Liver Module 11 PDF

1 When you look at the liver – considered accessory organ of digestion with numerous functions  read slide The liver has a major impact on health status and multiple important functions, but is also has excellent regenerative and restorative capabilities. Hepatic Failure is the most severe conse...

1 When you look at the liver – considered accessory organ of digestion with numerous functions  read slide The liver has a major impact on health status and multiple important functions, but is also has excellent regenerative and restorative capabilities. Hepatic Failure is the most severe consequence of liver disease – most patients die within a few weeks or months. It may follow years of low-grade hepatitis C infection or may occur suddenly with the onset of fulminating hepatitis B. Acute liver failure may also follow from an overdose of certain medications, including acetaminophen, taken either as a suicide attempt or inadvertently at high doses by individuals using the drug for pain relief. About 90% of hepatic function must be destroyed before failure occurs. The clinical features of hepatic failure are: Jaundice because of the failure to excrete bilirubin Ascites because of increased portal pressure and blood osmotic pressure Fector hepatitis, literally “liver breath,” because of an accumulation of volatile waste products such as ammonia Two conditions associated with liver failure are: hepatic encephalopathy and hepatorenal syndrome 2 Hepatic Encephalopathy is a complex neurologic syndrome characterized by memory lapses and personality changes. A particularly characteristic sign is asterixis, a rapid extension-flexion motion of the hand and extremities that can be demonstrated by testing for the “hepatic flap” – the arms are held extended and the hands dorsiflexed. A pulsating, flapping, or hand waving motion constitutes a positive test. Hepatic encephalopathy results from accumulation of toxins in the blood, which occurs when the liver fails to transform or detoxify the blood because of poor hepatocyte function. As toxins and metabolic byproducts accumulate, osmotic pressure increases, leading to brain swelling and cerebral edema. Cerebral edema herniation and death 3 One of the main toxins that accumulate and is implicated in causing many of the symptoms of hepatic encephalopathy is ammonia. Ammonia is a by-product of protein metabolism and intestinal bacterial action. An important function of the liver is to convert the ammonia to urea which is then excreted out by the kidneys. Well, in liver failure the ammonia is not converted and it reaches the brain altering cerebral metabolism and interfering with the function of neurotransmitters. Neurologic signs include rigidity, hyperreflexia, and, rarely seizures. Fatal coma may occur. 4 Hepatorenal syndrome is a complication of advanced liver disease. It refers to the occurrence of renal failure see in association with advanced liver disease. Pathophysiology generally accompanies sudden decrease in blood volume (which may be from GI bleeding …or…hypotension from failing liver. The hypotension  decreased GFR  tubular necrosis Also… the liver can not remove vasoconstrictive substances (angiotension, vasopressin, catecholeamines)  renal vasoconstriction With hepatorenal syndrome, blood volume expands, hydrogen ions accumulate, and electrolyte balance is disturbed. 5 The word Hepatitis refers to inflammation of the liver and can have numerous causes; the most notable being viral infection. But it can also be caused by: Reactions to drugs and toxins Infectious disorders  malaria, infectious mono, virus 6 Hepatitis A (previously known as infectious hepatitis) Caused by small RNA-containing virus Virus recovered from feces, bile and blood of infected individuals Mode of transmission fecal-oral route (contaminated food or water  eating shellfish from contaminated waters; poor hygiene) Virus replicated in the liver Is excreted in bile Shed in the stool The incubation period (time between exposure and onset of symptoms) for HAV is 2 to 4 weeks. Individuals who have the disease may be contagious for as long as 2 weeks before the onset of symptoms as fecal shedding greatest for 10-14 days before onset of symptoms. Infection is much more common that actual disease is; by mid adult life about half of people in developed countries have blood anti – HAV antibodies as evidence of infection, but few recall being ill. Rates are even higher in developing nations, where most children have evidence of disease (anti-hepatitis antibodies in blood) by age ten. HAV does not cause a carrier state or cause chronic hepatitis. The disease usually runs its course within approximately 4 months after exposure. 7 Hepatitis B (formerly known as serum hepatitis) Caused by a double stranded DNA virus (known as the Dane particle) Can produce acute hepatitis, chronic hepatitis, progression from chronic to cirrhosis, to fulminant hepatitis with massive necrosis Transmitted thru contact with infected blood, body fluids or contaminated needles No known risk factors in 30-40% of cases Maternal transmission can occur if mom infected during last trimester Risk ranges from 10-85% depending on mother’s HBV core antigen (HBeAg status) Infants who become infected have a 90% risk of becoming chronic carriers and up to 25% will die of chronic liver disease as adults 2 billion people in the world infected with HBV over 1 million people in US have chronic HBV infection HBV has a long incubation period, between 1 and 7 months with average onset of 1 to 2 months. The acute stage of an active infection may last up to 2 months. Approximately 5 to 10% of adults with HBV develop chronic hepatitis and continue to experience hepatic inflammation for longer than 6 months Chronic HBV infection associated with 10-100-fold risk of liver cancer Vaccine available to prevent transmission & development of hepatitis B Provides long-term protection against HBV infection As a health care worker you should have the HBV vaccine 9 Serologic markers Three well-defined antigens are associated with the virus: Two core antigens HBcAg HBeAg One surface antigen – HbsAg These antigens then provoke the development of specific antibodies to them Anti-HBs Anti-HBc Anti-HBe 10 12 Hepatitis C (formerly known as non-A, non-B hepatitis) was identified in 1989. Caused by single strand RNA Causes most cases of post-transfusion hepatitis (before screening was available). 