 There are usually no anterior venous tributaries, and a plane
can usually be developed between the neck of the pancreas
 Situated deep in the center of the abdomen and surrounded
by numerous important structures and major blood vessels.
 A seemingly minor trauma to the pancreas can result in the
release of pancreatic enzymes and cause life-threatening
pancreatitis.
Gross Anatomy
 Retroperitoneal organ
 Llies in an oblique position
 Sloping upward from the C-loop of the duodenum to the
splenic hilum.
 Weighs 75-100 g and is about 15-20 cm long (adult)
The fact that the pancreas is situated so deeply in the abdomen
and is sealed in the retroperitoneum explains the poorly
localized and sometimes ill-defined nature with which
pancreatic pathology presents. Patients with pancreatic CA
without bile destruction without bile obstruction usually present
after months of vague upper abdominal discomfort, or no
antecedent symptoms at all. Due to its retroperitoneal
location, pain associated with pancreatitis often is
characterized as penetrating through to the back.
Regions of the Pancreas
Head, Neck, Body and Tail
Head
 Nestled in the C-loop of the duodenum and is posterior to the
transverse mesocolon.
 Located posterior to the head:
Vena Cava
Right Renal Artery
Right and Left Renal Vein
Neck
 Lies directly anterior to the portal vein
 At the inferior border of the neck of the pancreas, the
superior mesenteric vein joins the splenic vein and then
continues toward the porta hepatis as the portal vein. The
inferior mesenteric vein often joins the splenic vein near its
junction with the portal vein.
Sometimes, the inferior mesenteric vein joins the superior
mesenteric vein or merges with the superior mesenteric portal
venous junction to form a trifurcation.
 The superior mesenteric artery lies parallel to and just to the
left of the superior mesenteric vein.
 The uncinate process and the head of the pancreas wrap
around the right side of the portal vein and end posteriorly
near the space between the superior mesenteric vein and
superior mesenteric artery.
 Venous branches draining the pancreatic head and uncinate
process enter along the right lateral and posterior sides of
the portal vein.
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and the portal and superior mesenteric veins during
pancreatic resection, unless the tumor is invading the vein
anteriorly.
 The common bile duct runs in a deep groove on the posterior
aspect of the pancreatic head until it passes through the
pancreatic parenchyma to join the main pancreatic duct at
the ampulla of Vater.
Body & Tail
 Both lie anterior to the splenic artery and vein. The vein runs
in a groove on the back of the pancreas and is fed by
multiple fragile venous branches from the pancreatic
parenchyma. (These branches must be divided to perform a
spleen-sparing distal pancreatectomy.)
 The splenic artery, often tortuous, runs parallel and just
superior to the vein alog the posterior superior edge of the
body and tail of the pancreas.
 The anterior surface of the body of the pancreas is covered
by peritoneum. Once the gastrocolic omentum is divided, the
body and tail of the pancreas can be seen along the floor of
the lesser sac, just posterior to the stomach. Pancreatic
pseudocysts commonly develop in this area, and the
posterior aspect of the stomach can form the anterior wall of
the pseudocyst, allowing drainage to the stomach.
 The base of the transverse mesocolon attaches to the inferior
margin of the body and tail of the pancreas. The transverse
mesocolon often forms the inferior wall of the pancreatic
pseudocysts or inflammatory processes, allowing surgical
drainage through the transverse mesocolon
 The body of the pancreas is anterior to the aorta at the origin
of the superior mesenteric artery.
 The neck of the pancreas is anterior to the vertebral body of
L1 and L2, and blunt anteroposterior trauma can compress
the neck of the pancreas against the spine, causing
parenchymal and sometimes, ductal injury.
 The neck divides the pancreas into approximately two equal
halves.
 The small portion of the pancreas anterior to the left kidney
is referred to As the tail and is nestled in the hilum of the
spleen near the splenic flexure of the left colon.
Pancreatic Duct Anatomy
 The pancreas is formed by the fusion of the ventral and
dorsal bud.
 The duct from the smaller ventral bud - arises from the
hepatic diverticulum, and connects directly to the common
bile duct.
 The duct from the larger dorsal bud - arises from the
duodenum, and drains directly into the duodenum.
 The duct of the ventral anlage becomes the duct of Wirsung.
 The duct from the dorsal anlage becomes the duct of
Santorini.
 With gut rotation, the ventral anlage rotates to the right and
around the posterior side of the duodenum to fuse with the
dorsal bud.
 The ventral anlage becomes the inferior portion of the
pancreatic head and the uncinate process.
 The dorsal anlage becomes the body and tail of the pancreas.
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  The ducts from each anlage usually fuse together in the
pancreatic head such that most of the pancreas drains
through the duct of Wirsung or main pancreatic duct, into the
common channel formed from the bile duct and pancreatic
duct.
 The length of the common channel is variable.
 Commonly, the duct from the dorsal anlage, the duct of
Santorini, persists as the lesser pancreatic duct, and
sometimes drains directly into the duodenum through the
lesser papilla just proximal to the major papilla.
Pancreas Divisum - the ducts of Wirsung and Santorini fail to
fuse resulting to the majority of the pancreas draining through
the duct of Santorini and the lesser papilla. The minor papilla
can be inadequate to handle the flow of pancreatic juices from
the majority of the gland. This relative outflow obstruction can
result in pancreatitis and is sometimes treated by
sphincteroplasty of the minor papilla.
 The main pancreatic duct is usually only 2-3mm in diameter.
