Acute Pancreatitis

• Moderator:- Dr. Dagmawi (Internist, Gastroenterologist)

• Presenter:- Dr. Mesay A. (R1)
• JUMC, Department of Internal Medicine (August 2021 G.C)

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 Outline
–INTRODUCTIN & EPIDEMIOLOGY
–DEFINITION & NATURAL HISTORY
–PATHOGENESIS & ETIOLOGY
–CLINICAL FEATURES & DIAGNOSIS
–SEVERITY PREDICTORS

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 INTRODUCTION
• Acute pancreatitis is an acute inflammatory
process of the pancreas.
• AP should be suspected in patients with
severe acute upper abdominal pain.
• ~ 5 to 10 % of patients with acute severe
pancreatitis may have painless disease and
have unexplained hypotension.

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 Incidence
• Worldwide - about 5–35 per 100,000 new
cases per year, with a mortality rate of about
5% (3 versus 17 percent).
• US – AP is the most common gastrointestinal
diagnosis requiring hospitalization.
• In ~30% of patients with AP the etiology
initially can be obscure.

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 Clinical definitions

• The diagnosis of acute pancreatitis requires two

of the following three features:
(1) abdominal pain characteristic of acute pancreatitis;
(2) serum amylase and/or lipase three or more times
the ULN; and
(3) characteristic findings of acute pancreatitis on
transabdominal US , CECT or MRI.

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 Pathological definitions

• Inflammation can remain localized to the

gland, or can involve other regional tissues or
distant organ systems.
• Acute pancreatitis is divided into two
pathological types:
– Interstitial edematous pancreatitis and
– Necrotizing pancreatitis.

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 Pathology…
Interstitial edematous pancreatitis
• The gland is diffusely enlarged due
to inflammatory edema.
• On macroscopic analysis scattered
foci of fat necrosis are found.
• Hemorrhage and necrosis are
absent, and changes resolve
partially or completely over the
course of 1 week.
• Microscopically, collections of
fibrin and neutrophils are present
in the swollen interlobular septa.
Necrotizing pancreatitis
• necrosis and hemorrhage .
• involves both peripancreatic
tissue and peripheral
pancreatic parenchyma.
• produces a large collection of
peripancreatic fluid
• leads to significant organ loss
• Neutrophils dominate the
inflammatory cell infiltrate
and increase over time.
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• Figure 82.1 (a) Macroscopic and (b) microscopic appearance of
acute pancreatitis. Note the fat necrosis within the pancreas
(arrow). Strong infiltration
and accumulation of immune cells are detectable around
pancreatic lobules in acute pancreatitis (*).
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 CLASSIFICATION
• Acute pancreatitis is divided into the following:
– Mild acute pancreatitis, which is characterized by
the absence of organ failure and local or systemic
complications.
– Moderately severe acute pancreatitis, transient
organ failure (resolves within 48 hours) and/or local
or systemic complications without persistent organ
failure (>48 hours).
– Severe acute pancreatitis, persistent organ failure
that may involve one or multiple organs.
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NATURAL HISTORY AND COMPLICATIONS
Early Phase (within 1 week)
• Usually lasts 1 week.
• Infectious complications are
uncommon in this phase.
• SIRS
• Multiple cytokines are involved
• The initial state of inflammation
evolves dynamically
– Resolution (75-80%)- Interstitial AP
– Irreversible necrosis and
liquefaction, or
– Fluid collections in and around the
pancreas
Late Phase ( > 1 week)
• Develops in fewer than 20% of
patients
• Related to the anatomic
complications that develop, such as
pancreatic necrosis.
• 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
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 Local complications
• Local complications of acute pancreatitis
include
– acute peripancreatic fluid collection ,
– pancreatic pseudocyst,
– acute necrotic collection , and
– walled-off necrosis .

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• Portosplenomesenteric venous thrombosis
(PSMVT) develops in approximately 50
percent of patients with necrotizing acute
pancreatitis and is rare in the absence of
necrosis.

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 Systemic complications 
• According to the revised Atlanta classification
of acute pancreatitis, a systemic complication
of acute pancreatitis is defined as an
exacerbation of an underlying comorbidity
(eg, coronary artery disease or chronic lung
disease).

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PATHOGENESIS & ETIOLOGY OF
ACUTE PANCREATITIS
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PHYSIOLOGY OF PANCREATIC EXOCRINE SECRETION

• The pancreas secretes 1.5–3L of isosmotic alkaline (pH

>8) fluid per day containing about 20 enzymes.
• Gastric acid secretin water and electrolytes.
• long-chain FA, essential AA, and gastric acid itself
cholecystokinin (CCK) an enzyme-rich secretion.
• The parasympathetic nervous system (via the vagus
nerve) exerts significant control over pancreatic secretion.
• Secretion evoked by secretin and CCK depends on
permissive roles of vagal afferent and efferent pathways.

