Liver failure

Question 1

What is normal plasma bilirubin?

Answer 1

17μmol/L

Question 2

What leads to yellow sclera and mucous membranes?

Answer 2

BR > 30μmol/L

Question 3

What leads to yellow skin?

Answer 3

BR > 34μmol/L

Question 4

What is the meaning of cholestasis and what does it normally result in?

Answer 4

Slow/cessation of bile flow, normally results in jaundice
Jaundice does not mean cholestasis however

Question 5

What are the intra-hepatic causes of jaundice?

Answer 5

Specific defects:
-Decreased BR uptake
Gilberts syndrome
-Decreased conjugation BR
Crigler-Najar syndrome
-Decreased secretion BR into biliary canaliculi
Dubin-Johnson syndrome
Rotor syndrome

Intrahepatic cholestasis (↓ed outflow):
Sepsis, TPN & drugs

Liver failure (acute & chronic)

Question 6

What are the pre-hepatic causes of jaundice?

Answer 6

Haemolysis
Haemolytic anaemia
Toxins
Massive transfusion
(transfused erythrocytes short-lived)
Large haematoma resorption
Ineffective erythropoiesis

Question 7

What is the meaning of liver failure, what can cause it and what is the clinical result?

Answer 7

When hepatocyte death rate>regeneration rate

Combination of apoptosis &/or necrosis
Apoptosis (e.g. Acetaminophen=Paracetamol):
Necrosis (ischaemia):

Clinical result = catastrophic illness
Can rapidly lead to coma/death due to multi-organ failure

Question 8

What is the difference between acute and chronic liver failure and what are the acute subtypes?

Answer 8

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

Sub-fulminant = < 6 months

Chronic Liver Failure
Over years
Cirrhosis

Question 9

What are the commonest causes of acute liver failure in eastern and western countries and give some other causes?

Answer 9

Toxins (West)
Paracetamol
Amanita phalloides
Bacillus cereus
Inflammation (East)
Exacerbations of chronic Hep B (Hong Kong)
Hepatitis E (India)

Other causes:
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 10

Give some causes of chronic liver failure

Answer 10

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 11

3 major functions of hepatocytes

Answer 11

Metabolic & catabolic functions:synthesis & utilization of carbohydrates, lipids and proteins.

Secretory& excretory functions:synthesis &secretion of proteins, bile and waste products.

Detoxification & immunological functions:breakdown of ingested pathogens & processing of drugs

Question 12

Give some consequences of liver failure

Answer 12

Question 13

Within liver failure, what are the consequences of reduced protein synthesis?

Answer 13

↓ albumin → ascites
Plasma vol ↓
→ 20 hyperaldosteronism
→ hypokalaemia (↓K+)
→ alkalosis

↓ plasma [clotting factors]
Hepatocytes synthesis all coagulation proteins except von Willebrand factor & factor VIIIC

Question 14

Within liver failure, what are the consequences of cholestasis?

Answer 14

→ liver damage
aggravates any bleeding tendency
↓ bile salts
→ ↓ micelles & absorption of vit K
→ ↓ γ-carboxylation of vit K
-dependent clotting factors
prothrombin (II), VII, IX, & X

Question 15

What are the mechanisms causing cholestasis and what are the consequences?

Answer 15

Mechanisms
Canalicular dilation
↓ cell membrane fluidity
Deformed brush border
Biliary transporters
↑ tight junction permeability
↓ mitochondrial ATP synthesis

Consequences
↑ BR → jaundice
Pruritus (itching)
Cholesterol deposition
Malabsorption
Cholangitis

Question 16

What are some consequences of portal hypertension?

Answer 16

Malabsorption
Splenomegaly (anaemia & thrombocytopaenia)
Vasodilators (glucagon, VIP, substance P, prostacyclins, NO, etc.)
→ ↓BP → ↑CO → hyperperfusion of abdo. organs & varices
Encephalopathy
Toxins from intestine (NH3, biogenic amines, FFAs, etc.) normally extracted from portal blood by hepatocytes → CNS
Varices
Thin walled collateral vessels + thrombocytopenia & ↓ clotting factors → bleeding +++

Question 17

What are the causes of portal hypertension?

Answer 17

↑ed vascular resistance
-Prehepatic
PV thrombosis

-Posthepatic
right heart failure
constrictive pericarditis

-Intrahepatic
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 18

What is encephalopathy and what are some of the causes of hepatic encephalopathy?

Answer 18

Encephalopathy - apathy, memory gaps, tremor & liver coma
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 19

?

Answer 19

Varicose vein

Question 20

How is liver failure severity measured

Answer 20

Child-pugh score:
Use of Child-Pugh scores:
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 21

What parameters are used to measure severity of liver failure?

Answer 21

Total bilirubin
Serum albumin
INR(international normalised ratio)
Ascites
Hepatic encephalopathy
SHAIT

Question 21

What is the purpose of a child-pugh score?

Answer 21

Assesses disease severity for end-stage liver disease, and a prognosticator for peri-op death

Question 22

In liver failure, how can you treat:
Encephalopathy
Hypoglycaemia
Renal failure
Respiratory failure
Hypotension
Infection
Bleeding?

Answer 22

Encephalopathy
reduce protein intake
phosphate enemas/lactulose
no sedation

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 23

What are the potential causes of death from liver failure?

Answer 23

Bacterial and fungal infections

Circulatory instability

Cerebral Oedema

Renal failure

Respiratory failure

Acid-base and electrolyte disturbance

Coagulopathy

BRRACCC

Question 24

What liver supportive devices can be used for liver failure patients?

Answer 24

Artificial (MARS, Bio-Logic DT) - Albumin exchange system
-Based on selective removal of albumin-bound toxins from blood

Bioartificial (Hepatocytes in culture)

Hepatocyte transplantation

Question 25

What are the indicators for liver transplantation

Answer 25