KHARKIV NATIONAL MEDICAL UNIVERSITY

Pediatrics Assignment : Topic 6

Student : Ambalapurathu Jayan

Ariyalekshmi
Group.No : 45th ,Faculty : 7th
Couse : 4th

Teacher: Prof.Irina Mikolaiva

Pidubbna
Date: 7/05/2021
 Topic 6. Diseases of pancreas in
children ( Acute & Chronic pancreatitis )

Introduction
Pancreatitis, an uncommon condition in
pediatric patients, is characterized by
inflammation of the pancreas, clinical
signs of epigastric abdominal pain, and
elevated serum digestive enzymes. The
disease is associated with significant
morbidity and mortality. [1] Pancreatitis
can be local or diffuse and is classified as
acute, chronic, inherited, necrotic, or
hemorrhagic. Occasionally, pancreatitis
is complicated by the formation of a
fibrous-walled cavity filled with
pancreatic enzymes, termed a
pseudocyst.
Definition
Pancreatitis, an uncommon condition in
pediatric patients, is characterized by
inflammation of the pancreas, clinical
signs of epigastric abdominal pain, and
elevated serum digestive enzymes. The
disease is associated with significant
morbidity and mortality.
Signs and symptoms
Most commonly, a child with acute
pancreatitis presents with the following:
 Abdominal pain (87%)
 Vomiting (64%)
  Abdominal tenderness (77%)
 Abdominal distention (18%)

Less common clinical signs include the

following:
 Fever
 Tachycardia
 Hypotension
 Jaundice
 Abdominal guarding
 Rebound tenderness
 Decreased bowel sounds
 Acute hemorrhagic pancreatitis

Physical examination findings

associated with hemorrhagic
pancreatitis may include a bluish
discoloration of the flanks (ie, Grey
Turner sign) or periumbilical region (ie,
Cullen sign) because of blood
accumulation in the fascial planes of
the abdomen. Additional signs include
pleural effusions, hematemesis,
melena, and coma.

Chronic pancreatitis
Patients with chronic pancreatitis have
recurrent episodes of upper abdominal
pain associated with varying degrees of
pancreatic dysfunction.
Pancreatic pseudocysts
Children with pancreatic pseudocysts
may present with localized abdominal
pain and a palpable, tender epigastric
mass or abdominal fullness. Additional
symptoms include the following:
 Jaundice
 Chest pain
 Nausea
 Vomiting
 Anorexia
 Weight loss
 Fever
 Ascites
  Gastrointestinal (GI) hemorrhage
(rarely)
Etiology and Pathophysiology
Pediatric pancreatitis represents a
diagnostic challenge for clinicians.
Although most adult cases of
pancreatitis are caused by alcohol abuse
or gallstone disease, the etiology for
pancreatitis in children is diverse.

The predominant causes include

abdominal trauma (23%), anomalies of
the pancreaticobiliary system (15%),
multisystem disease (14%), drugs and
toxins (12%), viral infections (10%),
hereditary disorders (2%), and metabolic
disorders (2%). In up to 25% of cases,
the etiology of childhood pancreatitis is
unknown. In the United States, trauma is
responsible for 15-37% of cases. [2]
Common causes of pancreatitis are
extensive but include blunt abdominal
trauma (eg, motor vehicle collision,
abuse, bicycle accident where the
abdomen is compressed by the
handlebars), systemic infection (eg,
mumps, rubella, coxsackie virus B,
cytomegalovirus [CMV], human
immunodeficiency virus [HIV]),
pancreaticobiliary malunion, congenital
anomalies of the pancreatobiliary
junction, pancreas divisum, congenital
sphincter of Oddi abnormality,
choledochal cysts, or
choledocholithiasis.

Use of hyperalimentation, medications

(eg, azathioprine, tetracycline, L-
asparagine, valproic acid, steroids, and
immunosuppressive agents), and
metabolic abnormalities (eg,
hypertriglyceridemia, hypercalcemia,
cystic fibrosis) may also incite
pancreatitis.
Hereditary pancreatitis in children, the
second most common congenital
pancreatic disorder following cystic
fibrosis, is characterized by an alteration
in the long arm of chromosome 7, which
yields an aberrant trypsinogen protein
that may induce autodigestion of the
pancreas.

The specific inciting factors causing

pancreatitis remain to be elucidated,
including induction by primary acinar cell
injury as a result of viral infections,
drugs, ischemia, and direct trauma, as
well as disruption of the ductal system
and subsequent excretion of digestive
enzymes from the acinar cells of the
pancreas.
Normally, the acinar cells release
inactive enzymes into collecting ducts,
which then drain into the main or
accessory pancreatic ducts emptying
directly into the duodenal lumen. If
obstruction or disruption of these ducts
occurs, the pancreatic secretions are
activated within the parenchyma of the
pancreas and initiate autodigestion of
the pancreatic tissue.

