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DocMegz2017 Page 1
The ducts from each anlage usually fuse together in the of the pancreas along the medial aspect of the C-loop of the
pancreatic head such that most of the pancreas drains duodenum and head of the pancreas.
through the duct of Wirsung or main pancreatic duct, into the Therefore, it is impossible to resect the head of the pancreas
common channel formed from the bile duct and pancreatic without devascularizing the duodenum, unless a rim of
duct. pancreas containing the pancreaticoduodenal arcade is
The length of the common channel is variable. preserved.
Commonly, the duct from the dorsal anlage, the duct of The right hepatic artery, common hepatic artery or
Santorini, persists as the lesser pancreatic duct, and gastroduodenal arteries can arise from the superior
sometimes drains directly into the duodenum through the mesenteric artery.
lesser papilla just proximal to the major papilla.
Replaced Right Hepatic Artery- the right hepatic artery will
Pancreas Divisum - the ducts of Wirsung and Santorini fail to arise from the superior mesenteric artery and travel upwards
fuse resulting to the majority of the pancreas draining through toward the liver along the posterior aspect of the head of the
the duct of Santorini and the lesser papilla. The minor papilla pancreas.
can be inadequate to handle the flow of pancreatic juices from
the majority of the gland. This relative outflow obstruction can The body and tail of the pancreas are supplied by multiple
result in pancreatitis and is sometimes treated by branches of the splenic artery. The splenic artery arises from
sphincteroplasty of the minor papilla. the celiac trunk and travels along the posterior-superior
border of the body and tail of the pancreas toward the
The main pancreatic duct is usually only 2-3mm in diameter. spleen.
Pressure in the pancreatic duct is about twice that in the The inferior pancreatic artery usually arises from the superior
common bile duct to prevent reflux of bile into the pancreatic mesenteric artery and runs to the left along the inferior
duct. border of the body and tail of the pancreas, parallel to the
The main pancreatic duct joins with the common bile duct splenic artery.
and empties at the ampulla of Vater or major papilla, which is
nd
located on the medial aspect of the 2 portion of the Three vessels run perpendicular to the long axis of the
duodenum. pancreatic body and tail and connect the splenic artery and
inferior pancreatic artery. From medial to lateral..
Sphincter of Oddi – muscle fibers around the ampulla which Dorsal Pancreatic Artery
controls the flow of pancreatic and biliary secretions into the Great Pancreatic Artery
duodenum. Contraction and relaxation of the sphincter is Caudal Pancreatic artery
regulated by complex neural and hormonal factors.
These arteries form arcades within the body and tail of the
Two (2) cm proximal to the ampulla of Vater lies the lesser pancreas, and account for the rich vascular blood supply.
papilla from the duct of Santorini. The veins are usually superficial to the arteries within the
parenchyma of the pancreas.
Vascular & Lymphatic Anatomy There is an anterior and posterior venous arcade within the
Blood supply from the pancreas comes from multiple head of the pancreas.
branches from the celiac and superior mesenteric arteries. The superior veins drain directly into the portal vein just
The common hepatic artery gives rise to the gastroduodenal above the neck of the pancreas.
artery before continuing toward the porta hepatis as the The posterior inferior arcade drains directly into the inferior
proper hepatic artery. mesenteric vein at the inferior border of the neck of the
The right gastric artery branches off the gastroduodenal pancreas. These venous tributaries must be divided during a
artery just superior to the duodenum. The gastroduodenal Whipple procedure.
artery then travels inferiorly anterior to the neck of the The anterior inferior pancreaticoduodenal vein joins the right
pancreas and posterior to the duodenal bulb. A posterior gastroepiploic vein and the middle colic vein to form a
ulcer in the duodenal bulb can erode into the gastroduodenal common venous trunk, which enters into the superior
artery in this location. mesenteric veins.
