What is the pancreas?
The pancreas is an organ about 15 to 18 centimeters long and weighing 100 grams that is located in the abdominal cavity. The head of the organ is situated in the loop of the small intestine that forms at the site where the small intestine joins the stomach. The pancreas is enclosed in a thin connective tissue capsule. As an accessory gland of the digestive system, the pancreas is an exocrine gland. Scattered within the tissue of this exocrine gland, however, are small distinct regions known as the islets of Langerhans, which are a part of the endocrine system. The exocrine portion composes by far the greatest mass of tissue. In the guinea pig, for example, about 82 percent of pancreatic cells are exocrine cells, while the endocrine portion is about 2 percent. The remaining cells are associated with the duct system and the blood vessels.
The exocrine pancreas is an arrangement of tubules that continue to branch until they form very fine ducts called the intercalated ducts. Along the edges of the intercalated ducts are the acinar cells. These cells produce the pancreatic juices that aid in the digestion of food in the small intestine and help neutralize the contents of the small intestine. The products drain from the ducts into the main collecting duct, which joins the common bile duct and empties into the duodenum.
The islets of Langerhans, as is the case with all endocrine glands, have a well-developed blood supply. The hormones produced by these endocrine cells are emptied into the surrounding capillaries. The hormones flow into the general circulation where they are distributed to target cells throughout the body. Since the two portions of the pancreas are anatomically as well as functionally different, they will be considered independently.
The exocrine portion of the pancreas produces about 1 liter of aqueous fluid per day that is delivered directly to the duodenum. The two major components of the pancreatic juices are ions, which are used to neutralize the stomach contents as they enter the small intestine, and enzymes, which metabolize intestinal contents for absorption.
The various ions that are secreted include sodium, potassium, chloride, and bicarbonate ions. The sodium, potassium, and chloride are present in concentrations similar to their concentrations in the bloodstream. The bicarbonate ions act as the major buffer of the body. With only a few exceptions, the bloodstream and the contents of the body must be maintained at a pH of 7.4. Bicarbonate ions ensure that there is no change in pH.
The stomach is one of the areas of the body in which the pH varies. It may be as low as pH 1, which is highly acidic. The contents of the stomach empty directly into the duodenum, and while the cells of the stomach are capable of withstanding an acid environment, the cells of the small intestine are not. The acid must be rapidly neutralized in order to protect these cells. In addition, the enzymes that help to digest the food reaching the small intestine work optimally at about pH 7. If the pH varies significantly, the food will not be properly digested and vital nutrients will not be absorbed by the intestinal cells.
The production of bicarbonate by the duct cells is controlled by a hormone called secretin. The contents of the small intestine become acidic as food moves into the area from the stomach. When the pH is lowered, the cells of the small intestine release secretin, which in turn stimulates the pancreas to produce more bicarbonate. As bicarbonate enters the small intestine, it neutralizes the acid, and the stimulus to produce secretin is removed.
The pancreas also produces a variety of enzymes that digest proteins, sugars, lipids, and nucleic acids. In order for protein to be absorbed by the cells of the small intestine, it must be broken down into its building blocks, amino acids. This breakdown is an enzymatic process that occurs only when the appropriate enzymes are present and at a pH near neutrality. The enzymes that digest proteins include trypsin, chymotrypsin, and carboxypeptidase. Like protein, sugars, nucleic acids, and lipids must be digested to their subunits if they are to be absorbed. Sugars are metabolized by amylase, nucleic acids by either ribonuclease or deoxyribonuclease, and fats by lipase, phospholipase, or cholesterol esterase.
The secretion of enzymes by the pancreas is controlled by the hormone cholecystokinin. As the content of protein and fat increases in the lumen of the duodenum, the duodenal cells release cholecystokinin, which acts on the acinar cells of the pancreas to release the enzymes. As the food is digested, the level of cholecystokinin decreases and the release of enzymes from the pancreas also decreases.
The islets of Langerhans have four different cell types and produce four different hormones. The alpha and beta cells produce glucagon and insulin, respectively. The delta cells produce somatostatin, which inhibits the secretion of hormones by the alpha and beta cells. The F cells produce pancreatic polypeptide, the function of which is not yet understood.
Insulin secretion is stimulated or inhibited by a large number of factors. Blood glucose levels are the most important factor in the release of insulin from the beta cells. If blood glucose increases, insulin is released until glucose levels return to normal. When insulin is released into the bloodstream, it stimulates the uptake of glucose by target cells. Although insulin is best known for its action on glucose, it also stimulates the uptake of amino acids and fatty acids from the bloodstream during periods of adequate nutrition. Glucagon is an antagonist of insulin. It is released in response to low levels of glucose and acts on cells to release glucose, amino acids, and fatty acids into the circulatory system.
