PANCREATIC SECRETION - PANCREATIC SECRETION - EXOCRINEEXOCRINE

BY,BY, AJEETHA AAJEETHA A

I YEAR MBBS I YEAR MBBS MMC & RIMMC & RI

ANATOMY OF PANCREASANATOMY OF PANCREAS

HISTOLOGY OF PANCREASHISTOLOGY OF PANCREAS

CHYMOTRYPSINOGENCHYMOTRYPSINOGEN Chymotrypsin contains 246 amino acid. Molecular weight : 25700 Cleavage between 15-16th amino acid. It is called endopeptidase. Action : On peptide whose carboxyl group is provided with trypsin &

phenylalanine. Hydrolyses, proteins Polypeptides. Digests caesin.

GASTRINGASTRIN This hormone, is very similar to cholecystokinin, is secreted in large

amounts by the stomach in response to gastric distention and irritation.

In addition to stimulating acid secretion by the parietal cell, it stimulates pancreatic acinar cells to secrete digestive enzymes.

2HCl + Na2CO3 2NaCl + H2CO3 H2O + CO2

The carbonic acid (a weak acid) immediately dissociates into Carbon Dioxide and water.

The Carbon dioxide is absorbed into the blood stream. Pancreatic enzymes work best between a pH of 7-8. Sodium Bicarbonate has a pH of about 8

TESTS FOR ANALYSING PANCREATIC FUNCTIONTESTS FOR ANALYSING PANCREATIC FUNCTION Estimation of fecal fat content. Secretin & pancreozymin test Estimation of serum amylase activity Lundch test

The pancreas lies in the epigastrium and left hypochondrium areas of the abdomen.

It is composed of the following parts: The head lies within the concavity of the duodenum. The neck is the constricted part between the head

and the body.

The body lies behind the stomach. The tail is the left end of the pancreas. It lies in contact with

the spleen.

ANATOMYANATOMY

INTRODUCTIONINTRODUCTION

The pancreas is a gland organ in the digestive and endocrine system of vertebrates.

It is both an endocrine gland producing important hormones, and exocrine gland, secreting pancreatic juice containing digestive enzymes that pass to the small intestine.

These enzymes further break down the carbohydrates, proteins, and fats in the chyme.

HISTOLOGYHISTOLOGY Under a microscope, stained sections of the pancreas reveal two

different types of parenchymal tissue. Lightly staining clusters of cells are called islets of Langerhans,

which produce hormones that underlie the endocrine functions of the pancreas.

Darker staining cells form acini connected to ducts. Acinar cells belong to the exocrine pancreas and secrete

digestive enzymes into the gut via a system of ducts.

HistologyHistology ContdContd.

STRUCTURE APPEARANCE FUNCTION

Islets of Langerhans

Lightly staining, large, spherical clusters

Hormone production and secretion (endocrine pancreas)

Pancreatic acini Darker staining, small, berry-like clusters

Digestive enzyme production and secretion (exocrine pancreas)

EXOCRINE SECRETION EXOCRINE SECRETION

Pancreatic juice is composed of two secretory products critical to proper digestion: digestive enzymes and bicarbonate.

The enzymes are synthesized and secreted from the exocrine acinar cells, whereas bicarbonate is secreted from the epithelial cells lining small pancreatic ducts.

The pancreas secretes a magnificent battery of enzymes that collectively have the capacity to reduce virtually all digestible macromolecules into forms that are capable of, or nearly capable of being absorbed.

3 major groups of enzymes are needed for digestion.

PANCREATIC JUICEPANCREATIC JUICE Colourless, odourless, watery secretion isosmotic with

plasma. 1-1.5L/day pH : 8-9 Specific gravity : 1.010 – 1.018 Composition

water – 99% solid – 1%

Organic Inorganic

SOLID COMPOSITIONSOLID COMPOSITION

INORGANIC CONSTITUENTINORGANIC CONSTITUENT

Bicarbonate concentration : 135 - 140mEq/L

Chloride concentration :

10 - 15mEq/LSodium ion : 130mEq/LPotassium ion :

10 – 15mEq/L

ORGANIC CONSTITUENTORGANIC CONSTITUENT

MucusEnzymes

Proteolytic Lipolytic Amylolytic

Trypsin inhibitor

Digestion of proteins is initiated by pepsin in the stomach, but the bulk of protein digestion is due to the pancreatic proteases.

Several proteases are synthesized in the pancreas and secreted into the lumen of the small intestine.

The two major pancreatic proteases: Trypsin Chymotrypsin - are synthesized and packaged into

secretory vesicles as an the inactive proenzymes trypsinogen and chymotrypsinogen.

