Pancreas

Pancreas

Introduction

The pancreas is both an organ of the digestive system and endocrine system in humans. It is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an endocrine and a digestive exocrine function. 99% of the pancreas is exocrine and 1% is endocrine. 

As an endocrine gland, it functions mostly to regulate blood sugar levels secreting the hormones insulin, glucagon, somatostatin, and  pancreatic polypeptide.

As a part of the digestive system, it functions as an exocrine gland  secreting pancreatic juice into the duodenum through the pancreatic duct. This juice contains bicarbonate, which neutralizes acid entering the duodenum from the stomach and digestive enzymes, which break down  carbohydrates,  proteins, and  fats in food entering the duodenum from the stomach.

The word pancreas comes from the Greek  pân meaning all & kréas meaning flesh. The function of the pancreas in diabetes has been known since at least 1889, with its role in insulin production identified in 1921.

Structure

The pancreas is an organ that in humans lies in the abdomen, stretching from behind the stomach to the left upper abdomen near the spleen. In adults, it is about 12–15 centimeters long, lobulated, and salmon-colored in appearance.. The pancreas stretches from the inner curvature of the duodenum, where the head surrounds two blood vessels: the superior mesenteric artery and vein. The longest part of the pancreas, the body, stretches across behind the stomach, and the tail of the pancreas ends adjacent to the spleen.

Anatomically, the pancreas is divided into following parts 

·        Head 

·        Neck 

·        Body 

·        Tail

Head

The head of the pancreas sits within the curvature of the duodenum, and wraps around the superior mesenteric artery and vein. To the right sits the descending part of the duodenum, and between these travels the superior and inferior pancreaticoduodenal arteries. Behind rests the inferior vena cava, and the common bile duct. In front sits the peritoneal membrane and the transverse colon. A small uncinate process emerges from below the head, situated behind the superior mesenteric vein and sometimes artery.

Neck

The neck of the pancreas separates the head of the pancreas, located in the curvature of the duodenum, from the body. The neck is about 2 cm wide, and is present in front of where the portal vein is formed. The neck lies mostly behind the pylorus of the stomach, and is covered with peritoneum. The anterior superior pancreaticoduodenal artery travels in front of the neck of the pancreas.

 Body

The body is the largest part of the pancreas, and mostly lies behind the stomach, tapering along its length. The peritoneum sits on top of the body of the pancreas, and the transverse colon in front of the peritoneum. Behind the pancreas are several blood vessels, including the aorta, the splenic vein, and the left renal vein, as well as the beginning of the superior mesenteric artery. 

Below the body of the pancreas some part of the small intestine is present, specifically the last part of the duodenum and the jejunum to which it connects, as well as the suspensory ligament of the duodenum which falls between these two. In front of the pancreas sits the transverse colon.

 

 Tail

The pancreas narrows towards the tail, which is near to the spleen. It is 1.3 to 3.5 cm long, and presents between the layers of the ligament between the spleen and the left kidney. The splenic artery and vein, which also passes behind the body of the pancreas, pass behind the tail of the pancreas.

Ducts

Two ducts are found in the structure of pancreas

·        Main pancreatic duct 

·        Accessory pancreatic duct 

Both run through the body of the pancreas. The larger main pancreatic duct joins with the common bile duct forming a small ballooning called the ampulla of Vater (hepatopancreatic ampulla). This ampulla is surrounded by a muscle, the sphincter of Oddi.

This ampulla opens into the descending part of the duodenum. The opening of the common bile duct into main pancreatic duct is controlled by sphincter of Boyden. The smaller accessory pancreatic duct opens into duodenum with separate openings located above the opening of the main pancreatic duct.

Blood Supply

The pancreas has a rich blood supply, with vessels originating as branches of both the celiac artery and superior mesenteric artery. The splenic artery runs along the top of the pancreas, and supplies the left part of the body and the tail of the pancreas through its pancreatic branches, the largest of which is called the greater pancreatic artery. The superior and inferior pancreaticoduodenal arteries run along the back and front surfaces of the head of the pancreas adjacent to the duodenum. These supply the head of the pancreas. These vessels join together (anastamose) in the middle.

The body and neck of the pancreas drain into the splenic vein, which is present behind the pancreas. The head drains into, and wraps around, the superior mesenteric and portal veins, via the pancreaticoduodenal veins

Histology

The majority of pancreatic tissue has a digestive function. The cells with this function, form clusters called acini around small ducts, and are arranged in lobes that have thin fibrous walls. The cells of each acinus secrete inactive digestive enzymes called zymogens into the small intercalated ducts which they surround. In each acinus, the cells are pyramid-shaped and situated around the intercalated ducts, with the nuclei resting on the basement membrane, a large endoplasmic reticulum, and a number of zymogen granules visible within the cytoplasm.

The intercalated ducts drain into larger intralobular ducts within the lobule, and finally interlobular ducts. The ducts are lined by a single layer of column-shaped cells. There is more than one layer of cells as the diameter of the ducts increases.

The tissues with an endocrine role within the pancreas exist as clusters of cells called pancreatic islets also called islets of Langerhans that are distributed throughout the pancreas. Pancreatic islets contain alpha cells, beta cells, and delta cells, each of which releases a different hormone.

