Pancreas: Structure, Composition and Regulation

In this article we will discuss about:- 1. Structure of Pancreas 2. Composition of Pancreatic Juice 3. Regulation 4. Pancreatic 5. Effects.

Structure of Pancreas:

Pancreas is a dual organ. It has endocrine portion and exocrine portion.

The exocrine part resembles the salivary glands in histology; being formed of acini arranged into lobules. Cells of the acini contain numerous mitochondria, a nucleus and granular cytoplasm. The zymogen granules are located more towards the apex and contain enzyme precursors of pancreatic juice. Each acinus drains into a duct.

The cells lining the intra- acinar portion of the duct are called centroacinar cells. The acinar cells secrete various enzymes of the pancreatic juice while the centroacinar and duct cells contribute to the secretion of electrolytes, most important of which is HCO₃^–. All the minute ducts from the various lobules unit to form main pancreatic duct of Wirsung. This duct opens into the second part of duodenum along with bile duct.

In most of the normal people, there is also an accessory pancreatic duct of Santorini which opens into the second part of duodenum just above the main duct. In this manner, the exocrine pancreatic secretion drains into the duodenum. Pancreas is supplied by the vagus and sympathetic fibers from celiac ganglion, just like heart, the ganglia for vagus are in the pancreas itself.

Composition of Pancreatic Juice:

Pancreatic juice is a colorless, odorless, highly alkaline fluid of low viscosity, pH = 8- 8.4. Alkalinity is because of HCO₃^–.

The important components of pancreatic juice are (Figs 5.17 to 5.19):

i. H₂O

ii. Cations: Na⁺, K⁺, Mg⁺⁺, Ca⁺⁺

iii. Anions: HCO₃^–, Cl^–, SO₄^–, HOP₄^–

Others:

i. Amylase

ii. Deoxyribonuclease

iii. Ribonuclease

Miscellaneous:

i. Immunoglobulins

ii. Albumins

iii. Kallikrein

iv. Trypsin inhibitor

v. Co-lipase

Functions of the Individual Components:

Bicarbonates make the pancreatic juice alkaline and alkaline medium is essential for the pancreatic enzymes to perform their digestive functions.

1. The chyme received from the stomach is acidic and acidity is harmful to duodenal mucosa and also does not permit pancreatic and intestinal enzymes to act. HCO₃^– neutralizes the acidity rendering the pH of intestinal contents between 7 and 8 which is essential for digestive processes to occur in the small intestine.

2. HCO₃^– inactivates pepsin because pepsin being a proteolytic enzyme will digest all pancreatic enzymes.

Normal HCO₃^– content of pancreatic juice: 80-120 mEq/liter

Enzymes: Proteolytic Enzymes:

Trypsinogen:

Trypsinogen is the inactive form of trypsin.

It is activated by another enzyme known as enteropeptidase (also called enterokinase) secreted by intestinal mucosa.

It activates trypsinogen to trypsin. Once trypsin is formed, trypsin by itself activates trypsinogen. This type of a reaction is known as an autocatalytic reaction.

Trypsin is a powerful endopeptidase because it acts inside the protein molecule and breaks the peptide bonds adjacent to arginine or lysine; thereby breaking larger protein molecules into smaller polypeptides. It requires a pH of 7-8 for its action. Other actions include a weak coagulting action on milk.

All the enzymes of pancreatic juice are secreted into duodenum in the inactive form, if not enzymes themselves will digest the entire pancreas.

Besides this, trypsin has got a specific inhibitor in the pancreas itself.

Chymotrypsinogen:

This is also an endopeptidase. Chymotrypsinogen is activated to chymotrypsin by trypsin.

Chymotrypsin breaks peptide bonds adjacent to aromatic amino acids. The pH required for this action is about 7-8. This enzyme helps to digest large proteins into smaller peptides. Compared to trypsin, it has got more powerful coagulating action on milk.

Some believe that there are 6 different types of chymotrypsinogen and one of these is used to dissolve the lens capsule in the eye to remove cataract.

Procarboxypeptidase A and B:

Both are activated by trypsin into carboxypeptidase A and B, respectively. They are exopeptidases because they cleave or break peptide bonds at the carboxy terminal of the protein.

Carboxypeptidase A, breaks peptide bonds of carboxy terminal attached to branched aliphatic amino acids. Whereas B attacks and breaks peptide bonds of carboxy terminal attached to basic amino acids. These exopeptidases help to form or break individual amino acids from peptides produced by the action of trypsin and chymotrypsin.

Proelastase:

Activated to elastase by trypsin. An elastase acts on the protein elastin attacking peptide bonds adjacent to aliphatic amino acids.

Lipolytic Enzymes:

Pancreatic lipase:

It is the most important fat splitting enzyme in the GIT. It acts on emulsified fats, emulsification having been brought about by bile salts in the presence of lecithin and monoglycerides. Bile salts activate pancreatic lipase.

Although from the reaction, it is seen that triglycerides can be broken down by lipase into glycerol and fatty acids, actually since the final two steps are slow, the usual products of lipase action are 2 monoglyceride and fatty acids.

Lipase also requires alkaline pH of 7-8 for the action. Colipase helps to expose the triglyceride molecule which has formed a complex with bile salts. This exposure is necessary for lipase to hydrolyze the triglyceride.

If pancreatic lipase is absent either due to complete destruction of pancreas because of disease or removal of entire pancreas surgically, the digestion and absorption of fats and fat-soluble vitamins is significantly disturbed and more fat is excreted in fecal matter. Normal fat content of feces is up to 5 g/day. If lipase is completely absent, fat content increases to 40-50 g/day. Presence of abnormal amounts of fatty stool is called steatorrhea.

