Acute Pancreatitis: Pathophysiology, Definition, and Clinical Presentation

ACUTE PANCREATITIS
PHUNG HUY HOANG, MD
Resident in Internal Medicine
Pham Ngoc Thach University of Medicine
September, 2017

DEFINITION
PHUNG HUY HOANG, MD
September, 2017

INTRODUCTION
▪ Episode of inflammation resulting from intrapancreatic activation of potent pancreatic
enzymes (particular trypsin)
▪ May extend to local and distant extrapancreatic tissues
▪ Wide spectrum of severity, complications, and outcome
▪ Classifed as acute unless there are fndings on CT, MRI, ERCP suggestive of chronic pancreatitis
 “Exacerbation of chronic pancreatitis”
▪ DEFINITION
▪ Pathologic definition
▪ Clinical definition

PATHOLOGIC DEFINITION
▪ An inﬂammatory process of the pancreas
▪ Remain localized to the gland
▪ Involve other regional tissues (peripancreatic) or distant organ systems
▪ Pathologic classification
▪ Interstitial edematous pancreatitis
▪ (Hemorrhagic) necrotizing pancreatitis

INTERSTITIAL EDEMATOUS PANCREATITIS
▪ Most common form
▪ Gland diﬀusely enlarged (inﬂammatory edema)
▪ Scattered foci of fat necrosis (calcium binds to glycerol freed up by lipase-mediated cleavage of
fatty acids)
▪ Hemorrhage and necrosis: absent
▪ Fibril, neutrophils/swollen interlobular septa, some ducts dilated

NECROTIZING PANCREATITIS
▪ Hemorrhage: may extend into the surrounding tissues (e.g, mesentery, pararenal space) 
subcutaneous tissues (Grey Turner’s sign, Cullen’s sign)
▪ Necrosis: Peripancreatic tissue and peripheral pancreatic parenchyma (a core of viable
pancreas tissue remains in the center of the gland)
▪ Large collection of peripancreatic ﬂuid
▪ Fat necrosis: also develops at distant sites
▪ Thrombosis within severely aﬀected areas

Grimm I. S. (2008), "Pancreatitis", Netter's Internal Medicine, Marschall S. Runge , M.
Andrew Greganti, Editors, pp. 394-398

Grimm I. S. (2008), "Pancreatitis", Netter's Internal Medicine, Marschall S. Runge , M. Andrew Greganti, Editors, pp. 394-398

CLINICAL DEFINITION(1)
▪ Atlanta Criteria revision of 2012
▪ 2/3 following features
▪ Abdominal pain consistent with acute pancreatitis (acute onset of a persistent, severe,
epigastric pain often radiating to the back)
▪ Serum lipase activity (or amylase activity) ≥ x3 greater than laboratory’s UNL
▪ Characteristic findings of acute pancreatitis on contrast-enhanced computed tomography
(CECT) and less commonly magnetic resonance imaging (MRI) or transabdominal
ultrasonography
Banks P. A., Bollen T. L., Dervenis C., et al. (2013), Gut, 62 (1), pp. 102-11

CLINICAL DEFINITION (2)
▪ If serum enzyme levels < x3 UNL  CT scan must be performed to confirm diagnosis
▪ If diagnosis established = abdominal pain +  serum pancreatic enzyme activities  CECT NOT
usually required in emergency room or on admission to hospital
▪ Allows for possibility that presence of abdominal pain cannot be assessed in some patients with
severely altered mental status

Quinlan J. D. (2014), Am Fam Physician, 90 (9), pp. 632-639

PATHOPHYSIOLOGY
PHUNG HUY HOANG, MD
September, 2017

ANATOMY (1)
▪ Retroperitoneal, posterior to the stomach
▪ Related structures:
▪ Head: curvature of the duodenum, to the right of the portal vein confluence (union of superior
mesenteric vein + splenic vein)
▪ Neck: anterior to the portal vein
▪ Body: between portal confluence and abdominal aorta, midline portion of body lies anterior to
lumbar spine
▪ Tail: terminates in the superior portion of the splenic hilum
▪ Uncinate process: tucks in posteriorly behind the superior mesenteric artery and vein
▪ Splenic vein and artery course along the length of the pancreas

Drake R. L., Vogl A. W., Mitchell A. W. M. (2015), Gray's Anatomy for Student, Churchill
Livingstone, pp. 253-420

Jensen E. H., Borja-Cacho D., Al-Refaie W. B., et al. (2012), Sabiston Textbook of Surgery, Courtney M.
Townsend, R. Daniel Beauchamp, B. Mark Evers, Editors, Elsevier Saunders, pp. 1515-1547

ANATOMY (2)
• Distal portion of bile duct runs through the pancreatic parenchyma in the head // joins with the
pancreatic duct  major papilla
• Pancreatic ducts (usually communicates)
• Greatest diameter in the head of the pancreas
• “3-2-1 rule”: diameter measures approximately 3mm (head), 2mm (body), 1mm (tail)
• Accessory pancreatic duct (the duct of Santorini)  minor papilla
• Main pancreatic duct (the duct of Wirsung)  major papilla

Drake R. L., Vogl A. W., Mitchell A. W. M. (2015), Gray's Anatomy for Student, Churchill Livingstone, pp. 253-420

FUNCTION
• Exocrine pancreas (90% of pancreas structure): acinus + a corresponding ductule  larger
interlobular ducts  main pancreatic duct, centroacinar cells.
• Secretes 1 – 2.5 L of fluid/day (dehydration can occur in patients with a pancreatic fistula)
• Endocrine pancreas: Langerhan’s islet

Ross M. H., Pawlina W. (2016), Histology A Text And Atlas, Wolters Kluwer, pp. 626-661

COMPOSITION OF PANCREATIC JUICE
• Pancreatic digestive enzymes (enzymatic fraction)
• Pancreatic acini
• Multilple, for digesting all of the three major types of food (P, C, L)
• Proteolytic digestive enzymes: in enzymatically inactive forms (trypsinogen,
chymotrypsinogen, procarboxypolypeptidase)  activated only after being secreted into
intestinal tract with enterokinase, trypsin (once activated, cleaves + activates all other
zymogens
• Aqueous fraction
• NaHCO3: ductules and ducts, neutralize HCl from stomach (Cystic fibrosis transmembrane
conductance regulator (CFTR) channel): recycle Cl from lumen into cell to sustatin rate of
Cl/HCO3 exchange)
• Other cations, anions, water

Barrett K. E., Raybould H. E. (2010), Berne and Levy Physiology, Bruce M. Koeppen , Bruce A. Stanton, Editors, Mosby Elsevier, pp. 516-532

Hall J. E. (2016), Guyton and Hall Textbook of Medical Physiology, Elsevier, Editor, Elsevier, pp. 817-833

Fisher W. E., Andersen D. K., Windsor J. A., et al. (2015), Schwartz’s Principles of Surgery, F. Charles Brunicardi, Dana K. Andersen, Timothy R. Billiar, Editors, McGraw Hill, pp. 1341-
1422

REGULATION OF EXOCRINE PANCREATIC SECRETION
• Most abundantly in response to the presence of chyme in the upper portions of small intestine
• Characteristics of the pancreatic juice ∈ types of food in the chyme
• 3 basic stimuli: ACh, CCK, secretin
• Combined eﬀects of the multiple basic stimuli, not from one alone + Other neurotransmitters
(GRP, VIP,…)
• Phases of pancreatic secretion: cephalic, gastric, intestinal phase
ACh Parasympathetic vagus nerve endings
Other cholinergic nerves in enteric
nervous system
Acinar cells 
pancreatic enzymes
CCK Duodenal and upper jejunal mucosa
(I cells)
When food enters small
intestine
Secretin Duodenal and jejunal mucosa (S cells) When highly acidic food enters
small intestine
Water
HCO3
-

Mulroney S. E., Myers A. K., Netter F. H. (2009), "Netter’s Essential Physiology", Elsevier Saunders

Fox S. I. (2011), Human Physiology, McGraw Hill, pp. 612-653

AUTOPROTECTION OF PANCREAS (1)
• Most enzymes are produced as inactive precursors: zymogens (in the zymogen granules in
apical aspect of acinar cells)
• Enzymes sequestered in membrane-limited vesicles throughout synthesis to the point of
exocytosis  avoiding contact with the acinar cell cytoplasm
• Activation of zymogens occurs in the small intestine (outside pancreas)
• Normally, small amounts of trypsinogen are spontaneously activated within the pancreas,
protection mechanism:
• Intracellular Ca2+ homeostasis (low intracellular Ca in cytosol of acinar cell promotes the
destruction of spontaneously activated trypsin)
• Acid-base balance
• Protective protease inhibitors

AUTOPROTECTION OF PANCREAS (2)
• Protective protease inhibitors:
• Prevent activation of zymogens within the pancreas if trypsin is inappropriately activated
inside the gland
• Sourse: acinar cell, pancreatic secretions, α1- and α2-globulin fractions of plasma
• Inhibitors:
• Pancreatic secretory trypsin inhibitor (SPINK1, PSTI)
• Nonspecifc antiproteases (α1-antitrypsin and α2-macroglobulin)
• Chymotrypsin C

Kibble J. D., Halsey C. R. (2009), Medical Physiology - The big picture, McGraw Hill, pp. 259-306

MECHANISM OF INJURY IN AP (1)
• Activation of pancreatic proenzymes into active forms within pancreatic acinar cells
• Autodigestion of pancreatic tissue
• Activate other enzymes (e.g, elastase, phospholipase A2), activate complement and kinin
systems  inflammatory cascade
• Cell death: liberation of bradykinin peptides, vasoactive substances, histamine
• Consequences: proteolysis, edema, interstitial hemorrhage, vascular damage, coagulation
necrosis, fat necrosis, parenchymal cell necrosis
• Failure of normal protective mechanisms to inactivate trypsin (e.g, SPINK1 dysfunction)
• A number of factors (e.g., endotoxins, exotoxins, viral infections, ischemia, oxidative stress,
lysosomal calcium, and direct trauma): facilitate premature activation of trypsin
• Bilirary AP:  pressure/main pancreatic duct (obstruction), bile reflux into the pancreatic duct
 triggering enzyme activation

• Microcirculatory injury (vasoconstriction, capillary stasis, decreased oxygen saturation,
progressive ischemia) + damage to vascular endothelium in pancreas (e.g, expression of
endothelial adhesion molecules): activation of complement system, release proinflammatory
mediators, translocation of bacteria into systemic circulation

Penman I. D., Lees C. W. (2014), Davidson’s Principles and Practice of Medicine, Brian R. Walker, Nicki R.
Colledge, Stuart H. Ralston, Editors, Churchill Livingstone Elsevier, pp. 837-920

Doig A. K., Huether S. E. (2014), Pathophysiology the Biologic Basis for Disease in Adults
and Children, Kathryn L. McCance , Sue E. Huether, Editors, Elsevier, pp. 1423-1485

Algül H., Weber A., Huber W., et al. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 1653-
1691

Mills J. C., Stappenbeck T. S. (2014), Pathophysiology of Disease: An Introduction to Clinical Medicine, Gary D. Hammer, Editor, McGraw Hill, pp. 333-383

Beger H. G., Warshaw A. L., Büchler M. W., et al. (3008), "The Pancreas: An Integrated Textbook of Basic Science, Medicine, and Surgery", Wiley Blackwell.

