Download Bile secretion

‫كلية الطب‬
GIT physiology
‫المحاضرة الخامسة‬
Phases of Pancreatic Secretion
Pancreatic secretion occurs in three phases:1- Cephalic phase:
The thought, smell, and taste of food produces the cephalic phase of pancreatic
secretion. Both acinar and to less extent the ductal cell secretion are enhanced by
vagal stimulation. Most the enzymes are stored in the acini .
2- Gastric phase:
Pancreatic secretion is enhanced during the gastric phase by :
A- Distention of the antrum and the body of the stomach which initiates avagovagal reflex
resulting in a low volume of pancreatic secretion containing both bicarbonate ions and enzymes.
B- Food breakdown products (amino acid and peptides) stimulate pancreatic secretion by
release gastrin ( from G cells of antrum) which produces a low-volume, high enzyme pancreatic
secretion.
3 - Intestinal phase:
The most important for pancreatic secretion are hormone CCK( and secretin. They are
released from endocrine cells in the duodenum and jejunum during the intestinal phase in
response to the entrance of chyme into the small intestine.
The amino acids, fatty acids are the major stimuli for (CCK) secretion from I cells which
found in upper small intestine . CCK( in addition to its effect on the gallbladder, is a potent
stimulant of pancreatic enzyme secretion ,by its effect on the acinar cells which trigger the
second messenger inisitol tri phosphate(IP3) and then cells makes the enzymes. H⁺ or acid
chyme from the stomach with (Low pH<4.5) stimulates release of Secretin From S cells that
found in upper small intestine, secretin triggers cAMP in the ductal cells to stimulates large
quantities of pancreatic juice containing HCO3.
Phenylalanine, methionine, tryptophan
small peptides
Fatty acids
Regulation of pancreatic secretion)
Disorders of the pancreas
Pancreatic Failure
Is failure of the pancreas to secrete pancreatic juice into the small intestine.
occurs (1) in pancreatitis (2) by a gallstone at the papilla of Vater, (3) removed of head
of the pancreas in malignancy.
means loss of trypsin, chymotrypsin, carboxypolypeptidase, pancreatic amylase,
pancreatic lipase, and still a few other digestive enzymes. Without these enzymes, as
much as 60 per cent of the fat, as well as one third to one half of the proteins
and carbohydrates entering the small intestine may be unabsorbed,
As a result, large portions of the ingested food cannot be used for nutrition, and copious,
fatty feces are excreted.
The gallbladder
is a thin walled green muscular sac on the inferior surface of the liver. The gallbladder
stores bile that is not immediately needed for digestion and concentrates it. When the
muscular wall of the gallbladder contracts bile is expelled into the bile duct.
Bile secretion:
Bile is necessary for digestion and absorption of lipids in the small intestine. Bile is a
mixture of bile acids, bile pigments and cholesterol. Bile is produced and secreted by liver,
stored in gallbladder, and ejected into the lumen of small intestine. It emulsify lipids to
prepare them for digestion.
When chyme reaches the small intestine CCK is secreted which stimulates contraction of
gallbladder and relaxation of sphincter of Oddi, to flow bile into the lumen of the
duodenum. When lipid absorption is complete, bile acids are recirculated to liver.
bile secretion
The function of the gall bladder is :1-to store bile
2- to concentrate bile ( epithelial cells of gall bladder absorb ions and water)
3 -to eject bile into the lumen of the small intestine.
Ejection of bile from gall bladder begins within 30 minutes after a meal.
Bile is constituents of *bile acid (50%) *cholesterol (4%) *and phospholipids (40%).*Bile
contains electrolytes and water..
95% of secreted bill acids are recirculated to the liver, bile acid excreted in feces 5% , must
be replaced by synthesis of new bile acids.
Role of bile secretion
A-detergent action :
Bile secretion decrease the surface tension of the substance so it will break them into
smaller particle called micelles to increase the surface area to about 1000 times original
one in which lipase will do it’s effect .
B –hydrotropic effect :
Which means makes lipid (water soluble) to pass easily via epithelial cell membrane bile
secretion regarded as amphipathic molecule which means that it has 2 poles one is the
hydrophilic pole which is formed from dissociate carboxyl group or hydroxyl group and the
other is the methyl group which represent the hydrophobic pole of the bile salts .bile salts
arrange themselves around the lipid molecule in such away that the hydrophilic group in
the surface and the hydrophobic toward the lipid particles so the surface of lipid will be
water soluble.
Gallstone Formation:Bile salts are formed in the hepatic cells from cholesterol in the blood plasma. In the
process of secreting the bile salts, about 1 to 2 grams of cholesterol are removed from the
blood plasma and secreted into the bile each day. Cholesterol is almost completely
insoluble in pure water, but the bile salts and lecithin in bile combine physically with the
cholesterol to form ultramicroscopic micelles in the form of a colloidal solution. When the
bile becomes concentrated in the gallbladder, the bile salts and lecithin become
concentrated along with the cholesterol, which keeps the cholesterol in solution. Under
abnormal conditions, the cholesterol may precipitate in the gallbladder, resulting in the
formation of cholesterol gallstones.
