Contents
What is the Pancreas
The pancreas is a flattened, spongy, retroperitoneal gland pressed between the body wall and the greater curvature of the stomach. It measures 12 to 15 cm long and about 2.5 cm thick. It has a globose head encircled by the duodenum, a midportion called the body, and a blunt, tapered tail on the left.
The pancreas is both an endocrine and exocrine gland. The endocrine part of the pancreas consists of groups of cells that are closely associated with blood vessels. These groups form “islands” of cells called pancreatic islets (islets of Langerhans). The pancreatic islets include two distinct types of cells—alpha cells, which secrete the hormone glucagon, and beta cells, which secrete the hormone insulin.
About 99% of the pancreas is exocrine tissue, which secretes 1,200 to 1,500 mL of pancreatic juice per day. Pancreatic islets are relatively concentrated in the tail of the pancreas, whereas the head is more exocrine. Over 90% of pancreatic cancers arise from the ducts of the exocrine portion (ductal carcinomas), so cancer is most common in the head of the gland.
Figure 1. Pancreas location
Figure 2. Pancreas
Figure 3. Relationship of the pancreas to the liver, gallbladder, and duodenum
What does the pancreas do ?
The cells of the secretory acini exhibit a high density of rough ER (endoplasmic reticulum) and secretory vesicles (zymogen granules) (Figure 3). The acini open into a system of branched ducts that eventually converge on the main pancreatic duct. This duct runs lengthwise through the middle of the gland and joins the bile duct at the hepatopancreatic ampulla. The hepatopancreatic sphincter thus controls the release of both bile and pancreatic juice into the duodenum. Usually, however, there is a smaller accessory pancreatic duct (duct of Santorini) that branches from the main pancreatic duct and opens independently into the duodenum at the minor duodenal papilla, proximal to the major papilla. The accessory duct bypasses the sphincter and allows pancreatic juice to be released into the duodenum even when bile is held back.
Pancreatic juice is an alkaline mixture of water, enzymes, zymogens, sodium bicarbonate, and other electrolytes. The acini secrete the enzymes and zymogens, whereas the ducts secrete the sodium bicarbonate. The bicarbonate buffers HCl (hydrochloric acid) arriving from the stomach.
The pancreatic zymogens are trypsinogen, chymotrypsinogen and procarboxypeptidase. When trypsinogen is secreted into the intestinal lumen, it is converted to trypsin by enteropeptidase, an enzyme on the brush border of the duodenum. Trypsin is autocatalytic—it converts trypsinogen into still more trypsin. It also converts the other two zymogens into chymotrypsin and carboxypeptidase, in addition to its primary role of digesting dietary protein.
Other pancreatic enzymes include pancreatic amylase, which digests starch; pancreatic lipase, which digests fat; and ribonuclease and deoxyribonuclease, which digest RNA and DNA, respectively. Unlike the zymogens, these enzymes are not altered after secretion. They become fully active, however, only upon exposure to bile or ions in the intestinal lumen.
Regulation of Pancreatic Secretion
Three stimuli are chiefly responsible for the release of pancreatic juice and bile.
- Acetylcholine (ACh), coming from the vagus nerves and enteric neurons. ACh stimulates the pancreatic acini to secrete their enzymes even during the cephalic phase of gastric control, before food is swallowed. The enzymes remain stored in the pancreatic acini and ducts, however, in preparation for release later when chyme enters the duodenum.
- Cholecystokinin (CCK), secreted by the mucosa of the duodenum and proximal jejunum (the next segment of the small intestine), primarily in response to fats in the small intestine. CCK also stimulates the pancreatic acini to secrete enzymes, but it is named for its strongly stimulatory effect on the gallbladder. It induces contractions of the gallbladder and relaxation of the hepatopancreatic sphincter, discharging bile into the duodenum.
- Secretin, produced by the same regions of the small intestine, mainly in response to the acidity of chyme from the stomach. Secretin stimulates the ducts of both the liver and pancreas to secrete an abundant sodium bicarbonate solution. In the pancreas, this flushes the enzymes into the duodenum.
Sodium bicarbonate buffers the hydrochloric acid arriving from the stomach, with the reaction:
HCl + NaHCO3 ⟶ NaCl + H2CO3 (carbonic acid).
The carbonic acid then breaks down to carbon dioxide and water. CO2 is absorbed into the blood and ultimately exhaled. What is left in the small intestine, therefore, is salt water—NaCl and H2O. Sodium bicarbonate is therefore important in protecting the intestinal mucosa from HCl as well as raising the intestinal pH to the level needed for activity of the pancreatic and intestinal digestive enzymes.