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 Exocrine Endocrine
• Regulatory influences of the islet hormones on
the function of the exocrine pancreas and vice
versa.
• Glucagon, somatostatin, and PP inhibit
pancreatic exocrine secretion.
• Insulin potentiates the stimulatory effect of CCK
on pancreatic exocrine secretion.
• In addition, exocrine pancreatic secretion can
influence pancreatic hormone release.
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 ENZYME SECRETION
• Human pancreatic juice
contains a concentration
of 0.7%–10% protein.
• The four major enzyme
groups are amylolytic,
lipolytic, proteolytic, and
nucleolytic.
• The proteolytic enzymes
are secreted as inactive
proenzymes.

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• Activation of digestive enzymes within the pancreas
is prevented in a number of ways.
1. Digestive enzymes are stored in the acinar cells as inert
zymogens
2. Within the acinar cell, the zymogen granules remain
physically separate from the lysosomal granules
enclosed in membrane-bound organelles.
3. pancreatic secretory trypsin inhibitor (PSTI) within the
acinar cells allows for immediate inhibition of trypsin
4. Should any activated trypsin be released into the
circulation, larger antiproteases in the blood
theoretically have the capacity to deactivate
some circulating trypsin.

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 Autodigestion

• The earliest event in pancreatitis is activation of

trypsinogen to trypsin within the acinar cell.
• The proposed mechanism
–Colocalization hypothesis
– cathepsin B, a trypsin-like lysosomal enzyme

–The concept of basolateral exocytosis

• Activated pancreatic enzymes initiate the pancreatic
inflammatory response.

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 Inflammation
• The inflammatory mediators also enter the
general circulation multiple organ
dysfunction

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Etiology

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 Gallstones
• Two hypotheses have been proposed
– Ductal hypertension hypothesis
– Common-channel hypothesis
• Incidence —are the most common cause (35
to 40 %) of AP in most areas of the world.
• However, only 3 to 7% of patients with
gallstones develop pancreatitis.
• Risk factors — Gender and stone size.

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 Alcohol
• 2nd most common- ~25– 35% of cases
• Only 5-10% of chronic alcoholic patients develop
chronic pancreatitis.
• It’s metabolites are toxic to acinar cells and can also
lead to intracellular enzyme activation
• The fatty acid esters can destabilize lysosomes and
granules and promote colocalization of zymogen
granules and lysosomes.

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 Alcohol
• Alcohol induces oxidative stress, which also appears
to be linked to zymogen granules and induction of
apoptosis.
• acetaldehyde blocks exocytosis by covalently binding
to proteins of the acinar cytoskeleton.
• The diagnosis should not be entertained unless a
person has a history of over 5 years of heavy alcohol
consumption
– “ Heavy” alcohol consumption is generally considered to
be > 50 g per day, but is often much higher

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 Hypertriglyceridemia-induced acute
pancreatitis
• Hypertriglyceridemia (HTG) is defined by
fasting serum triglyceride level of >150 mg/Dl.
• Mild (150 to 199 mg/dL
• Moderate (200 to 999 mg/Dl)
• Severe HTG (1000 to 1999 mg/dL)
• Very severe HTG (≥2000 mg/dL)
• HTG is considered a significant risk for AP
when levels are >1000 mg/dL (11.3 mmol/L)

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• HTG may account for 1 to 4 percent of cases of acute
pancreatitis.
• Primary HTG - Types I, IV and V dyslipidemias are
associated with severe HTG and an increased risk of AP.
• Acquired causes of HTG - obesity, diabetes mellitus,
hypothyroidism, pregnancy, estrogen or tamoxifen
therapy, glucocorticoid excess, nephrotic syndrome, and
beta blockers.
• Patients with HTGP tend to have severe pancreatitis as
compared with patients with other causes of pancreatitis.

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• Laboratory findings — At high triglyceride levels, the
serum becomes lactescent (milky coloration).
• Elevated triglyceride levels can alter routine measurements
of sodium, amylase, and low density lipoprotein.
• The excess triglyceride in a serum sample can displace
water containing sodium and cause pseudo-hyponatremia.
• Serum triglyceride levels >500 mg/dL (5.6 mmol/L) may
cause a falsely normal amylase level, likely from
interference of the calorimetric reading. Serial dilutions of
the serum amylase sample can reduce the triglyceride
interference
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 POST-ERCP 
• Asymptomatic hyperamylasemia occurs in 35 to 70 percent
of patients undergoing ERCP .
• A diagnosis of post-ERCP pancreatitis is generally made if the
hyperamylasemia is accompanied by persistent severe upper
abdominal pain, often with nausea and vomiting.
• Acute pancreatitis occurs in about
– 3 percent of patients undergoing diagnostic ERCP,
– 5 percent undergoing therapeutic ERCP, and
– up to 25 percent undergoing sphincter of Oddi manometric studies.
• Several strategies can decrease the risk of post-ERCP
pancreatitis.

