Bile

Dr. Dinesh Veera

Physiology Unit AIMST
Specific Learning Outcomes
• 13.1Describe the formation and functions of bile.
• 13.2Describe neural and humoral influences on bile
secretion and flow.
• 13.3Describe the functions of the gall bladder.
• 13.4Describe enterohepatic circulation and its
functional significance
 Bile
Bile is a bitter-tasting, dark green to yellowish brown
fluid, produced by the liver (hepatocytes) and stored in
the gallbladder.

It is discharged into the GIT tract through the duodenal

opening

VOLUME OF HEPATIC BILE =

600ml to 1000ml/DAY
Bile
• The main components of bile are water, bile salts,
bile pigments, and cholesterol

Physical properties:
• Hepatic bile: pH 7.4, color is golden yellow ,
• Bladder bile: pH 6.8, color is green dark to yellow
(darker)
Bile

• Hepatocytes
secrete - bile acids,
cholesterol,
bilirubin
• Bile ducts secrete -
watery solution,
Na+, HCO3-
Composition of bile
• Water
• Bile salts
• Bilirubin
• Cholesterol
• Fatty acids
• Lecithin
• Electrolytes
Biliary System
• The components of the biliary system are:
• liver
• gallbladder and bile duct
• Duodenum
• Ileum
• Portal circulation
Function of Bile
 Emulsify the large fat particles to facilitate the action of
lipase enzymes
 Essential for intestinal absorption of dietary cholesterol ,
fats and vitamins
 excretion of several important waste products from the
blood- bilirubin, lipid soluble xenobiotics, drugs and
heavy metals
 The only route for disposal of cholesterol—either in its
native form, or following conversion to bile acids
 Bile Secretion
• 2 stages
1. The liver hepatocytes will secret an initial secretion
that is rich in bile salts , cholesterol, and other organic
components. Then the initial secretion will drain
through the many minute bile canaliculi that
penetrate the liver.
2. The initial secretion will flow towards the bile ducts.
During its flow in the ducts a secondary secretion is
added to the initial bile which is a watery solution of
sodium bicarbonate ions.
*The second secretion is stimulated especially by
secretin!
-causes release of additional quantities of
bicarbonate ions
 Bile acids
• The most important components of bile
• Synthesized from cholesterol , secreted into the bile
conjugated to glycine or taurine to form bile salts
• Bile salts - sodium taurocholate and sodium glycocholate
• Primary bile acids are synthesized by hepatocytes -
cholic acid and chenodeoxycholic acid
• In the colon, bacteria convert a portion of primary bile
acids into secondary bile acids
cholic acid  deoxycholic acid
chenodeoxycholic acid  lithocholic acid
Bile salts
• 90-95% of the bile salts are absorbed from
the small intestine
• Most bile salts are reabsorbed into the portal
circulation and returned to the liver for
reexcretion into bile (enterohepatic
circulation)
Enterohepatic circulation
• About one half of reabsorption is
by diffusion through (early
portions of the small intestine)
and the remainder by an active
transport process (the intestinal
mucosa in the distal ileum)
• The quantity of bile secreted by
the liver each day is highly
dependent on the availability of
bile acids/salts—the greater the
quantity of bile salts in the
enterohepatic circulation, the
greater the rate of bile secretion
Bile salts
• The remaining 5–10% of the bile salts enter the
colon and are converted to the salts of
deoxycholic acid (deoxycholate) and lithocholic
acid (lithocholate)
• Lithocholate is relatively insoluble and is mostly
excreted in the stools; only 1% is absorbed
• Deoxycholate is absorbed
• Those lost in the stool are replaced by synthesis in
the liver; the normal rate of bile acid synthesis is
0.2–0.4 g/day
• The rate-limiting enzyme in the biosynthetic
pathway, cholesterol 7α-hydroxylase, is inhibited by
bile salts.
• When greater quantities of bile salts are
recirculated to the liver, there is decreased demand
for synthesis and the enzyme is inhibited – vice
versa
Actions of bile acids
• Decreases the surface tension of the fat
particles ; allows agitation in the intestinal tract
to break the fat globules into minute sizes -
emulsifying or detergent function
• Help in the absorption of fatty acids,
monoglycerides, cholesterol, and other lipids
from the intestinal tract
 Emulsification

