Liver Failure Flashcards
What are normal Bilirubin levels?
•Normal plasma [bilirubin (BR)] – 17 μmol/L •If [BR] ↑s > 30 μmol/L → yellow sclera & mucous membranes •If [BR] ↑s > 34 μmol/L → skin turns yellow
What is cholestasis?
- Cholestasis - slow/cessation of bile flow
- Cholestasis - normally results in jaundice
- Jaundice does not necessarily mean there is cholestasis
What are prehepatic causes of jaundice?
- Haemolysis
- Haemolytic anaemia
- Toxins - Massive transfusion (transfused erythrocytes short-lived)
- Large haematoma resorption
- Ineffective erythropoiesis
What are specific defects in intrahepatic causes of jaundice?
1. ↓ed BR uptake •Gilberts syndrome 2.. ↓ed conjugation BR •Crigler-Najar syndrome 3. ↓ed secretion BR into biliary canaliculi •Dubin-Johnson syndrome •Rotor syndrome
What are other causes of intrahepatic jaundice?
1.Intrahepatic cholestasis (↓ed outflow):
•Sepsis, TPN & drugs
2. Liver failure (acute & chronic)
What happens in liver failure?
When rate of hepatocyte death > regeneration
Describe the pathophysiology in liver failure?
- 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 fulminant hepatic failure in 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
What is sub-fulminant hepatic in acute liver failure?
< 6 months
What happens in chronic liver failure?
- Over years
* Cirrhosis
What are the common causes of acute liver failure in west?
- Toxins (West)
- Paracetamol
- Amanita phalloides
- Bacillus cereus
What are the common causes of acute liver failure in the east?
- Inflammation (East)
- Exacerbations of chronic Hep B (Hong Kong)
- Hepatitis E (India)
What are the pregnancy causes of acute liver failure?
•AFLP, HELLP syndrome, hepatic infarction, HEV, Budd-Chiari
What are some causes of acute liver failure with Idiosyncratic drug reactions?
- Single Agent: Isoniazid, NSAID’s, valproate
* Drug combinations: Amoxicillin/clavulanic acid, trimethoprim/sulphamethoxazole, rifampicin/isoniazid
What vascular diseases can causes acute liver disease?
•Ischaemic hepatitis, post-OLTx hepatic artery thrombosis, post-arrest, VOD
What are the metabolic causes of acute liver disease?
- Wilson’s disease
* Reye’s syndrome
What are the inflammatory causes of chronic liver failure?
•chronic persistent viral hepatitis
What else can cause chronic liver failure?
- Alcohol abuse
- Non alcoholic steatohepatitis (NASH)
- Autoimmune Hepatitis, PBC, PSC
What drug side effects can lead to chronic liver failure?
folic acid antagonists phenylbutazone
What are cardiovascular causes of chronic liver failure?
•↓venous return - right heart failure
What are some inherited diseases that can lead to chronic liver failure?
•Glycogen storage diseases, Wilson’s disease, Galactosaemia, Haemochromatosis, α1-antitrypsin deficiency
What can chronic liver failure lead to?
cirrhosis
What are the metabolic and catabolic functions of hepatocyte?
synthesis & utilization of carbohydrates, lipids and proteins
What are the secretory and excretory functions of hepatocyte?
synthesis &secretion of proteins, bile and waste products
What are the detoxification and immunological functions of hepatocyte?
breakdown of ingested pathogens & processing of drugs
What happens in cirrhosis?
- Necrosis of hepatocyte and release enzymes that cause cytokines
- activate Kuppfner cells that realise growth factors stimulates Ito fat cell get myofibrilbast and lots of ECM deposition and fibroblasts activated and lead to fibrosis
- Called cholestasis as well, portal hypertension and metabolic failure
What is normal liver function?
- Production of clotting factors
- Protein synthesis
- Detoxification
- Glycogen storage
- Immunological functionalists and globulin production
- Maintenance of homeostasis
What are the consequences of hepatocytes failure?
- Coagulopathy and bleeding
- Ascites
- Encephalopathy and cerebral oedema
- Hypoglycaemia
- increased susceptibility to infection
- Circulatory collapse, renal failure
What is the problem with low albumin?
