Liver failure Flashcards
What is normal plasma bilirubin?
17μmol/L
What leads to yellow sclera and mucous membranes?
BR > 30μmol/L
What leads to yellow skin?
BR > 34μmol/L
What is the meaning of cholestasis and what does it normally result in?
Slow/cessation of bile flow, normally results in jaundice
Jaundice does not mean cholestasis however
What are the intra-hepatic causes of jaundice?
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)
What are the pre-hepatic causes of jaundice?
Haemolysis
Haemolytic anaemia
Toxins
Massive transfusion
(transfused erythrocytes short-lived)
Large haematoma resorption
Ineffective erythropoiesis
What is the meaning of liver failure, what can cause it and what is the clinical result?
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
What is the difference between acute and chronic liver failure and what are the acute subtypes?
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
What are the commonest causes of acute liver failure in eastern and western countries and give some other causes?
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
Give some 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
3 major functions of hepatocytes
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
Give some consequences of liver failure
Within liver failure, what are the consequences of reduced protein synthesis?
↓ albumin → ascites
Plasma vol ↓
→ 20 hyperaldosteronism
→ hypokalaemia (↓K+)
→ alkalosis
↓ plasma [clotting factors]
Hepatocytes synthesis all coagulation proteins except von Willebrand factor & factor VIIIC
Within liver failure, what are the consequences of cholestasis?
→ 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
What are the mechanisms causing cholestasis and what are the consequences?
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
What are some consequences of portal hypertension?
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 +++
What are the causes of portal hypertension?
↑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).
What is encephalopathy and what are some of the causes of hepatic encephalopathy?
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.
?
Varicose vein
How is liver failure severity measured
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
What parameters are used to measure severity of liver failure?
Total bilirubin
Serum albumin
INR(international normalised ratio)
Ascites
Hepatic encephalopathy
SHAIT
What is the purpose of a child-pugh score?
Assesses disease severity for end-stage liver disease, and a prognosticator for peri-op death
In liver failure, how can you treat:
Encephalopathy
Hypoglycaemia
Renal failure
Respiratory failure
Hypotension
Infection
Bleeding?
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
What are the potential causes of death from liver failure?
Bacterial and fungal infections
Circulatory instability
Cerebral Oedema
Renal failure
Respiratory failure
Acid-base and electrolyte disturbance
Coagulopathy
BRRACCC
What liver supportive devices can be used for liver failure patients?
Artificial (MARS, Bio-Logic DT) - Albumin exchange system
-Based on selective removal of albumin-bound toxins from blood
Bioartificial (Hepatocytes in culture)
Hepatocyte transplantation
What are the indicators for liver transplantation