Interstitial edema is an early finding.

Exacerbation of pancreatitis may result
in pancreatic necrosis, blood vessel
occlusion or disruption inciting
hemorrhage, and systemic inflammatory
response syndrome with multiorgan
failure. Collections of pancreatic
secretions often become walled off by
granulation tissue to form a pseudocyst
either within or adjacent to the
pancreas. Predominantly, the
pseudocyst is localized in the lesser sac
behind the stomach. The stomach,
duodenum, colon, small bowel, or
omentum may abut or form part of the
pseudocyst capsule.

Clinical presentation
History and Physical Examination
Classically, pancreatitis in adults
presents with mid epigastric pain
radiating to the back. In children, the
presenting signs and symptoms can be
quite varied. Most commonly, a child
with acute pancreatitis presents with
abdominal pain (87%), vomiting (64%),
abdominal tenderness (77%), and
abdominal distention (18%). Other, less
common clinical signs include fever,
tachycardia, hypotension, jaundice,
abdominal guarding, rebound
tenderness, and decreased bowel
sounds. Eating may exacerbate the
abdominal pain.

Acutely ill children may lie on their side

with the hips and knees flexed. The pain
typically increases in intensity for 24-48
hours. The clinical course for acute
pancreatitis is variable. Often, children
may require hospitalization for
analgesia, bowel rest, and rehydration
with fluid and electrolyte therapy.
Acute hemorrhagic pancreatitis
Acute hemorrhagic pancreatitis rarely
occurs in children. This is a life-
threatening condition with a mortality
rate approaching 50% because of shock,
systemic inflammatory response
syndrome with multiple organ
dysfunction, acute respiratory distress
syndrome (ARDS), disseminated
intravascular coagulation (DIC), massive
gastrointestinal bleeding, and systemic
or peritoneal infection.
Physical examination findings associated
with hemorrhagic pancreatitis may
include a bluish discoloration of the
flanks (ie, Grey Turner sign) or
periumbilical region (ie, Cullen sign)
because of blood accumulation in the
fascial planes of the abdomen.
Additional signs include pleural
effusions, hematemesis, melena, and
coma.

Chronic pancreatitis
Chronic pancreatitis in children is
associated with trauma, systemic
disease, and pancreaticobiliary
malformations, most commonly
pancreatic divisum. In the United States,
the most common cause of chronic
relapsing pancreatitis in children is
hereditary pancreatitis. Patients with
this disease typically present with
chronic abdominal pain that can be
difficult to treat. These patients have
recurrent episodes of upper abdominal
pain associated with varying degrees of
pancreatic dysfunction and have
increased risk of developing pancreatic
insufficiency, adenocarcinoma, and
pancreatic pseudocysts.
Pancreatic pseudocysts
Children with pancreatic pseudocysts
may present with localized abdominal
pain and a palpable tender epigastric
mass or abdominal fullness. Additional
symptoms include jaundice, chest pain,
nausea, vomiting, anorexia, weight loss,
fever, ascites, and rarely, GI
hemorrhage.
Prognosis
In general, the prognosis of children with
acute pancreatitis is excellent, although
pseudocysts have been reported to
complicate 10-23% of acute episodes. In
addition, when associated with
abdominal trauma, the frequency rate of
pseudocyst identification is higher than
50%. Approximately 60% of pancreatic
pseudocysts that are caused by blunt
trauma require surgical intervention.
Complications
Although pseudocyst formation is an
uncommon sequela of acute or chronic
pancreatitis in children, complications of
pancreatic pseudocysts include
spontaneous rupture, hemorrhage, and
infection. Pseudocysts can be medically
managed with pancreatic rest or
surgically by internal or external
drainage. While under medical therapy,
rupture is the major complication
associated with pseudocysts larger than
10 cm.
Differential Diagnoses
 Biliary Colic
 Pediatric Cholecystitis
 Pediatric Gastroenteritis
 Peptic Ulcer
Diagnostic Tests
Amylase levels
 Elevated serum or urine amylase
levels aid in the diagnosis of
pancreatitis and peak 48 hours after
onset, although 10-15% of patients
with pancreatitis may have levels
within the reference range. Serum
amylase levels are typically elevated
for as long as 4 days—although
amylase levels can be elevated in
patients with other abdominal
conditions, the levels are typically not
 as high as those found in patients
with pancreatitis.