• ARDS: induced by active phospholipase A (lecithinase)  digests lecithin (major
component of lung surfactant) + microthrombi in pulmonary vessels
• Acute renal failure: hypovolemia and hypotension
• Myocardial depression: secondary to vasoactive peptides, myocardial depressant factor
• Shock: distributive shock, myocardial depression, hypovolemia
• Metabolic complications:
• Hypocalcemia (multifactorial and includes hypoalbuminemia, sequestration of calcium in
fat necrosis)
• Hyperlipidemia
• Hyperglycemia with or without ketoacidosis, and hypoglycemia (disruption of islets of
Langerhans with altered insulin/glucagon release)

• Reduced serum albumin: increased capillary permeability
• Pancreatic infection (infected necrosis and infected pseudocyst):
• Hematogenous route
• Translocation of bacteria from the colon into the lymphatics  barriers breakdown (gut
ischemia secondary to hypovolemia and pancreatitisinduced arteriovenous shunting in the
gut)

Algül H., Weber A., Huber W., et al. (2016), Yamada’s Textbook of Gastroenterology, Daniel K.
Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 1653-1691

GENETICS FACTORS
• A number of genetic factors can increase susceptibility and/or modify the severity of pancreatic
injury in acute pancreatitis, recurrent pancreatitis, and chronic pancreatitis
• Center on the control of trypsin activity within pancreatic acinar cell
• Identified genetics variant*: PRSS1, SPINK1, CFTR, CTRC, CASR
(*) Conwell D. L., Banks P., Greenberger N. J. (2016), Harrison's Principles of Internal Medicine, Dennis L. Kasper, Anthony S. Fauci, Stephen L. Hauser, Editors, McGraw Hill Education,
pp. 2090-2102

PHASES OF INJURY
3 phases
1. Initial phase: intrapancreatic digestive enzyme activation (early neutrophil-independent
and neutrophil-dependent phase), and acinar cell injury
2. Second phase: activation, chemoattraction, sequestration of leukocytes and
macrophages in pancreas  enhanced intrapancreatic inflammatory reaction
3. Third phase: effects of activated proteolytic enzymes and cytokines (inflamed pancreas) on
distant organs (SIRS, MOF, ARDS,…)

Turner J. R., Lingen M. W. (2013), Robbins Basic Pathology, Elsevier Saunders, pp. 645-657

Klimstra D. S., Stelow E. B. (2012), Rubin’s Pathology : Clinicopathologic Foundations of Medicine, Raphael
Rubin, David S. Strayer, Emanuel Rubin, Editors, Wolster Kluwer, pp. 887

ETIOLOGY
Most common:
GALLSTONE, ALCOHOL
PHUNG HUY HOANG, MD
September, 2017

1. Obstruction: gallstones, tumors, parasites, duodenal diverticula, annular pancreas,
choledochocele, papillary stenosis, foreign bodies obstructing the ampulla, sphincter of oddi
dysfunction, (± pancreas divisum)
2. Alcohol/drugs/other toxins: ethyl alcohol, methyl alcohol, scorpion venom (Tityus trinitatis),
organophosphorous insecticides, drugs
3. Trauma: penetrating or blunt trauma to abdomen, iatrogenic (post ERCP, postoperative)
4. Metabolic abnormalities: hypertriglyceridemia, diabetes mellitus, hypercalcemia
5. Genetics, inherited conditions: cystic fibrosis, hereditary pancreatitis
6. Infections: bacteria, viral, parasite
7. Vascular: vasculitis (sle, polyarteritis nodosa), emboli to pancreatic blood vessels,
hypotension/ischemia
8. Miscellaneous: PUD, crohn’s disease, reye syndrome, hypothermia, autoimmune
9. Idiopathic

Kumar M., Mullady D. K. (2012), The Washington Manual of Critical Care Marin H. Kollef , Warren Isakow, Editors, Lippincott Williams & Wilkins, pp. 416-422

• Pregnancy: gallstone, hypertriglyceridemia, drugs
• AIDS: multifactorial, most common: drug (didanosine, pentamidine, TMP-SMZ, protease
inhibitors) and infections (CMV, Candida species, Cryptococcus neoformans, Toxoplasma gondii,
possibly Mycobacterium avium complex1)
• Diabetes mellitus:  prevalence of gallstones and hypertriglyceridemia, concurrent
dyslipidemia (cholesterol crystals), bile stasis in the gallbladder
• > 40 years old: a pancreatic tumor should be considered2
• Young patients (<30 years old) + no cause is evident and a family history of pancreatic
disease is present: consider genetic testing2
Special individuals
1. Parenti D. M., Steinberg W., Kang P. (1996), Pancreas, 13 (4), pp. 356-71
2. Tenner S., Baillie J., DeWitt J., et al. (2013), Am J Gastroenterol, 108 (9), pp. 1400-1415

• <5 mm in diameter is x4 greater risk than with larger stones (more likely to pass through the
cystic duct, cause ampullary obstruction)1
• Cholithiasis or microlithiasis: present 50% to 90% of AP cases with pregnancy (other
causes: hyperlipidemia and medications), most episodes after 2nd trimester and have favorable
overall prognosis.2
• Only 3-7% of patients with gallstones develop pancreatitis3
• Women > men (women with gallstones > men)
• 15-20% have normal serum concentrations of hepatic enzymes4
GALLSTONE, INCLUDING MICROLITHIASIS
1. Diehl A. K., Holleman D. R., Jr., Chapman J. B., et al. (1997), Arch Intern Med, 157 (15), pp. 1674-8
2. Fernandez H. J., Barkin J. S. (2010), GI/Liver Secrets Plus, Peter R. McNally, Editor, Mosby Elsevier, pp. 264-273
3. Tenner S., Steinberg W. M. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier
Saunders, pp. 969-993
4. Algül H., Weber A., Huber W., et al. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 1653-
1691

• Biliary sludge:
• Viscous suspension in gallbladder bile that may contain small (<3 mm) stones (i.e.,
microlithiasis)
• Composed of cholesterol monohydrate crystals or calcium bilirubinate granules
• May be referred as “idiopathic acute pancreatitis” (60-80% cases of intact gallbladder)
• Functional bile stasis (prolonged fasting, total parenteral nutrition), mechanical stasis
(distal bile duct obstruction), ceftriaxone (its solubility in bile is exceeded)
• Recurrent AP
GALLSTONE, INCLUDING MICROLITHIASIS

• Amount of alcohol ingested, person’s susceptibility to pancreatic injury (e.g, cigarette
smoking)
• Most common etiology of chronic pancreatitis
• Directly toxic to the acinar cell through a change in its metabolism
ALCOHOL

Ethanol, its metabolites, and oxidant stress
• Destabilization of lysosomes and zymogen
granules, mediated by reactive oxygen species,
cholesteryl esters, fatty acid ethyl esters, and
decreased GP2;  digestive and lysosomal
enzyme content ( synthesis ( mRNA),
impaired secretion
•  activation of transcription factors (NF-κB, AP-1)
which regulate cytokine expression
• Sustained  in cytoplasmic Ca and mitochondrial
Ca overload  mitochondrial depolarization.
Beger H. G., Warshaw A. L., Büchler M. W., et al. (3008), "The Pancreas: An Integrated Textbook of Basic Science, Medicine, and Surgery", Wiley Blackwell.

• 5-10% patient undergoing ERCP1
• Mechanism: edema, papillary spasm, or local injury
• Risk factors2,3:
• Patient related: famle, < 60 y.o, (suspected) sphincter of Oddi dysfunction, recurrent
pancreatitis, prior history of post-ERCP pancreatitis, normal serum bilirubin level
• Procedure related: > 2 contrast injections into the pancreatic duct, diffcult cannulation,
pancreatic sphincterotomy, precut access, balloon dilation
• Operator or Technique related: trainee (fellow) participation, non-use of a guidewire for
cannulation, failure to use a pancreatic duct stent in a high-risk procedure
POST-ERCP
1. Akshintala V. S., Hutfless S. M., Colantuoni E., et al. (2013), Aliment Pharmacol Ther, 38 (11-12), pp. 1325-37
3. Conwell D. L., Banks P., Greenberger N. J. (2016), Harrison's Principles of Internal Medicine, Dennis L. Kasper, Anthony S. Fauci, Stephen L. Hauser, Editors, McGraw Hill Education,
pp. 2090-2102

• 3rd most common AP1
• HTG classification2
• Risk for AP: > 11.3 mmol/L (> 1000 mg/dL) (may not be substantially elevated at presentation)
• Evidence of an underlying derangement in lipid metabolism (e,g. xanthoma)
• Prone to recurrent episodes of pancreatitis
• Hydrolysis of TGs by pancreatic lipase: release fatty acids (damage pancreatic acinar cells or
endothelial cells), induce free radical damage (directly injure cell membranes)
HYPERTRIGLYCERIDEMIA (1)
1. Fortson M. R., Freedman S. N., Webster P. D., 3rd (1995), Am J Gastroenterol, 90 (12), pp. 2134-9
2. Berglund L., Brunzell J. D., Goldberg A. C., et al. (2012), The Journal of Clinical Endocrinology & Metabolism, 97 (9), pp. 2969-2989
mg/dL mmol/L
Mild 150 -199 1.7 - 2.2
Moderate 200 - 999 2.3 - 11.2
Severe 1000 - 1999 11.2 - 22.4
Very severe >2000 >22.4

