Acute pancreatitis

Acute Pancreatitis

1. Acute pancreatitis
Dr.Rajesh K. Mandal
MD, Internal Medicine
Bir Hospital,Nepal

2. INCIDENCE
•Human and financial burden of acute
pancreatitis continues to grow
•Incidence of acute pancreatitis in the US
–Varies from 4.9 to 73.4 per 100,000 patients
–increasing
•Death may occur before diagnosis
– 10% of patients with severe disease

3. •14th most common cause of death due to GI
diseases
•Second most common inpatient GI diagnosis
in the united states
–After cholelithiasis and acute cholecystitis
–ahead of acute appendicitis
•Overall mortality rate less than 5%

4. DEFINITIONS
•PHYSIOLOGICALLY
–as an acute inflammatory process of the
pancreas
–with variable involvement of other regional
tissues or remote organ System

5. CLINICALLY
Presenting with 2 of the following 3 criteria:
1.Symptoms (e.g, Epigastric pain) consistent
with pancreatitis
2.Serum amylase or lipase level greater than 3
times the laboratory’s upper limit of normal
3.Radiologic imaging consistent with
pancreatitis,
₋(usually using CT or MRI)

6. Causes of Acute Pancreatitis

7. Causes

20. •The initial phase is characterized by intrapancreatic
digestive enzyme activation and acinar cell injury
•The second phase of pancreatitis involves the
activation, chemoattraction, and sequestration of
leukocytes and macrophages in the pancreas,
resulting in an enhanced intrapancreatic
inflammatory reaction
•The third phase of pancreatitis is due to the effects
of activated proteolytic enzymes and cytokines,
released by the inflamed pancreas, on distant organs
pathogenesis

21. Pathogenesis
•conversion of trypsinogen to trypsin, within
acinar cells
•Trypsin catalyzes conversion of proenzymes,
including trypsinogen and inactive precursors
of elastase, phospholipase A2 (PLA2), and
carboxypeptidase, to active enzymes
•Trypsin also may activate the complement and
kinin systems.
•Active enzymes autodigest the pancreas and
initiate a cycle of releasing more active
enzymes

22. •Pancreatic secretory trypsin inhibitor (PSTI,
now called SPINK1) binds and inactivates
about 20% of the trypsin activity.
• Low intraacinar calcium concentrations also
prevent further autoactivation of trypsin.

23. Clinical Features
•acute onset of persistent, severe epigastric
abdominal pain .
• In some patients, the pain may be in the right
upper quadrant or, rarely, confined to the left
side.
•In patients with gallstone pancreatitis, the pain is
well localized and the onset of pain is rapid,
reaching maximum intensity in 10 to 20 minutes.

24. •in patients with pancreatitis due to hereditary or metabolic
causes or alcohol, the onset of pain may be less abrupt and the
pain may be poorly localized.
• In approximately 50 percent of patients, the pain radiates to
the back. The pain persists for several hours to days and may be
partially relieved by sitting up or bending forward.
•Approximately 90 percent of patients have associated nausea
and vomiting which may persist for several hours.
•Patients with severe acute pancreatitis may have dyspnea due
to diaphragmatic inflammation secondary to pancreatitis,
pleural effusions, or adult respiratory distress syndrome.

25. • there may be significant tenderness to
palpation in the epigastrium or more diffusely
over the abdomen
• may have abdominal distention and
hypoactive bowel sounds due to an ileus
secondary to inflammation
•Patients may have scleral icterus due to
obstructive jaundice due to
choledocholithiasis or edema of the head of
the pancreas.

