BILE Acids And gallstones Flashcards
The primary bile acids are ?
- Cholic acid
- Chenodeoxycholic acid
The primary bile acids are synthesized from ?
Cholesterol in the liver
Primary bile acids are secreted into the bile as ?
They are secreted into the bile as sodium salts, conjugated with amino acids glycine or taurine.
What are primary bile salts ?
They are Sodium salts of bile acids
How are the primary bile salts converted into secondary bile salts?
They are converted into secondary bile salts by bacteria within the intestinal Lumen
Secondary bile salts examples?
- Deoxycholate ( deoxycholic acid)
- Lithocholate (lithocholic acid)
Fate of secondary bile salts after they are produced in the intestinal ?
They are partially absorbed from the terminal ileum and colon and re-enter into the liver through the enterohepatic circulation
The bile excreted by the liver contain?
A mixture of primary and secondary bile salts
The parent steroid compound and precursor of bile acids and salts is the ?
Cholesterol (27c)
Primary bile acid (24c structure)
- CooH at side chain
- cholic acid - 3 OH
- Chenodeoxycholic acid - 2 OH
In the hepatic synthesis of bile acids, the rate limiting step is ?
Cholesterol 7-a-hydroxylase
Regulation of 7-a-hydroxylase and bile acid synthesis
- Downregulated by end products (bile acids) — Enzyme repression
- Upregulated by Cholesterol — Enzyme induction
List the Bile acids to their bile salt
Cholic acid
- Glycocholic
- Taurocholic
Chenocholic acid
- Glycochenodeoxycholic acid
- Taurochenodeoxycholic acid
Bile salts are basically ?
Conjugated bile acids. Amide-linked with glycine or taurine
The ratio of glycine to taurine forms in the bile is ?
3:1
The addition of glycine or taurine results in ?
- Results in the presence of fully ionized groups at pH of 7.0
- COOH of glycine
- SO3 of taurine
Example: Na or K (bike salt)
- they are more effective detergents than bile acids
- only bile salts but not bile acids are found in bile
Hormonal control of bile secretion
Stimulus;
- undigested lipids
- partially digested proteins in duodenum
Hormone from gut cells
- Cholecystokinin (CCK)
Response
- Secretion of pancreatic enzymes
- Bile secretion
- Slow release of gastric contents
Function of bile salts
- Cholesterol excretion
- Dietary fat emulsification which is essential for lipid digestion
- Co-factor for phospholipase A2 (PL-A2)
- Facilitate intestinal lipid absorption by formation of mixed micelle
Process of Emulsification of lipids in the duodenum ?
- Emulsification increases surface areas of lipid droplets So that digestive enzymes can act effectively
Mechanisms
- Mechanical mixing by peristalsis
- Detergent effect of bile acids
Detergent effect of bile acids
- Bile salts interact with lipid particles and aqueous duodenal contents, stabilizing the particles as they become smaller and preventing them from coalescing
Facilitation of intestinal lipid absorption: How?
Formation to mixed micelles;
- Disc shaped clusters of amphipathic lipids
- arranged with their hydrophobic groups (inside) and their hydrophilic group (outside)
- micelles include end products of lipid digestion, bile salts and fats soluble vitamins
Short and medium chain fatty acids do not require mixed micelle for absorption by intestinal cells
List the primary and secondary bile salts and acids
Primary bile acids
- Cholic acid
- Chenodeoxycholic acid
Primary bile salts
- Taurocholic acid
- Glycocholic acid
- TauroChenodeoxycholic acid
- GlycoChenodeoxycholic acid
Secondary bile acids
- Deoxycholic acid
- Lithocholic acid
Secondary bile salts
- ?
- ?
How many grams of bile salt is produced every day ?
- 15-30g bile salt/day (same amount passed through the portal circulation everyday
- 1-2L produced daily in the liver
- fecal excretion (0.5g/day)
What’s the function of cholestyramine?