1. PROTEOLYTIC1. PROTEOLYTIC

TRYPSINOGEN Trysin contains 229 amino acids. Molecular weight : 25000 Cleavage between 5th & 6th amino acid. Activation by acid, enterokinase, magnesium sulphate, calcium

chloride & trysin (autocatalytic action) itself. Action : On polypeptide bonds located in the interior of protein molecule . Polypeptide bonds carboxyl group is provided with arginine &

lysine. Converts : Chymotryinogen Chymotrysin Procarboxypeptidase Carboxypeptidase Procolipase Colipase Activates collagenase, phospholipase A & B

PROCARBOXYLASE APROCARBOXYLASE A

Activated by trypsin. Acts on terminal peptide bonds of end product of chymotrypsin &

elsatase digestion.

PROCARBOXYLASE BPROCARBOXYLASE B Acts on terminal peptide bonds of end product of trypsin

digestion. These 2 enzymes exopeptidases. End products are dipeptides, tripeptides & aminoacids.

PROELASTASEPROELASTASE Activated into elastase. Elastin fibres & other polypeptides are digested.

COLLAGENASECOLLAGENASE Activated by trypsin. Digests collagen.

TRYPSIN INHIBITORTRYPSIN INHIBITOR The secretory vesicles also contain a trypsin inhibitor which

serves as an additional safeguard. Molecular weight : 5000-6000 Inhibits both trypsin & chymotrypsin. Protects the pancreas from auto digestion by small quantities of

trypsin resulting in pancreatic damage. Any damage in this inhibitor causes unopposed trypsin activity. When pancreas is severely damaged or duct gets blocked, large

quantity of pancreatic secretion effect of trypsin inhibitor is overwhelmed, in which the pancreatic secretion is rapidly activated & can digest the entire pancreas leading to ACUTE PANCREATITIS.

2. LIPOLYTIC2. LIPOLYTIC

Major component of dietary fat is triglyceride or neutral lipid. A triglyceride molecule cannot be directly absorbed across the

intestinal mucosa.

Digested into 2-monoglyceride and two free fatty acids. Lipolytic enzyme present are :

Pancreatic lipase. Cholesterol ester hydrolase Phospholipase A Phospholipase B Colipase

Normal digestion and absorption of dietary fat is critically dependent on secretions from both the pancreas and liver.

PANCREATIC LIPASEPANCREATIC LIPASE Powerful lypolytic enzyme. Optimum pH : 7- 9 Requires : Sufficient quantities of bile salts – emulsification of fat Colipase – coenzyme for lipase

Lipase Triglycerides Monosaccharide + Free

Bile salts/Colipase fatty acids + Glycerol Recently in limelight as a target for management of obesity. Orlistat (Xenical) is a pancreatic lipase inhibitor that interferes

with digestion of triglyceride and thereby reduces absorption of dietary fat.

PHOSPHOLIPASE BPHOSPHOLIPASE B

Small coenzyme. Facilitate hydrolysis of fats by lipase.

Activated byActivated by trypsintrypsin.. Converts Converts lysophospholipids lysophospholipids (lysolecithin & lysocephalin)(lysolecithin & lysocephalin) Lysophospholipids Phosphoryl choline + Free fatty acidsLysophospholipids Phosphoryl choline + Free fatty acids

BILE SALT-ACTIVATED LIPASEBILE SALT-ACTIVATED LIPASE Weak lipolytic action. Hydrolyses a variety of lipids like phospholipids, cholesterol

esters & triglycerides. Activated by bile salts. Digests esters of soluble vitamins.

COLIPASECOLIPASE

CHOLESTEROL ESTER HYDROLASECHOLESTEROL ESTER HYDROLASE Digests cholesterol esters. Cholesterol esters Cholesterol + Free fatty acid

PHOSPHOLIPASEPHOSPHOLIPASE A Activated by trypsin. Acts on lecithin & cephalin. Digests them to lysophospholipids. Lecithin Lysolecithin.

Cephalin Lysocephalin.

Optimum pH : 6.5-7.0 Molecular weight : 45000 Amylase (alpha-amylase) is the enzyme that hydrolyses starch &

related polysaccharides to maltose (a glucose-glucose disaccharide), as well as the trisaccharide maltotriose and small branchpoints fragments called limit dextrins.

The major source of amylase in all species is pancreatic secretions, although amylase is also present in saliva of some animals, including humans.

3. AMYLASE3. AMYLASE

TYPES OF ENZYMES &THEIR EFFECTSTYPES OF ENZYMES &THEIR EFFECTSEnzyme Type

Effects A shortage may cause

Lipase Works with bile from the liver to break down fat molecules so they can be absorbed.