26. • severe pancreatitis may have fever,
tachypnea, hypoxemia, and hypotension.
• In 3 percent of patients with acute
pancreatitis, ecchymotic discoloration may be
observed in the periumbilical region (Cullen's
sign) or along the flank (Grey Turner sign.
•Nonspecific, suggest the presence of
retroperitoneal bleeding in the setting of
pancreatic necrosis

28. Lab Findings
•Serum amylase rises within 6 to 12 hours of the
onset
•short half-life of approximately 10 hours and in
uncomplicated attacks returns to normal within
three to five days.
• Serum amylase elevation of greater than three times
the upper limit of normal has a sensitivity for the
diagnosis of acute pancreatitis of 67 to 83 percent
and a specificity of 85 to 98 percent

29. •Serum lipase has a sensitivity and specificity
for acute pancreatitis ranging from 82 to 100
percent.
•Serum lipase rises within four to eight hours
of the onset of symptoms, peaks at 24 hours,
and returns to normal within 8 to 14 days

30. Laboratory Features

33. • Trypsinogen activation peptide (TAP), a five 
amino-acid peptide that is cleaved from 
trypsinogen to produce active trypsin, is 
elevated in acute pancreatitis.
•TAP may be useful in detection of early acute 
pancreatitis and as a predictor of the severity 
of acute pancreatitis 

34. •Markers of immune activation —Acute 
pancreatitis is associated with elevations in C-
reactive protein (CRP), interleukin (IL)-6, IL-8, 
IL-10, tumor necrosis factor (TNF), and PMN 
elastase.
• A CRP level above 150 mg/dL at 48 hours is 
associated with severe pancreatitis.

35. • Patients with pancreatitis may have 
leukocytosis and an elevated hematocrit from 
hemoconcentration due to extravasation of 
intravascular fluid into third spaces. 
•Metabolic abnormalities including elevated 
blood urea nitrogen (BUN), hypocalcemia, 
hyperglycemia, and hypoglycemia may also 
occur

36. USG
• In patients with acute pancreatitis, the 
pancreas appears diffusely enlarged and 
hypoechoic on abdominal ultrasound. 
Gallstones may be visualized in the gallbladder 
or the bile duct
•Peripancreatic fluid appears as an anechoic 
collection on abdominal ultrasound. These 
collections may demonstrate internal echoes 
in the setting of pancreatic necrosis

37. •approximately 25 to 35 percent of patients 
with acute pancreatitis, bowel gas due to an 
ileus precludes evaluation of the pancreas or 
bile duct 

38. CT
•CT in acute pancreatitis are to
• (1) exclude other serious intra-abdominal conditions (e.g., 
mesenteric infarction or a perforated ulcer)
•(2) stage the severity of acute pancreatitis, and 
•(3) determine whether complications of pancreatitis are 
present (e.g., involvement of the GI tract or nearby blood 
vessels and organs, including liver, spleen, and kidney).
•Helical CT is the most common technique.
•Pancreatic necrosis manifested as perfusion defects after IV 
contrast may not appear until 48 to 72 hours after onset of 
acute pancreatitis.

39. MRI
• On MR T1 weighted images with fat suppression, 
diffuse or focal enlargement of the pancreatic gland 
can be seen in patients with acute pancreatitis and the 
margins of the pancreas may be blurred.
• Due to pancreatic edema, the signal intensity of the 
pancreatic parenchyma might be hypointense relative 
to the liver on T1-weighted images, and hyperintense 
on T2-weighted images. 
•On contrast-enhanced magnetic resonance imaging 
(MRI), failure of the pancreatic parenchyma to enhance 
indicates the presence of pancreatic necrosis.

44. Scoring systems
•Ranson ’s Criteria
•Acute Physiology and Chronic Health
Examination (APACHE)-II Scoring
•Computed Tomography Severity Index (CTSI)
•Bedside Index for Severity in Acute
Pancreatitis (BISAP) Scoring

49. APACHE II score
•Apache score of ≥ 8 Organ failure Substantial
pancreatic necrosis (at least 30% glandular
necrosis according to contrast-enhanced CT)
•Interpretation:
– If the score ≥ 3: severe pancreatitis likely.
–If the score < 3, severe pancreatitis is unlikely
•Score 0 to 2 : 2% mortality
•Score 3 to 4 : 15% mortality
•Score 5 to 6 : 40% mortality
•Score 7 to 8 : 100% mortality

