Functional Anatomy of Pancreas .
[1]. Pancreas is a dual organ having two functions, namely endocrine function and exocrine function .
[2]. Endocrine function is concerned with the production of hormones .
[3]. The exocrine function is concerned with the secretion of digestive juice called pancreatic juice.
Functional anatomy of Exocrine Part of Pancreas .
[1]. Exocrine part of pancreas resembles salivary gland in structure. It is made up of acini or alveoli.
[2]. Each acinus has a single layer of acinar cells with a lumen in the center.
[3]. Acinar cells contain zymogen granules, which possess digestive enzymes. A small duct arises from lumen of each alveolus.
[4]. Some of these ducts from neighboring alveoli unite to form intralobular duct.
[5]. All the intralobular ducts unite to form the main duct of pancreas called Wirsung duct.
[6]. Wirsung duct joins common bile duct to form ampulla of Vater, which opens into duodenum .
[7]. In some persons, an accessory duct called duct of Santorini exists. It also opens into duodenum, proximal to the opening of ampulla of Vater.
Nerve Supply of Pancreas .
[1]. Pancreas is supplied by both sympathetic and parasympathetic fibers.
[2]. Sympathetic fibers are supplied through splanchnic nerve and parasympathetic fibers are supplied through vagus nerve.
Properties & Composition of Pancreatic Juice .
Properties of Pancreatic Juice .
Volume : 500 to 800 mL/day
Reaction : Highly alkaline with a pH of 8 to 8.3 .
Specific gravity : 1.010 to 1.018 .
Composition of Pancreatic Juice .
[1]. Pancreatic juice contains 99.5% of water and 0.5% of solids.
[2]. The solids are the organic and inorganic substances.
[3]. Bicarbonate content is very high in pancreatic juice. It is about 110 to 150 mEq/ L, against the plasma level of 24 mEq/L.
[4]. High bicarbonate content of pancreatic juice is important because of two reasons
1. High bicarbonate content makes the pancreatic juice highly alkaline, so that it protects the intestinal mucosa from acid chyme by neutralizing it
2. Bicarbonate ions provide the required pH (7 to 9) for the activation of pancreatic enzymes.
Functions of Pancreatic Juice .
Pancreatic juice has digestive functions and neutralizing action.
Digestive Functions of Pancreatic Juice .
[1]. Pancreatic juice plays an important role in the digestion of proteins and lipids.
[2]. It also has mild digestive action on carbohydrates.
Proteins digestion .
[1]. Major proteolytic enzymes of pancreatic juice are trypsin and chymotrypsin.
[2]. Other proteolytic enzymes are carboxypeptidases, nuclease, elastase and collagenase.
1. Trypsin .
[1]. Trypsin is a single polypeptide with a molecular weight of 25,000. It contains 229 amino acids.
[2]. It is secreted as inactive trypsinogen, which is converted into active trypsin by enterokinase.
[3]. Enterokinase is also called enteropeptidase and it is secreted by the brush-bordered cells of duodenal mucus membrane.
[4]. Once formed, trypsin itself activates trypsinogen by means of autocatalytic or autoactive action.
Trypsin inhibitor .
[1]. Trypsinogen is activated only when it reaches the small intestine.
[2]. If trypsin is activated when it is in pancreas, it may hydrolyze the pancreatic tissue proteins, resulting in pancreatic damage.
[3]. But its activation in the secretory cells, acini and ducts of pancreas is prevented by an inhibitor protein called trypsin inhibitor.
[4]. Any abnormality or deficiency of the trypsin inhibitor will result in unopposed trypsin activity, which damages the pancreas.
Actions of trypsin .
[1]. Digestion of proteins: Trypsin is the most powerful proteolytic enzyme. It is an endopeptidase and breaks the interior bonds of the protein molecules and converts proteins into proteoses and polypeptides.
