Pancreas

A retroperitoneal organ with both endocrine and exocrine functions.

Embryology

• Dorsal and ventral pancreatic buds form separately from evaginations of the endodermal epithelium of the duodenum, at the junction of foregut and midgut, in 4th week
  • Pluripotent pancreatic epithelial stem cells give rise to both exocrine (acinar) and endocrine (islet) cell lines, and the ductal network
  • First organised islets appear around 10 weeks
• Ventral bud rotates from ventral mesogastrium to dorsal mesogastrium
• These buds fuse around day 40
  • Dorsal bud -> anterior part of head of pancreas, pancreatic body and tail (Dorsal = Dominant)
  • Ventral bud -> posterior part of head of pancreas, uncinate process
• Both ventral and dorsal buds develop their own primitive ductal system, and both systems contribute to the mature pancreatic ductal system
  • Proximal aspect of the dorsal anlage duct forms the duct of Santorini (accessory duct)
  • Distal aspect of dorsal duct combines with the duct of the ventral bud to form the duct of Wirsung
  • Duct of Wirsung is eventually the major drainage pathway, and enters the duodenum through the major papilla on medial wall of D2, at major duodenal papilla
• Pancreas divisum = failure of dorsal and ventral ducts to fuse (see separate topic)

Gross anatomy

• Smooth, soft gland with lobulated surface
• 75-125g
• 10-20cm long
• 85% acinar cells, 2% islet cells, 10% ECM, 3% ducts/vessels

Zones:

• Head
  • Lies to right of midline, within C loop of duodenum
  • Tends to overlap the duodenum a bit anteriorly and posteriorly, so that the duodenum makes a gutter within the substance of the pancreas
  • 3-4cm thick, relatively flat
  • Anterior to IVC at confluence of renal veins
• Uncinate process (perhaps part of head)
  • A projection which extends from the left inferior margin of the head of the pancreas, tracking behind SMV
  • Terminates adjacent to SMA
• Neck
  • The short segment immediately overlying SMV
  • Thinner (1-2cm) than the head
• Body
  • Extends across midline
  • Anterior to Gerota fascia
  • Triangular in shape with anterior, posterior and inferior surfaces
• Tail
  • Splenic hilum
  • Nebulous transition to body

Ductal system

• Usually two ducts passing through the head
• Major duct (of Wirsung)
  • 70% join with CBD to open into the major papilla, 7cm distal to pylorus, usually D2, can be D3
  • If the bile duct is seen to overlie the vertebral column on IOC, it should alert the surgeon to the possibility of an abnormally distal major papilla
• Accessory duct (of Santorini)
  • Opens into the minor papilla, which lies about 2cm proximal to the major papilla, and more anteriorly
  • In 6-9%, can persist with no connection with the main duct (pancreas divisum) - see separate topic
• Main duct
  • Runs closer to posterior surface than anterior
  • Begins as an identifiable structure about 2.5cm from the tip of the tail, where its diameter is 0.5mm
  • Diameter increases to 1.5-3mm at 10cm from tail
  • Diameter in head is 3.5mm, which may increase somewhat with age
  • Can bifurcate into two ducts in mid-pancreas

Relationships

• Posterior
  • PV forms from splenic vein and SMV behind the neck
  • L1
  • IVC and renal veins lie posterior to head
  • Aorta (SMA origin) lies posterior to body)
  • Splenic vein lies behind the body of the pancreas, sometimes largely enveloped by pancreatic tissue. It usually runs superior to pancreatic tail as it comes towards the splenic hilum.
  • Splenic artery along the superior aspect
  • Posterior superior pancreaticoduodenal artery crosses posteriorly to head
• Anterior
  • Pancreatic neck is a landmark for origin of transverse mesocolon and middle colic artery (arising from SMA)
  • Anterior surface covered by layer of visceral peritoneum, which is the floor of the lesser sac
  • Stomach resting on body of pancreas
  • Left adrenal gland lies posterior to the inferior aspect of the mid-body of the pancreas
• Tail
  • Splenic hilum - easy to injury tail during splenectomy