At the inferior border of the duodenum, the gastroduodenal Traction on the transverse colon during colectomy can tear
artery gives rise to the right gastroepiploic artert then these fragile veins.
continues on as the anterior superior pancreaticoduodenal There are also numerous small venous branches coming from
artery, which branches into the anterior and posterior the pancreatic parenchyma directly into the lateral and
superior pancreaticoduodenal arteries. posterior aspect of the portal vein. Venous return from the
As the superior mesenteric artery passes behind the neck of body and tail of the pancreas drains into the splenic vein.
the pancreas, it gives off the inferior pancreaticoduodenal The lymphatic drainage from the pancreas is diffuse and
artery at the inferior margin of the neck of the pancreas. This widespread. The profuse network of lymphatic vessels and
vessel quickly divides into the anterior and posterior lymph nodes draining the pancreas provides egress to tumor
pancreaticoduodenal arteries. The superior and inferior cells arising from the pancreas.
pancreaticoduodenal arteries join together within the Pancreatic cancer often presents with positive lymph nodes
parenchyma of the anterior and posterior sides of the head 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
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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 Pancreatic polypeptide – 36 amino acid straight chain peptide.
endogenous (hepatic) glucose production and to facilitate
glucose transport into cells thus lowering plasma glucose Enteral neural stimulation of PP release:
levels. PROTEIN (most potent) > FAT > GLUCOSE
Insulin also inhibits glycogenolysis, fatty acid breakdown, Stimulated by: Inhibited by:
ketone formation. Hypoglycemia Glucagon
Insulin stimulates protein synthesis Phenylalanine Somatostatin
If the remaining portion of the pancreas is healthy, about Tryptophan
80% of the pancreas can be resected without the patient Fatty acids in the duodenum
becoming diabetic. In patients with chronic pancreatitis, or Insulin
other conditions with glands diseased, resection can result in Gastric Inhibitory Peptide
pancreatogenic or type 3C diabetes.
Vagal stimulation is the most important regulator of PP
Insulin receptors - dimeric, tyrosine kinase-containing secretion. Vagotomy eliminates the rise in PP levels usually
transmembrane proteins located on all cells. seen after a meal. This can be used as a test for the
completeness of a surgical vagotomy or for the presence of
Insulin deficiency results in an overexpression or upregulation diabetic autonomic neuropathy
of insulin receptors, which causes an enhanced sensitivity to PP has been shown to inhibit choleresis (bile secretion) and
insulin in muscle and adipocytes. gallbladder contraction and secretion by the exocrine
Type 2 diabetes is associated with a downregulation of pancreas.
insulin receptors and relative hyperinsulinemia, with resulting PP’s most important role is in glucose regulation.
insulin resistance. Deficiency in PP secretion is associated with diminished
hepatic insulin sensitivity
Glucagon – 29 amino acid, single chain peptide that promotes
hepatic glycogenolysis and gluconeogenesis and counteracts Ghrelin – secreted from Epsilon cells; also present in the gastric
the effects of insulin through its hyperglycemic action; fundus in large amounts and stimulates growth hormone
primarily regulated by glucose but has an inhibitory rather than secretion; Orexigenic or appetite stimulating; block insulin
stimulatory effect. effects on the liver and inhibits Beta cell response to incretin
and glucose.
Stimulated by: Inhibited by:
Hypoglycemia GLP-1 (in-vivo) Amylin/Islet Amyloid Polypeptide (IAPP) – found in pancreatic
Amino acids alanin and arginine. Insulin Beta cells stored along with insulin; modulates or
Cholinergic and beta sympathetic fibers Somatostatin counterregulates insulin secretion and function.
