Pancreas: Anatomy

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Pancreas Anatomy Physiology

• Ajith Uliyargoli
• 10/30/07

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Pancreas

• Gland with both exocrine and endocrine functions
• 6-10 inch in length
• 60-100 gram in weight

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• Location Retro-peritoneum, 2nd lumbar vertebral
  level
• Extends in an oblique, transverse position
• Parts of pancreas head, neck, body and tail

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Embryology

• Endodermal in origin
• Develops from ventral and dorsal pancreatic buds
• Ventral bud rotates posteriorly and becomes the
  uncinate process and inferior head of pancreas
• Dorsal bud becomes superior head, neck, body and
  tail
• Ventral bud duct fuses with dorsal bud duct to
  become main pancreatic duct (Wirsung)

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Embryology of Pancreas
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Head of Pancreas

• Includes uncinate process
• Flattened structure, 2 3 cm thick
• Attached to the 2nd and 3rd portions of duodenum
  on the right
• Merges into neck on the left
• Border between head neck is determined by GDA
  insertion
• SPDA and IPDA anastamose between the duodenum and
  the rt. lateral border

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Neck of Pancreas

• 2.5 cm in length
• Straddles SMV and PV
• Superior border relates to the pylorus
• Superior mesenteric vessels emerge from the
  inferior border
• Posteriorly, SMV and splenic vein confluence to
  form portal vein
• Posteriorly, most often no branches to pancreas

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Pancreas
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Body of Pancreas

• Elongated, long structure
• Anterior surface, separated from stomach by
  lesser sac
• Posterior surface, related to aorta, Lt. adrenal
  gland, Lt. renal vessels and upper 1/3rd of Lt.
  kidney
• Splenic vein runs embedded in the post. surface
  closer to the superior border
• Inferior surface is covered by transverse
  mesocolon

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Tail of Pancreas

• Narrow, short segment
• Lies at the level of the 12th thoracic vertebra
• Ends within the splenic hilum
• Lies in the splenophrenic ligament
• Anteriorly, related to splenic flexure of colon
• May be injured during splenectomy (fistula)

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Pancreatic Duct

• Main duct (Wirsung) runs the entire length of
  pancreas
• Joins CBD at the ampulla of Vater
• 2 4 mm in diameter, drains up to 20 secondary
  branches
• Ductal pressure is 15 30 mm Hg (vs. 7 17 in
  CBD) thus preventing reflux and damage to panc.
  duct
• Lesser duct (Santorini) drains superior portion
  of head and empties separately into 2nd portion
  of duodenum

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Arterial Supply of Pancreas

• Variety of major arterial sources (Celiac, SMA
  and Splenic)
• Celiac ? Common Hepatic Artery ? Gastroduodenal
  Artery ? Superior pancreaticoduodenal artery
  which divides into anterior and posterior
  branches
• SMA ? Inferior pancreaticoduodenal artery which
  divides into anterior and posterior branches

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Arterial Supply of Pancreas

• Anterior and posterior collateral arcade between
  the superior and inferior PDA supply head
• Body and tail supplied by splenic artery by about
  10 branches
• Three big branches from splenic are
• Dorsal pancreatic artery
• Pancreatica Magna (midportion of body)
• Caudal pancreatic artery (tail)

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• Arterial Supply of Pancreas

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Approx 25-27 variation in the arterial vascular
anatomy
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Venous Drainage of Pancreas

• Follows arterial supply
• Anterior and posterior arcades drain head and the
  body
• Splenic vein drains the body and tail
• Major drainage areas are
• Suprapancreatic PV
• Retropancreatic PV
• Splenic vein
• Infrapancreatic SMV
• Ultimately, into portal vein

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• Venous Drainage of Pancreas

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Lymphatic Drainage

• Rich periacinar network that drain into 5 nodal
  groups
• Superior nodes
• Anterior nodes
• Inferior nodes
• Posterior PD nodes
• Splenic nodes

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Innervation of Pancreas

• Sympathetic fibers from the splanchnic nerves
• Parasympathetic fibers from the vagus
• Both give rise to intrapancreatic periacinar
  plexuses
• Parasympathetic fibers stimulate both exocrine
  and endocrine secretion
• Sympathetic fibers have a predominantly
  inhibitory effect

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Innervation of Pancreas

• Rich afferent sensory fiber network
• Ganglionectomy or celiac ganglion blockade
  interrupt these somatic fibers (pancreatic pain)
• However the origin of pancreatic pain is
  difficult to explain anatomically

