Anatomy and physiology of pancreas

This ppt. Is about surgical anatomy and physiology of pancreas. Anatomical anamolies of the pancreas and variation of the ducts has been touched also.
Basic phsiology and pancreatic functions have been explanied with diagrams.
This ppt is only for postgraduates.

1. ANATOMY AND PHYSIOLOGY OF PANCREAS Dr. Sajad Nazir

2. ANATOMY The pancreas is a J shaped retroperitoneal organ that lies in an oblique position , sloping upward from the C-loop of the duodenum to the splenic hilum. In an adult, the pancreas weighs 75 to 100 g and is about 15 to 20 cm long.

3. EMBROLOGY OF PANCREAS The pancreas is formed by the fusion of a ventral and dorsal bud . The ventral anlage becomes the inferior portion of the pancreatic head and the uncinate process, while the dorsal anlage becomes the body and tail of the pancreas. The duct from the smaller ventral bud, which arises from the hepatic diverticulum, connects directly to the common bile duct. The duct from the larger dorsal bud, which arises from the duodenum, drains directly into the duodenum. The duct of the ventral anlage becomes the duct of Wirsung, and the duct from the dorsal anlage becomes the duct of Santorini. With gut rotation, the ventral anlage rotates to the right and around the posterior side of the duodenum to fuse with the dorsal bud. The ducts from each anlage usually fuse together in the pancreatic head such that most of the pancreas drains through the duct of Wirsung, or main pancreatic duct , into the common channel formed from the bile duct and pancreatic duct

4. The main pancreatic duct is usually only 2 to 3 mm in diameter and runs midway between the superior and inferior borders of the pancreas, usually closer to the posterior than to the anterior surface . Pressure inside the pancreatic duct is about twice that in the common bile duct, which is thought to prevent reflux of bile into the pancreatic duct . The main pancreatic duct joins with the common bile duct and empties at the ampulla of Vater or major papilla, which is located on the medial aspect of the second portion of the duodenum.

5. PANCREATIC DUCT VARIATIONS The length of the common channel is variable. In about one third of patients, the bile duct and pancreatic duct remain distinct to the end of the papilla, the two ducts merge at the end of the papilla in another one third, and in the remaining one third, a true common channel is present for a distance of several millimeters. The muscle fibers around the ampulla form the sphincter of Oddi, which controls the flow of pancreatic and biliary secretions into the duodenum. Contraction and relaxation of the sphincter is regulated by complex neural and hormonal factors.

6. PANCREAS DIVISUM Commonly , the duct from the dorsal anlage, the duct of Santorini, persists as the lesser pancreatic duct, and sometimes drains directly into the duodenum through the lesser papilla just proximal to the major papilla. In approximately 30% of patients, the duct of Santorini ends as a blind accessory duct and does not empty into the duodenum. In 10% of patients, the ducts of Wirsung and Santorini fail to fuse. This results in the majority of the pancreas draining through the duct of Santorini and the lesser papilla, while the inferior portion of the pancreatic head and uncinate process drains through the duct of Wirsung and major papilla. This normal anatomic variant, which occurs in one out of 10 patients, is referred to as pancreas divisum.

7. TYPES  Type I, or classic pancreatic divisum, is a complete failure of the dorsal and ventral buds to fuse. Type II pancreatic divisum is characterized by the absence of the ventral duct, so the minor papilla drains the entire pancreas and the major papilla drains some of the common bile duct . Type III presents with a small remnant communication between the dorsal duct and ventral duct

8. In a minority of these patients, the minor papilla can be inadequate to handle the flow of pancreatic juices from the majority of the gland. This relative outflow obstruction can result in pancreatitis and is sometimes treated by sphincteroplasty of the minor papilla.

9. PARTS OF PANCREAS

10. T he location of pathology within the pancreas in relation to four regions: the head, neck, body, and tail . HEAD The head of the pancreas is nestled in the C-loop of the duodenum and is posterior to the transverse mesocolon . 3 borders ; superior, inferior and right lateral. 2 surfaces; anterior and posterior. Uncinate process Just posterior to the head of the pancreas lie the vena cava, the right renal , and both renal veins.

