Bile, bilirubin and jaundice Flashcards

1
Q

State three roles of bile.

A

CAT:

  1. Cholesterol homeostasis, using secretion and excretion to fine-tune serum concentration
  2. Absorption and digestion, Lipids and lipid-soluble vitamins (ADEK)
  3. Toxin excretion: Endogenous and exogenous
    - Removal of xenobiotics (foreign drug products), drugs and endogenous waste products (e.g. steroid hormones)
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2
Q

List the major components of bile.

What colour is bile

A

Bile salts, cholesterol, bilirubin, phospholipids, bicarbonate, WATER, enzymes

Bile is an aqueous solution so lots of WATER and other solutes.

Bile is a green colour because of pigments like bilirubin and biliverdin.

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3
Q

How much bile is produced daily?

A

500 mL

The capacity of the gallbladder = 15-60 mL

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4
Q

Which cell types produce bile? State the relative proportions of bile produced by each cell type.

A

Hepatocytes - 60%

Cholangiocytes lines the biliary tree, the biliary epithelium - 40%

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5
Q

Describe what happens as the bile travels down the bilary tree

A

40% bile secreted by cholangiocytes (biliary epithelium)

Alters pH, fluidity and modifies bile as it flows through

H20 drawn INTO bile (osmosis through paracellular junctions)

Luminal glucose and some organic acids also reabsorbed.

HCO3- and Cl- actively secreted INTO bile by CFTR mechanism (Cystic Fibrosis Transmembrane Regulator)

Cholangiocytes contribute IgA by exocytosis

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6
Q

What does bile flow depend on?

A

The concentration of the bile and salts in the blood

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7
Q

What regulates bile concentration?

A

The transporters in the cholangiocytes

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8
Q

what does biliary excretion do and where does this take place?

A

Biliary excretion of bile salts and toxins performed by transporters on apical surface of hepatocytes + cholangiocytes

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9
Q

What channel transports bicarbonate and chloride ions into the bile?

When is bile released?
what does the gall bladder do?

A

CFTR

Constantly being synthesised. Stored in the gallbladder.
CCK stimulates gall bladder contraction for a big dose.

  • Stores bile
  • acidifies bile
  • concentrates bile (by reabsorbing ions, creating an osmotic gradient) May remove volume
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10
Q

State some of the main transporters that regulate bile concentration.

A

Bile Salt Excretory Pump (BSEP): active transport of bile acids across hepatocyte canalicular membranes into bile, and secretion of bile acids is a major determinant of bile flow

MDR related proteins (MRP1, MRP3)

MDR1: mediates canalicular excretion of xenobiotics, cytotoxins

MDR 3: encodes a phospholipid transporter protein that translocates phosphatidylcholine from inner to outer leaflet of canalicular membrane

products of the familial intrahepatic cholestasis gene (FIC1) and multidrug resistance genes (MDR1 & MDR3).

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11
Q

What are the primary bile acids and their respective secondary bile acids? What is the difference between primary and secondary bile acids?

A
  • Bile acids are synthesised from cholesterol.
  • we have 2 primary and 2 secondary

Primary bile acids are produced by the liver. They are converted to secondary bile acids by the action of colonic bacteria. Deoxycholate is reabsorbed but 99% of lithocholic acid is excreted in the stool.
Primary = Cholic Acid + Chenodeoxycholic Acid
Secondary = Deoxycholic Acid + Lithocholic Acid

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12
Q

What percentage of bile is water?

A

97%

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13
Q

what is the function of bile?

what special properties does Micelles have?

A

Reduce surface tension of fats
Emulsify fat preparatory to its digestion/absorption

Bile Salts form Micelles

Bile salts amphipathic
One surface has hydrophilic domains, facing OUT
2nd has hydrophobic domains, facing IN
free Fatty Acids and Cholesterol INSIDE
thus transported to GIT epithelial cells for absorption

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14
Q

what is the effect of high concentrations of bile salts?

A

Detergent-like actions make bile salts potentially cytotoxic in high concentrations.

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15
Q

what does the right and left lobe of the lung drain into

A

right lobe drains into the right hepatic duct and the left lobe drains into the left hepatic duct

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16
Q

How does the bile enter the duodenum

A

Bile is synthesised by hepatocytes and cholangiocytes.

Between meals duodenal orifice closed, therefore bile diverted into gall bladder for storage

Eating causes sphincter of Oddi to relax

Gastric contents (F.As, A.As > CHOs) enter duodenum causing release of cholecystikinin, CCK (Gut mucosal hormone)

Cholecystikinin causes gall bladder to contract, this causes large dose of bile to be secreted.

17
Q

describe the anatomy of the biliary system?

A

Each hepatocyte is apposed to several bile canaliculi

these drain intralobular bile ducts, coalesce
interlobular ducts —– Right/Left Hepatic Ducts
join outside liver to form Common Hepatic Duct

Cystic Duct drains the gall bladder

Cystic Duct unites with Common Hepatic Duct to form COMMON BILE DUCT (CBD)

CBD joined by Pancreatic Duct prior to entering duodenal papilla

18
Q

What percentage of bile salts are reabsorbed in the terminal ileum?

A

95%

19
Q

what is the enterohepatic circulation?

A
  • cycle between the gut and the liver by continuous reabsorption in the gut, carriage in portal blood to liver and hepatocyte secretion into bile canaliculi to be secreted via the common bile duct.
  • many drugs can do this, not the whole drg can do this maybe 90%, therefore increasing their half life.
20
Q

give an example of something that goes through this enteropathic circulation?

