Functional Anatomy Of Pancreas

Functional Anatomy And Nerve Supply Of Pancreas

Pancreas is a dual organ having two functions, the endocrine function and the exocrine function. The endocrine function involves production of the hormones. The exocrine function involves the secretion of digestive juice – pancreatic juice.

Functional Anatomy Of Exocrine Part Of Pancreas:

• The portion of the pancreas which secretes the pancreatic juice is called the exocrine part. Like the salivary glands, the exocrine part of the pancreas is also made up of acini or alveoli. Each acinus has a single layer of acinar cells with a lumen in the center. The acinar cells contain zymogen granules, which possess digestive enzymes.
• A small duct arises from the lumen of each alveolus. Some of these ducts from neighboring alveoli unite to form intralobular ducts. All the intralobular ducts unite to form the main duct of the pancreas called Wirsung’s duct. Wirsung’s duct joins the common bile duct to form the ampulla of Vater which opens into the duodenum.

Read And Learn More: Medical Physiology Notes

• The duct of Santorini is an accessory pancreatic duct, which exists in some persons only. It also opens into the duodenum proximal to the opening of the ampulla of Vater.

Nerve Supply To Pancreas: Pancreas is supplied by both sympathetic and para-sympathetic fibers. The sympathetic fibers are supplied through the splanchnic nerve and parasympathetic fibers are supplied through the vagus nerve.

Pancreas Functions

Properties And Composition Of Pancreatic Juice

Properties Of Pancreatic Juice

• Volume              : 500-800 mL/day
• Reaction            : Highly alkaline with pH of 8-8.3
• Specific gravity : 1.010-1.018

Composition Of Pancreatic Juice: Pancreatic juice contains 99.5% of water and 0.5% of solids. The solids are organic and inorganic substances. The composition of pancreatic juice is given in. The bicarbonate content is very high in pancreatic juice. It is about 110-150 mEq/ L against the concentration of 24 mEq/L in plasma. This high concentration of bicarbonate is responsible for the alkalinity of pancreatic juice

Functions Of Pancreatic Juice

The pancreatic juice has digestive functions and a neutralizing action.

Digestive Functions Of Pancreatic Juice: Pancreatic juice plays an important role in the digestion of proteins and lipids. It also has mild digestive action on carbohydrates.

Pancreas Functions

Digestion Of Proteins: The major proteolytic enzymes of pancreatic juice are trypsin and chymotrypsin. Other proteolytic enzymes are carboxypeptidases, nuclease, elastase, and collagenase.

1. Trypsin:

• Trypsin is a single polypeptide with a molecular weight of 25,000. It contains 229 amino acids. It is secreted as inactive trypsinogen which is converted into active trypsin by enterokinase.
• Enterokinase is also called enteropeptidase and it is secreted by the brush-bordered cells of the duodenal mucus membrane. Once formed, trypsin itself activates trypsinogen by means of autocatalytic or autoreactive action.

Trypsin inhibitor:

• Trypsinogen is activated only when it reaches the small intestine. If trypsin is activated when it is in the pancreas, it may hydrolyze the pancreatic tissue proteins resulting in pancreatic damage.
• But, its activation in the secretory cells, acini, and ducts of the pancreas is prevented by an inhibitor protein called trypsin inhibitor. 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. By the process of hydrolysis, it converts proteins into proteoses and polypeptides
2. Curdling of milk – It converts caseinogens in the milk into casein
3. Acceleration of blood clotting
4. Activation of other enzymes of pancreatic juice.
5. Trypsin converts:
   • Chymotrypsinogen into chymotrypsin
   • Procarboxypeptidases into carboxypeptidases
   • Proelastase into elastase
   • Procolipase into colipase
6. Trypsin also activates collagenase, phospholipase A, and phospholipase B
7. Autocatalytic action – once formed trypsin itself converts trypsinogen into trypsin.

2. Chymotrypsin: Chymotrypsin is a polypeptide with a molecular weight of 25,700 and 246 amino acids. It is secreted as inactive chymotrypsinogen which is activated into chymotrypsin by trypsin.

