BILE SECRETION AND

METABOLISM

Dr Sara Amjad

FUNCTIONS OF LIVER

Synthetic functions

Metabolic functions

Bile secretion

Detoxification

Immunity

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GALLBLADDER FUNCTION

• The gallbladder concentrates bile and stores much of

the bile salt pool during fasting

Isotonicity maintained as a result of micelles

having minimal osmotic activity

• Postprandially the gallbladder contracts in

response to CCK (cholecystokinin)

BILE

Is made up of bile salts, bile pigments and other

substances dissolved in alkaline electrolyte solution

Enter duodenum through bile duct

Storage in gall bladder( in between meals sphinctor of

oddi closed,when food enter duodenum sphinctor

releases and gall bladder evacuates)

PROPERTIES OF BILE

pH : 7.2

Daily secretion: 500 ml.

Colour: Yellow

Taste: Bitter

BILE SECRETION

Bile is secreted in two stages ;

Stage one;

Hepatocytes will secret an initial secretion that is rich

bile salts

cholesterol,

organic components,

initial secretion will drain through the many minute bile

canaliculi that penetrate the liver.

Stage Two ;

Initial secretion will flow towards the bile ducts ,

secondary secretion is added to the initial bile

which is a watery solution of sodium bicarbonate

ions.

The bile then will either empty into the

duodenum when the sphincter of Oddi is open

when the sphincter of Oddi is closed, it will be

prevented from draining into the intestine and

instead flows into the gallbladder, and

concentrated to up to five times its original

potency

COMPOSITION OF BILE

Water : 97 percent

Solids : 3 percent

Solids

Organic

Inorganic

Inorganic mainly bicarbonates

Na, Cl and K and calcium palmitate

Organic

Bile salts

Bile pigments

Mucin

lipids

Alkaline phosphatase

Gall bladder bile differs from Hepatic bile

1. Gall bladder capacity is 50ml

Inflammation of gall bladder

2. Exchange of H for Na

pH acidic

raised pH precipitates CaCO3

3. Mucin secretion

other subtances secreted are copper ,zinc and mercury

COMPOSITION OF BILE

Bile acids

Bile acid :Primary bile acids are produced by

hepatocytes from cholesterol. They are cholic acid &

chenodeoxycholic acid.

They reach duodenum through bile duct and in the

small intestine and colon they are converted into

secondary bile acids deoxycholic acid and lithocholic

acid by bacterial action.

7-dehydroxylation

by gut bacteria

Cholic acid

(3 OH groups)

Chenodeoxycholic acid

(2 OH groups)

Secondary Bile Acids

Deoxycholic acid

(2 OH groups)Lithocholic acid

(1 OH group)

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3 3

7 7

12

12 24

24

24

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Primary Bile Acids

John Williams

BILE ACID SYNTHESIS

Bile acids synthesized in the liver from cholesterol

In the “classical pathway” the first and most important regulated step is 7α hydroxylation by 7α hydroxylase

Next 12α hydroxylation is followed by several steps leading to cholic acid

The “alternative pathway” starts with initial formation of oxysterols and leads to chenodeoxycholic acid

BILE SALTS

Bile acids are first conjugated with taurine and glycine

to form bile salts in combination with Na or K

Sodium taurocholate & glycocholates

Potassium taurocholate & glycocholate.

PRIMARY BILE ACIDS AND SALTS

Chenodeoxycholic

acid

Bile salts (Conjugated bile acids)

amide-linked with glycine or taurine

The ratio of glycine to taurine forms in the bile is

3:1

Glycocholic

Taurocholic

Glycochenodeoxycholic

Taurochenodeoxycholic

Cholic acid BILE ACIDS

BILE SALTS

BILE PIGMENTS

They are excretory products in the bile.

Formed by breakdown of Hb

15 to 20 % of the total solid of hepatic bile

Hemolytic disease

CHOLESTEROL

Every day 2gm of cholesterol is excreted in bile

Increased polyunsaturated fatty acids

Ratio of cholesterol to bile salt 1:20 and 1:30

If ratio falls1:13 , cholesterol precipitated

Immunoglobulins…IgA

Calcium palmitate…Formation of biliary calculi

Alkaline phosphatase…raised level of this

enzyme indicates obstruction to biliary flow

ROLE OF BILE

Emulsification of Fat

Breaking down of the large fat globules into smaller globules and make them water

soluble.

Bile …...Amphipathic

FORMATION OF MICELLE

After digestion, monoglycerides and fatty acids

associate with bile salts and phopholipids to form

micelles.

