Liver and Biliary System Lecture 17 PDF

The Liver and the Biliary System Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com. Learning Objectives Describe the normal structure of the liver, and explain the functions of the liver as they relate to the major diseases of the liver. 2. List t...

The Liver and the Biliary System Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com. Learning Objectives Describe the normal structure of the liver, and explain the functions of the liver as they relate to the major diseases of the liver. 2. List the major causes of liver injury, and describe their effects on hepatic function. 3. Compare the three major types of viral hepatitis in terms of their pathogenesis, incubation period, incidence of complications, and frequency of carriers. Explain the diagnostic tests used to identify each type of viral infection, and describe methods of prevention. 4. Explain the adverse effects of excess alcohol intake on liver structure and function. 5. Explain how gallstones are formed, and describe their causes and effects. 6. Compare the three major causes of jaundice. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com 1. The Liver Main functions ▪ Metabolism: Carbohydrates (glucose), protein, and fat delivered through the portal circulation ▪ Synthesis: Plasma proteins (albumin), clotting factors, bile production ▪ Storage: iron, vitamin B12 and other materials ▪ Detoxification and catabolism: toxins (alcohol, drugs), hormones, ammonia (aa breakdown) ▪ RBC/platelet maintenance and Immune surveillance (80% of Tissue Macrophages) https://en.wikipedia.org/wiki/Liver Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Largest organ in body, right upper quadrant abdominal area, beneath the diaphragm The Liver’s Blood Supply Portal triad, portal tracts travel together ▪ Hepatic artery branches ▪ Portal vein ▪ Bile ducts – converge to form larger ducts and empty into the common bile duct Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Has a double blood supply ▪ Portal vein: 70% of blood, drains spleen and gastrointestinal tract, rich in nutrients absorbed from intestines, low in oxygen. ▪ Hepatic artery: Rest of blood, high in oxygen, low in nutrients ▪ Both blood sources mix in the liver, eventually collecting in right and left hepatic veins that drain into inferior vena cava Liver lobule- functional unit Anatomy of the Biliary Duct System Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com FIGURE 21-4 Anatomy of the biliary duct system. Right and left hepatic ducts form the common hepatic duct, which is joined by the cystic duct to form the common bile duct, which opens into the duodenum along with the pancreatic duct through a common channel. Types of Liver Injury Manifestations ▪ Cell necrosis or apoptosis ▪ Fatty changes ▪ Mixed necrosis and fatty change Liver has regenerative capacity FIGURE 21-5 Summary of causes and effects of liver injury. Many agents can cause injury to liver cells, manifested as fatty change, necrosis, or a combination of both. Mild injury is followed by complete recovery. Severe, chronic, or progressive injury may lead to hepatic failure or diffuse scarring with impaired hepatic function. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Common types of liver injury ▪ Viral infection ▪ Fatty liver (metabolic syndrome or FLD) ▪ Toxins/ alcoholic liver disease or alcoholic hepatitis Leads to cirrhosis (scarring/fibrosis) of the liver and potential for cancer development Viruses Associated with Hepatitis Diagnosis: ▪ ALT (alanine aminotransferase) ▪ AST (aspartate aminotransferase) Released by injured hepatic cells into the blood stream ▪ Antibody detection of immune response to viral antigens All cause liver inflammation leading to swelling leading to cellular necrosis and apoptosis (ultrasound) Can cause liver damage (detected by liver enzyme tests) that may or may not result in Jaundice (bilirubin). Can produce acute illness, or progress slowly (subclinical infection) ▪ Detection of viral load Biliary tree: ▪ ALP (alkaline phosphatase) – biliary tree ▪ GGT(gamma-glutamyl transferase) hepatocytes/biliary tree Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Blood Tests Hepatitis A Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com RNA virus Incubation period: 2 to 6 weeks Excreted through nose, throat, stools Transmission: ▪ Direct person-to-person contact ▪ Fecal contamination of food or water Self-limiting ▪ no carriers ▪ no chronic liver disease Prevention/Treatment ▪ Hepatitis A vaccine ▪ Hepatitis A immune globulin: Given after exposure Hepatitis B Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ds DNAvirus Incubation period: 6 weeks to 4 months Transmission: Blood or body fluids (primarily sexual transmission) Diagnosis: Antigen–antibody test results ▪ Infected persons: Hepatitis B surface antigen (HBcAg) positive ▪ Immune persons: Presence of anti-HBsAg (vaccination/exposure) ▪ 10% don’t clear the infection and become carriers – may develop chronic liver disease and liver cancer ▪ Hepatic injury is caused by chronic inflammation in response to virus causing scarring and necrosis Prevention/Treatment ▪ Hepatitis B vaccine ▪ Hepatitis B immune globulin: Given immediately after exposure ▪ Antiviral drug