Pressure in the pancreatic duct is about twice that in the
common bile duct to prevent reflux of bile into the pancreatic
duct.
 The main pancreatic duct joins with the common bile duct
and empties at the ampulla of Vater or major papilla, which is
nd
located on the medial aspect of the 2 portion of the
duodenum.
Sphincter of Oddi – muscle fibers around the ampulla which
controls the flow of pancreatic and biliary secretions into the
duodenum. Contraction and relaxation of the sphincter is
regulated by complex neural and hormonal factors.
 Two (2) cm proximal to the ampulla of Vater lies the lesser
papilla from the duct of Santorini.
Vascular & Lymphatic Anatomy
 Blood supply from the pancreas comes from multiple
branches from the celiac and superior mesenteric arteries.
 The common hepatic artery gives rise to the gastroduodenal
artery before continuing toward the porta hepatis as the
proper hepatic artery.
 The right gastric artery branches off the gastroduodenal
artery just superior to the duodenum. The gastroduodenal
artery then travels inferiorly anterior to the neck of the
pancreas and posterior to the duodenal bulb. A posterior
ulcer in the duodenal bulb can erode into the gastroduodenal
artery in this location.
 At the inferior border of the duodenum, the gastroduodenal
artery gives rise to the right gastroepiploic artert then
continues on as the anterior superior pancreaticoduodenal
artery, which branches into the anterior and posterior
superior pancreaticoduodenal arteries.
 As the superior mesenteric artery passes behind the neck of
the pancreas, it gives off the inferior pancreaticoduodenal
artery at the inferior margin of the neck of the pancreas. This
vessel quickly divides into the anterior and posterior
pancreaticoduodenal arteries. The superior and inferior
pancreaticoduodenal arteries join together within the
parenchyma of the anterior and posterior sides of the head
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of the pancreas along the medial aspect of the C-loop of the
duodenum and head of the pancreas.
 Therefore, it is impossible to resect the head of the pancreas
without devascularizing the duodenum, unless a rim of
pancreas containing the pancreaticoduodenal arcade is
preserved.
 The right hepatic artery, common hepatic artery or
gastroduodenal arteries can arise from the superior
mesenteric artery.
Replaced Right Hepatic Artery- the right hepatic artery will
arise from the superior mesenteric artery and travel upwards
toward the liver along the posterior aspect of the head of the
pancreas.
 The body and tail of the pancreas are supplied by multiple
branches of the splenic artery. The splenic artery arises from
the celiac trunk and travels along the posterior-superior
border of the body and tail of the pancreas toward the
spleen.
 The inferior pancreatic artery usually arises from the superior
mesenteric artery and runs to the left along the inferior
border of the body and tail of the pancreas, parallel to the
splenic artery.
Three vessels run perpendicular to the long axis of the
pancreatic body and tail and connect the splenic artery and
inferior pancreatic artery. From medial to lateral..
Dorsal Pancreatic Artery
Great Pancreatic Artery
Caudal Pancreatic artery
 These arteries form arcades within the body and tail of the
pancreas, and account for the rich vascular blood supply.
 The veins are usually superficial to the arteries within the
parenchyma of the pancreas.
 There is an anterior and posterior venous arcade within the
head of the pancreas.
 The superior veins drain directly into the portal vein just
above the neck of the pancreas.
 The posterior inferior arcade drains directly into the inferior
mesenteric vein at the inferior border of the neck of the
pancreas. These venous tributaries must be divided during a
Whipple procedure.
 The anterior inferior pancreaticoduodenal vein joins the right
gastroepiploic vein and the middle colic vein to form a
common venous trunk, which enters into the superior
mesenteric veins.
 Traction on the transverse colon during colectomy can tear
these fragile veins.
 There are also numerous small venous branches coming from
the pancreatic parenchyma directly into the lateral and
posterior aspect of the portal vein. Venous return from the
body and tail of the pancreas drains into the splenic vein.
 The lymphatic drainage from the pancreas is diffuse and
widespread. The profuse network of lymphatic vessels and
lymph nodes draining the pancreas provides egress to tumor
cells arising from the pancreas.
 Pancreatic cancer often presents with positive lymph nodes
and a high incidence of local recurrence after resection.
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  Lymph nodes can be palpated along the distal bile duct and  The pancreatic juice is a combination of acinar cell and duct
posterior aspect of the head of the pancreas in the cell secretions.
pancreaticoduodenal groove, where the mesenteric vein
passes under the neck of the pancreas, along the inferior Acinar cells – pyramid shaped, with their apices facing the
border of the body, at the celiac axis and along the hepatic lumen of the acinus. Near the apex of each cell are numerous
artery ascending into the porta hepatis, and along the splenic enzyme-containing zymogen granules that fuse with the apical
artery and vein. cell membrane. Individual acinar cells secrete all types of
 The pancreatic lymphatics also communicate with lymph enzymes.
nodes in the transverse mesocolon and mesentery of the
proximal jejunum. Secretions:
 Tumors in the body and tail of the pancreas often Amylase
metastasize to the nodes and lymph nodes along the splenic Proteases
vein and in the hilum of the spleen. Lipases

Neuroanatomy Pancreatic amylase – only pancreatic enzyme secreted in

 The pancreas is innervated by the sympathetic and active form; hydrolyzes starch and glycogen to glucose,
parasympathetic nervous systems. maltose, maltotriose, and dextrins.
 The acinar cells responsible for exocrine secretion.
