Pancreas

The pancreas /ˈpæŋkriəs/ is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity behind the stomach.

The pancreas is a mixed gland, having both an endocrine and an exocrine function. As an endocrine gland, it secretes into the blood several important hormones, including insulin, glucagon, somatostatin, and pancreatic polypeptide. As an exocrine gland, it secretes 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 lipids in ingested food entering the duodenum from the stomach.

Pancreas
Blausen 0699 PancreasAnatomy2
Anatomy of the pancreas
Illu pancreas duodenum
1: Head of pancreas
2: Uncinate process of pancreas
3: Pancreatic notch
4: Body of pancreas
5: Anterior surface of pancreas
6: Inferior surface of pancreas
7: Superior margin of pancreas
8: Anterior margin of pancreas
9: Inferior margin of pancreas
10: Omental tuber
11: Tail of pancreas
12: Duodenum
Details
PrecursorPancreatic buds
ArteryInferior pancreaticoduodenal artery, anterior superior pancreaticoduodenal artery, posterior superior pancreaticoduodenal artery, splenic artery
VeinPancreaticoduodenal veins, pancreatic veins
NervePancreatic plexus, celiac ganglia, vagus nerve[1]
LymphSplenic lymph nodes, celiac lymph nodes and superior mesenteric lymph nodes
Identifiers
LatinPancreas
GreekΠάγκρεας (Pánkreas)
MeSHD010179
TAA05.9.01.001
FMA7198
Anatomical terminology

Structure

Biliary system multilingual
1. Bile ducts: 2. Intrahepatic bile ducts, 3. Left and right hepatic ducts, 4. Common hepatic duct, 5. Cystic duct, 6. Common bile duct, 7. Ampulla of Vater, 8. Major duodenal papilla
9. Gallbladder, 10–11. Right and left lobes of liver. 12. Spleen.
13. Esophagus. 14. Stomach. 15. Pancreas: 16. Accessory pancreatic duct, 17. Pancreatic duct.
18. Small intestine: 19. Duodenum, 20. Jejunum
21–22. Right and left kidneys.
The front border of the liver has been lifted up (brown arrow).[2]

The pancreas is an organ that in humans lies in the upper left part of the abdomen. It is found behind the stomach.[3] The pancreas is about 15 cm (6 in) long.[4]

Anatomically, the pancreas is divided into the head of pancreas, the neck of pancreas, the body of pancreas, and the tail of pancreas. The head is surrounded by the duodenum in its concavity. The head surrounds two blood vessels, the superior mesenteric artery and vein. From the back of the head emerges a small uncinate process, which extends to the back of the superior mesenteric vein and ends at the superior mesenteric artery.[5] The neck is about 2.5 cm (1 in) long and lies between the head and the body and in front of the superior mesenteric artery and vein. Its front upper surface supports the pylorus (the base) of the stomach. The neck arises from the left upper part of the front of the head. It is directed first upward and forward, and then upward and to the left to join the body; it is somewhat flattened from above downward and backward. On the right it is grooved by the gastroduodenal artery. The body is the largest part of the pancreas and lies behind the pylorus, at the same level as the transpyloric plane.[6] The tail ends by abutting the spleen.

The pancreas is a secretory structure with an internal hormonal role (endocrine) and an external digestive role (exocrine). The endocrine part is composed of hormonal tissue distributed along the pancreas in discrete units called islets of Langerhans. Islets of Langerhans have a well-established structure and form density routes through the exocrine tissue. The exocrine part has two main ducts, the main pancreatic duct and the accessory pancreatic duct. These drain enzymes through the ampulla of Vater into the duodenum.[7]

Margins

The upper margin of the pancreas is blunt and flat to the right, and narrow and sharp to the left, near the tail.

It begins on the right in the omental tuber, and is in relation with the celiac artery, from which the hepatic artery courses to the right just above the gland, while the splenic artery runs toward the left in a groove along this border.

The lower margin of the pancreas separates the posterior from the inferior surface; the superior mesenteric vessels emerge under its right extremity.

The frontal margin of the pancreas separates the anterior from the inferior surface of the pancreas, and along this border the two layers of the transverse mesocolon diverge from one another, one passing upward over the frontal surface, the other backward over the inferior surface.

Surfaces

The inferior surface of the pancreas is narrow on the right, broader on the left, and covered by peritoneum; it lies upon the duodenojejunal flexure and on some coils of the jejunum; its left extremity rests on the splenic flexure of the colon.

The anterior surface of the pancreas faces the front of the abdomen. Most of the right half of this surface is in contact with the transverse colon, with only areolar tissue intervening.

From its upper part, it joins to the neck of the pancreas at a well-marked prominence, the omental tuber, which abuts the lesser omentum. Its right edge is marked by a groove for the gastroduodenal artery.

