liver, Biliary, & pancreatic secretions.pptx

LIVER AS AN ORGAN &
BILIARY SECRETION
BY
Prof. Dr. Nusrat Tariq

LEARNING OBJECTIVES
By the end of the lecture you should
be able to:
1. Describe the functions of liver.
2. Differentiate between the hepatic
and gall bladder bile and the
hormones acting on them.
3. Enumerate the causes and
composition of developing gall

FUNCTIONS OF THE LIVER
• Filtration and storage of blood;
• Metabolism of carbohydrates,
proteins, fats, hormones, and
foreign chemicals
• Storage of vitamins and iron
• Formation of bile
• Formation of coagulation factors.

1-FILTRATION AND STORAGE OF
BLOOD
• The liver is an expandable organ,
large quantities of blood can be
stored in its blood vessels.
• Its normal blood volume, is
about 450 ml (10 % of the body’s
total blood volume.)

BLOOD-CLEANSING
FUNCTION
Blood flowing through the intestinal
capillaries picks up bacteria from intestines.
KUPFFER CELLS:
• Large phagocytic macrophages that line the
hepatic venous sinuses.
• Efficiently cleanse blood when a bacterium
comes into contact.

2-METABOLIC FUNCTIONS
OF THE LIVER
The liver , a large chemically
reactant pool of cells , has a high
rate of metabolism .

CARBOHYDRATE
METABOLISM
1.Stores large amounts of glycogen
2. Converts galactose and fructose to
glucose
3. Gluconeogenesis
4. Forms many chemical compounds
from intermediate products of
carbohydrate metabolism

FAT METABOLISM
1.Oxidation of fatty acids to supply
energy.
2. Synthesis of cholesterol,
phospholipids, and lipoproteins
3. Synthesis of fat from proteins and
carbohydrates

PROTEIN METABOLISM
1. Deamination of amino acids
2. Formation of urea for removal of
ammonia from the body fluids.
3. Formation of plasma proteins
4. Interconversions of the various
amino acids and synthesis of other
compounds from amino acids.

3-A STORAGE SITE FOR
VITAMINS AND IRON.
• Stores vitamin A , D and B12 .
• The Liver Stores Iron as Ferritin.
Extra quantities of iron in body fluids
combines
with apoferritin to form
• ferritin is stored until needed
elsewhere.

4-FORMS BLOOD SUBSTANCES
USED IN COAGULATION
•fibrinogen,
•prothrombin,
•accelerator globulin,
•Factor VII.
Vitamin K is required by the metabolic
processes of the liver for the formation of
several of these substances, especially
prothrombin and Factors VII, IX, and X.

5-REMOVES OR EXCRETES DRUGS,
HORMONES, AND OTHER
SUBSTANCES
• The liver detoxifies or excretes into the bile many drugs,
including sulfonamides,penicillin,ampicillin,and
erythromycin.
• Several of the hormones are either chemically altered or
excreted by the liver, e.g. thyroxin and steroid hormones,
such as estrogen, cortisol, and aldosterone.
• the liver excretes calcium from the body into the bile,
which passes into the gut and is lost in the feces.

LIVER REGENERATION
• The liver can restore itself after hepatic tissue loss from
either partial hepatectomy or acute liver injury
uncomplicated by viral infection or inflammation.
• In Partial hepatectomy, up to 70 per cent of the liver is
removed. The remaining lobes enlarge and restore the liver
to its original size.
• This regeneration is very rapid.

CONTROL OF RAPID REGENERATION
Hepatocyte growth factor (HGF):
HGF is produced by mesenchymal cells in the liver and in
other tissues .
Other growth factors:
 Epidermal growth factor.
 Cytokines such as:
 Tumor Necrosis factor.
 Interleukin-6

TERMINATION OF REGENERATION
After the liver has returned to its original size,
the process of hepatic cell division is terminated.
TRANSFORMING GROWTH FACTOR-β:
• A cytokine secreted by hepatic cells
• A potent inhibitor of liver cell proliferation and
regeneration.

BILE
Bile secreted continuously by
the liver hepatocytes, flows into
the duodenum via the CBD.

