print pancreatic secretion - exocrine
TRANSCRIPT
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