Pancreatic Exocrine Function PDF

EXOCRINE FUNCTION OF PANCREAS: (Dr. Hızır Kurtel) Functional Anatomy: The pancreas, which lies parallel to and beneath the stomach, is a large compound gland with an internal structure similar to that of the salivary glands. Digestive enzymes ar...

EXOCRINE FUNCTION OF PANCREAS: (Dr. Hızır Kurtel) Functional Anatomy: The pancreas, which lies parallel to and beneath the stomach, is a large compound gland with an internal structure similar to that of the salivary glands. Digestive enzymes are secreted by the pancreatic acini. The centroacinar cells, which are the initial components of the duct system, drains the acinus, appear to be the primary sites of electrolyte and water secretion.  The intercalated ducts converge to form intralobular ducts, which in turn, drain into interlobular ducts. The interlobular ducts empty their contents into one of the two main ducts that deliver the secretion to the duodenum. The major pancreatic duct (duct of Wirsung) enters the duodenum at the ampulla of Vater alongside the common bile duct, both being surrounded by a ring of smooth muscle called the sphincter of Oddi.  The acinar cells make up approximately 80% of the pancreas by volume. Ductule cells comprise about 4% of the gland, together with the centroaciner cells. The endocrine cells of the pancreas account for only 2% of its mass and are found in the islets of langerhans distributed throughout the pancreatic parenchyma.  Sympathetic innervation is provided by postganglionic fibers from the celiac and superior mesenteric plexuses. Sympathetic fibers enter the pancreas along with arteries to the organ. Sympathetic nerves are largely inhibitory. Parasympathetic preganglionic fibers to the pancreas are contained in branches of the vagus nerves. Within the pancreas the vagal fibers terminate either at acini and islets or on other intrinsic cholinergic nerves of pancreas. Regulation of Pancreatic Mass:  It is well recognized that starvation or parenteral feeding results in pancreatic atrophy. Cholecystokinin (CCK), a hormone released from the intestinal mucosa in response to luminal nutrients, is considered to be a major regulator of pancreatic growth. Exogenous administration of CCK to experimental animals results in pancreatic growth. Composition of Pancreatic Juice:  The human pancreas can secrete roughly one liter of pancreatic juice per day. The secreted juice contains a variety of electrolytes and proteins, the concentrations of which vary with the mode of stimulation.  The principal anions are Cl- and HCO-3 and principal cations are Na+, and K+. Pancreatic enzymes account for more than 90 per cent of the proteins in juice. The electrolytes and enzymes secreted primarily by the ductular and acinar cells, respectively. Electrolytes:  In contrast to saliva, pancreatic juice is isotonic with plasma at all rates of secretion. The most likely explanation for this phenomenon is that water moves freely across pancreatic epithelia when an osmotic gradient is generated by active transport of solutes, primarily electrolytes.  The sum of the concentration of cations equals that of the anions in the secreted juice and this balance is maintained at all rates of secretion.  Although the Na+ and K+ concentrations of pancreatic juice are not affected by secretion rate, the concentrations of the major anions Cl-, and HCO3, vary dramatically with the rate of secretion.  The reciprocal relationship between the concentrations of Cl- and HCO3 ions in such that the sum of the two anions remains the same regardless of the rate of secretion. Enzymatic Component of the Pancreatic Secretion.  The pancreas supplies the principal enzymes for the digestion of all foodstuffs. All pancreatic enzymes are synthesized and secreted by the acinar cells  Pancreatic juice contains a variety of proteins, the majority of which (>90 per cent) are hydrolyses and can be classified according to the specific substrates upon which they act.  Most of the enzymes of pancreatic juice are proteolytic. They are synthesized, stored and secreted as inactive precursors (called proenzymes) which are activated in the duodenal lumen.  Activation of the proteases involves hydrolytic cleavage of key peptide bonds, thereby inducing a conformational change in the enzyme which unmasks the catalytic site or the binding site.  The initial step in duodenal activation is accomplished by an endopeptidase secreted by the enterocytes.  Amylase, ribonuclease, and the lipolytic enzymes, except phospholipase A2, are secreted in their active forms.  Pro-phospholipase A2 like the proteases, is activated in the duodenal lumen by trypsin.  Pancreatic juice also contains two small proteins that are not enzymes yet play an important role in regulating the activity of certain pancreatic hydrolyses.  One of these, typsin inhibitor, combines with trypsin in a one-to-one ratio to produce a complex that is inactive. Complex between the pancreatic trypsin inhibitor (PTI) and trypsin. PTI is a small protein, binds to trypsin with high affinity because it contains a peptide bond that is a transition state analog.  The presence of trypsin inhibitor in the gland serves to protect the tissue from autodigestion by the small amounts of trypsin which may become activated prematurely within the pancreas.  The molar concentration of trypsin inhibitor in the juice, however is much less than the molar concentration of trypsinogen therefore activation of the pancreatic proteases in the duodenal lumen is not prevented.  Colipase, another small polypeptide present in the secreted juice, enhances the lipolytic activity of pancreatic lipase. This cofactor prevents the bile salt-induced inhibition of lipase activity by anchoring the lipase molecule to the lipid-water interface of oil droplets.  The concentration of Colipase in pancreatic juice is roughly equivalent to the concentration of lipase.  A minor proportion (