Gastrointestinal Diseases

1. Gastrointestinal Diseases

2. Esophagus

3. Selected disorders of the esophagus • Motor disorders: Achalasia • Esophagitis: Reflux, infections, drugs, irradiation • Barrett’s esophagus

4. Achalasia (failure to relax) • Incomplete relaxation of lower sphincter during swallowing leading to functional obstruction and proximal dilatation • Aperistalsis, incomplete relaxation, increased resting tone • Ganglion cells of the myenteric plexus are diminished or absent • Clinical picture: dysphagia, regurgitation and aspiration • Histology: Inflammation in the area of M. plexus • Hypotheses: autoimmune, viral infections • May occur secondary to Trypanosoma cruzi infection (Chagas disease) • 5% develop squamous cell carcinoma, at younger age Loss of inhibitory innervation to the sphincter

5. Esophagitis • Reflux esophagitis • Infections • Crohn disease, acute graft versus host disease • Prolonged gastric intubation • Ingestion of irritant substance • Chemotherapy and irradiation

6. Reflux esophagitis • Reflux of gastric contents into esophagus • Possible etiologies: inadequate function of lower sphincter; sliding hiatal hernia • CP: “heart burn” • Complications: ulceration, bleeding, stricture, Barrett esophagus

7. Infection-induced esophagitis • More common in patients with impaired immunity • Fungal : Candida • Viruses: Herpes and Cytomegalovirus

8. Barrett esophagus • A complication of long standing reflux esophagitis • Replacement of squamous epithelium by columnar epithelium with goblet cells • 30- to 40-fold greater risk to develop adenocarcinoma

9. Stomach • 1) Cardia • 2) Body: Parietal and Chief cells • 3) Antrum: Mucin secretion and G-cells that secrete gastrin 2 1 3

10. Selected disorders of the stomach • Gastritis • Peptic ulcers

11. Chronic Gastritis • Infiltration of the mucosa by chronic inflammatory cells (lymphocytes and plasma cells) • Causes: • Helicobacter pylori: G-ve bacilli; • Autoimmune: rare disease, autoantibodies to parietal cells (decreased acid and intrinsic factor) • Helicobacter pylori is present in 70-90% of patients with gastric and duodenal ulcers, respectively • Look for intestinal (goblet cell) metaplasia as a precancerous lesion

12. Helicobacter pylori and associated disorders • Gastritis (chronic and acute), peptic (gastric and duodenal) ulcers • Gastric adenocarcinoma, intestinal type • Gastric lymphoma H. pylori Gastric ulcer

13. Mechanisms of H. pylori-induced pathology • Although the organism is not invasive, it induces intense inflammatory and immune response: cytokines and B-cell activation • Enhances gastric acid secretion • Bacterial products such as urease, lipases and proteases that induce epithelial injury

14. Acute gastritis • Injury to the gastric mucosa (erosions) with no significant participation of inflammatory cells • Causes include: • Non-steroidal antiinflammatory drugs • Alcohol • Hypovolemia • Shock • Stress • Uremia • Enterogastric reflux

15. Peptic ulcer • Location: stomach or first portion of duodenum • More frequent in patients with alcoholic cirrhosis, chronic obstructive pulmonary disease, chronic renal failure and hyperparathyroidism. • Causes include: H. pylori and causes of acute gastritis (especially NSAID) • Clinical features: Epigastric pain (worse at night and relieved by food), bleeding (30%) and perforation (5%; accounts for 2/3 of deaths).

16. Small and large bowel • Developmental: Meckeldiverticulum • Vascular • Diarrheal disease: • Infections: viruses, bacteria, protozoa • Idiopathic inflammatory bowel disease • Malabsorption • Diverticular disease

17. Types and causes of diarrheal illness • Secretory diarrhea: loss of intestinal fluid that is isotonic with plasma and persists during fasting • Viruses: rotavirus • Toxin-mediated: Vibrio cholera, E.coli (need time) • Preformed toxin: Stapylococcusaureus (immediate effect) • Excessive laxatives

18. Types and causes of diarrheal illness, continued • Osmotic diarrhea: secondary to intraluminal fluids with high osmolarity; it abates with fasting. • Specific therapies: • Lactulose therapy: used for constipation and hepatic encephalopathy • Gut lavage before endoscopy • Antacids