Lipase levels
 Serum lipase is more specific than
amylase for acute pancreatitis, and
typically, lipase levels remain
elevated 8-14 days longer than
amylase levels. Serum lipase levels
can also be elevated in patients with
other diseases or conditions;
therefore, all laboratory results
should be evaluated in the context of
the clinical presentation.

Other
  Other laboratory abnormalities found
in patients with pancreatitis may
include coagulopathies, leukocytosis,
hyperglycemia, glucosuria,
hypocalcemia, hyperbilirubinemia,
and elevated gamma glutamyl
transpeptidase.
 Urinary levels of trypsin activator
peptide (TAP) may help determine
the severity of the pancreatitis.
As many as 20% of children who present
with acute pancreatitis develop severe
disease that carries an increased
morbidity, longer hospitalization, and
need for aggressive medical
management. A retrospective study
showed that malnourished children
were more likely to experience a
protracted hospitalization independent
of all the conventional biochemical
parameters associated with an increased
risk of disease severity in adults,
including hypertriglyceridemia, ethnicity,
or history of hepatobiliary disease. [5] In
that study, most children with severe
malnutrition had comorbid conditions,
including cerebral palsy and
encephalopathy, that could have masked
the typical early clinical symptoms of
acute pancreatitis.
One study provided a prognostic tool
that may be used clinically to predict the
severity of acute pancreatitis in children.
In that study, a predictive model based
on a high serum lipase level (>19 the
upper limit of normal) and a low albumin
and white blood cell count was
associated with an increased risk of
morbidity.

Diagnostic Imaging Studies

Ultrasonography is the primary
screening tool for evaluation of the
pediatric pancreas, due to the absence
of ionizing radiation and ability to image
without sedation. Computed
tomography (CT) scanning may be better
suited for evaluation of chronic
pancreatitis and its complications,
pancreatic trauma, and neoplastic
conditions and is often used to further
evaluate abnormalities found on
ultrasonography. Magnetic resonance
imaging (MRI) is another modality to
diagnose pancreatitis and is used for the
same indications as CT scanning.

Ultrasonography
Ultrasonography findings may include a
focally or diffusely enlarged, hypoechoic,
sonolucent, or edematous pancreas;
dilated pancreatic ducts; a pancreatic
mass; a fluid collection or peripancreatic
fluid; an abscess; or a pseudocyst
demonstrated as a well-defined,
hypoechoic mass, which may be
multilocular.
CT scanning
CT scan findings include an enlarged
gland with ill-defined margins;
peripancreatic fluid; areas of decreased
or enhanced density; or pseudocysts
with a well-defined wall or capsule and
central area of low attenuation (see the
following images). CT scanning is a
better modality for evaluating presence
and extent of pancreatic necrosis and
inflammation of peripancreatic fat.
Of note, findings on imaging studies
initially appear normal in 20% of children
with acute pancreatitis.
ERCP and MRCP
Endoscopic retrograde
cholangiopancreatography (ERCP) is
essential for evaluation of pancreatic
and biliary anomalies. ERCP can aid in
the diagnosis of various ductal
abnormalities or obstructions and may
serve as a therapeutic intervention (ie,
sphincterotomy, stent placement) (see
the images below). Magnetic resonance
cholangiopancreatography (MRCP) is a
noninvasive alternative to ERCP but lacks
therapeutic capabilities.
Radiography
Roentgenography may demonstrate
nonspecific findings ranging from a
distended loop of small intestine (ie,
sentinel loop), calcifications, radio-
opaque gallstones, dilatation of the
transverse colon (ie, cutoff sign), ascites,
peripancreatic extraluminal gas bubbles,
ileus, left-sided basal pleural effusion,
and blurring of the left psoas margin to
pancreatic calcifications from chronic or
recurrent pancreatitis.
Histologic Features
Acute pancreatitis is characterized by
enzymatic necrosis and inflammation of
the pancreas. Focal areas of fat necrosis
are interspersed with areas of interstitial
hemorrhage secondary to destruction of
blood vessels. In severe cases, large,
blue-black hemorrhagic foci are
interspersed with yellow-white chalky
areas of fat necrosis.

Chronic pancreatitis is characterized by

irreversible destruction of the pancreatic
parenchyma and subsequent
replacement with fibrous tissue.
Histologic features include
intraglandular fibrosis, acinar cell
destruction, lymphocytic infiltration, and
pancreatic duct obstruction. The
pancreatic ducts are dilated and
obstructed with protein plugs in their
lumens. Grossly, the gland is hard.
Pancreatic pseudocysts are localized
collections of pancreatic secretions
walled off by granulation tissue that lack
a true epithelial lining. The stomach,
duodenum, small bowel, colon, or
omentum may abut or form part of the
pseudocyst capsule.
Treatment and management
Management
Acute pancreatitis should resolve in 2-7
days with adequate resuscitation, with
management being predominantly
supportive through the use of
intravenous hydration, pain control, and
bowel rest. Parenteral nutrition may be
required for prolonged episodes.