Alpha
sympathetic fibers Pancreastatin – inhibits insulin and possibly somatostatin
release; augments glucose release; inhibits pancreatic exocrine
In pancreatogenic or type 3c diabetes, glucagon secretion.
responsiveness to a fall in blood glucose is lost, thereby
increasing the risk for hypoglycemia. Islet Distribution
70% total islet cell mass - made up of Beta cells located in the
Somatostatin – wide anatomic distribution not only in neurons center, while the rest are in the periphery
but in pancreas, gut, and other tissues; highly conserved 5% - Delta cells
peptide hormone; stimulated during meal. 10% - Alpha cells
15% - PP cells
One gene encodes for a common precursor that is
differentially processed to generate tissue-specific amounts In reality, more than 20 different hormones are secreted by
of two bioactive products, somatostatin-14 and the islets, and the exact functions of this milieau are very
somatostatin-28. These peptides INHIBIT endocrine and complex.
exocrine function. Alpha and Beta cells are evenly distributed throughout the
Somatostatin receptors (SSTRs): SSTR 1, SSTR 2, SSTR 3, SSTR pancreas but islets in the head and uncinate process (ventral
4, SSTR 5 anlage) have a higher % of PP cells and fewer Alpha cells
In the body and tail (dorsal anlage), majority are Alpha cells
Stimulated by: Inhibited by: and few PP cells.
Intraluminal fat Acetylcholine Pancreatoduodenectomy removes 95% of PP cells in the
Acidification of the gastric and pancreas leading to higher incidence of glucose intolerance
duodenal mucosa 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 Organ systems frequently involved:
the cytosol, initiates apoptotic death. There is release of Cardiovascular
Cytochrome C that initiates apoptotic cascade. Inhibition of Respiratory
cathepsin B by pharmacological inhibitors or by genetic Renal
depletion of cathepsin B eliminates trypsin activation.
Management of the Patient
4. Injurious stimuli leads to sustained cytosolic Calcium General Considerations
increase. Blocking the Calcium increase prevents co-localization
and activation of trypsin. Pre-ERCP (Endoscopic Retrograde Mild acute pancreatitis – less than a week in the hosp
Cholangipnacreatography) supplementation of Magnesium, Severe/Critical type – weeks or months
antagonist of Calicum is currently evaluated. The risk of mortality reflects the spectrum of severity.
THE EARLIER IDENTIFICATION OF HIGH RISK CATEGORIES AND
B. Intrapancreatic Events TRANSFER OF PATIENTS TO SPECIALIZED CENTERS IS AN
1. Activated Neutrophils in tissue injury release superoxides IMPORTANT PRIORITY OF MANAGEMENT.
(“respiratory burst”) and proteolytic enzymes (cathepsins, Use Ranson’s Criteria to identify high risk patients.
elastase, and collagenase) which cause further injury.
Diagnosis
2. Macrophage release cytokines (TNF Alpha, IL6, IL8) which
Acute onset of severe constant epigastric pain which often
mediate local and systemic inflammatory response leading to
radiates through to the mid back
pancreatic vascular permeability resulting to edema,
Elevation of serum amylase or lipase (>3x upper limit of
hemorrhage and microthrombi. Failure of pancreatic
normal) – to rule out hyperamylasemia
microcirculation results in hypoperfusion and necrosis.
Imaging (usually by contrast enhanced CT scanning) is ONLY
required for the diagnosis of acute pancreatitis when these
Interstitial Edematous Pancreatitis – is acute inflammation of
diagnostic criteria are NOT MET.
the pancreatic parenchyma and peripancreatic tissues but
without recognizable necrosis. Serum Amylase conc increases almost immediately with the
onset of disease and peaks within several hours. It remains
Necrotizing Pancreatitis – term when necrosis is present, elevated for 3-5 days before returning to normal.
should be evidenced by pancreatic hypoperfusion with contrast There is NO significant correlation between the magnitude of
CT. serum amylase elevation and severity of pancreatitis.
Hyperamylasemia can occur NOT INVOLVING the
C. Systemic Events pancreatitis. (Small bowel obstruction, perforated duodenal
1. There is systemic inflammation and multiorgan failure. ulcer)
In patients with hyperlipidemia, serum amylase can be
2. The NFkB-dependent inflammatory pathway is the KEY NORMAL because of the interference of lipids with chemical
pathway. It activates typsin independently from sustained determination of serum amylase.