A

95% bile salts absorbed from small (terminal) ileum
by Na+/bile salt co-transport Na+-K+ ATPase system
5% converted to 2o bile acids in colon:
- deoxycholate absorbed
- lithocholate 99% excreted in stool
absorbed B.salts back to liver
re-excreted in bile

21
Q

Describe how terminal ileal disease can cause steatorrhoea.

A

Terminal ileal disease e.g. crohns disease, cancer etc. will mean that less bile salts are reabsorbed so less bile salts are released in the bile into the duodenum so there is less fat emulsification, digestion and absorption so more fat passes through the small intestines and enters the colon and leaves the body. It also means that the bile continues to the colon which is where it can cause irritation as it is toxic.
This is called bile acid malabsorption.

22
Q

What is another important consequence of fat digestion and absorption is reduced?

A

They also absorb fewer fat soluble vitamins - ADEK.

-Malabsorption of fat soluble vitamins.

23
Q

State three important roles of the gallbladder.

A
  1. Stores bile (50ml), released after meal for fat digestion
  2. Acidifies bile
  3. Concentrates bile by H20 diffusion following net absorption of Na+, Cl-, Ca2+, HCO3 ( intra-cystic pH)
    • Gall bladder can reduce volume of its stored bile by 80 – 90%
24
Q

What are the effects of cholecystectomy?

A

The bile drips into the duodenum and you can function perfectly fine. However, you will not be able to produce a large/concentrated release of bile due to gallbladder contraction so there may be some discomfort after eating a fatty meal.

25
Q

What are the main sources of bilirubin?

A

75% Breakdown of haem group in haemoglobin
22% Breakdown of other haem proteins
3% from ineffective erythropoiesis

26
Q

which organ breaks down red blood cells and construction?

A

Spleen, this is also where bilirubin get there.

27
Q

What plasma protein carries bilirubin to the liver?

A

Albumin

28
Q

What happens to bilirubin when it reaches the liver, what is the equation for total BR?

A

BR bound to albumin most dissociates in liver

Free BR enters hepatocyte, Bilirubin is conjugated with glucuronic acid to make it more water soluble by the action of UDPGA from smooth ER

transported ACROSS concentration gradient into bile canaliculi GIT

TOTAL BR = FREE BR (UNCONJUGATED) + CONJUGATED BR

29
Q

What two substances can bilirubin be converted to in the intestines and how are they excreted?

A

Bilirubin can be converted to urobilinogen and excreted via the kidneys. Urobilinogen is formed mainly in the intestines by bacterial action. GIT mucosa is impermeable to conjugated bilirubin but is permeable to unconjugated bilirubin and urobilinogens. So some unconjugated BR enters the enterohepatic circulation, and some forms urobilinogens.
Half of urobilinogens formed are reabsorbed and taken up via the portal vein to the liver, enters circulation and is excreted by the kidneys. 20% of urobilinogens are reabsorbed into the general circulation.
It can be converted to stercobilinogen and then to stercobilin and excreted with the stools - stercobilin is brown.

30
Q

What concentration of bilirubin is considered jaundice?

A

> 34 mcmol/L

31
Q

What are the three types of jaundice?

A

Dependant on were in the pathway the problem is.

Pre-hepatic
Hepatic
Post-hepatic

32
Q

State some causes of pre-hepatic jaundice. What would be the expected conjugated: unconjugated ratio?

A

-Problem in the bilirubin before i hits the liver.
-Increased unconjugated bilirubin because there is too much bilirubin being produced for the liver to conjugate it all
It is caused by haemolysis (could be autoimmune), haematoma resorption, massive transfusion, ineffective erythropoiesis

-due too much red blood cell break down

33
Q

What causes hepatic/ hepatocellular jaundice?

A
  • Problem in the liver.
  • amount of bilirubin being produced is normal
  • hepatocytes not working.

Defective uptake

Defective conjugation

Defective BR excretion

Main cause is Liver failure:
Defective uptake
Defective conjugation
Defective BR excretion

-Lots of unconjugated BR

34
Q

How can you distnguish between pre-hepatic and hepatic jaundice?

A

Pre-heptic jaundice, liver is normal so patient has no liver disease.

-liver enzymes will be very high in hepatic jaundice

35
Q

What can cause post-hepatic/obstruction jaundice?

A
  • amount of bilirubin produced in the spleen is normal
  • liver is fine
  • problem, there is a physical obstruction that s reducing the flow of bile in the duodenum, therefore less bilirubin the gut, so amount of bilirubin in colon decreased so less stercobilin.

Defective Transport of BR by Biliary duct system e.g. common bile duct stones, HepPancBil malignancy, local LNpathy

Look out for sepsis (cholangitis)

Dilated bile ducts on scans

-Lots more conjugated than unconjugated

36
Q

What are some simple clinical features of post-hepatic/obstructive jaundice?

A

Pale stools - because bile isn’t entering the intestines so there is less stercobilin being produced
Dark urine - the body is trying to excrete some of the bilirubin via the urine, which would contain a lot of urobilinogen, which is dark

37
Q

What is Gilbert’s Syndrome?

A
  • The most common hereditary cause of increased bilirubin
  • 5% affected
  • Leads to elevated unconjugated bilirubin.
  • Caused by a 70-80% decrease in the glucuronidation activity of UDPGA, so they conjugate their bilirubin slower.
  • Autosomal recessive