• Bile acids are amphipathic (both hydrophilic and

hydrophobic domains)
• The coating of lecithin and bile acids  surface
tension  agitation by segmentation breaks up the
fats into droplets  exposes its surface to enzymatic
action
• Lipase acts on emulsified fat
• the product of lipase action are two free
fatty acids (FFAs) and a monoglyceride
Lipid Absorption
• Absorption of free fatty acids, monoglycerides, and other
lipids depends on minute droplets in the bile called micelles
• Made in the liver, pass down the bile duct into the
duodenum
• Consist of bile acid molecules aggregated with their
hydrophilic side groups facing outward and their
hydrophobic steroid rings facing inward
 Lipid Absorption
• Micelles transport lipids to the
surface of the intestinal
absorptive cells  lipids diffuse
through the plasma membrane
into the cells
• Intestinal cell : free fatty acids
and monoglycerides are
transported to the smooth ER
 resynthesized into
triglycerides
• Golgi complex coats these with
phospholipids and protein to
form chylomicrons
Functional significance –
enterohepatic circulation
• In persons who have had an ileal resection (removal
of the ileum), the recirculation of bile salts to the
liver is interrupted and large quantities of bile salts
are excreted in feces.
• Excessive fecal loss diminishes the total bile salt/bile
acid pool because synthesis of new bile acids, even
though it is strongly stimulated, cannot keep pace
with the loss.
• One consequence of decreased bile salt content of
bile is impaired absorption of dietary lipids and
steatorrhea
 Gallbladder
• Gallbladder stores bile, concentrates bile, empties bile
• Bile is stored in the gallbladder until it is needed
• The maximum storage volume is 30-60 mL
• Watery components are reabsorbed by the gallbladder
mucosa
• reabsorbing Na+, Cl- and HCO3-, H2O
• Organic constituents are highly concentrated (5 – 20
fold)
• concentrating the remaining bile constituents (bile
salts, cholesterol, lecithin, and bilirubin)
Filling of the gallbladder
• The hepatocytes and ductal cells produce bile
continuously.
• As bile is produced by the liver, it flows through the
bile ducts into the gallbladder, where it is stored for
later release.
• During the interdigestive periods, the gallbladder
can fill because it is relaxed and the sphincter of
Oddi is closed.
Concentration of bile
• The epithelial cells of the gallbladder absorb ions
and water in an isosmotic fashion
• The organic components of bile are not absorbed
• They become concentrated as the isosmotic fluid is
removed.
Ejection of bile
• Ejection of bile from the gallbladder begins within 30
minutes after a meal is ingested.
• The major stimulus for ejection of bile is CCK
• CCK has two simultaneous effects that result in ejection
of bile from the gallbladder:
• (1) contraction of the gallbladder and
• (2) relaxation of the sphincter of Oddi (a thickening of
the smooth muscle of the bile duct at its entrance to the
duodenum).
• Bile is ejected in pulsatile “spurts,” not in a steady
stream.
Neural and Humoral influences
on bile secretion and flow.
Humoral-
(Cholecystokinin) CCK
• Secreted by the CCK cells of intestinal glands in
the small intestine
• Released in response to small peptides and fatty
acids in the duodenum
• Causes relaxation of the sphincter of the
hepatopancreatic ampulla (sphincter of Oddi)
• Causes contraction of the wall of the gallbladder
 ejection of bile
• Stimulates secretion of pancreatic juice rich in
digestive enzymes
 Humoral-
Secretin
• The hormone secretin— increases bile &
pancreatic secretion rich in a sodium
bicarbonate watery solution by epithelial cells
in ductules; does not represent increased
secretion by the liver parenchymal cells
• Minor effects: Enhances effects of CCK, inhibits
secretion of gastric juice, promotes normal
growth and maintenance of pancreas
Humoral-
Choleretic effect

• Recirculation of bile salts to the liver also stimulates

biliary secretion, which is called a choleretic effect
 (Neural)
• acetylcholine-secreting
nerve fibers from both
the vagi and the
intestinal enteric
nervous system
• acetylcholine causes
contraction of the
gallbladder
Effect of deficiency of bile on digestion and
absorption of fat and fat-soluble vitamins

• Feeling abdominal tightness, bloating and having a

difficulty digesting fats
• Up to 40 % of the ingested fats (and fat soluble
vitamins) are lost into the feces  steatorrhea
• Fat indigestion, fat and fat soluble
vitamin malabsorption, growth failure etc
• Poor lipid absorption  poor hormone synthesis
because hormones are made from lipids
Quick Review
• Bile- definition- characteristics and composition
• Biliary System components
• Function of bile
• Enterohepatic circulation and significance
• Humoral and Neural Regulation – CCK, Secretin, Ach
References
• Guyton and Hall Textbook of Medical Physiology
14th Edition
• Linda S Costanzo Physiology 6th Edition
Homework
• What abnormalities in the bile can contribute to
gallstone formation
• Other functions of CCK in GIT system
Aim higher and work harder!

Thank You!!!