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Alimentary system > Liver Failure and Jaundice > Flashcards

Liver Failure and Jaundice Flashcards

1
Q

What is xenobiotic?

A

Foreign substance

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2
Q

What percentage of bile is water?

A

97%

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3
Q

What are the roles of bile?

A
  • Cholesterol homeostasis
  • Dietary lipid/vitamin absorption
  • Removal of xenobiotics/drugs/endogenous waste product.
  • E.g. cholesterol metabolites, hormones etc.
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4
Q

How much bile is produced daily and what % from where?

A

500ml
60% from hepatocytes
40% from cholangiocytes (biliary epithelial cells in biliary tree)

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5
Q

What are the roles of the biliary tree?

A
  • Alter pH, fluidity and modifies bile
  • Facilitates passage of H2O into the bile via osmosis (through paracellular junctions)
  • Reabsorbs glucose and some organic acids
  • Secretes HCO3- and Cl- into the bile through CFTR
  • Cholangiocytes contribute IgA antibodies into mucosa
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6
Q

What is bile flow related to?
What is involved in secreting bile salts?
What happens when they fail?

A
  • Bile flow is closely related to the concentrations of bile acids and salts in the blood
  • Apical transporters on hepatocytes and cholangiocytes secrete the bile salts and toxins which also govern flow rate of bile
  • If these transporters stop then you get cholestasis
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7
Q

What are some examples of biliary transporters?

A

BSEP – Bile Salt Excretory Pump

MDR related proteins - MRP1, MRP3

Products of the familial intraheptic cholestestasis gene - FIC1

Prodcuts of the mutlifrug resistance gene - MDR1, MDR3

Genetic mutations can occur in these genes and cause cholestasis

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8
Q

What do BSEP, MDR1 and MDR3 do?

A

MDR1 – mediates canalicular excretion of xenobiotics and cytotoxins

MDR3 – Encodes a phospholipid transporter protein to translocate phosphatidlycholine to from inner to outer leaflet of canalicular membrane

BSEP - Active transport of bile acids across heptocyte cancalicular membranes into bile

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9
Q

Bile salts/bile acids and their synthesis and how many are there?

A
  • Na and K salts of bile acids conjugates to glycine/taurine
  • Bile acids are synthesised from cholesterol
  • There are 4 bile acids in humans
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10
Q

What are the 2 primary and secondary bile acids?

A

cholic acid -> deoxycholic acid (secondary)

chenodeoxycholic acid -> litocholic acid ( secondary)

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11
Q

How are primary bile acids converted to secondary bile acids?

A

By colonic bacteria

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12
Q

What are the functions of bile salts?

A
  • reduces surface tension of fats

- emulsify fats

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13
Q

Why can bile salts form micelles?

A

Because they are amphiphatic - have hydrophilic and hydrophobic face
Cholesterol and fatty acids are inside

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14
Q

Bile salt toxicity

A

Detergent like actions of bile salts means they can be toxic at high concentrations by irritating the gut and cause diarrhoea

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15
Q

Bilary tree

What do the cystic duct and common hepatic duct join to form?

A

The bile in the right hepatic lobe drains into the right hepatic duct

The bile in the left hepatic lobe into the left hepatic duct
The two ducts join at hilum just outside the liver to form common hepatic duct

The cystic duct from the gallbladder and common hepatic duct join to form the common bile duct.

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16
Q

Sphincter of Oddi

A

At the ampulla of the bile duct, the sphincter of Oddi controls bile secretion into the 2nd duodenum
When we are not eating the sphincter is closed and duodenal orifice is closed so bile is diverted into the gallbladder to be stored.

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17
Q

What does CKK do when you have eaten?

