Pancreatic Secretion

Objectives

•

Describe the two components of pancreatic exocrine secretion, their cells of origin, and their functions.
•

Understand the mechanisms involved in the formation of both the electrolyte (aqueous) and enzymatic components of pancreatic secretion.
•

Explain the hormonal and neural regulation of both the aqueous and enzymatic components of pancreatic secretion.
•

Discuss the cellular basis for potentiation and its importance in the pancreatic response to a meal.
•

Discuss the various clinical conditions resulting from the decreased production of either or both the aqueous and enzymatic components of pancreatic juice.
•

Understand how the preceding clinical conditions may arise.

Pancreatic exocrine secretion is divided conveniently into an aqueous or bicarbonate ( HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
) component and an enzymatic component. The function of the aqueous component is the neutralization of the duodenal contents. As such, it prevents damage to the duodenal mucosa by acid and pepsin and brings the pH of the contents into the optimal range for activity of the pancreatic enzymes. The enzymatic or protein component is a low-volume secretion containing enzymes for the digestion of all normal constituents of a meal. Unlike the enzymes secreted by the stomach and salivary glands, the pancreatic enzymes are essential to normal digestion and absorption.

Functional Anatomy

The exocrine pancreas can best be likened to a cluster of grapes, and its functional units resemble the salivons of the salivary glands. Groups of acini form lobules separated by areolar tissue. Each acinus is formed from several pyramidal acinar cells oriented with their apices toward the lumen. The lumen of the spherical acinus is drained by a ductule whose epithelium extends into the acinus in the form of centroacinar cells. Ductules join to form intralobular ducts, which in turn drain into interlobular ducts. These join the major pancreatic duct draining the gland.

The acinar cells secrete a small volume of juice rich in protein. Essentially all the proteins present in pancreatic juice are digestive enzymes. Ductule cells and centroacinar cells produce a large volume of watery secretion containing sodium (Na ⁺) and HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
as its major constituents.

Distributed throughout the pancreatic parenchyma are the islets of Langerhans or the endocrine pancreas. The islets produce insulin from the beta cells and glucagon from the alpha cells. In addition, the pancreas produces the candidate hormone pancreatic polypeptide and contains large amounts of somatostatin, which may act as a paracrine to inhibit the release of insulin and glucagon.

The efferent nerve supply to the pancreas includes both sympathetic and parasympathetic nerves. Sympathetic postganglionic fibers emanate from the celiac and superior mesenteric plexuses and accompany the arteries to the organ. Parasympathetic preganglionic fibers are distributed by branches of the vagi coursing down the antral-duodenal region. Hence surgical vagotomy for peptic ulcer disease affects not only the intended target organ, the hypersecreting stomach, but also the pancreas. More recently, more selective operations have been designed to resect only the vagal branches passing to the stomach. Vagal fibers terminate either at acini and islets or at the intrinsic cholinergic nerves of the pancreas. In general, the sympathetic nerves inhibit, and the parasympathetic nerves stimulate, pancreatic exocrine secretion.

Mechanisms of Fluid and Electrolyte Secretion

The pancreas secretes approximately 1 L of fluid per day. At all rates of secretion, pancreatic juice is essentially isotonic with extracellular fluid. At low rates the primary ions are Na ⁺and chloride (Cl ⁻). At high rates Na ⁺and HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
predominate. Potassium ions (K ⁺) are present at all rates of secretion at a concentration equal to their concentration in plasma. The concentrations of Na ⁺in pancreatic juice and in plasma also are approximately equal.

The aqueous component is secreted by the ductule and centroacinar cells and may contain 120 to 140 milliequivalents (mEq) of HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
/L, several times its concentration in plasma. The electropotential difference across the ductule epithelium is 5 to 9 millivolts (mV), lumen negative. Hence HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
is secreted against both electrical and chemical gradients. This is often considered evidence that HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
is transported actively across the luminal surface of the cells. Although the exact mechanism involved in pancreatic HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
secretion is unknown, the current model is shown in Fig. 9.1 . This model is based on information that shows the following: (1) more than 90% of HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
in pancreatic juice is derived from plasma; (2) the secretion of HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
occurs against an electrochemical gradient and is an active process; (3) HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
secretion is blocked by ouabain, meaning that Na ⁺,K ⁺-adenosine triphosphatase (ATPase) is involved; (4) HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
secretion involves Na ⁺-hydrogen ion (H ⁺) and Cl ⁻– HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
exchangers and carbonic anhydrase; and (5) HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
secretion is decreased significantly in the absence of extracellular Cl ⁻. In Fig. 9.1 , most of the HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
enters the cell across the basolateral membrane cotransported with Na ⁺. Intracellular HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
is also produced by the diffusion of carbon dioxide (CO ₂) into the cell, its hydration by carbonic anhydrase, and dissociation into H ⁺and HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
. The H ⁺is transported across the basolateral membrane by the Na ⁺-H ⁺exchanger. Both these steps depend on the Na ⁺gradient established by Na ⁺,K ⁺-ATPase. When H ⁺reaches the plasma, it combines with HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
to produce additional CO ₂. In some species, such as the rat, HCO−¿3
HCO3−¿
HCO−¿3
HCO 3 − ¿
enters the lumen in exchange for Cl ⁻.