BILE
Amount:
About 600-1000ml/day.
Secretion rate depends on whether
a fed or fasting state exist.

Storage
The Gallbladder is a storage
reservoir that can deliver bile to the
duodenum for solubilization of
dietary lipids

Secretion of Bile
Bile Is Secreted In Two Stages

(1) AN INITIAL PORTION
Secreted by the hepatocytes into
bile canaliculi.
Contains bile acids, cholesterol
and other organic constituents.

(2) A SECOND PORTION
Is added to the initial bile
(watery solution of sodium and
HCO3 ions).
 Secreted by epithelial cells lining
the ducts and ductules in its
course through the bile ducts.
Stimulated by secretin

SECRETION AND ENTEROHEPATIC CIRCULATION OF BILE
SALTS

STORING AND CONCENTRATING
BILE IN THE GALLBLADDER
• GB can hold 30 to 60 ml bile.
• Gallbladder concentrates the bile by:
 active transport of sodium.
 followed by secondary absorption
of Cl- ions, water
• Concentrated 5-fold to 20-fold.

PH of Bile secreted from Liver ??
PH of Bile from Gall Bladder ???

PH of Bile secreted from Liver is
Alkaline.
PH of Bile from Gall Bladder ??.

PH of Bile from Gall Bladder is
acidic.
WHY?

PH of Bile from Gall Bladder is
acidic.
Because most of the HCO3, H2O
and Na is reabsorbed during
storage of bile in gall bladder.
Bile acids and the remaining
solutes get concentrated in gall
bladder.

FORMATION AND FUNCTION OF BILE
SALTS
The liver cells synthesize about 6 grams
of bile salts daily.

PRIMARY BILE ACIDS
CHOLIC ACID AND CHENODEOXYCHOLIC ACID:
The precursor of the bile Acids is cholesterol.
The cholesterol is first converted to cholic acid or
chenodeoxycholic acid in about equal quantities.
These acids in turn combine principally with glycine
and to a lesser extent with taurine to form glyco- and
tauro-conjugated bile acids.

SECONDARY BILE ACIDS
• Formed by deconjugation nd dehydroxylation of
the primary bile salts by intestinal bacteria.
• Forming Deoxycholic acid from Cholic acid and
Lithocholic acid from Chenodeoxycholic acid
• Lithocholic acid is hepatotoxic and is excreted in
urine

PRIMARY AND SECONDARY BILE ACIDS

FUNCTIONS OF BILE
The main digestive function of the liver is
the secretion of Bile.
Bile serves two important functions:
1- fat digestion and absorption
2- excretion of waste products :

1- FAT DIGESTION AND ABSORPTION
Bile salts in the bile perform two functions:
I. Emulsification of the large fat particles.
II. Micelle formation

FAT DIGESTION
• Emulsification
• They have a detergent action (emulsifying) on the fat
particles in the food which decreases the surface tension of
the particles thus breaking the fat globules into minute
sizes.
• The surface of minute fat globules is then attacked by
pancreatic lipase

FAT ABSORPTION
Micelles formation:
• Help in the absorption of lipids from the intestinal tract by
forming small physical complexes with lipids; the
complexes are called micelles.
• The micelles act as a transport medium to carry the
monoglycerides, cholesterol, and free fatty acids to the
brush borders of the intestinal epithelial cells.

2- EXCRETION OF WASTE PRODUCTS :
Bile serves as a mean for excretion
of waste products from the
blood e.g:
 Bilirubin, and
 Excess cholestrol.

Secretion and enterohepatic circulation of bile salts

ABSORPTION OF BILE SALTS
• Occurs largely in ileum where an active
transport mechanism exists.
• In healthy people, the bile acid pool ranges
from 2 to 4 g.
• About 94 % of total pool is reabsorbed.

ENTEROHEPATIC CIRCULATION
OF BILE SALTS.
• Recycling of bile salts between the small
intestine and the liver.
• Reabsorption occurs mainly in ileum.
• Bile acids are taken up by hepatocytes
from the blood, reconjugated and then
re-secreted into bile .
• Bile acids must be recirculated 3-5 time
for digestion of a normal meal.

