biliary secretion & enterohepatic circulation of bile salts Flashcards
what is bile
an aqueous, alkaline, greenish-yellow liquid
main function of bile
to emulsify fats in the small intestine and to eliminate substances from the liver.
minor function of bile
serves as an excretory pathway for most steroid hormones, many drugs as well some toxins metabolised by the liver
how much bile does the liver produce a day
0.25-1L of bile per day
it is secreted by hepatocytes almost continuously
what is bile made up of (6)
- bile acids
- cholesterol
- phospholipids
- bile pigments (eg bilirubin & biliverdin)
- electrolytes
- water
what are the 2 groups that the constituents of bile are split into
- the bile acid-dependent
- bile acid-independent components
what produces the bile acid-dependent component
hepatocytes
they secrete bile acids, bile pigments and cholesterol into canaliculi, which are small channels that transport the bile acid dependent portion towards the bile ducts
what makes the bile acid independent components
is made by the ductal cells that line the bile ducts.
These cells secrete an alkaline solution – similar to the fluid made by pancreatic duct cells.
secretin stimulates this secretion
where do the dependent and independent components of bile go
they both enter the intrahepatic bile ducts which drain into the biliary tree, a series of ducts which transport bile from the liver to the gallbladder and duodenum.
when do we need bile
during and after meals
where is bile stored
in the gallbladder
it removes the water and ions
what stimulates the flow of bile
- after eating
- the hormone cholecystokinin is released from the duodenum
- this stimulates gallbladder contraction and relaxes the sphincter of Oddi
- allowing bile to flow into the duodenum.
what are the 2 primary bile acids
- Cholic acid
- Chenodeoxycholic acid
how are bile salts formed
when the bile acids are joined with the amino acids glycine and taurine
compare solubility of bile salts and bile acids
bile salts are more soluble than bile acids and act as detergents to emulsify lipids.
structure of bile salts
they are amphipathic
they have a hydrophobic end which is lipid-soluble and a hydrophilic end which is water-soluble.
allows bile salts to emulsify fats into smaller droplets, increasing SA for lipids to be broken down by duodenal lipases.
what are micelles
the bile acids coat the products of lipid breakdown as well as cholesterol and phospholipids to form spherical structures known as micelles
what do micelles do
play an important role in the digestion of fats and transport their contents to the intestinal epithelium where they can be absorbed
what is enterohepatic circulation
the way bile acids recirculate back to the liver because they don’t enter the gut epithelial cells with the lipids
what are bile pigments
excretory products of the liver
2 examples of bile pigments
biliverdin and bilirubin
what is bilirubin
a breakdown product of haemoglobin and is conjugated in the liver and secreted into bile
what causes faeces to appear brown
bile pigments as they are usually secreted into faeces
what causes jaundice
problems in the liver or biliary tree often which cause accumulation of bilirubin in the blood
how does bile pass in and out of the liver
through bile ducts
what happens to bile after a meal (process of enterohepatic circulation)
- bile is excreted from the gall bladder by contraction and passes into the duodenum through the common bile duct.
- Most of the bile acids are reabsorbed in the terminal ileum by Na+ coupled transporters and returned to the liver via the hepatic portal vein.
- The liver then extracts the bile salts.
what does the enterohepatic circulation allow the liver to do
allows the liver to recycle and preserve a pool of bile acids
how is the liver connected to the GI tract
via the portal vein which collects blood
from the superior mesenteric vein
(which in turn is effectively the venous drainage of both the small and large intestines)
what causes secretion of bile
cholecystokinin (CCK)
what is CCK released in response to
increased fatty acid concentration in duodenum
how is bilirubin produced
through the breakdown of red blood cells - haemolysis
formed from the haem portion of haemoglobin
what colour is bilirubin
yellow
2 forms of bilirubin
unconjugated and conjugated
difference between unconjugated and conjugated bilirubin
unconjugated - insoluble in water - so can only travel in the bloodstream if bound to albumin and it cannot be directly excreted from the body.