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Histology-Exocrine Pancreas

• 2 major components Acinar cells and Ducts
• They constitute 80 to 90 of the pancreatic mass
• 20 to 40 acinar cells coalesce into a unit
  called the acinus
• Acinar cells secrete the digestive enzymes
• Centroacinar cell (2nd cell type in the acinus)
  is responsible for fluid and electrolyte
  secretion by the pancreas

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Histology-Exocrine Pancreas

• Ductular system - network of conduits that carry
  the exocrine secretions into the duodenum
• Acinus ? small intercalated ducts ? interlobular
  duct ? pancreatic duct
• Interlobular ducts contribute to fluid and
  electrolyte secretion along with the centroacinar
  cells

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Histology-Endocrine Pancreas

• Accounts for only 2 of the pancreatic mass
• Nests of cells - islets of Langerhans
• Four major cell types
• Alpha (A) cells secrete glucagon
• Beta (B) cells secrete insulin
• Delta (D) cells secrete somatostatin
• F cells secrete pancreatic polypeptide

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Histology-Endocrine Pancreas

• B cells are centrally located within the islet
  and constitute 70 of the islet mass
• PP, A, and D cells are located at the periphery
  of the islet

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Physiology Exocrine Pancreas

• Secretion of water and electrolytes originates in
  the centroacinar and intercalated duct cells
• Pancreatic enzymes originate in the acinar cells
• Final product is a colorless, odorless, and
  isosmotic alkaline fluid that contains digestive
  enzymes (amylase, lipase, and trypsinogen)

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Physiology Exocrine Pancreas

• 500 to 800 ml pancreatic fluid secreted per day
• Alkaline pH results from secreted bicarbonate
  which serves to neutralize gastric acid and
  regulate the pH of the intestine
• Enzymes digest carbohydrates, proteins, and fats

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Bicarbonate Secretion

• Centroacinar cells and ductular epithelium
  secrete 20 mmol of bicarbonate per liter in the
  basal state
• Fluid (pH from 7.6 to 9.0) acts as a vehicle to
  carry inactive proteolytic enzymes to the
  duodenal lumen
• Sodium and potassium concentrations are constant
  and equal those of plasma
• Chloride secretion varies inversely with
  bicarbonate secretion

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Bicarbonate Secretion

• Bicarbonate is formed from carbonic acid by the
  enzyme carbonic anhydrase
• Major stimulants
• Secretin, Cholecystokinin, Gastrin, Acetylcholine
• Major inhibitors
• Atropine, Somatostatin, Pancreatic polypeptide
  and Glucagon
• Secretin - released from the duodenal mucosa in
  response to a duodenal luminal pH lt 3

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Enzyme Secretion

• Acinar cells secrete isozymes
• amylases, lipases, and proteases
• Major stimulants
• Cholecystokinin, Acetylcholine, Secretin, VIP
• Synthesized in the endoplasmic reticulum of the
  acinar cells and are packaged in the zymogen
  granules
• Released from the acinar cells into the lumen of
  the acinus and then transported into the duodenal
  lumen, where the enzymes are activated.

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Enzymes

• Amylase
• only digestive enzyme secreted by the pancreas in
  an active form
• functions optimally at a pH of 7
• hydrolyzes starch and glycogen to glucose,
  maltose, maltotriose, and dextrins
• Lipase
• function optimally at a pH of 7 to 9
• emulsify and hydrolyze fat in the presence of
  bile salts

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Enzymes of Pancreas

• Proteases
• essential for protein digestion
• secreted as proenzymes and require activation for
  proteolytic activity
• duodenal enzyme, enterokinase, converts
  trypsinogen to trypsin
• Trypsin, in turn, activates chymotrypsin,
  elastase, carboxypeptidase, and phospholipase
• Within the pancreas, enzyme activation is
  prevented by an antiproteolytic enzyme secreted
  by the acinar cells

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Insulin

• Synthesized in the B cells of the islets of
  Langerhans
• 80 of the islet cell mass must be surgically
  removed before diabetes becomes clinically
  apparent
• Proinsulin, is transported from the endoplasmic
  reticulum to the Golgi complex where it is
  packaged into granules and cleaved into insulin
  and a residual connecting peptide, or C peptide

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Insulin

• Major stimulants
• Glucose, amino acids, glucagon, GIP, CCK,
  sulfonylurea compounds, ß-Sympathetic fibers
• Major inhibitors
• somatostatin, amylin, pancreastatin,
  a-sympathetic fibers

