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Year 1: Alimentary System > 7. Liver Failure & Jaundice > Flashcards

7. Liver Failure & Jaundice Flashcards

1
Q

What is jaundice?

A

High levels of bilirubin

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2
Q

Why do we produce bile?

A

Cholesterol homeostasis
Dietary lipid/vitamin absorption
Removal of xenobiotics/drugs/endogenous waste productsd

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3
Q

What is the composition of bile?

A

97% water, in an alkaline salt solution

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4
Q

How much bile is produced/secreted daily?

A

500ml

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5
Q

What is the colour of bile?

A

Green/yellow

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6
Q

What is reason for the colour of bile?

A

glucoronides of bile pigments

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7
Q

Where is bile made?

A

60% by hepatocytes

40% by cholangiocytes

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8
Q

What is the path of bile production

A

Bile drains from liver, through bile ducts, into duodenum at duodenal papilla. Stored in the gall bladder

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9
Q

What is the role of the biliary tree?

A

Alters pH, fluidity and modifies bile as it flow through.
H2O drawn into bile
Luminal glucose and some organic acids are also reabsorbed
HCO3- and Cl- are actively secreted into bile the CFTR mechanism
Cholangioctytes contribute IgA by exocytosis

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10
Q

What is biliary excretion of bile salts performed by?

A

Transporters on the apical surface of hepatocytes and cholangiocytes

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11
Q

What do biliary transporters also govern?

A

The rate of bile flow

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12
Q

What is the dysfunction of the transporters called?

A

cholestasis

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13
Q

What is the main bile transporter?

A

Bile Salt Excretory Pump (BSEP) - active transport

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14
Q

What is MDR1?

A

Mediates canalicular excretion of xenobiotics, cytotoxins

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15
Q

What is MDR3?

A

Encodes a phospholipid transporter protein that translocate phasphatidylcholine from inner to outer leaflet of canalicular membrane

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16
Q

What are bile salts synthesised from?

A

Cholesterol

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17
Q

Where are the primary bile salts formed?

A

Liver

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18
Q

What are two primary bile salt acids?

A

Cholic and chenodeoxycholic acid

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19
Q

How are primary bile salts converted to secondary acids?

A

Colonic bacteria in the colon

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20
Q

What are the two secondary bile salts?

A

Deoxycholic acid and lithocholic acid

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21
Q

What is the function of bile salts?

A

Reduce surface tension of fats

Emulsify fat preparatory to its digestion/absorption

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22
Q

What do bile salts form?

A

Micelles because they are amphipathic

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23
Q

Describe the structure of bile salts and micelles?

A

Bile salts has one hydrophilic surface (out) and one hydrophobic face (in). Micelles transport fatty acids and cholesterol inside bringing the contents to the GIT epithelial cells for absorption

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24
Q

What happens if you have too much bile salt?

A

Detergent like actions make bile salts potential cytotoxic in high concentrations

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25
Q

What is the ampulla of bile duct controlled by?

A

Sphincter of Oddi

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26
Q

What do the left and right hepatic ducts drain from?

A

The left and right sides of the liver

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27
Q

What do the left and right hepatic duct form to join?

A

The Common Hepatic duct (outside the liver)

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28
Q

What does the sphincter of Oddi do?

A

Controls the flow of pancreatic juice and bile juice into the duodenum

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29
Q

What is the name of the duct that arises from the gall bladder?

A

Cystic duct

30
Q

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

A

Common bile duct

31
Q

What is the CBD joined by before entering the duodenal papilla?

A

Pancreatic duct

32
Q

In terms of CCK, what happens when you eat food?

A

Cholesystikinine causes the gall bladder to contract squeezing bile into the duodenum

33
Q

Where does bile go when the sphincter of Oddi is closed?

A

Gall bladder

34
Q

Describe the enterohepatic circulation

A

Circulation of biliary acids, bilirubin etc. from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver. Acts as a reservoir

35
Q

Where do the bile salts not absorbed go?

A

5% converted to secondary bile salts in the colon

36
Q

What are the soluble vitamins?

A

A, D, E, K, B12

37
Q

How much bile salt is re-cycled repeatedly in enterohepatic circulation?

A

3g

38
Q

How are bile salts absorbed in the ileum?

