 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.
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 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.
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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.
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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
Stone Formation
Pancreatic stones are composed largely of calcium carbonate
crystals trapped in a matrix of fibrillar and other material
The fibrillar center contains no calcium but a mixture of other
metals. This suggests that stones form from an initial
noncalcified protein precipitation. The same low MW protein is
present in stones and protein plugs and was initially named
Pancreatic Stone Protein (PSP)
PSP was found to be a potent inhibitor of Calcium carbonate
crystal growth and has subsequently been renamed
Lithostanthine
Independently, Pancreatic Thread protein has been shown to
be homologous with lithostanthine.
Finally, reg protein was subsequently found to be homologous
with lithostanthine
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 The PSP/Pancreatic Thread Protein/reg/Lithostathine gene
codes for a 166-amino acid product that undergoes post
translational modification to produce isoforms present in
pancreatic juice. High concentrations found in pyramidal
neurons in Alzheimer’s disease and Down Syndrome, and also
found in renal tubules which is consistent with its biologic
action of preventing calcium carbonate precipitation.
Presentation, Natural History, and Complications
Presenting Signs & Symptoms
 Pain is the most common symptom of chronic pancreatitis.
 Midepigastric but may localize or involve either the left or
right upper quadrant of the abdomen
 Occasionally it is perceived in the lower midabdomen
 Frequently described as penetrating through to the back
 Persists for hours or days
 May be chronic with exacerbation caused by eating/drinking
alcohol
 Chronic alcoholic also describe a steady, constant pain
temporarily relieved by alcohol, followed by more severe
recurrence hours later
 Patients with chronic pancreatic pain typically flex their
abdomen
 Either sit or lie with hips flexed of in a fetal position
 The pain causes the patient to be still
 Nausea/vomiting may accompany the pain
 Anorexia is the most common assoc symptom
Etiologies
1. Ductal hypertension due to strictures or stones, may
predispose to pain that is initiated or exacerbated by
eating.
2. A chronic pain without exacerbation may be related to
parenchymal disease or retroperitoneal inflammation with
persistent neural involvement.
3. Acute exacerbations of pain in the setting of chronic pain
may be due to acute increase in duct pressure or recurrent
episodes of acute inflammation in the setting of chronic
parenchymal disease.
 Pain that is found in association with ductal hypertension is
most readily relieved by pancreatic duct decompression,
through endoscopic stenting or surgical decompression.
 The surgical relief of pain due to obstructive pancreatopathy
may be dependent on the degree of underlying fibrosis
rather than the presence of ductal obstruction
Minimal change Chronic Pancreatitis – there is minimal fibrosis
but there is chronic pain due to extrapancreatic or `peri-
pancreatic inflammatory events which are NOT ameliorated by
decompression.
Burned out Pancreatitis – pain from chronic pancreatitis
decreases or disappears completely over a period of years, as
symptoms of exocrine and endocrine deficiency become
apparent; there is progression of disease from a mild or
moderate stage to severe destruction of the pancreas.
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 The role of chronic inflammation and development of nerve
damage in the diseased gland also thought to contribute to
pain.
 Chronic inflammation results in the infiltration of tissue by
macrophages which secrete prostaglandins and other
nociceptive agents
 Inflammatory damage to the perineural layers surrounding
the unmyelinated pancreatic nerves and a focal infiltration of
inflammatory cells around nerves suggest that neural fibers
are a target for cellular response to inflammation in the
pancreas
Strategies to relieve Pain:
1. Reducing secretion and/or decompress that secretory
compartment
2. Resecting the focus of chronic inflammatory change
3. Interrupting the transmission of afferent neural impulses
through neural ablative procedures
Malabsorption and Weight Loss
 Pancreatic exocrine capacity falls <10% of normal = diarrhea
& steatorrhea
 Bulky, foul-smelling, loose (but not watery) stool, pale in
color and float on the surface of toilet water.
 Oil slick stool on the water surface
 In severe steatorrhea, an orange oily stool is often reported
 As exocrine deficiency increases, symptoms of steatorrhea
are often accompanied by weight loss.
