Copyright © 2000 by W. B. Saunders Company. All rights reserved. Gastrointestinal Physiology and Disorders Section VI

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Figure: 37-1 Liver, biliary, and pancreatic anatomy

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Submucosa Lumen Circular muscle longitudinal muscle Myenteric plexus Submucosal plexus PSNSSNS Basic Structure of the GI tract

ENTERIC NERVOUS SYSTEM Myenteric Submucosal PSNS Pelvic nerves SNS Ach NE Smooth muscle Secretory Cells Endocrine Cells Blood Vessels Enteric Nervous System Influenced by ANS Copyright © 2000 by W. B. Saunders Company. All rights reserved.

Gastric Motility LES fundus Antrum pylorus approx 3 contractions per minute receptive relaxation

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Control of Gastric Emptying GASTRIC EMPTYING PSNS + SNS - Duodenal acid secretin- Duodenal fats CCK - Duodenal hypertonicity -

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Small and Large Bowel Motility Small Intestine 2-4 hours to traverse Segmental contractions to mix Peristaltic waves to move forward Large Intestine Slow progression at 5-10 cm per hour Segmental contractions produce haustra 1-3 mass movements per day

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Secretion in the Stomach Parietal Cells HCL Intrinsic Factor Chief Cells Pepsinogen Surface epithelia and mucous cells HCO3- and mucus

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Gastric Parietal Cell Acid Secretion muscarinic receptor H 2 receptorgastrin receptor AchHistamine Gastrin Vagus Mast Cells G cells Control of Acid Secretion Cells that produce gastrin that are present predominantly in the distal stomach (gastric antrum).

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Secretion in the Small Intestine Secretions from Pancreas HCO3-, Proteases, Lipases, Amylases Secretion from Gallbladder Bile acids, pigment, phospholipid Secretions from intestinal epithelia Brush border enzymes pancreatic lipase. the triacylglycerol lipase secreted by the pancreas; it is the major intestinal lipase, digesting ingested fats to fatty acids and monoglycerides. The enzyme requires bile salts and colipase for activity

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Digestion and Absorption Carbohydrates: O amylose has alpha linkage O cellulose has beta linkage amylase breaks down amylose

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Brush Border Enzymes Lactase:lactoseglucose, galactose Sucrase:sucrosefructose, glucose Dextrinase:cleaves amylose branch points Glucoamylase: maltoseglucoses Only Monosaccharides are Absorbed

Digestion and Absorption of Proteins Pepsin: 15% of peptide bonds broken Pancreatic proteases Trypsin Chymotrypsin Carboxypeptidases Brush Border Peptidases cleave into 1 to 4 aa chains Copyright © 2000 by W. B. Saunders Company. All rights reserved.

Digestion and Absorption of Fat Bile salts are amphipathic molecules that break up large fat globs into droplet Lipase are water soluble - only work at surface of droplet Triglycerides > FFA and glycerol Bile forms micelles with FFA to keep soluble. FFA are lipid soluble so absorb directly

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Reabsorption of Bile Bile is reabsorbed at terminal ileum Passive diffusion and active transport Transported to liver via portal blood ALL reabsorbed bile is taken up on first pass by liver Entire bile pool circulates 2 to 5 times per meal. 5-10% lost per day in stool

Copyright © 2000 by W. B. Saunders Company. All rights reserved. GI Disorders

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Dysphagia Neuromuscular: pharynx Stricture or tumor: Progressive solid food dysphagia Achalasia: esophageal motility disorder, loss of peristalsis in lower 2/3 plus impaired LES relaxation Mallory-Weiss syndrome: mucosal tears at distal esophagus, bleeding, pain failure of the esophagogastric sphincter to relax with swallowing, due to degeneration of ganglion cells in the wall of the organ hematemesis or melena that follows typically upon many hours or days of severe vomiting and retching, traceable to one or several slitlike lacerations of the gastric mucosa, longitudinally placed at or slightly below the esophagogastric junction.

