Liver Failure Flashcards
What is jaundice?
Plasma bilirubin conc >30 mu m/L (normal is 17). - yellow sclera and mucous membranes
Above 34 - skin turns yellow
Cholestasis - slow/cessation of bile flow, normally results in jaundice
But jaundice dosa not necessarily mean there is cholestasis
What causes jaundice?
Pre hepatic: haemolysis, massive transmission, had mariam resorption, ineffective erythropoiesis
Intra hepatic: specific defects (eg. Gilberts syndrome - decreased bilirubin uptake), acute and chronic liver failure, drug side effects, oestrogens, CF etc , intrahepatic cholestasis (sepsis, TPN, drugs)
Post hepatic : gall stones, tumours etc
What is the pathophysiology of liver failure?
When rate of hepatocyte death > regeneration
A combination of apoptosis (paracetamol) and/or necrosis (ischaemia)
Clinical result = catastrophic illness.
Can rapidly lead to death/coma due to multi organ failure
What are the definitions of acute and chronic liver Failure?
Acute:
Fulminant hepatic failure = rapid (<8 weeks) development of Severe acute liver injury
Impaired synthetic function (INR/PT, albumin)
Encephalopathy
Previously normal liver or well compensated liver disease
Sub-fulminant = < 6 months
Chronic liver failure:
Over years
Cirrhosis
What causes acute liver failure?
Toxins(west) :
Paracetamol
Amantia phalloides
Bacillus cereus
Inflammation (east):
Exacerbations of chronic Hep B (Hong Kong)
Hepatitis E (india)
Other (less common): diseases of pregnancy (AFLP, HELLP syndrome, hepatic infarction, HEV, Budd-chiari). Idiosyncratic drug reactions (NSAIDS, co amoxiclav). Vascular diseases (ischaemic hepatitis, post OLTx hepatic artery thrombosis, post arrest, VOD). Metabolic causes (Wilson’s disease, Reye’s syndrome)
What causes chronic liver failure?
Causes (of cirrhosis):
Inflammation - chronic persistent viral hepatitis
Alcohol abuse
Side effects of drugs - folic acid antagonists, phenylbutazone
Cardiovascular causes - decreased venous return, right heart failure
Inherited diseasss - glycogen storage diseases, Wilson’s disease, galactosaemia, haemachromatosis, a1-antitrypsin deficiency
Non alcoholic steatohepatitis (NASH)
Auto immune hepatitis, PBC, PSC
What is cirrhosis?
Noxious factors -> necrosis of hepatocytes -> enzyme leak (lysozymes) -> activation of kuppfer cells and granulocytes -> activation of hepatic Stellate cells which turn into myofibroblasts. Also fibroblast proliferation -> extracellular matrix production -> FIBROSIS
Then the fibrosis causes cirrhosis
What are the functions of the liver?
Metabolic and catabolic:
Synthesis and utilisation of carbohydrates, lipids and proteins
Secretory and excretory:
Synthesis and secretion of proteins, bile and waste products
Detoxification and immunological functions: breakdown of ingested pathogens and processing of drugs
What are the consequences of liver failure?
Coagulopathy and bleeding (reduce production of clotting factors)
Ascites (less proteins synthesis)
Encephalopathy and cerebral oedema (lack of detoxification)
Hypoglycaemia (reduced glycogen storage)
Increased susceptibility to infection (lack of immunological function and globulin production)
Circulatory collapse, renal failure (bad maintenance of homoeostasis)
What are the consequences of a lack of protein synthesis?
Decreased protein synthesis
Decreased albumin -> ascites :
- plasma volume decreases:
Leads to secondary hyperaldosteronism
Hypokalemia
Alkalosis
Decreases plasma conc of clotting factors :
Hepatocytes synthesise all coagulation proteins except VWF and factor VIII
What is cholestasis?
Leads to liver damage
Aggravates any bleeding tendency:
Decreasss bile salts ->
Decreased micelles and absorption of vitamin K ->
Decreased carbozylation of Bitamin K- dependant clotting factors (II, IV, VII, IX, X)
What mechanisms lead to pathophysiology in cholestasis? And what does this cause?
Canalicular dilation
Decreased cell membrane fluidity
Deformed brush border
Biliary transporters (eg. Carriers on the wrong side)
Increased tight junctions permeability
Decreased mitochondrial ATP synthesis
Consequences:
Increased bilirubin -> jaundice
Pruitus (itching)
Cholesterol deposition
Malabsorption
Cholangitis
What is portal hypertension in liver failure?
Decreased lymphatic flow -> makes ascites worse
Thrombocytopenia resulting from splenomegaly
Oesophageal varices
Decrease in active clotting factors, thrombocytopenia, varices -> severe bleeding
Exudative enteropathy:
Increased ascites -> loss of albumin from plasma
Favours bacteria in large bowel being fed with proteins
Increased liberation of ammonium (toxic to the brain)
What causes portal hypertension?
Increased vascular resistance
Pre hepatic:
Portal vein thrombosis
Post hepatic:
Right heart failure, constructive pericarditis
Intra hepatic:
Presinusoidal - chronic hepatitis PBC, granulomas
Sinusoidal - acute hepatitis, alcohol, fatty liver, toxins, amyloidosis
Post sinusoidal - Venus occlusive disease of venules and small veins; budd-Chiari syndrome
What are the consequences of portal hypertnesion?
Increased portal vein pressure:
Malabsorption
Splenomagaly - anaemia and thrombocytopenia
Vasodilators - glucagon, VIP, substance P, prostacyclins, NO). -> low BO -> high cardiac output -> hyperperfusion of abdominal organs and varices
Encephalopathy- toxins from intestine (NH3, biogenic amines, FFSs) normally extracted from portal blood by hepatocytes -> CNS
Varices - thin walled collateral vessels, thrombocytopenia and decreased clotting factors —> bleeding tons