Surgical access:

• Enter lesser sac by dividing gastrocolic ligament (in greater omentum), then dissecting through peritoneum posterior to stomach
• Trans-gastric access to lesser sac
• Through transverse mesocolon (although risk of damaging vessels e.g. middle colic artery)
• Removal of greater omentum from transverse mesocolon - wide exposure
• Kocher maneuvre for posterior pancreatic head and neck - incise peritoneum between D2 and IVC, leaving fascia of Treitz attached to pancreas, so that the IVC is bare, and the pancreaticoduodenal arcades are not interfered with. If this move is carried through across midline, SMA and SMV can be reached.

Arterial supply

• Supplied by a complex network arising from coeliac trunk and SMA
  • See 'liver' for full description of GDA
• All major vessels approach pancreas and duodenum from medially, so Kocher manoeuvre can be safely used to medially rotate the duodenum and pancreas without any interruption to blood supply
• However, avoid dissection in the plane between pancreas and duodenum, which can risk devascularising duodenum by damaging the pancreaticoduodenal arcades
• Four major arcades:
  • Superior pancreaticoduodenal - from GDA. Divides into anterior and posterior branches as it runs inferiorly within the pancreaticoduodenal groove.
  • Inferior pancreaticoduodenal - from a single branch of SMA, which runs posteriorly to SMV before diving into anterior and posterior branches. The arteries anastomose with their superior namesakes and supply head and uncinate process.
  • Dorsal pancreatic artery - from coeliac trunk, proximal CHA, or splenic artery. Continues as transverse pancreatic artery along inferior edge of pancreas.
  • Great pancreatic artery - one of 2-10 small pancreatic branches off the splenic artery. Together with the above, forms inferior pancreatic artery.
• Additionally
  • Supraduodenal - small vessel arising from proximal GDA or right gastric, and crossing above or behind the first part of the duodenum, in front of the bile duct, to enter the posterior aspect of the duodenum
  • Beware of RHA with aberrant origin from SMA, passing usually posterior to pancreas
  • Beware of middle colic artery with high origin, emerging directly from the substance of the pancreas, or from GDA and then passing anteriorly across pancreas

Venous drainage

• Typically mimics arterial supply
• ASPDV usually drains into right gastro-epiploic vein
• PSPDV usually drains into PV
• Inferior pancreaticoduodenal veins are somewhat variable in number and mode of drainage - often brought into view, and are troublesome, when dissecting uncinate process free of SMV
• Middle colic vein drains into SMV at about the point that SMV passes behind the neck of the pancreas, and is thus a useful guide to SMV location
• Inferior pancreatic vein accompanies the artery of the same name along the inferior edge of the pancreas posteriorly.
• Variable number of unnamed smaller veins, which are easily torn when dissecting spleen from pancreas. These veins nearly always enter the superior or anterior aspect of the splenic vein, so that the posterior and inferior aspects are relatively free of tributaries (other than SMV).

Lymphatic drainage

• Four quadrants
  • Left side drains to lymph nodes in the splenic hilum or gastrosplenic omentum, via lymphatics along the superior and inferior border of itself
  • Right side drains superiorly to gastroduodenal lymph nodes and inferiorly to infra-pancreatic nodes
• Secondary drainage via retro-pancreatic lymph nodes located anterior to the aorta between the coeliac and SMA. Can either receive drainage directly from the pancreas or from the above 'ring'
• HOP carcinoma typically metastasises along the SMA

Innervation

• Afferent pathways exist, but little is known. Likely SNS, interconnecting through coeliac and SMA plexuses.
• Denervation more centrally relies on division of the greater, lesser and least splanchnic nerves (splanchnicectomy) and removal of the sympathetic trunks from T9 to L1 segments. However, this has very mixed success, suggesting other pathways.