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Oropharyngeal vs Esophageal Nasal regurgitation Airway obstruction with eating Coughing when swallowing Immediate regurgitation Hoarse voice No airway distress Late regurgitation Chest meals Frequent heartburn Presence of collagen disease Presence of Left supraclavicular node

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Figure: 38-9 Balloon tamponade of esophageal varices Bleeding esophageal varices result from dilated veins in the walls of the lower part of the esophagus and sometimes the upper part of the stomach. Bleeding varices are a life-threatening complication of portal hypertension (increased blood pressure in the portal vein caused by liver disease). Increased pressure causes the veins to balloon outward. The vessels may rupture, causing vomiting of blood and bloody stools or tarry black stools. If a large volume of blood is lost, signs of shock will develop. Any cause of chronic liver disease can cause bleeding varices.liver diseaseblack stoolsshock

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Dyspepsia Present with heartburn, indigestion, epigastric distress Up to 2/3 will have no identifiable cause One-half will have relief from placebo Symptom profile does not differentiate between GERD, PUD, and non-ulcer dyspepsia (functional) Physical exam is rarely helpful

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Differential Diagnosis NSAID: suspect PUD and treat Helicobacter pylori: urea breath test or biopsy during endoscopy GERD: Trial of H2 therapy Functional: may improve with agents that increase motility Zollinger-Ellison syndrome: gastrin level

Copyright © 2000 by W. B. Saunders Company. All rights reserved. PUD with H. pylori H. pylori is nearly always a factor in non- NSAID peptic ulcer disease Conventional therapy with H2 blockers or H+ pump inhibitors has a 75-80% one-year recurrence rate Treatment for H. pylori reduced recurrence rate to less than 5%

Copyright © 2000 by W. B. Saunders Company. All rights reserved. High fever? Bloody diarrhea? YESNO Noninflammatory watery large volume periumbilical pain small volume LLQ pain + fecal leukocytes Viral: rotavirus, Norwalk S. aureus food poisoning Giardia Shigella, Salmonella, C. difficile, E. coli (bad) Campylobacter, HIV- associated Rehydrate, symptomatic Culture and treat Acute Infectious Diarrhea Inflammatory

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Chronic Diarrhea: Stool Studies Stool Osmolality: normal gap < 50 Laxative screen: Mg, PO4, SO4 Fecal leukocytes: Inflammatory disease Ova and parasites: Giardia, cryptosporidium Fecal Fat analysis: > 10 g/24 hrs indicates malabsorption Fecal weight: > 1000 g is secretory

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Osmotic Diarrhea: Lactase Def. Incidence 90% of Asian Americans 95% of Native Americans 50% of Mexican Americans 60% of Jewish Americans 25% of other Caucasians DX: empiric trial of lactose-free diet for two weeks

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Inflammatory Bowel Disease Ulcerative Colitis Involves only the colon and rectum Mucosal layer is affected Hallmark is bloody diarrhea and lower abdominal cramps Associated with increased cancer risk after years of disease

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Assess UC Disease Severity Number of stools per day Hematocrit Sed rate Albumin level

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Crohn Disease Intermittent bouts of fever, diarrhea, and RLQ pain May have RLQ mass, tenderness Can affect any portion of GI tract 30% are small bowel only 50% are small and large bowel 15-20% are large bowel only

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Crohn Disease Transmural process in the intestinal wall predisposes to fistula formation If suspected, obtain upper GI series with small bowel follow through plus either colonoscopy or barium enema Suggestive findings are ulcerations, strictures, and fistulas RX: stop smoking, drugs similar to UC

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Motility Diarrhea: IBS Irritable bowel syndrome is a chronic (>3months) functional disorder with no identifiable pathology Fluctuations in stool frequency and consistency (no nocturnal diarrhea) Perceived abd distention, bloating, pain Often associated with anxiety or depression

Copyright © 2000 by W. B. Saunders Company. All rights reserved. IBS It is not IBS if fever, bloody stools, nocturnal diarrhea, or weight loss are present Consider checking CBC, sed rate, albumin, and stool for occult blood to rule out inflammatory disease, consider lactose-free trial. RX: restrict caffeine, gas producing food, high fiber. Rx depression

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Occult GI Bleeding Detected by FOBT: worry colorectal CA Indicated for iron deficiency anemia in males or postmenopausal females Unless S&S suggest Upper GI etiology (heartburn, dyspepsia PUD) start with colonoscopy (or barium enema) If no source, follow with endoscopy