The amount of cholesterol in the bile is determined partly by the quantity of fat that the
person eats, because liver cells synthesize cholesterol as one of the products of fat
metabolism in the body. For this reason, people on a high-fat diet over a period of years are
prone to the development of gallstones.
Disorders of the Small Intestine:1-Malabsorption or “sprue''
In this case nutrients are not adequately absorbed from the small intestine even though
the food has become well digested. Can occur when large portions of the small intestine
have been removed or Several diseases can cause decreased absorption by the mucosa
like:A- Nontropical Sprue:One type of sprue called idiopathic sprue or(celiac disease) occur in children, its
autoimmune disease occur genetically ,or called gluten enteropathy in adult, results from
the toxic effects of gluten present in certain types of grains, especially wheat and rye.
Only some people are susceptible to this effect, gluten has a direct destructive effect on
intestinal enterocytes. This case either milder forms ,only the microvilli are destroyed, or
more severe forms, the villi themselves disappear ,this will lead to reducing the absorptive
area of the GIT tract. Removal of wheat and rye flour from the diet frequently results in
cure within weeks, especially in children with this disease.
B-Tropical Sprue.
Frequently occurs resulting from unidentified infectious agents and can often be treated
with antibacterial agents.
Digestion
I t is chemical breakdown of ingested food into absorbable molecules, The digestive
enzymes are secreted by salivary gland, gastric gland, pancreatic glands, and apical
membrane of intestinal epithelial cells.
Digestion of carbohydrates:Three major sources of carbohydrates exist in the normal human diet. These are sucrose
(table sugar) disaccharide, lactose (disaccharide) in milk and starches (polysaccharides)
present in all non animal foods, and grains.
Other carbohydrates ingested are glycogen, alcohol . The diet also contains a large amount
of cellulose, which is a carbohydrate, however, no enzymes capable of hydrolyzing it , then
it expelled out.
Digestion of carbohydrates in the mouth:ptyalin (an a-amylase) in saliva hydrolyzes starch into the disaccharide maltose and other
small polymers of glucose that contain three to nine glucose molecules, the food remains in
the mouth only a short time, 5 % of all the starches will have become hydrolyzed by the
time, when the food is swallowed..
Digestion of carbohydrate in the stomach:
salivary ptyalin can continue be active for as long as1 hour after the food has entered
the stomach ,then blocked by acid of gastric secretions. 30-40 % of the starches will have
been hydrolyzed mainly to maltose.
Digestion of carbohydrate in small intestine:
a-amylase in Pancreatic secretions continue splitting starches into maltose and other
small polymers of glucose,before passing the duodenum or upper jejunum,then
the brush border epithelial cells which lining the small intestine contain enzymes lactase,
sucrase, maltase and a-dextrinase which are capable of splitting the disaccharide lactose,
sucrose and maltose into their monosaccharide, Lactose splits into galactose and glucose.
Sucrose splits into fructose and a glucose. Maltose and other small glucose polymers all
split into multiple molecules of glucose ,which are absorbed and delivered to the liver by
way of the hepatic portal vein. After the liver processes, the nutrients enter into the blood
stream circulating throughout the body .
Digestion of carbohydrate
Lactose intolerance:
It is the most common cause of carbohydrate malabsorption. It result from inability of the
intestinal mucosa to produce lactase in the infant. The diarrhea produce dehydration can
be life threatening.
Digestion of protein:
The dietary proteins are derived from meats and vegetables.
Digestion of proteins in stomach:
Pepsin hydrolysis the peptide linkages between the amino acid and convert the protien
to proteosis,peptons and polypeptides.
Collagen is a major constituent of the intercellular connective tissue of meats, its an
albuminoid type of protein , pepsin digest this protien that is affected little by other
digestive enzymes.; it is first necessary that the collagen fibers be digested to penetrate
meats and digest the other meat proteins, Pepsin digestion represents 10-30 % of total
protein digestion.
Digestion of protein by pancreatic secretion:
Most protein digestion occur in small intestine under proteolytic enzymes of the
pancreatic secretion. Trypsin, chymotrypsin, and carboxypolypeptidase which split protein
molecules into small polypeptides.
