section10chapter 56

1、1515 CHAPTER 56 ANATOMY The average pancreas weighs between 75 and 125 g and mea- sures 10 to 20 cm. It lies in the retroperitoneum just anterior to the first lumbar vertebrae and is anatomically divided into four portions, the head, neck, body and tail. The head lies to the right of midline within

2、the C loop of the duodenum, immediately anterior to the vena cava at the confluence of the renal veins. The uncinate process extends from the head of the pancreas behind the superior mesenteric vein (SMV) and terminates adja- cent to the superior mesenteric artery (SMA). The neck is the short segmen

3、t of pancreas that immediately overlies the SMV. The body and tail of the pancreas then extend across the midline, anterior to Gerotas fascia and slightly cephalad, terminating within the splenic hilum (Fig. 56-1). Arterial Blood Supply The pancreas is supplied by a complex arterial network arising

4、from the celiac trunk and SMA. The head and uncinate process are supplied by the pancreaticoduodenal arteries (anterior and posterior), which arise from the hepatic artery via the gastro- duodenal artery (GDA) superiorly and the SMA inferiorly. The neck, body, and tail receive arterial supply from t

5、he splenic arte- rial system. Several small branches originate from the length of the splenic artery, supplying arterial blood flow to the superior portion of the organ. The dorsal pancreatic artery arises from the splenic artery and courses posterior to the body of the gland to become the inferior

6、pancreatic artery. The inferior pancreatic artery then runs along the inferior border of the pancreas, terminating at its tail. Venous Drainage The venous drainage mimics the arterial supply, with blood flow from the head of the pancreas draining into the anterior and posterior pancreaticoduodenal v

7、eins. The posterior superior pancreaticoduodenal vein enters the SMV laterally at the supe- rior border of the neck of the pancreas. The anterosuperior pancreaticoduodenal vein enters the right gastroepiploic vein just prior to its confluence with the SMV at the inferior border of the pancreas. The

8、anterior and posteroinferior pancreatico- duodenal veins enter the SMV along the inferior border of the uncinate process. The remaining body and tail are drained via the splenic venous system. EMBRYOLOGY The exocrine pancreas begins development during the fourth week of gestation. Pluripotent pancre

9、atic epithelial stem cells give rise to exocrine and endocrine cell lines, as well as the intricate pancreatic ductal network. Initially, dorsal and ventral buds appear from the primitive duodenal endoderm (Fig. 56-2A). The dorsal bud typically appears first and ultimately develops into the superior

10、 head, neck, body, and tail of the mature pancreas. The ventral bud develops as part of the hepatic diverticulum and maintains communication with the biliary tree throughout development. The ventral bud will become the infe- rior part of the head and uncinate process of the gland. Between the fourth

11、 and eighth week, the ventral bud rotates posteriorly in a clockwise fashion to fuse with the dorsal bud (see Fig. 56-2B). At approximately 8 weeks gestation, the dorsal and ventral buds are fused (see Fig. 56-2C). The initiation of pancreas bud formation and differentia- tion of the ventral bud fro

12、m the hepatic-biliary fates is depen- dent on the expression of pancreatic duodenal homeobox 1 (PDX1) protein and pancreas-specific transcription factor 1 (PTF1). In the absence of PDX1 expression in mice, pancreatic agenesis occurs, indicating its importance in the early phases of organogenesis. PT

13、F1 expression is first detectable shortly after PDX1 in cells of the early endoderm, which will become the dorsal and ventral pancreas. By lineage analysis, 95% of acinar cells express PTF1. In PTF1 null mice, acini do not form. The notch signaling pathway is also critical to duct and acinar dif- fe

14、rentiation. In the absence of notch signaling, embryonic cells commit to endocrine lineage, suggesting that notch signaling is vital to exocrine differentiation. In addition to PDX1, PTF1, and notch signaling, complex interactions between mesenchy- mal growth factors such as transforming growth fact

15、or- (TGF- ) and other signaling pathways, including hedgehog and Wnt, seem to play critical roles in pancreas development.1 The precise interactions that lead to normal organogenesis continue to be defined. Table 56-1 summarizes the factors and pathways that affect pancreas development. anatomy embr

16、yology physiology acute pancreatitis chronic pancreatitis cystic neoplasms of the pancreas adenocarcinoma of the exocrine pancreas pancreatic trauma EXOCRINE PANCREAS Eric H. Jensen, Daniel Borja-Cacho, Waddah B. Al-Refaie, and Selwyn M. Vickers 1516 SECTIONX ABDOMEN FIGURE 56-1 Anatomy.(N.ElsevierI

