Liver Pathophysiology and Disease Study Guide PDF

- Liver Pathophysiology / Diseases - Liver diseases are classified into: - Parenchymal (Hepatocellular) or Obstructive - Acute or Chronic - Pre-Hepatic (increased unconjugated bilirubin) - Hemolysis - Hematoma reabsorption - Hepatoce...

- Liver Pathophysiology / Diseases - Liver diseases are classified into: - Parenchymal (Hepatocellular) or Obstructive - Acute or Chronic - Pre-Hepatic (increased unconjugated bilirubin) - Hemolysis - Hematoma reabsorption - Hepatocellular (Parenchymal) Injury (increased conjugated bilirubin, ALT/AST, PT, and AP; decreased albumin if chronic) - Acute: - Drug toxicity - "tylenol is the \#1 cause of acute liver failure" - Other drugs that are toxic to the liver: NSAIDs, amiodarone, anabolic steroids, long-term glucocorticoids, carbon tetrachloride, TPN, cancer chemotherapeutic agents, some herbal remedies - Halothane (Fluothane) Hepatitis - Acetaminophen is not the only drug that can cause acute liver failure - Halothane: VA introduced in 1950's - Found to cause ALF (hepatic necrosis) - incidence 1:35,000 ("extremely rare") - Reactive TFA (trifluoroacetyl) metabolite (halothane is 20% metabolized this way) - Can occur with Enflurane (2%) \> Iso (0.2%) \> Des (0.01%) - Halothane is not longer available in the US - still used in developing countries - Two distinct suspected manifestations: - Elevated LFTs without evidence of liver failure - due to combination of halothane and hypoxia? - Severe ALF - immune mediated process? - Infection (presumably Hepatitis A and B) - Alcoholic hepatitis - Pregnancy-related - Hyperemesis Gravidarum - 1st trimester, emesis that warrants IVFs; elevated liver enzymes in up to 50% - Intrahepatic Cholestasis - 2md or 3rd trimester; impaired bile acid transport in lobule; high-risk pregnancy - Preeclampsia (HTN, Edema and Proteinuria) - 3rd trimester; "treatment is to deliver the baby" - Elevated aminotransferases = severe preeclampsia - HELLP syndrome: Hemolysis, Elevated Liver Enzymes, Low Platelet Count; treatment is to deliver the baby - AFLP: Acute Fatty Liver of Pregnancy - 3rd trimester; fatty infiltration of the liver that causes portal HTN and hepatic encephalopathy; treatment is to deliver the baby - Chronic: - Alcoholic liver disease - Non-alcoholic fatty liver disease - Caused by excessive fatty deposits in the liver - Ranges in severity from steatosis (simple fat deposits) → steatohepatitis/NASH (hepatocellular necrosis) - Associated with metabolic syndrome - Insulin resistance - Obesity - Central Adiposity - Type-II Diabetes - HTN - Elevated triglycerides - Most common cause of elevated liver enzymes in adults - NASH: Liver biopsy shows steatosis with inflammation and fibrosis - Treatment: weight loss (bariatric surgery) - Acute vs Chronic Hepatitis: - Acute Hepatitis - - Hepatocellular injury due to viral infection, drug reaction or exposure to hepatotoxin - Acetaminophen - Alcohol - Mushrooms - Chronic Hepatitis - - Lasting \>6 months - Lab values do not correlate with disease severity - Liver biopsy -\> classification into one of three types - Chronic Persistent Hepatitis - Chronic Lobular Hepatitis - Chronic Active Hepatitis- \*assume cirrhosis - "Hepatitis C - most likely to develop into chronic liver failure" - Hepatocellular Carcinoma - Most common primary liver malignancy - 3rd most common cause of death globally - Men \> women - Risk: - Treatment: - Treatment for non surgical patients: - "Typically have an ultrasound every 6 months" - Cholestatic / Post-Hepatic (increased conjugated bilirubin; AST/ALT if late dx; AP, GGTP, and 5'-NT; decreased albumin late dx) - Biliary disease - affects \> 20 million in the U.S. - Causes: - Biliary obstruction - Cholestatic disease - Chronic: - Impaired bile flow increases biliary pressure and backflow into liver → hepatocyte destruction - If bacteria in bile → ascending cholangitis, hepatic abscess, sepsis, and acute kidney injury can occur - Deficiencies in Vitamin K-dependent clotting factors (II, VII, IX, X) - Hypercoagulability - S&S: fatigue, pruritus, dark urine, pale stools - Diagnosis: Abdominal US to determine extrahepatic vs. intrahepatic cause - Extrahepatic causes: bile duct obstruction by stone, stricture, mass - Intrahepatic causes: immune-mediated, infectious, drug-induced, paraneoplastic, ischemic - Labs: Elevated serum AP and GT; may have elevated bilirubin - Check AMA (antimicrobial antibody) titers to rule out Primary Biliary Cholangitis - Treatment: Endoscopic Retrograde Pancreatography (ERCP) - Primary biliary cholangitis (PBC) - autoimmune "no test questions" - Primary sclerosing cholangitis (PSC) - autoimmune "no test questions" - Sepsis - Cirrhosis - **End-result** of chronic liver diseases - Lobules are replaced with fibrosis and regenerative nodules - "What zone cells are most susceptible to ischemia? Zone 3 → these are responsible for glycolysis, lipogenesis, and detoxification / biotransformation" - Disrupts blood flow thru liver → leading to shunt formation → "blood backs up into portal venous circulation" → Portal HTN, Esophageal Varices, Ascites Hepato-renal syndrome (HRS), Pulm HTN - Increased hepatic resistance and intrahepatic vasoconstriction- portal pressure continues to increase → portal HTN - Body responds with splanchnic vasodilation → causes a decreased effective arterial circulation - Now the SNS and RAAS get activated → leads to sodium and water retention, hypervolemia, increased CO - viscous cycle - S&S: - Jaundice, thrombocytopenia, bleeding, endocrine abnormalities, diabetes, hepatocellular carcinoma - Labs: - Increased ALT, AST, AP, GGT, bilirubin, PT, - Decreased albumin - Causes: - Alcoholic Liver Disease - Chronic Hepatitis - Nonalcoholic Steatohepatitis Hemochromatosis - Wilson's Disease - Primary Biliary Cirrhosis - Primary Sclerosing Cholangitis - Alpha-1 Antitrypsin Deficiency Prolonged Cholestasis - Toxins / Drugs - Hepatic Venous Outflow Obstruction - Cystic Fibrosis - Treatment: depends on disease severity - Multiple Systems are affected: - Coagulation - Hemostasis - mechanisms at play affecting both intrinsic and extrinsic pathways - \*\*\*Leads to disrupted balance between bleeding and clotting\*\*\* - Decreased synthesis of both clotting and inhibiting factors - Decreased synthesis of Vitamin-K dependent clotting factors (II, VII, IX, X) - Especially in cholestatic diseases (bile salts are needed for absorption of Vitamin K) - Liver synthesizes all procoagulant and anticoagulant factors EXCEPT: III (thromboplastin), IV (calcium), and VIII (VWB) - Liver is also how activated clotting factors are cleared from the body - Vitamin K administration can correct this - Decreased synthesis of thrombopoietin → leads to thrombocytopenia → low and dysfunctional platelets - Decreased synthesis of inhibiting factors (protein C, protein S, antithrombin III,) - Increased consumption of platelets and clotting factors - Decreased clearance of activated factors - Hyperfibrinolysis - Accelerated intravascular coagulation/DIC - Renal dysfunction / Hepatorenal Syndrome - Sodium and water retention - Renal hypoperfusion and decreased GFR - Increased prostaglandin levels help maintain renal perfusion - "caution w/ meds that affect prostaglandins - no NSAIDS" - Increased sensitivity to nephrotoxic drugs: - Aminoglycosides - ACE-Inhibitors - ARBs - Definitive treatment: Transplant (in severe cases - combined liver and kidney transplants) - Hepatic encephalopathy - Seen with both acute and chronic liver disease - Result of accumulated neurotoxins (commonly ammonia, but can occur without it) - Neuropsychologic and neuromotor symptoms - Neuropsychological Symptoms: - Impaired LOC and attention - Impaired ability to follow commands - Altered affect - Neuromotor Symptoms: - Hyper-reflexiveness (Asterixis, Clonus, Babinski) - Nystagmus - Decerebrate posturing - Cirrhotic cardiomyopathy - Liver disease patients (cirrhosis) have hyperdynamic circulation - "take home message" - High cardiac output - Low BP (systolic and diastolic dysfunction) - "especially post induction" - Low SVR (from release of nitric oxide) - Increased overall fluid volume with decreased circulating volume - Decreased responsiveness to beta-adrenergic stimulation - Prolonged Q-T interval - Dr. Schlesinger's Notes: portal HTN causes release of vasodilators (esp. NITRIC OXIDE)... "overproduction of vasodilators" means sympathetic responsiveness is less effective - Pulmonary complications - Hepatopulmonary Syndrome (HPS) - Affects up to 20% of liver transplant patients - **Triad** of liver dysfunction, unexplained hypoxemia and intrapulmonary vascular dilation - Intrapulmonary vascular dilation (IPVD) - Type I lesions: precapillary dilations = functional shunts - Type II lesions: larger dilations in central lungs = anatomic shunts - Post Pulmonary HTN - Affects 4-6% of liver transplant patients - Pulmonary HTN in a patient with portal HTN - Increased risk in female patients and autoimmune hepatitis - Hepatic Hydrothorax (HH) - Ascites fluid passes from peritoneal cavity into pleural space thru defects in the diaphragm - Dr. Schlesinger's Notes: - Other causes: **Cystic fibrosis and A1 Antitrypsin Disease -** metabolic syndrome (Lung and Liver consequences) - Ascites - "Remember they are 'puff balls' and seem fluid overloaded but are intravascularly dry" - Associated with a 50% mortality within 3 years - Infections common - Treatment: - Paracentesis + slow correction of hyponatremia - Needed with serum Na+ is \< 120-125 - If corrected too quickly: central pontine myelinolysis - Sodium restriction - Diuretics - Albumin replacement if \> 6-8 L drained by paracentesis - Varices - End result of portal HTN - Treated with beta-blockers to decrease portal pressure and endoscopic ligation - Decrease portal pressure by: decreasing CO and decreasing splanchnic vasoconstriction