Liver Lecture Notes PDF

Liver Basic Concepts of Liver Function Located in RUQ Hepatocytes ◦ Functional cells of liver Blood supply ◦ Hepatic artery ◦ Portal vein ◦ Venous drainage from GI tract Liver disease ◦ Hepatocellular injury ◦ Obstructive injury ◦ Both Basic Functions of the Liver Bile ◦ Liver: Synthesis ◦ Ga...

Liver Basic Concepts of Liver Function Located in RUQ Hepatocytes ◦ Functional cells of liver Blood supply ◦ Hepatic artery ◦ Portal vein ◦ Venous drainage from GI tract Liver disease ◦ Hepatocellular injury ◦ Obstructive injury ◦ Both Basic Functions of the Liver Bile ◦ Liver: Synthesis ◦ Gallbladder: Storage Route ◦ Hepatic duct ◦ Common bile duct ◦ Duodenum Enterohepatic recycling ◦ Ileum: Reabsorb bile salts ◦ Return to liver Basic Functions of the Liver: Bilirubin Metabolism Bilirubin Yellow-colored compound, RBC breakdown Hemoglobin broken down to heme and globin Heme broken down to iron and porphyrin Bilirubin metabolism Porphyrin converted to biliverdin Biliverdin converted to free or unconjugated bilirubin Unconjugated bilirubin travels to liver  Bilirubin metabolism (continued) 6. In liver, unconjugated bilirubin converted to water-soluble form Bilirubin 7. (conjugation) Conjugated bilirubin excreted in Metaboli 8. bile Some conjugated bilirubin in sm colon converted to urobilinogen by bacteria 9. Later excreted in urine (yellow color) Liver and Carbohydrate Metabolism  Basic Functions of the Liver Detoxification ◦ Ingested substances and drugs ◦ Portal vein brings venous drainage from GI tract to liver Other functions ◦ Stores vitamins, iron, copper ◦ Produces insulin- like growth factor 1 ◦ Synthesizes thrombopoietin for platelet synthesis  Hepatocyte injury may result in the following: Basic ◦ Decreased clotting factor synthesis ◦ Decreased albumin Functions ◦ Decreased detoxification activity of the ◦ Excess accumulation of drugs, hormones, and metabolites Liver ◦ Decreased storage of nutrients ◦ Decreased conjugation of bilirubin ◦ Decreased deamination activity Hyperbilirubinemia and Jaundice Factor Characteristic Jaundice Yellowing of skin and sclera Hyperbilirubinemia High bilirubin levels in blood Leads to jaundice (icterus) Excessive RBC Prehepatic jaundice hemolysis Hepatocellular injury Intrahepatic jaundice Bile duct obstruction Posthepatic jaundice Hepatocytes Inflammation and Infection Inflammation ◦ Caused by virus, drugs, or toxic substances ◦ Hepatitis virus: A, B, C, D, G ◦ CMV and Epstein-Barr virus can also cause inflammation ◦ Viral hepatitis may become chronic ◦ Increases risk for hepatocellular cancer ◦ Toxic hepatitis ◦ Liver affected by drugs § Acetaminophen ◦ Enzymes § Cytochrome P450 system  Alcohol damage Nonalcoholic fatty liver Hepatocyt disease (NAFLD) es Fatty buildup in liver Inflammati Can lead to cirrhosis on and Infection Nonalcoholic steatosis (NASH) May progress to liver failure Bile Duct Obstruction Biliary obstruction ◦ Blockage of any duct that carries bile from liver to intestines Presentation ◦ Conjugated bilirubin backs up (cholestasis) ◦ Builds up in the blood ◦ Hyperbilirubinemia ◦ Jaundice Assessment and Signs and Symptoms Patient history Dark urine ◦ Changes in appetite, digestion, bowel changes Pruritus (itching) Abdominal pain Spider angioma ◦ RUQ tenderness ◦ Fine capillaries that fan out ◦ Hepatomegaly Caput medusa Anorexia ◦ Dilated veins in umbilical area Weakness Ascites Hyperbilirubinemia ◦ Jaundice Steatorrhea Spider Angioma Diagnostic Tests in Liver Disorder Liver Enzymes Bilirubin Other Tests Alanine Direct (conjugated) Albumin level transaminase (ALT) Aspartate Indirect Prothrombin time transaminase (AST) (unconjugated) Alkaline Hepatitis serology: phosphatase HAV, HBV, HCV Ultrasound CT, MRI Liver biopsy Treatment Supportive care with rest, fluids Small high-calorie, high-protein meals Lifestyle changes Avoid alcohol or any drugs (not prescribed) Hepatitis Interferon, nucleoside analogues, protease inhibitors, and other antiviral agents Liver transplant, if needed  Hepatitis A (HAV) Hepatitis B (HBV) Hepatitis C (HCV) Hepatitis D (HDV) Hepatitis Hepatitis E (HEV) Hepatitis G (HGV) Other viruses: EBV, CMV Nonviral hepatitis: Toxic chemicals, certain drugs, autoimmune disease Hepatitis Signs and Symptoms (General) Fever Anorexia Abdominal pain Loss of taste for food Flu-like symptoms Smokers often lose their taste for tobacco Nausea and vomiting Hepatomegaly Fatigue Jaundice Malaise Stool that