These cells have characteristic positions, with alpha cells (secreting glucagon) tending to be situated around the periphery of the islet, and beta cells (secreting insulin) more numerous and found throughout the islet. 

Enterochromaffin cells are also scattered throughout the islets. Islets are composed of up to 3,000 secretory cells, and contain several small arterioles to receive blood, and venules that allow the hormones secreted by the cells to enter the systemic circulation

Functions

Digestion

The pancreas plays a vital role in the digestive system. It does this by secreting a fluid that contains digestive enzymes into the duodenum. These enzymes help to break down carbohydrates, proteins and lipids. This role is called the exocrine role of the pancreas. The cells that do this are arranged in clusters called acini. Secretions into the middle of the acinus accumulate in intralobular ducts, which drain to the main pancreatic duct, which drains directly into the duodenum. About 1.5 - 3 liters of fluid are secreted in this manner every day.

The cells in each acinus are filled with granules containing the digestive enzymes. These are secreted in an inactive form termed zymogens or proenzymes. When released into the duodenum, they are activated by the enzyme enterokinase present in the lining of the duodenum. The proenzymes are cleaved, creating a cascade of activating enzymes.

• Enzymes that break down proteins begin with activation of trypsinogen to trypsin. The free trypsin then cleaves the rest of the trypsinogen, as well as chymotrypsinogen to its active form chymotrypsin.
• Enzymes secreted involved in the digestion of fats include lipase, phospholipase A2, lysophospholipase, and cholesterol esterase.
• Enzymes that break down starch and other carbohydrates include amylase.

These enzymes are secreted in a fluid rich in bicarbonate. Bicarbonate helps maintain an alkaline pH for the fluid, a pH in which most of the enzymes act most efficiently, and also helps to neutralize the stomach acids that enter the duodenum. Secretion is influenced by hormones including         secretin,  cholecystokinin, and  VIP, as well as acetylcholine stimulation from the vagus nerve.

Secretin is released from the S cells which form part of the lining of the duodenum in response to stimulation by gastric acid. Along with VIP, it increases the secretion of enzymes and bicarbonate.

Cholecystokinin is released from Ito cells  (perisinusoidal fat-storing cells, stellate cells, called lipocytes in the liver) of the lining of the duodenum and jejunum mostly in response to long chain fatty acids, and increases the effects of secretin. 

At a cellular level, bicarbonate is secreted from centroacinar and ductal cells through a sodium and bicarbonate co transporter that acts because of membrane depolarization caused by the cystic fibrosis transmembrane conductance regulator. Secretin and VIP act to increase the opening of the cystic fibrosis transmembrane conductance regulator, which leads to more membrane depolarization and more secretion of bicarbonate.

A variety of mechanisms act to ensure that the digestive action of the pancreas does not act to digest pancreatic tissue itself. These include

·        the secretion of inactive enzymes (zymogens)

·        the secretion of the protective enzyme trypsin inhibitor, which inactivates trypsin

·        the changes in pH that occur with bicarbonate secretion that stimulate digestion only when the pancreas is stimulated

·        low calcium within cells causes inactivation of trypsin

Maintenance of blood glucose level

Cells within the pancreas help to maintain blood glucose levels (homeostasis). The cells that do this are located within the pancreatic islets that are present throughout the pancreas. When blood glucose levels are low alpha cells secrete glucagon which increases blood glucose levels.

When blood glucose levels are high beta cells secrete insulin to decrease glucose in blood. Delta cells in the islet also secrete somatostatin which decreases the release of insulin and glucagon.

Glucagon acts to increase glucose levels by promoting the creation of glucose and the breakdown of glycogen to glucose in the liver. It also decreases the uptake of glucose in fat and muscle. Glucagon release is stimulated by low blood glucose or insulin levels, and during exercise. 

Insulin acts to decrease blood glucose levels by facilitating uptake by cells (particularly skeletal muscle), and promoting its use in the creation of proteins, fats and carbohydrates. Insulin is initially created as a precursor form called preproinsulin.

This is converted to proinsulin and cleaved by C-peptide  to insulin which is then stored in granules in beta cells. Glucose is taken into the beta cells and degraded. The end effect of this is to cause depolarization of the cell membrane which stimulates the release of the insulin.

The main factor influencing the secretion of insulin and glucagon are the levels of glucose in blood plasma. Low blood sugar stimulates glucagon release, and high blood sugar stimulates insulin release.

Other factors also influence the secretion of these hormones. Some amino acids, that are byproducts of the digestion of protein, stimulate insulin and glucagon release. Somatostatin acts as an inhibitor of both insulin and glucagon.

The autonomic nervous system also plays a role. Activation of Beta-2 receptors of the sympathetic nervous system by catecholamines secreted from sympathetic nerves stimulates secretion of insulin and glucagon, whereas activation of Alpha-1 receptors inhibits secretion. M3 receptors of the parasympathetic nervous system act when stimulated by the right vagus nerve to stimulate release of insulin from beta cells.

Other secretions

The pancreas also secretes vasoactive intestinal peptide and pancreatic polypeptide. 

Enterochromaffin cells of the pancreas secrete the hormones motilin, serotonin, and substance P.