In cases of intractable vomiting or ileus,

nasogastric suction is indicated to aid
intestinal-pancreatic rest by eliminating
gastric secretions in the duodenum, the
most potent activator of pancreatic
secretion.

Because most resolve spontaneously,

acute pancreatic pseudocysts smaller
than 5 cm in diameter are managed with
observation for 4-6 weeks. (Pancreatic
pseudocysts larger than 5 cm in
diameter may require surgical
intervention.)
Surgery
Most surgical interventions are used in
patients with chronic or relapsing
pancreatitis. However, operative
management of chronic pancreatitis in
children is controversial. Indications for
operative intervention include
unsuccessful conservative medical
therapy, intractable pain, impaired
nutrition, and narcotic addiction.
Surgical options include the following:
Distal pancreatectomy with Roux-en-Y
pancreaticojejunostomy (ie, Duval
procedure)
Lateral pancreaticojejunostomy (ie,
Puestow procedure)

ERCP sphincteroplasty
Chronic pancreatic pseudocysts (>3 mo)
are best treated surgically. Surgical
approaches for internal drainage, as
follow, are largely determined by the
anatomic location of the pseudocyst:
Cystogastrostomy: If the pseudocyst is
adherent to the posterior wall of the
stomach
Cystoduodenostomy: If the cyst is
present in the head of the pancreas

Cystojejunostomy: For cysts that are not

adherent to the stomach or duodenum
Distal pancreatectomy: Considered
when the pseudocyst is in the tail of the
gland.
Acute pancreatitis
Signs and symptoms
Symptoms of acute pancreatitis include
the following:
Abdominal pain (cardinal symptom):
Characteristically dull, boring, and
steady; usually sudden in onset and
gradually becoming more severe until
reaching a constant ache; most often
located in the upper abdomen and may
radiate directly through to the back
 Nausea and vomiting, sometimes
with anorexia
 Diarrhea

Patients may have a history of the

following:

 Recent operative or other invasive

procedures
 Family history of hypertriglyceridemia
 Previous biliary colic and binge
alcohol consumption (major causes of
acute pancreatitis)
The following physical findings may be
noted, varying with the severity of the
disease:
 Fever (76%) and tachycardia (65%);
hypotension
 Abdominal tenderness, muscular
guarding (68%), and distention (65%);
diminished or absent bowel sounds
 Jaundice (28%)
 Dyspnea (10%); tachypnea; basilar
rales, especially in the left lung
 In severe cases, hemodynamic
instability (10%) and hematemesis or
melena (5%); pale, diaphoretic, and
listless appearance
  Occasionally, extremity muscular
spasms secondary to hypocalcemia

The following uncommon physical

findings are associated with severe
necrotizing pancreatitis:

 Cullen sign (bluish

discoloration around the
umbilicus resulting from
hemoperitoneum)
 Grey-Turner sign (reddish-
brown discoloration along the
flanks resulting from
retroperitoneal blood dissecting
along tissue planes); more
commonly, patients may have a
ruddy
 erythema in the flanks secondary
to extravasated pancreatic
exudate.
 Erythematous skin nodules,
usually no larger than 1 cm and
typically located on extensor skin
surfaces; polyarthritis

Diagnosis
Once a working diagnosis of acute
pancreatitis is reached, laboratory tests
are obtained to support the clinical
impression, such as the following:

 Serum amylase and lipase

 Liver-associated enzymes
  Blood urea nitrogen (BUN),
creatinine, and electrolytes
 Blood glucose
 Serum cholesterol and triglyceride
 Complete blood count (CBC) and
hematocrit; NLR
 C-reactive protein (CRP)
 Arterial blood gas values
 Serum lactic dehydrogenase (LDH)
and bicarbonate
 Immunoglobulin G4 (IgG4)

Diagnostic imaging is unnecessary in

most cases but may be obtained when
the diagnosis is in doubt, when
pancreatitis is severe, or when a given
study might provide specific information
required. Modalities employed include
the following:

 Abdominal radiography (limited role):

Kidneys-ureters-bladder (KUB)
radiography with the patient upright
is primarily performed to detect free
air in the abdomen

 Abdominal ultrasonography (most

useful initial test in determining the
etiology, and is the technique of
choice for detecting gallstones)
 Endoscopic ultrasonography (EUS)
(used mainly for detection of
microlithiasis and periampullary
lesions not easily revealed by other
methods)

 Abdominal computed tomography

(CT) scanning (generally not indicated
for patients with mild pancreatitis but
always indicated for those with
severe acute pancreatitis)

 Endoscopic retrograde
cholangiopancreatography (ERCP);
to be used with extreme caution in
this
 disease and never as a first-line
diagnostic tool.