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Acute Abdominal Pain Tension: spasm, associated with intense peristalsis (irritant, infection, obstruction) Ischemia: intense constant pain (bowel strangulation, volvulus adhesion) Inflammation: first localized to serosa covering inflamed part then extends to abdominal wall causing reflex muscle spasms (rigidity, involuntary guarding)

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Assessment of the Pain Is it nongastric? consider aortic aneurysm, ectopic pregnancy, PID, kidney Is it an acute surgical abdomen? Involuntary guarding, rigidity Absent bowel sounds Is there shock

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Localization of Abdominal Pain Stomach, duodenum: mid epigastric Small bowel: periumbilical Colon: low abdomen, midline Rectum: sacrum and perineum Gallbladder: mid epigastric radiates to RUQ or right scapula Pancreas: mid epigastric radiate to back Appendix: RLQ, but variable

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Bowel Obstruction Presentation Pain, distention, vomiting, obstipation Evaluation Flat and upright abdominal film Small bowel: less urgent intestinal tube, decompression Large bowel: urgent, danger of cecal perf immediate surgical consult

Copyright © 2000 by W. B. Saunders Company. All rights reserved. “itis”EtiologyClinical Findings esophagitisreflux (GERD)- pain after meals - “heartburn” gastritis -PUDASA, ETOH- epigastric pain H. pylori regional enteritis? Etiology- diarrhea with (Crohn) blood and mucus ulcerative colitis? Etiology- bloody diarrhea “Itis” from TOP to BOTTOM

Copyright © 2000 by W. B. Saunders Company. All rights reserved. “Itis” from TOP to BOTTOM “itis”EtiologyClinical Findings diverticulitislow fiber dietlow abdominal pain, fever appendicitisobstruction- RLQ pain, fever “fecalith”- rebound pain peritonitisperforation- severe pain, ileus bowel ischemia- guarding, rigid pancreatitisbiliary disease- pain to back, shock ETOH- high lipase, amylase

Copyright © 2000 by W. B. Saunders Company. All rights reserved. “Itis” from TOP to BOTTOM “itis”EtiologyClinical Findings cholecystitischolelithiasis- RUQ pain - steatorrhea hepatitisviral, acute ETOH- jaundice, big liver - high AST, ALT - flu-like symptoms

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Diverticulitis Etiology: Microperforation with peridiverticular inflammation Presentation: Elderly with LLQ pain, severe constipation, nausea, fever Evaluation: CBC, abd film, CT if peritoneal signs Rx: NPO, antibiotics, IV fluids

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Cholecystitis Etiology: 95% associated with stone in cystic duct Presentation: Often obese female, fever, RUQ pain with scapular or epigastric pain, colicky, N&V Evaluation: CBC, RUQ ultrasound, HIDA scan RX: Prompt cholecystectomy

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Acute Pancreatitis Etiology: unknown Associated with ETOH, biliary disease Presentation: Severe epigastric and back pain Evaluation: CBC, glucose, calcium, electrolytes, amylase, lipase (renal studies) Severity index

Copyright © 2000 by W. B. Saunders Company. All rights reserved. During first 48 hours HCT drop of >10% BUN rise >5 mg/dl PaO2 < 60 Calcium < 8 mg/dl Fluid sequestration of > 6 liters Severity Scale: Pancreatitis Initially Age over 55 WBC > 16,000 Blood glucose > 200 Base deficit > 4 Serum LDH >350 AST > 250

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Pancreatitis Severity Mortality RateNumber of criteria 1% 16% 40% 100%

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Appendicitis Etiology: Obstruction by fecalith, inflammation Presentation: RLQ pain (classic, but may be anywhere), N&V, fever, diarrhea, RLQ tenderness Evaluation: CBC, abdominal ultrasound RX: immediate surgical consult

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Diff Dx: Steatorrhea Pancreatic steatorrhea: > 90% of exocrine function lost Bile salt deficiency: decreased ileal reabsorption (Crohn) blocked secretion (cholestasis) Bacterial overgrowth syndromes: stasis of small bowel contents Mucosal defects: Celiac disease (sprue)

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Diff Dx: Jaundice Jaundice occurs with bilirubin level > 3 mg/dl (normal ) Increased RBC breakdown Impaired liver uptake of bilirubin Impaired excretion of bilirubin

BLOOD BILE Unconjugated Bilirubin conjugated bilirubin biliary obstruction Copyright © 2000 by W. B. Saunders Company. All rights reserved.