Figure 4. Pancreas anatomy
Hormones of the Pancreatic Islets
The pancreas is primarily an exocrine digestive gland. Scattered throughout the exocrine tissue, are 1 to 2 million endocrine groups of cells that are closely associated with blood vessels called pancreatic islets (islets of Langerhans). Although they are less than 2% of the pancreatic tissue, the islets of Langerhans secrete the hormone glucagon and the hormone insulin of vital importance, especially in the regulation of glycemia, the blood glucose concentration. The pancreatic islets of Langerhans include two distinct types of cells—alpha cells, which secrete the hormone glucagon, and beta cells, which secrete insulin hormone. A typical islet measures about 75 × 175 μm and contains from a few to 3,000 cells. Islets of Langerhans main cell types are alpha cells (20%), beta cells (70%), and delta cells (5%). Islets of Langerhans respond directly to blood nutrient levels associated with the cycle of eating and fasting. Their functions are as follows:
- Alpha (α) cells, or A cells, secrete glucagon between meals when the blood glucose concentration falls below 100 mg/dL (5.6 mmol/L). Glucagon exerts two primary actions on the liver: (1) glycogenolysis, the breakdown of glycogen into glucose; and (2) gluconeogenesis, the synthesis of glucose from fats and proteins (see Figure 2). These effects lead to the release of glucose into circulation, thus raising the blood glucose level. In adipose tissue, glucagon stimulates fat catabolism and the release of free fatty acids. Glucagon is also secreted in response to rising amino acid levels in the blood after a high-protein meal. It promotes amino acid absorption and thereby provides cells with the raw material for gluconeogenesis.
- Beta (β) cells, or B cells, secrete two hormones, insulin and amylin. Insulin, “the hormone of nutrient abundance,” is secreted during and immediately following a meal when blood nutrient levels are rising. Osteocalcin, a hormone from the osteoblasts of bone, also stimulates multiplication of beta cells, insulin secretion, and insulin sensitivity of other body tissues. The principal targets of insulin are the liver, skeletal muscles, and adipose tissue. In times of plenty, insulin stimulates cells to absorb glucose, fatty acids, and amino acids and to store or metabolize them; therefore, it lowers the level of blood glucose and other nutrients. It promotes the synthesis of glycogen, fat, and protein, thereby promoting the storage of excess nutrients for later use and enhancing cellular growth and differentiation. It also antagonizes glucagon, thus suppressing the use of already-stored fuels. The brain, liver, kidneys, and red blood cells absorb and use glucose without need of insulin, but insulin does promote glycogen synthesis in the liver. Insulin insufficiency or inaction is well known as the cause of diabetes. The beta cells also secrete another hormone, amylin, simultaneously with insulin. Amylin helps to reduce spikes in blood glucose by slowing the emptying of the stomach; modulating the secretion of gastric enzymes, acid, and bile; inhibiting glucagon secretion; and stimulating the sense of satiety (having had enough to eat).
- Delta (δ) cells, or D cells, secrete somatostatin (growth hormone–inhibiting hormone) concurrently with the release of insulin by the beta cells. Somatostatin works with amylin to limit the secretion of stomach acid.
- Other, minor types of pancreatic cells, about 5% of the total, are called PP and G cells. Their functions remain obscure and controversial.
Any hormone that raises blood glucose concentration is called a hyperglycemic hormone. You may have noticed that glucagon is not the only hormone that does so; so do growth hormone, epinephrine, norepinephrine, cortisol, and corticosterone. Insulin is called a hypoglycemic hormone because it lowers blood glucose levels.
Glucagon raises the blood sugar concentration by stimulating the liver to break down glycogen and convert certain noncarbohydrates, such as amino acids, into glucose. These actions raise the blood glucose concentration. Glucagon much more effectively elevates blood glucose than does epinephrine (adrenaline).
A negative feedback system regulates glucagon secretion. A low blood glucose concentration stimulates alpha cells to release glucagon. When the blood glucose concentration rises, glucagon secretion falls. This control prevents hypoglycemia when the blood glucose concentration is relatively low, such as between meals, or when glucose is used rapidly, such as during exercise.
The main effect of insulin is to lower the blood glucose level, exactly opposite that of glucagon. Insulin does this in part by promoting facilitated diffusion of glucose into cells that have insulin receptors, for use in cellular respiration. Such cells include those of adipose tissue, liver, and skeletal muscle. (Glucose uptake by active skeletal muscle does not require insulin.) Insulin also stimulates the liver to form glycogen from glucose and inhibits conversion of noncarbohydrates into glucose. In addition, insulin promotes transport of amino acids into cells, increases the rate of protein synthesis, and stimulates adipose cells to synthesize and store fat.
A negative feedback system sensitive to the blood glucose concentration regulates insulin secretion. When the blood glucose concentration is high, such as after a meal, beta cells release insulin. Insulin helps prevent too high a blood glucose concentration by promoting glycogen formation in the liver and entrance of glucose into adipose and muscle cells.
When glucose concentration falls, such as between meals or during the night, insulin secretion decreases. As insulin secretion decreases, less glucose enters adipose and resting muscle cells. Cells that lack insulin receptors and are therefore not dependent on insulin, such as nerve cells, can still take up glucose from the blood. At the same time that insulin is decreasing, glucagon secretion is increasing. Nerve cells, including those of the brain, obtain glucose by a facilitated diffusion mechanism that does not require insulin, but rather depends only on the blood glucose concentration. For this reason, nerve cells are particularly sensitive to changes in blood glucose concentration. Conditions that cause such changes—for example, oversecretion of insulin leading to decreased blood glucose—are likely to affect brain functions.
Insulin and glucagon are coordinated to maintain a relatively stable blood glucose concentration, despite great variation in the amount of carbohydrates a person eats. About 85% to 90% of people with diabetes mellitus have type 2, in which the beta cells produce insulin but body cells lose the ability to recognize it. On the other hand, type 1 diabetes mellitus usually appears before age twenty and it is an autoimmune disease: the immune system destroys the beta cells of the pancreas.