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 DRUGS
• Pancreatitis due to medications is rare (0.3 to 1.4
percent).
• Drug-induced pancreatitis is classified (class I-IV)
based on
• the number of cases reported,
• demonstration of a consistent latency period (time from
initiation of drug to development of pancreatitis), and
• reaction with rechallenge .
• Class I and II drugs have the greatest potential for
causing acute pancreatitis.
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 IDIOPATHIC
• No obvious etiology is identifiable by history,
laboratory tests, and gallbladder ultrasound in
up to 30 percent of patients with acute
pancreatitis.
• After an extensive work-up for recurrent
pancreatitis, approximately 15 to 25 percent
of patients with acute pancreatitis are
idiopathic.

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 CLINICAL FEATURES
• Abdominal pain  
– acute onset of persistent, severe epigastric .
– the pain may be in the right upper quadrant or, rarely, confined
to the left side.
– gallstone pancreatitis, the pain is well localized and the onset of
pain is rapid, reaching maximum intensity in 10 to 20 minutes.
– hereditary or metabolic causes or alcohol, the onset of pain may
be less abrupt and the pain may be poorly localized.
– ~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.

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• ~90 percent of patients have associated nausea
and vomiting which may persist for several
hours.
• Patients with severe AP may have dyspnea due
to diaphragmatic inflammation secondary to
pancreatitis, pleural effusions, or ARDS.
• ~5 to 10 percent of patients with acute severe
pancreatitis may have painless disease and have
unexplained hypotension.
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 PHYSICAL EXAMINATION 
• mild acute pancreatitis, the epigastrium may be
minimally tender to palpation.
• severe pancreatitis, there may be significant
tenderness to palpation in the epigastrium or more
diffusely over the abdomen.
• Patients may have abdominal distention and
hypoactive bowel sounds due to an ileus secondary to
inflammation.
• scleral icterus due to OJ due to choledocholithiasis or
edema of the head of the pancreas.
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• Patients with 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).

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• In rare cases, patients may have subcutaneous
nodular fat necrosis or panniculitis.
• tender red nodules that frequently occur on the distal
extremities but may occur elsewhere.
• Hepatomegaly may be present in patients with
alcoholic pancreatitis,
• xanthomas in hyperlipidemic pancreatitis, and
• parotid swelling in patients with mumps.

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 LABORATORY FINDINGS
• Pancreatic enzymes and products — Early in
the course of acute pancreatitis, there is a
breakdown in the synthesis-secretion coupling
of pancreatic digestive enzymes; synthesis
continues while there is a blockade of
secretion.

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 LABORATORY FINDINGS
Serum amylase
• Serum amylase rises within 6 to 12 hours of the onset of acute
pancreatitis.
• half-life of ~10 hours
• In uncomplicated attacks returns to normal within 3-5 days.
• Serum amylase elevation of >3x ULN has a sensitivity for the diagnosis of
AP of 67 to 83 percent and a specificity of 85 to 98 percent.
• Limitations
– may not be seen in ~20 % of patients with alcoholic pancreatitis due to the
inability of the parenchyma to produce amylase, and
– may not be seen in 50 % of patients with HTGP as triglycerides interfere with the
amylase assay.
– may be missed in patients who present >24 hours after the onset of pancreatitis.

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 Serum lipase
• Serum lipase has a sensitivity and specificity for AP
ranging from 82 to 100 percent.
• Serum lipase rises within 4-8 hours of the onset of
symptoms, peaks at 24 hours, and returns to normal
within 8 to 14 days.
• Especially useful in patients who present >24 hours
after the onset of pain.
• Serum lipase is also more sensitive as compared with
amylase in patients with pancreatitis secondary to
alcohol.
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 Other enzymes and products
• Trypsinogen activation peptide (TAP), a five
amino-acid peptide that is cleaved from
trypsinogen to produce active trypsin, is
elevated in acute pancreatitis.
• Other pancreatic digestive enzymes that leak
into the systemic circulation and are elevated
in serum include trypsin, phospholipase,
carboxypeptidase, carboxylester lipase,
colipase, and pancreatic isoamylase.
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• Markers of immune activation — AP is
associated with elevations in CRP, IL-6, IL-8, IL-
10, TNF, and PMN elastase.
• A CRP level above 150 mg/dL at 48 hours is
associated with severe pancreatitis.
• Other laboratory findings — Patients with
pancreatitis may have leukocytosis and an
elevated hematocrit from hemoconcentration
• Metabolic abnormalities including elevated
BUN, hypocalcemia, hyperglycemia, and
hypoglycemia may also occur.
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 IMAGING 
• Abdominal and chest radiographs  
– unremarkable in mild disease to localized ileus of a
segment of small intestine (sentinel loop) or the
colon cutoff sign in more severe disease .
– A ground glass appearance may indicate the
presence of an acute peripancreatic fluid collection.
– ~one-third of patients with acute pancreatitis have
abnormalities visible on the CXR
– such as elevation of a hemidiaphragm, pleural effusions, basal
atelectasis, pulmonary infiltrates, or ARDS