Diseases of the pancreas can be divided into two basic categories: diseases of the exocrine cells of the organ and those diseases that effect the function of the endocrine portion, the islets of Langerhans. The exocrine cells of the pancreas can be affected by various conditions, including acute pancreatitis, chronic pancreatitis, cystic fibrosis, and carcinoma of the pancreas. Also, because the pancreas is a gland and glandular organs typically have a large blood supply, it is at risk of injury any time that circulation is impaired. The islets of Langerhans may be affected by diabetes mellitus.
Inflammation of the pancreas (pancreatitis) can be either acute or chronic. While some cases are mild, it is considered a serious disease and has a high mortality rate. Although the acute form is more serious, patients with chronic pancreatitis may suffer from acute episodes.
Acute pancreatitis may result from obstruction of the pancreatic duct (possibly by gallstones from the gallbladder or by mucous plugs, as in cystic fibrosis), bile reflux, acute intoxication by alcohol, shock, infection by the mumps virus, hypothermia, or trauma. The diagnosis, pathology, and prognosis are the same regardless of the cause.
The onset of the disease is usually quite sudden, with severe pain in the abdomen, nausea, and vomiting. Diagnosis is made by the presence of amylase in the blood serum. Amylase is an enzyme produced by the pancreas that is used to digest carbohydrates in the small intestine. The presence of elevated levels of the enzyme is an indication that it is not reaching the small intestine and is spilling over into the bloodstream.
The powerful enzymes produced by the pancreas are used to digest proteins, carbohydrates, and fats. If for any reason these substances are not released from the pancreas, they will digest the cells of the pancreas and destroy them. As pancreatitis progresses, it will cause tissue inflammation and will lead to swelling of the organ. In addition, the enzymes may start to digest the cells of the blood vessels in the immediate area, causing bleeding into the tissue. The inflammation, combined with the bleeding, may lead to greater swelling and further inflammation.
Acute pancreatitis can lead to complications in other tissue as well, such as fat necrosis leading to the release of fatty acids from adipose tissue. The fatty acids bind to circulating calcium and may cause tetanus of the skeletal muscle as a result of calcium deficiency. If the enzymes released from the exocrine cells destroy the endocrine cells, the resulting loss of hormone production will lead to hyperglycemia and the complications that stem from it. Cysts or abscesses may also result from acute pancreatitis. Although this disease is usually self-limiting, in many cases it will lead to death.
Chronic pancreatitis is a recurring disease that may also demonstrate acute episodes. It has generally been associated with chronic alcoholism, which seems to be the major cause. Chronic pancreatitis is primarily a disease of middle age and occurs more frequently in men than in women. The patient generally complains of abdominal or back pain, often after a large meal or excessive alcohol consumption. Because of the lack of enzymes for lipid digestion, patients often excrete large quantities of undigested lipids. Without fat absorption, many fat-soluble substances such as vitamins A, D, E, and K will not be absorbed.
Because the patient with chronic pancreatitis is often malnourished from inadequate digestion and absorption of food and from vitamin deficiencies, there is associated weight loss and muscular wasting. The exocrine portion of the pancreas is gradually replaced by scar tissue, but the endocrine cells remain unaffected.
Disease of the pancreas can also be caused by cystic fibrosis. Cystic fibrosis, also known as mucoviscidosis, is an autosomal recessive disease of the exocrine glands. It occurs in about 1 in 2,500 live births of Caucasians but rarely occurs in African Americans or Asians. Cystic fibrosis affects the mucus-secreting glands in the body and leads to the production of abnormally thick mucus. About 80 percent of these patients have involvement of the pancreas. The onset and severity of the disease vary widely, but most infants born with cystic fibrosis have a pancreas that appears to be normal. As the abnormal mucus is produced, however, it may block the ducts of the exocrine glands and lead to the destruction of the exocrine tissue. The glandular tissue is progressively replaced by fibrous or adipose tissue or by cysts. The loss of pancreatic activity may lead to malabsorption of nutrients and vitamins. Although the islets of Langerhans are not affected by the disease in its early stages, eventually they also may be destroyed.
Tumors of the pancreas are primary tumors; there is almost no incidence of tumors metastasizing to the pancreas from other locations in the body. The exocrine tumors are generally adenocarcinomas, a type of cancer that is increasing in frequency throughout the world. An association with cigarette smoking and diabetes mellitus has been established. The tumors most commonly occur in the area of the gland where the major ducts leave the pancreas. As the tumors enlarge, they may put excessive pressure on the common bile duct, which is located in the same region. This pressure leads to the backup of bile in the liver known as obstructive jaundice; this is one of the earliest signs of pathology. Tumors located at other sites will not be detected until much later because they do not produce symptoms. Metastases of these tumors may be to the liver or surrounding lymph nodes. Because diagnosis is usually after the disease has progressed, the prognosis is poor even in operable cases.