 The islets for endocrine secretion. Cholecystokinin (CCK) releasing peptide, CCK and secretin –
 The islet vasculature are innervated by both systems. released by endocrine cells that stimulate the pancreas to
 The parasympathetic system stimulates endocrine and secrete enzymes and bicarbonate into the intestine from
exocrine secretion. gastric hydrolysis of protein
 The sympathetic system inhibits secretion.
Proteolytic enzymes – secreted as proenzymes that require
The pancreas is also innervated by neurons that secrete amines activation.
and peptides:
Somatostatin Trypsinogen – converted to its active form, Trypsin – by
Vasoactive Intestinal Peptide (VIP) another enzyme, Enterokinase (from duodenal mucosal cells)
Calcitonin gene-related peptide (CGRP)
Galanin Trypsin in turn activates other proteolytic enzymes. But its
activation is also prevented by the presence of inhibitors that
are also secreted by the acinar cells.
 The pancreas also has a rich supply of afferent sensory fibers,
which are responsible for the intense pain associated with
Familial Pancreatitis - caused by a failure to express a normal
advanced pancreatic cancer, as well as acute and chronic
trypsinogen inhibitor, Pancreatic Secretory Trypsin Inhibitor
pancreatitis. These somatic fibers travel superiorly to the
(PSTI) aka Serine Protease Inhibitor Kazal Type 1 (SPINK1).
celiac ganglia. Interruption of these fibers can stop
transmission of pain sensation.
Inhibition of trypsinogen activation ensures that enzymes
WITHIN the pancreas remain inactive and are activated only
Histology and Physiology
within the duodenum.
85% - exocrine function
PRSS1 mutation – results in premature, intrapancreatic
10% - extracellular matrix
activation of trypsinogen; accounts for 2/3 of cases of
4% - blood vessels and major ducts
hereditary pancreatitis.
2% - endocrine tissue
Chymotrypsinogen – activated to form chymotrypsin.
 Although patients can live without a pancreas when insulin
and digestive enzyme replacement are administered, the loss
Elastase, Carboxypeptidase A&B, Phospholipase – also
of the islet-acinar coordination leads to impairment in
activated by trypsin.
digestive function.
 Although only approximately 20% of the normal pancreas is Trypsin, Chymotrypsin and Elastase – cleave bonds between
required to prevent insufficiency, in many patients amino acids within a target peptide chain
undergoing pancreatic resection, the remaining pancreas is
not normal, and pancreatic endocrine and exocrine Carboxypeptidase A & B – cleave amino acids at the end of
insufficiency can develop with removal of smaller portions of
peptide chains.
the gland.
Individual amino acids and small dipeptides are then actively
The Exocrine Pancreas transported into the intestinal epithelial cells.
 Secretes approximately 500-800 mL per day of colorless,
odorless, alkaline, isosmotic pancreatic juice.

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 Pancreatic lipase – hydrolyzes triglycerides to 1-monoglyceride Endocrine Pancreas
and fatty acid. It is secreted in an active form. Islets of Langerhans – 1 million in the normal adult pancreas
and vary greatly in size from 40 to 900 um.
Colipase – also secreted by the pancreas and binds to lipase,
changing its molecular configuration and increasing its activity. Most islets contain 3000-4000 cells of five major types:
Alpha cells – secrete glucagon
Phospholipase A2 – secreted by the pancreas as a proenzyme Beta cells – secret insulin
that becomes activated by trypsin. It hydrolyzes phospholipids Delta Cells – secrete somatostatin
and as with all lipases, requires bile salts for its action. Epsilon Cells – secrete ghrelin
PP cells – secrete PP
Carboxylic Ester Hydrolase & Cholesterol Esterase – hydrolyze
neutral lipid substrates. Insulin – 56-amino acid peptide with two chains, alpha and
beta chain, joined by two disulfide bridges and a connecting
The hydrolyzed fat is then packaged into micelles for transport peptide or C peptide.
into the intestinal epithelial cells, where the fatty acids are
reassembled and packaged inside the chylomicrons for Proinsulin – made in the endoplasmic reticulum and then is
transport through the lymphatic system into the bloodstream. transported to the Golgi complex, where it is packaged into
granules and the C-peptide is cleaved off.
Centroacinar and Intercalated duct cells – secrete water and
electrolytes present in the pancreatic juice; also contain the Phases of Insulin Secretion
enzyme carbonic anhydrase which is needed for bicarbonate First Phase – lasts about 5 minutes after a glucose challenge
secretion. Second Phase – longer, sustained release due to ongoing
production of new insulin.
Acinus – composed of 40 acinar cells arranged into a spherical
unit with centroacinar cells located in the center. Beta cell synthesis of insulin is regulated/influenced by the
following:
The amount of bicarbonate secreted varies with the pancreatic Plasma glucose levels
secretory rate, with greater concentrations of bicarbonate Neural signals
being secreted as the pancreatic secretory rate increases. Paracrine influence of other islet cells
Plasma amino acid levels (arginine, lysine, leucine)
Chloride secretion varies inversely with bicarbonate secretion. Free fatty acids
Sodium and potassium concentrations are kept constant.