Calcium increase. Once activated, it synthesizes multiple Urinary clearance levels of pancreatic enzymes is a more
cytokines and chemokines leading to recruitment of various sensitive marker than serum levels in pancreatitis! It is
inflammatory cells. recommended that amylase concentrations also be measured
in the urine. Urinary amylase levels usually remain elevated
TAKE NOTE that although intra-acinar events initiate acute for several days after serum levels have returned to normal..
pancreatitis, events occurring SUBSEQUENT to acinar cell injury even in patients with severe pancreatitis associated with
will determine the SEVERITY. Elucidation of inflammatory significant necrotic damage where the pancreas may not
mediators (TNF A, IL1, IL2, IL6) can modulate the course of release large amounts of enzymes into the circulation.
severe acute pancreatitis. With increasing severity of disease, the intravascular fluid
loss may become life-threatening as a result of sequestration
3. Organ failure can develop at any stage of acute of edematous fluid in the retroperitoneum.
pancreatitis associated with an overwhelming proinflammatory There may also be bleeding into the retroperitoneum or
response. The proinflammatory constituents can appear in the peritoneal cavity. Blood from necrotizing pancreatitis may
mesenteric lymph bypassing the liver may contribute to the dissect through soft tissues and manifest as a bluish
development of organ failure. discoloration around the umbilicus (CULLEN’s SIGN) or in the
flanks (GREY TURNER’S SIGN)
4. The development of Pancreatic Necrosis, breakdown of Severe fluid loss may lead to prerenal azotemia,
intestinal barrier, suppression of the immune response (peak in hyperglycemia, hypoalbuminemia, and hypocalcemia to
rd th
the 3 to 4 week) may cause deterioration in the patient and produce tetany.
may result to late development of Systemic Inflammatory
Response Syndrome (SIRS) and Multiorgan Dysfunction
syndrome/failure (MODS/F)
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Pain Management MR is superior to CT scanning in detecting any sold
PAIN is the CARDINAL SYMPTOM of acute pancreatitis component within collections
Those with mild pain can usually be managed with NSAID Arterial Phase CT Scan (CTa) is useful in detecting
Severe pain are best managed with Opioid analgesia pseudoaneurysm, active bleeding and/or hematoma.
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Alcohol
Chronic Pancreatitis Drunkard’s Pancreas
There is a linear relationship between exposure to alcohol
Incurable, chronic, multifactorial cause, highly variable in and the development of chronic pancreatitis.
presentation and difficult to treat. 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
Etiology 15%
Genetic Mutations However, the duration of alcohol consumption is definitely
Alcohol exposure associated with the development of pancreatic disease.
Duct obstruction due to trauma, gallstones and tumors The onset occurs between ages 35 to 40 years after 16-20
Metabolic diseases (hyperlipidemia, hyperparathyroidism, years of alcoholic consumption.
autoimmune) Recurrent episodes of acute pancreatitis are typically
Nutritional (Tropical Pancreatitis) followed by chronic symptoms after 4 or 5 years
Idiopathic It was proposed that chronic pancreatitis was the result of
multiple episodes of acute inflammation, with residual and
Genetic Causes progressively increasing chronic inflammation.
Others proposed that initial acute inflammation was not
Patients first present in childhood or adolescence with necessarily linked to chronic changes in the pancreas. Other
abdominal pain and are found to have chronic calcific additional factors were necessary for repeated exposure
pancreatitis on imaging studies. Regardless, the concept of multiple episodes of pancreatic
Progressive pancreatic dysfunction is common injury ultimately leads to chronic disease is widely accepted
Increase risk of subsequent carcinoma but typically at the age as the pathophysiologic sequence.