50. Computed Tomography Severity Index (CTSI)

51. Bedside index of severity in acute 
pancreatitis (BISAP) score
Evaluates the following Clinical Criteria:
•BUN >25 mg/dL (8.9 mmol/L)
•Impairment of mental status with a Glasgow coma 
score <15
•SIRS (systemic inflammatory response syndrome)
•Age >60 years old
•Pleural effusion
Each determinant is given one point
SIRS is defined as 2 or more of the following variables;
•Fever of more than 38°C (100.4°F) or less than 36°C (96.8°F)
•Heart rate of more than 90 beats per minute
•Respiratory rate of >20 breaths per minute or PaCO
2
 <32mm Hg
•Abnormal white blood cell count (>12,000/µL or < 4,000/µL or >10% immature [band] forms)
Wu BU et al GUT 2008
Singh VK et al Am.J.Gastro 2009

53. BISAP Score  BISAP Score Observed Mortality
•0  0.1%
•1  0.4%
•2 1.6%
•3 3.6%
•4 7.4%
•5 9.5%
Wu et al, Gut 2008

55. Brun et al. Prognosis in Acute Pancreatitis; Practical
Gastroenterology March 2012

57. •Natural History of Acute 
Pancreatitis

58. Natural ho

60. Management

62. Acute pancreatitis
Management
•Severe pancreatitis carries a mortality of 80%
•Interventions in the first 24hrs can help to minimise the
morbidity and mortality.

63. Management Points:
•IV fluids
•Relief of pain
•Role of antibiotics
•Nutritional support
•Role of endoscopy

64. Acute pancreatitis
IV Fluids
•1-2 liters of fluid rapidly in first 4hrs
•200 – 250 ml / hr for 24 to 72 hrs
•Ringer lactate better than normal saline
•Take precautions in CCF, elderly

67. Acute pancreatitis
Relief of pain
•Narcotic analgesics
•Non narcotic analgesics

68. Acute pancreatitis
Role of prophylactic Antibiotics
•Debatable
•SIRS v/s Infection
•Infection is unlikely in the first week
•No role of prophylatic antibiotics

72. Acute pancreatitis
Nutritional Support
Enteral has distinct advantages
•Decreased morbidity
•Decreased multi organ failure
•Decreased systemic infection
•Decreased need for operative intervention

73. Acute pancreatitis
Nutritional Support
Enteral has distinct advantages
–Mild – oral feeds in 1 – 3 days
–Severe – Enteral feeds by 3 – 4 days
Use NJ or NG tubes
Better than TPN

80. Drugs in Acute Mild Pancreatitis
•H
2
RA, PPI -No role
•Aprotinin -Not effective
•Gabexate -? Effective
•Octreotide -Not effective
•Somatostatin - Effective – ERCP
•Dextran - NOT known
•Lexipafant -? Effective

81. Role of Endoscopy
•Biliary pancreatitis
•Pancreatic Necrosis
•Ductal Disruption

82. Role of Endoscopy
Gall stone pancreatitis
Pancreatitis with suspected gall
stones
Abnormal Liver function tests
USG Abd/MRCP
ERCP
CBD Clearance

83. Role of Endoscopy
•Pancreatic Necrosis

86. Role of Endoscopy
•Ductal Disruption
–Can result in unilateral pleural effusion, pancreatic
ascites, or enlarging fluid collection
–MRCP and ERCP might be used to identify a large
disruption in ducts
–Bridging stent across the disruption usually
promotes duct healing

89. Roles of Advanced Imaging Techniques
•Role of CT changed over time
•Best use of an early-stage CT scan is to confirm a
diagnosis
•Best use of a CT scan after the first 5 to 7 days is
to evaluate the presence of local complications
•MRI is helpful in distinguishing walled-off
necrosis from a pseudocyst.
•Endoscopic ultrasonography highly sensitive test
for detecting cholelithiasis and
choledocholithiasis and could be an alternative to
MRCP, which has limited accuracy for detecting
smaller gallstones or sludge.