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Glucagon

• Secreted by the A cells of the islet
• Glucagon elevates blood glucose levels through
  the stimulation of glycogenolysis and
  gluconeogenesis
• Major stimulants
• Aminoacids, Cholinergic fibers, ß-Sympathetic
  fibers
• Major inhibitors
• Glucose, insulin, somatostatin, a-sympathetic
  fibers

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Somatostatin

• Secreted by the D cells of the islet
• Inhibits the release of growth hormone
• Inhibits the release of almost all peptide
  hormones
• Inhibits gastric, pancreatic, and biliary
  secretion
• Used to treat both endocrine and exocrine
  disorders

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Pancreatic function tests
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Exocrine function

• Secretin test
• Overnight fast
• Double lumen tube
• Basal secretion
• 2u/kg of Secretin
• Four 20 min collections of secretions
• Test for volume, bicarbonate, amylase

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Fecal fat test

• Distinguish between pancreatic dysfunction and
  intestinal malabsorption
• In Pancreatic disease when lipase secretion is
  reduced by 90- 24-hour fecal fat content is
  elevated to more than 20 g.
• Intestinal dysfunction - Steatorrhea with low
  levels of fecal fat
• Use- Efficacy of pancreatic enzyme replacement

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The dimethadione (DMO) test

• Pancreas degrades Trimethadione (anticonvulsant),
  and secretes its metabolite, DMO.
• Trimethadione - 0.45 g Po TID for 3 days.
• Secretin test is performed.
• The duodenal output of DMO measured
• Impaired in exocrine insufficiency

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The Lundh test

• Based on endogenous secretion of secretin and CCK
  in addition to pancreatic secretion
• Overnight fast
• Basal collection of duodenal fluid
• Meal of 18 g of corn oil, 15 g of casein, and 40
  g of glucose in 300 mL of water.
• Thirty-minute collections - for 2 hours
• Analyzed for trypsin, amylase, and lipase
• Abnormal in patients with chronic pancreatitis
• Limitations - Need for duodenal intubation
• Abnormal - Dis. involving the GI mucosa

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Triolein breath test

• Noninvasive test of exocrine insufficiency
• 25 grams of corn oil containing 5 mCi of
  14Ctriolein is given orally
• 4 hours later - metabolite 14C-carbon dioxide
  measured in breath
• In fat digestion or malabsorption less than 3 of
  the 14Ctriolein dose per hour measured.
• Test repeated after oral pancreatic enzyme
  replacement.
• In exocrine insufficiency achieve a normal rate
  of excretion of 14Ccarbon dioxide, whereas
  patients with enteric disorders show no
  improvement

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Paraaminobenzoic(PABA) acid test

• Noninvasive test of pancreatic insufficiency
• N-benzoyl-l-tyrosyl-PABA is cleaved by
  chymotrypsin to form PABA.
• PABA is absorbed from the small intestine
  excreted in the urine
• One gram of BT-PABA in 300 mL of water is given
  orally, and urine collections are obtained for 6
  hours.
• Patients with chronic pancreatitis excrete less
  than 60 of the ingested dose of BT-PABA.

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Islet hormone - PP levels

• Basal and meal stimulated levels of plasma PP
  measured
• Overnight fast- Test meal consisting of 20
  protein, 40 fat, and 40 carbohydrate is given
• Basal levels
• Normal- 100 to 250 pg/mL)
• Less than 50 pg/mL in severe chronic
  pancreatitis
• After meal PP -Normally rise to 700 to 1,000
  pg/mL
• Reduced to 250 pg/mL
  in severe disease.
• Limitations
• Depends on intact pancreatic innervation,
  depressed in cases of diabetic autonomic
  neuropathy, after truncal vagotomy and antrectomy

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DIFFERENTIAL DIAGNOSIS OF INTESTINAL AND
PANCREATIC STEATORRHEA
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Endocrine function

• Oral GTT
• Confirm the diagnosis of diabetes.
• Indirect assessment of the insulin response to an
  oral glucose load.
• Overnight fastlng
• 2 basal blood samples for Blood sugar
• Oral glucose load of 40 g/m2 is given over 10
  minutes.
• Blood samples are drawn every 30 minutes for 2
  hours

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INTERPRETATION OF ORAL GLUCOSE TOLERANCE TEST
RESULTS
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• Intravenous glucose tolerance test
• Eliminates the GI influences on glucose
  metabolism that affects the oral GTT
• IV bolus of 0.5 g of glucose per kg over 2 to 5
  minutes.
• Blood samples - every 10 minutes for 1 hour.
• The decline in glucose concentration (percentage
  of disappearance per minute) is called the K
  value.
• A K value of 1.5 or higher is normal.

