Liver failure

Question 1

what is normal plasma bilirubin and bilirubin in jaundice?

Answer 1

Normal : 17 micromol/L

Bilirubin > 30 mmol/L = yellow sclera and mucous membranes

Bilirubin >34 mmol/L = yellow skin

Question 2

What is Cholestasis

Answer 2

slow bile flow

Cholestasis - normally results in jaundice

Jaundice does not necessarily mean there is cholestasis

Question 3

Pre-hepatic jaundice causes?

Answer 3

Haemolysis = increased production = conjugated bilirubin

Having a massive transfusions : red cells are short lived

Large haematoma resorption

Ineffective erythropoiesis

Question 4

Intrahepatic causes of jaundice?

Answer 4

Gilbert - decreased BR uptake

Crigler-Najjar - Decreased conjugation BR

Dubin-Johnson, Rotor syndrome - decreased secretion BR in canaliculi

Drug side effects, sepsis, TPN

Acute and chronic liver damage

Estrogens, cystic fibrosis

All cause decreased cholestasis

Question 5

Post - Hepatic causes of jaundice?

Answer 5

Gall stones, tumors

Cause extrahepatic outflow decrease

Question 6

What is Acute liver failure?

Answer 6

Fulminant hepatic failure = rapid development under 8 weeks

• impaired synthetic function e.g. albumin, INR/PT
• Encephalopathy
• sub-fulminant = < 6 months

Question 7

What is chronic liver failure?

Answer 7

Over years

Cirrhosis

Question 8

What toxins are a common cause of acute liver failure in the west?

Answer 8

Paracetamol

Amanita Phalloides

bacillus cereus

Acetaminophen

Question 9

How can inflammation cause acute liver failure in the east?

Answer 9

Exacerbations of chronic Hep B - Hong Kong

Hep E - India

Question 10

What other causes of acute liver failure are there?

Answer 10

• Diseases of pregnancy:
  AFLP, HELLP syndrome, hepatic infarction, HEV, Budd-Chiari
• Idiosyncratic drug reactions:
  Single Agent: Isoniazid, NSAID’s, 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 syndrome

Question 11

What are the causes of chronic liver failure?

Answer 11

• 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

Question 12

What are the consequences of liver failure?

Answer 12

Coagulopathy and bleeding

Ascites

Encephalopathy and cerebral oedema

Hypoglycaemia

Increased susceptibility to infection

Circulatory collapse, renal failure

Question 13

What is the effect of decreased protein synthesis?

Answer 13

↓ albumin → ascites

Plasma vol ↓
→ secondary hyperaldosteronism
→ hypokalaemia (↓K+)
→ alkalosis

Question 14

What is the effect of decreased plasma clotting factors?

Answer 14

Hepatocytes synthesis all coagulation proteins except von Willebrand factor & factor VIIIC

Question 15

What does Cholestasis cause?

Answer 15

Liver damage

Worsens any bleeding tendency

Decreases bile salts which causes decreased micelles and absorption of Vit K and decreases gamma carboxylation of vit K dependent clotting factors II, VII, IX, X

Question 16

What are the mechanisms of cholestasis?

Answer 16

Canalicular dilation

Decreased cell membrane fluidity

Deformed brush border

Biliary transporters

Increase tight junction permeability

Decrease mitochondrial ATP synthesis

Question 17

What are the consequences of Cholestasis?

Answer 17

Increased Bilirubin causing jaundice

• Pruritus ( itching )
• Cholesterol deposition
• Cholangitis

Question 18

What is portal hypertension and what does it cause?

Answer 18

• Decreased lymphatic flow which makes ascites worse

Can also cause splenomegaly which caused thrombocytopenia

Oesophageal varices

Question 19

Why is severe bleeding seen in Liver failure?

Answer 19

↓ active clotting factors, thrombocytopenia, & varices

Question 20

What is exudative enteropathy seen in liver failure?

Answer 20

↑ ascites → loss of albumin from plasma
favours bacteria in large bowel being “fed” with proteins
↑ liberation of ammonium (toxic to brain)

Question 21

What can cause pre-hepatic portal hypertension?

Answer 21

Portal vein thrombosis

Question 22

What can cause post-hepatic portal hypertension?

Answer 22

Right heart failure, constrictive pericarditis

Question 23

What can cause intrahepatic portal hypertension?

Answer 23

• 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).

Question 24

What are the consequences of portal hypertension?

Answer 24

Increased portal vein pressure:

• malabsorption
• Splenomegaly ( anaemia + thrombocytopaenia )
• Vasodilators ( glucagon, VIP, substance Pm prostacyclins, NO )

= Decreased blood pressure, increases CO, hyperperfusion of abdomen organs and varices

• Encephalopathy ( toxins from intestine e.g. NH3, biogenic amines, FFAs, end up in CNS
• Varices( Thin walled collateral vessels + thrombocytopenia = decreased Clotting factors leading to bleeding )

Question 25

Give examples of Encephalopathies?

Answer 25

Apathy, memory gaps, tremor, liver coma

Question 26

Give examples of how liver failure can cause encepthalopathy?

Answer 26

- Hyperammonaemia ↑s : GI bleeding ↑s colonic proteins liver can’t convert (NH3 NH4+) to urea - Hypokalaemia → intracellular acidosis → activates ammonium formation in proximal tubules → systemic alkalosis. - Toxins (amines, phenols & FFAs) bypass liver → not extracted → encephalopathy. - “false transmitters” (e.g., serotonin) from aromatic amino acids in brain → ↑ed in liver failure transmitters → encephalopathy.

Question 27

What vessels can become varices?

Answer 27

Portal-systemic anastomoses

Question 28

What is the child-pugh score?

Answer 28

Assesses disease severity for end-stage liver disease, and a prognosticator for peri-op death - Class A: 5-6 points: 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

Question 29

Child pugh score parameters and scores?

Answer 29

Total bilirubin : <34 = 1 point 34-51 = 2 points >51 = 3 points Serum albumin : >35 = 1 point 28-35 = 2 points <28 = 3 points INR : <1.7 = 1 point 1.71-2.3 = 2 points >2.3 = 3 points Ascites: None = 1 point Slight and suppressed with meds = 2 points moderate despite diuretics = 3 points Hepatic Encephalopathy : None = 1 point Grade I-II = 2 points grade III-IV = 3 points

Question 30

How to treat encephalopathy?

Answer 30

Reduce protein intake Phosphate enemas/lactulose No sedation

Question 31

How to treat: Hypoglycaemia? Hypocalcaemia? Renal failure? Respiratory failure? Hypotension? Infection? Bleeding?

Answer 31

- Hypoglycaemia infusion 10-50% dextrose - Hypocalcaemia 10 ml 10% calcium gluconate - Renal failure haemofiltration - Respiratory failure ventilation - Hypotension albumin vasoconstrictors - Infection frequent cultures A/Bs - Bleeding Vit K FFP platelets

Question 32

What usually causes death in liver failure patients?

Answer 32

Bacterial and fungal infections Circulatory instability Cerebral Oedema Renal failure Respiratory failure Acid-base and electrolyte disturbance Coagulopathy

Question 33

What is artificial MARS, Bio- Logic DT?

Answer 33

Albumin exchange system based on selective removal of albumin-bound toxins from blood * can also use bioartifical hepatocytes made in culture or hepatocyte transplantation

Question 34

What can require a liver transplant?

Answer 34

``` Cirrhosis Cancer Cholestatic disease Acute liver failure Metabolic disease Budd- Chairi Benign liver tumor polycystic liver disease ```