OF BILE SALTS.
Inflammation of the ileum can
lead to malabsorption of bile
acid and result in the loss of
large quantities of bile salts in
the feces (malabsorption of fat).

SIGNIFICANCE OF ENTEROHEPATIC
CIRCULATION
?????

SIGNIFICANCE OF
By cycling several times during a
meal, a relatively small bile acid
pool can provide the body with
sufficient amounts of bile salts to
promote lipid absorption.

REGULATION OF BILE SECRETION
AND GALL BLADDER EMPTYING

BILE SECRETION IS
REGULATED BY:
1- Hormonal Control
2- Neural Control
3-Negative feedback from
intestine.

1-HORMONAL CONTROL
CCK
Secretin
 Estrogen

2 -NEURAL CONTROL:
Parasympathetic (vagal) stimulation
results in:
1- contraction of the gallbladder
2-relaxation of the sphincter of Oddi
3- increased bile formation.
 Sympathetic stimulation results in:
1- reduced bile secretion
2-relaxation of the gallbladder.

3- NEGATIVE FEEDBACK FROM
INTESTINE
• Bile salts regulate their own
synthesis by Negative feedback
from intestine
• Bile salts synthesis is increased with
decreased return of bile acids from
intestine and vice versa

• If a bile fistula empties the bile
salts to the exterior for several
days to several weeks:
• bile salts cannot be reabsorbed
from the ileum
• the liver increases its production of
bile salts 6- to 10-fold

CONTRACTION OF THE GALLBLADDER
CCK
■ is released in response to small peptides and fatty
acids in the duodenum.
■ tells the gallbladder that bile is needed to emulsify
and absorb lipids in the duodenum.
■ causes contraction of the gallbladder and relaxation
of the sphincter of Oddi.
ACh
■ causes contraction of the gallbladder.

PANCREATIC SECRETION
Prof.Dr. Nusrat Tariq

Pancreatic Secretion (Exocrine)
Learning Objectives:
By end of the lecture you must be able to describe
the:
1. Major components of pancreatic juice and their
physiologic roles.
2. Activation of pancreatic enzymes
3. Cellular mechanisms of bicarbonate secretion.
4. Hormonal & neural regulation of pancreatic
secretion
5. Potentiation of the secretory response.
6. Phases of Pancreatic Secretions

FORMATION OF PANCREATIC
SECRETION
EXOCRINE PANCREAS:
• Pancreatic Acini:
Secrete pancreatic digestive enzymes
• Small Ductules and Larger Ducts leading from
the Acini:
Secrete large volumes of sodium bicarbonate
solution

STIMULUS FOR SECRETION OF
PANCREATIC JUICE
• Presence of chyme in the upper
portions of the small intestine.
• Contains a high concentration of
HCO3– to neutralize the acidic
chyme that reaches the
duodenum.

COMPOSITION OF PANCREATIC
SECRETION
Digestive enzymes.
Water
Electrolytes
–Na+, K+ ( concentration same as in plasma)
–HCO3
- (concentration much higher than in
plasma 100-145mEq/L (24 mEq/L)
– Cl- (Much lower Cl– concentration than plasma)
–Ca++, Mg++
April 2, 2024 65

PROTEIN DIGESTION
1. Trypsin.
2. Chymotrypsin.
3.Carboxypolypeptidase.
Trypsin and chymotrypsin
split proteins into peptides of
various sizes but not into
individual amino acids.
Carboxypolypeptidase splits
some peptides into individual
amino acids, thus completing
digestion of some proteins.

PROTEOLYTIC PANCREATIC ENZYMES
When first synthesized, the proteolytic
digestive enzymes are in the inactive
forms:
1. Trypsinogen
2. Chymotrypsinogen
3. Procarboxypolypeptidase

ACTIVATION OF
PROTEOLYTICTIC ENZYMES
These enzymes become activated
only after they are secreted into
the intestinal tract.

ACTIVATION OF TRYPSINOGEN
• Trypsinogen is converted to trypsin by
Enteropeptidase (enterokinase) secreted
by the intestinal mucosa when chyme
comes in contact with mucosa.
• Trypsinogen can be autocatalytically
activated by trypsin formed from
previously secreted trypsinogen.

