Pancreas Basics

Question 1

4 Parts of Pancreas

Answer 1

• Head - in curve of duodenum; small extension into uncinate process w/ SMA and SMV in front of this extension
• Neck - SMV and splenic vein join to form portal vein behind this (susceptible to injury in pancreatitis or pancreatic cancer - “vascular groove”); covered by pylorous
• Body - in front of L2-L4 (blunt trauma) and in front of aorta (held against aorta by lesser sac peritoneum)
• Tail - ends at spleen hilus near L kidney; b/n 2 layers of splenorenal ligament

Question 2

Blood Supply

Answer 2

• Well vascularized w/ anastomoses coming from celiac trunk and SMA
• Common hepatic artery
  
  • Hepatic artery
  • Gastroduodenal artery
    
    • Ant and post pancreatico- duodenal arch
    • R gastro- omental/epiploic
• SMA
  
  • Inf pancreatic artery
  • Ant and post pancreatico- duodenal arch

Question 3

Innervation of Pancreas

Answer 3

• Efferent
  
  • Parasymp - vagus - stimulate acini, islet and ducts
  • Symp - T5-T9 - blood vessels; inc glucagon/dec insulin secretion
  • Interneuons from myenteric plexus of stomach and duodenum also innervate pancreas
• Afferent
  
  • Sensing of nutrients in duodenum –> CCK –> stim afferents w/ vagus –> inferior ganglion –> nucleus tractus solaritus
  • Sensing pain –> thru celiac and symp nerves –> DRG
    
    • Capsaicin receptors (like transient receptor potential vanilloid 1 TRPV1) that respond to AA mediators like leukotrienes

Question 4

Ducts

Answer 4

• Main pancreatic duct - fuses w/ common bile duct and opens into duodenum at ampulla of Vater
  
  • Constricted by sphincter of Oddi (smooth muscle ring)
• Accessory pancreatic duct (in 30% population)

Question 5

Pancreas Embryology

Answer 5

• Starts from buds off endoderm
• 4 wks - ventral and dorsal endoderm outpockets form
• Ventral: head and uncinate; contributes to main pancreatic duct (duct of Wirsung)
• Dorsal: small part of head, neck, body, tail; contributes to accessory pancreatic duct (duct of Santorini)
• 7 wks - ventral bud migrates behind duodenum and fuses w/ dorsal bud
• 12 wks - pancreatic acini form at ends of ducts
• 12-16 wks - endocrine cells differentiate from exocrine acini
• Normally duct of Wirsung (from ventral) and duct of Santorini (from dorsal) FUSE
• *If proximal Santorini persists –> accessory pancreatic duct (in 30% pop)

-Endocrine function is mature at birth while exocrine function con to develop (this is why babies can have physiological steatorrhea until 6 mo old)

Question 6

Genetics of Pancreas Embryology

Answer 6

• PDX1 must be present in pancreatic buds (knockout = atresia)
• Shh must be absent in pancreatic bud endoderm but expressed in rest of endoderm
• Notch signaling responsible for subsequent progression from stem cells –> duct cells –> acinar cells –> endocrine cells

Question 7

Exocrine Function

Answer 7

DUCTS AND ACINI

• Ducts secrete bicarb into duodenum (neutralize stomach acid)
• Intercalated ducts (w/ centroacinar cells) –> intralobular excretory ducts –> interlobular excretory ducts
• Acini secrete digestive enzymes into duodenum (breakdown of proteins, carbs, lipids, nucleic acids)
• Acinus = functional unit; cluster of serous secreting cells w/ tight junctions that store zymogen granules at apical surface
• Each cell can secrete MULTIPLE ENZYMES
• Proteases - trypsinogen, chymotrypsinogen, pro-carboxypepidase, pro-elastase
• alpha-amylase, pancreatic lipase, pro-colipase, pro- cholesterol esterase, pro- phospholipase A2, pro- ribonuclease, pro-deoxyribonuclease, acinar pancreatic inhibitor (SPINK-1)

Question 8

How are pancreatic ducts regulated?

Answer 8

• Secretin - from enteroendocrine cells of duodenum/jejunem; inc secretions by inc cAMP
• VIP - inc release of bicarb

Question 9

How are acini regulated?

Answer 9

• CCK - (intestinal phase) from enteroendocrine cells of duodenum/jejunem; stim sensory afferents –> vagal activity –> inc secretions
  - At high conc CCK can directly stimulate acinar cells
• Ach - (cephalic phase) vagal neuroT –> secretion of zymogens by inc cytosolic Ca++
• Gastrin releasing peptide (bombesin) - stimulate secretion by inc cytosolic Ca++
• Insulin - from endocrine release into local blood of pancreas itself; potentiates enzyme synthesis and secretion (via receptor tyrosine kinase)

Question 10

Acinar Blood Supply

Answer 10

• Capillaries of islet cont as capillaries surrounding acini (insulin exposure)
• Acini farther from islet have independent blood supply

Question 11

Endocrine Function

Answer 11

• Islets of Langerhans (1 million in pancreas)
• Islets contain secretory cells arranged in endocrine core and surrounded by network of fenestrated capillaries
• Secrete hormones into circulation
• Ea cell type only secretes 1 hormone

Question 12

5 Endocrine Cell Types

Answer 12

• Alpha = glucagon (at periphery 15-20%)
• Beta = insulin (at core 60-80%)
• Delta = somatostatin (scattered 5-10%)
• F Cells = pancreatic polypeptide (scattered 15-20%)
• Epsilon = ghrelin (scattered, minor)

Question 13

Trypsin (activation v inhibition)

Answer 13

• ENTEROKINASE - Once in duodenum trypsinogen –> trypsin by enterokinase on brush border; cleaves TAP; trypsin then act all others (amylase and lipase already active)
• Inhibited by PSTI (pancreatic secretory trypsin inhibitor) and SPINK1 (acute phase reactant)
• Ca - inc Ca++ turns trypsin on by allowing second trypsin to cleave TAP and by blocking autolysis site (if low Ca++ then second trypsin cannot bind an

Question 14

9 Protections Against Premature Trypsin Activation

Answer 14

• Pro- form
• Enterokinase located far away in duodenum
• Compartmentalizing zymogens in sep granules
• Low intracellular Ca++
• PSTI/SPINK1 production also in acinar cells
• If excessive trypsin activation then self-destructs
• If in duct then flush w/ bicarb-rich fluid (bicarb maintains inactive form)
• Trypsin activity outside acinar cell activates protease activated receptor (PAR) which protects acinar and duct cells
• Liver makes a1-antitrypsin and b2-macroglobulin –> blood; which inhibit trypsin that leaks