Plasma vol ↓
→ 20 hyperaldosteronism
→ hypokalaemia (↓K+)
→ alkalosis
What is the problem with low plasma (clotting factors)?
Hepatocytes synthesis all coagulation proteins except von Willebrand factor & factor VIIIC
What does choleostasis lead to?
•→ liver damage
•aggravates any bleeding tendency
•↓ bile salts
→ ↓ micelles & absorptn of vit K
→ ↓ γ-carboxylation of vit K
-dependent clotting factors
prothrombin (II), VII, IX, & X
What is the mechanism of cholestasis?
- Canalicular dilation
- Decrease cell membrane fluidity
- Deformed brush border
- Biliary transporters
- Increase tight junction permeability
- Decreased mitochondrial ATP synthesis
What are the consequences of cholestasis?
- Increased bilirubin lead to jaundice
- Pruritus (itching)
- Cholesterol deposition
- Malabsorption
- Cholangitis
What is portal hypertension and what does it lead to?
-Blood doesn’t go in portal vein instead side little routes (small blood vessels)
•↓ lymphatic flow → makes ascites worse
•thrombocytopenia resulting from splenomegaly
•oesophageal varices (back pressure) (lots where blood goes)
•↓ active clotting factors, thrombocytopenia, & varices → severe bleeding (v low platelets)
•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 preheptic causes of portal hypertension?
PV thrombosis
What are postheptic causes of portal hypertension?
- right heart failure
- constrictive pericarditis
What are intraheptic 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 portal hypertension causes?
- Increased portal vein pressure causes
1. Malabsorption
2. Splenomegaly (anaemia & thrombocytopaenia)
3. Effect on vasodilators
4. Encephalopathy
5. Varices
How are vasodilators affected in portal hypertension?
- Vasodilators (glucagon, VIP, substance P, prostacyclins, NO, etc.)
- → ↓BP → ↑CO → hyperperfusion of abdo. organs & varices
Why does portal hypertension cause encephalopathy?
Toxins from intestine (NH3, biogenic amines, FFAs, etc.) normally extracted from portal blood by hepatocytes → CNS
Why does portal hypertension affect varices?
Thin walled collateral vessels + thrombocytopenia & ↓ clotting factors → bleeding +++
What is hepatic encephalopathy?
apathy, memory gaps, tremor & liver coma
How does Hyperammonaemia cause encephalopathy?
- Hyperammonaemia ↑s
- GI bleeding ↑s colonic proteins
- liver can’t convert (NH3 NH4+) to urea
How does Hypokalaemia cause encephalopathy?
- → intracellular acidosis → activates ammonium formation in proximal tubules → systemic alkalosis.
- respiratory component with hyperventilatn 20 encephalopathy.
How do toxins and false transmitters cause encephalopathy?
- 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 is the child Pugh score?
-assess disease celerity for end stage liver disease and a prognosticator for peri-op death
1. Bilrubin
2. Serum albumin
3. INR
4. Ascites
5. Hepatic encephalopathy
Class A: 5-6 points (15-20 years)
Class B: 7-9 (transplant candidates)
Class C: 10-15 (1-3 months)
What is the supportive treatment for encephalopathy?
- reduce protein intake
- phosphate enemas/lactulose
- no sedation
What is the supportive treatment for hypoglycaemia?
infusion 10-50% dextrose
What is the supportive treatment for hypocalaemia?
10 ml 10% calcium gluconate
What is the supportive treatment for renal failure?
haemofiltration
What is the supportive treatment for respiratory failure?
ventilation
What is the supportive treatment for hypotension?
- albumin
* vasoconstrictors
What is the supportive treatment for infection?
- frequent cultures
* A/Bs
What is the supportive 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 some liver support devices?
•Artificial (MARS, Bio-Logic DT) - Albumin exchange system
-based on selective removal of albumin-bound toxins from blood
•Bioartificial (Hepatocytes in culture)
•Hepatocyte transplantation
Describe liver transplant?
- 5% of all transplants in UK
- 5 year survival rate with OLTx btwn 60-80%
- No recurrence of disease BUT patient will require life-long immunosuppression