>50 y/o Repeated or severe episodes of toxin-induced injury activates
Autosomal dominant pattern of inheritance (80% a cascade of cytokines, which, in turn, induces pancreatic
penetrance) stellate cells (PSCs) to produce collagen and cause fibrosis
Incidence is equal in both sexes Alcohol may interfere with intracellular transport and
discharge of digestive enzymes and may contribute to the co-
PRSS1 mutation - gain-of-function missense mutation in an Arg localization of digestive enzymes and lysosomal hydrolase
to His substitution at position 117 at chromosome 7q35 within acinar cells leading to autodigestion.
resulting to proteolysis of trypsin and excess production of High protein, low bicarbonate, low volume secretory output
trypsinogen is seen in chronic alcohol exposure. Calcium is complexed to
protein plugs that in the end promotes an inflammatory
R122H and N291 – additional mutations of PRSS1 response.
PRSS2 – gain of function mutation in the anionic typsinogen Cigarette smoking has been strongly associated with chronic
gene pancreatitis but until recently it was unclear whether this was
a causative factor. Recently, smoking accelerates the
SPINK1 mutation – loss-of-function of inhibiting trypsin action development of alcoholic pancreatitis, and the risk of cancer
by competitively blocking the active site of the enzyme; in chronic pancreatitis is increased significantly. Smoking
associated with familial and idiopathic forms of chronic appears to be an independent risk factor.
pancreatitis, and tropical pancreatitis.
Hyperparathyroidism
Cystic Fibrosis Transmembrane Receptor (CFTR) – present in Hypercalcemia is a known cause of pancreatic
pancreatic duct cells and controls the amount of chloride and hypersecretion, and chronic hypercalcemia caused by
bicarbonate secreted into the normally alkaline pancreatic untreated hyperparathyroidism is associated with chronic
juice; CFTR mutations are associated with Cystic Fibrosis, calcific pancreatitis, calculus formation, and obstructive
Classic Pulmonary disease (F508), Chronic idiopathic pancreatopathy.
Pancreatitis, Autoimmune Pancreatitis Treatment: Correction of hyperparathyroidism
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Idiopathic Pancreatitis – lacks definable cause; young adults
Classification and adolescents without family history of pancreatitis; SPINK 1
and CFTR mutations; also found in the elderly with biliary tract
TIGAR-O Categorizing Scheme disease.
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The PSP/Pancreatic Thread Protein/reg/Lithostathine gene
codes for a 166-amino acid product that undergoes post The role of chronic inflammation and development of nerve
translational modification to produce isoforms present in damage in the diseased gland also thought to contribute to
pancreatic juice. High concentrations found in pyramidal pain.
neurons in Alzheimer’s disease and Down Syndrome, and also Chronic inflammation results in the infiltration of tissue by
found in renal tubules which is consistent with its biologic macrophages which secrete prostaglandins and other
action of preventing calcium carbonate precipitation. nociceptive agents
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14
Pancreatogenic diabetes is most common in cases of Triolein Breath test – measurement of exhaled CO2 after
14 14
chronic pancreatitis, and is often seen after surgical ingestion of ( C)-triolein or ( C)-olein; less cumbersome than
resection intubation methods, and avoids the necessity of stool
Distal pancreatectomy and Whipple procedures have a collections and analysis; high false-negative rate
higher incidence of diabetes than do drainage procedures,
and the severity of diabetes is usually worse after subtotal Fecal levels of chymotypsin and elastase have been
or total pancreatectomy 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
Type 3C Diabetes classification; the loss of functioning mild to moderate chronic pancreatitis and may be more
pancreatic tissue by disease or surgical removal results in a sensitive for other causes of pancreatic dysfunction,
global deficiency of all three glucoregulatory islet cell including cystic fibrosis.
hormones: insulin, glucagon and PP Fecal elastase C1 measurements, levels below 100 ug/g are
There is a paradoxical combination of enhanced peripheral indicative of pancreatic exocrine insufficiency. However,
sensitivity to insulin and decreased hepatic sensitivity to the sensitivity and specificity of fecal elastase C1
insulin. measurements fall short of those needed for definitive
diagnosis of pancreatic exocrine insufficiency
Brittle diabetes – patients are hyperglycemic when insulin
replacement in insufficient (due to unsuppressed hepatic Radiologic imaging – the PRINCIPAL METHOD of diagnosis of
glucose production) or hypoglycemis when insulin replacement chronic pancreatitis, with the codification of classification
is barely excessive (due to enhanced peripheral insulin systems that correlate with proven disease.
sensitivity and a deficiency of pancreatic glucagon secretion to
counteract the hypoglycemia). ERCP has been considered the MOST SENSITIVE
RADIOLOGIC TEST fpr diagnosis of chronic pancreatitis.