Binds to bile acids in the gut
- Prevents their reabsorption
- Promote their excretion
- used to treat hyoercholesterolemia
Chilestyramine is also called?
Bile acid sequestrants
Function of dietary fiber ?
Binds to bile acids and increases their excretion
Causes of malabsorption of lipids
Liver diseases
- Hepatitis
- Liver cirrhosis
Gall bladder disease
- Gall stones
Malabsorption causes what in feces?
Steatorrhea
- excess lipid in feces
Hepatic bile contains ?
Bile salts
Phospholipids
Bilirubin
Cholesterol
Electrolytes/proteins
What happens to bike in the gall bladder?
- There’s active reabsorption of sodium, chloride and bicarbonate, water in the gall bladder
- Gall bladder is 10times more concentrated than hepatic bile
- sodium is the main cation and bile salt is the main anion
What is cholelithiasis?
Gallstones; concretions in the biliary tracts usually in the hall bladder
If stones occur in the common bile duct, it’s called?
Choledocholithiasis
How many types of gallstones do we have?
Three types
- Cholesterol
- pigment
- mixed
They can get infected to cause Cholecystits - inflammation of the gall bladder
cholangitis - infection of the bile duct
Pathophysiology of gall stone formation ?
- Certain bile components exceed their solubility limits so they crystallize and precipitate. Forming sludge
- Stasis further dehydrates the sludges which then hardens and aggregate to form stones
- smaller stone coalesce becoming bigger and obstructing the flow of bile into the gut
- there’s resultant effects in fat digestion and malabsorption
- fat soluble vitamins are also affected
- Stasis encourages proliferation of local bacteria leading to cholecystitis and ascending cholangitis
What are biliary colicks?
- Biliary Colicks arise from forceful contractions of the gall bladder in attempt to overcome the obstruction (especially following fatty meal ingestion)
Two main substances involved in stone formation?
cholesterol and calcium bilirubinate
How are cholesterol stones formed ?
- Liver secretes cholesterol and bile salts into the gall bladder
- Cholesterol is secreted in vesicles with Lecithin
- Bile salts are detergents which dissolve the vesicles to form mixed micelles in the gall bladder
- Micelles have lower capacity to hold Cholesterol compared to lecithin
- So cholesterol will rise rapidly and precipitate in the gall bladder in hypercholesterolemic states
Three factors determine Cholesterol Stone formation?
1.Relative amounts of Cholesterol, lecithin and bile salts secreted into bile
2.The extent of Concentration of the bile in the gall bladder**
3.The extent of stasis of bile within the gall bladder
CALCIUM, BILIRUBIN Stones
- Calcium enter bile with other electrolytes
- Unconjugated bilirubin form insoluble precipitates with Calcium
- In chronic hemolysis or liver cirrhosis, unconj bilirubin rises, binds calcium and precipitate and form stones
➢These undergo series of oxidations over time and turn “jet black”
➢Normally, bile is sterile but strictures in the biliary system may predispose to bacteria colonisation of bile above the stricture
Pigment stone formation?
- Bacteria deconjugates bilirubin raising unconjugated bilirubin level which binds Ca+
- Bacteria also hydrolyses lecithin to release FFAs which also binds calcium this results in claylike brown concretions
- Brown pigment bile stones often form de-novo in bile ducts.
- Processes leading to Cholesterol & pigment Stones may co-exist to form MIXED STONES
CLINICAL FEATURES
- Cholesterol stones are commoner in fair skinned
females
Fat
Fertile
Forty years - Medications e.g Estrogen in contraceptives and in treatment of prostate cancers in males
- Fibrates used in treating hypercholestrolemia bind bile salts to prevent reabsorption through enterohepatic circulation.
DIAGNOSIS & TREATMENT
- History & PE, confirmation mainly radiological
- Abdominal X-rays, USS, MRCP, ERCP
- Treatment mainly Surgical (Cholecystectomy) but depends the condition and the situation
- Treated Medically especially in asymptomatic patients
