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Year 3 Gastro > Liver Failure > Flashcards

Liver Failure Flashcards

1
Q

What is normal plasma bilirubin?

A

17 μmol/L

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2
Q

What happens if BR is high?

A

If [BR] ↑s > 30 μmol/L
→ yellow sclera & mucous membranes

If [BR] ↑s > 34 μmol/L
→ skin turns yellow

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3
Q

What is cholestasis?

A

Slow/cessation of bile flow
Normally results in jaundice
Jaundice does not

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4
Q

What are the pre-hepatic causes of jaundice?

A 
Haemolysis
Haemolytic anaemia
Toxins
Massive transfusion 
     (transfused erythrocytes short-lived)
Large haematoma resorption
Ineffective erythropoiesis
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5
Q

What are the intra-hepatic causes of jaundice?

A 
Specific defects:
↓ed BR uptake 
Gilberts syndrome
↓ed conjugation BR 
Crigler-Najar syndrome
↓ed secretion BR into biliary canaliculi
Dubin-Johnson syndrome
Rotor syndrome
Intrahepatic cholestasis (↓ed outflow):
Sepsis, TPN & drugs

Liver failure

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6
Q

Define the pathophysiology of liver failure

A

When rate of hepatocyte death > regeneration

Combination of apoptosis &/or necrosis

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7
Q

What is the clinical result of liver failure?

A

Clinical result = catastrophic illness

Can rapidly lead to coma/death due to multi-organ failure

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8
Q

What is acute liver failure?

A

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
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9
Q

What is chronic failure?

A

Over years

Cirrhosis

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10
Q

What are the causes of acute liver failure in the west?

A

Toxins
Paracetamol
Amanita phalloides
Bacillus cereus

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11
Q

What are the causes of acute liver failure in the west?

A

Inflammation
Exacerbations of chronic Hep B (Hong Kong)
Hepatitis E (India)

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12
Q

What are the other causes of acute liver failure?

A

Disease of pregnancy
AFLP/HELLP/Hepatic infarction/ Budd-Chiari

Idiosyncratic drug reactions
Single Agent: Isoniazid, NSAID’s, valproate
Drug combinations: Amoxicillin/clavulanic acid, trimethoprim/sulphamethoxazole, rifampicin/isoniazid

Vascular disease

Metabolic causes
Wilson’s disease- copper deposition
Reye’s syndrome- children taking aspirin after chickenpox

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13
Q

What are the causes of chronic liver failure?

A

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

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14
Q

Describe the mechanisms of cirrhosis

A

Necrosis of heptoctyes causes release of enzymes

Kick off cytokines

Activate Kupffer cells

Release growth factors

Stimulate hepatic stellae cell

Monocytes to macropahges

Stimulates fibroblast proliferation

Causes fibrosis and cholestasis

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15
Q

What are the consequences of hepatocyte failure?

A 
Coagulopathy and bleeding
Ascites
Encephalopathy & cerebral oedema
Hypoglycaemia
Increased susceptibility to infection
Circulatory collapse, renal failure
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16
Q

What does the decrease in protein synthesis result in?

A 
Decreased albumin
Decreased plasma (clotting factors)
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17
Q

What is the consequence of decreased albumin?

A 
↓ albumin → ascites
Plasma vol ↓ 
     	→ 20 hyperaldosteronism
     	→ hypokalaemia (↓K+)
     	→ alkalosis
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18
Q

What is the consequence of decreased plasma (clotting factors)?

A

Hepatocytes synthesis all coagulation proteins except von Willebrand factor & factor VIIIC

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19
Q

What can cholestasis cause?

A 
→ 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
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20
Q

What are the mechanisms of cholestasis?

A 
Canalicular dilation
↓ cell membrane fluidity
Deformed brush border
Biliary transporters
↑ tight junction permeability
↓ mitochondrial ATP synthesis
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21
Q

What are the consequences of cholestasis?

A 
↑ BR → jaundice
Pruritus (itching)
Cholesterol deposition
Malabsorption
Cholangitis
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22
Q

What is portal hypertension?

A

Blood cannot travel through portal vein
Takes another route via blood vessel not designed to take high blood flow
Caused by increased vascular resistance

23
Q

What does portal hypertension result in?

A

thrombocytopenia (destroy platelets) resulting from splenomegaly

Oesophageal varices

↓ active clotting factors, thrombocytopenia, & varices → severe bleeding

exudative enteropathy

24
Q

What is exudative enteropathy?