 Patients may describe a good appetite despite weight loss, or
diminished food intake due to abdominal pain
 Anorexia and nausea may occur with or separate from
abdominal pain
 Decreased food intake and malabsorption of nutrients usually
results in chronic weight loss
 Lipase deficiency tend to manifest itself before trypsin
deficiency, so the presence of steatorrhea may be the first
functional sign of pancreatic insufficiency.
 As pancreatic exocrine function deteriorates further, the
secretion of bicarbonate into the duodenum is reduced,
which causes duodenal acidification and further impairs
nutrient absorption.
Pancreatogenic Diabetes
 The islets comprise only 2% of the mass of the pancreas,
but they are preferentially conserved when pancreatic
inflammation occurs.
 Acinar tissue loss and replacement by fibrosis is greater
than the dregree of loss of islet tissue
 Endocrine insufficiency commonly occurs
Frank Diabetes – chronic pancreatitis and impaired glucose
metabolism.
 Ketoacidosis and diabetic nephropathy are relatively
uncommon in pancreatogenic diabetes but retinopathy and
neuropathy are seen
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 Pancreatogenic diabetes is most common in cases of
chronic pancreatitis, and is often seen after surgical
resection
 Distal pancreatectomy and Whipple procedures have a
higher incidence of diabetes than do drainage procedures,
and the severity of diabetes is usually worse after subtotal
or total pancreatectomy
 Type 3C Diabetes classification; the loss of functioning
pancreatic tissue by disease or surgical removal results in a
global deficiency of all three glucoregulatory islet cell
hormones: insulin, glucagon and PP
 There is a paradoxical combination of enhanced peripheral
sensitivity to insulin and decreased hepatic sensitivity to
insulin.
Brittle diabetes – patients are hyperglycemic when insulin
replacement in insufficient (due to unsuppressed hepatic
glucose production) or hypoglycemis when insulin replacement
is barely excessive (due to enhanced peripheral insulin
sensitivity and a deficiency of pancreatic glucagon secretion to
counteract the hypoglycemia).
 PP deficiency correlates with the severity of chronic
pancreatitis.
 A recent study of type 1 and type 3c diabetic patients on
insulin pump therapy revealed that the addition of a
continuous subcutaneous infusion of PP reduced the insulin
requirement for glycemic control.
Laboratory Studies
 The direct measurement of pancreatic enzymes by blood
test is highly sensitive and fairly specific in ACUTE
pancreatitis but SELDOM HELPFUL in the diagnosis of
CHRONIC pancreatitis.
 The pancreatic endocrine product that correlates more
strongly with chronic pancreatitis is the PP response to a
test meal
 Severe chronic pancreatitis is associated with a blunt or
absent PP response to feeding
 The measurement of pancreatic exocrine secretion requires
aspiration of pancreatic juice from the duodenum after
nutrient (Lundh test meal) or hormonal (CCK or secretin)
stimulation.
 Indirect tests of pancreatic exocrine function are based on
the measurement of metabolites of compounds that are
altered (digested) by pancreatic exocrine products and can
be quantified by serum or urine measurements.
Bentiromide test – N-benzoyl-L-tyrosyl-p-aminobenzoic acid;
ingested by the subject and the urinary excretion of the
proteolytic metabolite p-aminobenzoic acid (PABA) is
measured; highly sensitive
 Quantification of stool fat has also been used as a measure
of pancreatic lipase secretion, either through the direct
measurement of total fecal fat levels while the subject
consumes a diet of known fat content
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14
Triolein Breath test – measurement of exhaled CO2 after
14 14
ingestion of ( C)-triolein or ( C)-olein; less cumbersome than
intubation methods, and avoids the necessity of stool
collections and analysis; high false-negative rate
 Fecal levels of chymotypsin and elastase have been
proposed as simpler, less expensive test of exocrine
function and correlate well with loss of pancreatic function.
However, these tests lose their sensitivity in patients with
mild to moderate chronic pancreatitis and may be more
sensitive for other causes of pancreatic dysfunction,
including cystic fibrosis.
