Bile, gallbladder and gallstones Flashcards
(22 cards)
Describe the physiology and functions of the gallbladder
-storage and concentration of bile
-concentrated because of active Na+ transport and H20 from gallbladder
-the pH of bile drops as Na+ is exchanged for H+
-pancreatic juice: bile salts, bile pigments and dissolved substances in alkaline electrolytes
Explain characteristics of bile
-Bile —-> larger ductless and ducts
-water is added via specific tight junctions within ductules (cholangiocytes)
-the ductules scavenge glucose, amino acids; GSH is hydrolysed
-ductules secrete IgA, HCO3- and H20 in response to secretin in the postprandial period
Explain bile flows
bile flows as follows:
-hepatocytes —> bile canaliculi —> terminal bile ducts —-> hepatic ducts —-> common bile duct
Discuss components of bile
These are secreted by 2 different cell types:
Hepatocytes: cholesterol, lecithin, bile acids, bile pigments (bilirubin, biliverdin, urobilin, etc.)
Epithelial cells of bile ducts: bicarbonate-
rich salt solution
– Secretin & ACh influence the secretion of
bicarbonate-rich salt solutions and H2O
* Secretion of bile is greatest during and after a meal
Sphincter of Oddi contracts during periods of fasting
Sphincter of Oddi relaxes during and after meals (CCK)
What substances are secreted across the bile canalicular membrane
Substances secreted across the bile canalicular membrane:
* Bile acids
* Phosphatidylcholine
* Conjugated bilirubin
* Cholesterol
* Xenobiotics (foreign chemicals/substances, e.g. drugs)
– Specific transporters ferry the above into bile
– Substances such as water, glucose, Ca2+, GSH, amino acids and
urea enter the bile by diffusion
Explain composition of hepatic and gallbladder bile
-Hepatic bile = 97% water; cholesterol, lecithin, bile acids, bile pigments, etc.
* Gallbladder bile: 89% water; HCO3-, Cl-, Ca2+, Mg2+, Na+, cholesterol, bilirubin, bile salts, etc.
– Bile concentrated in gallbladder (NaCl and H2O loss → increased solid content)
– Bile goes to the gallbladder between meals when sphincter of Oddi
is closed
Explain bile acids
Bile acids are important in GI:
- Made from cholesterol – helps to reduce cholesterol levels
- Secreted into bile and conjugated to glycine or taurine
- Conjugated bile acids are major acids in human bile
Glycine and taurine conjugated cholic acid - Glycine conjugated cholic acid: glycocholic acid
- Taurine conjugated cholic acid: taurocholic acid
Glycine and taurine conjugated chenodeoxycholic acid - Glycine conjugated chenodeoxycholic acid: glycochenodeoxycholic acid
- Taurine conjugated chenodeoxycholic acid: taurochenodeoxycholic acid
- Conjugation → ↑ amphipathic nature of bile acids
- Conjugation helps to increase the ability of bile acids to be secreted and
also decreases their cytotoxicity - Bile acids conjugated with taurine or glycine are also called bile salts
Name 4 major bile acids found in humans
1) Cholic acid (50%)=0.5 quantitatively more important
2) Chenodeoxycholic acid (30%)
3) $Deoxycholic acid (15%)
4) $Litocholic avid (5%)
Discuss main functions of vile acids: metabolic regulators
1) Elimination of cholesterol to bile acids:
-synthesis and subsequent excretion of bile acids in the faeces represents a significant mechanism for the elimination of excess cholesterol
2) Reduce the precipitation of cholesterol in gallbladder; bile acids and phospholipids help solubilise cholesterol in the bile
3) Facilitate the absorption of fat soluble vitamins (ADEK)
4) Regulate their own transport and metabolism via enterohepatic circulation
5) Facilitate the digestion of triglycerides- works together with phospholipids and monoglycerides to ensure the emulsification of fats
Explain the phases of the control of release of bile/bile salts
1) Cephalic phase; taste, smell and presence of food in the mouth —-> impulses via vagus nerve
2) Gastric impulse; distension of stomach generates impulses in vagus nerve
3) Intestinal phase; period of most gallbladder emptying- key mediators for the increased release are:
1) CCK
2) secretin
Explain mechanisms controlling the secretion of bile into the duodenum
To get into the duodenum, two main things need to happen:
The gallbladder needs to squeeze to push the bile out.
The gate (Sphincter of Oddi) between the bile duct and the duodenum needs to open.
Here’s how these happen:
When fatty food (nutrients) enters the duodenum:
The duodenum releases a hormone called CCK into the bloodstream.
CCK travels to the gallbladder and tells it to contract its smooth muscles, squeezing out the bile.
CCK also travels to the Sphincter of Oddi and tells it to relax and open, allowing the bile to flow into the duodenum.
