Liver Failure Flashcards by Ishi Datta

What is normal plasma bilirubin?

17 μmol/L

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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

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What is cholestasis?

Slow/cessation of bile flow
Normally results in jaundice
Jaundice does not

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What are the pre-hepatic causes of jaundice?

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

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What 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 &amp; drugs

Liver failure

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Define the pathophysiology of liver failure

When rate of hepatocyte death > regeneration

Combination of apoptosis &/or necrosis

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What is the clinical result of liver failure?

Clinical result = catastrophic illness

Can rapidly lead to coma/death due to multi-organ failure

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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

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What is chronic failure?

Over years

Cirrhosis

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What are the causes of acute liver failure in the west?

Toxins
Paracetamol
Amanita phalloides
Bacillus cereus

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What are the causes of acute liver failure in the west?

Inflammation
Exacerbations of chronic Hep B (Hong Kong)
Hepatitis E (India)

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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

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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

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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

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What are the consequences of hepatocyte failure?

Coagulopathy and bleeding
Ascites
Encephalopathy &amp; cerebral oedema
Hypoglycaemia
Increased susceptibility to infection
Circulatory collapse, renal failure

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What does the decrease in protein synthesis result in?

Decreased albumin
Decreased plasma (clotting factors)

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What is the consequence of decreased albumin?

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

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What 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 &amp; absorptn of vit  K 
- → ↓ γ-carboxylation of vit K
 - dependent clotting factors
 prothrombin (II), VII, IX, &amp; 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?

What is the 5 year survival with a liver transplant?

60-80%