Direct and Indirect Bilirubin Indirect bilirubin Unconjugated Elevated with increased RBC breakdown or impaired liver uptake Bound by albumin so no urine bilirubin Direct bilirubin Conjugated Elevated with impaired excretion of bilirubin from liver Water soluble, so is found in urine

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Diff Dx: High Indirect Bilirubin Hemolytic process, hematoma Gilbert’s syndrome: genetic impairment of bilirubin uptake by liver -benign Crigler-Najjar syndrome: genetic deficiency of enzyme for conjugation Liver bypass: portocaval shunt, cirrhotic shunt

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Diff Dx: High Direct Bilirubin Hepatocellular injury: hepatitis drugs hemochromatosis Alpha-1 antitrypsin deficiency Cholestasis: stones, tumors, strictures cholangitis

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Acute Hepatitis Etiology: acute liver inflammation and cellular injury: viral, toxic Presentation: jaundice, anorexia, fatigue, diffuse abd discomfort, dark urine Evaluation: History of viral or toxin exposure, AST, ALT, Alk phos, bilirubin, serology for viral hepatitis

Copyright © 2000 by W. B. Saunders Company. All rights reserved. TypeAB+(D)CE Transmissionoral-fecalblood andblood andoral-fecal body fluids Riskcontaminatedsexual, IVsexual, IVwaterborne food Prognosisgoodmore severe85% chronic? 5% carrier B+D more severe Viral Hepatitis

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Acute Toxic Hepatitis Etiology: exposure to hepatotoxin or its metabolite Evaluation: No definitive tests: history of exposure is important negative viral serology screen improvement after discontinuing drug if alcohol is the toxin, AST > ALT, 2:1

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Chronic Alcoholic Liver Disease Etiology: chronic, heavy ETOH exposure Only 15-20% of alcoholics develop liver disease Men > 4-6 drinks/day, Women > 3-4/day Pathogenesis: unknown Presentation: fatty liver hepatitis cirrhosis

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Functions of the Liver Nutrient metabolism (glucose, protein, fat, fat soluble vitamins) Production of serum proteins and enzymes (albumin, clotting factors etc.) Detoxification of hormones, drugs Bile synthesis (conjugation of bilirubin) Urea synthesis

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Manifestations of Liver Dysfunction Impaired protein synthesis bleeding (clotting factor deficiency) edema (hypoproteinemia) immune deficiency (substrate for antibody) Accumulation of toxins and hormones feminization (excess estrogens) poor metabolism of drugs spider nevi (estrogen)

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Manifestations of Liver Dysfunction Inadequate bile synthesis increased bilirubin level jaundice Inadequate urea synthesis increased blood ammonia level (NH 3 ) hepatic encephalopathy Release of marker enzymes into blood AST (SGOT) ALT (SGPT)

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Cirrhosis of the Liver Fibrotic liver loss of hepatocellular functions obstruction to bloodflow from the gut Etiology Chronic alcohol use (most common) Biliary (obstruction in bile drainage) Postnecrotic (viral, toxic hepatitis) Cardiac (right heart failure, liver congestion)

Copyright © 2000 by W. B. Saunders Company. All rights reserved. To vena cava From GI tract Hepatic vein Portal vein jaundice bleeding low albumin -edema immune deficient estrogen excess encephalopathy cell failure portal hypertension ascites esophageal varices hemorrhoids anorexia Liver Cirrhosis

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Treatment & Monitoring Abstinence from alcohol Restore nutrition: (high protein diet unless hepatic encephalopathy) Monitor PT, AST, ALT, albumin, bilirubin Vitamin K Abnormal PT despite vitamin K indicates a severely compromised liver

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Treatment & Monitoring Ascites: caput medusae: flow outward from navel sodium restriction spironolactone monitor for spontaneous bacterial peritonitis If ascites is present, high likelihood of esophageal varices

Copyright © 2000 by W. B. Saunders Company. All rights reserved. Treatment & Monitoring Hepatic Encephalopathy Altered mental status due to accumulation of toxins, including ammonia (NH 3 ) Precipitated by GI bleed, drugs, increased shunting of blood around liver Monitor NH 3 level lactulose withhold protein