ACTIVATION OF
CHYMOTRYPSINOGEN AND
PROCARBOXYPOLYPEPTIDASE
Both are activated by trypsin
to form chymotrypsin and
carboxypolypeptidase.

Proteolytic enzymes of the
pancreatic juice do not
become activated until
after they have been
secreted into the intestine.
Why?

Why?
because the trypsin and
the other enzymes would
digest the pancreas itself.

Secretion of Trypsin
Inhibitor Prevents
Digestion of the
Pancreas Itself.

TRYPSIN INHIBITOR
• The same cells that secrete
proteolytic enzymes ,secrete
trypsin inhibitor.
• Prevents activation of trypsin
both inside the secretory cells
and in the acini and ducts of the
pancreas.

CHO DIGESTION
PANCREATIC AMYLASE:
Hydrolyzes starches, glycogen,
and most other carbohydrates
(except cellulose) to form :
• Mostly disaccharides and
• A few trisaccharides.

FAT DIGESTION
The main enzymes for fat
digestion are:
(1)Pancreatic lipase
(2) Cholesterol esterase
(3) Phospholipase A2

PANCREATIC SECRETIONS
ARE RICH IN BICARBONATE
IONS
• The pancreas secrets about 1
L/day of HCO3 –rich fluid from
the epithelial cells of the ductules
and ducts.
• The osmolarity of pancreatic fluid
is equal to that of plasma

SECRETION OF BICARBONATE IONS FROM
PANCREATIC DUCTAL CELL
Blood
around
the
pancreas;
acidic
tide

1-NERVOUS STIMULI:
• Acetylcholine
2-HORMONAL STUMULI:
• Secretin
• Cholecystokinin (CCK)
• Gastrin.
REGULATION OF
PANCREATIC SECRETION

1-NERVOUS STIMULI
Acetylcholine(via vagovagal reflexes)
• production of pancreatic digestive
enzymes, water, and electrolytes.
• Accounts for 20% of the total
secretion of the digestive enzymes
after a meal.

2-HORMONAL STIMULI
1-SECRETIN:
• Present in an inactive form, prosecretin
(in S cells in the mucosa of the
duodenum and jejunum).
• Secreted and activated in response to
acidic chyme (pH less than 4.5-5.0)
entering the duodenum

2-HORMONAL STIMULI
• Absorbed and passes by way of the blood
to the pancreas.
• Stimulates a HCO3 rich but low chloride
secretion by activating ductal cells.
• HCO3 neutralize Acidic Stomach Chyme.
HCl + NaHCO3 → NaCl + H2CO3
• H2CO3 dissociates into CO2 and H2O.

2- CHOLECYSTOKININ (CCK) :
• Secreted in response to the presence of
food in the upper small intestine
especially proteoses and peptones
(products of partial protein digestion)
and long-chain fatty acids in the chyme.
• Released from the I cells in the mucosa
of the duodenum and upper jejunum.

• Passes by way of the blood to the
pancreas and causes secretion of
pancreatic digestive enzymes.
• Accounts for 70-80% of the total
secretion of the pancreatic digestive
enzymes after a meal.

Regulation of Pancreatic Secretion

Usually, pancreatic secretions
are the result of multiple stimuli
rather than one stimulus.
MULTIPLICATIVE OR POTENTIATION
EFFECTS OF DIFFERENT
PANCREATIC SECRETION STIMULI

Pancreatic secretion is phasic
Mediators
stimulus
Phase
Release of Ach
Smell, taste,
chewing and
swallowing
Cephalic phase
Vago-vagal
reflex
Protein, gastric
distention
Gastric phase
Secretin, CCK
and vago-vagal
reflex
Acid in chyme,
fatty acids
Intestinal phase

FUNCTIONS OF PANCREATIC
SECRETION
1.Neutralize the acids in the duodenal
chyme to range (pH= 7.0-8.0) for
activity of pancreatic enzymes.
2.Prevents damage to duodenal
mucosa by acid & pepsin
3.Produce enzymes involved in the
digestion of dietary carbohydrate, fat,
and protein

liver, Biliary, & pancreatic secretions.pptx

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