A
  • Relax the sphincter of Oddi so the duodenal orifice is opened
  • Contract the smooth muscle around gall bladder
    This means bile is forced into the duodenum
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18
Q

Enterohepatic circulation of bile salts - between small intestine and liver

A
  • 95% of bile salts reabsorbed in the terminal ileum by Na+/bile-salt co-transport
  • 5% are converted to secondary bile acids in the colon by colonic bacteria:
    Deoxycholate absorbed, lithocholate excreted in stool (99% of it)
  • Reabsorbed salts go via the portal veins, back to the liver to be re-excreted in bile
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19
Q

What effect will terminal ileum disease/removal have?

What happens if bile cannot enter the gut?

A

Less resorption = more fatty stool as less bile salt excreted (liver cannot sustain production)
Malabsorption of fat-soluble vitamins (A, D, E, K).

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20
Q

How much bile salt recycles repeatedly and how many times?

A

3g of bile salts at any one time, secreted 2x a meal

21
Q

What are the functions of the gallbladder?

A
  • store bile (50ml)
  • acidify bile
  • concentrate bile by H20 diffusion following absorption of ions
22
Q

What are the effects of cholecystectomy (gall bladder removal)?

A
  • Periodic discharge of bile from GB aids digestion but is not essential
  • Normal health but continous slow bile discharge into duodenum
  • Avoid food with high fat content
23
Q

Bilirubin production

A

75% - Hb breakdown – in the spleen
22% - Catabolism of other haem proteins
3% - Ineffective bone marrow erythropoiesis

24
Q

What are the features of bilirubin - colour and solubilty?

A

H2O insoluble, yellow pigment.

25
Q

How does bilirubin enter the bile?

A

BR-albumin in blood dissociates at the liver and free BR enters the hepatocyte and conjugates to glucoronic acid by UDPGT. This forms diglucoronide BR (this is water soluble so can get into bile canciculi into GIT

Total BR = free/unconjugated BR + conjugated BR.

26
Q

Urobilinogens

A

– H2O-soluble, colourless derivatives of BR formed by gut bacterial action

  • Half of urobilinogen formed is reabsorbed and taken into the portal vein to liver to circulation then to kidney to be excreted
  • GIT mucosa is impermeable to conjugated BR but permeable to unconjugated BR and urobilinogens
  • Hence some unconjugated BR eneters enterohepatic curculation and some forms urobilinogen
  • 50% formed is reabsorbed from the gut, 50% is excreted in stool
  • 20% of the 50% reabsorbed into the general circulation is excreted in urine
  • 50% of urobilinogen is passed in the stool as stercobilinogen
  • Faeces are brown as stercobilinogen is oxidised to stercobilin
27
Q

What is jaundice?

A

Excess BR in the blood (>34-50 microMl/L), should be <20 microM/L

Yellow tinge to skin, sclerae and mucous membranes caused by deposition of bilirubin

28
Q

What are the causes of jaundice?

A

Can be pre-hepatic
Can be hepatic
Can be post hepatic

29
Q

Causes of prehepatic jaundice
What should be present?
What investigations should be done?

A

Increased quantity of BR (red cells dying faster) due to:

  • Haemolysis
  • Massive transfusion
  • Haematoma resorption
  • Ineffective erythropoiesis

Look for Hb drop without overt bleeding. Can check for amount of conjugated and unconjugated BR and should be mostly unconjugated

Investigations:
Blood film

30
Q

Causes of hepatic jaundice

A

Hepatcocytes aren’t working

  • Defective uptake/conjugation and defective BR excretion into GI
  • Caused by liver failure (viruses, sepsis, drugs, alcohol, cirrhosis)
31
Q

Causes of post hepatic jaundice/obstructive and what is it characterised by?

What investigations should be done?

A

Defective transport of BR, due to:

  • Common bile duct stones
  • HepPancBil Malignancy

Characterised by:

  • Cholangitis (infection of bile duct)
  • Stool pale as less stercobilin.
  • Urine dark as more BR sent to kidneys

Investigations:
- CT or MRCP, ultrasound etc.