• Any factor (e.g., drugs, alcohol, contraception pills) causes abrupt  serum triglycerides can
precipitate about of acute pancreatitis
• More severe course compared to other etiologies
• HTG etiology:
• Primary
• Types I (familial chylomicronemia) and V: can present with AP without an exacerbating
factor ≠ type IV usually requires another factor
• Type IV (familial HTG or familial combined hyperlipidemia): autosomal dominant,
presents in adulthood
• Secondary
HYPERTRIGLYCERIDEMIA (2)

Stone N. J., Robinson J. G., Lichtenstein A. H., et al. (2014), J Am Coll Cardiol, 63 (25 Pt B), pp. 2889-934
Berglund L., Brunzell J. D., Goldberg A. C., et al. (2012), The Journal of Clinical
Endocrinology & Metabolism, 97 (9), pp. 2969-2989

• Hypersensitivity reaction, generation of a
toxic metabolite, some cases not clear
• Immediately upon initiation of the drug or be
delayed by months
• Classification (∈ published weight of
evidence and clinical presentation)
• Tends to be mild and self-limited
• Only evaluation after alcohol, gallstones,
hypertriglyceridemia, hypercalcemia, tumors
DRUGS
Badalov N., Baradarian R., Iswara K., et al. (2007), Clin Gastroenterol Hepatol, 5
(6), pp. 648-61; quiz 644

Badalov N., Baradarian R., Iswara K., et al. (2007), Clin Gastroenterol Hepatol, 5 (6),
pp. 648-61; quiz 644
*
*
*
*
*
*
*
*
*
*
*
*
*

Fernandez H. J., Barkin J. S. (2010), GI/Liver Secrets Plus, Peter R. McNally, Editor, Mosby Elsevier, pp. 264-273

• Bacterial (e.g., Mycoplasma, Legionella, Leptospira, Salmonella)
• Viral (e.g., mumps, coxsackie, hepatitis B, cytomegalovirus, varicella zoster, herpes)
• Parasitic (e.g., Ascaris, Cryptosporidium, Toxoplasma)
INFECTIONS

• Infrequent but high mortality
• After cardiopulmonary bypass, thoracic, and abdominal surgical procedures (gastrectomy, biliary
tract surgery, splenectomy, pancreatic biopsy)
HYPERCALCEMIA
POSTOPERATIVE PANCREATITIS
• Calcium activation of the trypsinogen to trypsin
• Calcification and stone formation in the pancreatic duct  obstruction

John T. Potts J., Jüppner H. (2016), Harrison's Principles of Internal Medicine, Anthony S.
Fauci Dennis L. Kasper, Stephen L. Hauser, Editor, McGraw Hill Education, pp. 2466-
2488

Beger H. G., Warshaw A. L., Büchler M. W., et al. (3008), "The Pancreas: An Integrated
Textbook of Basic Science, Medicine, and Surgery", Wiley Blackwell.
PANCREAS DIVISUM

MANIFESTATION
History
Physical examination
Laboratory data
Imaging
PHUNG HUY HOANG, MD
September, 2017

• Abdominal pain (or discomfort): primarily inflammatory pain due to local mediator release, may
be exacerbated by abdominal ischemia (fluid loss, hemoconcentration)
• At the onset of most attacks, not as abrupt as perforated viscus
• Location: entire upper abdomen (usually), epigastric, RUQ, or confined to the left
(infrequent), lower abdomen (rapid spread of pancreatic exudation to the left colon)
• Intensity: maximal (gradually increase)
• Steady and moderate to very severe (usually unbearable)
• Little pain relief with changing position
• Radiation: Band-like to the back (50%)
• Absent in 5-10% of attacks*
• Nausea and vomiting (90%): may be severe, accompanied by retching, may not alleviate pain
(related to severe pain or to inflammation involving posterior gastric wall)
HISTORY (1)
(*) Tenner S., Steinberg W. M. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier Saunders,
pp. 969-993

• Pain free:
• Analgesic/steroid use
• Immunosuppressed
• Change in mental status
• ICU
• Post operation
HISTORY (2)

Steer M. L. (2012), Irwin and Rippe’s Intensive Care Medicine, James M. Rippe Richard S. Irwin, Editor, Lippincott Williams & Wilkins, pp. 1115-1129

• Disorientation, hallucinations, agitation, or coma: may be (alcohol withdrawal, hypotension,
electrolyte imbalance such as hyponatremia, hypoxemia, fever, toxic effects of pancreatic enzymes
on the central nervous system)
• Vital signs: markedly abnormal if 3rd-space fluid losses and systemic toxicity
• HR > 100 bpm
• BP: can be initially higher than normal (pain)  lower than normal (3rd-space losses,
hypovolemia)  shock
• Temperature: may be normal  increase (1-3 days) (severe retroperitoneal inflammatory
process, release of inflammatory mediators from the pancreas, infection)
• Tachypnea with shallow respirations, dyspnea: subdiaphragmatic inflammatory exudate
causes painful breathing, abdominal distention, pleural effusions, atelectasis, ARDS, congestive
heart failure
PHYSICAL EXAMINATION (1)

• Severity vary:
• Mild: not appear acutely ill, mild abdominal tenderness, absent abdominal guarding
• Severe: severely ill, often have abdominal distention, guarding (more marked in upper
abdomen), abdominal rigidity (diffuse peritonitis, is unusual)
• Palpable epigastric mass: may appear (pseudocyst or a large inﬂammatory mass)
• Bowel sounds: reduced and may be absent (ileus)
• Abdominal distention (gastric-intestinal hypomotility, chemical peritonitis)
• Ecchymosis in 1 or both ﬂanks (Grey Turner’s sign), or about periumbilical area (Cullen’s
sign)
• Extravasation of hemorrhagic pancreatic exudate
• 1% of cases, associated with a poor prognosis

Tenner S., Steinberg W. M. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier Saunders,
pp. 969-993

• Jaundice: may be due to choledocholithiasis, bile duct obstruction from edema of the head
of pancreas, coexistent liver disease
• Panniculitis (inflammation of subcutaneous adipose tissue) with subcutaneous nodular fat
necrosis, may be accompanied by polyarthritis (PPP syndrome: Pancreatitis, Panniculitis and
Polyarthritis)
• Thrombophlebitis in the legs
• Physical fndings point to a specifc cause of acute pancreatitis
• Hepatomegaly, spider angiomas, and thickening of palmar sheaths (alcohol)
• Eruptive xanthomas and lipemia retinalis (hyperlipidemia)
• Parotid pain and swelling (mumps)
• Band keratopathy (infiltration on the lateral margin of cornea) (hypercalcemia)

• Pancreatic enzymes (degree of pancreatic enzyme elevation or trend over time does not
correlate with the patient’s prognosis!)
• Serum amylase level
• Serum lipase level
• Others: phospholipase A2, trypsin/trypsinogen, carboxylester lipase, carboxypeptidase A,
colipase, elastase, ribonuclease  None are superior to serum amylase or lipase, and most
are not available on routine basis
• Standard blood tests
LABORATORY

• Amylase: salivary, pancreas (45-45%)
• Normal total serum amylase test CAN NOT separate pancreatic isozym (p-amylase)
• 2–12h after the onset of symptoms, level peaks at 12–72h, usually returns to normal values
within 3-5 days (in uncomplicated attacks)1,2
• Might remain within normal range at the time of presentation or admission
• Limitation: NOT highly sensitive or specific
• May be falsely normal in hypertriglyceridemia-associated (amylase inhibitor may be
associated)  serial dilution of serum often reveals
• Normal serum amylase levels who have AP is between 20-30%3
• Hyperamylasemia/salivary origin: 40% cases of acute alcohol intoxication
LABORATORY Serum amylase
1691
4. Yadav D., Agarwal N., Pitchumoni C. S. (2002), Am J Gastroenterol, 97 (6), pp. 1309-18.

• Hyperamylasemia: Occurs in many other conditions (50% patients with  serum amylase
level may not have pancreatic disease1), usually < x2-3 UNL2 (≠ AP)
• Macroamylasemia (chronic  serum amylase, without amylasuria): normal serum amylase
bound to Ig or abnormal serum protein  complex too large to be filtered by renal  prolonged
serum half-life.
• Pancreatic hyperamylasemia on a familial basis
• Nonpancreatic diseases in other organs normally produce amylase (e.g., salivary glands,
fallopian tubes)
• Mass lesions produce secrete S-isoamylase
• Transmural leakage of P-isoamylase and peritoneal absorption (intestinal perforation)
• Renal failure, HD
• Acidemia (DKA)
LABORATORY
1. Sternby B., O'Brien J. F., Zinsmeister A. R., et al. (1996), Mayo Clin Proc, 71 (12), pp. 1138-44.
2. Potts D. E., Mass M. F., Iseman M. D. (1975), Am J Med, 58 (3), pp. 417-23.
Serum amylase

CONDITIONS ASSOCIATED WITH A HIGH SERUM AMYLASE
Pancreatic disease: pancreatitis, complications of pancreatitis (pseudocysts, abscess), trauma, surgery,
ERCP, ductal obstruction, pancreatic carcinoma, cystic fibrosis
Salivary disease: infection, trauma, radiation, ductal obstruction
GI disease: perforated or penetrating pud, perforated bowel, obstructed bowel, mesenteric infarction,
appendicitis, cholecystitis, liver disease, severe gastroenteritis, celiac disease
Gynecologic disease: ruptured ectopic pregnancy, ovarian or fallopian cysts, pelvic inflammatory
disease
Neoplasms: solid tumors (ovary, prostate, lung, esophagus, breast, and thymus), multiple myeloma,
pheochromocytoma
Other: renal failure, alcoholism, macroamylasemia, burns, acidosis (ketotic and nonketotic), pregnancy,
AIDS, cerebral trauma, abdominal aortic aneurysm, anorexia nervosa, bulimia, postoperative, drug
induced, idiopathic, following double-balloon enteroscopy, myocardial infarction
Gelrud D., Gress F. G. (2016), UpToDate, David C Whitcomb, Editor, Wolters Kluwer

Gelrud D., Gress F. G. (2016), UpToDate, David C Whitcomb, Editor, Wolters Kluwer