A

↑ ascites → loss of albumin from plasma
favours bacteria in large bowel being “fed” with proteins
↑ liberation of ammonium (toxic to brain)

25
Q

What are the prehepatic causes of portal hypertension?

A

Portal vein thrombosis

26
Q

What are the intrahepatic causes of portal hypertension?

A

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).

27
Q

What are the posthepatic causes of portal hypertension?

A

right heart failure

constrictive pericarditis

28
Q

What are the consequences of portal hypertension?

A 
Malabssorption
Splenomegaly
Vasodilation
Encephalopathy
Varices
29
Q

How does it cause encephalopathy?

A

Toxins from intestine (NH3, biogenic amines, FFAs, etc.) normally extracted from portal blood by hepatocytes → CNS
Varices

30
Q

How does it cause varices?

A

Thin walled collateral vessels + thrombocytopenia & ↓ clotting factors → bleeding +++

31
Q

What is hepatic encephalopathy?

A

memory gaps, tremor & liver coma

32
Q

How do you assess the severity of liver failure?

A

Child-Pugh score

Assesses disease severity for end-stage liver disease, and a prognosticator for peri-op death

33
Q

How do you use child-push scores?

A

Class A: 5-6 points - Expectancy of 15-20 years, 10% peri-operative mortalityClass B: 7-9 points - Transplant candidates, may have 30% P-O MClass C: 10-15 points - Life expectancy 1-3 months, 82% P-O M

34
Q

What is the treatment for encephalopathy?

A

reduce protein intake
phosphate enemas/lactulose
no sedation

35
Q

What is the treatment for hypoglycaemia?

A

infusion 10-50% dextrose

10 ml 10% calcium gluconate

36
Q

What is the treatment for renal failure?

A

haemofiltration

37
Q

What is the treatment for respiratory failure?

A

ventilation

38
Q

What is the treatment for hypotension?

A

Albumin

Vasoconstrictors

39
Q

What is the treatment for infection?

A

Frequent cultures

Antibiotics

40
Q

What is the treatment for bleeding?

A

Vit K
FFP
Platelets

41
Q

What are the causes of death?

A

Bacterial and fungal infections

Circulatory instability

Cerebral Oedema

Renal failure

Respiratory failure

Acid-base and electrolyte disturbance

Coagulopathy

42
Q

What are the indications for liver transplantation?

A 
Acute liver failure
Cholestatic disease
Cancer
Cirrhosis
Metabolic disease
43
Q

What percentage of transplants in the UK are livers?

A

5%

44
Q

What is the 5 year survival with a liver transplant?

A

60-80%

45
Q

What are the causes of portal hypertension?

A

Pre-hepatic: Portal vein obstruction

Intra-hepatic: Cirrhosis, schistosomaiasis, sarcoidosis

Post-hepatic: Right sided HF
Constrictive pericarditis
Budd-Chiari syndrpme

46
Q

What triad of symptoms are seen in Budd-Chiari?

A

Abdo pain
Ascites
Tender hepatomegaly

47
Q

What does the portal vein have connections to the systemic venous system? And what does back flow of blood to these regions cause?

A

Creation of porto-systemic shunts

Interior portion of the eospahgus - cause oesophageal varices

Superior portion of the anal canal - haemorrhoids

Round ligament - caput medusae

48
Q

Why do you get diminished liver function in portal hypertensions?

A

Less blood to the liver

Build up of toxic metabolites

49
Q

What does build up of toxins crossing BBB cause?

A

Hepatic encephalopathy

Confusion

50
Q

What does black flow of blood to the spleen cause?

A

Splenomegaly

Traps RBCs causing anaemia

Traps WCC causing leukopenia

Traps platelts causing thrombocytomenia

51
Q

What are the investigations for portal hypertension?

A 
FBS (decreased platelets, Hb, WCC)
LFTs
Hepatic venous pressure gradient measurement - gold standard
Liver US
Upper GI endoscopy
52
Q

What is the management of portal hypertension?

A 
Treat underlying cause 
Beta-blockers to decrease portal venous pressure
Diuretics and Na restrict
Terlipressin or ligation for Varices 
TIPS
53
Q

What is a sensitive investigation for cirrhosis?

A

Low Platelet count

Year 3 Gastro (39 decks)

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