[2]. Curdling of milk: It converts caseinogen in the milk into casein
[3]. Blood clotting: It accelerates blood clotting
[4]. It activates the other enzymes of pancreatic juice, viz.
a. Chymotrypsinogen into chymotrypsin
b. Procarboxypeptidases into carboxypeptidases
c. Proelastase into elastase
d. Procolipase into colipase
[5]. Trypsin also activates collagenase, phospholipase A and phospholipase B
[6]. Autocatalytic action: Once formed, trypsin itself converts trypsinogen into trypsin.
2. Chymotrypsin .
[1]. Chymotrypsin is a polypeptide with a molecular weight of 25,700 and 246 amino acids.
[2]. It is secreted as inactive chymotrypsinogen, which is activated into chymotrypsin by trypsin.
Actions of chymotrypsin .
1. Digestion of proteins: Chymotrypsin is also an endopeptidase and it converts proteins into polypeptides
2. Digestion of milk: Chymotrypsin digests caseinogen faster than trypsin. Combination of both enzymes causes rapid digestion of milk
3. On blood clotting: No action.
3. Carboxypeptidases .
[1]. Carboxypeptidases are carboxypeptidase A and carboxypeptidase B.
[2]. Carboxypeptidase A is derived from the precursor procarboxypeptidase A.
[3]. Carboxypeptidase B is derived from procarboxypeptidase B.
[4]. Procarboxypeptidases are activated into carboxypeptidases by trypsin.
Actions of carboxypeptidases .
[1]. Carboxypeptidases are exopeptidases and break the terminal bond of protein molecules.
[2]. Exopeptidases split the polypeptides and other proteins into amino acids.
[3]. Carboxypeptidase A splits the proteins into amino acids having aromatic or aliphatic side chains .
[4]. Carboxypeptidase B converts the proteins into amino acids having basic side chains.
4. Nucleases .
[1]. Nucleases of pancreatic juice are ribonuclease and deoxyribonuclease, which are responsible for the digestion of nucleic acids.
[2]. These enzymes convert the ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) into mononucleotides.
5. Elastase .
[1]. Elastase is secreted as inactive proelastase, which is activated into elastase by trypsin.
[2]. Elastase digests the elastic fibers.
6. Collagenase .
[1]. Collagenase is secreted as inactive procollagenase, which is activated into collagenase by trypsin .
[2]. It digests collagen.
Lipids digestion .
Lipolytic enzymes present in pancreatic juice are pancreatic lipase, cholesterol ester hydrolase, phospholipase A, phospholipase B, colipase and bilesaltactivated lipase.
1. Pancreatic lipase .
[1]. Pancreatic lipase is a powerful lipolytic enzyme.
[2]. It digests triglycerides into monoglycerides and fatty acids.
[3]. Activity of pancreatic lipase is accelerated in the presence of bile.
[4]. Optimum pH required for activity of this enzyme is 7 to 9.
[5]. Digestion of fat by pancreatic lipase requires two more factors:
1. Bile salts, which are responsible for the emulsification of fat, prior to their digestion
2. Colipase, which is a coenzyme necessary for the pancreatic lipase to digest the dietary lipids.
[6]. About 80% of the fat is digested by pancreatic lipase. Deficiency or absence of this enzyme leads to excretion of undigested fat in feces .
2. Cholesterol ester hydrolase .
Cholesterol ester hydrolase or cholesterol esterase converts cholesterol ester into free cholesterol and fatty acid by hydrolysis.
3. Phospholipase A .
[1]. Phospholipase A is activated by trypsin.
[2]. Phospholipase A digests phospholipids, namely lecithin and cephalin and converts them into lysophospholipids.
[3]. It converts lecithin into lysolecithin and cephalin into lysocephalin.
4. Phospholipase B .
[1]. Phospholipase B is also activated by trypsin.
[2]. It converts lysophospholipids (lysolecithin and lysocephalin) to phosphoryl choline and free fatty acids.