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 Abdominal ultrasound 
• pancreas appears diffusely enlarged and hypoechoic.
• 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.
• Limitations
– In ~25 to 35 percent of patients, bowel gas due to an ileus precludes
evaluation of the pancreas or bile duct.
– Cannot clearly delineate extrapancreatic spread of pancreatic
inflammation or
– Cannot identify necrosis within the pancreas.
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 Computed Tomography
• The most important imaging test

• 3 benefits
1. Exclude other serious intra-abdominal conditions (e.g.,
mesenteric infarction or a perforated ulcer),
2. Stage the severity of acute pancreatitis, and
3. Detect complications

• CECT is the most common technique

– Sensitivity and specificity >90%
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 MRI
• As good as CT in detecting necrosis and fluid collections.

• MRCP is better than CT, but equal to EUS and ERCP in

detecting choledocholithiasis
– Can detect stones down to 3 mm diameter and pancreatic duct
disruption

• Helpful in patients with a contrast allergy and renal

insufficiency
– T2W-weighted images without gadolinium contrast can diagnose
pancreatic necrosis

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 Diagnostic Imaging
• Routine use of CECT in patients with AP is
unwarranted, as the diagnosis is apparent in many
patients and most have a mild, uncomplicated
course.

• However, in a patient failing to improve after 48–

72hrs (e.g., persistent pain, fever, nausea, unable to
begin oral feeding), CECT or MRI imaging is
recommended to assess local complications such as
pancreatic necrosis.
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 Diagnostic Imaging
• Pancreatic ca should be suspected in any patient > 40
years of age with idiopathic pancreatitis, especially
those with a prolonged or recurrent course

• Thus, a contrast-enhanced CT scan or MRI is needed in

these patients.

• A more extensive evaluation including endoscopic

ultrasound (EUS) and/or MRCP may be needed initially
or after a recurrent episode of IAP
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 Diagnostic Imaging
EUS & ERCP
• EUS is equivalent to MRCP and ERCP but far more sensitive
than either abdominal US or CT in detecting common duct
stones.
• In a patient with biliary pancreatitis whose serum bilirubin is
rising in the setting of biliary sepsis, ERCP should not be
delayed by first performing EUS
– Concern over worsening AP; ERCP appears safe during AP
– Induction of infection in the necrotic areas during contrast
insillation
• For this reason, EUS might be the best method of evaluating
the bile duct in a patient with necrotizing pancreatitis.

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PREDICTING THE SEVERITY OF
ACUTE PANCREATITIS

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 CLINICAL PREDICTORS
• Older age —  although the age cutoff has varied from 55 to 75
years in different reports.
• Sex — The patient's sex has not been a predictor of outcome in
most reports.
• Alcoholic pancreatitis — increased risk of pancreatic necrosis and
need for intubation in some reports.
• Short time interval to symptom onset — A time interval between
the onset of symptoms and hospital admission of less than 24
hours.
• Obesity — found to be a risk factor for severe AP.
• Organ failure — Early and persistent organ failure is a reliable
indicator of a prolonged hospital stay and increased mortality.

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 LABORATORY AND RADIOLOGIC
PREDICTORS
• Hemoconcentration - a normal or low hematocrit at admission
and during the first 24 hours is generally associated with a milder
clinical course.
• C-reactive protein —Levels of CRP above 150 mg/L at 48 hours
discriminate severe from mild disease.
• Blood urea nitrogen — serial BUN measurements were the most
reliable routine laboratory test to predict the mortality in AP.
• Chest radiographs — A pleural effusion and/or pulmonary
infiltrates during the first 24 hours may be associated with
necrosis and organ failure.
• CT scan — is probably the most frequently used radiologic
investigation when severe AP is suspected.

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Scores used to assess prognosis in AP

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An APACHE-II score ≥8 is predictive for severe
pancreatitis.
Studies suggest that mortality is less than 4
percent with a score <8 and is 11 to 18 percent
with a score >8.
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BISAP

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 REFERENCES
• Harrison’s principle of internal medicine 20th
• Yamada’s Textbook of Gastroenterology 6th
• UTD 2018
• Am J Gastroenterol 2013

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THANK YOU!

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