may have a Myalgias pale appearance Arthralgias Dark urine Mild headache Pruritus  Hepatitis A Virus (HAV) Factor Characteristic Transmission Fecal-oral Shellfish can concentrate the virus particles Endemic in part of world Cooking Will kill virus Signs/Symptoms Fever, abdominal pain Mild flu-like symptoms Vaccine Primary prevention Postexposure prophylaxis HAV alone HAV-HBV combination Treatment Supportive HAV immunoglobulin (Ig) available for contacts of patients with HAV infection Hepatitis B Virus (HBV) Overview Course is variable Transmission: Most do not recover Blood products, body completely fluids, sexual contact Contacts can obtain Does not directly kill HBIg (rapid, passive cell immunity) Host’s immune Chronic HBV system destroys viral- Can be healthy infected cells carriers without disease evidence Can lead to hepatocellular cancer HBV General Signs and Symptoms Anorexia Spider angioma Nausea and vomiting Palmar erythema Fatigue Jaundice can last for Flu-like symptoms months ◦ Fever, malaise, myalgias Patients with severe Jaundice infection: Hepatomegaly ◦ Hepatic encephalopathy Splenomegaly Lymphadenopathy  HBV Stages Stage 1 Stage 2 Stage 3 Stage 4 Incubation Inflammation Immune Virus cannot period hepatocytes system reacts be detected No signs or Flu-like Viral Antibodies symptoms symptoms replication to HBsAg, slows HBcAg, and HBeAg Can infect Jaundice Lack of Antibodies others Serology: sign/symptom for HBsAg HBeAg, HBsAg, s long-term and HBV DNA immunity 2–4 week Elevated AST, HBV low or Anti-HBcAg duration ALT undetectable only with infection, not vaccination 3–4 week Normal AST, HBV: Diagnosis Not correlated with disease HBsAg: Diagnosis severity Time of active replication of the virus HBeAg blood levels Most closely monitored during convalescent phase HBV DNA in the liver and bloodstream are also available Acute and chronic IgM- versus IgG-type infection  Treatment ◦ Based on symptoms ◦ Supportive with rest ◦ Small, high-calorie and high- protein meals ◦ Interferon alpha HBV: ◦ Prevention is key ◦ Current antiviral therapies Treatment ◦ Achieve suppression of HBV replication ◦ Complete clearance of the virus rarely achieved Hepatitis C Virus (HCV) Various genotypes Progression Infection normally with Acute infection usually one principle genotype mild Directs treatment options Long incubation period 2 weeks to 8 months Asymptomatic, can spread the virus Remain dormant for years before symptoms Progress to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) Hepatitis C Virus Treatment Protease Anti-viral Current drug inhibitor drugs therapy combinations Nondetectabl Paritaprevir- e levels of ritonavir- virus in 12 ombitasvir- weeks based regimen  Other Hepatis Viruses Hepatitis D Hepatitis E Hepatitis G Requires Hep B Similar to HAV Similar to Hep C IV drug usage Fecal-oral Similar Sexual contact transmission to Hep C Accelerates Most common Rare progression in cause of hepatitis those HBV+ in parts of the world Serology testing to Most recover Virus eventually confirm diagnosis without treatment cleared No specific No specific treatments treatments Nonalcoholic Fatty Liver Disease (NAFLD) Most common cause chronic liver disease in the United States Unrelated to alcohol consumption Etiology: Unclear Associated with metabolic syndrome, insulin resistance, obesity Hepatocytes: Accumulate triglycerides Steatosis: Greater than 5% of liver contains fat Nonalcoholic steatohepatitis (NASH) Extreme form of NAFLD Scarring and inflammation of liver occurs Nonalcoholic Fatty Liver Disease (NAFLD) Accumulation fat disrupts cellular function Insulin resistance causes more fat storage in liver Cells can rupture Damaging inflammatory response Signs and symptoms Mild cases: None, abnormal liver enzyme levels may be present NASH: Obvious signs of liver impairment Edema, jaundice, fatigue Can lead to hepatocellular carcinoma (HCC)  NAFLD: Diagnosis Factor Characteristic Specific biomarker or blood None test Rule out all other possible liver disease causes Serology Viral hepatitis rule out Biomarker procollagen C3 Discriminate between patients with or without histological diagnosis of NASH Increases with severity of NASH Liver enzymes May be normal Indices NAFLD Liver Fat Score (NLFS) Hepatic Steatosis Index (HSI) Fatty Liver Index (FLI) Liver biopsy Gold standard Magnetic resonance imaging- Accurate derived proton density fat Limited availability fraction (MRI-PDFF)  Weight loss