17、nc.Allrightsreserved.) Common hepatic artery Left hepatic artery Right hepatic artery Cystic artery Cystic triangle (of Calot) Cystic duct Common hepatic duct Common bile duct Gall bladder Proper hepatic artery Right gastric artery Right gastroepiploic (gastroomental) artery Left gastroepiploic (gas

18、troomental) artery Left gastric artery Splenic artery Dorsal (superior) pancreatic artery Inferior (transverse) pancreatic artery Anastomotic branch Middle colic artery (cut) Superior mesenteric artery Caudal pancreatic artery Great pancreatic artery Portal vein Posterior superior pancreaticoduodena

19、l artery (phantom) Anterior superior pancreaticoduodenal artery Superduodenal artery Gastroduodenal artery Inferior (common) pancreaticoduodenal artery Posterior inferior pancreaticoduodenal artery Anterior inferior pancreaticoduodenal artery Abdominal aorta Short gastric arteries Celiac trunk Right

20、 and left inferior phrenic arteries (shown here from common stem) FIGURE 56-2 Embryologic development of the pancreas. Common bile duct Dorsal pancreatic duct Dorsal pancreas Ventral pancreas Ventral pancreatic duct Accessory pancreatic duct (Santorini) Common bile duct Main pancreatic duct (Wirsung

21、) C A B Stomach Gallbladder Ventral pancreas Dorsal pancreas Liver ExOcrINEPANcrEAs ChapTEr56 1517 SECTION X ABDOMEN chronic backpressure in the duct. This relative outflow obstruc- tion has been implicated in the development of relapsing acute or chronic pancreatitis. Although 10% of the population

22、 is affected by pancreas divisum, only rarely do affected individuals develop pancreatitis. Annular Pancreas Annular pancreas results from aberrant migration of the ventral pancreas bud, which leads to circumferential or near- circumferential pancreas tissue surrounding the second portion of the duo

23、denum. This abnormality may be associated with other congenital defects, including Down syndrome, malrota- tion, intestinal atresia, and cardiac malformations. If symptoms of obstruction occur, surgical bypass via duodenojejunostomy is performed. Ectopic Pancreas Ectopic pancreas may arise anywhere

24、along the primitive foregut, but is most common in the stomach, duodenum, and Meckels diverticulum. Clinically, ectopic nodules may result in bowel obstruction caused by intussusception, bleeding, or ulceration. They can sometimes be found incidentally as firm yellow nodules that arise from the subm

25、ucosa. Although there have been rare case reports of adenocarcinoma arising in ectopic pancreas tissue, resection is not necessary unless symptoms occur. PHYSIOLOGY The human pancreas is a complex gland, with endocrine and exocrine functions. It is mainly composed of acinar cells (85% of the gland)

26、and islets cells (2%) embedded in a complex extra- cellular matrix, which comprises 10% of the gland. The remain- ing 3% to 4% of the gland is comprised of the epithelial duct system and blood vessels. Major Components of Pancreatic Juice The main function of the exocrine pancreas is to provide the

27、vast majority of the enzymes needed for alimentary digestion. Acinar cells synthesize many enzymes (proteases) that digest food pro- teins such as trypsin, chymotrypsin, carboxypeptidase, and elas- tase. Under physiologic conditions, acinar cells synthesize these proteases as inactive proenzymes tha

28、t are stored as intracellular zymogen granules. With stimulation of the pancreas, these pro- enzymes are secreted into the pancreatic duct and eventually the duodenal lumen. The duodenal mucosa synthesizes and secretes enterokinase, which is the critical enzyme in the enzymatic activation of trypsin

29、 from trypsinogen.2 Trypsin also plays an important role in protein digestion by propagating pancreatic enzyme activation through autoactivation of trypsinogen and other proenzymes, such as chymotrypsinogen, procarboxypepti- dase, and proelastase. Figure 56-4 summarizes the mechanisms of pancreatic

30、exocrine secretion. In addition to protease production, acinar cells also produce pancreatic amylase and lipase, also known as glycerol ester hydro- lase, as active enzymes. With the exception of cellulose, pan- creatic amylase hydrolyzes major polysaccharides into small oligosaccharides, which can

