Liver Failure Flashcards
What causes jaundice?
High bilirubin concentration
Normal plasma {BR} is 17 micromol/L
If {BR} is > 30 micromol/L then you get yellow sclera and mucous membranes
If [BR] > 34 micro mol/L then skin turns yellow
What is the term given to slow/ cessation of bile flow?
Cholestasis
It normally results in jaundice but doesn’t mean a patient with jaundice has cholestasis
What are pre- hepatic causes of jaundice?
Haemolysis (haemolytic anaemia, toxins)
Massive transfusion (transfused erythrocytes are short-lived)
Large haematoma resorption
Ineffective erythropoiesis
What are intrahepatic causes of jaundice?
Specific defects:
- Reduced BR uptake- Gilberts syndrome
- Reduced conjugated BR- Crigler Najar syndrome
- Reduced excretion of BR into biliary canaliculi- Dubin-Johnson syndrome and Rotor syndrome
Intrahepatic cholestasis- reduced bile flow (sepsis, TPN and drugs)
Liver failure (Acute and chronic)
What’s the pathophysiology of liver failure?
Occurs when hepatocyte destruction > regeneration
Can be a cause of apoptosis (e.g. due to paracetamol) and/or necrosis (e.g. ischaemia)
The clinic result is catastrophic illness and can rapidly lead to coma/ death due to multi-organ failure
What is acute liver failure?
Fulminant hepatic faliure:
- Has rapid development (<8 weeks) of severe liver injury
- Impaired synthetic function (INR/PT, albumin)
- Encephalopathy
- Previous normal liver or well compensated liver disease
Sub-fulminant = <6 months
What is chronic liver failure?
Occurs over years
Cirrhosis
What are common causes of acute liver failure?
Toxins (west)
- Paracetamol
- Amanita phalloides
- Bacillus cereus
Inflammation (East)
- Exacerbations of chronic Hep B (Hong Kong)
- Hepatitis E (india)
What are other causes of acute liver failure?
Disease of pregnancy: AFLP, HELLP, hepatic infarction, HEV, Budd-Chiari
Idiosyncratic drug reactions:
- single agent- Isoniazid, NSAIDs, valproate
- drug combinations- Amoxicillin/ clavulanic acid, trimethoprim/ sulphamethoxazole, rifampicin/isoniazid
Vascular diseases: ischaemic hepatitis, post-OLTx hepatic artery thrombosis, post-arrest, VOD
Metabolic causes: Wilson’s disease, Reye’s disease
What are causes of chronic liver failure and cirrhosis?
Inflammation - e.g. by chronic persistent viral hepatitis
Alcohol abuse
Side effects of drugs- e.g. folic acid antagonist phenylbutazone
Cardiovascular causes e.g. reduced venous return- right heart faliure
Inherited diseases
Glycogen storage diseases, Wilson’s disease, Galactosaemia, Haemochromatosis, alpha1-antitrypsin deficiency
Non-alcoholic steatohepatitis
Autoimmune Hepatitis, PCB, PSC
What is the pathophysiology of cirrhosis?
Activation of kupffer cells and activation of granulocytes and lymphocytes leads to release of growth factors and cytokines
These lead to an increase in ECM and then fibrosis
What are consequences of liver failure vs normal liver function?
Coagulopathy and bleeding vs production of clotting factors
Ascitis vs protein synthesis
Encephalopathy and cerebral oedema vs detoxification
Hypoglycaemia vs glycogen storage
Increased susceptibility to infection vs immunological function and globulin production
Circulatory collapse, renal failure vs maintenance of homeostasis
What causes ascites and what are consequences of ascites?
Decreases albumin synthesis leads to ascities
This leads to decreased plasma volume which leads to:
- 2nd degree hyperaldosteronism
- hypokalaemia
-alkalosis
What clotting factors are affected in liver failure?
Hepatocytes synthesis all clotting factors apart from VWF and factor VIII
What does cholestasis lead to?
