓ effectivenessof other drugs (e.g., tetracycline).

• Mechanism:
• A monoclonal antibody to TNF, proinflammatory cytokine.

• Clinical Use:
• Crohn’s disease, rheumatoid arthritis.

• Toxicity:
• Respiratory infection (including reactivation of latent TB), fever, hypotension.

• Mnemonic:
• INFLIXimab INFLIX pain on TNF.

• Mechanism:
• A combination of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory). Activated by colonic bacteria.

• Clinical Use:
• Ulcerative colitis, Crohn’s disease.

• Toxicity:
• Malaise, nausea, sulfonamide toxicity, reversible oligospermia.

• Mechanism:
• 5-HT3 antagonist. Powerful central-acting antiemetic.

• Clinical Use:
• 3 Control vomiting postoperatively and in patients undergoing cancer chemotherapy.

• Toxicity:
• Headache, constipation.

• Mnemonic:
• You will not vomit with ONDANSetron, so you can go ON DANCing.

• Mechanism:
• D2 receptor antagonist. ↑ resting tone, contractility, LES tone, motility. Does not influence colon transport time.

• Clinical Use:
• Diabetic and post-surgery gastroparesis.↑

• Toxicity:
• ↑ parkinsonian effects. Restlessness, drowsiness, fatigue, depression, nausea, diarrhea. Drug interaction with digoxin and diabetic agents. Contraindicated in patients with small bowel obstruction.