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 Liver is Composed of “plates” or one cell thick layers of

hepatocytes, that are bathed on either side by blood from
hepatic sinusoids.
 Between each row of cells is a small space created by
cavitations in plasma membranes of two apposing cells.
 Theses spaces join to form channels or canaliculi, that
connect to the Bile ductules.

 Bile is secreted from hepatocytes into canaliculi , from

which it flows into the bile duct system.

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 Functionally, canaliculi may be perceived as acini lined

by hepatocytes and emptying into the Biliary duct
system.

 Bile duct epithelium is metabolically active and

capable of altering the composition of Canalicular bile
by adding water and electrolytes especially
bicarbonate .

 Bile Acids (Cholic Acid, Chenodeoxycholic acid)

 Phospholipids (Lecithin)
 Cholesterol
 Bile Pigments
 Electrolytes
 Water

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 In Ruminants and Pigs

◦ There is relatively continuous secretion of hepatic bile into the
intestine, because Sphincter of Oddi is less well defined in these
species.

 In Horses
◦ Horses don’t have a gall bladder, so there is a continuous secretion
of bile into intestine.

 In dogs and cats

◦ A continuous bile secretion is not necessary because these species
only eat few times in a day (twice or thrice). Therefore, Gall bladder
can store bile.

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 During Inter-digestive period, the sphincter is closed

and gall-bladder muscle is relaxed; therefore hepatic
bile backs up into gall bladder.

 During Digestive period, the gall-bladder contracts,

sphincter relaxes under CCK, and large amount of gall-
bladder bile is released into the duodenum.

 Different absorptive surfaces modify concentration and relative

composition of hepatic bile during storage in Gall-bladder.

 Hepatic bile consists of electrolytes, water and several organic

compounds such as bile salts, cholesterol, lecithin, bilirubin.

 Gall bladder epithelium reabsorbs water and electrolytes (Na,

Cl, HCO3) with some passive absorption of lipid-soluble
compounds such as cholesterol. (However, at pH of gallbladder
bile, bile salts exist primarily in charged form and are not
soluble in lipid membranes)

 Bile salts are concentrated some 10 to 20 fold in gallbladder

bile.

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Hepatocytes
Bile Acids Also
Cholesterol called (Primary
bile acids)
Totally Insoluble in Water Renders lipids soluble in Water

Conversion of Cholesterol into Cholic acid (Bile Acid). Note the presence of two additional
Hydroxyl groups on ring structure o f cholic acid as compared to cholesterol. These
Hydroxyl groups enhance water solubility and detergent action of bile acid molecule.

 Conversion of cholesterol into bile acids results in a

molecule with water-soluble (hydrophilic-water loving) side
and a lipid soluble (Hydrophobic-water hating) side.

 This combination of hydrophilic-hydrophobic attribute is

characteristic property of detergent.

 Detergents can render lipids soluble in water because of

this and so does the bile acids that emulsify and solubilise
fats.

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 Bile acids are synthesized in smooth endoplasmic

reticulum of hepatocytes.

 They dissolve away some of the cell membrane

components: phospholipids and cholesterol.

 Bile acids are secreted into canaliculi as their sodium salts.

 The presence of Sodium draws water by osmosis.

 The electrolyte composition of canalicular bile resembles

that of plasma but is low in chloride.

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Conjugation with
Primary Bile acids Taurine or Glycine Tauro-cholic Acid and
Cholic Acid, Glyco-cholic acid also
Chenodeoxycholic Acid known as Bile Salts

 Primary Bile acids have pK (Dissociation constant) of 6.0. If

they are secreted in unconjugated form, they are
protonated and become less water soluble.
 Glycine Conjugates have pK of about 4.0.
 Taurine Conjugates have pK of 2.0.
 Conjugation lowers the pK so that they are always in
their deprotonated form (Ionised) in duodenum, making
them more water soluble.

Information Slide
 Consider the general acid-base reaction in aqueous solution: Where HA is the "acidic
form", or "protonated form" of any given substance, and A- is the "basic form", or
"deprotonated form“.
HA H+ + A-
The pertinent equilibrium expression for the above reaction is:
Ka= [H+][A-] /[HA] Where Ka is Acid Dissociation Constant
Taking the logarithm on both sides of the equation we obtain:
Log Ka = Log ([H+][A-] /[HA])
Log Ka = Log [H+] + log [A-] - log [HA]
Multiplying both sides of the equation by -1 we obtain:
-Log Ka = -Log [H+] - Log [A-] + Log [HA]
Substituting "–log" by its equivalent, "p“:
pKa = pH + log [HA] - log [A-]
And finally, combining logarithm parts of this equation we obtain the Henderson-
Hasselbach equation
pKa = pH + log ([HA]/[A-])
pKa =pH + log ([Protonated form]/[Deprotonated Form])
For Acids pKa =pH + log ([Unionized Form]/[Ionized Form])

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 Active re-absorption of bile salts

in Ileum (90%). Some passive
diffusion in jejunum.
 Under normal circumstances,
hepatic synthesis of bile salts
equals Faecal loss.
 Rest of bile salts are re-circulated.
 In human of 70kg, bile salt pool
size is 4g.
 For fat digestion, this pool turns
over to about 6 to 8 times per 24
hours (32g/24 hrs of bile salts).
 This requires Entero-hepatic
circulation.
 Bile acids synthesis stimulated by
bile acids reaching the liver
through portal circulation.

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 Bile secretion is initiated by the presence of fat-

containing food in the duodenum.

 This stimulates endocrine cells to produce CCK.

 CCK causes relaxation of the Sphincter of Oddi and

contraction of bladder forcing stored bile into the
intestine.