 Magnetic resonance
cholangiopancreatography
(MRCP) (not as sensitive as ERCP
but safer and noninvasive)

Other diagnostic modalities include the

following:
 CT-guided or EUS-
guided aspiration and
drainage
 Genetic testing

Acute pancreatitis is broadly classified as

either mild or severe. According to the
Atlanta classification, severe acute
pancreatitis is signaled by the following:

 Evidence of organ failure (eg, systolic

blood pressure below 90 mm Hg,
arterial partial pressure of oxygen [Pa
O2] 60 mm Hg or lower, serum
creatinine level 2 mg/dL or higher, GI
bleeding amounting to 500 mL or
more in 24 hours)

 Local complications (eg, necrosis,

abscess, pseudocyst)

 Ranson score of 3 or higher or

APACHE score of 8 or higher
Management
Medical management of mild acute
pancreatitis is relatively straightforward;
however, patients with severe acute
pancreatitis require intensive care.
Initial supportive care includes the
following:
 Fluid resuscitation
 Nutritional support

Antibiotic therapy is employed as

follows:
Antibiotics (usually of the Imipenem
class) should be used in any case of
pancreatitis complicated by infected
pancreatic necrosis but should not be
given routinely for fever, especially early
in the presentation

Antibiotic prophylaxis in severe

pancreatitis is controversial; routine use
of antibiotics as prophylaxis against
infection in severe acute pancreatitis is
not currently recommended

Surgical intervention (open or minimally

invasive) is indicated when an anatomic
complication amenable to a mechanical
solution is present. Procedures
appropriate for specific conditions
involving pancreatitis include the
following:

 Gallstone pancreatitis:
Cholecystectomy
 Pancreatic duct disruption: Image-
guided percutaneous placement of a
drainage tube into the fluid collection
; stent or tube placement via ERCP; in
refractory cases, distal
pancreatectomy or a Whipple
procedure.
 Pseudocysts: None necessary in
most cases; for large or symptomatic
pseudocysts, percutaneous
 aspiration, endoscopic transpapillary
or transmural techniques, or surgical
management
 Infected pancreatic necrosis: Image-
guided aspiration; necrosectomy

 Pancreatic abscess: Percutaneous

catheter drainage and antibiotics; if
no response, surgical debridement
and drainage

Pathophysiology
Normal pancreatic function
The pancreas is a gland located in the
upper posterior abdomen. It is
responsible for insulin production
(endocrine pancreas) and the
manufacture and secretion of digestive
enzymes (exocrine pancreas) leading to
carbohydrate, fat, and protein
metabolism. Approximately 80% of the
gross weight of the pancreas supports
exocrine function, and the remaining
20% is involved with endocrine function.
The focus of this article is on the
exocrine function of the pancreas.

The pancreas accounts for only 0.1% of

total body weight but has 13 times the
protein-producing capacity of the liver
and the reticuloendothelial system
combined, which together make up 4%
of total body weight. Digestive enzymes
are produced within the pancreatic
acinar cells, packaged into storage
vesicles called zymogens, and then
released via the pancreatic ductal cells
into the pancreatic duct, where they are
secreted into the small intestine to begin
the metabolic process.
In normal pancreatic function, up to 15
different types of digestive enzymes are
manufactured in the rough endoplasmic
reticulum, targeted in the Golgi
apparatus and packaged into zymogens
as proenzymes. When a meal is ingested,
the vagal nerves, vasoactive intestinal
polypeptide (VIP), gastrin-releasing
peptide (GRP), secretin, cholecystokinin
(CCK), and encephalins stimulate release
of these proenzymes into the pancreatic
duct.
The proenzymes travel to the brush
border of the duodenum, where
trypsinogen, the proenzyme for trypsin,
is activated via hydrolysis of an N-
terminal hexapeptide fragment by the
brush border enzyme enterokinase.
Trypsin then facilitates the conversion of
the other proenzymes into their active
forms.
A feedback mechanism exists to limit
pancreatic enzyme activation after
appropriate metabolism has occurred. It
is hypothesized that elevated levels of
trypsin, having become unbound from
digesting food, lead to decreased CCK
and secretin levels, thus limiting further
pancreatic secretion.
Because premature activation of
pancreatic enzymes within the pancreas
leads to organ injury and pancreatitis,
several mechanisms exist to limit this
occurrence. First, proteins are translated
into the inactive proenzymes. Later,
posttranslational modification of the
Golgi cells allows their segregation into
the unique subcellular zymogen
compartments. The proenzymes are
packaged in a paracrystalline
arrangement with protease inhibitors.
Zymogen granules have an acidic pH and
a low calcium concentration, which are
factors that guard against premature
activation until after secretion has
occurred and extracellular factors have
triggered the activation cascade. Under
various conditions, disruption of these
protective mechanisms may occur,
resulting in intracellular enzyme
activation and pancreatic autodigestion
leading to acute pancreatitis.
Pathogenesis of acute pancreatitis
Acute pancreatitis may occur when
factors involved in maintaining cellular
homeostasis are out of balance. The
initiating event may be anything that
injures the acinar cell and impairs the
secretion of zymogen granules;
examples include alcohol use, gallstones,
and certain drugs.

