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Transcript of BILE S M - prime.edu. Year MBBS/Bile BILE Is made up of bile salts, bile pigments and

  • BILE SECRETION AND

    METABOLISM Dr Sara Amjad

  • FUNCTIONS OF LIVER

     Synthetic functions

     Metabolic functions

     Bile secretion

     Detoxification

     Immunity

    3

  • 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)

    33

    3 3

    7 7

    12

    12 24

    24

    24

    24

    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 secretion 3. 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