liver failure Flashcards
- What bilirubin concentration [BR] will lead to yellow sclera and a persons skin turning yellow respectively?
Yellow sclera and mucous membrane: >30 micromol/L
Skin turns yellow: >34 micromol/L
- Define cholestasis
Slow/cessation of bile flow, which normally results in jaundice
(Jaundice doesn't necessarily mean there is cholestasis)
- List and explain the causes of pre-hepatic jaundice
Haemolysis- from haemolytic anaemia, toxins and massive blood transfusion-
Transfused short-lived erythrocytes
Haematoma - Collection of erythrocytes deep to skin → Degradation and haemolysis of erythrocytes increases levels of unconjugated bilirubin for resorption
ineffective erythropoiesis- more RBC to break down
- List and explain the intrahepatic causes of jaundice
Reduced uptake of BR into hepatocytes → increased serum unconjugated BR levels within sinusoidal space and systemic circulation eg Gilbert Syndrome
Decreased conjugation of BR → Enters into systemic circulation and passes through BBB eg Crigler-Najjar Syndrome
Reduced BR secretion into biliary canaliculi → Black liver eg Dubin-Johnson and Rotor Syndrome
Intrahepatic cholestasis- Sepsis TPN (total parenteral nutrition) feeding, drugs
- What are the post-hepatic causes of jaundice?
Gallstones and tumours
- Define acute LF
Fulminant epatic failure leading to rapid development (<8 weeks) of severe acute liver injury:
- Impaired synthetic function (clotting factors, albumin) - Encephalopathy - Previously normal liver or well-compensated liver disease
Sub-fulminant: <6 months
- Define chronic LF
Failure persisting over years , concerned with liver cirrhosis
- Outline the pathophysiology of liver failure (LF)
Rate of hepatocyte death > regeneration
Hepatocyte death is attributed with a combination of apoptosis (acetaminophen=paracetamol) and necrosis (ischaemia) Within a hepatic acinus, Zone 3 (central vein region) is sensitive to necrosis and ischaemia due to its relative distance to oxygenated blood supply Clinically, LF is concerned with coma/death due to multi-organ failure. (catastrophic)
- What are the commonest causes of acute LF?
Toxins (West) - paracetamol, amanita phalloides, bacillus cereus
Inflammation (East) - exacerbations of chronic Hep-B (Hong Kong) and Hep-E (India)
- What are the other causes of acute LF and give examples of each?
Diseases of pregnancy
- Acute fatty liver of pregnancy (AFLP), HELLP syndrome, hepatic infarction, Hepatitis-E Virus (HEV), Budd-Chiari
Idiosyncratic drug reactions
- Single agent - isoniazid, NSAIDs, valproate - Combinations of drugs
Vascular diseases
- Ischaemic hepatitis, post Orthotopic Liver Transplantation hepatic artery thrombosis, post-arrest, veno-occlusive disease (VOD)
Metabolic diseases - Wilson’s disease , Reye’s disease
- What are the causes of chronic LF?
Inflammation - chronic persistent viral hepatitis.
Alcohol abuse
Side effects of drug (folic acid antagonists e.g. phenylbutazone)
CV causes - decreased venous return (right HF)
Inherited diseases - glycogen storage disease, Wilson’s disease, galactosaemia, haemochromatosis, A1AT deficiency
Non-alcoholic steatohepatitis (NASH)
Autoimmune hepatitis, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC)
- Outline the pathophysiology of cirrhosis
1) Necrosis concerned with ischaemia results in hepatocyte degradation
2) Releasing intracellular enzymes, in addition to cytokine release.
3) Intracellular contents stimulate chemotaxis of inflammatory cells. (neutrophils and monocyte differentiation into macrophages)
4) Cytokines activate Kupffer cells → Growth factor and cytokine release → Activation of hepatic stellate cells
5) Hepatic stellate cells and macrophages undergo fibroblast proliferation, depositing ECM
6) Increased collagen, proteoglycans and matrix glycoprotein deposition → Fibrosis of hepatic tissue
- What are the main hepatocyte functions?
Metabolic and catabolic - synthesis/ use of carbohydrates, lipids and proteins
Secretory and excretory - excretion of bile and waste products Detoxification and immunological- process drugs, breakdown of pathogens
- List the causes of death as a consequence of LF
Bacterial and fungal infections - due to loss of immunological ability
Circulatory instability - lack of homeostasis Cerebral oedema - encephalopathy Renal failure Respiratory failure Acid-base and electrolyte disturbance Coagulopathy- as loss of clotting factors
- Which vitamin is lacking due liver failure and what does this lead to?
- Why is it lacking?
Vitamin K essential cofactor for the carboxylation for glutamic acid residues for the synthesis of factors II, VII, IX, X → coagulopathy & bleeding
lack of bile salts, decreased micelles and absorption of vitamin K
- Why does ascites occur in liver failure?