 Fecal elastase C1 measurements, levels below 100 ug/g are
indicative of pancreatic exocrine insufficiency. However,
the sensitivity and specificity of fecal elastase C1
measurements fall short of those needed for definitive
diagnosis of pancreatic exocrine insufficiency
Radiologic imaging – the PRINCIPAL METHOD of diagnosis of
chronic pancreatitis, with the codification of classification
systems that correlate with proven disease.
 ERCP has been considered the MOST SENSITIVE
RADIOLOGIC TEST fpr diagnosis of chronic pancreatitis.
 CT Scan is sensitive for the diagnosis of chronic pancreatitis
when calcification, duct dilation or cystic disease is present,
but NOT accurate in the ABSENCE of these findings.
 CT is helpful as a screening study to guide interventional
therapy or other diagnostic modalities, although EUS has
become the preferred method for the diagnosis of
pancreatic disease and offers the advantage of very-high-
resolution images of the pancreatic parenchyma, the main
and secondary ductal systems, cystic lesions, and calcific
changes.
 EUS findings may be inconclusive in mild or minimal change
pancreatitis.
Prognosis and Natural History
 Dependent on the etiology of the disease, development of
complications, age, patient’s socioeconomic status.
 Although symptoms of pain decrease over time, this decline
is also accompanied by a progression of exocrine and
endocrine insufficicency.
 The likelihood of eventual pain relief is dependent upon the
stage of disease at diagnosis, and the persistence of alcohol
use in patients with chronic alcoholic pancreatitis.
 The long-term survival of patients with chronic pancreatitis
is less than for patients without pancreatitis.
 There is a significant long-term progressive development
of carcinoma in patients with chronic pancreatitis.
 Carcinoma can be cryptic and the diagnosis of early-stage
tumor is particulary difficult. Awareness of this risk justifies
close surveillance for cancer in patients with chronic
pancreatitis like CA1 19-9, and periodic imaging of the
pancreas with CT Scan and EUS
Complications
Pseudocyst – a chronic collection of pancreatic fluiod
surrounded by nonepithelialied wall of granulation tissue and
fibrosis.
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 In chronic pancreatitis, a pancreatic duct leak with
extravasation of pancreatic juice results in a pero-pancreatic
fluid collection. (PPFC)
Acute Pseudocyst – occurs when the PPFC is sealed by an
inflammatory reaction that leads to the development of a wall
of acute granulation tissue without much fibrosis; may resolve
spontaneously over a course of 6 weeks or longer; may occur
intrapancreatically or extend beyond the reigon of the
pancreas into other cavities.
 Pseudocysts may become secondarily infected, in which they
become abscesses.
 They can compress or obstruct adjacent organs or structure
leading the superior mesenteric vein thrombosis or splenic
vein thrombosis.
 They can erode into visceral arteries and cause
pseudoaneurysms
 They can perforate and cause peritonitis or intraperitoneal
bleeding
 Pseudocysts usually cause symptoms of pain, fullness or early
satiety
 Sometimes pseudocysts resemble cystadenoma and
cystadenocarcinoma radiographically and should be
examined by EUS and aspirate to determine whether it is a
true neoplasm or pseudocyst.
 If infection is suspected, the pseudocyst should be aspirated
(NOT drained) by CT or US-guided FNA and the contents
examined for organisms by Gram’s stain and culture.
 If pseudocyst failed to resolve with conservative therapy,
internal drainage is usually preferred to avoid complication of
a pancreaticocutaneous fistula.
Internal drainage may be performed with:
Percutaneous catheter-based methods (Transgastric puncture
and stent Placement
Endoscopic methods (Transgastric or transduodenal puncture
and multiple stent placements, with or without a nasocystic
irrigation catheter)
Surgery (True cystoenterostomy, biopsy of cyst wall, and
evacuation of all debris and contents – cystogastrostomy, Roux-
en-Y cystojejunostomy, or cystoduodenostomy)
Transductal drainage may be a safe and effective approach to
the management of pseudocystic disease.
