Gastroenterology and Liver Disease-2023 Part 2 PDF

Structure and Function of the Digestive System Learning Objectives ▪ Discuss the pathophysiology, clinical manifestations, and treatment of appendicitis, and irritable bowel syndrome ▪ Discuss the five major complications of liver dysfunction: portal hypertension, ascites, hepatic encephalopathy, ja...

Structure and Function of the Digestive System Learning Objectives ▪ Discuss the pathophysiology, clinical manifestations, and treatment of appendicitis, and irritable bowel syndrome ▪ Discuss the five major complications of liver dysfunction: portal hypertension, ascites, hepatic encephalopathy, jaundice, and hepatorenal syndrome. ▪ Discuss the pathophysiology of viral hepatitis and fulminant hepatitis. ▪ Discuss the causation, treatment options, and prognosis for alcoholic and biliary cirrhosis. ▪ Discuss the pathophysiology of cholelithiasis and cholecystitis. ▪ Compare and contrast acute and chronic pancreatitis. ▪ Discuss the risk factors, incidence, manifestations, treatment, morbidity, and mortality of the various cancers of the digestive system. Appendicitis The Liver FUNCTIONAL HISTOLOGY OF THE LIVER 8 CIRRHOSIS Represents the final common morphologic change for a wide variety of chronic liver diseases. is defined histologically as a diffuse hepatic process characterized by: 1) Fibrosis 2) The transformation of normal liver architecture into regenerative parenchymal nodules surrounded by fibrous band. Many forms of liver injury are marked by fibrosis(excess collagens, glycoproteins, proteoglycans) 9 Causes of Cirrhosis ❖ Alcoholic liver disease (most common ) ❖ Postnecrotic cirhosis (HBV, HCV) ❖ Autoimmune disease ❖ Autoimmune hepatitis ❖ Primary biliary cirrhosis ❖ Metabolic/ genetic diseases ▪ Hemochromatosis ▪ Wilson disease ▪ Alpha-1 antitrypsin deficiency ❖Cryptogenic causes (18%) 10 Pathophysiology of Cirrhosis 11 Pathophysiology of Cirrhosis cont.. The induction of fibrosis occurs with activation of hepatic stellate cells This results in a decrease in hepatocellular mass, and thus function, and an alteration of blood flow. In most patients, cirrhosis is not a reversible process. Other individuals have a multitude of the most severe symptoms of end-stage liver disease and have a limited chance for survival. 12 Regenerative nodules ▪ Hepatocytes reaction to injury ▪ Lack normal liver architecture ▪ Surrounds by bands of fibrosis ▪ Compress sinusoids and central veins Intrasinusoidal hypertension Increase in hydrostatic pressure in portal vein 13 Signs and Symptoms of Cirrhosis Complication Associated With Cirrhosis Hepatic Failure Portal hypertension Ascites Hepatorenal syndrome Hyperestrinism/ Hyperestrogenemia Hepatopulmonary syndrome Hepatocellular carcinoma 15 Portal Hypertension Normal portal pressure : 5 - 10 mm Hg. ≥ 10 mm Hg Portal Hypertension ❖ Two important factors exist in the development of portal hypertension 1) Vascular resistance 2) Increase Blood flow 16 18 Esophageal Varices Affects one-third of patients with cirrhosis One-third of patients with varices will develop bleeding Variceal bleeding is a life-threatening complication of portal hypertension Risk factors for bleeding Variceal size and location (esophageal >gastric) Degree of portal hypertension (portal venous pressure >12 mmHg) Severity of cirrhosis 19 Varices 21 Ascites Ascites refers to accumulation of fluid within the peritoneal cavity Major causes ▪ Cirrhosis ▪ Malignancy ▪ Congestive heart failure ▪ Tuberculosis (rare in the US) The development of ascites in a patient with cirrhosis is associated with poor prognosis 22 24 Hepatic Encephalopathy (HE) ❖ Define as a spectrum of neuropsychiatric abnormalities in patients with liver dysfunction, after exclusion of brain disease. Characterized by: ✓ Personality changes ✓ Intellectual impairment ✓ Depressed level of consciousness Clinical Features Confusion Slurred speech Change in personality Asterixis Coma 25 27 Physiology of Bilirubin Metabolism Jaundice (icterus) Obstructive jaundice Extrahepatic obstruction Intrahepatic obstruction Hemolytic jaundice Prehepatic jaundice Excessive hemolysis of red blood cells or absorption of a hematoma Acute liver failure (ALF) ❖ A disease that produces rapid deterioration of liver functions that results in development of : 1) Coagulopathy, (prothrombin time >20 sec or prolonged by 4-6 seconds or INR > 1.5) 2) Encephalopathy – (any degree of mental alteration ) 3) Previously healthy individual patient without preexisting cirrhosis and with an illness of less than 6 months duration. Fulminant liver failure – encephalopathy develops within 2 weeks Subfulminant liver failure – develops within 3 months ALCOHOLIC LIVER DISEASE (ALD) Alcohol Abuse ❑Worldwide, ≈3.3 million deaths every year result from harmful use of alcohol (5.9% of all deaths) ❑Attributable to 25% of total deaths in the age group 20-29 years ❑Third leading cause of death in the US ❑4.65% and 3. 