Your brain (via the vagus nerve) also plays a role:
Even before food reaches the duodenum, just thinking about or smelling food can stimulate the dorsal vagal complex in your brain.
This sends signals (via vagal efferents) that cause the gallbladder to contract a little (using ACh) and the Sphincter of Oddi to relax a bit.
There are also other signals involved:
ACh (acetylcholine) released by the vagus nerve also directly stimulates the gallbladder to contract.
NO (nitric oxide) and VIP (vasoactive intestinal peptide) help relax the Sphincter of Oddi.
Motilin is another substance that increases gallbladder movement.
What controls the contraction of the gallbladder and he release of bile into the duodenum
-control of gallbladder motility
-presence of fatty meal stimulates secretion of cholecystokinin (CCK)
-increased flow of bile into common duct
-increased flow of bile into duodenum
Explain the steps into the release of bile into the duodenum
1) Chyme entering duodenum causes release of CCK and secretin from duodenal enteroendocrine cells
2) CCK and secretin enters the bloodstream
3) CCK induces secretion of enzyme rich pancreatic juice —-> secretin causes secretion of HCO3- rich pancreatic juice
4) Bile salts and, to a lesser extent—> secretin transported via bloodstream stimulate liver to produce bile more rapidly
5) CCK (via bloodstream) causes gallbladder to contract and hepatopancreatic sphincter to relax; bile enters duodenum
6) During cephalic and gastric phases; vagal nerve stimulation causes weak contractions of gallbladder
Explain bile secretion and enterohepatic circulation
-Bile salts, lecithin
(phospholipids): synthesised in liver
- HCO3- and other ions – neutralise acids in duodenum
- Bile salts are the most important as far as GI function is
concerned - Most of bile salts are reabsorbed (95%) by Na+-bile salt coupled
transporters - The bile salts are returned to the liver and secreted again into bile
- The cycling of bile from intestine to liver and back to intestine =
enterohepatic circulation – recycling of bile salts - The body’s content of bile acid pool (~3.5g) may be recycled ~twice per
meal
What will an interruption of enterohepatic circulation cause?
Interruption of enterohepatic circulation will cause the following:
-excess synthesis of bile salts by the liver
-kidneys will excrete the synthesised bile salts (and some cholesterol)
Explain gallstones (cholelithiasis)
-ratio of incidence of gallstones= 2:1 in women and men
-bile salts, cholesterol and phospholipids
-the higher the cholesterol content of bile, the greater the concentrations of phospholipids and salts.
What causes the increased cholesterol
what causes the increased cholesterol:
-liver secretes excess
-reabsorption of salt and water
-the cholesterol crystallises and forms gallstones (precipitation of bile pigments)
Explain two types of gallstones and factors involved in gallstone formation
there are 2 types:
-cholesterol stones (85%); obesity, decreased in bile acids and phospholipids
-calcium bilirubinate stones —> due to increase of conjugated bilirubin
Factors involved in gallstone formation:
Bile stasis: stones form in bile that is sequestered in the gallbladder rather than bile that is flowing in the bile ducts into the duodenum
. Decreased amount of bile acids due to malabsorption (in cystic fibrosis
– dehydrated and acidic; 10% higher incidence; Crohn’s disease);
problems with bile production – gallbladder and cystic ducts can be
blocked by thick mucus
. Chronic infection – bacteria help in the formation of pigment stones
. Super-saturation of bile with cholesterol
Explain ex vivo studies
Ex vivo studies:
-bile from gallstone sufferers: stone forms within 2-3 days
-bile from normal individuals: stone formation takes 2 weeks
Explain characteristics of gallstones
Small gallstones easy passage via bile duct
* Larger gallstones lodge in the opening of gallbladder (right upper quadrant
pain; jaundice)
* Duct from pancreas joins the bile duct before it joins the duodenum
* Lodging of gallstones at this point causes the stoppage of bile and
pancreatic secretions (pressure builds up; right upper quadrant pain;
jaundice)
* Further pressure build up causes decreased
– Consequence → nutritional deficiency as digestion of fats is inefficient
secretion of bile and right upper quadrant pain
Jaundice (increased accumulation of bilirubin in
blood)
Explain how there are different diagnoses of gallstones
-Ultrasonography and computer tomography; explore the right upper quadrant of the gallbladder to detect gallstones
-Cholescintigraphy; administer technetium-99m- labelled derivative of iminodiacetic acid
-endoscope retrograde chlangiopancreaotography (ERCP); inject contrast media from an endoscope channel and visualise the biliary tree
Discuss clinical features of gallstones
-85% of cases are asymptomatic
-if the neck of the cystic duct is impaired —> biliary pain of right upper quadrant ensues
-gallstones that impact common bile duct —-> obstruction of bile flow and cholestatic jaundice which can cause bacterial infections and right upper quadrant ensues
-gallbladder will secrete mucus if inflamed and rupture
