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Chemical Pathology > BILE Acids And gallstones > Flashcards

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
Q

Function of dietary fiber ?

A

Binds to bile acids and increases their excretion

26
Q

Causes of malabsorption of lipids

A

Liver diseases
- Hepatitis
- Liver cirrhosis
Gall bladder disease
- Gall stones

27
Q

Malabsorption causes what in feces?

A

Steatorrhea
- excess lipid in feces

28
Q

Hepatic bile contains ?

A

Bile salts
Phospholipids
Bilirubin
Cholesterol
Electrolytes/proteins

29
Q

What happens to bike in the gall bladder?

A
  • 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
Q

What is cholelithiasis?

A

Gallstones; concretions in the biliary tracts usually in the hall bladder

31
Q

If stones occur in the common bile duct, it’s called?

A

Choledocholithiasis

32
Q

How many types of gallstones do we have?

A

Three types
- Cholesterol
- pigment
- mixed

They can get infected to cause Cholecystits - inflammation of the gall bladder
cholangitis - infection of the bile duct

33
Q

Pathophysiology of gall stone formation ?

A
  • 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
Q

What are biliary colicks?

A
  • Biliary Colicks arise from forceful contractions of the gall bladder in attempt to overcome the obstruction (especially following fatty meal ingestion)
35
Q

Two main substances involved in stone formation?

A

cholesterol and calcium bilirubinate

36
Q

How are cholesterol stones formed ?

A
  • 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
Q

Three factors determine Cholesterol Stone formation?

A

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
Q

CALCIUM, BILIRUBIN Stones

A
  • 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
Q

Pigment stone formation?

A
  • 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
Q

CLINICAL FEATURES

A
  • 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
Q

DIAGNOSIS & TREATMENT

A
  • 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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