32
Q

Gilbert’s syndrome - hepatic cause of jaundice

A
  • Commonest hereditary (A recessive) BR, affects up to 5% of the population
  • Causes a raise of unconjugated bilirubin in the blood stream
  • Cause: 70-80% reduction in enzyme activity (UDPGT-1A1) = reduction in conjugation of BR
  • Usually asymptomatic but can result in slight jaundice under exertion, stress and fasting (affects enzyme more)
33
Q

What is acute liver failure?

A

The rate of hepatocyte death > regeneration rate

Has various aetiologies and a combination of necrotic and/or apoptotic cell death

34
Q

What can cause apaptosis of the liver?

A

Paracetemol overdose

Cytokines active Caspase cascade after oxidative mitochondrial damage

35
Q

What can cause necrosis of the liver?

A

Ischaemia

Mitcohondria badly damaged so no ATP left

36
Q

What is fulminant hepatic failure and the types?

A

Rapid development (<8 weeks) of severe liver injury with impaired synthetic function (such as albumin) and encephalopathy

  • Hyperacute hepatic failure is 0-7 days
  • Acute hepatic failure is 8-28 days
  • Sub-acute hepatic failure is 29 days -12 weeks
37
Q

What is sub falminant liver failure?

A

Less rapid - less than 6 months

38
Q

What are the clinical differences between sub falminant and falminant?

A
  • Cerebral oedema common in fulminant

- Renal failure and portal hypertension common in sub-fulminant

39
Q

Epidemiology of ALF in the UK

A
  • relatively uncommon
  • less than 500 deaths a year
  • less than 15% of liver transplants
40
Q

Commonest causes of ALF ?

A

Paracetemol

41
Q

What are some causes of ALF?

A
  • Toxins: paracetamol, Amanita phalloides, Bacillus cereus
  • Diseases of pregnancy: Budd-Chiari, HEV, hepatic infarction
  • Idiosyncratic drug reactions: single agent: NSAIDS
    drug combinations: Amoxicillin/Clavulanic acid
  • Vascular distress: VOD, Ischaemic hepatitis
  • Metabolic causes: Wilson’s disease, Reye’s syndrome
42
Q

Paracetemol danger doses

A

Toxicity possible >10g
severe toxicity certain>25g
Lower doses can be toxic if fasting, in chronic alcoholics

43
Q

Paracetemol poisoning in the UK

A
  • upto 70% of ALF cases
  • Uk has highest rates of overdose in the world
  • 10% of cases get severe LD
  • 2% develop ALF
44
Q

Normal liver functions vs if you have liver failure

A

detoxification -> toxins in blood can cause encephalopathy and cerebral odema

glycogen storage -> hypoglycaemia

protein production -> less albumin causes ascites and oedema

production of clotting factors -> coagulopathy and bleeding

immunological functions and globulin production and complement production -> increased susceptibility to infection

maintenance of homeostasis -> circulatory collapse and renal failure

protein catabolism and ammonia clearance - low urea and encephalopathy/coma

45
Q

Symptoms of liver failure

A

Initially non-specific – malaise, nausea and lethargy.

Jaundice and then encephalopathy (possibly via accumulation of neurotoxic substances in brain affecting astrocyte function).

46
Q

Differences between ALF in the UK and far east

A
  • In UK, ALF accounts for <15% of liver transplants but in the far-east, ALF attributes to 70% of transplants.
  • Usually drug-induced in the west.
  • Usually viral hepatitis in the far-east.
47
Q

What are the causes of death due to liver failure?

A
  • Bacterial/fungal infection.
  • Circulatory instability.
  • Renal and/or respiratory failure.
  • Coagulopathy.
48
Q

Liver transplant for ALF

A

Emergency liver transplant is the only intervention of proven benefit

  • Timing is important
  • Unnecessary selection can causes mortality
  • Immunosupression
  • Expense
  • Wastes gift
  • 5% of all transplants in UK
  • 5 year survival ranges from 60-80%

Alimentary system (14 decks)

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