The lower part of the right half, below the transverse colon, is covered by peritoneum continuous with the inferior layer of the transverse mesocolon, and is in contact with the coils of the small intestine.

The superior mesenteric artery passes down in front of the left half across the uncinate process; the superior mesenteric vein runs upward on the right side of the artery and, behind the neck, joins with the lienal vein to form the portal vein.

Blood supply

The pancreas receives blood from branches of both the coeliac artery and superior mesenteric artery. The splenic artery runs along the top margin of the pancreas, and supplies the neck, body and 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 anterior and posterior surfaces of the head of the pancreas at its border with the duodenum. These supply the head of the pancreas.[5]

The body and neck of the pancreas drain into the splenic vein; the head drains into the superior mesenteric and portal veins.[5]

Histology

Blausen 0701 PancreaticTissue
Pancreatic tissue, including a pancreatic islet

The pancreas contains tissue with an endocrine and exocrine role, and this division is also visible when the pancreas is viewed under a microscope.[7]

The tissues with an endocrine role can be seen under staining as lightly-stained clusters of cells, called pancreatic islets (also called islets of Langerhans).[7]

Darker-staining cells form clusters called acini, which are arranged in lobes separated by a thin fibrous barrier. The secretory cells of each acinus surround a small intercalated duct. Because of their secretory function, these cells have many small granules of zymogens that are visible. The intercalated ducts drain into larger ducts within the lobule, and finally interlobular ducts. The ducts are lined by a single layer of columnar epithelium. With increasing diameter, several layers of columnar cells may be seen.[7]

Variation

The size of the pancreas varies considerably.[3] Several anatomical variations exist, relating to the embryological development of the two pancreatic buds. The pancreas develops from these buds on either side of the duodenum. The ventral bud eventually rotates to lie next to the dorsal bud, eventually fusing. If the two buds, each having a duct, do not fuse, a pancreas may exist with two separate ducts, a condition known as a pancreas divisum. This condition has no physiologic consequence.[8] If the ventral bud does not fully rotate, an annular pancreas may exist. This is where sections of the pancreas completely encircle the duodenum, and may even lead to duodenal atresia.[5]

An accessory pancreatic duct may exist if the main duct of the pancreas does not regress.[9]

Development

Suckale08FBS fig1 pancreas development.jpeg
Schematic illustrating the development of the pancreas from a dorsal and a ventral bud. During maturation, the ventral bud flips to the other side of the gut tube (arrow) where it typically fuses with the dorsal lobe. An additional ventral lobe that usually regresses during development is omitted.

As part of embryonic development, the pancreas forms from the embryonic foregut and is therefore of endodermal origin. Pancreatic development begins with the formation of a ventral and a dorsal pancreatic bud. Each structure communicates with the foregut through a duct. The dorsal pancreatic bud forms the neck, body, and tail, whereas the ventral pancreatic bud forms the head and uncinate process.[9]

Differential rotation and fusion of the ventral and dorsal pancreatic buds results in the formation of the definitive pancreas.[10] As the duodenum rotates to the right, it carries with it the ventral pancreatic bud and common bile duct. Upon reaching its final destination, the ventral pancreatic bud fuses with the much larger dorsal pancreatic bud. At this point of fusion, the main ducts of the ventral and dorsal pancreatic buds fuse, forming the main pancreatic duct. The duct of the dorsal bud regresses, leaving the main pancreatic duct.[9]

Differentiation of cells of the pancreas proceeds through two different pathways, corresponding to the dual endocrine and exocrine functions of the pancreas. In progenitor cells of the exocrine pancreas, important molecules that induce differentiation include follistatin, fibroblast growth factors, and activation of the Notch receptor system.[10] Development of the exocrine acini progresses through three successive stages. These are the predifferentiated, protodifferentiated, and differentiated stages, which correspond to undetectable, low, and high levels of digestive enzyme activity, respectively.

The multi-potent pancreatic progenitor cells have the capacity to differentiate into any of the pancreatic cells: acinar cells, endocrine cells, and ductal cells. These progenitor cells are characterised by the co-expression of the transcription factors PDX1 and NKX6-1. Under the influence of neurogenin-3 and ISL1, but in the absence of notch receptor signaling, these cells differentiate to form two lines of committed endocrine precursor cells. The first line, under the direction of a Pax gene, forms α- and γ- cells, which produce glucagon and pancreatic polypeptides, respectively. The second line, influenced by Pax-6, produces beta cells (β-) and delta cells (δ-), which secrete insulin and somatostatin, respectively.

Insulin and glucagon can be detected in the human fetal circulation by the fourth or fifth month of fetal development.[10]

Function

The pancreas is involved in blood sugar control and metabolism within the body, and also in the secretion of substances (collectively pancreatic juice) which help digestion. Classically, these are divided into an "endocrine" role, relating to the secretion of insulin and other substances within pancreatic islets and helping control blood sugar levels and metabolism within the body, and an "exocrine" role, relating to the secretion of enzymes involved in digesting substances from outside of the body.