Complications of endoscopic or radiologic drainage:
Bleeding from cystoeneterostomy
Incoulation of a pseudocyst with failure of resolution
Persistence of infection
Pancreatic Ascites
When a disrupted pancreatic duct leads to pancreatic fluid
extravasation that does not become sequestered as a
pseudocyst, but drains freely into the peritoneal cavity,
pancreatic ascites occurs.
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Internal Pancreatic fistula – occurs when pancreatic fluid
tracks superiorly into the thorax, an a pancreatic pleural
effusion occurs.
Patients present with subacute or history of progressive
abdominal swelling despite weight loss, pain, nausea,
paracentesis or thoracentesis reveals noninfected fluid with a
protein level of >25 g/L and a markedly elevated amylase level.
Serum albumin may be low.
ERCP is most helpful
Pancreatic-Enteric Fistula - the erosion of a pancreatic
pseudocyst into an adjacent hollow viscus can result in a
pancreatic-enteric fistula.
The most common site – transverse colon or splenic flexure
Fistula presents with evidence of GI or colonic bleeding and
sepsis
Head-of-Pancreas Mass
Inflammatory mass in the head of the pancreas in advanced
chronic pancreatitis
Clinical Presentation
Severe pain
Stenosis of the distal common bile duct
Duodenal stenosis
Compression of Portal vein
Stenosis of the proximal main pancreatic duct
An accelerated transformation from hyperplasia to dysplasia
exist in patients with pancreatic head enlargement (also,
mutation and polymorphisms of p53)
Splenic and Portal Vein Thrombosis
Left sided or Sinistral Portal Hypertension – formation of
variceal as a consequence of either portal or splenic venous
occlusion and splenic vein thrombosis
Treatment
Medical Therapy
Analgesics
Cessation of alcohol use
Oral enzyme therapy
Selective use of antisecretory therapy
Analgesia
Oral analgesics are prescribed as needed, alone or with
analgesia-enhancing agents (gabapentin).
Narcotics for adequate pain control
Essential to abstain from alcohol
Enzyme Therapy
Pancreatic enzyme administration serves to reverse the effects
of pancreatic exocrine insufficiency.
All patients with chronic pancreatitis pain begin with
nonenteric-coated enzyme supplement together with acid-
suppressive medication.
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 Antisecretory Therapy
Somatostatin administration – inhibit pancreatic exocrine
secretion and CCK release
Octreotide Acetate – somatostatin analogue
Neurolytic Therapy
Cardiac plexus neurolysis with alcohol injection has been an
effective form of analagesic treatment in patients with
pancreatic carcinoma; short-acting
Endoscopic Management
Pancreatic Duct Stenting – used for treatment of proximal
pancreatic duct stenosis, decompression of a pancreatic duct
leak, and for drainage of pancreatic pseudocysts that can be
catheterized through the main pancreatic duct
Extracorporeal shock wave Lithotripsy (ESWL) – used for
pancreatic duct stones, together with endoscopic stenting and
stone removal.
Surgical Therapy
 Surgery should be considered only when the medical therapy
of symptoms has failed.
 The choice of operation and the timing of surgery are based
on each patient’s pancreatic anatomy, the likelihood that
further medical and endoscopic therapy will halt the
symptoms of the disease, and the chance that a good result
will be obtained with the lowest risk of morbidity and
mortality.
 Preparation for surgery should include restoration of protein-
caloric homeostasis, abstinence from alcohol and tobacco.
Sphincteroplasty
 The Sphincter of Oddi and the pancreatic duct sphincter
serve as gatekeeper for the passage of pancreatic juice into
the duodenum.
 Stenosis of either sphincter (sclerosing papillitis) due to
scarring from pancreatitis or from the passage of gallstones
may result in obstruction of the pancreatic duct
 Transduodenal sphincterectomy with incision of the septum
between the pancreatic duct and common bile duct appear
to offer significant relief.