Diagnosis: using oral and intravenous (IV) glucose tolerance
Secretin – hormone released from cells in the duodenal tests.
mucosa in response to acidic chime passing through the pylorus
in the duodenum; major stimulant for bicarbonate secretion Oral glucose does not only enters the bloodstream but also
which buffers the acidic fluid entering the duodenum from the stimulates the release of ff enteric hormones:
stomach. Glucose-dependent Insulinotropic Polypeptide (GIP)
Glucagon-like peptide 1 (GLP-1)
CCK also stimulates bicarbonate secretion but to a much lesser Incretins
extent than secretin. CCK potentiates secretin-stimulated
bicarbonate secretion. Oral glucose tolerance test (OGTT)
 Patient is fasted overnight
Gastrin & Acetylcholine – both stimulants of gastric acid  Basal glucose value is determined
secretion and weak stimulants of pancreatic bicarbonate  75 g of glucose is given orally over 10 minutes
secretion.  Blood samples are taken every 30 minutes for 2 hours.
 Normal values and criteria for diabetes vary by age, but
Truncal vagotomy reduces bicarbonate and fluid secretion. essentially all values should be <200 mg/dL and the 120-
Inhibits exocrine secretion: minute value should be <140 mg/dL.
Somatostatin
Pancreatic polypeptide (PP) Stimulate insulin release: Inhibit Insulin release:
Glucagon Glucagon Somatostatin
GIP Amylin
Destruction of the branching ductal tree from recurrent GLP-1 Pancreastatin
inflammation, scarring, and deposition of stones eventually CCK Alpha sympathetic fibers
contributes to destruction of the exocrine pancreas and Cholinergic fibers
exocrine pancreatic insufficiency. Beta sympathetic fibers

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 INSULIN`S GLUCOREGULATORY FUNCTION is to inhibit
endogenous (hepatic) glucose production and to facilitate
glucose transport into cells thus lowering plasma glucose
levels.
 Insulin also inhibits glycogenolysis, fatty acid breakdown,
ketone formation.
 Insulin stimulates protein synthesis
 If the remaining portion of the pancreas is healthy, about
80% of the pancreas can be resected without the patient
becoming diabetic. In patients with chronic pancreatitis, or
other conditions with glands diseased, resection can result in
pancreatogenic or type 3C diabetes.
Insulin receptors - dimeric, tyrosine kinase-containing
transmembrane proteins located on all cells.
 Insulin deficiency results in an overexpression or upregulation
of insulin receptors, which causes an enhanced sensitivity to
insulin in muscle and adipocytes.
 Type 2 diabetes is associated with a downregulation of
insulin receptors and relative hyperinsulinemia, with resulting
insulin resistance.
Glucagon – 29 amino acid, single chain peptide that promotes
hepatic glycogenolysis and gluconeogenesis and counteracts
the effects of insulin through its hyperglycemic action;
primarily regulated by glucose but has an inhibitory rather than
stimulatory effect.
Stimulated by: Inhibited by:
Hypoglycemia GLP-1 (in-vivo)
Amino acids alanin and arginine. Insulin
Cholinergic and beta sympathetic fibers Somatostatin
Alpha
sympathetic fibers
 In pancreatogenic or type 3c diabetes, glucagon
responsiveness to a fall in blood glucose is lost, thereby
increasing the risk for hypoglycemia.
Somatostatin – wide anatomic distribution not only in neurons
but in pancreas, gut, and other tissues; highly conserved
peptide hormone; stimulated during meal.
 One gene encodes for a common precursor that is
differentially processed to generate tissue-specific amounts
of two bioactive products, somatostatin-14 and
somatostatin-28. These peptides INHIBIT endocrine and
exocrine function.
 Somatostatin receptors (SSTRs): SSTR 1, SSTR 2, SSTR 3, SSTR
4, SSTR 5
Stimulated by: Inhibited by:
Intraluminal fat Acetylcholine
Acidification of the gastric and
duodenal mucosa
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Pancreatic polypeptide – 36 amino acid straight chain peptide.
Enteral neural stimulation of PP release:
PROTEIN (most potent) > FAT > GLUCOSE
Stimulated by: Inhibited by:
Hypoglycemia Glucagon
Phenylalanine Somatostatin
Tryptophan
Fatty acids in the duodenum
Insulin
Gastric Inhibitory Peptide
 Vagal stimulation is the most important regulator of PP
secretion. Vagotomy eliminates the rise in PP levels usually
seen after a meal. This can be used as a test for the
completeness of a surgical vagotomy or for the presence of
diabetic autonomic neuropathy
 PP has been shown to inhibit choleresis (bile secretion) and
gallbladder contraction and secretion by the exocrine
pancreas.
 PP’s most important role is in glucose regulation.
 Deficiency in PP secretion is associated with diminished
hepatic insulin sensitivity
Ghrelin – secreted from Epsilon cells; also present in the gastric
fundus in large amounts and stimulates growth hormone
secretion; Orexigenic or appetite stimulating; block insulin
effects on the liver and inhibits Beta cell response to incretin
and glucose.
Amylin/Islet Amyloid Polypeptide (IAPP) – found in pancreatic
Beta cells stored along with insulin; modulates or
counterregulates insulin secretion and function.
Pancreastatin – inhibits insulin and possibly somatostatin
release; augments glucose release; inhibits pancreatic exocrine
secretion.
Islet Distribution
70% total islet cell mass - made up of Beta cells located in the
center, while the rest are in the periphery
5% - Delta cells
10% - Alpha cells
15% - PP cells
 In reality, more than 20 different hormones are secreted by
the islets, and the exact functions of this milieau are very
complex.