Lack of needed fats and fat-soluble vitamins. Diarrhea and fatty stools.

Protease Breaks down proteins.  Helps to keep the intestine free of parasites such as bacteria, yeast and protozoa.

Allergies or the formation of toxic substances due to incomplete digestion of proteins.Risk for intestinal infections.

Amylase Breaks down carbohydrates into sugars which are more easily absorbed.  Also found in saliva. 

Diarrhea due to the effects of undigested starch in the colon.

CONTROL OF PANCREATIC SECRETIONCONTROL OF PANCREATIC SECRETION

Secretion from the exocrine pancreas is regulated by both neural and endocrine controls.

Interdigestive periods - very little secretion As food enters the stomach and a little later - chyme flows into the

small intestine, pancreatic secretion is strongly stimulated. Like the stomach, the pancreas is innervated by the vagus nerve,

which applies a low level stimulus to secretion in response to anticipation of a meal.

However, the most important stimuli for pancreatic secretion comes from three hormones secreted by the enteric endocrine system:

CHOLECYSTOKININCHOLECYSTOKININ

This hormone is synthesized and secreted by enteric endocrine cells located in the duodenum.

Its secretion is strongly stimulated by the presence of partially digested proteins and fats in the small intestine.

As chyme floods into the small intestine, cholecystokinin is released into blood and binds to receptors on pancreatic acinar cells, ordering them to secrete large quantities of digestive enzymes.

SECRETINSECRETIN This hormone is also a product of endocrinocytes located in the

epithelium of the proximal small intestine. Secretin is secreted in response to acid in the duodenum, which of

course occurs when acid-laden chyme from the stomach flows through the pylorus.

The predominant effect of Secretin on the pancreas is to stimulate duct cells to secrete water and bicarbonate.

As soon as this occurs, the enyzmes secreted by the acinar cells are flushed out of the pancreas, through the pancreatic duct into the duodenum.

Released from parasympathetic vagus nerve endings & other cholinergic nerves in enteric nervous system.

ACETYLCHOLINEACETYLCHOLINE

Pancreatic secretions are also the major mechanism for neutralizing gastric acid in the small intestine.

When acid enters the small gut, it stimulates Secretin to be released, and the effect of this hormone is to stimulate secretion of lots of bicarbonate.

As proteins and fats are digested and absorbed, and acid is neutralized, the stimuli for cholecystokinin and Secretin secretion disappear and pancreatic secretion falls off.

Pancreatic secretions contain enzymes which are needed to digest proteins, starch and triglyceride.

When these substances enter stomach, and especially the small intestine, they stimulate release of gastrin and cholecystokinin, which in turn stimulate secretion of the enzymes of destruction.

FUNCTIONS OF PANCREATIC SECRETIONFUNCTIONS OF PANCREATIC SECRETION

SECRETION OF BICARBONATE IONSECRETION OF BICARBONATE ION Copious quantities of Bicarbonate ion rich solutions are secreted

by the ducts and ductules of the pancreas in response to the hormone Secretin.

The mechanisms are similar to that of the mucous cells of the stomach, except that large quantities of fluid are also produced.

Carbon dioxide and water enter the cell and combine to form carbonic acid under the influence of the enzyme carbonic anhydrase.

Hydrogen ions are actively secreted on the basal side of the cell in exchange for sodium.

Bicarbonate ions are actively secreted on the apical or lumen side of the cell in exchange for chlorine.

Sodium and Water ions follow either passively through tight junctions, or through cell by the above mechanism.

PANCRATITIS : PANCRATITIS : Inflammation of pancreatic aciniInflammation of pancreatic acini

ACUTE PANCRATITISACUTE PANCRATITIS More severe Cause :

Heavy alcoholics Gall stones

Features : Severe abdominal

pain Nausea & vomiting Loss of appetite Fever Shock

CHRONIC PANCREATITISCHRONIC PANCREATITIS Repeated acute inflammation or

chronic damage Cause:

Long time alcohol consumption Cystic fibrosis Malnutrition Hereditary Idiopathic

Features : Destruction of pancreas Absence of pancreatic enzymes Similar to acute pancreatitis

APPLIED PHYSIOLOGYAPPLIED PHYSIOLOGY

STEATORRHEASTEATORRHEA Formation of bulky, foul smelling, frothy & clay coloured stools. Contains large quantity of undigested fat. Due to impaired digestion & absorption of fat. Causes :

Lack of pancreatic lipase Liver disease affecting secretion of Bile. Celiac disease – Atrophy of intestinal villi Cystic Fibrosis

VERNER MORISSON SYNDROMEVERNER MORISSON SYNDROME Pancreatic cholera. Excessive production of VIP by VIP secreting tumors. Results in excess production of HCO3 & H2O from pancreas &

small intestine. Produces diahhorea.