At present, it is unclear exactly what

pathophysiologic event triggers the
onset of acute pancreatitis. It is believed,
however, that both extracellular factors
(eg, neural and vascular response) and
intracellular factors (eg, intracellular
digestive enzyme activation, increased
calcium signaling, and heat shock
protein activation) play a role. In
addition, acute pancreatitis can develop
when ductal cell injury leads to delayed
or absent enzymatic secretion, as seen in
patients with the CFTR gene mutation.
Once a cellular injury pattern has been
initiated, cellular membrane trafficking
becomes chaotic, with the following
deleterious effects:
 Lysosomal and zymogen granule
compartments fuse, enabling
activation of trypsinogen to trypsin

 Intracellular trypsin triggers the

entire zymogen activation cascade

 Secretory vesicles are extruded

across the basolateral membrane
into the interstitium, where
molecular fragments act as
 chemoattractants for inflammatory
cells

Activated neutrophils then exacerbate

the problem by releasing superoxide
(the respiratory burst) or proteolytic
enzymes (cathepsins B, D, and G;
collagenase; and elastase). Finally,
macrophages release cytokines that
further mediate local (and, in severe
cases, systemic) inflammatory
responses. The early mediators defined
to date are tumor necrosis factor-alpha
(TNF-α), interleukin (IL)-6, and IL-8.
These mediators of inflammation cause
an increased pancreatic vascular
permeability, leading to hemorrhage,
edema, and eventually pancreatic
necrosis. As the mediators are excreted
into the circulation, systemic
complications can arise, such as
bacteremia due to gut flora
translocation, acute respiratory distress
syndrome (ARDS), pleural effusions,
gastrointestinal (GI) hemorrhage, and
renal failure.

The systemic inflammatory response

syndrome (SIRS) can also develop,
leading to the development of systemic
shock. Eventually, the mediators of
inflammation can become so
overwhelming that hemodynamic
instability and death ensue.

In acute pancreatitis, parenchymal

edema and peripancreatic fat necrosis
occur first; this is known as acute
edematous pancreatitis. When necrosis
involves the parenchyma, accompanied
by hemorrhage and dysfunction of the
gland, the inflammation evolves into
hemorrhagic or necrotizing pancreatitis.
Pseudocysts and pancreatic abscess can
result from necrotizing pancreatitis
because enzymes can be walled off by
granulation tissue (pseudocyst
formation) or via bacterial seeding of
pancreatic or peripancreatic tissue
(pancreatic abscess formation).

Li et al compared two sets of patients

with severe acute pancreatitis—one with
acute renal failure and the other without
it—and determined that a history of
renal disease, hypoxemia, and
abdominal compartment syndrome
were significant risk factors for acute
renal failure in patients with severe
acute pancreatitis. [5] In addition,
patients with acute renal failure were
found to have a significantly greater
average length of stay in the hospital
and in the intensive care unit (ICU), as
well as higher rates of pancreatic
infection and mortality.

Etiology
Long-standing alcohol consumption and
biliary stone disease cause most cases of
acute pancreatitis, but numerous other
etiologies are known. In 10%-30% of
cases, the cause is unknown, though
studies have suggested that as many as
70% of cases of idiopathic pancreatitis
are secondary to biliary microlithiasis.

Biliary tract disease

One of the most common causes of
acute pancreatitis in most developed
countries (accounting for approximately
40% of cases) is gallstones passing into
the bile duct and temporarily lodging at
the sphincter of Oddi. The risk of a stone
causing pancreatitis is inversely
proportional to its size.