Drainage Procedures (see pictures on separate page)
Pancreaticojejunostomy
Duval Procedure / Caudal Roux-en-Y pancreaticojejunostomy
Puestow Procedure / Longitudinal or side-to-side Roux-en-Y
Pancreatojejunostomy – effective for pain relief when the
maximum duct diameter is 6 mm; preferred method
Resectional Procedures
Distal Pancreatectomy - for patients with focal inflammatory
changes localized to the body and tail, or in whom no
significant ductal dilatation exists; risk for recurrence
95% Distal Pancreatectomy – intended for patients with
sclerotic (small duct) disease, and which attempted to avoid
the morbidity of total pancreatectomy by preserving the rim of
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pancreas in the pancreaticoduodenal groove along with its
associated blood vessels and distal common bile duct; disadv:
high risk of brittle diabetes, hypoglycemia and malnutririon
Proximal Pancreatectomy/ Pancreatojejunostomy/ Whipple’s
Procedure – widely used, pain relief for 4-6 years, high rate of
symptomatic relief that outweighs metabolic consequences
and mortality risk
Total pancreatectomy – disadvantage: brittle diabetes, lethal
episodes of hypoglycemia, hypoglycemic unresponsiveness due
to absence of pancreatic glucagon, iatrogenic hypoglycemia;
rarely used for the tx of refractory chronic pancreatitis
Duodenum-preserving Pancreatic Head Resection (DPPHR)/
Beger’s Procedure – requires careful dissection of the
gastroduodenal artery and the creation of two anastomoses;
risk of pancreatic leakage and intra-abdominal fluid collections.
Local Resection of the Pancreatic Head with Longitudinal
Pancreaticojejunostomy (LR-LPJ)/ Frey’s procedure –
excavation of pancreatic head, including the ductal structures
in continuity with a long dichotomy of the dorsal duct;
decompression of the the head as well as the body and tail of
the gland; preservation of the neck and the capsule of the
posterior pancreatic head; ZERO mortality rate; less
complications than Whipple’s and DPPHR.
Organ-Preserving Pancreatic Head Resection (OPPHR) –
excavating the core of the pancreatic head and draining with
Lateral Pancreaticojejunostomy but without any effort to
include the dorsal duct.
Berne Modification of DPPHR – served as an alternative to
DPPHR procedure in patients with portal hypertension;
operative time and length of stay of patients were shorter. The
removal of the central portion of the head of the gland is the
key to the successful resolution of pain long term.
Total Pancreatectomy with Islet Auto-Transplantation – for tx
of diabetes in adjunct to pancreatic surgery from benign
pancreatic disease. The ability to recover a sufficient quantity
of islets from a sclerotic gland is dependent on the degree of
fibrotic disease present.
Pancreatic Neoplasms
Endocrine Neoplasms
Islet Cells originate from neural crest cells (amine precursor
uptake and decarboxylation cells.
MEN1 Syndrome – involves pituitary tumors, parathyroid
hyperplasia, pancreatic neoplasms
Insulinoma – most common functional pancreatic endocrine
neoplasm and present with typical clinical syndrome known as
WHIPPLE’S TRIAD; pxn present with profound syncopal
episode; common sx include palpitations, trembling,
diaphoresis, confusion orobtundation, seizure, personality
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 change, elevated C-peptide levels, serum insulin elevated; 90% malnutrition. Debulking operations are recommended in good
benign and solitary operative candidates to relieve symptoms

Whipple’s Triad: Somatostatinoma – present with gallstones due to bile stasis,

Symptomatic fasting hypoglycemia
Serum glucose level <50 mg/dL
Relief of symptoms with the administration of glucose
Noninsulinoma Hyperinsulinemia Hypoglycemia Syndrome –
beta cell hypertrophy, islet hyperplasia, increase beta cell mass.
If accompanied by ectopic islet tissue, multilobulated islets and
ductulo-insular complexes --- Nesideoblastosis
Gastrinoma/ Zollinger-Ellison Syndrome – endocrine tumor
that secretes gastrin, leading to acid hypersecretion and peptic
ulceration; 50% of gastrinomas metastasize to lymph nodes or
liver and therefore considered malignant.
Clinical Presentation
Abdominal Pain
Peptic Ulcer Disease
Severe Esophagitis
 The diagnosis of ZES is made by measuring serum gastrin
level.