PP deficiency correlates with the severity of chronic CT Scan is sensitive for the diagnosis of chronic pancreatitis
pancreatitis. when calcification, duct dilation or cystic disease is present,
A recent study of type 1 and type 3c diabetic patients on but NOT accurate in the ABSENCE of these findings.
insulin pump therapy revealed that the addition of a CT is helpful as a screening study to guide interventional
continuous subcutaneous infusion of PP reduced the insulin therapy or other diagnostic modalities, although EUS has
requirement for glycemic control. become the preferred method for the diagnosis of
pancreatic disease and offers the advantage of very-high-
Laboratory Studies resolution images of the pancreatic parenchyma, the main
The direct measurement of pancreatic enzymes by blood and secondary ductal systems, cystic lesions, and calcific
test is highly sensitive and fairly specific in ACUTE changes.
pancreatitis but SELDOM HELPFUL in the diagnosis of EUS findings may be inconclusive in mild or minimal change
CHRONIC pancreatitis. pancreatitis.
The pancreatic endocrine product that correlates more
strongly with chronic pancreatitis is the PP response to a Prognosis and Natural History
test meal Dependent on the etiology of the disease, development of
Severe chronic pancreatitis is associated with a blunt or complications, age, patient’s socioeconomic status.
absent PP response to feeding Although symptoms of pain decrease over time, this decline
The measurement of pancreatic exocrine secretion requires is also accompanied by a progression of exocrine and
aspiration of pancreatic juice from the duodenum after endocrine insufficicency.
nutrient (Lundh test meal) or hormonal (CCK or secretin) The likelihood of eventual pain relief is dependent upon the
stimulation. stage of disease at diagnosis, and the persistence of alcohol
Indirect tests of pancreatic exocrine function are based on use in patients with chronic alcoholic pancreatitis.
the measurement of metabolites of compounds that are The long-term survival of patients with chronic pancreatitis
altered (digested) by pancreatic exocrine products and can is less than for patients without pancreatitis.
be quantified by serum or urine measurements. There is a significant long-term progressive development
of carcinoma in patients with chronic pancreatitis.
Bentiromide test – N-benzoyl-L-tyrosyl-p-aminobenzoic acid; Carcinoma can be cryptic and the diagnosis of early-stage
ingested by the subject and the urinary excretion of the tumor is particulary difficult. Awareness of this risk justifies
proteolytic metabolite p-aminobenzoic acid (PABA) is close surveillance for cancer in patients with chronic
measured; highly sensitive pancreatitis like CA1 19-9, and periodic imaging of the
pancreas with CT Scan and EUS
Quantification of stool fat has also been used as a measure
of pancreatic lipase secretion, either through the direct Complications
measurement of total fecal fat levels while the subject Pseudocyst – a chronic collection of pancreatic fluiod
consumes a diet of known fat content surrounded by nonepithelialied wall of granulation tissue and
fibrosis.
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In chronic pancreatitis, a pancreatic duct leak with Internal Pancreatic fistula – occurs when pancreatic fluid
extravasation of pancreatic juice results in a pero-pancreatic tracks superiorly into the thorax, an a pancreatic pleural
fluid collection. (PPFC) effusion occurs.