• Increased in acute pancreatitis
• May remain elevated for 7-10 days after serum levels have returned to normal*
LABORATORY
(*) Avunduk C. (2008), Manual of Gastroenterology: Diagnosis And Therapy, Lippincott Williams & Wilkins, pp. 306-316
Urine amylase

• Rise within 4–8h after onset of symptoms, peak at 24h, return to normal after 8–14 days*
• In comparison with amylase:
• Greater specifcity for pancreatitis than amylase (more pancreatic specific  exluce salivary
gland dysfunction, tumors, gynecologic conditions, macroamylasemia)
• Higher sensitivy: remains elevated longer
• Combining amylase + lipase: INCREASE COST, NOT improve diagnostic accuracy
• NOT correlate with the severity of acute pancreatitis
• May increase < x2 UNL in renal insuffciency, intra-abdominal conditions, diabetics
LABORATORY Serum lipase
(*) Frank B., Gottlieb K. (1999), Am J Gastroenterol, 94 (2), pp. 463-9

• Leukocytosis (15,000–20,000 leukocytes/μL): frequently (with or without infection)
•  Hct (e.g, > 44%1), BUN (e.g, > 22 mg/dL1): loss of plasma into the retroperitoneal space and
peritoneal cavity  more severe disease
• Hyperbilirubinemia (~10%): transient, return to normal in 4–7 days (except gallstone)
• Serum ALP and AST: transiently elevated, parallel serum bilirubin (gallbladder-related disease
or inflammation in pancreatic head)
• 15%–20% acute biliary pancreatitis exhibit normal liver function tests2
• ALT > 150 U/L (or > 3x UNL): may refer biliary AP3 (Spe 96%, PPV 95%, but Sen only 48% 4)
(AST: nearly as useful)
LABORATORY Others
1. Conwell D. L., Banks P., Greenberger N. J. (2016), Harrison's Principles of Internal Medicine, Dennis L. Kasper, Anthony S. Fauci, Stephen L. Hauser, Editors, McGraw Hill Education,
pp. 2090-2102
2. Dholakia K., Pitchumoni C. S., Agarwal N. (2004), J Clin Gastroenterol, 38 (1), pp. 81-3
1691
4. Tenner S., Dubner H., Steinberg W. (1994), Am J Gastroenterol, 89 (10), pp. 1863-6

• Hyperglycemia: common, multiple factors ( insulin release,  glucagon release,  output of
adrenal glucocorticoids and catecholamines)
• Hypercalcemia or hypocalcemia (~25%): pathogenesis incompletely understood (impaired
response of the parathyroid gland, “soap formation”, decreased serum albumin)
• Hypomagnesia: vomiting, loss urine, deposition in areas of fat necrosis
• Hypertriglyceridemia (also with alcohol use, uncontrolled DM, defective TG metabolism)
• ABG: hypoxia (herald the onset of ARDS)
• ECG: occasionally abnormal with ST-segment and T-wave abnormalities simulating myocardial
ischemia
• Lactate, LDH, CRP, ALT, Na, K: monitoring and stratification
LABORATORY Others

• Abdominal plain film
• Chest radiography
• Abdominal US
• CT
• MRI
• EUS, ERCP
IMAGING

• No abnormalities (mild disease)
• “Sentinel loop”: localized ileus of a segment of small intestine
• Colon cut-off sign (spasm of that part of the colon  no air distally: exudate in that area)
• Generalized ileus
• Exclude other causes of abdominal pain (such as bowel obstruction, perforation,…)
• Images of hollow GI tract depend on the spread and location of pancreatic exudate
• Anterior displacement of the stomach, separation stomach contour from transverse colon
(exudate in the lesser sac)
• Displaced and stretched descending duodenum (enlarged head of the pancreas)
• Calcifed gallstones (gallstone pancreatitis), pancreatic stones or calcifcation (acute
exacerbation of chronic pancreatitis), ascites (severe pancreatitis).
• Gas in the retroperitoneum (pancreatic abscess)
IMAGING Abdominal plain film

Clarke C. G. D., Dux A. E. W. (2015), "Abdominal X-rays for Medical Students", Wiley Blackwell.

Colon cut-off sign
radiopaedia.org

• Elevation of hemidiaphragm
• Pleural effusion(s): may be bilateral, or confined to left side, rarely only on the right side
• Basal or plate-like atelectasis secondary to limited respiratory excursion
• Pulmonary infltrates
• Pericardial effusion: rare
IMAGING Chest radiography

• Should be performed in all patients with acute pancreatitis*
• Search for gallstones, dilation of the bile duct due to choledocholithiasis
• Ascites (moderate to severe acute pancreatitis)
• Visualize pancreas
• Bowel gas obscures the pancreas 25% to 35% of the time
• Diffusely enlarged and hypoechoic
• Focal hypoechoic areas: less frequently
• Evidence of chronic pancreatitis (intraductal or parenchymal calcifcation, dilation of the
pancreatic duct)
• Evaluate progression of a pseudocyst
IMAGING Abdominal US
(*) Tenner S., Baillie J., DeWitt J., et al. (2013), Am J Gastroenterol, 108 (9), pp. 1400-1415

Yokoe M., Takada T., Mayumi T., et al. (2015), J Hepatobiliary Pancreat Sci, 22 (6), pp. 405-32

• Not helpful early in acute pancreatitis (indistinguishable from chronic pancreatitis and
malignancy)
• After a month (esppatients with idiopathic interstitial pancreatitis)  determine presence of small
tumors, pancreas divisum, bile duct stones
• Detecting common duct stones: equivalent to MRCP and ERCP but far more sensitive than
abdominal US or CT
• Useful in occult biliary disease (microlithiasis)
• EUS: best method/necrotizing pancreatitis
IMAGING EUS

• Appears to be safe in acute pancreatitis if needed
• Contrast instillation into the pancreatic duct could introduce infection into necrotic areas of the
pancreas
• Indications1:
• Evidence of acute cholangitis in the setting of acute biliary pancreatitis
• Evidence of persistent CBD stone by radiologic or clinical features (persistent jaundice, 
liver function tests, and/or dilated CBD on abdominal US,  serum total bilirubin level of >
1.35 on hospital day2)
• Biliary pancreatitis that is severe or predicted to be severe
IMAGING ERCP (1)
2. Baillie J. (2007), Gastroenterology, 132 (5), pp. 2019-2021

• Most patients with gallstone pancreatitis + lack laboratory or clinical evidence of ongoing
biliary obstruction: NO NEED1
• Other benefits2:
• Bile duct stones or microlithiasis
• Bile duct stricture
• Pancreas divisum
• Pancreatic duct disruption
• Sphincter of oddi dysfunction
IMAGING ERCP(2)
2. Keilin S. (2012), Essentials of Gastroenterology, Shanthi V. Sitaraman , Lawrence S. Friedman, Editors, Wiley Blackwell, pp. 260-276

• Timing:
• Urgent ERCP (within 24h of admission): AP + concurrent acute cholangitis1,2
• Early ERCP (within 72h): high suspicion of a persistent CBD stone (visible CBD stone on
noninvasive imaging, persistently dilated CBD, jaundice)2
IMAGING ERCP (3)

Algül H., Weber A., Huber W., et al. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 1653-1691

• Most important imaging test for the diagnosis of APs and its intra-abdominal complications1
• Benefits2,3:
• Exclude other serious intra-abdominal conditions (e.g., mesenteric infarction or a perforated
ulcer)
• Stage severity of AP (5 grades, A to E, based on findings on unenhanced CT)
• Determine complications of pancreatitis e.g., involvement of the GI tract or nearby blood
vessels and organs, including liver, spleen, and kidney (peritonitis, signs of shock,
suggestive ultrasound fndings,…)
IMAGING CT (1)
1. Balthazar E. J., Freeny P. C., vanSonnenberg E. (1994), Radiology, 193 (2), pp. 297-306
2. Freeny P. C. (1993), Int J Pancreatol, 13 (3), pp. 147-58

• Helical CT: most common technique; Dual-phase (pancreatic protocol) CT scan
• Follow-up CT: should be based on clinical status of the patient, NOT performed routinely at
regular intervals2
• CT early in presentation: may understimate severity of AP
• Indications:
• Diagnosis is unclear1,2
• Fail to improve clinically within the first 48 – 72 h after hospital admission1
• Evaluate complications1,2
IMAGING CT (2)
2. Greenberg J. A., Hsu J., Bawazeer M., et al. (2016), Can J Surg, 59 (2), pp. 128-40

• Information regarding severity of pancreatitis, detecting necrosis and ﬂuid collections = CT
• Detecting choledocholithiasis:
• > CT
• = EUS, ERCP
• IV secretin prior to MRCP: better visualization of the pancreatic ducts  particularly useful in
evaluation idiopathic pancreatitis and recurrent pancreatitis
IMAGING MRI

Algül H., Weber A., Huber W., et al. (2016), Yamada’s Textbook of
Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory
Fitz, Editors, Wiley Blackwell, pp. 1653-1691

Quinlan J. D. (2014), "Acute Pancreatitis", Am Fam Physician, 90 (9), pp. 632-639

• Gallstones: ♂ > ♀, often > 40 years old (peak incidence between 50 and 60 years*)
• Alcohol: ♀ > ♂, ~ 40 years old, 1st clinical episode usually after 5-10 years of heavy alcohol
consumption
• Serum ALT
• Abdominal US  ERCP, MRCP
Distinguishing alcoholic from gallstone pancreatitis
• (*) Algül H., Weber A., Huber W., et al. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp.
1653-1691
• Tenner S., Steinberg W. M. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier

• US: safe, preferred (strong recommendation, low level of evidence)
• MRI without gadolinium: 2nd and 3rd trimester (conditional recommendation, low level of evidence)
• CT: risk of teratogenesis and childhood hematologic malignancies, may be used judiciously
with minimized radiation protocols (2–5 rads) (conditional recommendation, very low level of
evidence)
• Endoscopy
• Safe in pregnancy, but should be deferred until 2nd trimester if possible (strong recommendation,
low level of evidence).
• Meperidine and propofol can be used for endoscopic sedation (strong recommendation,
moderate level of evidence)
PREGNANCY
Tran T. T., Ahn J., Reau N. S. (2016), Am J Gastroenterol, 111 (2), pp. 176-94