 Stop taking proton pump inhibitors for this test.
 Serum gastrin is elevated.
Other causes of hypergastrinemia
Pernicious Anemia
Tx with Proton Pump Inhibitor
Renal Failure
G-cell Hyperplasia
Atrophic gastritis
Retained or excluded antrum
Gastric outlet obstruction
Pasaro’s Triangle – an area defined by a triangle with points
located at the junction of the cystic duct and common bile
nd rd
duct, the 2 and 3 portion of the duodenum, and the neck
and body of the pancreas.
Vasoactive Intestinal Peptide-Secreting Tumor – aka WDHA
syndrome
W-atery
D-iarrhea
H-ypokalemia
A-chlorhydria
 Serum VIP levels must be measured on multiple occasions
because the excess secretion of VIP is episodic and single
measurements might be normal and misleading
 EUS is the most sensitive imaging method
Glucagonoma – mild diabetes in association with dermatitis;
classic necrolytic migratory erythema that manifests as cyclic
migrations of lesions with spreading margins and healing
centers typically on the lower abdomen, perineum, perioral
area and feet. Also with enlarged sensitive tongue,
diabetes due to inhibition of insulin secretion, and steatorrhea
due to inhibition of pancreatic exocrine secretion and bile
secretion; originate in the proximal pancreas or
pancreatoduodenal groove, with ampulla and periamupllary
areas as the most common site.
Clinical presentations
Abdominal Pain
Jaundice
Cholelithiasis
Elevated somatostatin levels
Pancreatic Neuroendocrine Tumors (PNET) and Pancreatic
Endocrine Tumors (PET) – malignant tumors; often present
similar to patients with pancreatic adenocarcinoma with vague
pain or weight loss.
Markers that can be used for PNET and PET:
Synaptophysin
Chromogranin A – neuron specific enolase, monitor recurrence
Ostreoscan – somatostatin receptor scintigraphy; helpful to
stage the disease
Neoplasms of the Exocrine Panceas
Pancreatic Cancer – worst prognosis of all malignancies with a
5-year survival rate of only 6%; incidence continues to increase
with risk factors such as diabetes and obesity; difficult to treat
and exact cause is unknown; more common in the elderly >60
years old; more common in men and African Americans; risk is
2-3x higher if parent or sibling has the disease
Cigarette smoking – risk factor consistently linked to pancreatic
cancer; 2-fold increase due to carcinogens present
 Coffee and alcohol consumption are possible risk factors
 Diets high in fat, low in fiber, fruits, and vegetable are
increased risk
 Diabetes has been known to be associated with pancreatic
cancer
 The new onset of diabetes, or sudden increase in insulin
requirement in an elderly patient with pre-existing diabetes
should provoke concern for the presence of pancreatic
cancer.
Genetics
KRAS Oncogene – present in most cases of pancreatic cancer
Her2/Neu Oncogene – homologous to Epidermal growth Factor
receptor (EGFr) is overexpressed in pancreatic cancer
Multiple Tumor Supressor genes: p53, p16, SMAD4, and in
minority, BRCA2.
Pathology
Pancreatic Intraepithelial Neoplasia (PaIN) – precursor lesion

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 THE ABILITY TO DETECT THESE PRECURSOR LESIONS IN
HUMANS AT A STAGE WHERE THE CANCER CAN STILL BE
PREVENTED OR CURED IS AN IMPORTANT GOAL OF CURRENT
PANCEATIC CANCER RESEARCH!

About 2/3 of pancreatic adenocarcinomas arise within the head

or uncinate process of the pancreas.
Tumors in the pancreatic body and tail are generally larger at
the time of diagnosis,and therefore, less commonly resectable.
Tumors in the head are typically diagnosed earlier because they
cause obstructive jaundice.
Acinar cell carcinoma – uncommon type that usually presents
with a large tumor, often 10cm or more but prognosis is better.

Diagnosis & Staging (refer to the table for TNM staging)

GOD BLESS SA ATING LAHAT! 

#RoadtoVNeck

-DocMegz

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