Liver and Gallbladder Flashcards
Liver recap?
Normal adult liver weighs between 1.4 and 1.6 kg and it receives a dual blood supply: 60 to 70% is provided by the portal vein and the rest by the hepatic artery. The lobular model divides the liver into many different lobules each one with a terminal hepatic vein found at the center and portal tracts at the periphery. Three different zones are present, 1 being closest to the blood supply and and 3 being the farthest.
• Periportal Area : Closest to blood supply, hepatocytes perform oxygenation and gluconeogenesis. The cells are mostly affected by hepatitis and chronic liver conditions.
• Zone 2 : It hosts most of the oval cell, liver stem cells, has a high regenerative potential.
• Perivenular Area : It receives the least oxygenated blood thus being extremely sensitive to ischemic and toxic insults. Hepatocytes perform lipogenesis, triglyceride synthesis and glycolysis.
What are some important liver markers? And what do they represent?
• Aspartate Transaminase (AST) : Not liver specific as it is also found in other organs like heart and kidneys. It catalyzes the transfer of the amino group from aspartate to alpha ketoglutarate, in order to from glutamate and oxaloacetate. Its increase may be due to MI, cirrhosis, systemic infections, myopathies and hemolysis.
• Alanine Transaminase (ALT) : Liver specific and found only in the cytoplasm. Catalyzes the transfer of an amino group from alanine to alpha ketoglutarate, to form glutamate and pyruvate. It’s increase is related to autoimmune hepatitis, viral hepatitis, ischemic or toxic liver injury.
• Lactate dehydrogenase (LDH) : It is the final enzyme of anaerobic glycolysis, which catalyzes the conversion of lactate into pyruvate. It is a general marker of cellular damage.
• Alkaline Phosphatase (ALP) : it is present in bones, bile ducts, intestine and placenta. It’s increase can be either physiological like in the pregnancy or due to bile duct obstruction aka Cholestasis, medications, and infiltrative disease of the liver like sarcoidosis.
• Bilirubin increase is usually due to obstructive conditions or acute alcoholic hepatitis.
What does the ratio between ALT and AST tell us?
ALT/AST < 1 = mild liver damage. ALT/AST > 1 = necrotic, severe liver damage. In the first case alcohol abuse is the first suspect.
What is acute hepatitis?
It is a potentially reversible condition. It is the consequence of severe liver injury with the onset of encephalopathy within eight weeks of the appearance of the first symptoms. Every type of hepatitis can have an acute presentation. It can be induced by viral infections not HCV, drugs or toxins, acute alcoholic hepatitis and autoimmune hepatitis. Histologically it is characterized by lobular damage that extends from the portal tract to the central vein, cholestasis, no fibrosis, ballooned hepatocytes which are enlarged, apoptosis and necrosis around central vein.
What is chronic hepatitis?
It is defined by hepatocellular damage, inflammation, and fibrosis continuing without improvement for at least six months. It is attributable to viral infections like HBV, HBV+HDV and HCV, drugs reaction, autoimmune disorders, alcoholism, genetic disease or unknown causes. It can be chronically active in which fibrosis and cirrhosis are expected to develop or chronically persistent with the absence of cirrhosis.
What is acute liver failure?
Associated with encephalopathy and coagulopathy that occurs within 26 weeks of initial injury in absence of previous liver disease. It is caused by massive hepatic necrosis most often induced by drugs or toxins such as acetaminophen which accounts for almost 50% of failures, autoimmunity and acute viral infections. Clinically patients present nausea, vomiting and jaundice followed by life-threatening encephalopathy and coagulation defects. Portal hypertension is present due to diminished blood flow through the portal venous system because of an obstruction mainly in the intrahepatic zone causing ascites and encephalopathy. Serum level transaminases are elevated and there is initial hepatomegaly. Eventually multi organ failure and death occurs unless transplantation occurs. Morphologically it’s presents massive hepatic necrosis with areas filled with scarring and micro micro vesicular steatosis.
What is chronic liver failure?
The leading causes are chronic HBV infection, chronic HCV infection, non-alcoholic fatty liver disease and alcoholic liver disease. Liver failure in chronic liver disease is most often associated with cirrhosis which is a condition characterized by diffuse transformation of the entire liver into parenchymal nodules surrounded by fibrous bands. Keep in mind not all cirrhosis lead to liver failure and not all end stage chronic liver disease are cirrhotic. Clinically 40% of patients with cirrhosis are asymptomatic until the latest stages when they present anorexia, weight loss, weakness, jaundice, bacterial infections and encephalopathy.
Hepatitis A virus?
Usually benign disease with an incubation period of 2 to 6 weeks. Does not cause chronic hepatitis and very rarely causes acute failure. Clinically it presents none to very little symptoms which are non specific. Spread by contaminated food, water and close contact with other infected as it is present in serum and saliva. CD8+ T cells play a key role in hepatocellular injury during HAV infections.