Sugar control and metabolism

Negative Feedback Gif
Blood glucose levels are maintained at a constant level in the body by a negative feedback mechanism. When the blood glucose level is too high, the pancreas secretes insulin and when the level is too low, the pancreas then secretes glucagon. The flat line shown represents the homeostatic set point. The sinusoidal line represents the blood glucose level.

Approximately 3 million cell clusters called pancreatic islets are present in the pancreas. Within these islets are four main types of cells which are involved in the regulation of blood glucose levels. Each type of cell secretes a different type of hormone: α alpha cells secrete glucagon (increase glucose in blood), β beta cells secrete insulin (decrease glucose in blood), δ delta cells secrete somatostatin (regulates/stops α and β cells) and PP cells, or γ (gamma) cells, secrete pancreatic polypeptide.[11] These act to control blood glucose through secreting glucagon to increase the levels of glucose, and insulin to decrease it.

The islets are crisscrossed by a dense network of capillaries. The capillaries of the islets are lined by layers of islet cells, and most endocrine cells are in direct contact with blood vessels, either by cytoplasmic processes or by direct apposition. The islets function independently from the digestive role played by the majority of pancreatic cells.[12]

Activity of the cells in the islets is affected by the autonomic nervous system:

Sympathetic (adrenergic)
α2: decreases secretion from beta cells, increases secretion from alpha cells, β2: increases secretion from beta cells
Parasympathetic (muscarinic)
M3: increases stimulation of alpha cells and beta cells[13]

Digestion

The pancreas plays a vital role in the digestive system. It secretes a fluid that contains enzymes into the duodenum. These enzymes help to break down carbohydrates (usually starch), proteins and lipids (fats). This role is called the "exocrine" role of the pancreas. Cells are arranged in clusters called acini. Secretes into the middle of the acinus, which accumulates in intralobular ducts, which drain to the main pancreatic duct, which drains directly into the duodenum.

The cells 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 enteropeptidase present in the lining of the duodenum. The proenzymes are cleaved, creating a cascade of activating enzymes: enteropeptidase activates the proenzyme trypsinogen by cleaving it to form trypsin. The free trypsin then cleaves the rest of the trypsinogen, as well as chymotrypsinogen to its active form chymotrypsin.

The pancreas secretes substances which help in the digestion of starch and other carbohydrates, proteins and fats.[14] Proteases, the enzymes involved in the digestion of proteins, include trypsinogen and chymotrypsinogen. The enzyme involved in the digestion of fats is lipase. Amylase, also secreted by the pancreas, breaks down starch (amylum) and other carbohydrates. The pancreas also secretes phospholipase A2, lysophospholipase, and cholesterol esterase.

Secretion of these proenzymes is via the hormones gastrin, cholecystokinin and secretin, which are secreted by cells in the stomach and duodenum in response to distension and/or food.

Gene and protein expression

10,000 protein coding genes (50% of all genes) are expressed in the normal human pancreas.[15][16] Less than 100 of these genes are more specifically expressed in the pancreas. Similar to the salivary glands, most of the pancreas specific genes encode for secreted proteins. Corresponding pancreas specific proteins are either expressed in the exocrine cellular compartment and have functions related to digestion of food uptake such as digestive chymotrypsinogen enzymes and pancreatic lipase PNLIP, or expressed in the various cells of the endocrine pancreatic islets and have functions related to secreted hormones such as insulin, glucagon, somatostatin and pancreatic polypeptide.[17]

Clinical significance

Labeled Pancreas and duodenum
Pancreas parts

A perforation of the pancreas, which may lead to the secretion of digestive enzymes such as lipase and amylase into the abdominal cavity as well as subsequent pancreatic self-digestion and digestion and damage to organs within the abdomen, generally requires prompt and experienced medical intervention.

It is possible for one to live without a pancreas, provided that the person takes insulin for proper regulation of blood glucose concentration and pancreatic enzyme supplements to aid digestion.[18]

Inflammation

Inflammation of the pancreas is known as pancreatitis. Pancreatitis is most often associated with recurrent gallstones or chronic alcohol use, although a variety of other causes, including measles, mumps, some medications, the congenital condition alpha-1 antitrypsin deficiency and even some scorpion stings, may cause pancreatitis. Pancreatitis is likely to cause intense pain in the central abdomen, that often radiates to the back, and may be associated with jaundice. In addition, due to causing problems with fat digestion and bilirubin excretion, pancreatitis often presents with pale stools and dark urine.[19]

In pancreatitis, enzymes of the exocrine pancreas damage the structure and tissue of the pancreas. Detection of some of these enzymes, such as amylase and lipase in the blood, along with symptoms and findings on x-ray, are often used to indicate that a person has pancreatitis. A person with pancreatitis is also at risk of shock. Pancreatitis is often managed medically with analgesics, removal of gallstones or treatment of other causes, and monitoring to ensure a patient does not develop shock.[19]

Cancer

Pancreatic Cancer
Pancreatic Cancer.