1. Other abdominal causes
2. Other serum hyperamylase or hyperlipase conditions
3. Other critical scenerios (organ failure, SIRS)
DIFFERENTIATION
Avunduk C. (2008), Manual of Gastroenterology: Diagnosis And Therapy, Lippincott Williams & Wilkins, pp. 306-316

COMPLICATIONS
PHUNG HUY HOANG, MD
September, 2017

▪ Atlanta classification 2012:
▪ Local complications
▪ Systemic complications
▪ Organ failure
▪ Other complications (local or systemic)

• Persistence/recurrence of abdominal pain, secondary  serum pancreatic enzyme,  organ
dysfunction, and/or development of clinical signs of sepsis  IMAGING
• Atlanta 2012*:
1. Acute peripancreatic fluid collection: location (pancreatic, peripancreatic,…), nature of
content (liquid, solid, gas), thickness of any wall (thin, thick)
2. Pancreatic pseudocyst
3. Acute necrotic collection
4. Walled-off necrosis
LOCAL COMPLICATIONS (Atlanta 2012) (1)
(*) Banks P. A., Bollen T. L., Dervenis C., et al. (2013), Gut, 62 (1), pp. 102-112

• NOT necessary to document local complications by imaging during the 1st week
• Presence and extent of pancreatic and peripancreatic necrosis may not be defined clearly on
imaging during the first few days1 (CECT 5–7 days after admission: more reliable)
• Extent of morphologic changes and necrosis: NOT directly proportional to the severity of
organ failure2
• Even if imaging during 1st week identifies presence of peripancreatic fluid collections or
pancreatic necrosis, in general NO treatments are required at that time3
• Important to distinguish different morphologic characteristics of local complications (require a
variety of interventions to avoid a fatal outcome)
LOCAL COMPLICATIONS (Atlanta 2012) (2)
1. Spanier B. W., Nio Y., van der Hulst R. W., et al. (2010), Pancreatology, 10 (2-3), pp. 222-8
2. Perez A., Whang E. E., Brooks D. C., et al. (2002), Pancreas, 25 (3), pp. 229-33
3. Banks P. A., Bollen T. L., Dervenis C., et al. (2013), Gut, 62 (1), pp. 102-112

• Exacerbation of pre-existing co-morbidity (e.g, coronary artery disease or chronic lung
disease)
• Distinguish with persistent organ failure
SYSTEMIC COMPLICATIONS

• 3 organ systems should be assessed: respiratory, cardiovascular and renal*
• Organ failure: ≥ 2 organ system involved*
• Duration*:
• Transient: < 48h
• Persistent: > 48 h
• Parameter
• Modified Marshall scoring system: simplicity, universal applicability across international
centres, able to stratify disease severity easily and objectively
• SOFA scoring system (less preferred): for patients in ICU, takes into account the use of
inotropic and respiratory support
• Both scoring methods: being able to be used on presentation and repeated daily
ORGAN FAILURE
(*) Banks P. A., Bollen T. L., Dervenis C., et al. (2013), Gut, 62 (1), pp. 102-112

Fisher W. E., Andersen D. K., Windsor J. A., et al. (2015), Schwartz’s Principles of Surgery, F. Charles Brunicardi, Dana K. Andersen, Timothy R. Billiar, Editors,
McGraw Hill, pp. 1341-1422

LOCAL
• Gastric outlet dysfunction, Ileus
• Splenic complications: infarction, rupture, hematoma, thrombosis, pseudoaneurysm
• Colonic necrosis, fistulization to or obstruction of the small intestine or colon
• Hydronephrosis
• Pancreatic duct disruption (MRCP, ERCP), pancreatic ascites
• GI bleeding:
• Pancreatitis-related: rupture (splenic artery, splenic artery pseudoaneurysm, splenic vein,
portal vein), splenic vein thrombosis  gastroesophageal variceal bleeding, pseudocyst or
abscess hemorrhage, postnecrosectomy bleeding
• Nonpancreatitis-related: Mallory-Weiss tear, alcoholic gastropathy, stress-related mucosal
gastropathy
OTHERS

SYSTEMIC
• Pulmonary: pleural effusion, atelectasis, mediastinal fluid, pneumonitis, ARDS (between 2-7 days of
illness, after recovery  structure and function usually return to normal)
• DIC
• Congestive HF, MI, cardiac dysrhythmia
• Circulatory shock
• Hyperglycemia: impaired neutrophil function,  risk of infections; Hypocalcemia
• Fat necrosis: tender red nodules on the skin (subcutaneous tissue), bone, others
• Retinopathy (Purtscher’s): very rare complication due to occlusion of the posterior retinal artery with
aggregated granulocytes
• Altered mental status (psychosis, fat embolism, encephalopathy)
• Abdominal compartment syndrome (ACS)
• Extrapancreatic infection
OTHERS

•  intestinal permeability (severe AP), with endotoxemia: translocation from the gut
• 1/3 with necrotizing pancreatitis develop infected necrosis (usually after∼10 days of illness)1
• Definite diagnosis: only be established by sterile puncture (i.e., FNA)2
• Majority of organisms detected3
• Gram-negative aerobic or anaerobic species (E. coli, Enterobacter aerogenes,
Pseudomonas aeruginosa, Proteus species, Klebsiella pneumoniae, Citrobacter freundii,
Bacteroides species)
• Occasional Gram positives (Streptococcus faecalis, Staphylococcus aureus,
Streptococcus viridans, Staphylococcus epidermidis)
• Rare fungi (Candida species)
Infected pancreatitis
1. Banks P. A., Freeman M. L. (2006), Am J Gastroenterol, 101 (10), pp. 2379-2400.
1691.
3. Buchler M., Malfertheiner P., Friess H., et al. (1992), Gastroenterology, 103 (6), pp. 1902-8

Uomo G. (2005), Rocz Akad Med Bialymst, 50, pp. 116-21

Jensen E. H., Borja-Cacho D., Al-Refaie W. B., et al. (2012), Sabiston Textbook of Surgery, Courtney M. Townsend, R. Daniel Beauchamp, B. Mark Evers, Editors, Elsevier Saunders, pp.
1515-1547

Definitive diagnosis
Clinical course
Severity classification
Prognosis (predictors of severity)
APPROACH
PHUNG HUY HOANG, MD
September, 2017

IMPORTANCE OF CLEAR DEFINITION AND STRATIFICATION
▪ Rate of mortality in severe acute pancreatitis ~ 20-50% vs none in mild acute pancreatitis
group.
▪ Patients with potentially severe acute pancreatitis require intensive monitoring and therapy.
▪ Facilitates early transfer of patients from secondary care setting to a specialized tertiary centers.
▪ Early identifcation of severe acute pancreatitis allows for timely intervention with targeted
therapy
• Algül H., Weber A., Huber W., et al. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 1653-
1691.
• Banks P. A., Bollen T. L., Dervenis C., et al. (2013), Gut, 62 (1), pp. 102-11

CLINICAL COURSE (1)
▪ 2 phases of AP: early (< 1-2 weeks) and late (> 2 weeks)1,2
▪ Mortality in AP has two incidence peaks: within 1st week (early phase), lasts for weeks to
months (late phase)
EARLY PHASES
▪ Host response to local pancreatic injury  cytokin cascades  systemic disturbances
▪ Systemic inflammatory response syndrome (SIRS):  risk of developing organ failure3
▪ Define AP severity = clinical parameters (primarily presence and duration of organ failure)
rather than morphologic findings
▪ Local complications: may be identified >< NOT the predominant determinants of severity
2. Conwell D. L., Banks P., Greenberger N. J. (2016), Harrison's Principles of Internal Medicine, Dennis L. Kasper, Anthony S. Fauci, Stephen L. Hauser, Editors, McGraw Hill
Education, pp. 2090-2102
3. Singh V. K., Wu B. U., Bollen T. L., et al. (2009), Clin Gastroenterol Hepatol, 7 (11), pp. 1247-51

CLINICAL COURSE (2)
LATE PHASES
▪ Occurs only in patients with moderately severe or severe AP1
▪ Persistence of systemic signs of inflammation: remains the main determinant of severity
▪ Presence of local complications (may require imaging)
▪ Compensatory, anti-inflammatory response syndrome (CARS): may contribute to  risk of
infection, complex and poorly understood2
2. Cobb J. P., O'Keefe G. E. (2004), The Lancet, 363 (9426), pp. 2076-2083

Cobb J. P., O'Keefe G. E. (2004), The Lancet, 363 (9426), pp. 2076-2083

SEVERITY
▪ 3 severity classifications:
▪ Mild: early discharged, not require pancreatic imaging, very rare mortality
▪ Moderately severe: may resolve without intervention or may require prolonged specialist
care
▪ Severe: persistent organ failure, high mortality, development of infected necrosis associated
with an extremely high mortality
▪ Determinants:
▪ Organ failulre (trasient or persistant)
▪ Local complications
▪ Systemic complications
▪ Convenient time points to re-evaluate: 24h, 48h and 7 days after admission

Tenner S., Baillie J., DeWitt J., et al. (2013), Am J Gastroenterol, 108 (9), pp. 1400-1415

PREDICTORS/PROSPECTIVE SYSTEM
FOR SEVERITY

PREDICTORS/PROSPECTIVE SYSTEM FOR SEVERITY(1)
▪ To maximize therapy and to prevent and minimize organ dysfunction and complications
(due to inability to distinguish mild from severe disease during early stages)
▪ Initially at presentation and over the first 48 hours: should be temporarily considered at risk
for developing severe acute pancreatitis (and managed as such initially) if predictors indicate
▪ CLASSIFICATION
▪ Scoring systems: Ranson, Glassgow, APACHE-II, BISAP, SIRS, HAPS, Imrie
▪ Laboratory markers: BUN, Hct, CRP, IL-6, polymorphonuclear leukocyte elastase,
phospholipase A2, urinary trypsinogen activation peptide, procalcitonin
▪ Imaging: CT (Balthazar CT-enhanced scoring system), chest radiography
▪ Others: obese,…
▪ Early markers: Hct, blood glucose, BUN, BISAP score,…*  for early aggressive treatment
(*) Algül H., Weber A., Huber W., et al. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 1653-
1691.

Algül H., Weber A., Huber W., et al. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 1653-1691.