31、be further digested by the oligosac- charidases present in the duodenal and jejunal epithelium. Pan- creatic lipase hydrolyzes ingested fats into free fatty acids and 2-monoglycerides. In addition to pancreatic lipase, acinar cells produce other enzymes that digest fat, but they are secreted as proe

32、nzymes, like the proteases previously mentioned. These Pancreas Divisum During normal organogenesis, the dorsal and ventral buds most commonly fuse to form a common duct, which enters the duo- denum along with the common bile duct via the ampulla of Vater. Failure of the dorsal and ventral ducts to

33、fuse during embryogenesis leads to pancreas divisum, a condition identified by a ventral pancreatic duct and common bile duct, which enter the duodenum via a major papilla, whereas a dorsal pancreatic duct enters through a minor papilla, which is slightly proximal (Fig. 56-3). Because most pancreati

34、c exocrine secretions exit via the dorsal duct, pancreas divisum can lead to a condition of partial obstruction caused by a small minor papilla, leading to FIGURE 56-3 MrcPshowingpancreasdivisum,withthedorsalpan- creaticductdrainingthroughtheminorpapillaandtheventralpan- creaticductjoiningthebiliary

35、treedrainingthroughthemajorpapilla. Table56-1 MolecularFactorsandpathwaysassociatedWith pancreaticOrganogenesis MUTaTIONrELEVaNCE PDX1criticalroleinexocrine differentiation;knockoutmice developprimitivepancreaticbuds, butagenesisoftheorgan. PTF1coexpressionwithPDX1determines progenitorcellstopancrea

36、ticfate. Notchsignalingpathwaysuppressesendocrinedifferentiation, promotingexocrinedevelopment. HedgehogsignalingpathwayInhibitionofhedgehoginPDX1- positivecellsleadstoinitiationof endodermdifferentiationinto pancreaslineage. WntsignalingpathwaycomplexWntsignalingisimportant inallaspectsofpancreas d

37、evelopment;lackofWntsignaling resultsinabsenceofacinartissue. 1518 SECTIONX ABDOMEN apical membrane of pancreatic duct cells contains an anion exchanger that secretes intracellular HCO3 into the lumen of the cell and favors the exchange of luminal Cl inside the ductal epithelium. Recent studies have

38、 shown that this exchanger inter- acts with the cystic fibrosis transmembrane conductance regula- tor (CFTR). This may correlate with the inability of patients with cystic fibrosis to secrete water and bicarbonate. Although the nature of this exchanger has not been completely elucidated, it is possi

39、ble that this anion exchanger is an SLC26 family member. This family contains different anion exchangers that transport monovalent and divalent anions, such as Cl and HCO3. Some of these exchangers are known to interact with CFTR. In addition to HCO3, CO2 hydration also generates H+ ions, which are

40、secreted by Na+ and H+ exchangers present in the basolateral membrane of ductal cells. These exchangers belong to the SLC9 gene family. The main function of these exchangers is to maintain the intracellular pH within a physi- ologic range. In addition, the basolateral membrane of duct cells contains

41、 multiple Na+,K+-ATPases that provide the primary force that drives HCO3 secretion; the Na+,K+-ATPase maintains the Na+ gradient used to extrude H+ as well. Finally, K+ channels present in the basolateral membrane of acinar cells maintain the membrane potential to allow recirculation of K+ ions brou

42、ght by the Na+,K+ pump inside the cell. Figure 56-5 illustrates HCO3 secretion inside pancreatic duct cells. Once the HCO3 secreted by pancreatic duct cells reaches the duodenal lumen, it neutralizes the hydrochloric acid secreted by parietal cells. Pancreatic enzymes are inactivated at a low pH; th

43、erefore, pancreatic bicarbonate provides an optimal pH for acinar cell enzyme function. The optimal pH for the function include colipase, cholesterol ester hydrolase, and phospholipase A2. The main function of colipase is to increase the activity of pancreatic lipase. Cholesterol esters are cleaved

44、by cholesterol ester hydrolase into free cholesterol and one fatty acid, phospho- lipase A2 hydrolyzes phospholipids, and pancreatic acinar cells also secrete deoxyribonuclease and ribonuclease. These are enzymes required for the hydrolysis of DNA and RNA, respectively. Pancreatic enzymes are inacti

45、ve inside acinar cells because they are synthesized and stored as inactive enzymes. In addition to this autoprotective mechanism, acinar cells synthesize pancre- atic secretory trypsin inhibitor, which also protects acinar cells from autodigestion because it counteracts premature activation of tryps