Reduction in serum albumin
reduces the oncotic pressure within the capillaries
therefore this will reduce the water retention ability for interstitial fluid to be drawn into the capillaries
so water deposited to abdominal spaces
- What does the decreased plasma volume lead to as a result of liver failure?
Secondary hyperaldosteronism → Hypokalaemia and alkalosis
name the consequence to liver failure that corresponds with the liver function
- production of clotting factors
- protein synthesis
- detoxification
- glycogen storage
- production of globulins/ immunological function
- maintenance of homeostasis
coagulopathy and bleeding ascites encephalopathy and cerebral odema hypoglycaemia increased susceptibility to infection circulatory collapse and renal failure
- Explain the some pathogenesis of cholestasis
Biliary transporters are incorrectly positioned, insertion of carriers will reduce bile salt secretion into the biliary canaliculi, transporters may be present on the basolateral membrane
Bile salts increase tight junction permeabilty → increasing amount of bile passing through sinusoidal space → reducing bile flow in canaliculi Canalicular dilation - reduction in bile flow pressure and fluid mechanics Decreased cell membrane fluidity Decreased mitochondrial ATP synthesis - reduces ability for active transport of bile salts and xenobiotics into hepatocyte Deformed brush border
- Why might pruritis be a consequence of cholestasis?
- What is the general cause of portal hypertension?
Bile salts secreted into circulation are deposited as crystals deep to the skin resulting in irritation
Fibrotic portal veins coupled with obstruction to venous supply to the liver leads to hypertension
- Explain how thrombocytopenia, oesophageal varices and exudative enteropathy are all consequences of portal hypertension?
Thrombocytopenia - when too many platelets are destroyed or accumulate within an enlarged spleen
Oesophageal varices- Blood flow through the liver slows, the pressure in the portal vein goes up, pushes blood into vessels of oesophagus Exudative enteropathy - Increased ascites → Loss of albumin from plasma into intersititial fluid and GIT → Favours colonic bacteria → NH4+ compound liberation → Encephalopathy
- Why might splenomegaly result from portal hypertension?
blood backs up into the spleen- cant get out, causes an enlarged spleen, leading to breakdown of red blood cells (anaemia) white blood cells (leukopenia) and platelets (thromocytopenia)
- What is a pre-hepatic cause of portal hypertension?
- What are the post-hepatic causes of portal hypertension?
Portal vein thrombosis
Right heart failure - causes backwards pressure within venous system due to insufficient contractility of right atria Constrictive pericarditis - inflammation and reduced elasticity of the pericardium
- What are the intrahepatic causes of portal hypertension?
Presinusoidal - chronic hepatitis, primary biliary cholangitis, granulomas
Sinusoidal - acute hepatitis, alcohol, fatty liver, toxins, amyloidosis Post-sinusoidal - venous occlusive disease of venules and small veins: Budd-chiari
- How does hepatic encephalopathy present?
- How can hyperammonaemia lead to hepatic encephalopathy?
Apathy, memory gaps, tremor and liver coma
exudative enteropathy
when less albumin in plasma, colonic bacteria is fed proteins
liberation of ammonia (hyperammonaemia)
toxic to brain
- What 3 ways can toxins lead to encephalopathy?
toxins bypass liver → not extracted or detoxified → passes blood brain barrier → encephalopathy
False transmitters from aromatic amino acids in brain → encephalopathy
exudative enteropathy
- What is hepato-renal syndrome?
portal hypertension leads to arterial vasodilation through decreased vascular resistance → activating vasoconstrictor factors (RAAS, SNS, vasopressin ) → renal vasoconstriction decreased glomerular filtration rate
- What does the Child-Pugh score assess?
- what are the five areas assessed?
Disease severity for end-stage liver disease, and a prognosticator for peri-op death
bilirubin, serum albumin, INR/PT, ascites, hepatic encephalopathy
- How do you treat encephalopathy?
Reduce protein intake
Phosphate enemas/lactose No sedation
- How do you treat hypoglycaemia, hypocalcaemia and renal failure?
Hypoglycaemia - Infusion 10-50% dextrose
Hypocalcaemia - 10ml 10% calcium gluconate Renal failure - Hemofiltration
- How do you treat respiratory failure, hypotension and infection?
Respiratory failure - Ventilation
Hypotension - Albumin and Vasoconstrictors Infection - Frequent cultures and antibiotics
- How do you treat bleeding?
Vitamin K
Fresh Frozen Plasma Platelets
how does portal hypertension cause malnutrition
how does portal hypertension cause vasodilators to be released
nutrient filled blood cant get into liver, nutrients cant be processed
vasodilators (eg glucagon, VIP , substance P, prostacyclin and NO) released to decrease blood pressure, increased cardiac output, causes hyperperfusion of abdominal organs and varices