treatment are also available (control/slow progression, not cure) – liver transplant Hepatitis C ▪ Early on – typically asymptomatic (mild symptoms of fatigue, nausea, muscle/joint pain, jaundice in 20-30%) ▪ 75% do not clear infection and develop chronic liver disease with 10-20% leading to cirrhosis (20-30 years) and 1-5% develop cancer ▪ no immunization available – high mutation rate ▪ Treated with antiviral drugs (3 month course of protease inhibitors with a 95% cure rate) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ssRNA virus - Incubation period: 3 to 12 weeks Transmission: Blood and body fluids – primarily injection drug use, not as readily transmitted sexually Diagnosis: Antigen–antibody test results ▪ Hepatitis C virus (HCV) RNA: Presence of virus in blood and active infection (PCR) – and genotyping (1-6) ▪ Anti-HCV Ab: indicates infection but does not confer immunity ▪ Ultrasound, biopsy (cirrhosis staging) Hepatitis D: Delta Hepatitis Only infects persons with acute or chronic hepatitis B virus (HBV) infection Delta virus is unable to produce its own virus coat and uses HBsAg produced by HBV Most U.S. cases from sharing needles Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Small, defective RNA virus Hepatitis E Transmission ▪ Oral–fecal ▪ Contaminated water No prevention of disease after exposure Tends to be acute and self limiting (similar to hep A) No immunization available Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com RNA-containing virus Fatty Liver Disease Caused by injury to liver that either: ▪ Increases fatty acid synthesis, Decreases oxidation of FA or impairs release of lipids from carrier proteins Common in heavy drinkers and alcoholics and can be caused by drugs/chemicals and solvents Impaired liver function, but injury is still reversible If not controlled, can lead to liver injury, cirrhosis, cancer and liver failure FLD Diagnosis: ▪ Liver enzymes (AST/ALT), Ultrasound, CT/MRI, biopsy Most commonly associates with: • alcoholic liver disease (ALD) • NAFLD in type II diabetes patients or metabolic syndrome (central obesity, HBP, hyperglycemia (insulin resistance), elevated HDL/trigyleride levels) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Role in fat metabolism can lead to fat accumulation in liver cells (steatosis) - blood comes directly from Intestines through portal vein Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Alcoholic Liver Disease Refers to a group of structural and functional changes in the liver resulting from excessive alcohol consumption Three stages of progression 1.Alcoholic fatty liver: Mildest form – reversible 2.Alcoholic hepatitis: Causes degenerative changes and necrosis of liver cells (inflammation – neutrophil infiltration) 3. Alcoholic cirrhosis: Most advanced, progressive, diffuse scarring leading to disturbed liver function Mallory bodies ▪ irregularly shaped pink (cytokeratin filament) deposits in hepatocyte cytoplasm ▪ indicative of severe hepatic injury (irreparable) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Severity depends on amount and duration of alcohol consumption Cirrhosis Manifestations ▪ Liver failure ▪ Portal hypertension ▪ Ascites, collateral circulation formation Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Diffuse scarring of the liver from any cause with derangement of liver function and regeneration commonly caused by: ▪ Alcoholic liver disease ▪ Chronic hepatitis ▪ Severe liver necrosis Less common: ▪ Repeated liver injury: Drugs and chemicals ▪ Long-standing bile duct obstruction ▪ Genetic/Autoimmune disease Manifestations of Cirrhosis ▪ Hepatic encephalopathy – confusion, disorientation (decreased toxin clearance from blood – ammonia and bacterial breakdown products from gut) ▪ Clotting disorders ▪ Increased estrogen levels - (decreased metabolism) ▪ Loss of osmotic pressure (loss of albumin) edema/acites ▪ Portal hypertension: ascites – collection of fluid in abdomen Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Extensive scarring interrupts and disorganized lobule architecture eventually effecting all aspects of liver function ▪ Anastomoses: circulatory bypass routes are formed connect systemic-portal venous systems ▪ Blood shunted away from high-pressure portal system into low-pressure veins of systemic circulation ▪ Increased pressure causes esophageal veins become distended and weaken ▪ Risk of fatal hemorrhage from esophageal varices ▪ Stomach, spleen and rectum can also develop anastomoses (connection collateral circulation) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Interruption of blood circulation through the liver results in portal hypertension and reduced blood flow Treatment of Cirrhosis-portal hypertension Endoscopic ligation/ablation of varices – drugs to reduce portal hypertension (octetride) Liver transplant -5y survival is 75%, graft failure occurs in 10% - possibility of living donor – required if cirrhosis is advanced Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Surgical procedures ▪ Portal-systemic anastomoses to control varices ▪ Splenorenal shunt ▪ Portacaval shunt ▪ Intrahepatic portosystemic shunt ▪ Trans jugular intrahepatic portosystemic shunt (TIPS) ▪ An alternative to an open operative procedure ▪ Intrahepatic