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Year 1 - BRS > 11.10 - Liver Failure > Flashcards

11.10 - Liver Failure Flashcards

1
Q

What is normal plasma bilirubin?

A

17 umol/L

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2
Q

What happens if bilirubin increases above 30 umol/L?

A

Yellow sclera (eyes) and mucous membranes

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3
Q

What happens if bilirubin increases above 34 umol/L?

A

Skin turns yellow

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4
Q

What is cholestasis?

A
  • slow/cessation of bile flow
  • normally results in jaundice
  • but jaundice does not necessarily mean there is cholestasis
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5
Q

What are the three types of jaundice?

A
  • pre-hepatic
  • hepatic
  • post-hepatic
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6
Q

What causes pre-hepatic jaundice?

A
  • problems with bilirubin before liver
  • too much BR made in spleen than downstream structures can cope with, can be due to:
  • haemolysis (haemolytic anaemia, toxins)
  • massive transfusion (transfused erythrocytes short-lived)
  • large haematoma resorption (cells quickly die and BR released)
  • ineffective erythropoiesis
  • blood tests mainly show unconjugated BR (as conjugation occurs in liver)
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7
Q

What causes intrahepatic jaundice?

A
  • normal BR levels arrive at liver but hepatocytes killed/damaged –> defective uptake, conjugation and excretion of BR
  • can be due to liver failure - acute due to paracetamol overdose, chronic due to viral hepatitis, alcohol injury, autoimmunity etc
  • can be due to intrahepatic cholestasis (sepsis, TPN, drugs) –> reduced outflow
  • blood test shows mainly unconjugated BR but liver enzymes are abnormal (damaged hepatocytes)
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8
Q

What specific defects cause intrahepatic jaundice?

A
  • decreased BR uptake - Gilberts syndrome (autosomal recessive condition causes elevated unconjugated BR and episodes of mild jaundice when overexerting/fasting)
  • decreased BR conjugation - Crigler-Najar syndrome (autosomal recessive, decreases conjugation - high levels unconjugated BR in blood –> brain damage especially in infants)
  • decreased BR secretion into biliary canaliculi - Dubin-Johnson syndrome (autosomal recessive, increase in conjugated BR as it has been processed), Rotor syndrome (autosomal recessive, causes increase in conjugated BR)
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9
Q

What causes post-hepatic/obstructive jaundice?

A
  • physical obstruction reducing bile and thus BR flow into duodenum and colon
  • less BR can be excreted and it builds up
  • can be due to gallstones/CBD stones, tumour (hepatic, pancreatic, biliary)
  • blood tests show mainly conjugated BR
  • less BR in colon –> less stercobilinogen + stercobilin –> white pale faeces
  • some BR excreted from kidneys –> dark urine
  • pruritus (itching) can occur
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10
Q

In basic terms, when does liver failure happen?

A
  • when rate of hepatocyte death > regeneration
  • normally due to combination of apoptosis (e.g. paracetamol) and/or necrosis (e.g. ischaemia)
  • can rapidly lead to coma/death due to multi-organ failure
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11
Q

What is fulminant hepatic failure? (Acute liver failure)

A
  • rapid development (<8 weeks) of severe acute liver injury
  • impaired synthetic function –> e.g. increased PT time (as liver produces clotting factors)
  • encephalopathy
  • previously normal liver or well-compensated liver disease (liver is scarred but still able to function)
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12
Q

What is sub-fulminant hepatic failure? (Acute liver failure)

A

Acute liver disease that develops in <6 months

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13
Q

What are common causes of acute liver failure in the West?

A

Toxins:

  • paracetamol
  • Amanita phalloides (death cap mushroom)
  • Bacillus cereus
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14
Q

What are common causes of acute liver failure in the East?

A

Inflammation:

  • exacerbations of chronic Hep B (Hong Kong)
  • hepatitis E (India)
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15
Q

What diseases of pregnancy can cause acute liver failure?

A
  • AFLP - acute fatty liver of pregnancy
  • HELLP syndrome - haemolysis, elevated liver enzymes, low platelets
  • hepatic infarction
  • hepatitis E
  • Budd-Chiari syndrome
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16
Q

What idiosyncratic drug reactions can cause acute liver failure?

A
  • single agent - isoniazid, NSAIDs, valproate
  • drug combinations - amoxicillin/clavulanic acid, trimethoprim/sulphamethoxazole, rifampicin/isoniazid
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17
Q

What vascular diseases can cause acute liver failure?

