Liver Abnormalities 2 PDF

Gastro-intestinal Disorders  Esophageal Disorders Reflux Esophagitis-acid, infectious, toxic Motility disorders-Achalasia Obstruction-Stenosis, Schatzki ring Malignancies – Adenocarcinoma-metaplasia. P53, CDKI – Squamous call carcinoma-E-cadherin, Notc...

Gastro-intestinal Disorders  Esophageal Disorders Reflux Esophagitis-acid, infectious, toxic Motility disorders-Achalasia Obstruction-Stenosis, Schatzki ring Malignancies – Adenocarcinoma-metaplasia. P53, CDKI – Squamous call carcinoma-E-cadherin, Notch-1, p53, SOX2  Ulcer Disease Gastritis, gastric ulcers Peptic Ulcer Disease – H. pylori Gastric adenocarcinoma E-cadherin WNT, B-catenin  Inflammatory Bowel Disease Crohn’s disease - incidence is 70 to 150 per 100,000 persons per year in the United States Ulcerative colitis - incidence is 20 to 40 per 100,000 persons per year in the United States Cause unknown but may be familial _________________________________ Note: Symptoms may overlap, and in 20% of cases, it is impossible to tell them apart.  Crohn’s vs. Ulcerative Colitis Clinical Features Crohn’s Disease Ulcerative Colitis Familial ++ ++ Peak age 15–25 years 15–25 years Immune + + disturbances Extraintestinal + + complications Treatment + +  Crohn’s vs. Ulcerative Colitis Pathology Crohn’s Disease Ulcerative Colitis Distribution Segmental, Diffuse, colon including ileum only Transmural ++ () Granuloma + () Fistula + () Megacolon () + Cancer + ++ Crohn’s Disease Figure 10-09A Crohn’s Disease Figure 10-09B Ulcerative Colitis Figure 10-10A Ulcerative Colitis Figure 10-10B  Diarrhea Infectious Malabsorption  Malabsorption Celiac disease-gluten-sensitive enteropathy Fat Malabsorption Protein Malabsorption Carbohydrate Malabsorption  Intestinal Neoplasms Colon most often affected May be sporadic or familial (S:F = 8:2) May be benign or malignant (B:M = 3:1) Epithelial tumors (adenomas and carcinomas) - account for 90% of all tumors and are more common than lymphomas or mesenchymal tumors (benign soft tissue tumor, e.g., lipoma and leiomyoma, or sarcomas)  Large Intestinal Carcinoma Third most common cancer of internal organs Affects 190,000 persons per year in the United States Intestinal Polyps Figure 10-16 Tubular Adenomas of the Large Intestine Figure 10-15  Etiology of Colon Cancer Genetic factors (play important role) – Familial polyposis coli – Gardner’s syndrome – Hereditary non-polyposis colorectal cancer Adenocarcinoma of the Colon Figure 10-17 Adenocarcinoma of Cecum - Gross Appearance Figure 10-18A Adenocarcinoma of Sigmoid Colon - Gross Appearance Figure 10-18B Adenocarcinoma of the Colon - Microscopic Features Figure 10-18C Liver Disease  Liver Diseases Hereditary – Hemochromatosis, Wilson’s Disease, α-1 antitrypsin deficiency, storage diseases Toxic – Alcohol, medications (acetaminophen), carbon tetrachloride, mushrooms Immunologic Infectious – Viral, parasitic, bacterial Malignancy Liver Disease-Laboratory Tests Acute injury – Transaminase levels increase-ALT (serum alanine aminotransferase) and AST (serum aspartate aminotransferase) – Bilirubin increased (conjugated and unconjugated) Chronic injury – Alkaline Phosphatase – Bilirubin (conjugated) – Synthetic function-decreased albumin, increased protime (decreased coagulation factors II,VII, IX, IX) – Decreased blood urea nitrogen and increased ammonia  Viral Hepatitis Hepatitis A-ssRNA, fecal-oral, CAH-never Hepatitis B-dsDNA, parenteral/sexual, CAH-10% Hepatitis C-ssRNA, parenteral/? sexual, CAH-40-90% D, E, and G Chronic Liver Disease Alcohol Non-alcohol fatty liver disease Non-alcohol Steatohepatitis  Alcoholic Liver Disease Alcohol Dehydrogenase and acetaldehyde dehydrogenasd Increased NADH Suppresses fatty acid oxidation Increases CYP2E1 enzyme Decreased methionine, decreased glutathione  Liver Failure Portal Hypertension/Ascites Varices Encephalopathy Renal dysfunction-including hepato-renal syndrome, types 1 and 2 Coagulopathy  Fluid Retention Underfill Theory Overfill – Dilated Portal Theory Circulation – Renal – Decreased venous Sodium/water return retention – Renal – Increased CO, hypoperfusion, increased RAAS intravascular – Hypoalbuminemia volume  Overfill Theory Decreased PVR. BP=CO x PVR CO > 3 times normal Intravascular volume increased. Arterial volume increased.  Renal Circulation Renal Blood flow correlates with hepatic disease. Afferent renal vascular resistance markedly increased. Hepato-Renal Syndrome Renal dysfunction due to liver disease-hemodynamic and reversible. Severe afferent renal constriction. Etiology multifactorial-renal sympathetic nervous system, endotoxins, vasoconstrictor prostaglandins, endothelin, decreased NO  Gallstones Cholesterol Pigment-calcium and unconjugated bilirubin  Pancreatic Disorders Acute pancreatitis-cholelithiasis, alcohol, medications, ductal problems (atresia, stenosis, divisum). Chronic pancreatitis Pseudocysts Cancer