5. Colipase .
[1]. Colipase is a small coenzyme, secreted as inactive procolipase .
[2]. Procolipase is activated into colipase by trypsin.
[3]. Colipase facilitates digestive action of pancreatic lipase on fats.
6. Bile-salt-activated lipase .
[1]. Bile-salt-activated lipase is the lipolytic enzyme activated by bile salt. It is also called carboxyl ester lipase or cholesterol esterase.
[2]. This enzyme has a weak lipolytic action than pancreatic lipase. But it hydrolyses a variety of lipids such as phospholipids, cholesterol esters and triglycerides.
[3]. Human milk contains an enzyme similar to bile-salt-activated lipase .
Carbohydrates digestion .
[1]. Pancreatic amylase is the amylolytic enzyme present in pancreatic juice.
[2]. Like salivary amylase, the pancreatic amylase also converts starch into dextrin and maltose.
Neutralizing action of Pancreatic Juice .
[1]. When acid chyme enters intestine from stomach, pancreatic juice with large quantity of bicarbonate is released into intestine.
[2]. Presence of large quantity of bicarbonate ions makes the pancreatic juice highly alkaline.
[3]. This alkaline pancreatic juice neutralizes acidity of chyme in the intestine.
[4]. Neutralizing action is an important function of pancreatic juice because it protects the intestine from the destructive action of acid in the chyme.
Mechanism of Pancreatic Secretion .
pancreatic Enzymes Secretion .
[1]. Pancreatic enzymes are synthesized in ribosomes, which are attached to the endoplasmic reticulum of acinar cells in pancreas.
[2]. The raw materials for the synthesis of pancreatic enzymes are the amino acids, which are derived from the blood.
[3]. After synthesis, the enzymes are packed into different zymogen granules by Golgi apparatus and stored in cytoplasm.
[4]. When stimulated, the acinar cells release zymogen granules into the pancreatic duct. From the granules, the enzymes are liberated into intestine.
Bicarbonate ions Secretion .
Bicarbonate ions of pancreatic juice are secreted from the cells of pancreatic ductules and released into the pancreatic duct.
Mechanism of bicarbonate secretion
[1]. Carbon dioxide derived from blood or metabolic process combines with water inside the cell to form carbonic acid in the presence of carbonic anhydrase
[2]. Carbonic acid dissociates into hydrogen and bicarbonate ions
[3]. Bicarbonate ions are actively transported out of the cell into the lumen
[4]. Hydrogen ion is actively transported into blood in exchange for sodium ion
[5]. Sodium ion from the cell is transported into the lumen, where it combines with bicarbonate to form sodium bicarbonate
[6]. Because of the loss of sodium and bicarbonate ions from the blood, there is some disturbance in the osmotic equilibrium of the blood. To maintain the osmotic equilibrium, water leaves the blood and enters the lumen of pancreatic duct by osmosis
[7]. In the lumen, bicarbonate combines with water forming the solution of bicarbonate.
Regulation of Pancreatic Secretion .
Secretion of pancreatic juice is regulated by both nervous and hormonal factors.
Stages of Pancreatic Secretion .
Pancreatic juice is secreted in three stages like the gastric juice:
1. Cephalic phase .
2. Gastric phase .
3. Intestinal phase.
These three phases of pancreatic secretion correspond with the three phases of gastric secretion.
1. Cephalic Phase .
As in case of gastric secretion, cephalic phase is regulated by nervous mechanism through reflex action. Two types of reflexes occur:
1. Unconditioned reflex
2. Conditioned reflex.
Unconditioned Reflex
Unconditioned reflex is the inborn reflex. When food is placed in the mouth, salivary secretion and gastric secretion are induced. Simultaneously, pancreatic secretion also occurs.
Stages of reflex action:
[1]. Presence of food in the mouth stimulates the taste buds and other receptors in the mouth
[2]. Sensory (afferent) impulses from mouth reach dorsal nucleus of vagus and efferent impulses reach pancreatic acini via vagal efferent nerve fibers
[3]. Vagal efferent nerve endings secrete acetylcholine, which stimulates pancreatic secretion.