A
  • ischaemic hepatitis
  • post-liver transplant hepatic artery thrombosis
  • post-arrest
  • VOD
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18
Q

What metabolic causes can cause acute liver failure?

A
  • Wilson’s disease
  • Reye’s syndrome
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19
Q

Over what period of time does chronic liver failure develop and what usually causes it?

A
  • over many years
  • cirrhosis is a major cause
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20
Q

What are the causes of cirrhosis?

A
  • inflammation - chronic/persistent viral hepatitis
  • alcohol abuse
  • side effects of drugs - folic acid antagonists and phenylbutazone
  • cardiovascular causes - reduced venous return –> right heart failure –> back pressure on liver = cirrhosis
  • inherited diseases - e.g. glycogen storage diseases, Wilson’s disease, galactosaemia, haemochromatosis, a1-antitrypsin deficiency
  • non-alcoholic steatohepatitis (NASH)
  • autoimmune hepatitis - e.g. primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC)
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21
Q

Describe the process of developing cirrhosis.

A
  1. noxious factors (alcohol, virus) cause necrosis of hepatocytes
  2. causes lysosomal enzyme leak
  3. causes cytokine release
  4. activates Kupffer cells in sinusoids + granulocytes and lymphocytes
  5. releases more growth factors and cytokines
  6. Ito cells (hepatic stellate cells in space of Disse) are activated into myofibroblasts; cytokines also convert monocytes to macrophages = fibroblast proliferation along with cytokines
  7. causes ECM collagen, proteoglycans etc to increase –> fibrosis –> cirrhosis
  8. positive feedback loop - more fibrosis –> more inflammation –> more fibrosis
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22
Q

What are the consequences of liver failure for production of clotting factors?

A
  • less clotting factors since hepatocytes produce all coagulation proteins except VWF and factor VIIIC
  • leads to coagulopathy and bleeding
23
Q

What are the consequences of liver failure for protein synthesis?

A
  • decreased albumin = cannot retain fluid in vasculature –> ascites
  • decrease in plasma volume –> secondary hyperaldosteronism, hypokalaemia (lower K+) and alkalosis
24
Q

What are the consequences of liver failure for detoxification?

A

Encephalopathy and cerebral oedema

25
Q

What are the consequences of liver failure for glycogen storage?

A

Hypoglycaemia

26
Q

What are the consequences of liver failure for immunological function and globulin production?

A

Increased susceptibility to infection

27
Q

What are the consequences of liver failure for maintenance of homeostasis?

A

Circulatory collapse, renal failure

28
Q

What does cholestasis do?

A
  • leads to liver damage
  • decrease in bile salts
  • this means less micelle formation and absorption of vitamin K
  • this means less gamma-carboxylation of vitamin-K dependent clotting factors (II, VII, IX, X)
  • aggravates any bleeding tendency, particularly GI bleeding
29
Q

What are the mechanisms of cholestasis?

A
  • canalicular dilation + bile cannot get out
  • decreased cell membrane fluidity
  • deformed brush borders
  • biliary transporters problem e.g. carriers inserted on wrong side
  • increased tight junction permeability - due to increased bile in duct
  • decreased mitochondrial ATP synthesis
30
Q

What are the consequences of cholestasis?

A
  • increased BR –> jaundice
  • pruritus (itching)
  • cholesterol deposition (particularly around eyes)
  • malabsorption
  • cholangitis
31
Q

What does portal hypertension cause?

A
  • decreased lymphatic flow –> worsens ascites
  • thrombocytopenia from splenomegaly - blood trying to leave spleen via splenic vein into portal vein but cannot so platelets sequester and are used up (reduced active clotting factors)
  • oesophageal varices occur
  • these cause severe bleeding
  • exudative enteropathy
32
Q

What is exudative enteropathy?

A
  • blood trying to leave large bowel but cannot so you get increased ascites –> loss of albumin from plasma
  • this favours bacteria in large bowel being fed with proteins
  • causes liberation of ammonium (toxic to brain) –> encephalopathy
33
Q

What are the three types of causes of portal hypertension?

A
  • overall caused by increased vascular resistance
  • pre-hepatic
  • post-hepatic
  • intra-hepatic
34
Q

What are pre-hepatic causes of portal hypertension?

A
  • thrombus (blockage) outside liver
  • portal vein thrombosis
35
Q

What are post-hepatic causes of portal hypertension?

A
  • right heart failure
  • constrictive pericarditis - blood cannot leave so back pressure through liver occurs
36
Q

What are intrahepatic causes of portal hypertension?