90. Special Considerations
•Timing of ERCP for Patients With Biliary
Pancreatitis
•Post-ERCP Pancreatitis

93. Special Considerations
•Timing of ERCP for Patients With Biliary
Pancreatitis
•Post-ERCP Pancreatitis
•Secondary Prevention

94. E
R
C
P

96. other criteria or markers of
severity
•used in clinical studies include
• CT severity index,
•urinary concentration of trypsinogen
activating peptide (TAP), and
•serum levels of lactate dehydrogenase (LDH),
•procalcitonin,
•CAPAP-B, IL-6, and
•other markers of acute phase injury

97. Blood Urea Nitrogen
•Hemoconcentration has been shown to be an
accurate predictor of necrosis and organ
failure.
•Both the BUN level and the hematocrit or Hgb
level are routine laboratory tests that may
provide information on changes in
intravascular volume status.
•Either test may be used in monitoring the
early response to initial fluid resuscitation.

98. •Wu and colleagues recently performed a large
observational cohort study on data from 69 U.S.
hospitals and found that BUN may be superior to
Hgb (but not hematocrit).
• For every 5 mg/dL increase in BUN during the
first 24 hours, the age- and gender-adjusted odds
ratio for mortality increased by 2.2.

99. •BUN yielded the highest accuracy in
determining mortality at 24 and 48 hours.
• serial BUN measurements would be the most
valuable single routine laboratory test for
predicting mortality in acute pancreatitis.

100. Hematocrit
•A high hematocrit on admission, or 1 that fails to
decrease after 24 hours of rehydration,
•is thought to be a sign of hemoconcentration
from retroperitoneal fluid loss
 is a marker of severe disease.
• One study showed that a hematocrit greater
than 44% had a sensitivity of 72% on admission
and of 94% after 24 hours in detecting organ
failure.
•The negative predictive value at 24 hours was
96%.

101. •Although 1 study from Germany found no
correlation between admission hematocrit
and organ failure,
• most investigators have found hematocrit to
be important in the management of patients
with acute pancreatitis.
• An elevated hematocrit (>44%) is a predictor
for the development of necrosis.
• the hematocrit should be observed at
admission for prognostic purposes and
•followed prospectively to assist in guiding the
rate of IV volume resuscitation.

102. C-Reactive Protein
• an acute-phase reactant produced by the liver
is used extensively in Europe as a marker of
severe pancreatitis.
•CRP is inexpensive to measure and readily
available.
•At a cutoff of 21 mg/dL, the sensitivity of CRP
in detecting severe disease in patients with
acute pancreatitis is only 60%, but the test is
highly specific.
• At a lower cutoff (10 mg/L), CRP becomes
highly sensitive, but the test specificity drops
to 75%.

103. Interleukin-6
• an acute-phase reactant that is produced by a
variety of cells and induces hepatic synthesis
of CRP.
• Several studies have shown that this cytokine
is reasonably accurate in differentiating mild
from severe disease.

104. Polymorphonuclear Leukocyte
Elastase
• rises very early (before CRP) in acute
pancreatitis.
•High levels have been reported to
differentiate mild from severe disease.

105. Phospholipase A2
•PLA2 is involved in the release of prostaglandin
precursors such as arachidonic acid from cell
membranes.
•PLA2 also degrades surfactant in the lung and
may play a role in the pulmonary dysfunction
associated with acute pancreatitis.
• Levels of catalytic type II PLA2 have been
reported to differ- entiate between mild and
severe disease within 24 hours of admission.

106. Urinary Trypsinogen Activation
Peptide
•may serve as an early predictor of severity in
patients with acute pancreatitis.
•Normally, trypsinogen is cleaved to trypsin in
the intestinal lumen by the enzyme
enterokinase.
• Premature intrapancreatic activation of
trypsin during acute pancreatitis results in the
release of TAP.