conjugated - soluble in water - so travels through the bloodstream without requiring transport proteins like albumin, which means that it can also be excreted out of the body
what are the 3 parts of bilirubin metabolism
- creation of bilirubin
- bilirubin conjugation
- bilirubin excretion
where does breakdown of erythrocytes occur
mainly in the spleen & bone marrow but can also occur in the kupffer
cells (resident macrophages) of the liver
process of bilirubin metabolism
- RBCs ingested by macrophages/ Kupffer cells
- Haemoglobin broken down into haem and globin
- Globin broken into amino acids – used to make new RBCs in bone marrow
- Haem is further broken down into biliverdin and Fe2+ & CO. Catalysed by haem oxygenase (HO)
- Biliverdin (green pigment) is reduced by biliverdin reductase to make unconjugated bilirubin
- Unconjugated bilirubin (UCB) is bound to albumin and transported to liver
- Undergoes glucuronidation to make conjugated bilirubin. Catalysed by enzyme UDP Glucuronyl Transferase (UDPGT)
- Conjugated bilirubin (CB) is now soluble and is dissolved in bile
- Excreted into the duodenum with the rest of the bile
- Intestinal bacteria in terminal ileum REDUCE the CB into urobilinogen
- Urobilinogen is lipid-soluble. 10% is reabsorbed into blood, bound to albumin, transported to liver, and oxidised to urobilin
- Urobilin is re-cycled into bile or transported to kidneys and excreted in urine (responsible for yellow urine colour)
- Remaining 90% of urobilinogen is OXIDISED by a different intestinal bacteria into stercobilin
- Stercobilin is excreted in the faeces (responsible for brown colour)
what is jaundice
yellow discolouration of skin
when is jaundice clinically detectable
when bilirubin is above 50micromol/L
3 main types of jaundice
- pre hepatic
- hepatic/intra-hepatic
- post hepatic/obstructive
what is pre-hepatic jaundice
increased haemolysis.
results in the increased presence of unconjugated bilirubin in the blood as the liver is unable to conjugate it all at the same rate.
symptoms of pre hepatic jaundice
- brown stool
- normal urine
- yellow skin
- enlarged spleen ( due to excess breakdown)
causes of pre hepatic jaundice
malaria, sickle cell anaemia, thalassaemia, physiological
jaundice of the newborn
what causes physiological newborn jaundice
the excess breakdown of foetal
haemoglobin since its no longer required, meaning that there is an increase in unconjugated bilirubin and the liver cannot conjugate it fast enough since its not developed properly yet resulting in jaundice)
what is hepatic/intra hepatic jaundice
caused by liver impairment.
causes the decreased ability of the liver to conjugate bilirubin,
resulting in presence of conjugated and unconjugated bilirubin in the blood.
causes of liver damage
- viral hepatitis
- hepatotoxic drugs, e.g. paracetamol overdose, alcohol abuse
what is post hepatic jaundice
caused by the blockage of bile ducts.
results in backflow of conjugated bilirubin into the blood as it cannot move past the obstruction
causes of bile duct obstruction
- Gallstones
- Hepatic tumours
- Pancreatic tumours
why can cancer or inflammation of the pancreas cause jaundice
because the head of the pancreas is situated in the duodenal loop
which is near the common bile duct thus any inflammation or cancer of the
pancreas can eventually cause obstruction to the duct resulting in jaundice
how are gall stones formed
When the concentration of cholesterol in bile becomes high in relation to
the concentrations of phospholipid & bile salts, the cholesterol will
crystallise out of solution forming gall stones
impact of large gall stones that cant pass freely through the common bile duct
it lodges in the opening of the gallbladder causing painful contractile spasms of the smooth muscle
what happens if gallstone is lodged in the common bile duct
bile cant enter the intestine
very serious
how does the gallbladder receive bile
from the common hepatic duct which is formed from the left and right hepatic ducts
relationship between cholesterol and bile
- bile is synthesised from cholesterol
- the liver also secretes cholesterol extracted from the blood into the bile
what is a mechanism for maintaining cholesterol homeostasis in the blood
Bile secretion, followed by excretion of cholesterol in the faeces,
how is cholesterol soluble in bile
in bile cholesterol is incorporated into micelles so its soluble
whereas in water it is insoluble because it is incorporated into lipo proteins
when is bile secretion the greatest
during and just after a meal
what is the sphincter of Oddi.
a ring of smooth muscle surrounding the common bile duct at the ampulla of vater
what happens when the sphincter of oddi is closed
the dilute bile secreted by the liver is shunted into the gallbladder - here the bile is concentrated as some of the NaCl & water is absorbed into the blood
what happens to pressure when the gallbladder fills with bile
the bile duct system is a low pressure system
soo when the gallbladder fills
with bile it must exhibit adaptive
relaxation - which is where the
size increases but the pressure
doesn’t
impact of CCK on bile secretion
shortly after a fatty meal
cholecystokinin (CCK) is released in response to the presence of fat in the
duodenum
CCK causes the gallbladder to
contract & the sphincter of
Oddi to relax
resulting in the flow of bile down the cystic duct through the common bile duct and into the duodenum where it mixes with the food in the duodenum &
lipid digestion occurs
impact of a significant decrease in bile
can decrease fat digestion & absorption
result in an impaired absorption of fat-soluble vitamins A,DK & E
resulting in clotting problems (Vit K) or calcium malabsorption (Vit D)
what happens if a gall stone becomes lodged at a point that prevents both bile & pancreatic secretions from entering the intestine
failure to both neutralise acid &
adequately digest most organic
nutrients not just fat - this can result in
severe nutritional deficiencies