Hepatitis B virus?
HBV can lead to acute hepatitis, chronic hepatitis, hepatic failure and liver necrosis. It is also an important precursor for HCC development. It has a high incubation period 2 to 26 weeks. Transmission is perinatal in most cases but happens also because of unprotected sex and drugs use. Clinically 65% of newly infected don’t have any symptoms or mild symptoms, 25% has non specific symptoms and the rest develops in chronic disease. The hosts immune response is the main determinant of the outcome of the infection, HBV does not cause directly damage to the hepatocytes rather cytotoxic CD8+ T cells are responsible. The diagnostic hallmark is hepatocytes with swollen ER by HBaAg. HBV is the only DNA virus of the hepatitis family and thus complete cure is difficult. The goal is to slow down progression, reduce liver damaged and prevent HCC. Carrier state exist where an individual can transmit it and has no symptoms.
Hepatitis C?
HCV is major cause of liver disease work wide. The most common risk factors are drug abuse, multiple sex partners, surgery and unknown. Perinatal transmission occurs but at the very low percentage compared to HBV. HCV is very unstable giving rise to multiple genotypes and subtypes that there is no vaccine yet. Incubation period ranges from 4 to 26 weeks. Clinically about 85% of patients are asymptomatic the only signs could be high transaminases and HCV RNA is blood. Only rare cases are severe, there is also a small percentage of patients that are able to clear the infection for unknown reasons. Most patients develop chronic disease and 20% of them eventually show cirrhosis. HCV is associated with metabolic syndromes and is able to give rise to insulin resistance and nonalcoholic fatty liver disease. Histologically represents a very dense inflammatory infiltrate that becomes organized into a follicle with a germinal center, HCV may induce steatosis in the centrilobular area centrilobular area.
Hepatitis D?
Infections can occur in different settings: co infection which is exposure to both HDV and HBV it results in acute hepatitis, super infection which is a chronic carrier of HBV and is exposed to new HDV and causes sever acute hepatitis. Patience with HDV usually present very severe chronic hepatitis. HDV RNA is detectable in blood and liver days before acute symptomatic disease. IgM Anti HDV are the most reliable indicators. Histologically it shows interface hepatitis and many plasma cells and lymphocytes.
Hepatitis E?
It is a waterborne infection that occurs primarily in young or middle-aged adults. It is a zoonotic disease which uses monkeys cats pigs and dogs as reservoirs. It has a very high mortality rate among pregnant women approaching 20%. It accounts for 30 to 60% of cases of acute hepatitis in India. Clinically it is mostly asymptomatic, the course is characterized by a rise in ALT and then the appearance of IgM Anti HEV. Histologically is characterized by necrosis in the central area and bile plugs.
What is non hepatotrophic hepatitis?
Several bacteria, fungi and other parasite can cause liver damage. The most common are CMV and HSV which are non hepatotrophic viruses, bacteria such as S. Aureus, S. Typhi and T. Pallidum. They may proliferate in the biliary tree causing Ascending Cholangitis, jaundice may account due to biliary obstruction. Bacteria may give rise to abscesses and are associated with fever, pain and tender hepatomegaly. Parasites involved in the disease are malaria, schistosomiasis, ecchinococcosis, leishmaniasis and amebiasis.
Autoimmune hepatitis?
Chronic progressive hepatitis with features of autoimmune disease such as genetic predisposition, associated with other autoimmune diseases, presence of autoantibodies and response to immunosuppressants. Female predominance, 74% and highest in north Europe. Type 1 in middle aged and older patients with anti nuclear antibodies, anti smooth muscle antibodies and anti soluble liver antigen. Type 2 in children and teenager presents anti liver kidney microsome and anti liver cytosol antibodies. Clinically it may be indolent, but it usually has acute presentation. Prognosis is better in adults. Cirrhosis occurs in at least 40% of cases. Histologically it shows necrosis, plasma cells and sometimes even biliary duct damage. Immunosuppressants and steroid have a food response.
What is drug and toxin induced liver injury?
Predictable hepatotoxins such as acetaminophen, unpredictable hepatotoxins such as chlorpromazine, chemotherapy of colorectal cancer, glucocorticoid may cause steatosis and chemotherapy in general. Histologically presents with patters of acute hepatitis. There is an important amount of eosinophils, granulomas and necrosis.
What is alcohol liver disease?
Excessive alcohol consumption is the leading cause of liver disease. Daily intake of 80 g or more of ethanol a day generates a significant risk of severe hepatic injury. Other factors such as gender, ethnicity and other conditions are important. The exact causes our unknown but some factors are known to play important roles such as acetaldehyde which impacts reactive species.
Five year survival approached 90% with abstainers and those who are free of jaundice and ascites. It drops to 50% in those who continue drinking. In end stage alcoholic liver disease the main causes of death are HCC, hepatic coma, infection and GI hemorrhage.