Pancreatic cancers, particularly the most common type, pancreatic adenocarcinoma, remain very difficult to treat, and are mostly diagnosed only at a stage that is too late for surgery, which is the only curative treatment. Pancreatic cancer is rare in those younger than 40, and the median age of diagnosis is 71.[20] Risk factors include smoking, obesity, diabetes, and certain rare genetic conditions including multiple endocrine neoplasia type 1 and hereditary nonpolyposis colon cancer among others.[21] About 25% of cases are attributable to tobacco smoking,[22] while 5–10% of cases are linked to inherited genes.[20]

There are several types of pancreatic cancer, involving both the endocrine and exocrine tissue. Pancreatic adenocarcinoma, which affects the exocrine part of the pancreas, is by far the most common form. The many types of pancreatic endocrine tumors are all uncommon or rare, and have varied outlooks. However the incidence of these cancers has been rising sharply; it is not clear to what extent this reflects increased detection, especially through medical imaging, of tumors that would be very slow to develop. Insulinomas (largely benign) and gastrinomas are the most common types.[23] In the United States pancreatic cancer is the fourth most common cause of deaths due to cancer.[24] The disease occurs more often in the developed world, which had 68% of new cases in 2012.[25] Pancreatic adenocarcinoma typically has poor outcomes with the average percentage alive for at least one and five years after diagnosis being 25% and 5% respectively.[25][26] In localized disease where the cancer is small (< 2 cm) the number alive at five years is approximately 20%.[27] For those with neuroendocrine cancers the number alive after five years is much better at 65%, varying considerably with type.[25]

A solid pseudopapillary tumour is a low-grade malignant tumour of the pancreas of papillary architecture that typically afflicts young women.[28]

Diabetes Mellitus

Type 1 diabetes

Diabetes mellitus type 1 is a chronic autoimmune disorder in which the immune system attacks the insulin-secreting cells of the pancreas. Insulin is needed to keep blood sugar levels within optimal ranges, and its lack can lead to high blood sugar. As an untreated chronic condition, diabetic neuropathy can result. Type 1 diabetes can develop at any age but is most often diagnosed before adulthood. For people living with type 1 diabetes, insulin injections are critical for survival.[29]

An experimental procedure to treat type 1 diabetes is the transplantation of pancreatic islet cells from a donor into the patient's liver so that the cells can produce the deficient insulin.[30]

Type 2 diabetes

Diabetes mellitus type 2 is the most common form of diabetes. The causes for high blood sugar in this form of diabetes usually are a combination of insulin resistance and impaired insulin secretion, with both genetic and environmental factors playing an important role in the development of the disease. The management of type 2 diabetes relies on a series of changes in diet and physical activity with the purpose of reducing blood sugar levels to normal ranges and increasing insulin sensitivity.[29] Biguanides such as metformin are also used as part of the treatment along with insulin therapy.[31]

History

The pancreas was first identified by Herophilus (335–280 BC), a Greek anatomist and surgeon.[32] A few hundred years later, Rufus of Ephesus, another Greek anatomist, gave the pancreas its name. Etymologically, the term "pancreas", a modern Latin adaptation of Greek πάγκρεας,[33] [πᾶν ("all", "whole"), and κρέας ("flesh")],[34] originally means sweetbread,[35] although literally meaning all-flesh, presumably because of its fleshy consistency. It was only in 1889 when Oskar Minkowski discovered that removing the pancreas from a dog caused it to become diabetic (insulin was later discovered by Frederick Banting and Charles Herbert Best in 1921).

Other animals

Pancreatic tissue is present in all vertebrates, but its precise form and arrangement varies widely. There may be up to three separate pancreases, two of which arise from ventral buds, and the other dorsally. In most species (including humans), these "fuse" in the adult, but there are several exceptions. Even when a single pancreas is present, two or three pancreatic ducts may persist, each draining separately into the duodenum (or equivalent part of the foregut). Birds, for example, typically have three such ducts.[36]

In teleosts, and a few other species (such as rabbits), there is no discrete pancreas at all, with pancreatic tissue being distributed diffusely across the mesentery and even within other nearby organs, such as the liver or spleen. In a few teleost species, the endocrine tissue has fused to form a distinct gland within the abdominal cavity, but otherwise it is distributed among the exocrine components. The most primitive arrangement, however, appears to be that of lampreys and lungfish, in which pancreatic tissue is found as a number of discrete nodules within the wall of the gut itself, with the exocrine portions being little different from other glandular structures of the intestine.[36]

Cuisine

The pancreas of calf (ris de veau) and lamb (ris d'agneau), and, less commonly, of beef and pork, are used as food under the culinary name of sweetbread.[37]

Additional images

Gray1098

The duodenum and pancreas

Gray1102

Pancreas of a human embryo at end of sixth week

Dogpancreas100x4

Dog pancreas magnified 100 times

Sobo 1906 393

The pancreas and its surrounding structures

Slide2duo

Duodenum and pancreas. Deep dissection.