Microscopic anatomy

• Islets of Langerhans - endocrine cells
  • Comprise <2% of overall pancreatic mass - about 1 million islets, with each islet containing about 3000 cells and measuring from 40um to 1mm
  • Afferent arterioles enter the islet on the periphery into the centre of the islet, and then flows on to the exocrine parts of the pancreas, which facilitates endocrine regulation
  • Composed of four cell types:
• Exocrine system - acinar cells
  • Contained in clusters
  • Draining into a centralised ductal system

Variant anatomy

• Pancreas divisum 5-10%
• Anomalous pancreaticobiliary junction
• Annular pancreas (1:20,000)
• Bifid pancreas - rare branching anomaly of the pancreatic tail and duct system
• Ectopic pancreas tissue - gastric antrum, proximal duodenum, ileum, Meckel's diverticula
• Pancreatic clefts - linear clefts which can mimic lacerations

Physiology

Exocrine

• • Creation of enzymes
    • Provides most of the enzymes for alimentary digestion - lipase, amylase, trypsin, chymotrypsin, carboxypeptidase, and elastase
    • Enzymes are synthesised by acinar cells as inactive proenzymes
      • Acinar cells also synthesis pancreatic secretory trypsin inhibitor, which counteracts premature activation - encoded by SPINK1 gene, which if faulty, leads to chronic pancreatitis, especially in childhood
    • Proenzymes can then be secreted into the pancreatic duct, and eventually the duodenal lumen
    • Duodenal brush border cells express enterokinase, which catalyses the enzymatic activation of trypsin from trypsinogen
  • Pancreatic ductal cells
    • Primary function is to provide the water and electrolytes necessary to dilute and deliver the enzymes
    • Stimulated to release these substances by secretin
  • Secretion of bicarb
    • Bicarb produced and secreted to neutralise the HCl secreted by stomach
    • Pancreatic enzymes would be deactivated at low pH - optimal pH is >7
  • Regulation of secretion
    • Cephalic phase - stimulated by vagus nerve - increased acinar secretion of enzymes
    • Gastric phase - vagovagal reflexes triggered by gastric distension - increased acinar cell secretion
    • Intestinal phase (most important - majority of secretion) - mediated by secretin (from S cells) and CCK, in response to acidification of duodenum
      • Secretin receptors on pancreatic ductal cells but not present in other pancreatic cells
      • Secretin stimulation activates bicarb-chloride anion exchanger in the apical membrane of ductal cells, causing secretion of bicarb
      • CCK is the main mediator of the secretion of enzymes, and relaxation of the sphincter of Oddi
    • Islet cells regulate exocrine function
  • Function of enzymes
    • Amylase hydrolyses major polysaccharides into smaller ones
    • Lipase hydrolyses ingested fats into FFAs and 2-monoglycerides

Endocrine

• • Glucose homeostasis
    • Insulin is secreted by B cells within islets of Langerhans, and promotes glucose transport into cells, inhibits glycogenolysis and fatty acid breakdown, and stimulates protein synthesis.
      • Promotes glucose transport into all cells except B cells, hepatocytes and CNS cells.
      • Synthesised as proinsulin in response to pancreatic B cell stimulation. Transported to Golgi complex where it is cleaved into insulin and C-peptide, which are secreted in equimolar amounts.
    • Glucagon increases blood glucose levels through stimulation of glycogenolysis, lipolysis, and gluconeogenesis
      • Secreted by A cells
  • Somatostatin
    • Secreted by islet D cells
    • When administered exogenously, inhibits the release of insulin, glucagon, PP and inhibits gastric, pancreatic and biliary secretions
  • Pancreatic polypeptide (PP)
    • Secreted by islet F cells
    • True physiological role unclear - infusion causes loss of appetite and reduced food intake
  • VIP
  • Amylin
  • Galanin
  • Serotonin