11. ANTERIOR SURFACE

12. POSTERIOR SURFACE

13. UNCINATE PROCESS

14. NECK The neck of the pancreas lies directly anterior to the portal vein. At the inferior border of the neck of the pancreas, the superior mesenteric vein joins the splenic vein and then continues toward the porta hepatis as the portal vein.

15. The inferior mesenteric vein often joins the splenic vein near its junction with the portal vein. Sometimes , the inferior mesenteric vein joins the superior mesenteric vein or merges with the superior mesenteric portal venous junction to form a trifurcation .

16. The neck of the pancreas is anterior to the vertebral body of L1 and L2, and blunt anteroposterior trauma can compress the neck of the pancreas against the spine, causing parenchymal and, sometimes, ductal injury. The neck divides the pancreas into approximately two equal halves.

17. BODY 3 borders: anterior, superior and inferior. The splenic artery runs parallel and just superior to the vein along the posterior superior edge of the body and tail of the pancreas. The splenic artery often is tortuous. The anterior surface of the body of the pancreas is covered by peritoneum. Once the gastrocolic omentum is divided, the body and tail of the pancreas can be seen along the floor of the lesser sac , just posterior to the stomach.

18. The body of the pancreas is anterior to the aorta at the origin of the superior mesenteric artery.

19. TAIL The small portion of the pancreas anterior to the left kidney is referred to as the tail and is nestled in the hilum of the spleen near the splenic flexure of the left colon . Awareness of these anatomic relationships is important to avoid injury to the pancreatic tail during left colectomy or splenectomy.

20. PANCREAS INSITU

21. BLOOD SUPPLY The blood supply to the pancreas comes from multiple branches from the celiac and superior mesenteric arteries . The common hepatic artery gives rise to the gastroduodenal artery before continuing toward the porta hepatis as the proper hepatic artery . The gastroduodenal artery then travels inferiorly anterior to the neck of the pancreas and posterior to the duodenal bulb. At the inferior border of the duodenum, the gastroduodenal artery then gives rise to the right gastroepiploic artery then continues on as the anterior superior pancreaticoduodenal artery, which branches into the anterior and posterior superior pancreaticoduodenal arteries. As the superior mesenteric artery passes behind the neck of the pancreas, it gives off the inferior pancreaticoduodenal artery at the inferior margin of the neck of the pancreas. This vessel quickly divides into the anterior and posterior inferior pancreaticoduodenal arteries. The superior and inferior pancreaticoduodenal arteries join together within the parenchyma of the anterior and posterior sides of the head of the pancreas along the medial aspect of the C-loop of the duodenum to form arcades that give off numerous branches to the duodenum and head of the pancreas. Therefore, it is impossible to resect the head of the

22. pancreas without devascularizing the duodenum, unless a rim of pancreas containing the pancreaticoduodenal arcade is preserved. Variations in the arterial anatomy occur in one out of five patients. The right hepatic artery, common hepatic artery, or gastroduodenal arteries can arise from the superior mesenteric artery. In 15% to 20% of patients, the right hepatic artery will arise from the superior mesenteric artery and travel upwards toward the liver along the posterior aspect of the head of the pancreas (referred to as a replaced right hepatic artery). It is important to look for this variation on preoperative computed tomographic (CT) scans and in the operating room so the replaced hepatic artery is recognized and injury is avoided.

23. BODY AND TAIL The body and tail of the pancreas are supplied by multiple branches of the splenic artery. The splenic artery arises from the celiac trunk and travels along the posterior-superior border of the body and tail of the pancreas toward the spleen. The inferior pancreatic artery usually arises from the superior mesenteric artery and runs to the left along the inferior border of the body and tail of the pancreas , parallel to the splenic artery. Three vessels run perpendicular to the long axis of the pancreatic body and tail and connect the splenic artery and inferior pancreatic artery. They are, from medial to lateral, the dorsal, great, and caudal pancreatic arteries . These arteries form arcades within the body and tail of the pancreas, and account for the rich blood supply of the organ.