19. Types and causes of diarrheal illness, continued • Exudative diarrhea: purulent bloody stool (inflammation of the mucosa and/or hemorrhage) • Infections causing tissue damage: Shigella, Salmonella, Entamoebahistolytica • Infections causing both tissue damage and toxins: Clostridium difficile; with antibiotic therapy, leading to pseudomembranous colitis • Idiopathic inflammatory bowel disease

20. Types and causes of diarrheal illness, continued • Exudative diarrhea: pruluent bloody stool (inflammation of the mucosa and/or hemorrhage) • Infections causing tissue damage: Shigella, Salmonella, Entamoeba histolytica • Infections causing both tissue damage and toxins: Clostridium difficile; with antibiotic therapy, leading to pseudomembranous colitis • Idiopathic inflammatory bowel disease

21. Crohn disease Small bowel and colon (mostly right side) Patchy involvement Transmural inflammation, fistulas, strictures, serositis Non-caseating granulomas Poor response to surgery Increased risk for cancer Ulcerative colitis Colon only Continuous involvement Superficial inflammation No granulomas Good response to surgery Increased risk for cancer Idiopathic inflammatory bowel disease

22. Types and causes of diarrheal illness, continued • Malabsorption diarrhea (steatorrhea): voluminous bulky stool with increased osmolarity resulting from unabsorbed nutrients and excess fat; usually abates on fasting. • Malabsorption syndromes

23. Malabsorption syndromes • Defective intraluminal digestion: • pancreatic insufficiency • Defective bile secretion • Mucosal abnormalities: • Disaccharide deficiency (lactose intolerance) • Reduced surface area • Gluten-sensitive enteropathy (Celiac disease) • Surgical resection • Infections: Tropical sprue, whipple disease

24. Selected malabsorption syndromes • Gluten-sensitive enteropathy (celiac disease): 1:300 persons are affected, hypersensitivity to gliadin, a component of gluten (present in wheat flour) leading to blunted villi and increased intraepithelial lymphocytes. Increased risk for lymphoma. • Tropical sprue: malabsorption and diarrhea after a visit to the tropics. Infectious etiology, responds to antibiotics. • Whipple disease: systemic disease that affects GIT, nervous system and joints. Caused by T. whippelii (gram-positive actinomycete).

25. Clinical features of malabsorption syndromes • Hematopietic system: • Anemia: iron, folate and B12 deficiency • Bleeding: vitamin K deficiency • Musculoskeletal system: • Osteopenia: calcium and vitamin D deficiency • Endocrine system: • Amenorrhea, impotence, infertility • Skin: • Purpura: vitamin K deficiency • Dermatitis: vitamin A deficiency • Nervous system: • Peripheral neuropathy: folate and B12 deficiency.

26. Meckel diverticulum • A blind pouch located in distal small bowel • The most common congenital anomaly of the small intestine; results from failure of the involution of the omphalomesenteric (vitelline) duct • The rule of 2’s: • 2% of the population, 2 inches in length, 2 feet proximal to the ileocecal valve, 2 types of heterotopic tissue (pancreas and stomach); 2% are symptomatic. • Symptoms are rare: • Overgrowth of bacteria that depletes vitamin B12 leading to anemia • “Peptic” ulcer and bleeding Meckel diverticulum

27. The Pancreas

28. 85% exocrine: enzymes for digestion Acute and chronic pancreatitis 15% endocrine: insulin, glucagon and others Diabetes The Pancreas

29. Pancreatic exocrine enzymes

30. Acute pancreatitis

31. Acute pancreatitis • Clinical presentation: abdominal pain radiating to the back, elevated serum amylase and lipase, hypocalcemia • Rise in serum lipase is more specific for pancreatitis. • Complications: infections, abscess, pseudocyst • Mortality is high: 20-40%, from shock, sepsis or acute respiratory failure, acute renal failure, disseminated intravascular coagulation

