Liver Failure Flashcards
What is normal plasma bilirubin?
17 μmol/L
What happens if BR is high?
If [BR] ↑s > 30 μmol/L
→ yellow sclera & mucous membranes
If [BR] ↑s > 34 μmol/L
→ skin turns yellow
What is cholestasis?
Slow/cessation of bile flow
Normally results in jaundice
Jaundice does not
What are the pre-hepatic causes of jaundice?
Haemolysis
Haemolytic anaemia
Toxins
Massive transfusion
(transfused erythrocytes short-lived)
Large haematoma resorption
Ineffective erythropoiesisWhat are the intra-hepatic causes of jaundice?
Specific defects: ↓ed BR uptake Gilberts syndrome ↓ed conjugation BR Crigler-Najar syndrome ↓ed secretion BR into biliary canaliculi Dubin-Johnson syndrome Rotor syndrome
Intrahepatic cholestasis (↓ed outflow): Sepsis, TPN & drugs
Liver failure
Define the pathophysiology of liver failure
When rate of hepatocyte death > regeneration
Combination of apoptosis &/or necrosis
What is the clinical result of liver failure?
Clinical result = catastrophic illness
Can rapidly lead to coma/death due to multi-organ failure
What is acute liver failure?
Fulminant hepatic failure = rapid development (< 8wks) of severe acute liver injury
- impaired synthetic function (INR/PT, albumin)
- encephalopathy
- previously normal liver or well-compensated liver disease
What is chronic failure?
Over years
Cirrhosis
What are the causes of acute liver failure in the west?
Toxins
Paracetamol
Amanita phalloides
Bacillus cereus
What are the causes of acute liver failure in the west?
Inflammation
Exacerbations of chronic Hep B (Hong Kong)
Hepatitis E (India)
What are the other causes of acute liver failure?
Disease of pregnancy
AFLP/HELLP/Hepatic infarction/ Budd-Chiari
Idiosyncratic drug reactions
Single Agent: Isoniazid, NSAID’s, valproate
Drug combinations: Amoxicillin/clavulanic acid, trimethoprim/sulphamethoxazole, rifampicin/isoniazid
Vascular disease
Metabolic causes
Wilson’s disease- copper deposition
Reye’s syndrome- children taking aspirin after chickenpox
What are the causes of chronic liver failure?
Inflammation
- chronic persistent viral hepatitis
Alcohol abuse
Side effects of drugs
- folic acid antagonists
- phenylbutazone
Cardiovascular causes
- ↓venous return - right heart failure
Inherited diseases
Glycogen storage diseases, Wilson’s disease, Galactosaemia, Haemochromatosis, α1-antitrypsin deficiency
Non alcoholic steatohepatitis (NASH)
Autoimmune Hepatitis, PBC, PSC
Describe the mechanisms of cirrhosis
Necrosis of heptoctyes causes release of enzymes
Kick off cytokines
Activate Kupffer cells
Release growth factors
Stimulate hepatic stellae cell
Monocytes to macropahges
Stimulates fibroblast proliferation
Causes fibrosis and cholestasis
What are the consequences of hepatocyte failure?
Coagulopathy and bleeding Ascites Encephalopathy & cerebral oedema Hypoglycaemia Increased susceptibility to infection Circulatory collapse, renal failure
What does the decrease in protein synthesis result in?
Decreased albumin Decreased plasma (clotting factors)
What is the consequence of decreased albumin?
↓ albumin → ascites
Plasma vol ↓
→ 20 hyperaldosteronism
→ hypokalaemia (↓K+)
→ alkalosisWhat is the consequence of decreased plasma (clotting factors)?
Hepatocytes synthesis all coagulation proteins except von Willebrand factor & factor VIIIC
What can cholestasis cause?
→ liver damage aggravates any bleeding tendency - ↓ bile salts - → ↓ micelles & absorptn of vit K - → ↓ γ-carboxylation of vit K - dependent clotting factors prothrombin (II), VII, IX, & X
What are the mechanisms of cholestasis?
Canalicular dilation ↓ cell membrane fluidity Deformed brush border Biliary transporters ↑ tight junction permeability ↓ mitochondrial ATP synthesis
What are the consequences of cholestasis?
↑ BR → jaundice Pruritus (itching) Cholesterol deposition Malabsorption Cholangitis
What is portal hypertension?
Blood cannot travel through portal vein
Takes another route via blood vessel not designed to take high blood flow
Caused by increased vascular resistance
What does portal hypertension result in?
thrombocytopenia (destroy platelets) resulting from splenomegaly
Oesophageal varices
↓ active clotting factors, thrombocytopenia, & varices → severe bleeding
exudative enteropathy
What is exudative enteropathy?
↑ ascites → loss of albumin from plasma
favours bacteria in large bowel being “fed” with proteins
↑ liberation of ammonium (toxic to brain)
What are the prehepatic causes of portal hypertension?
Portal vein thrombosis
What are the intrahepatic causes of portal hypertension?
Presinusoidal -chronic hepatitis, PBC, granulomas (schistosomiasis, TB, etc.
Sinusoidal - acute hepatitis, alcohol, fatty liver, toxins, amyloidosis, etc.
Postsinusoidal - venous occlusive disease of venules & small veins; Budd– Chiari syndrome (obstruction of large HVs).
What are the posthepatic causes of portal hypertension?
right heart failure
constrictive pericarditis
What are the consequences of portal hypertension?
Malabssorption Splenomegaly Vasodilation Encephalopathy Varices
How does it cause encephalopathy?
Toxins from intestine (NH3, biogenic amines, FFAs, etc.) normally extracted from portal blood by hepatocytes → CNS
Varices
How does it cause varices?
Thin walled collateral vessels + thrombocytopenia & ↓ clotting factors → bleeding +++
What is hepatic encephalopathy?
memory gaps, tremor & liver coma
How do you assess the severity of liver failure?
Child-Pugh score
Assesses disease severity for end-stage liver disease, and a prognosticator for peri-op death
How do you use child-push scores?
Class A: 5-6 points - Expectancy of 15-20 years, 10% peri-operative mortalityClass B: 7-9 points - Transplant candidates, may have 30% P-O MClass C: 10-15 points - Life expectancy 1-3 months, 82% P-O M
What is the treatment for encephalopathy?
reduce protein intake
phosphate enemas/lactulose
no sedation
What is the treatment for hypoglycaemia?
infusion 10-50% dextrose
10 ml 10% calcium gluconate
What is the treatment for renal failure?
haemofiltration
What is the treatment for respiratory failure?
ventilation
What is the treatment for hypotension?
Albumin
Vasoconstrictors
What is the treatment for infection?
Frequent cultures
Antibiotics
What is the treatment for bleeding?
Vit K
FFP
Platelets
What are the causes of death?
Bacterial and fungal infections
Circulatory instability
Cerebral Oedema
Renal failure
Respiratory failure
Acid-base and electrolyte disturbance
Coagulopathy
What are the indications for liver transplantation?
Acute liver failure Cholestatic disease Cancer Cirrhosis Metabolic disease
What percentage of transplants in the UK are livers?
5%
What is the 5 year survival with a liver transplant?
60-80%