It is thought that acinar cell injury occurs

secondary to increasing pancreatic duct
pressures caused by obstructive biliary
stones at the ampulla of Vater, although
this has not been definitively proven in
humans. Occult microlithiasis is probably
responsible for most cases of idiopathic
acute pancreatitis.
Alcohol
Alcohol use is a major cause of acute
pancreatitis (accounting for at least 35%
of cases [6] ). At the cellular level,
ethanol leads to intracellular
accumulation of digestive enzymes and
their premature activation and release.
At the ductal level, it increases the
permeability of ductules, allowing
enzymes to reach the parenchyma and
cause pancreatic damage. Ethanol
increases the protein content of
pancreatic juice and decreases
bicarbonate levels and trypsin inhibitor
concentrations. This leads to the
formation of protein plugs that block
pancreatic outflow.
Most commonly, the disease develops in
patients whose alcohol ingestion is
habitual over 5-15 years. Alcoholics are
usually admitted with an acute
exacerbation of chronic pancreatitis.
Occasionally, however, pancreatitis can
develop in a patient with a weekend
binging habit, and several case reports
have described a sole large alcohol load
precipitating a first attack. Nevertheless,
the alcoholic who imbibes routinely
remains the rule rather than the
exception for the development of
pancreatitis.
Currently, there is no universally
accepted explanation for why certain
alcoholics are more predisposed to
developing acute pancreatitis than other
alcoholics who ingest similar quantities.

Endoscopic retrograde
cholangiopancreatography
Pancreatitis occurring after endoscopic
retrograde cholangiopancreatography
(ERCP) is probably the third most
common type (accounting for
approximately 4% of cases). Whereas
retrospective surveys indicate that the
risk is only 1%, prospective studies have
shown the risk to be at least 5%.
The risk of post-ERCP acute pancreatitis
is increased if the endoscopist is
inexperienced, if the patient is thought
to have sphincter of Oddi dysfunction, or
if manometry is performed on the
sphincter of Oddi. Aggressive
preintervention intravenous (IV)
hydration has been durably shown to
prevent post-ERCP pancreatitis in
randomized studies. More recently,
rectal indomethacin has been employed;
it has been shown to reduce the
incidence of post-ERCP pancreatitis and
is now widely accepted at most
institutions. The literature continues to
debate the role of rectal indomethacin.
Trauma
Abdominal trauma (approximately 1.5%)
causes an elevation of amylase and
lipase levels in 17% of cases and clinical
pancreatitis in 5% of cases. Pancreatic
injury occurs more often in penetrating
injuries (eg, from knives, bullets) than in
blunt abdominal trauma (eg, from
steering wheels, horses, bicycles). Blunt
injury to the abdomen or back may
crush the gland across the spine, leading
to a ductal injury.

Drugs
Considering the small number of
patients who develop pancreatitis
compared to the relatively large number
who receive potentially toxic drugs,
drug-induced pancreatitis is a relatively
rare occurrence (accounting for
approximately 2% of cases) that is
probably related to an unknown
predisposition. Fortunately, drug-
induced pancreatitis is usually mild.

Drugs definitely associated with acute

pancreatitis include the following:
 Azathioprine
 Sulfonamides
 Sulindac
  Tetracycline
 Valproic acid,
 Didanosine
 Methyldopa
 Estrogens
 Furosemide
 6-Mercaptopurine
 Pentamidine
 5-aminosalicylic acid compounds
 Corticosteroids
 Octreotide

Drugs probably associated with acute

pancreatitis include the following:
- Chlorothiazide and
hydrochlorothiazide
- Methandrostenolone
(methandienone)
- Metronidazole
- Nitrofurantoin
- Phenformin
- Piroxicam
- Procainamide
- Colaspase
- Chlorthalidone
- Combination cancer
chemotherapy drugs
(especially asparaginase)
- Cimetidine
- Cisplatin
- Cytosine arabinoside
- Diphenoxylate
- Ethacrynic acid
In addition, there are many drugs that
have been reported to cause acute
pancreatitis in isolated or sporadic cases.
Less common causes
The following causes each account for
less than 1% of cases of pancreatitis.
Infection
Several infectious diseases may cause
pancreatitis, especially in children. These
cases of acute pancreatitis tend to be
milder than cases of acute biliary or
alcohol-induced pancreatitis.

Viral causes include mumps virus,

coxsackievirus, cytomegalovirus (CMV),
hepatitis virus, Epstein-Barr virus (EBV),
echovirus, varicella-zoster virus (VZV),
measles virus, and rubella virus.
Bacterial causes include Mycoplasma
pneumoniae, Salmonella,
Campylobacter, and Mycobacterium
tuberculosis. Worldwide, Ascaris is a
recognized cause of pancreatitis
resulting from the migration of worms in
and out of the duodenal papillae.
Pancreatitis has been associated with
AIDS; however, this may be the result of
opportunistic infections, neoplasms,
lipodystrophy, or drug therapies.

Hereditary pancreatitis
Hereditary pancreatitis is an autosomal
dominant gain-of-function disorder
related to mutations of the cationic
trypsinogen gene (PRSS1), which has an
80% penetrance. Mutations in this gene
cause premature activation of
trypsinogen to trypsin.

