Dr. S.P. Hewawasam (MD)
Consultant Gastroenterologist/Senior Lecturer in Physiology
Incidence - 13–45/100,000 persons (US figures)
The median length of hospital stay - 4 days
mortality - 1%
Hospitalization rates increase with age
higher among males than females
Common Causes
Gallstones (including microlithiasis)
Alcohol (acute and chronic alcoholism)
Hypertriglyceridemia (usually >11.3 mmol/L (>1000 mg/dL)
Endoscopic retrograde cholangiopancreatography (ERCP),
especially after biliary manometry
Drugs (azathioprine, 6-MP, sulfonamides, estrogens, tetracycline,
valproic acid, anti-HIV medications, 5-ASA, corticosteroids
Trauma (especially blunt abdominal trauma)
Postoperative (abdominal and non-abdominal )operations)
Uncommon Causes
Vascular causes and vasculitis (ischemic-hypoperfusion states after
cardiac surgery)
Connective tissue disorders & TTP
CA pancreas
Hypercalcemia
Periampullary diverticulum
Pancreas divisum
Hereditary pancreatitis
Cystic fibrosis
Renal failure
Infections(mumps, coxsackie virus, cytomegalovirus, echovirus,
parasites)
Autoimmune (e.g., type 1 and type 2)- elevated Ig G4
Alcohol is the commonest cause among males
Gallstones is the commonest cause among females
In Sri Lanka
Risk is 4X greater in patients with at least one gallstone <5 mm
than in patients with larger stones
The incidence of pancreatitis in alcoholics is surprisingly low
(5/100,000), indicating that in addition to the amount of
alcohol ingested, other factors affect a person’s susceptibility to
pancreatic injury such as cigarette smoking
Post ERCP pancreatitis in 5%-10%
o prophylactic pancreatic duct stent & rectal NSAID used for prevention
0.1–2% of cases are drug related
Acute Pancreatitis
Interstitial Pancreatitis Necrotizing Pancreatitis
Blood supply maintained Blood supply interrupted
Generally self-limiting Extent of necrosis may correlate
with severity of attack and
systemic complications
Autodigestion is the currently accepted pathogenic mechanism
Proteolytic enzymes (e.g., trypsinogen, chymotrypsinogen, proelastase, and lipolytic
enzymes such as phospholipase A2) activated in the pancreas acinar cell
rather than in the intestinal lumen
Digest pancreatic and peripancreatic tissues but also can activate
other enzymes, such as elastase and phospholipase A2
Number of factors (e.g., endotoxins, exotoxins, viral infections, ischemia, oxidative stress,
lysosomal calcium, and direct trauma) are believed to facilitate premature
activation of trypsin
Spontaneous activation of trypsin can also occur
3 phases of acute pancreatitis
Initial phase - characterized by intrapancreatic digestive
enzyme activation and acinar cell injury
Second phase - activation, chemoattraction, and
sequestration of leukocytes and macrophages in the pancreas→
→enhanced intrapancreatic inflammation
• also evidence to support the concept that neutrophils can activate trypsinogen
Third phase - due to the effects of activated proteolytic
enzymes and cytokines released by the inflamed pancreas; on
distant organs
The active enzymes and cytokines → digest cell membranes and
cause proteolysis, edema, interstitial H’age, vascular damage,
coagulation necrosis, fat necrosis, and parenchymal cell necrosis
Cellular injury and death result in the liberation of bradykinin
peptides, vasoactive substances, and histamine → vasodilation,
↑vas. permeability & edema → profound effects on many organs
o SIRS
o ARDS
o Multiorgan failure
A number of genetic factors can ↑ the susceptibility and/or modify the severity of
acute pancreatitis, recurrent pancreatitis & chronic pancreatitis- all centred
around control of trypsin activity
Abdominal pain is the cardinal symptom
o Mild discomfort→severe, constant and incapacitating distress
o In the epigastrium and periumbilical region
o may radiate to the back(interscapular region), chest, flanks, and lower
abdomen
o May be slightly relieved by bending forward
o Nausea, vomiting, and abdominal distention due to gastric and intestinal
hypomotility
o Features of chemical peritonitis-guarding, rigidity
Physical examination frequently reveals a distressed and anxious
patient
Low-grade fever, tachycardia, and hypotension are fairly
common
Shock is not unusual-may result from
o hypovolemia IIry to exudation of blood and plasma proteins into the
retroperitoneal space
o increased formation and release of kinin peptides, which cause
vasodilation and increased vascular permeability
o systemic effects of proteolytic and lipolytic enzymes released into the
circulation.
Jaundice occurs infrequently
o usually due to edema of the head of the pancreas with compression of the
intrapancreatic portion of the CBD or passage of a biliary stone or sludge
Erythematous skin nodules due to fat necrosis may rarely occur
pulmonary findings in 10–20% of patients
o basilar rales, atelectasis, and pleural effusion, mostly left sided.