References

This article incorporates text in the public domain from page 1199 of the 20th edition of Gray's Anatomy (1918)

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External links

Acute pancreatitis

Acute pancreatitis is a sudden inflammation of the pancreas. Causes in order of frequency include a gallstone impacted in the common bile duct beyond the point where the pancreatic duct joins it; heavy alcohol use; systemic disease; trauma; and, in minors, mumps. Acute pancreatitis may be a single event; it may be recurrent; or it may progress to chronic pancreatitis.

Mild cases are usually successfully treated with conservative measures: hospitalization, pain control, nothing by mouth, intravenous nutritional support, and intravenous fluid rehydration. Severe cases often require admission to an intensive care unit to monitor and manage complications of the disease. Complications are associated with a high mortality, even with optimal management.

Artificial pancreas

The artificial pancreas is a technology in development to help people with diabetes, primarily type 1, automatically and continuously control their blood glucose level by providing the substitute endocrine functionality of a healthy pancreas.

The endocrine functionality of the pancreas is provided by islet cells which produce the hormones insulin and glucagon. Artificial pancreatic technology mimics the secretion of these hormones into the bloodstream in response to the body's changing blood glucose levels. Maintaining balanced blood sugar levels is crucial to the function of the brain, liver, and kidneys. Therefore, for type 1 patients, it is necessary that the levels be kept balanced when the body cannot produce insulin itself.The artificial pancreas is a broad term for different bio-engineering strategies currently in development to achieve these requirements. Different bio-engineering approaches under consideration include:

the medical equipment approach—using an insulin pump under closed loop control using real-time feedback data from a continuous blood glucose monitor.

the physiological approach—the development of a treatment with engineered stem cells to be integrated into the body to provide functional blood glucose regulation.

Chronic pancreatitis

Chronic pancreatitis is a long-standing inflammation of the pancreas that alters the organ's normal structure and functions. It can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pain or malabsorption. It is a disease process characterized by irreversible damage to the pancreas as distinct from reversible changes in acute pancreatitis.

Cystic fibrosis

Cystic fibrosis (CF) is a genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Other signs and symptoms may include sinus infections, poor growth, fatty stool, clubbing of the fingers and toes, and infertility in most males. Different people may have different degrees of symptoms.CF is inherited in an autosomal recessive manner. It is caused by the presence of mutations in both copies of the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Those with a single working copy are carriers and otherwise mostly normal. CFTR is involved in production of sweat, digestive fluids, and mucus. When the CFTR is not functional, secretions which are usually thin instead become thick. The condition is diagnosed by a sweat test and genetic testing. Screening of infants at birth takes place in some areas of the world.There is no known cure for cystic fibrosis. Lung infections are treated with antibiotics which may be given intravenously, inhaled, or by mouth. Sometimes, the antibiotic azithromycin is used long term. Inhaled hypertonic saline and salbutamol may also be useful. Lung transplantation may be an option if lung function continues to worsen. Pancreatic enzyme replacement and fat-soluble vitamin supplementation are important, especially in the young. Airway clearance techniques such as chest physiotherapy have some short-term benefit, but long-term effects are unclear. The average life expectancy is between 42 and 50 years in the developed world. Lung problems are responsible for death in 80% of people with cystic fibrosis.CF is most common among people of Northern European ancestry and affects about one out of every 3,000 newborns. About one in 25 people is a carrier. It is least common in Africans and Asians. It was first recognized as a specific disease by Dorothy Andersen in 1938, with descriptions that fit the condition occurring at least as far back as 1595. The name "cystic fibrosis" refers to the characteristic fibrosis and cysts that form within the pancreas.

Digestive enzyme

Digestive enzymes are a group of enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption by the body. Digestive enzymes are found in the digestive tracts of animals (including humans) and in the traps of carnivorous plants, where they aid in the digestion of food, as well as inside cells, especially in their lysosomes, where they function to maintain cellular survival. Digestive enzymes of diverse specificities are found in the saliva secreted by the salivary glands, in the secretions of cells lining

Proteases and peptidases split proteins into small peptides and amino acids.

Lipases split fat into three fatty acids and a glycerol molecule.