32. Chronic pancreatitis • Progressive destruction of pancreatic parenchyma and its replacement by fibrosis • Predisposing factors: alcohol, hypercalcemia or idiopathic • 30% of idiopathic cases have been found to have mutation in CFTR gene • Complications: Pseudocyst, malabsorption, 2ry diabetes • Diagnosis: abdominal pain, malabsorption, calcifications on X-ray

33. Diseases of the liver

34. Liver • Maintaining body metabolic homeostasis: • Lipid and carbohydrate metabolism: production and secretion of glucose • Protein synthesis: albumin, coagulation factors • Detoxification and drug metabolism • Conjugation and excretion of bilirubin • Synthesis and excretion of bile salts

35. Liver anatomy and histology

36. Patterns of hepatic injury • Inflammation • Steatosis: accumulation of fat droplets within hepatocytes • Cell death: those cells closer to the central vein are more susceptible to ischemia, toxins and drugs leading to “centrilobular” necrosis • Fibrosis: Irreversible, affect blood flow and hepatocyte function • Cirrhosis: End stage liver disease with diffuse fibrosis and regenerating nodules

37. Steatosis Alcohol Obesity Diabetes Hyperlipidemia Clinical picture: Silent, or fatigue, malaise, right upper quadrant discomfort

38. Liver cirrhosis • Definition: bridging fibrous septa and parenchymal nodules with disruption of architecture. End stage for many diseases affecting the liver Mechanism: cell death, regeneration and fibrosis

39. Hepatic dysfunction: Decrease synthesis capacity leading to : Hypoalbuminemia: edema, ascitis, muscle wasting, weight loss Hypoglycemia: weakness and syncope Coagulation factor deficiency: bleeding Decrease detoxification capacity leading to: Hyperammonemia and increase toxic metabolites: Encephalopathy (altered behavior and disturbances in consciousness that may lead to deep coma and death) Injury to other organs by active toxins Hepatorenal syndrome: Renal failure without intrinsic or functional causes of renal failure. ? Altered blood flow to the kidney. Clinical consequences of liver disease (life-threatening complications are in yellow)

40. Clinical consequences of liver disease, continued • Jaundice: yellow discoloration of skin and sclera due to accumulation of bilirubin • Cholestasis: systemic accumulation of bilirubin in addition to bile salts and cholesterol (usually secondary to obstruction) • Portal hypertension in cirrhosis: increased resistance to portal blood flow • Esophageal varices • Ascitis • Splenomegaly • Hemorrhoids • Malignancy on top of cirrhosis

41. Jaundice • Accumulation of bilirubin in tissue leading to yellow discoloration of skin and sclera (icterus) • Normal serum level: 0.3-1.2 mg/dl; jaundice appears with levels above 2.0-2.5 mg/dl • Source of bilirubin: the breakdown of senescent red blood cells in the spleen releases heme that changes into bilirubin by specific enzymes.

42. Unconjugated Albumin bound Insoluble in water, toxic Conjugated Loosely bound to albumin Water soluble, non-toxic, excreted in urine Bilirubin Conjugation is a function of the liver by adding glucuronic acid to bilirubin

43. Laboratory evaluation of liver disease • Hepatocyte function: • Serum albumin • Prothrombin time: measuring coagulation factors (II, V, VII, X); prolonged in liver cirrhosis • Serum ammonia • Hepatocyte injury (enzymes normally present inside the hepatocytes and released with injury): • Serum aspartate aminotransferase (AST) • Serum alanine aminotransferase (ALT) • Serum lactate dehydrogenase • Biliary excretory function: • Serum bilirubin • Serum alkaline phosphatase • Serum gamma-glutamyl transpeptidase

44. Laboratory evaluation of liver disease • Searching for etiology: • Hepatitis viral antigens and antibodies • Autoimmune antibodies: for autoimmune hepatitis • Tissue iron and copper: for hemochromatosis and Wilson disease

45. Biliary disease • Secondary biliary cirrhosis: secondary to extrahepatic bile obstruction by stones, atresia or tumors • Primary biliary cirrhosis: immune-mediated destruction of intrahepatic bile ducts, more in females, presence of anti-mitochondrial antibodies • Primary sclerosing cholangitis: chronic fibrosis of intra- and extra-hepatic bile ducts; more in men, association with ulcerative colitis