24. VENOUS DRAINAGE The venous drainage of the pancreas follows a pattern similar to that of the arterial supply. The veins are usually superficial to the arteries within the parenchyma of the pancreas. There is an anterior and posterior venous arcade within the head of the pancreas. The superior veins drain directly into the portal vein just above the neck of the pancreas. The posterior inferior arcade drains directly into the inferior mesenteric vein at the inferior border of the neck of the pancreas. These venous tributaries must be divided during a Whipple procedure. The anterior inferior pancreaticoduodenal vein joins the right gastroepiploic vein and the middle colic vein to form a common venous trunk, which enters into the superior mesenteric vein. Traction on the transverse colon during colectomy can tear these fragile veins, which then retract into the parenchyma of the pancreas, making control tedious. There also are numerous small venous branches coming from the pancreatic parenchyma directly into the lateral and posterior aspect of the portal vein. Venous return from the body and tail of the pancreas drains into the splenic vein.

25. LYMPHATICS The lymphatic drainage from the pancreas is diffuse and Widespread. The profuse network of lymphatic vessels and lymph nodes draining the pancreas provides egress to tumor cells arising from the pancreas. This diffuse lymphatic drainage contributes to the fact that pancreatic cancer often presents with positive lymph nodes and a high incidence of local recurrence after resection. Lymph nodes can be palpated along the distal bile duct and posterior aspect of the head of the pancreas in the pancreaticoduodenal groove, where the mesenteric vein passes under the neck of the pancreas, along the inferior border of the body, at the celiac axis and along the hepatic artery ascending into the porta hepatis, and along the splenic artery and vein . The pancreatic lymphatics also communicate with lymph nodes in the transverse mesocolon and mesentery of the proximal jejunum. Tumors in the body and tail of the pancreas often metastasize to these nodes and lymph nodes along the splenic vein and in the hilum of the spleen

26. Neuroanatomy The pancreas is innervated by the sympathetic and parasympathetic nervous systems. The acinar cells responsible for exocrine secretion , the islet cells responsible for endocrine secretion, and the islet vasculature are innervated by both system. The parasympathetic system stimulates endocrine and exocrine secretion and the sympathetic system inhibits secretion. The pancreas is also innervated by neurons that secrete amines and peptides , such as somatostatin, vasoactive intestinal peptide ( VIP), calcitonin gene-related peptide (CGRP), and galanin. The exact role of these neurons in pancreatic physiology is uncertain , but they do appear to affect both exocrine and endocrine function . The pancreas also has a rich supply of afferent sensory fibers , which are responsible for the intense pain associated with advanced pancreatic cancer, as well as acute and chronic pancreatitis . These somatic fibers travel superiorly to the celiac ganglia . Interruption of these somatic fibers can stop transmission of pain sensation.

27. HISTOLOGY The exocrine pancreas accounts for about 85% of the pancreatic mass ; 10% of the gland is accounted for by extracellular matrix, and 4% by blood vessels and the major ducts, whereas only 2% of the gland is comprised of endocrine tissue. The endocrine and exocrine pancreas are sometimes thought of as functionally separate, but these different components of the organ are coordinated to allow an elegant regulatory feedback system for digestive enzyme and hormone secretion. This complex system regulates the type of digestion, its rate, and the processing and distribution of absorbed nutrients. This coordination is facilitated by the physical approximation of the islets and the exocrine pancreas, the presence of specific islet hormone receptors on the plasma membranes of pancreatic acinar cells, and the existence of an islet-acinar portal blood system

28. Exocrine Pancreas The pancreas secretes approximately 500 to 800 mL per day of colorless, odorless, alkaline, isosmotic pancreatic juice. Pancreatic juice is a combination of acinar cell and duct cell secretions. The acinar cells secrete amylase, proteases, and lipases, enzymes responsible for the digestion of all three food types: carbohydrate , protein, and fat. The acinar cells are pyramid shaped , with their apices facing the lumen of the acinus. Near the apex of each cell are numerous enzyme-containing zymogen granules that fuse with the apical cell membrane .