Digestion of peptides by epithelial peptidase of small intestine:
The brush border of small intestine contains several different enzymes for
hydrolyzing the peptides linkage of the remaining dipeptides and other small
polypeptides as they come in contact with epithelium of the villi.The enzymes
responsible are aminopolypeptidase and several dipeptidase. About 98 % of all
the proteins finally become either amino acids or dipeptides that can be
absorbed into the blood. All of these smaller protein fragments go directly to the
liver by the hepatic portal vein. Once in the liver one of three things happens to
the proteins:
1. It converts to glucose
2. It converts to fat
3. It is directly released into the blood as amino acids.
Protien digestion
Digestion of fat:
Dietary lipids include triglycerides ,cholesterol (more in food of animal origin), phospholipid
, and cholesterol esters(fats). The lipids must be solubilized to be digested and absorbed.
small amount of triglycerides is digested in the stomach by lingual lipase from saliva
represent 10 % its unimportant.
The first step in fat digestion is emulsification of the fat by (bile) which break the fat
globules into very small sizes called micelles and makes lipid water soluble in which lipase
will do it’s effect. The lipase enzymes are water-soluble compounds and can attack the fat
globules only on their surfaces when it become water soluble. The bile salt play role in
converted cholesterol into monoglycerides and fatty acids, which is essential to absorption
of cholesterol. However 60 % of triglycerides can be digested and absorbed even in the
absence of bile salt. Most of the triglycerides of the diet are split by pancreatic lipase into
free fatty acids and 2-monoglycerides. When foods with high lipid content enter the
stomach, the hormone – gastric inhibitory peptide is released, slowing down movement
flow out of the stomach. This is why we feel full after eating high fat foods.
Absorption
It is movement of nutrients, water and electrolytes from the lumen of the
intestine into the blood. There are two path for absorption, a cellular path and
paracellular path. In the cellular path the substance must cross the apical (luminal)
membrane, then enter the tight junction intestinal epithelial cell, and be extruded
from the basolateral membrane. In paracellular, through intercellular spaces
between intestinal epithelial cells, and to the blood. The structure of intestinal
mucous is suited for absorption of large quantities of nutrients though villi and
microvilli which increase the surface of a small intestine. The villi are largest in the
duodenum, where digestion and absorption occur and shortest in the terminal
ileum.. The villi and microvilli increases total surface area by 600 fold. The epithelial
cells of small intestine are replaced every 3-6 days.
Absorption of carbohydrates:
Glucose and galactose are absorbed in separate mechanisms involving Na-depend
cotransport.,while Fructose is absorbed by facilitated diffusion.
Na-glucose cotransport and Na-galactose cotransport, using a gradient as the energy
source on basolateral membrane because the intracellular Na⁺ concentration is low
in intestinal cells ,as it in other cells ,Na⁺moves into the cell along gradient. Glucose
and galactose are extracted across the basolateral membrane into blood by
facilitated diffusion. Fructose is transported across luminal membrane by facilitated
diffusion, then extruded into blood.
Epithelial cell of the small intestine
blood
lumen
Epithelial cell of the small intestine
blood
absorption of monosaccharide
Absorption of protein:
 Amino acid are transported from the lumen into the cell by Na-amino acid
cotransporter in apical membrane energy by a gradient.
 There are four separation cotransporters; each one for neutral, acidic, basic, and
other amino acids.
 The amino acids then are transported across the basolateral membrane into the
blood by facilitated diffusion.
 Again by separation mechanism most ingested protein is absorbed by intestinal
epithelial cells in dipeptides and tripeptide form and free amino acids.
 Inside the cell, most of dipeptides and tripeptides are hydrolyzed to amino acid by
cystosolic peptidases,
 the remaining dipeptides and tripeptides are Absorbed unchanged.
lumen
Epithelial cell of the small intestine
blood
absorption of protein
Absorption of lipid
1- the product of lipid digestion are solubilized in the intestinal lumen in mixed micelles
except glycerol, which is water soluble.
The outer layer of micelle which is cylindrical shape is composed of bile acids.
2- The micelles diffuse to apical membrane of the intestinal epithelial cells. The lipids are
released from the micelle diffuse down concentration gradients into the cell. The micelles
do not enter the cell.
The bile acid are left behind in the intestinal lumen. Most of the digested lipid is
absorbed by the mid jejunum. The work of bile acid is completed inside the intestine before
they are returned to the liver via entrohepatic circulation .
3- The product of lipid (fatty acids) are re-esterified on the smooth endoplasmic reticulum
to form the original ingested lipid, triglyceride, cholesterol ester and phospholipids.
4- Inside cells, lipids are packaged with lipid-carrying particle called chylomicrons. The
chylomicrons , with an average diameter of 1000 A°, phospholipid cover 80 % of outside of
it, and remaining 20 % of surface covered with apoproteins which are synthesized by
intestinal epithelial cells, are essential for absorption of it.
5- The chylomicrons are packaged in secretary vesicles on the Golgi apparatus. The
secretary vesicles migrate to the basolateral membranes and there is exocytosis of the
chylomicrons. They are too large to enter vascular capillaries, they can enter the
lymphatic capillaries. The lymphatic circulation carries them to the thoracic duct which
empties into the blood stream.
lumen
Epithelial cell of the small intestine
blood
Figure (15)absorption of lipid