Conditioned Reflex .
[1]. Conditioned reflex is the reflex response acquired by previous experience .
[2]. Presence of food in the mouth is not necessary to elicit this reflex.
[3]. The sight, smell, hearing or thought of food, which induce salivary secretion and gastric secretion induce pancreatic secretion also.
Stages of reflex action:
[1]. Impulses from the special sensory organs (eye, ear and nose) pass through afferent fibers of neural circuits to the cerebral cortex. Thinking of food stimulates the cerebral cortex directly .
[2]. From cerebral cortex, the impulses pass through dorsal nucleus of vagus and vagal efferents and reach pancreatic acini .
[3]. Vagal nerve endings secrete acetylcholine, which stimulates pancreatic secretion.
2. Gastric Phase .
[1]. Secretion of pancreatic juice when food enters the stomach is known as gastric phase.
[2]. This phase of pancreatic secretion is under hormonal control. The hormone involved is gastrin.
[3]. When food enters the stomach, gastrin is secreted from stomach .
[4]. When gastrin is transported to pancreas through blood, it stimulates the pancreatic secretion.
[5]. The pancreatic juice secreted during gastric phase is rich in enzymes.
3. Intestinal Phase .
[1]. Intestinal phase is the secretion of pancreatic juice when the chyme enters the intestine. This phase is also under hormonal control.
[2]. When chyme enters the intestine, many hormones are released.
[3]. Some hormones stimulate the pancreatic secretion and some hormones inhibit the pancreatic secretion.
Hormones Stimulating Pancreatic Secretion
1. Secretin
2. Cholecystokinin.
Secretin .
[1]. Secretin is produced by S cells of mucous membrane in duodenum and jejunum.
[2]. It is secreted as inactive pro-secretin, which is activated into secretin by acid chyme.
[3]. The stimulant for the release and activation of pro-secretin is the acid chyme entering intestine.
[4]. Products of protein digestion also stimulate the hormonal secretion.
Action of secretin .
[1]. Secretin stimulates the secretion of watery juice which is rich in of bicarbonate ion and high in volume.
[2]. It increases the pancreatic secretion by acting on pancreatic ductules via cyclic AMP (messenger).
Cholecystokinin .
[1]. Cholecystokinin (CCK) is also called cholecystokinin-pancreozymin (CCKPZ).
[2]. It is secreted by I cells in duodenal and jejunal mucosa.
[3]. The stimulant for the release of this hormone is the chyme containing digestive products such as fatty acids, peptides and amino acids.
Action of cholecystokinin
Cholecystokinin stimulates the secretion of pancreatic juice which is rich in enzyme and low in volume, by acting on pancreatic acinar cells via inosine triphosphate (second messenger).
Hormones Inhibiting Pancreatic Secretion
[1]. Pancreatic polypeptide (PP) secreted by PP cells in islets of Langerhans of pancreas
[2]. Somatostatin secreted by D cells in islets of Langerhans of pancreas
[3]. Peptide YY secreted by intestinal mucosa
[4]. Peptides like ghrelin and leptin .
Collection of Pancreatic Juice .
In animals .
In animals, the pancreatic juice is collected by connecting a fistula between the pancreatic duct and the opening in the abdominal wall.
In Human .
[1]. In human beings, a multi-lumen tube is inserted through nose or mouth, till the tip of this tube reaches the intestine near the ampulla of Vater. The tube has a marking.
[2]. The entrance of the tip of the tube into the intestine near the ampulla is indicated when this line comes near the mouth. The tube has three lumens.
[3]. Small balloons are attached to the two outer lumens.
[4]. When balloons are inflated by air, the intestine near the ampulla is enlarged. Now, the pancreatic juice is collected through the middle lumen by means of aspiration.
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