Bile And biliary Secretions Flashcards
What is bile and what are its functions?
Bile is a complex lipid rich micellar solution.
500ml-600mls produced everyday
Produced by hepatocytes
95% of bile is recycled
Function = emulsify fats and hence aid lipid digestion and absorption. Also has a role in cholesterol homeostasis - facilitates dietary absorption and eliminates them as they are used in their synthesis.
Prevent calcium gallstones
What are the main primary bile acids?
The main secondary bile acid
Cholic and chenodeoxy cholic acid
These are water soluble unlike cholesterol
The main secondary bile acid = deoxycholic
What are bile acids synthesised from? Where?
How does this change their behaviour?
Bile acids are synthesised from cholesterol in pericentral hepatocytes of the acini.
Cholesterol is lipophilic where as the primary bile acids are water soluble!
CA and CDCA are conjugated before secretion into the bile canaliculus
This conjugation enhances the hydrophilicity
How does cholesterol form bile acids?
Via the classic pathway:
Cholesterol — cholic acid and chendeoxycholic acid (via Cyp7A1 enzyme)
The primary bile acids then form secondary bile acids e.g. deoxycholic acid via another enzyme
How do bile acids cause emulsification of fats?
What is the affect of this?
Bile acids are amphipathic meaning they have a hydrophilic and phobic part.
Hydrophobic part clings to fat, hydrophilic part faces the surrounding solution. Stops emulsion droplets from reunifying. Hence they reduce surface tension and aid emulsification.
By doing so they increase the SA for lipolysis - allowing Lipase and collapse to act at the surface of emulsified droplets and liberate FA from the glycerol backbone of the TG.
Once the monoglyceride and fatty acids have been released due to lipase what is the next step in the digestion of lipids?
Until reaching tissue…
There is an addition of more bile salts which causes the formation of micelles which will move to the surface of the enterocyte of the intestine.
From here the monoglyceride and fatty acids can diffuse into the cell.
Once in the cell the components reform a TG.
This TG is then secreted from the cell by exocytosis in the form of a chylomicron these also contain cholesterol and fat soluble vitamins.
The chylomicrons enter the lacteals
Which eventually feed into the general circulation
Once the chylomicrons are in the blood vessels they can be broken down by lipoprotein lipase into MG and FAs, which can then be absorbed into the cell that needs them.
Cholesterol excretion overview
Cholesterol is ingested in the diet and 50% is absorbed in the duodenum due to bile acids etc
50% will be excreted
Statins block the synthesis of cholesterol by the body
Ezetimibe block the absorption of cholesterol from the diet
What is the enteroheaptic circulation?
refers to the process whereby a drug or a metastable metabolite thereof in the liver is secreted into the bile, stored in the gall bladder, and subsequently released into the small intestine, where the drug can be reabsorbed back into circulation and subsequently returned to the liver
Overview of the enterohepatic circulation:
Fasted state =
Fed state =
In a fasted state = bile acids travel down biliary tract to gall bladder where they stored and concentrated 10X
In a fed state = CCK is released from the duodenal mucosa
CCK relaxes the sphincter of oddi and causes contraction of the gall bladder releasing BA, phospholipids etc…
The bile acids emulsify the fats and then are AT via the apical sodium bile acid by a transporter.
It re-enters the liver via the portal circulation.
The bile acids are reconjugated and secreted into the biliary canaliculi — GB
This process usually happens 2-3 x per meal
How can the production of bile be controlled?
as bile acids are reabsorbed by the ileum they attach to the a receptor which causes the synthesis of FGF19 this hormone inhibits the Cyp7A1 enzyme and as cholesterol is converted into primary bile acids by Cyp7A1, less bile is produced.
Therefore the more reabsorb ion of bile the less synthesis of it.
What is the name of the procedure removing the gall bladder?
Cholecystectomy
What can cause bile salt diarrhoea?
Cholecystectomy
Ileal resection -unabsorbed bile acids enter colon
What to do with bile can cause steatorrhoea?
Biliary obstruction - CBD stone or cancer…
Bile can not reach duodenum leading to a poor uptake of fats hence fatty diarrhoea produced.
