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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
What is the ampulla of bile duct controlled by?
Sphincter of Oddi
26
What do the left and right hepatic ducts drain from?
The left and right sides of the liver
27
What do the left and right hepatic duct form to join?
The Common Hepatic duct (outside the liver)
28
What does the sphincter of Oddi do?
Controls the flow of pancreatic juice and bile juice into the duodenum
29
What is the name of the duct that arises from the gall bladder?
Cystic duct
30
What does the cystic duct and common hepatic duct join to form?
Common bile duct
31
What is the CBD joined by before entering the duodenal papilla?
Pancreatic duct
32
In terms of CCK, what happens when you eat food?
Cholesystikinine causes the gall bladder to contract squeezing bile into the duodenum
33
Where does bile go when the sphincter of Oddi is closed?
Gall bladder
34
Describe the enterohepatic circulation
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
Where do the bile salts not absorbed go?
5% converted to secondary bile salts in the colon
36
What are the soluble vitamins?
A, D, E, K, B12
37
How much bile salt is re-cycled repeatedly in enterohepatic circulation?
3g
38
How are bile salts absorbed in the ileum?
Na+/bile salt co-transporter. Na+/K+ ATPase
39
What happens to the secondary bile salts in the colon?
Deoxycholate is absorbed while lithocholate 99% is excreted in stool
40
What happens during terminal ileal resection/disease?
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
What is the function of the gall bladder?
Stores bile (50ml) + releases it Acidifies bile Concentrates bile
42
How does the gall bladder concentrate bile?
H2O diffusion following the net absorption of ions
43
What are the effects of a cholecystectomy?
Normal health (avoid food with high fat content). Periodic discharge of bile from GB is not essential
44
What colour is bilirubin?
yellow
45
Is bilirubin water soluble?
yes
46
Where is BR produced from?
75% BR from Hb breakdown 22% from catabolism of other haem proteins 3% ineffective bone marrow erthropoiesis
47
What is BR bound to?
albumin
48
What happens to free BR?
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
Total BR =
Free BR (unconjugates) + Conjugated BR
50
What are urobilinogens?
H2O-soluble, colourless derivatives of BR formed by action of GIT bacteria
51
Where is urobilinogen formed?
In the intestines by bacterial action on bilirubin
52
What is urobilinogen reduced to?
sterocobilinogen passed as stool
53
What is bilirubin the breakdown product of?
Haem
54
Why are unconjugated BR converted to conjugated BR?
So it can pass into the GIT along with urobilinogen
55
What is jaundice?
Excess BR in blood (>34-50uM/L)
56
Define cholestasis
Cessation of bile flow
57
What are the symptoms of jaundice?
Yellow tinge to skin, sclerae, mucous membranes
58
What does cholestasis normally result in?
Jaundice
59
What are the three categories of jaundice?
Prehepatic, Hepatic and post hepatic
60
What can increase the quantity of BR?
Haemolysis Massive transfusion Haematoma resorption Ineffective erythropoiesis
61
What are the causes of pre-hepatic jaundice?
Increases quantity of BR so the liver can't cope with the high levels (NOT liver failure)
62
What are the causes of hepatic jaundice?
Hepatocytes not working (liver disease): | Defective uptake, conjugation and BR excretion
63
What are the causes of post-hepatic jaundice?
Problems to do with the flow of bile into intestine. Bile stones or cancer
64
What is gilberts syndrome?
An autosomal recessive disease where there is a 70-80% reduction of glucuronidation activity of the enzyme UDPGT-1A!
65
When does liver failure occur?
When the hepatocyte destruction is higher than hepatocyte regeneration
66
What can cause liver failure?
Paracetamol - Apoptosis | Ischaemia - necrosis
67
Define fulminant hepatic failure
Rapid development (<8wks) of sever acute liver injury with impaired synthetic function (albumin) + encephalopathy in person with a norrmal liver
68
What are the consequences of liver failure?
Encephalopathy and cerebral oedema, hypoglycaemia, coagulopathy and bleeding, increased susceptibility to infection, circulatory collapse, renal failure
69
What effect does Liver failure have on protein?
Diminished protein synthesis: Albumin = ascites and oedema Clotting factors = bruising and bleeding Complement = Infection and sepsis
70
What effect does liver failure have on metbolism?
Carbohydrates - Hypoglycaemia Protein catabolism - low urea Ammonia clearance - encephalopathy and coma
71
Is the GIT impermeable to BR?
Impermeable to conjugated BR | Permeable to unconjugated BR and urobilinogen

Year 1: Alimentary System (15 decks)

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