Amylases split carbohydrates such as starch and sugars into simple sugars such as glucose.

Nucleases split nucleic acids into nucleotides.In the human digestive system, the main sites of digestion are the oral cavity, the stomach, and the small intestine. Digestive enzymes are secreted by different exocrine glands including:

Salivary glands

Gastric glands in the stomach

Secretory cells(eyeslit) in the pancreas

Secretory glands in the small intestine

Exocrine pancreatic insufficiency

Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack of digestive enzymes made by the pancreas. EPI is found in humans afflicted with cystic fibrosis and Shwachman–Diamond syndrome, and is common in dogs. EPI is caused by a progressive loss of the pancreatic cells that make digestive enzymes; loss of digestive enzymes leads to maldigestion and malabsorption of nutrients from normal digestive processes.

Chronic pancreatitis is the most common cause of EPI in humans and cats. In dogs, the most common cause is pancreatic acinar atrophy, arising as a result of genetic conditions, a blocked pancreatic duct, or prior infection.

The exocrine pancreas is a portion of this organ that contains clusters of ducts (acini) producing bicarbonate anion, a mild alkali, as well as an array of digestive enzymes that together empty by way of the interlobular and main pancreatic ducts into the duodenum (upper small intestine). The hormones cholecystokinin and secretin secreted by the stomach and duodenum in response to distension and the presence of food in turn stimulate the production of digestive enzymes by the exocrine pancreas. The alkalization of the duodenum neutralizes the acidic chyme produced by the stomach that is passing into it; the digestive enzymes serve to catalyze the breakdown of complex foodstuffs into smaller molecules for absorption and integration into metabolic pathways. The enzymes include proteases (trypsinogen and chymotrypsinogen), hydrolytic enzymes that cleave lipids (the lipases phospholipase A2 and lysophospholipase, and cholesterol esterase), and amylase to digest starches. EPI results from progressive failure in the exocrine function of the pancreas to provide its digestive enzymes, often in response to a genetic condition or other disease state, resulting in the inability of the animal involved to properly digest food.

Glucagon

Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It works to raise the concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers the extracellular glucose.The pancreas releases glucagon when the concentration of insulin (and indirectly glucose) in the bloodstream falls too low. Glucagon causes the liver to convert stored glycogen into glucose, which is released into the bloodstream. High blood-glucose levels, on the other hand, stimulate the release of insulin. Insulin allows glucose to be taken up and used by insulin-dependent tissues. Thus, glucagon and insulin are part of a feedback system that keeps blood glucose levels stable. Glucagon increases energy expenditure and is elevated under conditions of stress. Glucagon belongs to the secretin family of hormones.

Human digestive system

The human digestive system consists of the gastrointestinal tract plus the accessory organs of digestion (the tongue, salivary glands, pancreas, liver, and gallbladder). Digestion involves the breakdown of food into smaller and smaller components, until they can be absorbed and assimilated into the body. The process of digestion has many stages. The first stage is the cephalic phase of digestion which begins with gastric secretions in response to the sight and smell of food. The next stage starts in the mouth.

Chewing, in which food is mixed with saliva, begins the mechanical process of digestion. This produces a bolus which can be swallowed down the esophagus to enter the stomach. Here it is mixed with gastric acid until it passes into the duodenum where it is mixed with a number of enzymes produced by the pancreas. Saliva also contains a catalytic enzyme called amylase which starts to act on food in the mouth. Another digestive enzyme called lingual lipase is secreted by some of the lingual papillae on the tongue and also from serous glands in the main salivary glands. Digestion is helped by the chewing of food carried out by the muscles of mastication, by the teeth, and also by the contractions of peristalsis, and segmentation. Gastric acid, and the production of mucus in the stomach, are essential for the continuation of digestion.

Peristalsis is the rhythmic contraction of muscles that begins in the esophagus and continues along the wall of the stomach and the rest of the gastrointestinal tract. This initially results in the production of chyme which when fully broken down in the small intestine is absorbed as chyle into the lymphatic system. Most of the digestion of food takes place in the small intestine. Water and some minerals are reabsorbed back into the blood in the colon of the large intestine. The waste products of digestion (feces) are defecated from the anus via the rectum.

Kidney transplantation

Kidney transplantation or renal transplantation is the organ transplant of a kidney into a patient with end-stage renal disease. Kidney transplantation is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantation depending on the source of the donor organ.

Living-donor renal transplants are further characterized as genetically related (living-related) or non-related (living-unrelated) transplants, depending on whether a biological relationship exists between the donor and recipient.

Exchanges and chains are a novel approach to expand the living donor pool. In February 2012, this novel approach to expand the living donor pool resulted in the largest chain in the world, involving 60 participants organized by the National Kidney Registry. In 2014 the record for the largest chain was broken again by a swap involving 70 participants.