Actions of chymotrypsin:

• Digestion of proteins: Chymotrypsin is also an endopeptidase and it hydrolyses the proteins into polypeptides
• Digestion of milk: Chymotrypsin digests casein faster than trypsin. The combination of both enzy¬mes causes more rapid digestion of milk.
• On blood clotting: No action.

3. Carboxypeptidases:

The two carboxypeptidases are carboxypeptidase A and carboxypeptidase B. Procarboxypeptidase A is the precursor of carboxypeptidase A. Procarboxypeptidase B is the precursor for carboxypeptidase B. The procar-boxypeptidases are activated into carboxypeptidases by trypsin.

Actions of carboxypeptidases:

• Carboxypeptidases break the terminal bond of protein molecules. Therefore, these enzymes are called exopeptidases. The exopeptidases split the polypeptides and other proteins into amino acids.
• Carboxypeptidase A splits the proteins into amino acids having aromatic or aliphatic side chains. Carboxy-peptidase B converts the proteins into amino acids having basic side chains.

4. Nucleases: The nucleases of pancreatic juice are ribonuclease and deoxyribonuclease, which are responsible for the digestion of nucleic acids. These enzymes convert ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) into mononucleotides.

5. Elastase: Proelastase is activated into elastase by trypsin. Elastase digests the elastic fibers.

6. Collagenase: Procollagenase is activated into collagenase by trypsin. It digests collagen.

Digestion Of Lipids: The lipolytic enzymes present in pancreatic juice are pancreatic lipase, cholesterol ester hydrolase, phospho-lipase A, and phospholipase B.

Pancreas Functions

1. Pancreatic lipase: Pancreatic lipase is a powerful lipolytic enzyme. It hydrolyses the triglycerides into monoglycerides and fatty acids. The activity of pancreatic lipase is accelerated in the presence of bile. The optimum pH required for the activity of this enzyme is 7 to 9.

Digestion of fat by pancreatic lipase requires two more factors:

• Bile salts which are responsible for the emulsification of fat prior to their digestion
• Colipase which is a coenzyme necessary for the pancreatic lipase to hydrolyze the dietary lipids. Colipase is secreted as an inactive procolipase which is activated into colipase by trypsin.
• About 80% of fat is digested by pancreatic lipase. The deficiency or absence of this hormone leads to the excretion of undigested fat in feces (see below).

2 Cholesterol ester hydrolase: Cholesterol ester hydrolase or cholesterol esterase converts cholesterol ester into free cholesterol and fatty acid by hydrolysis.

3. Phospholipase A: It is activated by trypsin. Phospholipase A digests phospholipids namely lecithin and cephalin and converts them into lysophospholipids; lecithin into lysolecithin and cephalin into lysocephalin.

4. Phospholipase B: Phospholipase B is also activated by trypsin. This enzyme converts the lysophospholipids (lysolecithin and lysocephalin) to phosphorylcholine and free fatty acids.

5. Co-lipase: Colipase is a small coenzyme which facilitates the efficient hydrolysis of fats by pancreatic lipase. Colipase binds to the C-terminal, the non-catalytic domain of lipase so that there is an overall increase in the hydrophobic binding site of lipase.

6. Bile salt-activated lipase: This enzyme has a weak lipolytic action than pancreatic lipase. But it hydrolyses a variety of lipids like phospholipids, cholesterol esters, and triglycerides. Since it is activated bile salt it is known as bile salt-activated lipase. Human milk contains an enzyme similar to bile salt-activated lipase.

Digestion Of Carbohydrates: Pancreatic amylase is the amylolytic enzyme present in pancreatic juice. Like salivary amylase, pancreatic amylase also converts starch into dextrin and maltose.

Pancreas Functions

Neutralizing Action Of Pancreatic Juice:

• When acid chyme enters the intestine from the stomach, pancreatic juice with a large quantity of bicarbonate is released into the intestine. The presence of a large quantity of bicarbonate ions makes the pancreatic juice highly alkaline. This alkaline pancreatic juice neutralizes the acidity of chyme in the intestine.
• Neutralizing action is an important function of pancreatic juice, because, it protects the intestine from the destructive action of acidic chyme.