Acute Pseudocyst – occurs when the PPFC is sealed by an Patients present with subacute or history of progressive
inflammatory reaction that leads to the development of a wall abdominal swelling despite weight loss, pain, nausea,
of acute granulation tissue without much fibrosis; may resolve paracentesis or thoracentesis reveals noninfected fluid with a
spontaneously over a course of 6 weeks or longer; may occur protein level of >25 g/L and a markedly elevated amylase level.
intrapancreatically or extend beyond the reigon of the Serum albumin may be low.
pancreas into other cavities. ERCP is most helpful
Pseudocysts may become secondarily infected, in which they Pancreatic-Enteric Fistula - the erosion of a pancreatic
become abscesses. pseudocyst into an adjacent hollow viscus can result in a
They can compress or obstruct adjacent organs or structure pancreatic-enteric fistula.
leading the superior mesenteric vein thrombosis or splenic
vein thrombosis. The most common site – transverse colon or splenic flexure
They can erode into visceral arteries and cause Fistula presents with evidence of GI or colonic bleeding and
pseudoaneurysms sepsis
They can perforate and cause peritonitis or intraperitoneal
bleeding Head-of-Pancreas Mass
Pseudocysts usually cause symptoms of pain, fullness or early Inflammatory mass in the head of the pancreas in advanced
satiety chronic pancreatitis
Sometimes pseudocysts resemble cystadenoma and
cystadenocarcinoma radiographically and should be Clinical Presentation
examined by EUS and aspirate to determine whether it is a Severe pain
true neoplasm or pseudocyst. Stenosis of the distal common bile duct
If infection is suspected, the pseudocyst should be aspirated Duodenal stenosis
(NOT drained) by CT or US-guided FNA and the contents Compression of Portal vein
examined for organisms by Gram’s stain and culture. Stenosis of the proximal main pancreatic duct
If pseudocyst failed to resolve with conservative therapy,
internal drainage is usually preferred to avoid complication of An accelerated transformation from hyperplasia to dysplasia
a pancreaticocutaneous fistula. exist in patients with pancreatic head enlargement (also,
mutation and polymorphisms of p53)
Internal drainage may be performed with:
Percutaneous catheter-based methods (Transgastric puncture Splenic and Portal Vein Thrombosis
and stent Placement
Left sided or Sinistral Portal Hypertension – formation of
Endoscopic methods (Transgastric or transduodenal puncture variceal as a consequence of either portal or splenic venous
and multiple stent placements, with or without a nasocystic occlusion and splenic vein thrombosis
irrigation catheter)
Treatment
Surgery (True cystoenterostomy, biopsy of cyst wall, and Medical Therapy
evacuation of all debris and contents – cystogastrostomy, Roux- Analgesics
en-Y cystojejunostomy, or cystoduodenostomy) Cessation of alcohol use
Oral enzyme therapy
Transductal drainage may be a safe and effective approach to Selective use of antisecretory therapy
the management of pseudocystic disease.
Analgesia
Complications of endoscopic or radiologic drainage: Oral analgesics are prescribed as needed, alone or with
Bleeding from cystoeneterostomy analgesia-enhancing agents (gabapentin).
Incoulation of a pseudocyst with failure of resolution Narcotics for adequate pain control
Persistence of infection Essential to abstain from alcohol
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Antisecretory Therapy pancreas in the pancreaticoduodenal groove along with its
Somatostatin administration – inhibit pancreatic exocrine associated blood vessels and distal common bile duct; disadv:
secretion and CCK release high risk of brittle diabetes, hypoglycemia and malnutririon
Octreotide Acetate – somatostatin analogue
Proximal Pancreatectomy/ Pancreatojejunostomy/ Whipple’s
Neurolytic Therapy Procedure – widely used, pain relief for 4-6 years, high rate of
Cardiac plexus neurolysis with alcohol injection has been an symptomatic relief that outweighs metabolic consequences
effective form of analagesic treatment in patients with and mortality risk
pancreatic carcinoma; short-acting
Total pancreatectomy – disadvantage: brittle diabetes, lethal
Endoscopic Management episodes of hypoglycemia, hypoglycemic unresponsiveness due
Pancreatic Duct Stenting – used for treatment of proximal to absence of pancreatic glucagon, iatrogenic hypoglycemia;
pancreatic duct stenosis, decompression of a pancreatic duct rarely used for the tx of refractory chronic pancreatitis
leak, and for drainage of pancreatic pseudocysts that can be
catheterized through the main pancreatic duct Duodenum-preserving Pancreatic Head Resection (DPPHR)/
Beger’s Procedure – requires careful dissection of the
Extracorporeal shock wave Lithotripsy (ESWL) – used for gastroduodenal artery and the creation of two anastomoses;
pancreatic duct stones, together with endoscopic stenting and risk of pancreatic leakage and intra-abdominal fluid collections.
