Pancreatic Anatomy and
Physiology
Tyler Stevens, M.D.
Assistant Professor
Cleveland Clinic, Cleveland, OH
Neck
Tail
Head
Uncinate
Body
1
2
Question 1
•
Which of the following are true regarding
the pancreas?
A. Over 90% of its mass is devoted to
endocrine function
B. Blood flow is exclusively supplied by the
pancreaticoduodenal artery
C. Sympathetic stimulation increase secretion
D. The acinus is the functional unit of the
exocrine portion
E. It has neural but not hormonal control
5 weeks
6 weeks
3
Pancreas Divisum
• Failure of dorsal and
ventral ducts to fuse
• Occurs in ~10% of
population
• Rarely causes
pancreatitis
Pancreas Divisum
• Endoscopic features
– Dorsal duct dilation
– Sanorinicele
– Arborization of ventral
duct
• Endoscopic therapy
– Minor papillotomy
4
Annular Pancreas
Yu J et al. AJR 2006;187:1544-1553
5
Exocrine & Endocrine Pancreas
Exocrine Portion:
Acinar tissue
Duct tissue
Endocrine Portion:
Islets of Langerhans
(hormones)
6
Microanatomy
Duct
Acinar tissue
Islet
Microanatomy
7
Question 2
•
Which of the following are true about
cholecystokinin?
A.
B.
C.
D.
E.
It is a peptide comprised of 8 amino acids
It inhibits gallbladder contraction
It speeds gastric empyting
It inhibits pancreatic acinar secretion
It stimulates pancreatic duct secretion
Acinar Cell Control
Zymogen
granules
Golgi
Nucleus
ER
CCK
+
+
Ach
8
Pancreatic Enzymes
• Peptidases
– Trypsinogen  Trypsin
– Chymotrypsinogen  Chymotrypsin
– Proelastase  Elastase
– Procarboxypeptidases  Carboxypeptidases
• Pancreatic lipase
• Pancreatic amylase
• Nucleases
Pancreatic Enzymes
Trypsin
EK
Active
Proteases
Other
Trypsinogen
Proenzymes
9
Genetics of Trypsin
• Mutations of cationic
trypsinogen
– PRSS1 mutation
– Prevents deactivation of
trypsin
Trypsin
• Hereditary pancreatitis
– Autosomal dominant
– 80% penetrance
Trypsinogen
• RAP and CP beginning in
childhood
• 40% lifetime risk of
pancreatic CA
Whitcomb, Nature Genet 1996;14:141
Genetics of Trypsin
• SPINK1: Trypsin
inhibitor
Trypsin
-
– “First line of defense”
• Strong association
with RAP1 and CP2
SPINK
Trypsinogen
1. Aoun, Am J Gastroenterol 2010;105:446
2. Witt, Nat Genet 2000;25:213
10
Duct Cell Control
Cl-
Na+
HCO3-
2 HCO3-
CA
ClCFTR
Secretin
↑cAMP
ACh
M3
11
Intestinal Phase
12
Question 3
•
Which of the following is true about exocrine
pancreatic insufficiency (EPI)?
A. Indirect pancreatic function tests (PFTs) use
hormone secretagogues and duodenal collection
tubes
B. Steatorrhea occurs after 20% of pancreatic
functional mass is lost
C. Fecal fat is both sensitive and specific for EPI
D. Fecal elastase is both non-invasive and accurate for
moderate to severe EPI
E. Patients with refractory celiac disease suffer with
EPI due to diminished acinar cell mass
Causes of EPI
• Loss of pancreatic parenchyma
– Chronic pancreatitis, severe acute pancreatitis, pancreatectomy
• Ductal obstruction
– Pancreatic cancer, main duct intraductal papillary mucinous
neoplasm, strictures/stones
• Duct dysfunction
– Cystic fibrosis
• Diminished stimulation
– Refractory celiac disease, duodenectomy
• Decreased activation of enzymes (loss of enterokinase)
– Celiac disease, Crohn’s disease
• Premature destruction of enzymes
– Zollinger-Ellison syndrome
• Mismatch of secretion with food passage
– Dumping syndrome, antrectomy, gastric bypass, gastroparesis
13
Indirect PFTs
• Do not involve direct hormonal stimulation
• Non-invasive
– “Tubeless” PFTs
• Reasonable accuracy for moderate to
severe EPI
Serum Trypsinogen
• Decreased in CP with EPI
– Reflects the ‘functional acinar mass’; correlates with
fecal fat
– Normal range 30-100
• <20 ng/dL suggests CP
• 20-29 ng/dl ‘intermediate’
• >100 ng/dl suggests acute pancreatitis
• Attribute: Ease of performance
– Used to screen for CF
• Limitations
– Low sensitivity
– Variable assays: ELISA vs. RIA
14
Fecal Fat
• Increased in patients with advanced EPI
– Sudan stain (>100 fat globules)
– Timed (e.g. 72 hour) collection (>8 g/day)
• Attributes
– Verifies and quantifies steatorrhea
– Monitors response to PERT
• Limitations
–
–
–
–
–
Misses mild and moderate EPI
Requires high-fat diet
Stool collection cumbersome and unpleasant
Difficult to assess compliance
Fat in stool is not specific for EPI (e.g. Crohn’s, celiac
disease, small intestinal bacterial overgrowth)
Fecal Elastase-1
• Decreased in moderate-severe EPI
– Minimal degradation during intestinal transit
– Normal range >200 µg/g
• <50 µg/g ‘severe EPI’—most specific and useful threshold
• 51-200 µg/g ‘moderate EPI’—not as specific or useful
– Sensitivity 41-93%; specificity 93-100%
• Attributes
– More specific than fecal fat
– Only small amount of stool required
– Test of choice in children
• Limitations
– False positives in watery diarrhea (dilutional effect)
– Insensitive for mild EPI
– Variability in assays (polyclonal vs. monoclonal)
15
Fecal Chymotrypsin
• Less accurate than elastase
• Cross-reacts with porcine chymotrypsin,
so good for monitoring compliance
• Less available than Elastase in U.S.
Test Performance of Indirect PFTs
1.
2.
3.
4.
5.
Freedman S, NEJM 1995, Kitagawa, Pancreas. 1997
Gullo L, Dig Dis Sci,1999.
Hahn, Pancreas. 2005
Amann, Pancreas 1996
Toskes NEJM, 1984.
Slide courtesy of Jonathan Lieb
16
Direct PFT
• Collection and analysis of
pancreatic fluid following
hormone stimulation
• ‘Gold standard’ for EPI
• EPI is a surrogate for
fibrosis
– PFTs considered a
‘reference standard’ for CP
17