Prophospholipase:

This is activated by trypsin to phospholipase. Phospholipase converts lecithin into lysolecithin by splitting of fatty acid and later can be absorbed.

Cholesterol esterase:

This enzyme hydrolyses cholesterol ester to yield free cholesterol which is absorbed along with fatty acids.

Pancreatic amylase:

Actions similar to salivary amylase.

Deoxyribonnclease:

This converts DNA into the respective nucleotide.

Ribonuclease:

This hydrolyses RNA to the respective nucleotide.

Regulation of Pancreatic Secretion:

Pancreatic secretion is regulated by neural and hormonal mechanism of which hormonal mechanisms is more important. Three different phases for pancreatic secretion have been recognized in animals and these are not so well defined in man.

The three phases are:

1. Cephalic Phase:

Taste of food stimulates pancreatic secretion. In addition to this, sight or smell also can also stimulate.

2. Gastric Phase:

Presence of food in the stomach by way of mechanical distension and chemical composition stimulates pancreatic secretion.

Distension of stomach causing pancreatic secretion of enzymes is called gastropancreatic reflex.

Cephalic and gastric phases are controlled by vagus. Stimulation of vagus promotes pancreatic secretion which is rich in enzymes, yet pancreatic secretion can go on in the absence of vagus. The action of vagus is through acetylcholine.

3. Intestinal Phase:

Presence of food, HCl, etc., in the small intestine promotes pancreatic secretion through mechanical distension as well as chemical composition.

This very important phase is brought about two hormones, viz.:

a. Secretin and

b. Cholecystokinin-pancreozymin (CCK-PZ)

Secretin:

This is the first hormone ever to be discovered (and synthesized) in the year 1902 by Bayliss and Starling.

This is a polypeptide hormone having 26 amino acids. This GI hormone is secreted by specialized cells in the mucosa of duodenum and jejunum.

Stimuli for release:

The most important stimulus is the presence of HCl in the duodenum (Fig. 5.20). Whenever pH of chyme in the duodenum falls to less than 4.5, secretin is released into the portal vein and then returns to GIT through the circulatory system.

Actions (functions): Secretin increases the volume of pancreatic juice which is rich in HC0₃^– and water. Therefore, its main site of action is centroacinar and duct cells of pancreas.

i. It potentiates action of CCK-PZ on pancreas.

ii. Increases secretion of bile from hepatocytes.

iii. Inhibits gastric motility and delays gastric emptying by contraction of pyloric sphincter.

iv. Inhibits gastrin release and gastric secretion.

v. Inhibits gastric motility and delays gastric emptying by contraction of pyloric sphincter.

vi. Releases insulin from beta cells of islets of Langerhans.

Cholecystokinin-pancreozymin (CCK-PZ) initially discovered as the separate hormones: pancreozymin and cholecystokinin, former acting on pancreas and the latter on gallbladder. Subsequently, they were found to be one and the same. This polypeptide GI hormone has got 33 amino acids and is produced from mucosa of duodenum and jejunum.

Stimuli for release of CCK-PZ (Fig. 5.21):

Presence of food in duodenum and jejunum stimulates secretion of this hormone. Although products of protein, fat and carbohydrate digestion all can release CCK-PZ, amino acids form the most powerful stimulus and the next potent stimulus is fatty acids. HCl is a weak stimulus for CCK-PZ.

Actions (functions):

CCK-PZ acts on pancreatic acini to produce pancreatic juice rich in enzyme content.

While secretin acts through cAMP, CCK-PZ acts not only through cAMP but also increases intracellular Ca⁺⁺ concentration in the acini which is necessary for release of pancreatic enzyme.

CCK-PZ promotes contraction of gallbladder. This results in expulsion of bile from the gallbladder into duodenum. An agent that causes contraction of gall­bladder is called cholegogues. CCK-PZ is a very powerful cholegogue.

1. Potentiates action of secretin on pancreas

2. Promotes secretion of bile.

3. Inhibits gastric motility and, therefore, delays gastric emptying.

4. Promotes release of insulin in from the B cells of islets of Langerhans.

5. Promotes pancreatic cell growth.

Pancreatic Function Test:

(Only for exocrine pancreas):

It is now possible to collect pure pancreatic juice right from the pancreatic duct by passing a thin catheter through the mouth into the duodenum with the help of an instrument called duodenoscope.

Pancreatic juice is collected and analyzed for HCO₃^– content and trypsin activity. After collecting the morning initial sample, with the individual in fasting condition, an injection of secretin and CCK-PZ is given.

A few minutes after the injection, pancreatic juice is again collected at intervals of 10 minutes and HCO₃^– content and trypsin activity are estimated every time. If pancreas is normal, secretin should cause an increase in HCO₃ content and PZ should increase in tryspin activity. If pancreas is not functioning normally, both will be reduced.

Effect of Total Pancreatectomy:

This is sometimes done for the carcinoma of the pancreas.

Removal of pancreas leads to following abnormalities:

1. Diabetes mellitus

2. Abnormalities in digestion and absorption of lipids and proteins, but carbohydrates digestion is not affected significantly because salivary amylase and enzymes present in intestinal secretion keep carbohydrate absorption and digestion normal.

Diminished digestion and absorption of lipids causes steatorrhea while impaired digestion and absorption of proteins is reflected by increased nitrogen content of stool which is normally up to 1 g/day.