 Alpha and Beta cells are evenly distributed throughout the
pancreas but islets in the head and uncinate process (ventral
anlage) have a higher % of PP cells and fewer Alpha cells
 In the body and tail (dorsal anlage), majority are Alpha cells
and few PP cells.
 Pancreatoduodenectomy removes 95% of PP cells in the
pancreas leading to higher incidence of glucose intolerance
after the Whipple procedure compared to a distal
pancreatectomy with an equivalent amount of tissue
resected.
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 Acute Pancreatitis Hereditary Pancreatitis
PRSS1 cationic trypsinogen gene mutation – premature
 HALLMARK: Acute pancreatic inflammation associated with activation of trypsinogen
little or no fibrosis. SPINK1 protein mutation from which blocks the binding site of
 Ranges from mild self-limiting inflammation to critical disease trypsin
characterized by infected pancreatic necrosis, multiple organ
failure, and a high risk of mortality Tumors
 Smoking – independent risk factor for acute pancreatitis. Pancreatic or periampullary tumor

Etiology
 Gallstones (females) and alcohol (males) – 80% of cases; most Hyperlipidemia
common Patients with Type I and V hyperlipoproteinemia with marked
 Idiopathic type – characteristic finding of microlithiasis, hypertriglyceridemia
birefringent crystals on bile microscopy Lipase liberates toxic fatty acids into the pancreatic
microcirculation leading to impairment and ischemia
Gallstones Hypothesis for Acute Pancreatitis Tx: Clofibrate, Dietary modification
1. Common channel hypothesis – it was proposed that a
gallstone transiently lodged in the distal common channel of Drugs & Miscellaneous
the ampulla of Vater allowed bile to reflux into the pancreatic
duct form. Thiazide diuretics Azathioprine
Furosemide Estrogens
2. Transient incompetence caused by the passage of a stone 1-asparaginase Methyldopa
through the sphincter might allow duodenal fluid and bile to 6-mercaptopurine Tetracycline
reflux into the pancreatic duct Sulfonamides Pentamidine
Procainamide Nitrofurantoin
3. Gallstone obstructing the pancreatic duct leading to ductal Dideoxyinosine Valproic acid
hypertension. This backpressure might lead to minor ductal AChe inhibitors
disruption, extravasation of pancreatic juice into the less Hypercalcemia from hyperparathyroidism
alkaline interstitium of the pancreas, and promotion of enzyme Ascaris lumbricoides
activation Clonorchis sinensis causing Oriental cholengitis
Azotemia
Alcohol Vasculitis
 Sustained alcohol ingestion + recurrent acute pancreatitis can Sting of the Trinidadian scorpion
lead to chronic pancreatitis (drinking for more than a decade)
 Type of alcohol consumed is less important than the amount Pathophysiology
consumed and the pattern of drinking. Pancreatitis begins with the activation of digestive zymogens
 It is common for patients with alcohol associated acute inside acinar cells, which cause acinar injury
pancreatitis to have a history of excess alcohol consumption
prior to the first attack. Precipitating Initial Events
 Ethanol is a metabolic toxin to pancreatic acinar cells
A. Acinar Cell Events
 The secretory burst coupled with ethanol induced spasm of
Pancreatitis is essentially the premature, intrapancreatic
the sphincter of Oddi incited acute pancreatitis
activation of digestive enzymes, resulting to autodigestion.
 Ethanol also induces ductal permeability
There is intra-acinar activation of trypsinogen from injurious
 Ethanol also increases protein content of pancreatic juice,
stimuli.
decrease bicarbonate levels and trypsin inhibitor
concentration
Several Protective mechanisms:
 Formation of protein plugs causing obstruction
1. Enzymes are synthesized as inactive precursors called
proenzymes or zymogens. The activation occurs safely in the
Iatrogenic duodenum where the brush border enteropeptidases (aka
Pancreatic Biopsy enterokinase) activates the trypsinogen and the resulting
Exploration of the extrahepatic biliary tree and AOV trypsin activates other zymogens.
Distal gastrectomy
Splenectomy 2. Synthesis of trypsin inhibitors which are transported and
Colectomy stored along with the digestive enzyme zymogens to inhibit
Nephrectomy prematurely activated trypsinogen within the pancreatic acinar
Aortic Aneurysmorraphy cells.
Retroperitoneal lymphadenectomy
Splanchnic hypoperfusion with cardio-pulmonary bypass 3. Acute Pancreatitis can occur locally (within the gland) with
Cathepsin B which is located in the cytoplasmic vacuole of the

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 cells. It activates trypsinogen. Cathepsin once activated and in
the cytosol, initiates apoptotic death. There is release of
Cytochrome C that initiates apoptotic cascade. Inhibition of
cathepsin B by pharmacological inhibitors or by genetic
depletion of cathepsin B eliminates trypsin activation.
4. Injurious stimuli leads to sustained cytosolic Calcium
increase. Blocking the Calcium increase prevents co-localization
and activation of trypsin. Pre-ERCP (Endoscopic Retrograde
Cholangipnacreatography) supplementation of Magnesium,
antagonist of Calicum is currently evaluated.
B. Intrapancreatic Events
1. Activated Neutrophils in tissue injury release superoxides
(“respiratory burst”) and proteolytic enzymes (cathepsins,
elastase, and collagenase) which cause further injury.
2. Macrophage release cytokines (TNF Alpha, IL6, IL8) which
mediate local and systemic inflammatory response leading to
pancreatic vascular permeability resulting to edema,
hemorrhage and microthrombi. Failure of pancreatic
microcirculation results in hypoperfusion and necrosis.