Abdominal tenderness, guarding and rigidity of variable degree
Bowel sounds - diminished or absent
Upper abdominal mass-
o An enlarged pancreas from acute fluid collection, walled off necrosis, or a
pseudocyst in the upper abdomen later on(4–6/52)
Cullen’s sign Grey-Turner sign
as the result of reflects tissue catabolism of Hb from
hemoperitoneum severe necrotizing pancreatitis with H’age
3x or more rise in serum amylase and lipase
o virtually diagnostic if gut perforation, ischemia & infarction excluded
o Amylase >1000 also virtually diagnostic
o no correlation between the severity & the level of lipase/amylase
o serum amylase tend to return toward normal after 3–7 days, despite
ongoing pancreatitis
o isoamylase and lipase levels may be elevated for 7–14 days
o many other causes for amylase elevations, incl. acidaemia(pH <7.32)
o serum lipase is the preferred test
Leukocytosis
With more severe disease
from loss of plasma into the
o Hemoconcentration with PCV >44%
retroperitoneal space and peritoneal
o prerenal azotemia cavity
o Hemoconcentration may be the harbinger of more severe disease (i.e.,
pancreatic necrosis),
o Whereas azotemia is a significant risk factor for mortality
Hyperglycemia is common and multifactorial
o ↓ insulin, ↑glucagon, ↑ adrenal glucocorticoids & catecholamines
Hypocalcemia occurs in ~25%
o pathogenesis incompletely understood
o Intraperitoneal saponification of Ca++ by fatty acids in areas of fat necrosis
occurs occasionally, with large amounts (up to 6.0 g) dissolved or
suspended in ascitic fluid
Hyperbilirubinemia in ~10% of patients
o However, jaundice is transient
Alk. Phos. & AST also transiently elevated,
o parallel serum bilirubin values and may point to GB-related disease or
inflammation in the pancreatic head
Hypertriglyceridemia in 5–10% of patients,
o serum amylase levels in these individuals are often spuriously normal d
5–10% of patients have hypoxemia
ECG abnormalities –occasional
o ST-segment and T-wave abnormalities simulating myocardial ischemia
Abdominal ultrasound
o Recommended as the initial diagnostic imaging modality
o Useful to evaluate for gallstone disease and the pancreatic head
o The revised Atlanta criteria have clearly outlined the morphologic features
of acute pancreatitis on computed tomography
Contrast Enhanced CT (CECT) abdomen
o Imaging modality of choice
• Wider availability, Faster examination time-good images in critically ill, Relatively cheaper
MRI
o for multiple follow-up examinations to reduce exposure to radiation
o when CECT is contraindicated
o when characterisation of specific lesions, mainly fluid collections, is
warranted
Revised Atlanta criteria have clearly outlined the
morphologic features of acute pancreatitis on CT
o (1) interstitial pancreatitis
o (2) necrotizing pancreatitis
o (3) acute pancreatic fluid collection
o (4) pancreatic pseudocyst
o (5) acute necrotic collection (ANC)
o (6) walled-off pancreatic necrosis (WON)
2 out of 3 criteria
o (1) typical abdominal pain in the epigastrium that may radiate to the back
o (2) threefold or greater elevation in serum lipase and/or amylase
o (3) confirmatory findings of acute pancreatitis on cross-sectional abdominal
imaging
Differential Diagnosis (DD of acute abdomen)
(1) perforated viscus, especially peptic ulcer
(2) acute cholecystitis and biliary colic;
(3) acute intestinal obstruction
(4) mesenteric vascular occlusion
(5) renal colic
(6) inferior myocardial infarction
(7) dissecting aortic aneurysm
(8) connective tissue disorders with vasculitis
(9) pneumonia
(10) diabetic ketoacidosis
Clinicians have been largely unable to predict severity
All severity scoring systems are cumbersome, needs 48 hrs to be
accurate
When the score demonstrates severe disease, the patient’s
condition is obvious regardless of the score
The new scoring systems, such as the BISAP, have not shown to be
more accurate than the other scoring systems
In general, AP-specific scoring systems have a limited value, as
they provide little additional information to the clinician in the
evaluation of patients and may delay appropriate management
Essence :
o Do not bother too much about the scoring systems
o Use APACHE II
Clinical findings associated with a severe course for initial risk assessment
Patient characteristics
Age >55 years
Obesity (BMI >30 kg/m2)
Altered mental status
Comorbid disease
The systemic inflammatory response syndrome (SIRS) Presence of ≥2 of the following criteria:
– pulse >90 beats/min
– respirations >20/min or PaCO2 >32 mm Hg
– temperature >38 °C or <36 °C
– WBC count >12,000 or <4,000 cells/mm3 or >10% immature neutrophils (bands)
Laboratory findings
BUN >20 mg/dl
Rising BUN
HCT >44%
Rising HCT
Elevated creatinine
Radiology findings
Pleural effusions
Pulmonary infiltrates
Multiple or extensive extrapancreatic collections
The presence of organ failure and/or pancreatic necrosis defines severe acute pancreatitis.
