Liver failure Flashcards
what is normal plasma bilirubin and bilirubin in jaundice?
Normal : 17 micromol/L
Bilirubin > 30 mmol/L = yellow sclera and mucous membranes
Bilirubin >34 mmol/L = yellow skin
What is Cholestasis
slow bile flow
Cholestasis - normally results in jaundice
Jaundice does not necessarily mean there is cholestasis
Pre-hepatic jaundice causes?
Haemolysis = increased production = conjugated bilirubin
Having a massive transfusions : red cells are short lived
Large haematoma resorption
Ineffective erythropoiesis
Intrahepatic causes of jaundice?
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
Post - Hepatic causes of jaundice?
Gall stones, tumors
Cause extrahepatic outflow decrease
What is Acute liver failure?
Fulminant hepatic failure = rapid development under 8 weeks
- impaired synthetic function e.g. albumin, INR/PT
- Encephalopathy
- sub-fulminant = < 6 months
What is chronic liver failure?
Over years
Cirrhosis
What toxins are a common cause of acute liver failure in the west?
Paracetamol
Amanita Phalloides
bacillus cereus
Acetaminophen
How can inflammation cause acute liver failure in the east?
Exacerbations of chronic Hep B - Hong Kong
Hep E - India
What other causes of acute liver failure are there?
- 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
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
What are the consequences of liver failure?
Coagulopathy and bleeding
Ascites
Encephalopathy and cerebral oedema
Hypoglycaemia
Increased susceptibility to infection
Circulatory collapse, renal failure
What is the effect of decreased protein synthesis?
↓ albumin → ascites
Plasma vol ↓
→ secondary hyperaldosteronism
→ hypokalaemia (↓K+)
→ alkalosis
What is the effect of decreased plasma clotting factors?
Hepatocytes synthesis all coagulation proteins except von Willebrand factor & factor VIIIC
What does Cholestasis cause?
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
What are the mechanisms of cholestasis?
Canalicular dilation
Decreased cell membrane fluidity
Deformed brush border
Biliary transporters
Increase tight junction permeability
Decrease mitochondrial ATP synthesis
What are the consequences of Cholestasis?
Increased Bilirubin causing jaundice
- Pruritus ( itching )
- Cholesterol deposition
- Cholangitis
What is portal hypertension and what does it cause?
- Decreased lymphatic flow which makes ascites worse
Can also cause splenomegaly which caused thrombocytopenia
Oesophageal varices
Why is severe bleeding seen in Liver failure?
↓ active clotting factors, thrombocytopenia, & varices
What is exudative enteropathy seen in liver failure?
↑ ascites → loss of albumin from plasma
favours bacteria in large bowel being “fed” with proteins
↑ liberation of ammonium (toxic to brain)
What can cause pre-hepatic portal hypertension?
Portal vein thrombosis
What can cause post-hepatic portal hypertension?
Right heart failure, constrictive pericarditis
What can cause intrahepatic 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 consequences of portal hypertension?
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 )
Give examples of Encephalopathies?
Apathy, memory gaps, tremor, liver coma
Give examples of how liver failure can cause encepthalopathy?
- 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.
What vessels can become varices?
Portal-systemic anastomoses
What is the child-pugh score?
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
Child pugh score parameters and scores?
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
How to treat encephalopathy?
Reduce protein intake
Phosphate enemas/lactulose
No sedation
How to treat:
Hypoglycaemia?
Hypocalcaemia?
Renal failure?
Respiratory failure?
Hypotension?
Infection?
Bleeding?
- 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
What usually causes death in liver failure patients?
Bacterial and fungal infections
Circulatory instability
Cerebral Oedema
Renal failure
Respiratory failure
Acid-base and electrolyte disturbance
Coagulopathy
What is artificial MARS, Bio- Logic DT?
Albumin exchange system
based on selective removal of albumin-bound toxins from blood
- can also use bioartifical hepatocytes made in culture
or hepatocyte transplantation
What can require a liver transplant?
Cirrhosis Cancer Cholestatic disease Acute liver failure Metabolic disease Budd- Chairi Benign liver tumor polycystic liver disease