▪ DIFFICULTIES
▪ Wide variety of etiologies, multiple endogenous (e.g., genetics, age) and exogenous
disease modifying factors: limited predictive capability of a single predictor (numerous
prognostic score)
▪ Inconsistencies in predictive capabilities of most parameters and scores used in diﬀerent
studies (such as stage of AP)
▪ Systematic comparison of prognostic capabilities is frequently impeded by diﬀerent
endpoints and outcome measures

RANSON SCORE (11 signs)1:
▪ Baseline: 5 parameters on admission (prognosis in the early emergency department setting)
▪ Follow-up: 6 parameters after 48h (early reevaluation 2 days after admission)
▪ Severe course: > 3 points (mortality 62%2)
▪ Higher Ranson’s score: higher incidence of systemic complications, necrosis, infected
necrosis.
▪ Cumbersome, 2 lists to follow depending on suspected etiology (alcohol, gallstones)
▪ Better use: to exclude severe disease
▪ Mnemonic: “GALAW CHOBBS”
1. Ranson J. H., Rifkind K. M., Roses D. F., et al. (1974), Surg Gynecol Obstet, 139 (1), pp. 69-81
2. Leese T., Shaw D., Holliday M. (1988), Annals of The Royal College of Surgeons of England, 70 (4), pp. 227-232

Mortality
• 0–2 points <1%
• 3–4 points 15%
• 5–6 points 40%
• > 6 points 100%
Fernandez H. J., Barkin J. S. (2010), GI/Liver Secrets Plus, Peter R. McNally, Editor, Mosby
Elsevier, pp. 264-273

APACHE-II SCORE
▪ Acute Physiology and Chronic Health Evaluation
▪ ICU
▪ 12 clinical or laboratory parameters of acute physiology + additional scoring points for older
age, chronic disease
▪ Predictive for severe pancreatitis: > 8 points
▪ Initially designed for the day of admission  being able to be used on a daily basis
▪ Similar PPV, NPV as the Ranson score at 48 hours

Burroughs A., Westaby D. (2012), Kumar & Clark’s Clinical Medicine, Parveen Kumar , Michael Clark, Editors, Elsevier, pp. 303-370

BISAP SCORE
▪ Bedside Index for Severity in Acute
Pancreatitis (Pancreas Center at
Brigham and Women’s Hospital)
▪ Simpler, useful within the first 12
hours from admission (≠ APACHE II,
Ranson)
▪ 1 point for each 5 parameters
▪ Score ≥ 3: associated with a 7- to 12-
fold  risk of developing organ failure Algül H., Weber A., Huber W., et al. (2016), Yamada’s Textbook of Gastroenterology, Daniel K.
Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 1653-1691.

GLASGOW CRITERIA
▪ Reduces the 11 indices used in Ranson’s criteria
to
▪ Used to obtain the prognosis of gallstone-
induced AP
▪ Solely determined after 48 hours of admission
Fernandez H. J., Barkin J. S. (2010), GI/Liver Secrets Plus, Peter R. McNally, Editor,
Mosby Elsevier, pp. 264-273

SIRS
Algül H., Weber A., Huber W., et al. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley
Blackwell, pp. 1653-1691.
▪ High-risk: SIRS persistent > 48 hours

BUN
▪ Following serial BUN measurements would be the most valuable single routine laboratory
test for predicting mortality in acute pancreatitis
▪ >25 mg/dL1
▪ Every 5 mg/dL increase during the first 24 hours: OR for mortality increased by 2.2 (age- and
gender-adjusted)2
HEMATOCRIT
▪ High Hct/admission (>44%), OR fails to  after 24 hours of rehydration: retroperitoneal ﬂuid
loss, predictor for the development of necrosis  a marker of severe disease3
1. Wu B. U., Johannes R. S., Sun X., et al. (2008), Gut, 57 (12), pp. 1698-1703
2. Sandrasegaran K., Lin C., Akisik F. M., et al. (2010), American Journal of Roentgenology, 195 (1), pp. 42-53
3. Lankisch P. G., Pflichthofer D., Lehnick D. (2000), Pancreas, 20 (3), pp. 319-22

CRP
▪ > 10-15 mg/dL1,2,3
▪ > 10 mg/L: highly sensitive, but the test specifcity drops to 75%
▪ Typical peak elevation 3–4 days after onset: limited use in ED
▪ CRP: at admission and daily for the fIrst 72h after admission3
1. Mayer A. D., McMahon M. J., Bowen M., et al. (1984), Journal of Clinical Pathology, 37 (2), pp. 207-211
2. Dervenis C., Johnson C. D., Bassi C., et al. (1999), Int J Pancreatol, 25 (3), pp. 195-210

CT
▪ CTSI = Balthazar Grade Score + Necrosis Score
▪ Inflammation, presence of collections, and degree of necrosis
▪ Correlate better with local complications (pseudocysts and abscesses) than with mortality
▪ Highest attainable score: 4 (Balthazar grade E) + 6 (necrosis of > 50%) = 10 points
▪ Hight risk: CTSI ≥ 5-6 points1,2
CHEST RADIOGRAPHY
▪ Pleural effusion within 72 hours of admission by chest radiography (or CT) correlates with
severe disease

Tenner S., Steinberg W. M. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier

OBESITY
Higher incidence of local complications, respiratory failure, severe acute pancreatitis, and
death from sterile necrosis
Tenner S., Steinberg W. M. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier Saunders,
pp. 969-993

MANAGEMENT
PHUNG HUY HOANG, MD
September, 2017

• Supportive care
• Fluid resuscitation
• Respiratory and cardiovascular care
• Metabolic complications correction
• Relief of symptoms (include Pain management)
• Antibiotics
• Nutrition support
• Intervention and surgery
• Special Considerations Based on Etiology
• Management of local complications

Working Party of the British Society of G., Association of Surgeons of Great B., Ireland, et al. (2005), Gut, 54 Suppl 3, pp. iii1-9

• Volume depletion in AP: nausea, vomiting, reduced fluid intake, paralytic ileus ( fluid and
energy absorption), ascites, pleural effusion, inflammatory (peri)pancreatic edema, exudation and
fluid collections (peritoneal cavity, retroperitoneum), capillary leakage due to SIRS1
• Aim: to maintain hemodynamic stability, adequately perfuse kidneys and pancreas (
perfusion pressure into the pancreas  microcirculatory changes   necrosis)
• Goal: maintaining hemodynamic stability (MAP > 65 mmHg2), proper urine output (>30-
60ml/h2, or > 0.5ml/kg/h3),  BUN
• Benefit: most apparent early (within the first 6-12h after admission), may not be benefcial after
the first 24 hours3,4
FLUID RESUSCITATION (1)
1691
2. Yokoe M., Takada T., Mayumi T., et al. (2015), J Hepatobiliary Pancreat Sci, 22 (6), pp. 405-32
3. Rahmani R., Marino D., Shamah S., et al. (2013), Pancreatology, 13 (3), pp. S6-S7

• Choice of fluid: CRYSTALLOIDS (colloid: nonsuperiority, or even detrimental eﬀects1,2)
• Normal saline: may cause hyperchloremic metabolic acidosis
• Ringer’s lactate (preferred!): reduced systemic inflammation3; more pH-balanced,
isotonic, its HCO3 content  prevent metabolic acidosis with or without large-volume
transfusion related4 (theorically  degranulation, enzyme release in pH-dependent manner
 stabilize pancreas), a better crystalloid than NS
• Careful consider with hypercalcemia (LR contains 3 mEq/L of Ca)5
1. Annane D., Siami S., Jaber S., et al. (2013), JAMA, 310 (17), pp. 1809-1817
2. Brunkhorst F. M., Engel C., Bloos F., et al. (2008), New England Journal of Medicine, 358 (2), pp. 125-139
3. Wu B. U., Hwang J. Q., Gardner T. H., et al. (2011), Clin Gastroenterol Hepatol, 9 (8), pp. 710-717 e1
5. Singh A., Gelrud A. (2015), Principles of Critical Care, Gregory A. Schmidt Jesse B. Hall, John P. Kress, Editor, McGraw Hill Education, pp. 1031-1036

• If evidence of severe predictors  aggressive fluid resuscitation as soon as possible
• Bolus 20 ml/kg over 60 to 90 minutes  250-500 ml/h for the next 48 hours1,2,3
• Require caution for certain groups of patients (e.g., older adults or those with a history of
cardiac and/or renal disease)  avoid complications: volume overload, pulmonary edema,
and abdominal compartment syndrome)1,3  consider 130–150 mL/h4
• Monitor fluid responsiveness:
• Filling pressure: CVP, PCWP
• Volumetric parameter: pulse contour analysis, transpulmonary thermodilution (TPTD)
• Dynamic parameter: stroke volume variation, pulse pressure variation
1. Tenner S., Baillie J., DeWitt J., et al. (2013), Am J Gastroenterol, 108 (9), pp. 1400-15; 1416
2. Quinlan J. D. (2014), Am Fam Physician, 90 (9), pp. 632-639
3. Eckerwall G., Olin H., Andersson B., et al. (2006), Clin Nutr, 25 (3), pp. 497-504
4. Yokoe M., Takada T., Mayumi T., et al. (2015), J Hepatobiliary Pancreat Sci, 22 (6), pp. 405-32
5. Marino P. L. (2014), Marino's the ICU Book, Wolters Kluwer, pp. 719-736

• Oxy supplement: SaO2 < 90% (nasal prongs, or face mark if needed)
• Endotracheal intubation and assisted ventilation: required early if fails to correct
hypoxemia or if there is fatigue and borderline respiratory reserve
• Ideal: Swan-Ganz catheter  determine whether hypoxemia is due to congestive heart
failure ( pulmonary artery wedge pressure) or to primary pulmonary damage (normal or low
PAWP)
• ARDS: endotracheal intubation, positive end-expiratory pressure ventilation (low Vt to
prevent volutrauma), NO specifc treatment
• Vasopressor therapy:
• Norepinephrine: appropriate choice*, initial rate: 0.1 g/kg/h
• Goal: MAP ≥ 65mmHg
• All vasoconstrictors:  splanchnic blood flow   pancreatic necrosis
RESPIRATORY-CARDIOVASCULAR CARE
(*) Marino P. L. (2014), Marino's the ICU Book, Wolters Kluwer, pp. 719-736