Interstitial Edematous Pancreatitis – is acute inflammation of
the pancreatic parenchyma and peripancreatic tissues but
without recognizable necrosis.
Necrotizing Pancreatitis – term when necrosis is present,
should be evidenced by pancreatic hypoperfusion with contrast
CT.
C. Systemic Events
1. There is systemic inflammation and multiorgan failure.
2. The NFkB-dependent inflammatory pathway is the KEY
pathway. It activates typsin independently from sustained
Calcium increase. Once activated, it synthesizes multiple
cytokines and chemokines leading to recruitment of various
inflammatory cells.
TAKE NOTE that although intra-acinar events initiate acute
pancreatitis, events occurring SUBSEQUENT to acinar cell injury
will determine the SEVERITY. Elucidation of inflammatory
mediators (TNF A, IL1, IL2, IL6) can modulate the course of
severe acute pancreatitis.
3. Organ failure can develop at any stage of acute
pancreatitis associated with an overwhelming proinflammatory
response. The proinflammatory constituents can appear in the
mesenteric lymph bypassing the liver may contribute to the
development of organ failure.
4. The development of Pancreatic Necrosis, breakdown of
intestinal barrier, suppression of the immune response (peak in
rd th
the 3 to 4 week) may cause deterioration in the patient and
may result to late development of Systemic Inflammatory
Response Syndrome (SIRS) and Multiorgan Dysfunction
syndrome/failure (MODS/F)
Organ failure is scored using the Marshall or Sequential Organ
Failure Assessment (SOFA) systems.
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Organ systems frequently involved:
Cardiovascular
Respiratory
Renal
Management of the Patient
General Considerations
 Mild acute pancreatitis – less than a week in the hosp
 Severe/Critical type – weeks or months
 The risk of mortality reflects the spectrum of severity.
 THE EARLIER IDENTIFICATION OF HIGH RISK CATEGORIES AND
TRANSFER OF PATIENTS TO SPECIALIZED CENTERS IS AN
IMPORTANT PRIORITY OF MANAGEMENT.
 Use Ranson’s Criteria to identify high risk patients.
Diagnosis
 Acute onset of severe constant epigastric pain which often
radiates through to the mid back
 Elevation of serum amylase or lipase (>3x upper limit of
normal) – to rule out hyperamylasemia
 Imaging (usually by contrast enhanced CT scanning) is ONLY
required for the diagnosis of acute pancreatitis when these
diagnostic criteria are NOT MET.
 Serum Amylase conc increases almost immediately with the
onset of disease and peaks within several hours. It remains
elevated for 3-5 days before returning to normal.
 There is NO significant correlation between the magnitude of
serum amylase elevation and severity of pancreatitis.
 Hyperamylasemia can occur NOT INVOLVING the
pancreatitis. (Small bowel obstruction, perforated duodenal
ulcer)
 In patients with hyperlipidemia, serum amylase can be
NORMAL because of the interference of lipids with chemical
determination of serum amylase.
 Urinary clearance levels of pancreatic enzymes is a more
sensitive marker than serum levels in pancreatitis! It is
recommended that amylase concentrations also be measured
in the urine. Urinary amylase levels usually remain elevated
for several days after serum levels have returned to normal..
even in patients with severe pancreatitis associated with
significant necrotic damage where the pancreas may not
release large amounts of enzymes into the circulation.
 With increasing severity of disease, the intravascular fluid
loss may become life-threatening as a result of sequestration
of edematous fluid in the retroperitoneum.
 There may also be bleeding into the retroperitoneum or
peritoneal cavity. Blood from necrotizing pancreatitis may
dissect through soft tissues and manifest as a bluish
discoloration around the umbilicus (CULLEN’s SIGN) or in the
flanks (GREY TURNER’S SIGN)
 Severe fluid loss may lead to prerenal azotemia,
hyperglycemia, hypoalbuminemia, and hypocalcemia to
produce tetany.
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 Pain Management
 PAIN is the CARDINAL SYMPTOM of acute pancreatitis
 Those with mild pain can usually be managed with NSAID
 Severe pain are best managed with Opioid analgesia
Buprenorphione
Pentazocine
Procaine Hydrochloride
Meperidine
*Morphine – is AVOIDED due to its potential to cause sphincter
of Oddi spasm.
Predicting Severity
 Accurately predicting acute pancreatitis severity is important
in making triage decisions.
 Use Ranson’s criteria or modified Glasgow criteria
 When 3 or more positive criteria, the disease is considered
“predicted severe”
Determining the Etiology
 History of alcohol ingestion and blood ethanol levels
 Gallstones by ultrasonography (females over age 50 with
elevated ALP >300 IU/L, ALT >100 IU/L and Amylase >4000
IU/L)
 In the absence of gallstone and alcohol, include history of
drug abuse, trauma, ERCP, infection, measure serum
Triglycerides, Calcium,
Fluid Resuscitation
 Fluid therapy to restore and maintain circulating blood
volume is the most important intervention in the early
management of acute pancreatitis.
 It is best to resuscitate with a balanced crystalloid and to
restore normal blood volume, blood pressure, and urine
output. Lactated Ringer’s solution may be superior to normal
saline in reducing systemic inflammatory response.
 Caution in patients with cardiac and renal disease and in the
elderly.
