Liver Failure

Question 1

What is jaundice?

Answer 1

Yellow skin or sclera
- normal bilirubin —> 17µmol/L
- >30 —> yellow sclera
- >34 —> yellow skin

Question 2

What are the 3 categories of causes of jaundice?

Answer 2

1. Pre-hepatic —> excess production
   - too much for liver to conjugate
2. Intrahepatic —> issue in hepatic cells
   - liver can’t conjugate
3. Post-hepatic —> obstructive jaundice
   - can’t be released

Question 3

What are the 4 pre-hepatic causes of jaundice?

Answer 3

Lots of erythrocytes die —> too much bilirubin produced:
1. Haemolysis - haemolytic anaemia
- toxins
2. Massive blood transfusion
3. Haematoma resorption
4. Ineffective erythropoiesis

Question 4

What are the 3 intrahepatic causes of jaundice?

Answer 4

Dec uptake, conjugation or secretion of bilirubin in liver:
1. Inherited syndromes - all auto rec
- Gilberts —> dec uptake
- inc unconjugated
- Crigler-Najar —> dec conjugation
- inc unconjugated
- Dubin-Johnson —> dec secretion
- inc unconjugated
- Rotor —> dec secretion
- inc unconjugated
2. Cholestasis —> dec secretion
- sepsis
- TPN (Total Parenteral Nutrition)
- drugs
3. Liver failure

Question 5

What are post-hepatic causes of jaundice?

Answer 5

1. Stone
2. Tumour

Question 6

What is liver failure?

Answer 6

Rate of hepatocyte death > regeneration
- death via apoptosis or necrosis
- consequences —> coma
—> multi-organ failure
—> death
- acute - fulminant = severe in < 8weeks
- sub-fulminant = severe in < 6months
- severe —> impaired synthetic function
(INR, PT, albumin)
—> encephalopathy (impaired brain)
- chronic = cirrhosis

Question 7

What are the 6 causes of acute liver failure?

Answer 7

1. Toxins —> usually in west
2. Inflammation —> usually in east (hep B, E)
3. Pregnancy disease
4. Drug reactions - single agent or combinations
5. Vascular diseases
6. Metabolic causes - eg. Wilson’s (Cu deposits), Reye’s

Question 8

What are the 7 causes of chronic liver failure?

Answer 8

1. Inflammation - eg. persistant hep
2. Alcohol abuse
3. Side effects of drugs
4. Cardiovascular —> dec venous return (right)
5. Inherited disease - eg. haemochromatosis
6. NASH (non-alcoholic steatohepatitis)
7. Autoimmune hepatitis , PBC, PSC

Question 9

What is cirrhosis?

Answer 9

Chronic liver failure
1. Noxious factor —> hepatocyte necrosis
2. Cell contents leak —> activate Kupffer cells
—> inflammatory cells recruited
3. Lots of growth factors and cytokines released
- fibrosis - inc ECM production —> inc chemotaxis
- fibroblast proliferation
- cholestasis
- portal hypertension
- metabolic failure

Question 10

What are the 3 main functions of hepatocyte?

Answer 10

1. Metabolic/catabolic —> carbs, lipids, proteins
2. Secretory/excretory —> proteins, bile, waste
3. Detoxification/immunological —> pathogens, drugs

Question 11

What are the 6 consequences of liver failure?

Answer 11

1. Ascites (fluid in abdomen)
   
   • dec protein synthesis (albumin)
     —> dec plasma volume —> 2° hyperaldosteronism
     —> hypokalaemia
     —> alkalosis
2. Coagulopathy and bleeding
   
   • dec clotting factor production (not vwf, VIIIC)
3. Cholestasis
   
   • bile blocked from leaving
4. Portal hypertension

+ Encephalopathy and cerebral oedma
∵ dec detoxification
+ Hypoglycaemia
∵ dec glycogen storage
+ Susceptible to infections
∵ dec immunity and globulin production
+ Circulatory collapse and renal failure
∵ dec homeostasis balance

Question 12

What is cholestasis?

Answer 12

Bile blocked from leaving liver
Effects:
- canalicular dilation
- dec cell membrane fluidity
- deformed brush barrier
- biliary transporter issues
- inc tight junctiin permeability
- dec mitochondrial ATP synthesis

Consequences:
- jaundice (inc bilirubin)
- pruritus (endorphins and bile salts in blood)
- cholesterol deposition
- fat soluble vitamin deficiencies - K —> bleeding

Question 13

What is portal hypertension?

Answer 13

High blood pressure in portal venous system

Causes:
- pre-hepatic —> PV thrombosis
- intrahepatic - presinusoidal —> chronic hep, PBC,
granuloma
- sinusoidal —> acute hep, alcohol, fatty
liver, toxins
- postsinusoidal —> venous occlusive
disease, Budd-Chiari
- post-hepatic —> right heart failure
—> constrictive pericarditis

Consequences:
- malabsorption
- splenomegaly
- vasodilation
- encephalopathy
- varices
- severe bleeds

Question 14

What is hepatic encephalopathy?

Answer 14

Damage to brain due to hepatic malfunction
due to:
- hyperammonaemia
- hypokalaemia
- toxins
- false transmitters

Question 15

Where to varices due to liver failure occur? (4)

Answer 15

1. Azygous vein tributaries
2. Paraumbilical veins
3. Superficial veins of anterior abdominal wall
4. Renal veins

Question 16

How is the severity of liver failure assessed?

Answer 16

Child-Pugh Score
- parameters - 1-3 points
—> total bilirubin
—> serum albumin
—> INR
—> ascites
—> hepatic encephalopathy
- sum of points —> class
- 5-6 = class A —> life expectancy 15-20 years
—> 10% POM
- 7-9 = class B —> transplant
—> 30% POM
- 10-15 = class C —> life expectancy 1-3 months
—> 82% POM

Question 17

How is liver failure treated?

Answer 17

Supportive treatments:
- encephalopathy —> dec protein intake
—> don’t sedate
—> phosphate enemas/lactulose
- hypoglycaemia —> dextrose infusion - 10-50%
- hypocalcaemia —> calcium gluconate - 10ml 10%
- renal failure —> haemofiltration
- respiratory failure —> ventilation
- hypotension —> albumin
—> vasoconstrictors
- infections —> antibiotics
—> do frequent cultures
- bleeding —> vit K
—> FFP
—> platelets

Liver Support Devices:
- artificial —> albumin exchange system (removes
albumin-bound toxins)
- bioartificial —> grow hepatocytes in culture
- hepatocyte transplantation

Full liver transplant

Question 18

How does liver failure cause death? (7)

Answer 18

1. Infections - bacterial, fungal
2. Circulatory instability
3. Cerebral oedema
4. Renal failure
5. Respiratory failure
6. Acid-base and electrolyte disturbance
7. Coagulopathy