29. Pancreatic amylase is secreted in its active form and completes the digestive process already begun by salivary amylase. Amylase is the only pancreatic enzyme secreted in its active form , and it hydrolyzes starch and glycogen to glucose, maltose , maltotriose, and dextrins. These simple sugars are transported across the brush border of the intestinal epithelial cells by active transport mechanisms . Gastric hydrolysis of protein yields peptides that enter the intestine and stimulate intestinal endocrine cells to release cholecystokinin (CCK)-releasing peptide , CCK, and secretin, which then stimulate the pancreas to secrete enzymes and bicarbonate into the intestine.

30. The proteolytic enzymes are secreted as proenzymes that require activation. Trypsinogen is converted to its active form, trypsin , by another enzyme, enterokinase, which is produced by the duodenal mucosal cells. Trypsin, in turn, activates the other proteolytic enzymes. Trypsinogen activation within the pancreas is prevented by the presence of inhibitors that are also secreted by the acinar cells. A failure to express a normal trypsinogen inhibitor, pancreatic secretory trypsin inhibitor (PSTI ), also known as serine protease inhibitor Kazal type 1 (SPINK1), is a cause of familial pancreatitis. Inhibition of trypsinogen activation ensures that the enzymes within the pancreas remain in an inactive precursor state and are activated only within the duodenum .

31. Chymotrypsinogen is activated to form chymotrypsin. Elastase, carboxypeptidase A and B, and phospholipase are also activated by trypsin. Trypsin , chymotrypsin, and elastase cleave bonds between amino acids within a target peptide chain, and carboxypeptidase A and B cleave amino acids at the end of peptide chains. Individual amino acids and small dipeptides are then actively transported into the intestinal epithelial cells.

32. Pancreatic lipase hydrolyzes triglycerides to 2-monoglyceride and fatty acid. Pancreatic lipase is secreted in an active form. Colipase is also secreted by the pancreas and binds to lipase, changing its molecular configuration and increasing its activity. Phospholipase A2 is secreted by the pancreas as a proenzyme that becomes activated by trypsin. Phospholipase A2 hydrolyzes phospholipids and, as with all lipases, requires bile salts for its action. Carboxylic ester hydrolase and cholesterol esterase hydrolyze neutral lipid substrates like esters of cholesterol, fat-soluble vitamins, and triglycerides. The hydrolyzed fat is then packaged into micelles for transport into the intestinal epithelial cells, where the fatty acids are reassembled and packaged inside chylomicrons for transport through the lymphatic system into the bloodstream.

33. Endocrine Pancreas There are nearly 1 million islets of Langerhans in the normal adult pancreas. They vary greatly in size from 40 to 900 μm. Larger islets are located closer to the major arterioles and smaller islets are embedded more deeply in the parenchyma of the pancreas . Most islets contain 3000 to 4000 cells of five major types: alpha cells that secrete glucagon, β-cells that secrete insulin, delta cells that secrete somatostatin, epsilon cells that secrete ghrelin , and PP cells that secrete PP.

34. INSULIN Insulin is the best-studied pancreatic hormone. The discovery of insulin in 1920 by Frederick Banting , an orthopedic surgeon , and Charles Best, a medical student, was recognized with the awarding of the Nobel Prize in Physiology or Medicine.