Mechanism Of Pancreatic Secretion

• Secretion Of Pancreatic Enzymes:
  • Pancreatic enzymes are synthesized in ribosomes, which are attached to the endoplasmic reticulum of acinar cells in the pancreas. The raw materials for the synthesis of pancreatic enzymes are the amino acids which are derived from the blood.
  • After synthesis, the enzymes are packed into different zymogen granules by the Golgi apparatus and stored in the cytoplasm. When stimulated, the acinar cells release zymogen granules into the pancreatic duct. From the granules, the enzymes are liberated into the intestine.
• Secretion Of Bicarbonate Ions: The bicarbonate ions of pancreatic juice are secreted from the cells of pancreatic ductules and released into the pancreatic duct.

Mechanism of bicarbonate secretion:

• The carbon dioxide derived from blood or metabolic process combines with water inside the ceil to form carbonic acid in the presence of carbonic anhydrase
• Carbonic acid dissociates into hydrogen and bicarbonate ions
• Bicarbonate ions are actively transported out of the cell into the lumen
• The hydrogen ion is actively transported into the blood in exchange for the sodium ion
• The sodium ion from the cell is transported into the lumen where it combines with bicarbonate to form sodium bicarbonate
• 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 the pancreatic duct by osmosis
• In the lumen, bicarbonate combines with water forming the solution of bicarbonate.

Pancreas Functions

Regulation Of Pancreatic Secretion

Secretion of pancreatic juice is regulated by both nervous and hormonal factors.

Stages Of Pancreatic Secretion:

The pancreatic secretion occurs in three stages:

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:

• Secretion of pancreatic juice by the stimuli arising from the head region (cephalus) is called the cephalic phase. When food is placed in the mouth, pancreatic secretion occurs through an unconditioned reflex. Sight, smell, and thought of the food also cause the secretion of pancreatic juice by conditioned reflex.
• The impulses from the mouth (during unconditioned reflex) or from the cerebral cortex (during conditioned reflex) reach the dorsal nucleus of the vagus.
• From the dorsal nucleus of the vagus, the efferent impulses reach the pancreas via efferent fibers of the vagus nerve. The vagal nerve endings release acetylcholine which stimulates the acinar cells to release the enzymes. Thus, the cephalic phase of pancreatic secretion is purely under nervous control.

2. Gastric Phase:

• Secretion of pancreatic juice, when food enters the stomach, is known as the gastric phase. This phase of pancreatic secretion is under hormonal control. The hormone involved is gastrin.
• When food enters the stomach, gastrin is secreted from the stomach. When gastrin is transported to the pancreas through blood, it stimulates pancreatic secretion. The pancreatic juice secreted during the gastric phase is rich in enzymes.

Pancreas Structure

3. Intestinal Phase:

• The intestinal phase is the secretion of pancreatic juice when the chyme enters the intestine. This phase is also under hormonal control.
• When chyme enters the intestine many hormones are released. Some hormones stimulate pancreatic secretion and some hormones inhibit pancreatic secretion.

Hormones Stimulating Pancreatic Secretion

1. Secretin
2. Cholecystokinin

1. Secretin:

• Secretin is produced by S cells of mucous membranes in the duodenum and jejunum. It is produced in an inactive form – prosecretin which is activated into secretin by acid chyme.
• The stimulant for the release and activation of prosecretin is the acid chyme entering the intestine. The products of protein digestion also stimulate hormonal secretion.

The action of secretin:

• Secretin acts on the cells of pancreatic ductules via cyclic AMP and stimulates the secretion of large amounts of watery juice which contains a high concentration of bicarbonate ions.
• The high bicarbonate content of pancreatic juice is important because of two reasons:
• High bicarbonate content makes the pancreatic juice highly alkaline so that it protects the intestinal mucosa from acid chyme by neutralizing it.
• Bicarbonate ions provide the required pH (7 to 9) for the activation of pancreatic enzymes. The other actions of secretin are explained in.