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Intravenous arginine test

• Arginine stimulates the secretion of islet
  hormones
• Diagnosis of hormone-secreting tumors
• Overnight fast, and given a 30-minute infusion of
  0.5 g of arginine per kilogram.
• Blood samples are taken every 10 minutes
• Radioimmunoassays are performed for the specific
  hormones in question.
• This test is particularly useful for the
  diagnosis of glucagon-secreting tumors
• Elevations of plasma glucagon to above 400 pg/mL
  usually indicate a glucagonoma

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Tolbutamide response test

• Useful in detecting hormone-secreting tumors.
• Sulfonylurea stimulates insulin secretion.
• Overnight fasting, basal blood samples are drawn.
• One gram of sodium tolbutamide is given
  intravenously
• Blood glucose level is monitored for 1 hour.
• Blood samples for radioimmunoassay of insulin or
  other suspected hormones, such as somatostatin
  obtained.
• In normal patients, the blood glucose level falls
  to 50 of basal values after 30 minutes.
• Sustained hypoglycemia with hypersecretion of
  insulin is consistent with an insulinoma.
• In the case of a somatostatinoma, somatostatin
  levels are more than twice as high as the
  prevailing normal values for the particular
  somatostatin radioimmunoassay

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Acute pancreatitis

• Blood Investigations CBC,LFT, serum calcium,
  serum amylase and lipase, ABG
• Chest Xray (for exclusion of perforated viscus)
• Abdominal Xrays (for detection of "sentinel
  loop", gallstones which are radioopaque in 10)
• CT abdomen
• U/S abdomen
• MRI/MRA

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Chr. Pancreatitis

• Study of exocrine pancreatic function
• CT- size, duct, stone, mass lesions
• ERCP-Duct size, stenosis, obstruction, stones,
  therapeutic stenting

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Pancreatic neoplasm's

• CBC, LFT, Amylase, Lipase
• Ca-19-9- 80 accurate, prognosis and f/u
• Genetic testing- Genetic syndrome associated with
  hereditary pancreatic cancer-(Peutz-Jeghers,
  Hereditary pancreatitis, FAMMM, HNPCC)
• Genetic Mutations-DPC4 gene(18Q)-missing in 90
  of pancreatic cancers. K-ras mutations common.
  Also changes in p53 and p16 tumor suppressor
  genes.

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• CAT scan - Spiral CT- Cuts taken through pancreas
  both in a arterial phase and a portal venous
  phase
• Local disease and metastatic disease
• MRCP-Non invasive, assess biliary tract in a
  jaundiced pt
• ERCP-90 accurate, in pts whom no mass is seen,
  brushings for biopsy
• U/S
• EUS- Detect early lesions lt2cm, L.N assessment,
  vascular involvement, FNAC

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Cystic neoplasms

• CT scan
• Serous mutilocular ,central calcification,
• Mucinous- more common in body and tail, 30
  malignant potential, needs to be resected
• ERCP- IPMN, common in the head and mucin secreted
  from the ducts

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Functional endocrine neoplasms

• Insulinomas
• Monitored fast test
• Insulin to glucose ratio gt0.4 (N lt0.3)
• Elevated C-peptide and pro-insulin levels
• CT, EUS
• STS (Somatostatin receptor scintigraphy-
  Octreotide scan)- Local tumors-75,
  metastatic-65, significant false negatives
• Visceral angiography- not performed anymore
• Selective arterial calcium stimulation test(GDA,
  splenic, Inferior Panc. Duo. Art)
• Intraop ultrasound

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• Gastrinoma
• Serum gastrin- Fasting gastringt200pgm/ml
• gt1000pgm.ml pathgnomonic
• Gastric acid analysis-Basal Acid Outputgt15mEq/hr
  (Non-ulcerogenic causes - Atrophic gastritis,
  Pernicious anemia, Vagotomy)
• Secretin Stimulation test- Increase by 200 pgm/ml
  above the basal level
• CT, EUS
• SRS- more sensitive than in Insulinoma
• Selective arterial secretin stimulation test
• Intra-op ultrasound

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• VIPOMA
• BMP- Hypokalemia, Metabolic acidosis
• Elevated VIP levels- repeated testing required
• Gastric acid levels- Achlorohydria
• CT, EUS

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• Glucagonoma
• Hyperglycemia
• Hypoproteniemia
• Glucagon levels
• CT, EUS

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• Somatostatinoma
• Hyperglycemia
• Hypocholorohydria
• Somatostatin levelgt100pgm/ml diagnostic