The Revised Atlanta Classification (1) defines phases of acute
pancreatitis, (2) defines severity of acute pancreatitis, and (3) clarifies
imaging definitions
Two phases
o Early (<2 weeks)
• primarily describes the hospital course of the disease
• severity is defined by clinical parameters rather than morphologic findings
• CT imaging is usually not needed or recommended during the first 48 h of admission
in acute pancreatitis
o Late (>2 weeks)
• protracted course of illness
• may require imaging to evaluate for local complications
• parameter of severity is persistent organ failure
• may require supportive measures such as renal dialysis, ventilator support, or need
for supplemental nutrition via the nasojejunal or parenteral route
• important to recognize the development of necrotizing pancreatitis on CT
Initial Management
Early Aggressive Intravenous Hydration
o 250–500 ml/ hour of isotonic crystalloid to provided to all patients
o unless CVS, renal, or other related comorbidity exist
o most beneficial during the first 12–24 h, little benefit beyond this time period
o Lactated Ringer’s solution may be preferred
o The goal of aggressive hydration should be to decrease the BUN
ERCP in Acute Pancreatitis
o Pt’s with AP and concurrent acute cholangitis should undergo ERCP within 24 h
o ERCP is not needed early in most patients with gallstone pancreatitis who lack
laboratory or clinical evidence of ongoing biliary obstruction
o In the absence of cholangitis and/or jaundice, MRCP or EUS rather than
diagnostic ERCP should be used to screen for choledocholithiasis
o Prophylaxis for post ERCP pancreatitis
Use for any extrapancreatic infection
o cholangitis, catheter-acquired infections, bacteremia, UTI, pneumonia
Routine prophylactic antibiotics for patients with severe AP is not
recommended
Not recommended for sterile necrosis to prevent infected necrosis
Infected necrosis considered in patients with pancreatic or
extrapancreatic necrosis who deteriorate or fail to improve after
7–10 days of hospitalization
o CT-guided fine-needle aspiration (FNA) for Gram stain and culture to
guide use of appropriate antibiotics
or
o Empiric antibiotics after obtaining necessary cultures for infectious agents,
without CT FNA
In infected necrosis, antibiotics that penetrate pancreatic necrosis,
(carbapenems, quinolones, and metronidazole) may be useful in
delaying or sometimes totally avoiding interventions
Routine administration of antifungals not recommended
Why not to use routine antibiotics
o Because of the consistency of pancreatic necrosis few antibiotics penetrate
when given intravenously
o From A meta-analysis NNT was 1429 for 1 patient to benefit
In mild AP, oral feedings started immediately if there is no N & V
and the abdominal pain has resolved
o low-fat solid diet appears as safe as a clear liquid diet
In severe AP, enteral nutrition is recommended to prevent
infectious complications
o Parenteral nutrition only if enteral nutrition not available, not tolerated,
or not meeting caloric requirements
o NG and NJ comparable in efficacy and safety
Cholecystectomy before discharge(or within 4-6 weeks) if gallstones are
found in the GB to prevent recurrence
cholecystectomy deferred until active inflammation subsides and fluid
collections resolve or stabilize in necrotizing pancreatitis due to stones
Asymptomatic pseudocysts and pancreatic and/or
extrapancreatic necrosis do not warrant intervention regardless of
size, location, and/or extension
In stable patients with infected necrosis, surgical, radiologic, and/or
endoscopic drainage may be delayed preferably for more than 4 weeks
to allow liquefication of the contents and the development of a fibrous
wall around the necrosis (walled-off necrosis
In symptomatic patients with infected necrosis, minimally invasive
methods of necrosectomy are preferred to open necrosectomy
Hypertriglyceridemia
o Initial therapy include insulin, heparin, or plasmapheresis
o Outpatient therapies
Hypercalcemia
o Treatment of hyperparathyroidism or malignancy is effective at reducing
serum calcium
Autoimmune pancreatitis
o Glucocorticoids
Harrison's Principles of Internal Medicine, 19e
American College of Gastroenterology Guideline: Management of Acute
Pancreatitis 30 July 2013; doi: 10.1038/ajg.2013.218
2012 revision of the Atlanta Classification of acute pancreatitis POLSKIE
ARCHIWUM MEDYCYNY WEWNĘTRZNEJ 2013
Acute Pancreatitis N Engl J Med 2006;354:2142-50