A

Na+/bile salt co-transporter. Na+/K+ ATPase

39
Q

What happens to the secondary bile salts in the colon?

A

Deoxycholate is absorbed while lithocholate 99% is excreted in stool

40
Q

What happens during terminal ileal resection/disease?

A

There is a decrease in bile salt reabsorption. This causes an increase in fatty stool since the enterohepatic circulation is interrupted and the liver can’t increase its rate of bile salt production to make up for it.

41
Q

What is the function of the gall bladder?

A

Stores bile (50ml) + releases it
Acidifies bile
Concentrates bile

42
Q

How does the gall bladder concentrate bile?

A

H2O diffusion following the net absorption of ions

43
Q

What are the effects of a cholecystectomy?

A

Normal health (avoid food with high fat content). Periodic discharge of bile from GB is not essential

44
Q

What colour is bilirubin?

A

yellow

45
Q

Is bilirubin water soluble?

A

yes

46
Q

Where is BR produced from?

A

75% BR from Hb breakdown
22% from catabolism of other haem proteins
3% ineffective bone marrow erthropoiesis

47
Q

What is BR bound to?

A

albumin

48
Q

What happens to free BR?

A

It enters the hepatocytes and is conjugated with glucoronic acid catalysed by the enzyme glucoronyl transferase to produce BR-diglucoronide (more soluble). BR-diglucoronide is transported into the bile canaliculi which then leads to the GIT.

49
Q

Total BR =

A

Free BR (unconjugates) + Conjugated BR

50
Q

What are urobilinogens?

A

H2O-soluble, colourless derivatives of BR formed by action of GIT bacteria

51
Q

Where is urobilinogen formed?

A

In the intestines by bacterial action on bilirubin

52
Q

What is urobilinogen reduced to?

A

sterocobilinogen passed as stool

53
Q

What is bilirubin the breakdown product of?

A

Haem

54
Q

Why are unconjugated BR converted to conjugated BR?

A

So it can pass into the GIT along with urobilinogen

55
Q

What is jaundice?

A

Excess BR in blood (>34-50uM/L)

56
Q

Define cholestasis

A

Cessation of bile flow

57
Q

What are the symptoms of jaundice?

A

Yellow tinge to skin, sclerae, mucous membranes

58
Q

What does cholestasis normally result in?

A

Jaundice

59
Q

What are the three categories of jaundice?

A

Prehepatic, Hepatic and post hepatic

60
Q

What can increase the quantity of BR?

A

Haemolysis
Massive transfusion
Haematoma resorption
Ineffective erythropoiesis

61
Q

What are the causes of pre-hepatic jaundice?

A

Increases quantity of BR so the liver can’t cope with the high levels (NOT liver failure)

62
Q

What are the causes of hepatic jaundice?

A

Hepatocytes not working (liver disease):

Defective uptake, conjugation and BR excretion

63
Q

What are the causes of post-hepatic jaundice?

A

Problems to do with the flow of bile into intestine. Bile stones or cancer

64
Q

What is gilberts syndrome?

A

An autosomal recessive disease where there is a 70-80% reduction of glucuronidation activity of the enzyme UDPGT-1A!

65
Q

When does liver failure occur?

A

When the hepatocyte destruction is higher than hepatocyte regeneration

66
Q

What can cause liver failure?

A

Paracetamol - Apoptosis

Ischaemia - necrosis

67
Q

Define fulminant hepatic failure

A

Rapid development (<8wks) of sever acute liver injury with impaired synthetic function (albumin) + encephalopathy in person with a norrmal liver

68
Q

What are the consequences of liver failure?

A

Encephalopathy and cerebral oedema, hypoglycaemia, coagulopathy and bleeding, increased susceptibility to infection, circulatory collapse, renal failure

69
Q

What effect does Liver failure have on protein?

A

Diminished protein synthesis:
Albumin = ascites and oedema
Clotting factors = bruising and bleeding
Complement = Infection and sepsis

70
Q

What effect does liver failure have on metbolism?

A

Carbohydrates - Hypoglycaemia
Protein catabolism - low urea
Ammonia clearance - encephalopathy and coma

71
Q

Is the GIT impermeable to BR?

A

Impermeable to conjugated BR

Permeable to unconjugated BR and urobilinogen

Year 1: Alimentary System (15 decks)

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