3.9 million Americans infected with HCV most common blood-borne infection in US concern that even small amount of blood during tattooing, acupuncture and body piercing can facilitate transmission surpassed alcoholic cirrhosis as predominant chronic liver disease in US Chronic hepatitis occurs in 50-80% of cases Most common cause of chronic liver disease, cirrhosis, liver cancer worldwide No vaccine  difficult to develop vaccine as there are over 50 subtypes of the virus Clinical symptoms tend to be milder than for HBV. Jaundice is uncommon (only about 25%) will exhibit jaundice. Hepatitis C seldom leads to fulminating hepatitis. Antibody and antigen testing is available Unlike HAV & HBV antibodies are not protective –they just serve as markers of the disease 13 Hepatitis D (delta) is actually a defective RNA virus that cannot on its own infect the hepatocyte to cause hepatitis. Instead, it co-infects with HBV, so it only occurs in those with hepatitis B (like a superinfection) as it depends on the hepatitis B virus for replication. The Delta agent often increases the severity of the HBV infection  can convert mild HBV infection into severe, fulminant disease. Hepatitis E Common in developing countries Clinically resembles hep A Does not cause chronic or carrier state Distinguishing feature There is high mortality (20%) among pregnant women  develop fulminant hepatitis Occurs primarily in underdeveloped countries Hepatitis G - not much known, ? if related to post-transfusions hep, no asoc with cancer 14 Nice chart showing the different characteristics of the hepatitis virus. 15 Two mechanisms of liver injury with hepatitis virus: 1. Direct cellular injury 2. Induction of immune responses against the viral antigen Pathophysiology of hepatitis includes: Hepatic cell necrosis Scarring  leading to fibrosis Kupffer cell hyperplasia & infiltration with phagocytic cells Cell injury promoted by cell-mediated immunity ( cytotoxic T-cells and natural killer cells) Regeneration of hepatic cells begins within 48 ours of injury Inflammatory process Damages and obstructs bile ducts Cholestasis Obstructive jaundice 16 Clinical course consists of four phases: 1. Incubation: period from initial exposure to the onset of symptoms 2. Prodromal (pre-icteric) Begins about 2 weeks after exposure & ends with appearance of jaundice Fatigue, nausea, vomiting, HA, low-grade fever RUQ pain common, weight loss (anorexia out of proportion to degree of illness) Infection highly transmissible at this phase Serum ALT & AST start to show variable increases 3. Icteric Begins about 1-2 weeks after prodromal Lasts ~2-6 weeks Jaundice  caused by hepatocellular destruction & intrahepatic bile stasis (though jaundice less likely to occur with HCV infection) Urine dark colored & stools clay colored (before onset of jaundice) from conjugated bili This is the actual phase of illness Liver enlarged, smooth, tender  abd pain persist or becomes more severe Jaundice lasts 2-6 wks or longer  severe itching Prolonged prothrombin time 4. Recovery phase (convalescent) Begins with resolution of jaundice (about 8wks after exposure) Symptoms diminish increased sense of well-being LFTs return to normal within 2-12 wks after onset of jaundice Chronic active hepatitis (constitutes a carrier state) May begin at this point Associated with HBV & HCV infection (evidence that HDV) 75-80% of chronic cases are d/t HCV Persistence of clinical manifestations & liver inflammation LFT remain abnormal for longer than 6 months HbsAg persists Fulminant hepatitis Clinical syndrome resulting in severe impairment or necrosis of liver cells Potential for liver failure Usually seen in hep C, and hep B (especially if co-infected with delta virus Can also be caused by drugs or metabolic disorders, immunologic damage Develops ~ 6-8 wks after initial symptoms Hepatic necrosis is irreversible 60-90% of children die Liver transplant may be needed for survival 17 Cirrhosis is an irreversible inflammatory disease that disrupts liver function and structure. It is a leading cause of death in the US. And, represents the end stage of chronic liver disease Normal liver architecture and function are disrupted with the development of diffuse fibrosis & nodular regeneration nodules form between fibrous bands gives liver a cobbly appearance liver hard, firm when palpated Obstruction can cause portal hypertension  increased resistance to flow in the portal venous system blood shunted  hypoxia necrosis, atrophy failure ascites  increased amount of peritoneal cavity (late-stage manifestations of cirrhosis and portal hypertension increased capillary pressure & obstruction of venous flow through liver salt and water retention by kidneys decreased colloidal osmotic pressure d/t impaired synthesis of albumin by the liver 18 Various causes include: 1. alcoholic cirrhosis (also called Laennec’s cirrhosis) occurs after years of alcohol abuse begins with fatty infiltration of liver toxic effects of alcohol on liver causes lipid peroxidation, disrupts cytoskeleton & membrane function 2. Biliary cirrhosis Damage & inflammation leading to cirrhosis begin in bile canalculi & bile ducts (rather than hepatocytes) Primary biliary cirrhosis  autoimmune disease of unknown etiology destruction of small intrahepatic bile ducts women more often than men usually after 30yrs of age asymptomatic to symptomatic. Life expectancy 8-10 yrs after onset of symptoms Secondary biliary cirrhosis develops with prolonged partial or complete obstruct of common bile ducts or branches obstruct could be by gall stones, tumors, chronic pancreatitis, biliary atresia and cystic fibrosis cause secondary cirrhosis in children 3. post-necrotic result of severe liver disease clinical manifestations portal hypertension, ascites, bleeding varices, encephalopathy are prominence symptoms death d/t bleeding or encephalopathy needle bx for diagnosis 25% of people with hep C develop post necrotic cirrhosis other causes: drugs or toxins alpha 1 –antitrypsin advanced alcoholic cirrhosis or primary cirrhosis that progresses 19 Flow map of pathogenesis of the clinical manifestations seen in cirrhosis 20 Ate one to many peeps at Easter. Hang in there….one more module (and quiz) and we are at the end! 21