Liver Failure Flashcards
What is normal plasma bilirubin (BR)?
17 micromol/L
What happens when bilirubin is high? (<30)
yellow sclera and mucous membranes
What happens when bilirubin is high? (<34)
skin turns yellow
What is cholestasis?
Cholestasis - slow/cessation of bile flow
What can cholestasis lead to?
Cholestasis - normally results in jaundice
Jaundice does not necessarily mean there is cholestasis
What are causes of jaundice?
What can lead to post-hepatic jaundice?
gallstones, tumors etc.
What are causes of pre-hepatic jaundice?
Haemolysis
- Haemolytic anaemia
- Toxins
Massive transfusion
- (transfused erythrocytes short-lived)
Large haematoma resorption
Ineffective erythropoiesis
What are intrahepatic causes of jaundice?
Specific defects:
↓ BR uptake
- Gilberts syndrome
↓ conjugation BR
- Crigler-Najar syndrome
↓ secretion BR into biliary canaliculi
- Dubin-Johnson syndrome
- Rotor syndrome
Intrahepatic cholestasis (↓ outflow):
- Sepsis, TPN & drugs
Liver failure (acute & chronic)
What is TPN in jaundice?
Cholestatic jaundice is the major complication of total parenteral nutrition (TPN) in infants and children
What is the pathophysiology of liver failure?
When rate of hepatocyte death > regeneration
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 are the types of acute liver failure?
Fulminant hepatic failure
Sub-fulminant
What is fulminant hepatic 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
What is sub-fulminant liver failure?
acute liver failure <6 months
What is chronic liver failure?
Over years
Cirrhosis
What are common causes of acute liver failure?
Toxins (West):
- Paracetamol
- Amanita phalloides
- Bacillus cereus
Inflammation (East):
- Exacerbations of chronic Hep B
- Hepatitis E
Describe how cirrhosis occurs.
What are the consequences of liver failure? (Big diagram)
What are the consequences of hepatocyte failure.
What happens to protein synthesis with liver disease?
Protein synthesis ↓…
↓ albumin → ascites
Plasma vol ↓
→ 2ary hyperaldosteronism
→ hypokalemia (↓K+)
→ alkalosis (hyperventilation and hyperammonemia, renal NH4+ increase, hypokalemia)
↓ plasma [clotting factors]
- Hepatocytes synthesise all coagulation proteins except von Willebrand factor & factor VIIIC
What does cholestasis do?
leads to 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 is the mechanism and consequence of cholestasis?
Mechanisms:
Canalicular dilation
↓ cell membrane fluidity
Deformed brush border
Biliary transporters
↑ tight junction permeability
↓ mitochondrial ATP synthesis
How does portal hypertension affect liver failure?
Portal hypertension
↓ lymphatic flow → makes ascites worse
thrombocytopenia (low platelet count) resulting from splenomegaly
oesophageal varices (enlarged or swollen veins)
↓ active clotting factors, thrombocytopenia, & varices → severe bleeding
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 causes of portal hypertension?
causes: ↑ vascular resistance
Prehepatic
Portal vein thrombosis (blocking of blood vessels)
Posthepatic
right heart failure
constrictive pericarditis (inflammation of lining around the heart)
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 are the consequences of portal hypertension?
(↑ portal vein pressure)
Malabsorption
Splenomegaly (anaemia & thrombocytopenia)
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 can encephalopathy cause?
Encephalopathy - apathy, memory gaps, tremor & liver coma)
Hyperammonemia ↑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 are the Porto-systemic anastomoses?
Porto-systemic anastomosis also known as portocaval anastomosis is the collateral communication between the portal and the systemic venous system
picture is of varices of portal-systemic anastomoses
Where are the varices of the portal-systemic system?
How does the child-pugh score work?
What are indications for liver transplantation?
(in order of most)
cirrhosis
cancer
cholestasis disease
acute liver failure
metabolic disease
other:
Budd-Chiari
Benign Liver tumours
Polycystic liver disease