107. •The degree of pancreatic necrosis and
systemic inflammatory response or sepsis is
directly related to TAP concentration.
•Elevated urinary TAP (>30 nmol/L) correlates
with disease severity.
•The test can be applied within 12 hours of
admission.
•The positive predictive value of an elevated
TAP for severe pancreatitis is 80%, and
• the negative predictive value approaches
100%

108. Procalcitonin
•This propeptide is another acute-phase
reactant that has been shown to differentiate
mild from severe acute pancreatitis within the
first 24 hours after symptom onset.
• A serum strip test has been developed that
has a sensitivity of 86% and a specificity of
95% in detecting organ failure.

109. Prognosis
•Approximately 75% to 80%, of patients with
acute pancre- atitis have a resolution of the
disease process (interstitial pan- creatitis) and
do not enter the second phase.
•20% of patients, a more protracted course
develops, often related to the necrotizing
process (necrotizing pancreatitis) lasting
weeks to months.

110. • Mortality in the second phase is related to a
combination of factors, including organ failure
secondary to sterile necrosis, infected
necrosis, or complications from surgical
intervention.
•There are 2 time peaks for mortality in acute
pancreatitis.

111. •Most studies in the United States and Europe
reveal that about half the deaths occur within
the first week or 2, usually from multiorgan
failure.
• Death can be very rapid.
• About one quarter of all deaths in Scotland
occurred within 24 hours of admission, and
one third within 48 hours.
• After the second week of illness,
patients succumb to pancreatic infection
associated with multiorgan failure

112. •Some studies in Europe report a very high late
mortality rate from infection.
• Patients who are older and have comorbid illnesses
have a substantially higher mortality rate than
younger healthier patients.
• In those who survive their illness, severe pancreatic
necrosis can scar the pancreas, resulting in a stricture
of the main pancreatic duct,
•with subsequent obstructive chronic pancreatitis and
•permanent diabetes mellitus and
•nutrient malabsorption

113. •In severe acute pancreatitis, a CT scan helps
determine the outlook or prognosis.
•If the scan indicates that the pancreas is only
mildly swollen,
the prognosis is excellent.
•If the scan shows large areas of destroyed
pancreas,
the prognosis is poor.

114. •When acute pancreatitis is mild,
•the death rate is about 5% or less.
•with severe damage and bleeding, or when
the inflammation is not confined to the
pancreas,
• the death rate can be as high as 10 to 50%.

115. Take Home Points
•The cornerstone in the diagnosis of acute pancreatitis is elevation in
amylase and lipase, but these enzymes are not useful in assessing
disease severity.
•At 24 hours of admission BISAP score is accurate, less cumbersome
for early identification of patients at risk for in-hospital mortality.
•Several simple and easy to obtain risk factors, including BMI, age,
hematocrit, BUN, and presence of pleural effusions on a chest x-ray,
should be documented to assist in severity assessment.
•C-reactive protein is the most heavily utilized, easy to employ,
readily available, and inexpensive acute phase reactant, and it
remains the gold standard for predicting severity of AP beyond 48
hrs of symptom onset.
•The development of persistent or multiorgan failure during acute
pancreatitis is associated with the highest risk of death.
•Managing pancreatitis is NOT just starving a patient, giving IV
fluids and analgesics. It’s about vigilantly observing for
complications, timely diagnosing and appropriate action.

116. Reference
•Sleisengers 10
th
•Harrisons principle of int med.19 Ed
•UPTODATE
•American journal of gastroenterology,guidelines of AC
Pancreatitis 2013
•IAP/APA evidence-based guidelines for the management of
acute pancreatitis,2013
•NEJM,Acute Pancreatitis Chris E. Forsmark, M.D., Santhi Swaroop
Vege, M.D., and C. Mel Wilcox, M.D.

117. •Thank you