GI 205 Alcoholism and Hepatitis Flashcards
Describe the pathway of metabolism of alcohol in the liver
Alcohol dehydrogenase –> Acetaldehyde–> Acetate –> Acetyl CoA
Why, in the metabolism of alcohol, is there a tendency towards hypoglycaemia and fatty acid accumulation
reduction of NAD+ is required in both reactions for the metabolism of alcohol
Accumulation of NADH
NADH inhibits gluconeogenesis and fatty acid breakdown
Describe the stage of Fatty Liver/Alcoholic steatosis in chronic alcohol consumption
Fatty acids accumulate in the liver due to NADH inhibiting its breakdown There is increase FA release from fat Decreased TAG excretion from the liver Decreased FA oxidation Increased lipid biosynthesis
What investigations might be done and what would they show if a patient had a fatty liver?
Raised MCV
Elevation of both aminotransferases
Raised gamma GT
Histology/CT/US showing fatty infiltration
Describe alcoholic hepatitis
Inflammation of the liver due to excess alcohol, this stage can be surpassed
Inflammatory cell infiltrates found in hepatocytes
What are Mallory bodies?
Dense cytoplasmic inclusions seen in Hepatocytes in Alcoholic Hepatitis
What will happen to the liver biochemistry in Alcoholic Hepatitis?
Raised: serum bilirubin, AST, ALT, ALP, PT and possible low serum albumin
Describe the pathology of cirrhosis of the liver
Necrosis of hepatocytes
Fibrosis due to initiation and activation of stellate cells to myofibroblasts
Nodule formation - in alcohol usually micronodular which encompass the whole liver
Interference therefore with liver blood flow and function
= clinical features of portal hypertension and impaired hepatocyte function
What would investigations show in cirrhosis of the liver?
Low serum albumin and PT indicate more severe cirrhosis
Liver biochemistry if often deranged
Low sodium indicates severe liver damage
Serum creatinine >130mcmols = wirse prognosis
What blood test is a sign of hepatocellular carcinoma?
Raised alpha feto-protein
List some of the clinical features of liver disease
Peristent jaundice Ascites Palmar erythema Caput medusa Dupuytrens contracture Spider naevi Gynaecomastia Umbilical hernia Leuconychia Clubbing Oesophageal varices
What three categories can you classify portal hypertension as?
Pre hepatic - blockage before the liver
Intra heptic - distortion of liver architechture (schistosomiasis or cirrhosis)
Post-hepatic - blockage outside the liver (rare)
What two liver function enzymes mainly indicate acute hepatocellular injury if raised?
ALT and AST
What liver enzyme is found in biliary liver cells and in bone so when raised can indicate a hepatic cholestatic injury?
ALP
What are causes of intrahepatic cholestatic injury?
Gallstones, CA pancreas
What are causes of extrahepatic cholestatic injury?
Viral cirrhosis, pregnancy, drugs
What is the main protein made by the liver?
Albumin
What does an increase in conjugated bilirubin indicate?
Obstructive jaundice
What does an increase in unconjugated bilirubin indicate?
Haemolytic jaundice
What is the most common viral hepatitis and how is it transmitted?
Hepatitis A - faeco-oral route through contaminated food and water
What is the general life cycle of Hepatitis A?
Replicates inside the hepatocytes
RNA uncoats and binds to ribosomes
Synthesis of the viral genome by RNA polymerase
Particles excreted through faeces via the billiary tree
What may you find on bloood investigations of HepA?
Slightly raised AST and ALT Increased bilirubin if patient has jaundicce Leucopenia Lymphocytosis Increased ESR
What are the complications of HepA infection?
Cholestatic hepatitis
Fulminant liver failure
Relapsing HAV infection
What main two Hep viruses are transmited through blood products and sexual contact?
Hep B and C
What are the possible complications of a Hep B infection?
Chronic hepatitis, hepatocellular ca and cirrhosis/fibrosis
What is the general presentation with hepatitis B infection?
Profound malaise, mild fever, RUQ ache, anorexia, nausea
If there is chronic hepatitis B infection what indicates prognosis?
The levels of viral replication
What hepatitis virus can only infect those with hepatitis B infection already?
Hepatitis D
Which hepatitis virus will most likely become a chronic infection?
Hepatitis C
What are other viral causes of hepatitis?
EBV, CMV, Herpes simplex
What only two viruses causes chronic hepatitis?
Hep B and C
What is the treatment for hepatitis B and C - in a chronic active infection
Antivirals - interferon, entecavir
What toxic metabolite is produced by alcohol that depletes glutathione stores?
Acetaldehyde
What is alcoholic steatosis?
Fat globules in the liver that obstruct venous flow and cause ischaemia
What is the general treatment for Alcoholic liver disease?
Alcohol withdrawal and sedation to prevent withdrawal seizures
Vitamins B,C and K
Steroids
and possible liver transplant
What is wernickes encephalopathy and why do alcoholics get it?
Thiamine deficiency - alcoholics have poor diet, required for production of the glutamate receptor