The most common disease of the endocrine portion of the pancreas is diabetes mellitus. In 2009, over 68,000 individuals died of diabetes in the United States. Diabetes is a chronic disorder affecting carbohydrate, fat, and protein metabolism. It may be further classified as insulin-dependent or juvenile diabetes (type 1), non-insulin-dependent or adult-onset diabetes (type 2), or secondary diabetes. All forms of diabetes have a common pattern in which insulin is present in insufficient quantities, is absent, or does not function normally—all of which lead to hyperglycemia. Both type 1 and type 2 diabetes are inherited. In identical twins, there is a 50 percent concordance rate for type 1 and a 90 percent concordance for type 2. The latter figure indicates that heredity plays a more important role in type 2 diabetes.
Patients with type 1 diabetes are insulin-dependent. The disease starts at an early age and is sometimes referred to as juvenile diabetes. The decrease in insulin supply is caused by a decrease in functional beta cells in the islets of Langerhans. Evidence indicates that the beta cells are damaged or destroyed by an autoimmune reaction, which may follow a viral infection. Type 1 diabetics often have other endocrine disorders that are a result of autoimmunity. Type 2 diabetics produce some insulin, but not sufficient quantities. It appears that the tissues of these patients are resistant to insulin. The symptoms are less severe than those associated with type 1. Secondary diabetes is a result of some other disease that causes injury or destruction of beta cells. Diseases such as chronic pancreatitis or carcinoma of the pancreas can interfere with insulin production. The severity of the three forms of the disease varies widely, as does the treatment. The type 1 diabetic requires insulin for survival, while in many type 2 diabetics the disease may be controlled by diet and exercise.
Although the presence of insulin has several effects on the body, the lack of insulin has the most pronounced effect on serum glucose levels. If insulin supply is diminished or if the cells do not respond to the insulin produced, there is a rise in blood glucose levels exceeding the amount that the kidney can retain. As a result, glucose is excreted in the urine along with large quantities of water. The loss of glucose and water may lead to hypoglycemia and dehydration. The problem is further complicated if there is inadequate glucose available, which causes the cells to metabolize fats. One of the by-products of fat metabolism is the production of chemicals known as ketones, which are acids. Thus the dehydration may be accompanied by a more acidic serum.
The symptoms described above are acute and demand immediate attention. In addition to these symptoms, many abnormalities may appear in patients who have diabetes for ten or more years. The cardiovascular system is highly vulnerable to the disease, and the cause of death in about 80 percent of diabetics is a cardiovascular abnormality.
Since the pancreas is a vital organ, any disease or injury to it will have serious consequences. Problems with the pancreas may be magnified because the diseases associated with the exocrine portion of the gland are not easily detected. In acute cases of pancreatitis, the onset is sudden and requires immediate treatment to control the extent of the disease. Even when the disease is treated early, many patients die. Surgery is complicated by the inflammation and hemorrhaging that may have previously occurred.
Chronic pancreatitis and cancer of the pancreas are even more difficult to diagnose since many of the symptoms are common to other ailments and may not even be present until the disease has progressed to an acute stage. The chronic condition is complicated because the body cannot absorb nutrients and vitamins. By the time that the diagnosis has occurred, the patient is weakened by the loss of weight and muscular wasting from malnutrition.
Diabetes presents its own unique set of problems. In type 1 diabetes, the patient is often unable to follow the prescribed diet and must continually monitor his or her glucose levels to ensure that the insulin doses are appropriate. Assuming that the patient is able to follow the diet and takes the medication as prescribed, there will still be complications—particularly of the cardiovascular system—that may include renal damage.
Pancreas transplants provide type 1 diabetics with hope when all other standard treatments have failed and they are faced with serious and often life-threatening complications. Pancreatic transplants are often performed in conjunction with a kidney transplant since the majority of patients are in the end states of renal failure, but the procedure is rarely performed on individuals suffering from pancreatic cancer because that form of cancer is highly malignant and the probability of it returning and attacking the new pancreas is very high .
Pancreatic transplants usually involve implanting a healthy (and insulin producing) organ into a patient while leaving the original pancreas in place since it is still able to produce essential digestive enzymes. Following surgery, many patients are able to maintain normal blood glucose levels, and diabetes-related nerve damage is often stabilized and sometimes repaired following transplantation. The risks involved in the surgery, however, are significant and should be taken into consideration: In addition to the potential for blood clots, infection, and inflammation of the new pancreas, rejection of the new organ is of great concern and can occur immediately following the surgery or at any time during the recipient's life. Because of this threat, the patient must take powerful immunosuppressive drugs for the remainder of his or her life, and these drugs come with their own set of potential side effects such as thinning of the bones, high cholesterol and blood pressure, weight gain, and acne and excessive hair growth over the body.
New procedures have been employed that involve the transplantation of only the beta cells of the islets of Langerhans rather than of the entire organ. Similar side effects and risks, such as blood clots and the necessity of immunosuppressive drugs, are also associated with this procedure.
It is likely that there will be significant progress with the treatment of diabetes as more becomes known about somatic gene therapy, cell transplants, immunosuppression, and the control of insulin receptors.
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