• Blood sugars ﬂuctuate  insulin should be administered cautiously
• Hypocalcemia
• Loss is non-ionized  asymptomatic and requires no specifc therapy
• Reduced serum ionized calcium may occur and cause neuromuscular irritability 
require treatment
• IV calcium:  Ca binding to myocardial receptors  displaces K  may induce a serious
dysrhythmia
• If hypomagnesemia coexists
• Mg replacement should restore serum calcium to normal
• Once serum Mg normal + signs or symptoms of neuromuscular irritability  may require IV
calcium gluconate (as long as serum K normal + digitalis is not being given)
METABOLIC COMPLICATIONS

CaR: diffusible calcium complexes (Combined with
anionic substances of plasma)
Berndt T. J., Thompson J. R., Kumar R. (2016), Brenner & Rector’s The Kidney, Karl Skorecki, Maarten W.
Taal, Glenn M. Chertow, Editors, Elsevier, pp. 185-203
CaProt: Protein-bound calcium, Nondiffusible through
capillary
Ca2+: ionized calcium

• Uses
• Prophylaxis
• Treatment (pancreatic and extrapancreatic1)
• Appropriate in pancreatic sepsis (e.g., infected necrosis, abscess), nonpancreatic sepsis
(e.g., line sepsis, urosepsis, pneumonia)
• Drugs with highest inhibitory concentrations in pancreatic tissue: carbapenem,
fluoroquinolones (ciprofloxacin, ofloxacin, pefloxacin), metronidazole2
• Routine use in prophylaxis: controversial
• NOT RECOMMENED!1,5
• Controversial3,4: only when > 30% necrosis in the pancreas (not  mortility)
ANTIBIOTICS (1)
2. Beger H. G., Bittner R., Block S., et al. (1986), Gastroenterology, 91 (2), pp. 433-8

Efficacy factor: ratio between bacterial spectrum covered and the pancreatic penetration, at least at the
minimal inhibitory concentration; the maximum efficacy factor is 1
Uomo G. (2005), Rocz Akad Med Bialymst, 50, pp. 116-21

INDICATIONS*
• Extrapancreatic infection (cholangitis, catheter-acquired infections, bacteremia, urinary
tract infections, pneumonia)
• Necrotizing pancreatitis + suspected infection (fever, leukocytosis, organ failure)
ANTIBIOTICS (2)
(*) Tenner S., Baillie J., DeWitt J., et al. (2013), Am J Gastroenterol, 108 (9), pp. 1400-1415

De Campos T., Assef J. C., Rasslan S. (2006), World Journal of Emergency Surgery, 1, pp. 20-20

OPIOIDS
• Morphine has been reported to  sphincter of Oddi pressure  worsening acute pancreatitis1
>< its use to treat the pain of pancreatitis shown no adversely affect outcome2
• Recommended:
• Meperidine (NOT affect Oddi  preferred >): relative short T1/2  repeated doses 
accumulation of the neurotoxic metabolite normeperidine
• Buprenorphine pentazocin: recommended (despite absence of clear superiority in humans)3
• Fentanyl, hydromorphone: usually preferred
EPIDURAL ANESTHESIA
• Invasiveness + potential of systemic vasodilation (patients with borderline hypotension)
• Should be limited to an ICU setting4
PAIN MANAGEMENT
1. Thompson D. R. (2001), Am J Gastroenterol, 96 (4), pp. 1266-1272
2. Tenner S., Steinberg W. M. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Elsevier Saunders, pp. 969-993
3. Forsmark C. E., Baillie J., Practice A. G. A. I. C., et al. (2007), Gastroenterology, 132 (5), pp. 2022-44
4. Richards E. R., Kabir S. I., McNaught C. E., et al. (2013), British Journal of Surgery, 100 (3), pp. 316-321

• Pancreatitis patients are at nutrition risk  should be screened
• Most with mild or moderate uncomplicated AP: NOT beneft from nutritional support1
• Nutritional support should be provided in those patients likely to remain “nothing by mouth”
for > 7 days1, 2 (other tolerate well with glucose IV if recovered soon), or as soon as possible
• Choice
• Enteral (oral, nasogastric, or nasojejunal tube)
• Parenteral
NUTRITION
1. Mirtallo J. M., Forbes A., McClave S. A., et al. (2012), JPEN J Parenter Enteral Nutr, 36 (3), pp. 284-91

• Mild to moderate AP: nil per os (NPO) with a gradual advancement to diet (usually within 3–
4 days) are recommended1
• “Gut rest”: prohibiting enteral intake  avoid stimulation of pancreas secretion
• Oral feedings/mild AP: immediately IF no nausea, vomiting + abdominal pain resolved, low-
fat solid diet appears as safe as a clear liquid diet2
• ET: preferred over parenteral even with severe pancreatitis1,3  should initiate 1st
• ET should still be considered as early as possible (feasible and improves outcome)1,4:
reduction in septic complications esp catheter-associated5, better maintenance of intestinal barrier,
prevention of bacterial translocation (source of infection/AP)
NUTRITION
4. Marik P. E., Zaloga G. P. (2004), BMJ, 328 (7453), pp. 1407
5. Ragins H., Levenson S. M., Signer R., et al. (1973), The American Journal of Surgery, 126 (5), pp. 606-614
Enteral (1)

• Nasogastric or nasojejunal tube (might be preferable: minimizes stimulation of enzyme,
HCO3, volume release from pancreas)
• May be used in the presence of pancreatic complications (fistulas, ascites, pseudocysts)
• Continuous EN infusion: preferred over cyclic or bolus administration
NUTRITION
Mirtallo J. M., Forbes A., McClave S. A., et al. (2012), JPEN J Parenter Enteral Nutr, 36 (3), pp. 284-91
Enteral (2)

• Should be avoided UNLESS the enteral route is not available, not tolerated, or not meeting
caloric requirements1
• Benefit
• Impeded by nausea, vomiting, paralytic ileus
• Electrolyte imbalances require parenteral supplementation
• High-grade reﬂux or prone positioning due to ARDS
• Combined enteral and parenteral
• IV fat emulsions: generally safe, well tolerated as long as baseline TG < 400 mg/dL (4.4
mmol/L) + no previous history of hyperlipidemia2
NUTRITION
Parenteral

• Antisecretory, antiinfammatory, antioxidant, antiprotease therapy
• NO clear evidence for benefcial eﬀects of these agents
• PPIs: for stress ulcer prophylaxis (not as a therapy for AP,  C.difficile infection1)
• Anti-inﬂammatory drugs: some efficacy in prevention of post-ERCP pancreatitis (rather
than in therapy of established AP)
THE 4 ANTI-
1. Tleyjeh I. M., Bin Abdulhak A. A., Riaz M., et al. (2012), PLoS One, 7 (12), pp. e50836

• Target of treatment: TG < 500 mg/dL1
• Triglyceride levels: should be monitored q12-24h1
PLASMAPHERESIS
• Removing a potential trigger for continued damage to the pancreas
• Indication: AP + serum TG > 1000 mg/dL + signs of hypocalcemia, lactic acidosis, or signs
of worsening inflammation or organ dysfunction + no contraindications to apheresis1
• TPE: treatment modality of choice for HTGP (because filters become clogged by plasma
triglycerides)2
• Heparin bolus at the beginning of apheresis: degrade large CM  smaller sizes (by 
triglyceride content,  CM fiterability across plasma separator)3
HYPERTRIGLYCERIDEMIA-induced (1)
1. Gelrud A., Whitcomb D. C. (2016), UpToDate, Lawrence S Friedman, Editor, Wolters Kluwer
2. Yeh J. H., Lee M. F., Chiu H. C. (2003), J Clin Apher, 18 (1), pp. 32-6
3. Kyriakidis A. V., Raitsiou B., Sakagianni A., et al. (2006), Digestion, 73 (4), pp. 259-64

INSULIN
• Enhancing lipoprotein lipase activity  accelerates CM, VLDL metabolism to glycerol and
fFA, inhibits hormone-sensitive lipase in adipocytes
• Indication: apheresis intolerant, or if serum glucose >500 mg/dL
• IV regular insulin: 0.1-0.3 U/kg/h*
• Glucose 5% supplementation when bood glucose 150-200 mg/dL (prevent hypoglycemia
due to insulin infusion)*
• Monitor bood glucose: q1h, insulin adjusted*
• Stop when TG < 500 mg/dL
HEPARIN
• Controversial, NOT recommended1
HYPERTRIGLYCERIDEMIA-induced (2)
(*) Gelrud A., Whitcomb D. C. (2016), UpToDate, Lawrence S Friedman, Editor, Wolters Kluwes

Gelrud A., Whitcomb D. C. (2016), UpToDate, Lawrence S Friedman, Editor, Wolters Kluwes

INDICATIONS1
• Suspected intraabdominal catastrophe (perforation, ischemia)
• Gallstone pancreatitis
• ERCP for obstructive jaundice
• Cholecystectomy to prevent recurrent attack (as soon as the patient has recovered and
the acute inﬂammatory process has subsided, should be performed before discharge to
prevent a recurrence of AP2,3, delay may carry substantial risk of recurrent biliary events4)
• Infected pancreatic necrosis
• Severe sterile pancreatic necrosis
• “Organized” pancreatic necrosis
• Delayed complications (pseudocyst, fistula)
SURGERY and INTERVENTION (1)
1. Beger H. G., Warshaw A. L., Büchler M. W., et al. (3008), "The Pancreas: An Integrated Textbook of Basic Science, Medicine, and Surgery", Wiley Blackwell.
2. Tenner S., Steinberg W. M. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier Saunders, pp. 969-993
4. Bakker O. J., van Santvoort H. C., Hagenaars J. C., et al. (2011), Br J Surg, 98 (10), pp. 1446-54

NO life-saving effect has been observed from peritoneal lavage for acute pancreatitis, and
therefore it is NOT RECOMMENDED
SURGERY and INTERVENTION (2)

Bakker O. J., van Santvoort H. C., van Brunschot S., et al. (2012), JAMA, 307 (10), pp. 1053-61

• Removal of a possibly impacted gallstone ± sphincterotomy (for any retained stones)
• Pancreatic duct stents (complications related to pancreatic duct disruption e.g., fistulas,
pseudocysts), may associated with polymicrobial contamination of the pancreas
ENDOSCOPY