35. Insulin was subsequently purified and found to be a 56-amino acid peptide with two chains, an α and a β chain, joined by two disulfide bridges and a connecting peptide, or C-peptide . Proinsulin is made in the endoplasmic reticulum and then is transported to the Golgi complex, where it is packaged into granules and the C-peptide is cleaved off. There are two phases of insulin secretion . In the first phase, stored insulin is released. This phase lasts about 5 minutes after a glucose challenge. The second phase of insulin secretion is a longer, sustained release due to ongoing production of new insulin. β-cell synthesis of insulin is regulated by plasma glucose levels, neural signals, and the paracrine influence of other islet cells.

36. Insulin secretion by the β- cell is also influenced by plasma levels of amino acids such as arginine, lysine, leucine, and free fatty acids . Glucagon, GIP, GLP-1, and CCK stimulate insulin release , while somatostatin, amylin, and pancreastatin inhibit insulin release . Cholinergic fibers and beta sympathetic fibers stimulate insulin release, while alpha sympathetic fibers inhibit insulin secretion.

37. Insulin’s glucoregulatory function is to inhibit endogenous ( hepatic) glucose production and to facilitate glucose transport into cells, thus lowering plasma glucose levels. Insulin also inhibits glycogenolysis, fatty acid breakdown, and ketone formation , and stimulates protein synthesis.

38. GLUCAGON Glucagon is a 29-amino-acid, single-chain peptide that promotes hepatic glycogenolysis and gluconeogenesis and counteracts the effects of insulin through its hyperglycemic action. Glucose is the primary regulator of glucagon secretion, as it is with insulin, but it has an inhibitory rather than stimulatory effect. Glucagon release is stimulated by hypoglycemia, and by the amino acids arginine and alanine. GLP-1 inhibits glucagon secretion in vivo, and insulin and somatostatin inhibit glucagon secretion in a paracrine fashion within the islet. The same neural impulses that regulate insulin secretion also regulate glucagon secretion , so that the two hormones work together in a balance of actions to maintain glucose levels. Cholinergic and beta sympathetic fibers stimulate glucagon release, while alpha sympathetic fibers inhibit glucagon release .

39. Islet Distribution The β-cells are generally located in the central portion of each islet and make up about 70% of the total islet cell mass. The other cell types are located predominantly in the periphery. The delta cells are least plentiful, making up only 5%; the α-cells make up 10 %, and the PP cells make up 15 %. In contrast to the acinar cells that secrete the full gamut of exocrine enzymes, the islet cells seem to specialize in the secretion of predominantly one hormone . However , individual islet cells can secrete multiple hormones . There is diversity among the islets depending on their location within the pancreas

40. The α- and δ-cells are evenly distributed throughout the pancreas , but islets in the head and uncinate process (ventral anlage) have a higher percentage of PP cells and fewer α-cells, whereas islets in the body and tail (dorsal anlage) contain the majority of α-cells and few PP cells. This is clinically significant because pancreatoduodenectomy removes 95% of the PP cells in the pancreas . This may partially explain the higher incidence of glucose intolerance after the Whipple procedure compared to a distal pancreatectomy with an equivalent amount of tissue resected. In addition , chronic pancreatitis, which disproportionately affects the pancreatic head, is associated with PP deficiency and pancreatogenic diabetes. The relative preponderance of α-cells in the body and tail of the pancreas explains the typical location of glucagonomas

41. Pancreatic function tests Exocrine function assessment. Endocrine assessment.

42. ASSESSMENT OF EXOCRINE FUNCTION DIRECT AND INDIRECT TESTS. indirect tests monitor the intestinal effects of secreted pancreatic digestive enzymes. D irect tests monitor the actual secretion of pancreatic exocrine products (enzymes, fluid, and bicarbonate). The indirect tests are the least invasive and most widely available of the tests, but they also are the least sensitive, and such tests are most likely to be normal in patients with mild degrees of pancreatic functional loss .