46、inogen inside acinar cells. Pancreatic secretory trypsin inhibitor is encoded by serine protease inhibitor Kazal type 1 (SPINK-1) gene. SPINK-1 gene mutations are associated with the development of chronic pancreatitis, especially in childhood. The primary function of pancreatic duct cells is to pro

47、vide the water and electrolytes required to dilute and deliver the enzymes synthesized by acinar cells. Although the concentra- tions of sodium and potassium are similar to their respective concentration in plasma, the concentrations of bicarbonate and chloride vary significantly, according to the s

48、ecretion phase. The mechanism responsible of the secretion of bicarbonate was first described in 1988 based on in vitro studies. According to this model, extracellular CO2 diffuses across the basolateral membrane of ductal cells. Once CO2 is inside pancreatic duct cells, it is hydrated by intracellu

49、lar carbonic anhydrase; as a result of this reaction, HCO3 and H+ are generated. The FIGURE 56-4 Physiologyofthesecretionofpancreatic enzymes.Thepresenceofpeptidesandfattyacidsfrom foodtriggersthereleaseofccK.ccKinducestherelease ofpancreaticenzymesintotheduodenallumen.con- versely,scellslocatedinth

50、eduodenumreleasesecretin inresponsetotheacidificationoftheduodenum.secre- tininducesthesecretionofHcO3frompancreaticcells intotheduodenum. Enterokinase CCK secretin Trypsin Chymotrypsin Carboxypeptidase Elastase Amylase Lipase Colipase Cholesterol ester Hydrolase Phospholipase A2 Trypsinogen Chymotr

51、ypsinogen Pro-carboxypeptidase Pro-elastase Cholesterol ester hydrolase Pancreatic lipase Colipase Phospholipase A2 Amylase ExOcrINEPANcrEAs ChapTEr56 1519 SECTION X ABDOMEN (cAMP), which activates the HCO3-Cl anion exchanger in the apical membrane of pancreatic duct cells. It also increases the act

52、ivity of the enzyme carbonic anhydrase, the excretion of H+ outside the duct cell, and the activity of the CFTR. The presence of lipid, protein, and carbohydrates inside the duodenum induces the secretion of CCK-releasing factor and monitor peptide. Both peptides induce release of CCK by I cells pre

53、sent in the duodenal mucosa. Whereas secretin is the main mediator of the secretion of water and bicarbonate in the intes- tinal phase, CCK is the main mediator of the secretion of pancreatic enzymes. CCK exerts a number of effects: 1. It travels through the bloodstream and induces the release of pa

54、ncreatic enzymes by acinar cells. 2. It induces local duodenal vagovagal reflexes that cause the release of acetylcholine, vasoactive intestinal peptide, and gastrin-releasing peptide, which pro- motes the release of pancreatic enzymes. 3. CCK induces the relaxation of the sphincter of Oddi. Also, i

55、t should be noted that CCK potentiates the effects of secretin, and vice versa. ACUTE PANCREATITIS The incidence of acute pancreatitis (AP) has increased during the past 20 years. AP is responsible for more than 300,000 hospital admissions annually in the United States. Most patients develop a mild

56、and self-limited course; however, 10% to 20% of patients have a rapidly progressive inflammatory response associated with prolonged length of hospital stay and significant morbidity and mortality. Patients with mild pancreatitis have a mortality rate of less than 1% but, in severe pancreatitis, this

57、 increases up to 10% to 30%.3 The most common cause of death in this group of patients is multiorgan dysfunction syndrome. Mortality in pancreatitis has a bimodal distribution; in the first 2 weeks, also known as the early phase, the multiorgan dysfunc- tion syndrome is the final result of an intens

58、e inflammatory cascade triggered initially by pancreatic inflammation. Mortality after 2 weeks, also known as the late period, is often caused by septic complications.4 Pathophysiology The exact mechanism whereby predisposing factors such as ethanol and gallstones produce pancreatitis is not complet

59、ely known. Most researchers believe that AP is the final result of abnormal pancreatic enzyme activation inside acinar cells. Immunolocalization studies have shown that after 15 minutes of pancreatic injury, both zymogen granules and lysosomes colo- calize inside the acinar cells. The fact that zymogen and lysosome colocalization occurs before amylase level elevation, pancreatic edema, and other markers of pancreatitis are evident suggests that colocalization is an early step in the pathophysiology and not a consequence of pancreatitis. In addition, the inflammatory response se