Nutritional support
 It is no longer acceptable to “rest the pancreas” by avoiding
enteral nutrition, and parenteral nutrition should only be
offered. Enteral nutrition should be commenced after initial
fluid resuscitation and within the first 24 hours of admission.
 A delay in commencing early enteral nutrition may contribute
to the development of intestinal ileus and feeding
intolerance.
 Aggressive early enteral feeding particularly prior to
adequate resuscitation may put the patient at risk of
nonocclusive mesenteric ischemia.
Cross-Sectional Imaging
 It may be necessary to perform CT Scan to diagnose acute
pancreatitis in patients who are severely ill, undifferentiated
abdominal pain.
 The primary purpose of cross sectional imagine is the
diagnosis of local complications, extent of pancreatic
necrosis, or presence of different fluid collections.
DocMegz2017
 MR is superior to CT scanning in detecting any sold
component within collections
 Arterial Phase CT Scan (CTa) is useful in detecting
pseudoaneurysm, active bleeding and/or hematoma.
Therapeutic Endoscopic Retrograde
Cholangiopancreatography (ERCP)
 Early ERCP reduces complications but not mortality in
patients with severe gallstone-associated acute pancreatitis.
 The benefits of this may be offset however there is risk in the
procedure – increase severity of pancreatitis, bleeding,
cholangitis, and duodenal perforation.
Antibiotics
 The use of broad-spectrum antibiotics to treat established
infection in acute pancreatitis is well-established practice but
not as prophylactic antibiotic.
Managing Local Complications
 Vigilance is required for the timely and accurate diagnosis of
local complications.
 The decision to intervene is based on the clinical status and
trajectory of the patient.
 Close monitoring: regular measurement of inflammatory
markers and pancreatic protocol CT Scan if local complication
is suspected.
 In practice, intervention is DELAYED in order to allow
demarcation of necrosis, and a reduced risk of bleeding,
disseminated infection and collateral damage to adjacent
organs.
Percutaneous Catheter drainage – used in pxn with suspected
infected complications; prefer than Fine Needle Aspiration
since it “buys time,” lesion becomes more walled, and safer to
treat.
 Surgical technique should only be considered in those who
fail to respond to the “step-up approach” that is prior
percutaneous drainage and minimally invasive intervention.
 Pseudocyst is usually conservative since half of these will
resolve spontaneously. In pseudocyst, percutaneous drainage
should be avoided for the risk of external pancreatic fistula.
Transpapillary Pancreatic Duct Stenting is the preferred
approach.
Managing Organ Failure
The responsiveness of orgain failure to resuscitation over the
first 48 hours is an important prognostic clue.
Cholecystectomy
While it is widely accepted that cholecystectomy is essential to
prevent gallstone pancreatitis recurrence, the timing is
important.
Index cholecystectomy – appears safe and accomplished
laparoscopically but not suitable for all patients, particulary
who had local complications which include a large phlegmon
that extends into the porta hepatis.
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Chronic Pancreatitis
Incurable, chronic, multifactorial cause, highly variable in
presentation and difficult to treat.
Etiology
Genetic Mutations
Alcohol exposure
Duct obstruction due to trauma, gallstones and tumors
Metabolic diseases (hyperlipidemia, hyperparathyroidism,
autoimmune)
Nutritional (Tropical Pancreatitis)
Idiopathic
Genetic Causes
 Patients first present in childhood or adolescence with
abdominal pain and are found to have chronic calcific
pancreatitis on imaging studies.
 Progressive pancreatic dysfunction is common
 Increase risk of subsequent carcinoma but typically at the age
>50 y/o
 Autosomal dominant pattern of inheritance (80%
penetrance)
 Incidence is equal in both sexes
PRSS1 mutation - gain-of-function missense mutation in an Arg
to His substitution at position 117 at chromosome 7q35
resulting to proteolysis of trypsin and excess production of
trypsinogen
R122H and N291 – additional mutations of PRSS1
PRSS2 – gain of function mutation in the anionic typsinogen
gene
SPINK1 mutation – loss-of-function of inhibiting trypsin action
by competitively blocking the active site of the enzyme;
associated with familial and idiopathic forms of chronic
pancreatitis, and tropical pancreatitis.
Cystic Fibrosis Transmembrane Receptor (CFTR) – present in
pancreatic duct cells and controls the amount of chloride and
bicarbonate secreted into the normally alkaline pancreatic
juice; CFTR mutations are associated with Cystic Fibrosis,
Classic Pulmonary disease (F508), Chronic idiopathic
Pancreatitis, Autoimmune Pancreatitis
CLDN2 gene – encodes a tight junction protein normally
present in ductal cells; In chronic pancreatitis, CLDN protein is
abnormally expressed in acinar cells, and may alter the
secretory dynamics of enzyme release.
Men with only one X chromosome have no protection if they
inherit a CLDN2 mutation unlike in women. This helps to
explain the high prevalence of alcoholic chronic pancreatitis
among men.
DocMegz2017
Alcohol
 Drunkard’s Pancreas
 There is a linear relationship between exposure to alcohol
and the development of chronic pancreatitis.
 Although the risk of disease is dose related and highest in
heavy (>150 g/d) drinkers, the prevalence of chronic
pancreatitis among confirmed alcohol abusers is only 5 to
15%
 However, the duration of alcohol consumption is definitely
associated with the development of pancreatic disease.
 The onset occurs between ages 35 to 40 years after 16-20
years of alcoholic consumption.
