Liver failure (45)

Question 1

What is normal plasma bilirubin?

Answer 1

17 micromol/L

• if [BR] > 30 –> yellow sclera and mucous membranes
• if [BR] > 34 –> skin turns yellow

Question 2

What is cholestasis?

Answer 2

• slow/cessation of bile flow

- normally results in jaundice

Question 3

What are pre-hepatic causes of jaundice?

Answer 3

• haemolysis
• massive blood transfusion (transfused erythrocytes short-lived)
• large haematoma resorption
• ineffective erythropoiesis–> overproduction of haem

Question 4

What are intrahepatic causes of jaundice?

Answer 4

• Gilberts syndrome: dec. BR uptake into liver, so raised unconjugated BR
• Crigler-Najar syndrome: dec. conjugation of BR
• Dubin-Johnson + Rotor syndrome: dec. secretion of BR into biliary canaliculi
  ^^^ autosomal recessive disorders
• intrahepatic cholestasis
• liver failure: acute and chronic

Question 5

When does liver failure occur?

Answer 5

• when rate of hepatocyte death> hepatocyte regeneration
• combination of apoptosis and necrosis (ischaemia–> most affects zone 3, bc furthest away from blood supply)
• can cause catastrophic illness and lead to coma/death

Question 6

What are the 2 types of acute liver failure?

Answer 6

• fulminant hepatic failure= rapid development of sever acute liver injury < 8weeks–> impaired synthetic function and encephalopathy
• sub-fulminant= < 6months

Question 7

What are the causes of acute liver failure?

Answer 7

• paracetamol overdoses
• amanita phalloides mushroom
• bacillus cereus
• exacerbations of chronic hep B (Hong Kong)
• hep E (India)
• pregnancy diseases: AFLP, HELLP syndrome, hepatic infarction, HEV, Budd-Chiari
• idiosyncratic drug reactions: single agent or drug combination
• vascular diseases: ischaemic hepatitis, post-OLTx hepatic artery thrombosis, post-arrest, VOD
• Wilson’s disease, Reye’s syndrome

Question 8

What are the causes of chronic liver failures?

Answer 8

• inflammation: chronic persistent viral hepatitis
• alcohol abuse
• cardiovascular disease: hepatic congestion due to right sided heart failure
• side effects of drugs
• inherited diseases: galactosaemia, alpha1-antitrypsin deficiency, glycogen storage diseases, Wilson’s disease
• non alcoholic steatohepatitis
• autoimmune hepatitis, PBC, PSC

Question 9

What are the consequences of liver failure?

Answer 9

• X production of clotting factors (except vwf and factor VIIIC)–> coagulopathy and bleeding
• X protein synthesis–> ascites bc inability to produce enough protein to retain fluid in the bloodstream
• X detoxification–> encephalopathy and cerebral oedema
• X glycogen storage–> hypoglycaemia
• inc. susceptibility to infection bc liver has immunological function
• renal failure and circulatory collapse

Question 10

Which clotting factors are dependent on vitamin K?

Answer 10

prothrombin (II), VII, IX and X

Question 11

What are the consequences of cholestasis?

Answer 11

bile leaks through tight junctions

• jaundice bc inc. BR
• pruritus/itching bc bile salts
• cholesterol deposition
• malabsorption in small intestine
• cholangitis

Question 12

What are the consequences of portal hypertension?

Answer 12

• blood cannot enter portal vein, so goes through small vessels/ forms portosystemic shunts–> they enlarge
• splenomegaly bc blood backs up here–> thrombocytopenia bc spleen traps platelets
• oesophageal varices (enlarged oesophageal veins)–> easily ruptured–> bleeding
• exudative enteropathy: bowel exudes protein

Question 13

What are the causes of portal hypertension?

Answer 13

prehepatic
- portal vein thrombosis, causing obstruction
intrahepatic
- cirrhosis
- schistosomiasis
- sarcoidosis (inflammatory cells form granulomas)
posthepatic
- right sided heart failure
- constrictive pericarditis

Question 14

What is encephalopathy and what causes it?

Answer 14

tremor, apathy, memory gaps

• hyperammonaemia
• hypokalaemia
• toxins bypassing liver and not being extracted
• false transmitters being released e.g. serotonin

Question 15

What parameters can be used to assess the severity of liver failure?

Answer 15

• total bilirubin
• serum albumin
• INR
• ascites
• hepatic encephalopathy
  Child-Pugh score system

Question 16

How do we treat portal hypertension supportively?

Answer 16

• encephalopathy: reduce protein intake, lactulose, no sedation
• hypoglycaemia: infusion 10-50% dextrose
• hypoglycaemia: 10ml 10% calcium gluconate
• renal failure: haemofiltration
• respiratory failure: ventilation
• hypotension: albumin, vasoconstrictors
• infection: frequent cultures
• bleeding: vit k, ffp, platelets

Question 17

What is the cause of death in portal hypertension?

Answer 17

• bacterial and fungal infections
• circulatory instability
• cerebral oedema
• renal failure
• respiratory failure
• acid-base and electrolyte disturbance
• coagulopathy

Question 18

What types of liver support devices exist?

Answer 18

• artificial (MARS, bio-logic DT)- albumin exchange system–> based on selective removal of albumin-bound toxins from blood
• bioartificial (hepatocytes in culture)
• hepatocyte transplantation