and exercise Caloric restriction Low fructose diet NAFLD Treatment Bariatric surgery Medication Lipid- Glucagon- lowering Insulin like peptide- SCD-1 agents sensitivity 1 (GLP-1) inhibitors (monitor for medications agonists liver toxicity)  Alcohol Steatosis Potent toxin to Initial cellular hepatocytes change Susceptible to repeated damage Alcoholic Liver Disease Common for patients to not provide Can progress accurate to cirrhosis history of alcohol intake AUDIT; a 10-item questionnaire  60 to 80 grams of alcohol/day Men for 10 years usually develop cirrhosis 20 to 40 grams of alcohol/day Women for 10 years Alcohol usually develop cirrhosis Consumpti on Ingestion of 25-fold 160 grams of increased risk of developing alcohol per alcoholic liver disease day [one beer = 12 g] Alcoholic Liver Disease Alcoholic Hepatitis Alcoholic Liver Disease Acute disorder AKA alcoholic Reversible and cirrhosis transient symptoms Development ◦ Long period of time Resolve with alcohol ◦ Permanent cessation Long-term effects Diagnosis may remain ◦ Liver biopsy Alcoholic Liver Disease Signs and Symptoms Acute Alcoholic Hepatitis Severe Alcoholic Hepatitis RUQ pain and Hepatic tenderness encephalopathy ◦ Confusion, disorientation, Nausea or stupor Coagulation Malaise dysfunction Low-grade fever Spontaneous bruising and bleeding Jaundice Hyperbilirubinemia Darkened urine Jaundice Hepatomegaly Hematemesis Alcoholic Liver Disease Signs and Symptoms Chronic alcohol liver disease Hepatomegaly and splenomegaly Portal hypertension with esophageal varices Bulging flanks with shifting abdominal dullness Ascites Spider angioma Proximal muscle wasting Gynecomastia in males  Alcoholic Liver Disease: Diagnosis Diagnostic Result Diagnostic Results (continued) AST elevation Alk Phos elevation ALT elevation Albumin decreased Hypertriglyceridemia Total protein decreased Hypercholesterolemia Liver biopsy results Coagulation disturbances Carbohydrate-deficient transferrin (CDT) Bilirubin levels Gamma-glutamyl transferase (GGT) Physical examination results Ethyl glucuronide: Biomarker alcohol usage  Cessation of alcohol Proper nutrition Treatment of Alcoholic Liver High-protein diet (unless Disease hepatic encephalopathy present) Improvement of liver function if there is 6 months of abstinence from alcohol Alcohol Withdrawal Syndrome (AWS) Alcohol-dependent Abruptly cease alcohol consumption 6 to 24 hours after last alcoholic drink patients Nausea/vomiting, hypertension, tachycardia, tremors, Symptoms: hyperreflexia, irritability, anxiety, headache Delirium tremens: More severe Requires close monitoring and management After the acute Nutrition, psychological support, medications syndrome is resolved Cirrhosis and End-Stage Liver Disease Silent and gradual Cirrhosis Irreversible damage Collagen and connective tissue infiltration HCV Causes Alcoholic liver disease NAFLD Portal hypertension develops Caput medusa Liver functions compromised Liver Cirrhosis Portal Hypertension  Liver Failure Complications Factor Characteristic Portal Esophageal varices hypertension Hematemesis Ascites Decrease bile Decreased fat digestion and steatorrhea synthesis Decreased fat-soluble vitamin absorption Decreased Bleeding, bruising coagulation factors Dupuytren Progressive fibrosis of the palmar fascia contracture Fetor hepaticus Sweet odor of breath due to dimethyl sulfide Anemia If GI bleed  Liver Failure Complications Factor Characteristic Decrease albumin Edema Decrease Low platelets thrombopoietin Decrease bilirubin Jaundice conjugation Decrease High drug/hormone levels detoxification Decrease High nitrogen levels deamination Hepatic Confusion, seizure encephalopathy Liver Failure Complicati ons Cirrhosis and End-Stage Liver Disease: Diagnosis Liver biopsy remains the gold standard Non-invasive Transient elastography Fibro-scan determines liver stiffness methods Metavir scoring system: Four grades Staging cirrhosis Child-Turcotte-Pugh (severity/mortality Model for end-stage liver disease Often used decision regarding liver transplantation risk) Cirrhosis and End-Stage Liver Disease: Treatment Analyze blood factors every 6 Recalculate Child-Turcotte-Pugh and MELD scores months Counseling and therapy: Abstain alcohol Reduce obesity and diabetes Health Vaccinations Medication evaluation (including OTC pain relievers) management Antiviral treatments when warranted Alert! HBV ◦ Persons recovered from HBV can still be carriers of inactive HBV