RENAL REPLACEMENT THERAPY
• Routine use NOT recommended in severe AP
• For severe cases
• Where circulation dynamics are not stable with anuria even after sufficient initial fluid
infusion
• Cases with abdominal compartment syndrome (ACS)

• > 30% of non-enhancement of the pancreas on a contrast-enhanced CT scan (or MRI with
gadolinium)1, sterile or infected
• Percutaneous aspiration of necrosis with Gram stain and culture
• Currently NO role for prophylactic antibiotics  NOT recommended2
• Septic appearance: start broad-spectrum antibiotics for bowel flora (while awaiting the
results of Gram stain and cultures2)
• If negative: should be discontinued (to minimize risk of opportunistic or fungal
superinfection)
• Repeated FNA and Gram stain + culture: may be done every 5–7 days in the presence
of persistent fever
• Routine antifungal agents along with prophylactic or therapeutic antibiotics: NOT
recommended2
LOCAL COMPLICATIONS MANAGEMENT Necrosis (1)
1. Tenner S., Steinberg W. M. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier Saunders, pp. 969-993

• A step-up approach (percutaneous or endoscopic transgastric drainage  open
necrosectomy): considered for infected necrosis (clinical decision influenced by response to
antibiotic treatment, overall clinical condition)
• If conservative therapy can be safely implemented for > 4 weeks (allow pancreatic collections
to resolve or “wall-off”): surgical or endoscopic intervention generally much safer and better
tolerated
LOCAL COMPLICATIONS MANAGEMENT Necrosis (2)

• Usually after 4-6 weeks
• Most acute collections resolve over time
• Most are sterile
• Asymptomatic: NOT require treatment (regardless of size, location, extension)1
• Drainage when indicated (symptomatic, progressive enlargement, presence of
complications, suspected malignancy2):
• Surgery: cystgastrostomy or cyst-duodenostomy (if pseudocyst wall broadly adherent to
the stomach or duodenum), Roux-en-Y cyst-jejunostomy or pancreatic resection (if in tail)
• Endoscopy: stent insertion in to cyst, endoscopic cystgastrostomy or cyst-duodenostomy
• Percutaneous route
LOCAL COMPLICATIONS MANAGEMENT Pseudocyst

COMPLICATIONS
• Infection
• Pancreatic ascites
• Fistula formation
• Rupture: abdominal or thoracic cavities
• Bleeding: most life threatening, erodes into an adjacent vessel (pseudoaneurysm)  embolism
of vessels
• Obstruction: biliary system, vessels (inferior vena cava, portal vein), intestinal duodenal, urinary
system
• Jaundice: due to obstruction
LOCAL COMPLICATIONS MANAGEMENT Pseudocyst

Massive left pleural effusion secondary to a
pancreaticopleural fstula
Jensen E. H., Borja-Cacho D., Al-Refaie W. B., et al. (2012), Sabiston Textbook of Surgery, Courtney M. Townsend, R. Daniel Beauchamp, B. Mark Evers, Editors, Elsevier Saunders, pp.
1515-1547

• If NO radiological or clinical suspicion of sepsis:
• Should be observed
• Image-guided fine needle aspiration (FNA) should be avoided (risk of introducing
infection into a sterile collection)*
LOCAL COMPLICATIONS MANAGEMENT
Acute peripancreatic ﬂuid collections
(*) Greenberg J. A., Hsu J., Bawazeer M., et al. (2016), Can J Surg, 59 (2), pp. 128-40

LOCAL COMPLICATIONS MANAGEMENT
Algül H., Weber A., Huber W., et al. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 1653-
1691.

MANAGEMENT OF ABDOMINAL COMPARTMENT SYNDROME
• Sequential measurement of IAP: recommended for cases with excessive fluid infusion,
high severity, renal and respiratory complications, fluid accumulation in multiple areas
(CT)
• Persistent or recurrent IAP ≥ 12mmHg: conservative treatment (gastrointestinal
decompression, intra-abdominal decompression, improvement of abdominal wall compliance,
appropriate fluid infusion and circulation management)  Goal: IAP ≤ 15 mmHg.
• Surgical decompression: considered only when internal treatment is not effective for patients
with IAP > 20mmHg and where the additional complication of organ failure

• Severe AP or other conventional criteria for ICU admission1
• Intensive care: does result in  hospital mortality and shorter lengths of stay2
ICU TREATMENT
2. Pronovost P. J., Angus D. C., Dorman T., et al. (2002), JAMA, 288 (17), pp. 2151-2162

• NO remedial effect of nasogastric tube insertion has been observed for mild acute pancreatitis.
• NOT used routinely in mild pancreatitis
• Routine use of nasogastric suction tubes is NOT required
NASOGASTRIC TUBE
• Yokoe M., Takada T., Mayumi T., et al. (2015), J Hepatobiliary Pancreat Sci, 22 (6), pp. 405-32
• Tenner S., Steinberg W. M. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors,
Elsevier Saunders, pp. 969-993

Steer M. L. (2012), Irwin and Rippe’s Intensive Care Medicine, James M. Rippe
Richard S. Irwin, Editor, Lippincott Williams & Wilkins, pp. 1115-1129

• ERCP: can be performed when indicated with biliary disease that strongly necessitates
intervention (biliary pancreatitis, symptomatic choledocholithiasis, and/or cholangitis).
Minimizing fetal exposure to fluoroscopy is imperative (strong recommendation, low level of
evidence).
• Symptomatic cholecystitis: should be managed with early surgical intervention with
laparoscopic cholecystectomy (strong recommendation, low level of evidence)
PREGNANCY
Tran T. T., Ahn J., Reau N. S. (2016), Am J Gastroenterol, 111 (2), pp. 176-94

PREVENTION
PHUNG HUY HOANG, MD
September, 2017
Primary
Secondary

• Prophylaxis of post-ERCP pancreatitis in high-risk patients (see risk above)
• Pancreatic duct stents
• And/or postprocedure rectal NSAID suppositories (e.g., indomethacin 100 mg or
diclofenac 100 mg) placed either just before or just after ERCP
PRIMARY

• Cholecystectomy and/or endoscopic sphincterotomy
• Alcohol
• Smoking abstinence
• Hypertriglyceridemia control
SECONDARY (1)

TRIGLYCERIDEMIA CONTROL1,2:
• A fat- and simple sugar-restricted diet, weight loss
• Control of diabetes if present
• Administration of lipid-lowering agents
• eg, oral gemfibrozil 600 mg twice daily
• Omega-3 fatty acids: capable of lowering high TG by 45%4
• Periodic apheresis: considered in noncompliant with diet and oral drug therapy,
recovered from their initial episode of AP4
• Avoidance of drugs that elevate lipid levels
SECONDARY (2)
1. Gelrud A., Whitcomb D. C. (2016), UpToDate, Lawrence S Friedman, Editor, Wolters Kluwes
1691
3. Harris W. S., Ginsberg H. N., Arunakul N., et al. (1997), J Cardiovasc Risk, 4 (5-6), pp. 385-91
4. Piolot A., Nadler F., Cavallero E., et al. (1996), Pancreas, 13 (1), pp. 96-9.

Catapano A. L., Graham I., De Backer G., et al. (2016), Eur Heart J, 37 (39), pp. 2999-3058

“ATP III”
NIH Publication No. 02-5215
September 2002

RECURRENT AP
PHUNG HUY HOANG, MD
September, 2017

• 2 most common: Alcohol, Cholelithiasis
• Differential diagnosis should encompass:
• Biliary tree and pancreatic ducts:
• Occult biliary tract disease including microlithiasis (2/3 actually have occult gallstone
disease due to microlithiasis)
• Choledochocele; ampullary tumors; pancreas divisum; pancreatic duct stones, stricture,
tumor
• Sphincter of Oddi dysfunction
• Drugs
• Hypertriglyceridemia
• Pancreatic cancer (2-4% present with acute pancreatitis)
• Genetic defects as in hereditary pancreatitis, cystic fibrosis mutations

Microlithiasis
• Diagnosis
• EUS: useful
• Duodenal aspiration of bile, direct CBD aspiration at ERCP after CCK stimulation:
limited usage
• Therapy is controversial
• Endoscopic biliary sphincterotomy
• Long-term treatment with ursodeoxycholic acid
• Laparoscopic cholecystectomy: sometimes recommended
• Algül H., Weber A., Huber W., et al. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 1653-
1691
• Tenner S., Steinberg W. M. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier
• Saraswat V. A., Sharma B. C., Agarwal D. K., et al. (2004), Journal of Gastroenterology and Hepatology, 19 (10), pp. 1206-1211

1. Akshintala V. S., Hutfless S. M., Colantuoni E., et al. (2013), "Systematic review with network meta-analysis: pharmacological prophylaxis against
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Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 1653-1691.
3. Annane D., Siami S., Jaber S., et al. (2013), "Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients
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4. Avunduk C. (2008), "Acute Pancreatitis", Manual of Gastroenterology: Diagnosis And Therapy, Lippincott Williams & Wilkins, pp. 306-316.
5. Badalov N., Baradarian R., Iswara K., et al. (2007), "Drug-induced acute pancreatitis: an evidence-based review", Clin Gastroenterol Hepatol,
5 (6), pp. 648-61; quiz 644.
6. Baillie J. (2007), "AGA Institute Medical Position Statement on Acute Pancreatitis", Gastroenterology, 132 (5), pp. 2019-2021.
7. Bakker O. J., van Santvoort H. C., Hagenaars J. C., et al. (2011), "Timing of cholecystectomy after mild biliary pancreatitis", Br J Surg, 98 (10),
pp. 1446-54.
8. Bakker O. J., van Santvoort H. C., van Brunschot S., et al. (2012), "Endoscopic transgastric vs surgical necrosectomy for infected necrotizing
pancreatitis: a randomized trial", JAMA, 307 (10), pp. 1053-61.
9. Balthazar E. J., Freeny P. C., vanSonnenberg E. (1994), "Imaging and intervention in acute pancreatitis", Radiology, 193 (2), pp. 297-306.
10. Banks P. A., Bollen T. L., Dervenis C., et al. (2013), "Classification of acute pancreatitis--2012: revision of the Atlanta classification and
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Acute Pancreatitis: Pathophysiology, Definition, and Clinical Presentation

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