Leads to liver damage which aggravates any bleeding tendency
It leads to:
reduced bile salts
reduced micelles and absorption of vitamin K
reduced gamma- carboxylation of vitamin K dependent clotting factors (prothrombin, 2, 7, 9, 10)
Through what mechanisms does cholestasis occur?
Canalicular dilation Decreased cell membrane fluidity Deformed brush border biliary transporters Increased tight junction permeability Decreased mitochondrial ATP synthesis
What are consequences of cholestasis?
Increased BR Pruritus (itching) Cholesterol deposition Malabsorption Cholangitis
What does portal hypertension lead to?
Decreased lymphatic flow makes ascites worst
Thrombocytopenia resulting from splenomegaly
Oesophageal varices
Decrease in active clotting factors, thrombocytopenia and varices- leads to severe bleeding
Exudative enteropathy (loss of proteins):
- increased ascites- loss of albumin from plasma
- favours bacteria in large bowel veins ‘fed’ with proteins
- increased liberation of ammonium (toxic to brain)
What are causes of portal hypertension?
Increased vascular resistance
Prehepatic- portal vein thrombosis
Posthepatic- right heart failure, constrictive pericarditis
Intrahepatic:
- Presinusoidal- chronic hepatitis, PBC, granulomas (schistosomiasis, TB, etc)
- Sinusoidal- acute hepatitis, alcohol, fatty liver, toxins, amyloidosis
-Postsinusoidal- venous occlusive disease (VOD) of venules and small veins, Budd-Chiari syndrome (obstruction of large hepatic veins)
What are consequences of portal hypertension?
Malabsorption
Splenomegaly (anaemia and thrombocytopenia)
Vasodilators (glucagon, VIP, substance P, prostacyclin, NO)
Increased BP leads to increased CO which leads to hyperperfusion of abdominal organs and varices
Encephalopathy: toxins from intestines are normally extracted from portal blood by hepatocytes . Instead they enter the CNS
Varices- thin walled collateral vessels along with thrombocytopenia and reduced clotting factors leads to increased bleeding
What are consequences of encephalopathy?
Apathy, memory gaps, tremor and liver coma
What are causes of encephalopathy?
Hyperammonaemia increases:
- GI bleeding increases colonic proteins. Liver can’t convert ammonia to urea
Hypokalaemia:
- leads to intracellular acidosis which activates ammonium formation in proximal tubules and leads to systemic alkalosis
Toxins: they bypass liver and are not extracted
“False transmitters” (e.g. serotonin) from aromatic amino acids in the brain are all increased in liver failure
How is the severity of liver failure measured?
Child- Pugh score
Class A: 5-6 points- Life expectancy of 15-20 years, 10% peri-operative mortality
Class B: 7-9 points- Transplant candidates. May have 30% P-O M
Class C: 10-15 points- Life expectancy 1-3 months, 82% P-O M
What is treatment for liver failure?
Supportative
Encephalopathy- reduce protein intake (decrease ammonia produced), phosphate enemas/lactulose, no sedation
Hypoglycaemia- infusion 10-50% dextrose
Hypocalcaemia- 10ml 10% calcium gluconate
Renal failure- haemofiltration
Respiratory failure- ventilation
Hypotension- albumin, vasoconstrictor
Infection- frequent cultures, antibiotics
Bleeding- vit K, FFP, platelets
What are causes of death in liver failure?
Bacterial and fungal infection most common Circulatory instability Cerebral oedema Renal failure Respiratory failure Acid-base and electrolyte disturbances Coagulopathy
What are liver support devices trailed for treatment?
Artificial (MARS, Bio-Logic DT)- albumin exchange system. Based on removal of albumin-bound toxins from blood
Bioartifical (Hepatocytes in culture)
Hepatocyte transplantation
What is the most common liver failure cause for transplantation?
Cirrhosis