Pancreas transplantation

A pancreas transplant is an organ transplant that involves implanting a healthy pancreas (one that can produce insulin) into a person who usually has diabetes. Because the pancreas is a vital organ, performing functions necessary in the digestion process, the recipient's native pancreas is left in place, and the donated pancreas is attached in a different location. In the event of rejection of the new pancreas, which would quickly cause life-threatening diabetes, there would be a significant chance the recipient would not survive very well for long without the native pancreas, however dysfunctional, still in place. The healthy pancreas comes from a donor who has just died or it may be a partial pancreas from a living donor. At present, pancreas transplants are usually performed in persons with insulin-dependent diabetes, who can develop severe complications. Patients with the most common, and deadliest, form of pancreatic cancer (pancreatic adenomas, which are usually malignant, with a poor prognosis and high risk for metastasis, as opposed to more treatable pancreatic neuroendocrine tumors or pancreatic insulinomas) are usually not eligible for valuable pancreatic transplantations, since the condition usually has a very high mortality rate and the disease, which is usually highly malignant and detected too late to treat, could and probably would soon return. Better surgical method can be chosen to minimize the surgical complications with enteric or bladder drainage. Advancement in immunosuppression has improved quality of life after transplantation.

Pancreatic abscess

Pancreatic abscess is a late complication of acute necrotizing pancreatitis, occurring more than 4 weeks after the initial attack. A pancreatic abscess is a collection of pus resulting from tissue necrosis, liquefaction, and infection. It is estimated that approximately 3% of the patients suffering from acute pancreatitis will develop an abscess.According to the Balthazar and Ranson's radiographic staging criteria, patients with a normal pancreas, an enlargement that is focal or diffuse, mild peripancreatic inflammations or a single collection of fluid (pseudocyst) have less than 2% chances of developing an abscess. However, the probability of developing an abscess increases to nearly 60% in patients with more than two pseudocysts and gas within the pancreas.

Pancreatic cancer

Pancreatic cancer arises when cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a mass. These cancerous cells have the ability to invade other parts of the body. There are a number of types of pancreatic cancer. The most common, pancreatic adenocarcinoma, accounts for about 85% of cases, and the term "pancreatic cancer" is sometimes used to refer only to that type. These adenocarcinomas start within the part of the pancreas which makes digestive enzymes. Several other types of cancer, which collectively represent the majority of the non-adenocarcinomas, can also arise from these cells. One to two percent of cases of pancreatic cancer are neuroendocrine tumors, which arise from the hormone-producing cells of the pancreas. These are generally less aggressive than pancreatic adenocarcinoma.Signs and symptoms of the most common form of pancreatic cancer may include yellow skin, abdominal or back pain, unexplained weight loss, light-colored stools, dark urine and loss of appetite. There are usually no symptoms in the disease's early stages, and symptoms that are specific enough to suggest pancreatic cancer typically do not develop until the disease has reached an advanced stage. By the time of diagnosis, pancreatic cancer has often spread to other parts of the body.Pancreatic cancer rarely occurs before the age of 40, and more than half of cases of pancreatic adenocarcinoma occur in those over 70. Risk factors for pancreatic cancer include tobacco smoking, obesity, diabetes, and certain rare genetic conditions. About 25% of cases are linked to smoking, and 5–10% are linked to inherited genes. Pancreatic cancer is usually diagnosed by a combination of medical imaging techniques such as ultrasound or computed tomography, blood tests, and examination of tissue samples (biopsy). The disease is divided into stages, from early (stage I) to late (stage IV). Screening the general population has not been found to be effective.The risk of developing pancreatic cancer is lower among non-smokers, and people who maintain a healthy weight and limit their consumption of red or processed meat. A smoker's chance of developing the disease decreases if they stop smoking, and almost returns to that of the rest of the population after 20 years. Pancreatic cancer can be treated with surgery, radiotherapy, chemotherapy, palliative care, or a combination of these. Treatment options are partly based on the cancer stage. Surgery is the only treatment that can cure pancreatic adenocarcinoma, and may also be done to improve quality of life without the potential for cure. Pain management and medications to improve digestion are sometimes needed. Early palliative care is recommended even for those receiving treatment that aims for a cure.In 2015, pancreatic cancers of all types resulted in 411,600 deaths globally. Pancreatic cancer is the fifth most common cause of death from cancer in the United Kingdom, and the fourth most common in the United States. The disease occurs most often in the developed world, where about 70% of the new cases in 2012 originated. Pancreatic adenocarcinoma typically has a very poor prognosis: after diagnosis, 25% of people survive one year and 5% live for five years. For cancers diagnosed early, the five-year survival rate rises to about 20%. Neuroendocrine cancers have better outcomes; at five years from diagnosis, 65% of those diagnosed are living, though survival varies considerably depending on the type of tumor.