2. Cholecystokinin:

Cholecystokinin (CCK) is also called cholecystokinin- pancreozymin (CCK-PZ). It is secreted by 1 cell in the duodenal and jejunal mucosa. The stimulant for the release of this hormone is the chyme-containing digestive products such as fatty acids, peptides, and amino acids.

The action of cholecystokinin:

• Cholecystokinin stimulates the pancreatic acinar cells via the second messenger inosine triphosphate. Cholecystokinin causes the secretion of pancreatic juice rich in enzymes and low in volume.
• The other actions of cholecystokinin are described in.

Pancreas Structure

Hormones Inhibiting Pancreatic Secretion:

1. Pancreatic polypeptide – Secreted by PP cells in islets of Langerhans of the pancreas
2. Somatostatin – Secreted by D cells in islets of Langerhans of the pancreas
3. Peptide YY – Secreted by the intestinal mucosa
4. Peptides like ghrelin and leptin.

Collection Of Pancreatic Juice

1. In Animals: In animals, the pancreatic juice is collected by connecting a fistula between the pancreatic duct and the opening in the abdominal wall.

2. Human:

• In human beings, a multi-lumen tube is inserted through the nose or mouth, till the tip of this tube reaches the intestine near the ampulla of Vater. The tube has a marking. 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. Small balloons are attached to the two outer lumens. 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.

Applied Physiology

1. Pancreatitis: Pancreatitis is the inflammation of the pancreatic acini. It is a rare but dangerous disease. There are two forms of pancreatitis:

1. Acute pancreatitis
2. Chronic pancreatitis.

1. Acute Pancreatitis: Acute pancreatitis is more severe and it occurs because of heavy alcohol intake or gallstones.

Features of acute pancreatitis:

• Severe upper abdominal pain
• Nausea and vomiting
• Loss of appetite and weight
• Fever
• Shock.

Pancreas Structure

2. Chronic Pancreatitis: Chronic pancreatitis develops due to repeated acute inflammation or chronic damage to the pancreas.

Causes of chronic pancreatitis:

• Long-time consumption of low alcohol
• Chronic obstruction of the ampulla of Vater by gall-stone
• Hereditary – Passed on genetically from one generation to another.
• Congenital abnormalities of the pancreatic duct
• Cystic fibrosis – Generalized disorder affecting the functions of many organs such as lungs (due to excessive mucus), exocrine glands like the pancreas, biliary system, and immune system
• Malnutrition – Poor nutrition (mal = bad).
• Idiopathic pancreatitis – Due to unknown cause.

Features of chronic pancreatitis:

• Complete destruction of the pancreas: During the obstruction of biliary ducts, more amount of trypsinogen and other enzymes are accumulated. In spite of the presence of trypsin inhibitors in acini, some trypsinogen is activated. Trypsin in turn activates other proteolytic enzymes. All these enzymes destroy the pancreatic tissues completely.
• Absence of pancreatic enzymes: Pancreatitis is more dangerous because the destruction of acinar cells in the pancreas leads to deficiency or total absence of pancreatic enzymes. So the digestive processes are affected; the worst affected is fat digestion which results in steatorrhea (see below).
• Severe pain in the upper abdominal region which radiates to the back
• Fever, nausea, and vomiting
• Tender and swollen abdomen
• Weight loss.

2. Steatorrhea:

Steatorrhea is the formation of bulky, foul-smelling, frothy, and clay-colored stools with large quantities of undigested fat because of impaired digestion and absorption of fat.

• Causes of Steatorrhea: Any condition that causes indigestion or malabsorption of fat leads to steatorrhea. Various causes of steatorrhea are:
• Lack of pancreatic lipase: Since, most of the fat is digested only by pancreatic lipase, its deficiency leads to steatorrhea
• A liver disease affecting the secretion of bile: Bile salts are essential for the digestion of fat by lipase and absorption of fat from the intestine. The absence of bile salts results in the excretion of fatty stool
• Celiac disease: Atrophy of intestinal villi leads to malabsorption resulting in steatorrhea
• Cystic fibrosis (see above).