 Recurrent episodes of acute pancreatitis are typically
followed by chronic symptoms after 4 or 5 years
 It was proposed that chronic pancreatitis was the result of
multiple episodes of acute inflammation, with residual and
progressively increasing chronic inflammation.
 Others proposed that initial acute inflammation was not
necessarily linked to chronic changes in the pancreas. Other
additional factors were necessary for repeated exposure
 Regardless, the concept of multiple episodes of pancreatic
injury ultimately leads to chronic disease is widely accepted
as the pathophysiologic sequence.
 Repeated or severe episodes of toxin-induced injury activates
a cascade of cytokines, which, in turn, induces pancreatic
stellate cells (PSCs) to produce collagen and cause fibrosis
 Alcohol may interfere with intracellular transport and
discharge of digestive enzymes and may contribute to the co-
localization of digestive enzymes and lysosomal hydrolase
within acinar cells leading to autodigestion.
 High protein, low bicarbonate, low volume secretory output
is seen in chronic alcohol exposure. Calcium is complexed to
protein plugs that in the end promotes an inflammatory
response.
 Cigarette smoking has been strongly associated with chronic
pancreatitis but until recently it was unclear whether this was
a causative factor. Recently, smoking accelerates the
development of alcoholic pancreatitis, and the risk of cancer
in chronic pancreatitis is increased significantly. Smoking
appears to be an independent risk factor.
Hyperparathyroidism
 Hypercalcemia is a known cause of pancreatic
hypersecretion, and chronic hypercalcemia caused by
untreated hyperparathyroidism is associated with chronic
calcific pancreatitis, calculus formation, and obstructive
pancreatopathy.
 Treatment: Correction of hyperparathyroidism
Hyperlipidemia
 Predisposing factor in women when they receive estrogen
replacement therapy
 Aggressive therapy of hyperlipidemia is important in peri- or
postmenopausal patients
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Classification
TIGAR-O Categorizing Scheme
T- Toxic metabolic
I- Idiopathic
G – Genetic
A – Autoimmune
R – Recurrent and severe acute pancreatitis
O – Obstructive
Chronic Calcific (Lithogenic) Pancreatitis
 Includes patients with calcific pancreatitis of most etiologies
 Although the majority of patients with calcific pancreatitis
has a history of alcohol abuse, stone formation and
parenchymal classification can develop in a variety of
etiologic subgroups.
 The clinician should therefore avoid the assumption that
calcific pancreatitis confirms the diagnosis of alcohol abuse
Chronic Obstructive Pancreatitis
Refers to chronic inflammatory changes that are caused by the
compression or occlusion of the proximal ductal system by
tumor, gallstone, posttraumatic scar, or inadequate duct
caliber. (Recall Pancreas Divisum)
Chronic Inflammatory Pancreatitis
 Diffuse fibrosis and loss of acinar elements with a
predominant mononuclear cell infiltration
 Increased levels of serum B-globulin or IgG4 are also present.
 Steroid therapy is uniformly successful.
Autoimmune Pancreatitis – a variant of chronic pancreatitis
that is nonobstructive, diffusely infiltrative disease associated
with fibrosis, a mononuclear cell infiltrate (lymphocyte, plasma
cell or eosinophil), and an increased titer of one or more
autoantibodies; associated with Sjogren’s syndrome, RA, Type I
DM
Types:
Type 1 AIP – with accompanying systemic or multiorgan
dysfunction
Type 2 – restricted to the pancreas only
Tropical (Nutritional) Pancreatitis – adolescent and young
adults; brittle form of pancreatogenic diabetes. Patients appear
malnourished, characteristic cyanotic coloration of the lips;
with SPINK1 mutation (20-55% of pxn) and CFTR mutations; the
accelerated deterioration of endocrine and exocrine function,
the chronic pain due to obstructive disease, and the recurrence
of symptoms despite decompressive procedures characterize
the course of the disease.
Asymptomatic Pancreatic Fibrosis – elderly pxn; diffuse
perilobular fibrosis and a loss of acinar cell mass but without a
main ductular component.
DocMegz2017
Idiopathic Pancreatitis – lacks definable cause; young adults
and adolescents without family history of pancreatitis; SPINK 1
and CFTR mutations; also found in the elderly with biliary tract
disease.
Pathology
Histology
 Unevenly distributed, induration, nodular scarring, lobular
regions of fibrosis
 As disease progress there is loss of normal lobulation with
thicker sheets of fibrosis
 Ductular epithelium is usually atypical, with dysplasia
 Cuboidal cells with hyperplastic feature
 Areas of mononuclear cell infiltrates or patchy areas of
necrosis
 Cystic changes seen
 Tropical pancreatitis and hereditary pancreatitis are
histologically indistinguishable from chronic alcoholic
pancreatitis.
 In obstructive chronic pancreatitis, calculi are absent
 In pancreatic lobular fibrosis seen in the elderly, small ducts
are dilated, sometimes with small calculi trapped within
Fibrosis
 Common feature of all forms of chronic pancreatitis is the
perilobular fibrosis the forms surrounding acini, then
propagates to surround small lobules, and eventually
coalesces to replace larger areas of acinar tissue.
 Pathogenesis involves the activation of pancreatic stellate
cells (PSCs)
 In response to pancreatic injury, the PSCs become activated
and proliferate, lose their lipid vesicles and transform into
myofibroblast-like cells. These cells respond to proliferative
factors (TGF Beta, PDGF), and synthesize and secrete Type I
and III collagen, fibronectin
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