Pancreatic islets

The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1 to 2% of the pancreas volume and receive 10–15% of its blood flow. The pancreatic islets are arranged in density routes throughout the human pancreas, and are important in the metabolism of glucose.

Pancreatic pseudocyst

A pancreatic pseudocyst is a circumscribed collection of fluid rich in pancreatic enzymes, blood, and necrotic tissue, typically located in the lesser sac of the abdomen. Pancreatic pseudocysts are usually complications of pancreatitis, although in children they frequently occur following abdominal trauma. Pancreatic pseudocysts account for approximately 75% of all pancreatic masses.

Pancreatic serous cystadenoma

Pancreatic serous cystadenoma a benign tumour of pancreas. It is usually found in the tail of the pancreas, and may be associated with von Hippel-Lindau syndrome.In contrast to some of the other cyst-forming tumors of the pancreas (such as the intraductal papillary mucinous neoplasm and the mucinous cystic neoplasm), serous cystic neoplasms are almost always entirely benign. There are some exceptions; rare case reports have described isolated malignant serous cystadenocarcinomas. In addition, serous cystic neoplasms slowly grow, and if they grow large enough they can press on adjacent organs and cause symptoms.

Pancreaticoduodenectomy

A pancreaticoduodenectomy, pancreatoduodenectomy, Whipple procedure, or Kausch-Whipple procedure is a major surgical operation most often performed to remove cancerous tumours off the head of the pancreas. It is also used for the treatment of pancreatic or duodenal trauma, or chronic pancreatitis. Due to the shared blood supply of organs in the proximal gastrointestinal system, surgical removal of the head of the pancreas also necessitates removal of the duodenum, proximal jejunum, gallbladder, and, occasionally, part of the stomach.

Pancreatitis

Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types, acute pancreatitis and chronic pancreatitis. Signs and symptoms of pancreatitis include pain in the upper abdomen, nausea and vomiting. The pain often goes into the back and is usually severe. In acute pancreatitis a fever may occur and symptoms typically resolve in a few days. In chronic pancreatitis weight loss, fatty stool, and diarrhea may occur. Complications may include infection, bleeding, diabetes mellitus, or problems with other organs.The two most common causes of acute pancreatitis are a gall stone blocking the common bile duct after the pancreatic duct has joined; and heavy alcohol use. Other causes include direct trauma, certain medications, infections such as mumps, and tumors. Chronic pancreatitis may develop as a result of acute pancreatitis. It is most commonly due to many years of heavy alcohol use. Other causes include high levels of blood fats, high blood calcium, some medications, and certain genetic disorders such as cystic fibrosis among others. Smoking increases the risk of both acute and chronic pancreatitis. Diagnosis of acute pancreatitis is based on a threefold increase in the blood of either amylase or lipase. In chronic pancreatitis these tests may be normal. Medical imaging such as ultrasound and CT scan may also be useful.Acute pancreatitis is usually treated with intravenous fluids, pain medication, and sometimes antibiotics. Typically eating and drinking are disallowed, and a nasogastric tube is placed in the stomach. A procedure known as an endoscopic retrograde cholangiopancreatography (ERCP) may be done to examine the distal common bile duct and remove a gallstone if present. In those with gallstones the gallbladder is often also removed. In chronic pancreatitis, in addition to the above, temporary feeding through a nasogastric tube may be used to provide adequate nutrition. Long-term dietary changes and pancreatic enzyme replacement may be required. And occasionally surgery is done to remove parts of the pancreas.Globally, in 2015 about 8.9 million cases of pancreatitis occurred. This resulted in 132,700 deaths, up from 83,000 deaths in 1990. Acute pancreatitis occurs in about 30 per 100,000 people a year. New cases of chronic pancreatitis develop in about 8 per 100,000 people a year and currently affect about 50 per 100,000 people in the United States. It is more common in men than women. Often chronic pancreatitis starts between the ages of 30 and 40 while it is rare in children. Acute pancreatitis was first described on autopsy in 1882 while chronic pancreatitis was first described in 1946.

Zollinger–Ellison syndrome

Zollinger–Ellison syndrome (ZES) is a disease in which tumors cause the stomach to produce too much acid, resulting in peptic ulcers. Symptoms include abdominal pain and diarrhea.

The syndrome is caused by a gastrinoma, a neuroendocrine tumor that secretes a hormone called gastrin. The tumor causes excessive production of gastric acid, which leads to the growth of gastric mucosa and proliferation of parietal and ECL cells.

ZES may occur on its own or as part of an autosomal dominant syndrome called multiple endocrine neoplasia type 1 (MEN 1). The primary tumor is usually located in the pancreas, duodenum or abdominal lymph nodes, but ectopic locations (e.g., heart, ovary, gallbladder, liver, and kidney) have also been described.

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