stone removal.
Local Resection of the Pancreatic Head with Longitudinal
Surgical Therapy Pancreaticojejunostomy (LR-LPJ)/ Frey’s procedure –
Surgery should be considered only when the medical therapy excavation of pancreatic head, including the ductal structures
of symptoms has failed. in continuity with a long dichotomy of the dorsal duct;
The choice of operation and the timing of surgery are based decompression of the the head as well as the body and tail of
on each patient’s pancreatic anatomy, the likelihood that the gland; preservation of the neck and the capsule of the
further medical and endoscopic therapy will halt the posterior pancreatic head; ZERO mortality rate; less
symptoms of the disease, and the chance that a good result complications than Whipple’s and DPPHR.
will be obtained with the lowest risk of morbidity and
mortality. Organ-Preserving Pancreatic Head Resection (OPPHR) –
Preparation for surgery should include restoration of protein- excavating the core of the pancreatic head and draining with
caloric homeostasis, abstinence from alcohol and tobacco. Lateral Pancreaticojejunostomy but without any effort to
include the dorsal duct.
Sphincteroplasty
The Sphincter of Oddi and the pancreatic duct sphincter Berne Modification of DPPHR – served as an alternative to
serve as gatekeeper for the passage of pancreatic juice into DPPHR procedure in patients with portal hypertension;
the duodenum. operative time and length of stay of patients were shorter. The
Stenosis of either sphincter (sclerosing papillitis) due to removal of the central portion of the head of the gland is the
scarring from pancreatitis or from the passage of gallstones key to the successful resolution of pain long term.
may result in obstruction of the pancreatic duct
Transduodenal sphincterectomy with incision of the septum Total Pancreatectomy with Islet Auto-Transplantation – for tx
between the pancreatic duct and common bile duct appear of diabetes in adjunct to pancreatic surgery from benign
to offer significant relief. pancreatic disease. The ability to recover a sufficient quantity
of islets from a sclerotic gland is dependent on the degree of
Drainage Procedures (see pictures on separate page) fibrotic disease present.
Pancreaticojejunostomy
Pancreatic Neoplasms
Duval Procedure / Caudal Roux-en-Y pancreaticojejunostomy
Endocrine Neoplasms
Puestow Procedure / Longitudinal or side-to-side Roux-en-Y Islet Cells originate from neural crest cells (amine precursor
Pancreatojejunostomy – effective for pain relief when the uptake and decarboxylation cells.
maximum duct diameter is 6 mm; preferred method
MEN1 Syndrome – involves pituitary tumors, parathyroid
Resectional Procedures hyperplasia, pancreatic neoplasms
Distal Pancreatectomy - for patients with focal inflammatory
changes localized to the body and tail, or in whom no Insulinoma – most common functional pancreatic endocrine
significant ductal dilatation exists; risk for recurrence neoplasm and present with typical clinical syndrome known as
WHIPPLE’S TRIAD; pxn present with profound syncopal
95% Distal Pancreatectomy – intended for patients with episode; common sx include palpitations, trembling,
sclerotic (small duct) disease, and which attempted to avoid diaphoresis, confusion orobtundation, seizure, personality
the morbidity of total pancreatectomy by preserving the rim of
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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
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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!
-DocMegz
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