WHEN ARE ENZYMES PRESCRIBED?WHEN ARE ENZYMES PRESCRIBED?

  Some of these conditions are: Following the Whipple procedure Following a total pancreatectomy Blockage or narrowing of the pancreatic or biliary duct (the

tubes that carry pancreatic juice or bile) Pancreatic or duodenal tumors Cystic fibrosis Pancreatitis

JULIUS WOHLGEMUTH JULIUS WOHLGEMUTH

Brunner is remembered for his experiments and studies of the pancreas and the internal secretions associated with the organ.

In 1683 he removed the pancreas from a dog and noticed that the animal experienced extreme thirst and polyuria.

In 1908,described a method for measuring the concentration of amylase in the serum, thereby introducing the potential for diagnosing acute pancreatitis prior to laparotomy or autopsy.

JOHANN CONRAD BRUNNEJOHANN CONRAD BRUNNE

NOBLE LAUREATESNOBLE LAUREATES

GEORGE PALADEGEORGE PALADE

In 1974, was awarded the Nobel Prize in Physiology or Medicine for his description in the exocrine pancreatic cell of the biochemical steps in protein synthesis, segregation, transport, storage and secretion and the ultra structural units related to each process.

The digestive enzymes, (amylase, lipase, trypsin, etc), secreted by the pancreas into the intestine, were discovered in the mid to late 19th century.

Demonstration of their effectiveness in breaking down fats, proteins and starches to smaller molecules which could be from the intestines was gradual.

Discovery of this principle of digestive enzymes, as a primary function of the pancreas, included these contributors.

Johann Nepomuk Eberle, Claude Bernard, Alexander Johann Nepomuk Eberle, Claude Bernard, Alexander Danilevsky, and Willy Kuhne. Danilevsky, and Willy Kuhne.

MCQsMCQs

Pancreatic Amylase hydrolyses most of the carbohydrates except :

a) Starchb) Glycogenc) Cellulose Answer : c) CelluloseReference : Page No. 799, Guyton & Hall, 11th Edition

Secretion of isosmotic sodium bicarbonate is by :a) Bloodb) Pancreatic ductules & ductsc) Lumen of the ductAnswer : b) Pancreatic ductules & ductsReference : Page No. 800, Guyton & Hall, 11th Edition

Production of large quantities of pancreatic digestive enzymes

(acinar cells of pancreas) is stimulated by :

a) Acetylcholine

b) Secretin

c) Cholecystokinin

d) Both (a) & (c)

Answer : d) Both (a) & (c)

Reference : Page No. 801, Guyton & Hall, 11th Edition

Truly potent constituent of chyme that cause secretin release :

a) HCl of stomach

b) Vagal stimulation

c) Bile acids Answer : a) HCl of stomach Reference : Page No. 801, Guyton & Hall, 11th Edition

Secretin causes pancreas to secrete large quantities of fluid containing high concentration of :

a) Chloride ion

b) Bicarbonate ion

c) Sodium ion

Answer : b) Bicarbonate ion [Also Cl ion but low conc.]

Reference : Page No. 800, Guyton & Hall, 11th Edition

Secretin begins to be released from the mucosa of the small intestine when the pH of the duodenal contents fall below:

a) 4.5 – 5.0

b) 7.5 - 8.0

c) 1.8 – 3.5

Answer : a) 4.5 – 5.0

Reference : Page No. 801, Guyton & Hall, 11th Edition

A polypeptide containing 33 amino acids released from mucosa of the duodenum, upper jejunum & I cells :

a) Secretin

b) Bicarbonate ion

c) Cholecystokinin

Answer : c) Cholecystokinin

Reference : Page No. 801, Guyton & Hall, 11th Edition

Release of cholecystokinin results especially due the presence of :

a) Proteases

b) Peptones

c) Long-chain fatty acids

d) All the above

Answer : d) All the above

Reference : Page No. 801, Guyton & Hall, 11th Edition

When pancreas is stimulated to secrete copious quantity of pancreatic juice, the bicarbonate ion concentration can rise to as high as :

a) 180 mEq/L

b) 145 mEq/L

c) 125 mEq/L

Answer : b) 145 mEq/L

Reference : Page No. 800, Guyton & Hall, 11th Edition

Trypsin inhibitor prevents the activation of :

a) Trypsin

b) Chymotrypsin

c) All proteolytic enzymes

Answer : c) All proteolytic enzymes

Reference : Page No. 800, Guyton & Hall, 11th Edition