81% of American adults meet the criteria for alcohol abuse and alcohol dependence respectively 34 Risk factors for ALD Ingestion of >35 drinks per week (one drink = 10 g of ethanol) Female gender (decrease level of alcohol dehydrogenase and lower total body fluid ) Chronic hepatitis C infection Acetaminophen overdose Hereditary hemochromatosis 35 ALD Interrelationship Not all those who consume alcohol will develop ALD and liver cirrhosis 36 Metabolism of Alcohol Within the liver, 3 enzyme systems can oxidize ethanol: 1. Cytosolic alcohol dehydrogenase (ADH) 2. The microsomal ethanol-oxidizing system (MEOS) 3. Peroxisomal catalase - uses hydrogen peroxide as an oxidizing agent. The product of all 3 reactions is acetaldehyde. Acetaldehyde is a reactive metabolite that can produce injury in a variety of ways. 37 Pathogenesis of ALD cont. 38 Clinical Features of ALD Asymptomatic Incidental finding of elevated liver enzymes Microvesicular and macrovesicular steatosis with inflammation on liver biopsy Alcoholic fatty liver (steatosis) ❑ Right upper quadrant discomfort ❑ Tender hepatomegaly ❑ Nausea ❑ Jaundice (rarely) 39 Acute alcoholic hepatitis Alcoholic Cirrhosis o Malaise Stigmata of chronic liver disease o Anorexia o Fever o Jaundice o Upper abdominal discomfort o Tender hepatomegaly ▪ ▪ ▪ ▪ ▪ ▪ ▪ ▪ ▪ ▪ Hepatomegaly Splenomegaly Palmar erythema Spider angioma Gynecomastia Dupuytren’s contracture Impotence Testicular atrophy Decreased body hair Peripheral muscle wasting 40 Signs and Symptoms of Cirrhosis The Gallbladder GALLSTONE DISEASE (CHOLELITHIASIS)  Low fiber, fat-, cholesterol- and sugar- rich diet increase the risk  >90% of gallstones consist mainly of cholesterol  Humans eliminate cholesterol from the body mostly as cholesterol itself rather than as bile acids (BAs)  Cholelithiasis is considered a disturbanceof cholesterol secretion Pathophysiology of Cholelithiasis 44 Clinical Findings in Cholelithiasis  Symptomatic gallstone disease without complications  Biliary colic     Obstruction of the cystic duct or common bile duct by a stone Severe visceral pain (epigastrium or right hypochondrium) Radiates to the interscapular area, right scapula, or shoulder Usually begins and subsides suddenly, lasts less than 5 hours  Concomitant nausea with or without vomiting  Many patients develop pain usually after a fatty meal ACUTE CHOLECYSTITIS  Acute cholecystitis is the most frequent complication of gallstone disease  Causes of acute cholecystitis  Transient or permanent obstruction of the cystic duct by a stone  Bacterial inflammation  Most frequently isolated organisms include Escherichia coli, Klebsiella species, Streptococcus species, and Clostridium species  An inflammatory response to mechanical, chemical, or bacterial causes 48 49 The Pancreas Acute Pancreatitis Definition: Acute inflammation of the exocrine pancreas caused by activation of intrapancreatic enzymes causing autodigestion of the pancreatic tissue Main Causes: ▪ Biliary obstruction - causing reflux of bile into the main pancreatic duct ▪ Chronic alcoholism are the main causes of acute pancreatitis - causes spasms of the sphincter of Oddi but also affects the pancreatic cells directly. Activation pancreatic proenzymes leads to autodigestion of the pancreas Mechanisms of activation of proenzymes include: Obstruction of the main pancreatic duct (MPD) or terminal CBD, This most often occurs in women with gallstones. Biliary sludge and microlithiasis are additional causes. thickened ductal secretions related to alcohol (40% of cases), which also increases duct permeability to the pancreatic enzymes. Alcohol-induced pancreatitis is most commonly seen in men. Additional causes of Pancreatitis 53 Clinical findings ▪ Fever, nausea, and vomiting ▪ severe, boring (“knife-like”) midepigastric pain with radiation into the back ▪ Hypovolemic shock caused by third space loss of fluids. ▪ Hypoxemia - Circulating pancreatic phospholipase destroys surfactant (alveoli, collapse). ▪ Acute respiratory distress syndrome (ARDS) may occur ▪ Grey-Turner sign (flank hemorrhage) ▪ Cullen sign (periumbilical hemorrhage) ▪ DIC caused by activation of prothrombin by trypsin ▪ Tetany (spasms of the hands and feet caused by a decrease in serum ionized [unbound] calcium) ▪ Hypocalcemia is caused by enzymatic fat necrosis - Calcium binds to FAs, which decreases the serum level of ionized calcium. Cancer of the Gastrointestinal Tract Esophagus Stomach Colon and rectum Liver Gallbladder Pancreas Colon Cancer THE END