A
  • perisinusoidal - chronic hepatitis, PBC, granulomas (schistosomiasis, TB etc)
  • sinusoidal - acute hepatitis, alcohol, fatty liver, toxins, amyloidosis
  • postsinusoidal - venous occlusive disease of venules and small veins, Budd-Chiari syndrome (obstruction of large hepatic veins - right, middle and left)
37
Q

What are the consequences of portal hypertension?

A
  • malabsorption
  • splenomegaly - anaemia and thrombocytopenia
  • vasodilators (glucagon, VIP, substance P, prostacyclin, NO etc release) - decrease BP = increased cardiac output to compensate –> hyperperfusion of abdominal organs –> varices
  • encephalopathy - toxins from intestine (NH3, biogenic amines, FFAs etc) normally extracted from portal blood by hepatocytes –> cross BBB –> CNS problems
  • varices
38
Q

What are varices?

A
  • since big arteries and veins blocked (e.g. SMV and portal vein), blood takes routes down other vessels that are not meant to take high volumes of blood
  • this dilates them –> thin-walled collateral vessels prone to sudden rupture
  • this combined with thrombocytopenia and decreased clotting factors –> bad bleeding
39
Q

What does encephalopathy cause?

A

Apathy, memory gaps, tremor, liver coma

40
Q

What physiological changes cause encephalopathy?

A
  • hyperammonaemia - GI bleeding increases colonic proteins and liver cannot convert toxic NH3 and NH4+ into urea
  • hypokalaemia - secondary hyperaldosteronism causes it –> intracellular acidosis –> activates NH4+ formation in proximal tubules –> systemic alkalosis
  • toxins (amines, phenols and FFAs) bypass liver and not extracted - contribute to encephalopathy
  • ‘false transmitters’ (e.g. serotonin) from aromatic amino acids in brain are increased in liver failure –> encephalopathy
41
Q

Where are the locations of varices (portal-systemic anastomoses)?

A
  • oesophageal varices - anastomoses open up between oesophageal tributaries of gastric vein and azygos veins
  • between middle and inferior rectal veins and superior rectal veins - can get torrential bleeds from rectal mucosa
  • between paraumbilical veins and superficial veins of anterior abdominal wall
42
Q

How is severity of liver failure assessed?

A
  • Child-Pugh score - also a prognosticator for peri-op death
  • more points on worsening total BR, serum albumin, INR, ascites and hepatic encephalopathy
  • score divided up into three classes:
  • class A: 5-6 points - expectancy of 15-20 years, 10% peri-op mortality
  • class B: 7-9 points - transplant candidates, may have 30% post-op mortality
  • class C: 10-15 points - life expectancy 1-3 months, 82% post-op mortality
43
Q

What is the supportive treatment for encephalopathy?

A
  • reduce protein intake
  • phosphate enema/lactulose - try to empty bowels
  • no sedation
44
Q

What is the supportive treatment for hypoglycaemia?

A

Infusion 10-50% dextrose

45
Q

What is the supportive treatment for hypocalcaemia?

A

10ml 10% calcium gluconate

46
Q

What is the supportive treatment for renal failure?

A

Haemofiltration

47
Q

What is the supportive treatment for respiratory failure?

A

Ventilation

48
Q

What is the supportive treatment for hypotension?

A
  • albumin
  • vasoconstrictors
49
Q

What is the supportive treatment for infection?

A
  • frequent cultures
  • antibiotics
50
Q

What is the supportive treatment for bleeding?

A
  • vitamin K
  • FFP
  • platelets
51
Q

What are the causes of death with liver failure?

A
  • bacteria and fungal infections
  • circulatory instability
  • cerebral oedema
  • renal failure
  • respiratory failure
  • acid-base and electrolyte disturbance
  • coagulopathy
52
Q

What are liver support devices?

A
  • artificial (MARS, Bio-Logic DT) - albumin exchange system, based on selective removal of albumin-bound toxins from blood
  • bioartificial hepatocytes in culture - to remove toxins, not very effective
  • hepatocyte transplantation - none really effective
53
Q

What are the indications for liver transplantation?

A
  • effective for hepatocellular cancer since it comes from cirrhotic liver (and originates in liver and does not metastasise)
  • cirrhosis
  • cholestatic disease
  • acute liver failure
  • metabolic disease
  • others - Budd-Chiari, benign liver tumours, polycystic liver disease

Year 1 - BRS (73 decks)

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