43. FAECAL FAT STAINING Conceptually, fecal fat analysis is the simplest of the indirect pancreatic function tests. It is based on the fact that pancreatic lipase is the enzyme responsible for most fat digestion, and diminished lipase secretion results in fat malabsorption. Fecal fat analysis can be accomplished by staining stool samples for fat with Sudan stain or by quantifying fecal fat when the patient is on a controlled-fat diet (Chowdhury & Forsmark, 2003; Lieb & Draganov, 2008). In the latter case, the patient is placed on a diet consisting of 100 g of fat per day for 5 days. Stool is collected on days 3 to 5, and fat content is measured. Fecal fat output of greater than 7 g/day is considered to be abnormal and diagnostic of steatorrhea . but fecal fat measurement is notoriously insensitive for the diagnosis of chronic pancreatitis, and it is most commonly abnormal only in patients with overtly symptomatic steatorrhea.

44. The bentiromide and the pancreolauryl tests The bentiromide and the pancreolauryl tests are noninvasive , indirect pancreatic function tests . The former involves ingestion of the chymotrypsin substrate bentiromide, which is hydrolyzed by chymotrypsin to yield paraaminobenzoic acid, which is absorbed in the small intestine, conjugated in the liver, and excreted in the urine. The test is completed by collecting urine for 6 hours and quantifying urinary paraaminobenzoic acid recovery, which is considered to be abnormal if less than 50 % ( Niederau & Grendell , 1985).

45. the pancreolauryl tests The pancreolauryl test involves ingestion of fluorescein dilaurate, which is hydrolyzed by pancreatic esterases to yield lauric acid and free fluorescein. The pancreolauryl test is completed by collecting urine, in this case for 10 hours, and measuring fluorescein excretion; in this test, excretion is compared with the patient’s excretion of orally ingested free fluorescein several days later.

46. DIRECT TESTS Direct pancreatic function tests can be subdivided further into noninvasive and invasive tests. The noninvasive tests involve measuring fecal or serum levels of pancreas-derived digestive enzymes (serum trypsinogen, fecal chymotrypsin, and fecal elastase ). Recently , direct function tests combining MRCP with secretagogue stimulation have been proposed (Schneider et al, 2006 ; Czako, 2007). These MRCP functional tests aim to either quantify juice flow into the duodenum or to provide contrast enhancement of the pancreatic parenchyma after hormonal stimulation ; to date, however, the overall sensitivity and specificity of these MRCP-based tests remain to be determined, and their overall value as diagnostic tests for early chronic pancreatitis is unproven. The invasive tests involve placing a collecting device into the duodenum or pancreatic duct, stimulating pancreatic exocrine secretion, and measuring the output or concentration of exocrine pancreatic products.

47. TRYPSINOGEN Circulating levels of trypsinogen are easily measured and frequently low in patients with severe pancreatic insufficiency ( Jacobson et al, 1984). Although measurement of serum trypsinogen may be helpful in evaluating the severity of chronic pancreatitis , the test has low sensitivity for the diagnosis of mild pancreatitis .

48. chymotrypsin and elastase Fecal levels of chymotrypsin and elastase also can be measured and used to assess exocrine pancreatic function ( Dominguez-Munoz et al, 1995; Dominici & Franzini , 2002; Goldberg , 2000; Katschinski et al, 1997; Loser et al, 1996; Luth et al, 2001 ). The levels of these enzymes are reduced in patients with advanced chronic pancreatitis. H owever , the sensitivity of fecal chymotrypsin and elastase measurement in diagnosing mild or moderate pancreatic insufficiency is only 40% to 60%.

49. invasive, direct pancreatic function The invasive, direct pancreatic function tests are the most sensitive of the tests used to identify patients with mild to moderate chronic pancreatitis. In these tests, pancreatic secretions are continuously aspirated from either the duodenum or the pancreatic duct after administration of a pancreatic

50. stimulant; this stimulant varies among the different tests. In some , secretin is administered to stimulate pancreatic secretion, and bicarbonate in duodenal juice is measured . In others, a combination of secretin and CCK or one of its analogs is used, and bicarbonate and protein (or pancreatic enzymes) in duodenal juice are measured (Chowdhury & Forsmark, 2003).

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