Micelles are necessary because they transport

the poorly soluble monoglycerides and fatty acids

to the surface of the enterocyte where they can be

absorbed

Activate pancreatic lipase

Role in fat digestion and absorption

BACTERIOSTATIC ACTION

Inhibits multiplication of pathogenic intestinal

bacteria

ROUTE FOR LOSS OF CHOLESTEROL

Major route for loss of cholesterol from body

Bile salts keeps cholesterol in soluble form, thus

prevents stone formation

Lubrication

Lubricating function due to mucus

Laxative action

Bile salts

Neutralization of HCl

High content of bicarbonate

Neutralize any HCl escape to intestine

Excretion

Drugs

Toxins

Bile pigments

Fat soluble vitamins

Steriods

Metabolism of Bile Pigment (Bilirubin)

Systemic Circulation

BR-Albumin Complex

SMALL INTESTINE

BR Urobilinogen

BILE DUCT

LIVER

SPLEEN

Stercobilin

KIDNEY

Urine

COLON

BR + UDPGlucuronic

Acid

BR Glucuronide

Senescencent

rbc destruction

Hemoglobin

Biliverdin

Bilirubin (BR)

Fe2+ + Globin

Stool

John Williams

HORMONAL CONTROL OF BILE

SECRETION

Hormone from gut cells:

Cholecystokinin (CCK)

Responses:

1. Secretion of pancreatic enzymes

2. Bile secretion3. Slow release of gastric contents

Stimulus:

Undigested lipids and partially digested

proteins in duodenum

FACTORS AFFECTING BILIARY SECRETION

Choleretic action

Bile salts

Ingestion of food

Heptocrinin , Secretin , CCK

CHOLAGOGUE ACTION

Bile salts, magnesium sulphate

CCK

stimulate contraction and evacuation of gall bladder

ENTEROHEPATIC CIRCULATION

94% of bile salts are reabsorbed from the small

intestine( by diffusion in early part of intestine &

by active transport from distal ileum).

portal blood

liver

bile salts are absorbed back into the hepatic cells

reexcreted into the bile.

94% bile salts re circulated into bile,

Salts make the entire circuit some 17 times before

being carried out in the feces.

Small quantities of bile salts lost in to the feces are

replaced by new amount formed continuously by liver

cells.

Necessary because of limited pool of bile salts

BILE ACID POOL

Fecal loss of bile acids 0.3 to 0.6g/day.

compensated by an equal daily synthesis of bile

acids by liver and bile acid pool is maintained.

Normal bile acid pool 2 to 4g.

Bile acids returning to the liver suppress hepatic

synthesis of bile acids by inhibiting the rate

limiting enzyme

Maximum rate of synthesis is approximately

0.5g/day

ENTEROHEPATIC CIRCULATION

Cholestyramine:

Bile acid sequestrants

It binds to bile acids in the gut

Prevents reabsorption

Promoting their excretion

It is used for treatment of

hypercholesterolemia

GALLSTONES

Cholesterol, ordinarily insoluble in water, comes

into solution by forming vesicles with

phospholipids

If ratio of cholesterol, phospholipids, and bile

salts altered, cholesterol crystals may form

Gallstone formation involves a variety of factors:

Cholesterol supersaturation

Mucin hypersecretion by the gallbladder mucosa

creates a viscoelastic gel that fosters nucleation.

GALLSTONES

80% of patients, gallstones are clinically

silent

20% of patients develop symptoms over 15-

20 years

Almost all become symptomatic before

complications develop

Biliary-type pain due to obstruction of the

bile duct lumen

GALLSTONES

Gender

Higher among females than males

Due to endogenous sex hormones (enhance cholesterol

secretion and increase bile cholesterol saturation)

Progesterone may contribute by relaxing smooth muscle

and impairing gallbladder emptying.

Age

Increased age is associated with lithogenic bile and

increased rate of gallstones

GALLSTONES SYMPTOMS

Abdominal pain

Nausea and vomiting

Jaundice

Fatigue

Weight loss

Fatty food intolerance

STEATORRHEA

An increase in stool fat excretion of > 6% of dietary fat

Absence of bile acids, fats become indigestible and are

excreted in feces.

OBSTRUCTIVE JAUNDICE

Jaundice resulting from blockage of the bile ducts

or abnormal retention of bile in the liver.

CAUSES

gallstones

inflammation

tumors

trauma

pancreatic cancer

narrowing of the bile ducts

structural abnormalities present at birth

MCQ

The major site for synthesis of conjugated

bilirubin in human body is

A. Liver

B. Spleen

C. Kidney

D. Pancreas

MCQ

Primary bile acids are produced from cholesterol

in

A intestine

B kidney

C liver

D gall bladder

MCQ

Every day amount of cholesterol excreted in bile

A 3gm

B 2gm

C 4gm

D 1gm

ENTEROHEPATIC CIRCULATION