Bile, Bilirubin and Jaundice Flashcards
State three roles of bile.
Cholesterol homeostasis
Dietary lipid/vitamin absorption
Removal of xenobiotics, drugs and endogenous waste products (e.g. steroid hormones)
List the major components of bile.
Bile salts, cholesterol, bilirubin, phospholipids, bicarbonate, WATER
How much bile is produced daily?
500 mL
The capacity of the gallbladder = 15-60 mL
Which cell types produce bile? State the relative proportions of bile produced by each cell type.
Hepatocytes - 60%
Cholangiocytes - 40%
What does bile flow depend on?
The concentration of the bile
What regulates bile concentration?
The transporters in the cholangiocytes
What channel transports bicarbonate and chloride ions into the bile?
CFTR
State some of the main transporters that regulate bile concentration.
Bile Salt Excretory Protein (BSEP)
MDR related proteins
Multidrug Resistance Genes
Familial Intrahepatic Cholestasis gene
What are the primary bile acids and their respective secondary bile acids? What is the difference between primary and secondary bile acids?
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
What percentage of bile is water?
97%
Describe the effect of cholecystokinin on bile release.
Cholecystokinin causes contraction of the gallbladder and relaxation of the sphincter of Oddi
What percentage of bile salts are reabsorbed in the terminal ileum?
95%
Describe how terminal ileal disease can cause steatorrhoea.
Terminal ileal disease 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.
What is another important consequence of fat digestion and absorption is reduced?
They also absorb fewer fat soluble vitamins - ADEK
State three important roles of the gallbladder.
Store bile
Acidify bile
Concentrate the bile
What are the effects of cholecystectomy?
The bile drips into the duodenum and you can function perfectly fine. However, you will not be able to produce a large release of bile due to gallbladder contraction so there may be some discomfort after eating a fatty meal.
What are the main sources of bilirubin?
75% Breakdown of haem group in haemoglobin
22% Breakdown of other haem proteins
3% from ineffective erythropoiesis
What plasma protein carries bilirubin to the liver?
Albumin
What happens to bilirubin when it reaches the liver?
Bilirubin is conjugated with glucuronic acid to make it more water soluble by the action of UDPGA from smooth ER
What two substances can bilirubin be converted to in the intestines and how are they excreted?
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.
What concentration of bilirubin is considered jaundice?
> 34 mcmol/L
What are the three types of jaundice?
Pre-hepatic
Hepatic
Post-hepatic
State some causes of pre-hepatic jaundice. What would be the expected conjugated: unconjugated ratio?
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
What causes hepatic jaundice?
Caused by ineffective uptake, conjugation and bilirubin excretion
What can cause post-hepatic jaundice?
An obstruction to the biliary system e.g. pancreatic carcinoma or a gallstone
What are some simple clinical features of post-hepatic/obstructive jaundice?
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
What is Gilbert’s Syndrome?
The most common hereditary cause of increased bilirubin
Caused by a 70-80% decrease in the glucuronidation activity of UDPGA.
Leads to elevated unconjugated bilirubin.
Autosomal recessive
