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BILE Acids And gallstones Flashcards

1
Q

The primary bile acids are ?

A
  • Cholic acid
  • Chenodeoxycholic acid
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2
Q

The primary bile acids are synthesized from ?

A

Cholesterol in the liver

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3
Q

Primary bile acids are secreted into the bile as ?

A

They are secreted into the bile as sodium salts, conjugated with amino acids glycine or taurine.

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4
Q

What are primary bile salts ?

A

They are Sodium salts of bile acids

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5
Q

How are the primary bile salts converted into secondary bile salts?

A

They are converted into secondary bile salts by bacteria within the intestinal Lumen

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6
Q

Secondary bile salts examples?

A
  • Deoxycholate ( deoxycholic acid)
  • Lithocholate (lithocholic acid)
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7
Q

Fate of secondary bile salts after they are produced in the intestinal ?

A

They are partially absorbed from the terminal ileum and colon and re-enter into the liver through the enterohepatic circulation

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8
Q

The bile excreted by the liver contain?

A

A mixture of primary and secondary bile salts

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9
Q

The parent steroid compound and precursor of bile acids and salts is the ?

A

Cholesterol (27c)

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10
Q

Primary bile acid (24c structure)

A
  • CooH at side chain
  • cholic acid - 3 OH
  • Chenodeoxycholic acid - 2 OH
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11
Q

In the hepatic synthesis of bile acids, the rate limiting step is ?

A

Cholesterol 7-a-hydroxylase

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12
Q

Regulation of 7-a-hydroxylase and bile acid synthesis

A
  • Downregulated by end products (bile acids) — Enzyme repression
  • Upregulated by Cholesterol — Enzyme induction
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13
Q

List the Bile acids to their bile salt

A

Cholic acid
- Glycocholic
- Taurocholic
Chenocholic acid
- Glycochenodeoxycholic acid
- Taurochenodeoxycholic acid

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14
Q

Bile salts are basically ?

A

Conjugated bile acids. Amide-linked with glycine or taurine

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15
Q

The ratio of glycine to taurine forms in the bile is ?

A

3:1

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16
Q

The addition of glycine or taurine results in ?

A
  • 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
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17
Q

Hormonal control of bile secretion

A

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

18
Q

Function of bile salts

A
  • 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
19
Q

Process of Emulsification of lipids in the duodenum ?

A
  • 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

20
Q

Facilitation of intestinal lipid absorption: How?

A

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

21
Q

List the primary and secondary bile salts and acids

A

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
- ?
- ?

22
Q

How many grams of bile salt is produced every day ?

A
  • 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)
23
Q

What’s the function of cholestyramine?

A

Binds to bile acids in the gut
- Prevents their reabsorption
- Promote their excretion
- used to treat hyoercholesterolemia

24
Q

Chilestyramine is also called?

A

Bile acid sequestrants

25
Function of dietary fiber ?
Binds to bile acids and increases their excretion
26
Causes of malabsorption of lipids
Liver diseases - **Hepatitis** - **Liver cirrhosis** Gall bladder disease - **Gall stones**
27
Malabsorption causes what in feces?
Steatorrhea - excess lipid in feces
28
Hepatic bile contains ?
Bile salts Phospholipids Bilirubin Cholesterol Electrolytes/proteins
29
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
30
What is cholelithiasis?
Gallstones; **concretions in the biliary tracts usually in the hall bladder**
31
If stones occur in the common bile duct, it’s called?
**Choledocholithiasis**
32
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
33
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**
34
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)
35
Two main substances involved in stone formation?
**cholesterol** and **calcium bilirubinate**
36
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
37
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
38
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
39
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
40
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.
41
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

Chemical Pathology (8 decks)

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