shunt between hepatic and portal vein branches Reye Syndrome Pathogenesis Characteristics ▪ Affects infants and children ▪ Fatty liver with liver dysfunction ▪ Cerebral edema with neurologic dysfunction ▪ No specific treatment – mortality rate of 25% Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Evidence suggests the combined effect of viral illness and use of acetylsalicylic acid (aspirin) Aspirin may increase injurious effects of virus causing ▪ Liver swelling - damage ▪ Brain swelling - damage Bile Other substances present in bile ▪ Lecithin: Lipid that also functions as a detergent ▪ Cholesterol ▪ Water ▪ Minerals Bile is secreted continually ▪ Concentrated and stored in gallbladder ▪ During digestion, gallbladder contracts, releasing bile into the duodenum ▪ Bile does not contain digestive enzymes, but acts as a biologic detergent – aids in digestion of fats Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Bile: Aqueous solution with various dissolved substances ▪ Conjugated bilirubin ▪ Bile salts: Major constituent of bile; derivatives of cholesterol and amino acids; emulsify fat; function as detergents Bilirubin ▪ When red blood cells break down, iron is reused, and iron-free heme pigment or bilirubin is excreted in the bile ▪ Small quantities of bile are continually present in blood ▪ When blood passes through liver, bilirubin is removed by conjugation (combining bilirubin with glucuronic acid, making it soluble – reduced toxicity ▪ Bilirubin is eliminated in feces (stercobilin) and urine (urobilin) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Bilirubin is produced by the liver, from the breakdown of red blood cells in spleen and liver by resident macrophages Jaundice Causes of accumulation ▪ Hemolytic jaundice: Increased breakdown of red cells (prehepatic) ▪ Hepatocellular jaundice: Liver injury that impairs conjugation of bilirubin and downstream elimination (hepatic) ▪ Obstructive jaundice: Bile duct obstructed by tumor or stone that impairs delivery of bile into duodenum (post hepatic) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Yellow discoloration of skin and sclera from accumulation of bile pigment (bilirubin) in tissues and body fluids Biliary Cirrhosis Secondary biliary cirrhosis ▪ Obstruction of large extrahepatic bile ducts ▪ Gallstone, carcinoma in pancreas, cancer from common bile duct ▪ Increased pressure causes damage with inflammation and scarring of hepatocytes ▪ Treatment: Relieve or bypass duct obstruction Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Primary biliary cirrhosis ▪ Autoimmune disease that attacks small intrahepatic bile ducts ▪ Slow/progressive destruction of small intrahepatic bile ducts from chronic inflammation ▪ Eventually spreads up to lobules ▪ No specific treatment, may lead to liver failure ▪ Require liver transplant Cholelithiasis Formation of stones in the gallbladder – excess cholesterol Factors influencing stone formation ▪ Increased cholesterol in bile (obesity, high fat diet) ▪ Decreased bile excretion (dieting) ▪ Once seeded – continue to grow in size Blockage leads to cholecystitis : inflammation Cholangitis – bile duct obstruction/inflammation Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Incidence (estrogen increases hepatic secretion of cholesterol) ▪ Higher in women than men ▪ Higher in women who have borne several children ▪ Twice as high in women who use contraceptive pills ▪ Higher in obese women Cholelithiasis Diagnosis: ▪ Elevated bilirubin ▪ ALP,GGT elevated ▪ Ultrasound, CT Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Complications ▪ Asymptomatic if remain in gall bladder ▪ Biliary colic if stone is extruded into cystic duct bile from liver can still empty into duodenum ▪ Common duct obstruction: Obstructive jaundice ▪ Cystic duct obstruction: pain, but no jaundice, acute cholecystitis may occur with preexisting infection in gallbladder ▪ Can also be blocked by pancreatitis – or in turn cause pancreatitis ▪ Stasis in ducts can result in bacterial infection, inflammation and mucosal irritation Cholecystitis ▪ ▪ ▪ ▪ Treatment Antibiotics, analgesics Removal of stone by endoscopy (Endoscopic Retrograde CholangioPancreatography -ERCP) Cholecystectomy (removal of gall bladder) Chenodeoxycholic acid dissolves gallstones Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Inflammation of gallbladder ▪ RUQ pain, fever, nausea ▪ 90% caused by gall stone blockage ▪ Chronic infection is commonly associated – inflammation/damage ▪ Impaction of a stone in neck of gallbladder may cause acute cholecystitis Liver Tumors Liver cancer is most rapidly increasing incidence of any cancer in United States ▪ Increase due to obesity, excess alcohol consumption and chronic hepatitis C infection Also common site of metastatic carcinoma (from GI, breast, lung etc.) ▪ Common in developed countries ▪ Spread from primary sites, such as gastrointestinal tract, lung, breast ▪ Tumor cells carried in the blood and delivered to the liver via hepatic artery Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Hepatocellular carcinoma (white arrows) most common liver cancer – Associated with HBV infection cases worldwide The Liver and the Biliary System Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com.