In addition, the CFTR mutation plays a

role in predisposing patients to acute
pancreatitis by causing abnormalities of
ductal secretion. At present, however,
the phenotypic variability of patients
with the CFTR mutation is not well
understood. Certainly, patients
homozygous for the CFTR mutation are
at risk for pancreatic disease, but it is not
yet clear which of the more than 800
mutations carries the most significant
risk. In addition, the role of CFTR
heterozygotes in pancreatic disease is
unknown.
Mutations in the SPINK1 protein, which
blocks the active binding site of trypsin,
rendering it inactive, also probably play
a role in causing a predisposition to
acute pancreatitis.

This probably explains the

predisposition, rather than the cause, of
acute pancreatitis in these patients. If
enough mutant enzymes become
activated intracellularly, they can
overwhelm the first line of defense (ie,
pancreatic secretory trypsin inhibitor)
and resist backup defenses (ie,
proteolytic degradation by mesotrypsin,
enzyme Y, and trypsin itself). Activated
mutant cationic trypsin can then trigger
the entire zymogen activation cascade.

Hypercalcemia
Hypercalcemia from any cause can lead
to acute pancreatitis. Causes include
hyperparathyroidism, excessive doses of
vitamin D, familial hypocalciuric
hypercalcemia, and total parenteral
nutrition (TPN). Routine use of
automated serum chemistries has
allowed earlier detection and reduced
the frequency of hypercalcemia
manifesting as pancreatitis.
Developmental abnormalities of
pancreas
The pancreas develops from two buds
stemming from the alimentary tract of
the developing embryo. There are two
developmental abnormalities commonly
associated with pancreatitis: pancreas
divisum and annular pancreas.
Pancreas divisum is a failure of the
dorsal and ventral pancreatic ducts to
fuse during embryogenesis. Probably a
variant of normal anatomy, it occurs in
approximately 5% of the population (see
the images below); in most cases, it may
actually protect against gallstone
pancreatitis. It appears that the
presence of stenotic minor papillae and
an atretic duct of Santorini are
additional risk factors that together
contribute to the development of acute
pancreatitis through an obstructive
mechanism.
Medication
 Analgesics
- Acetaminophen
- Tramadol
- Meperidine
 Antibiotics
 - Imipenem & Clistatin
- Ampicillin
- Ceftriaxone

Chronic Pancreatitis
Chronic pancreatitis is commonly
defined as a continuing, chronic,
inflammatory process of the pancreas,
characterized by irreversible
morphologic changes.
Epidemiology
Based on the estimates from hospital
discharge data in the United States,
approximately 87,000 cases of
pancreatitis occur annually.
Comparing the hospital admissions data
from several cities around the globe, the
overall frequency is similar. Expressed as
number of cases per 1000 hospital
admissions, the value for Marseille is
3.1; for Cape Town, 4.4; for Sao Paulo,
4.9; and for Mexico City, 4.4. When the
data from several centers were
compared over time, the incidence of
chronic pancreatitis from 1945-1985
appeared to be increasing.
Race-, sex-, and age-related
demographics
Hospitalization rates for blacks are 3
times higher than for whites in the
United States. In population studies,
males are affected more commonly than
females (6.7 vs 3.2 per 100,000
population).

Differences in the hospitalization rates

of patients with chronic pancreatitis
exist with respect to sex. Rates in males
peak between ages 45 and 54 years and
then decline; female rates reach a
plateau, which remains stable after age
35 years.

Sex differences with respect to etiology

also exist. Alcohol-induced illness is
more prevalent in males, idiopathic and
hyperlipidemic-induced pancreatitis is
more prevalent in females, and equal
sex ratios are observed in chronic
pancreatitis associated with hereditary
pancreatitis.

In aggregate, the mean age at diagnosis

is 46 years, plus or minus 13 years. In
idiopathic chronic pancreatitis, a
bimodal age distribution has been
reported, designated as the early onset
form (median age 19.2 y) and the late-
onset form (median age 56.2 y).
Signs and symptoms
For most patients with chronic
pancreatitis, abdominal pain is the
presenting symptom. The patient
experiences intermittent attacks of
severe pain, often in the mid-abdomen
or left upper abdomen and occasionally
radiating in a bandlike fashion or
localized to the midback. The pain may
occur either after meals or
independently of meals, but it is not
fleeting or transient and tends to last at
least several hours.
Other symptoms associated with chronic
pancreatitis include diarrhea and weight
loss.
Clinical presentation
History
For most patients with chronic
pancreatitis, abdominal pain is the
presenting symptom. Either the patient's
age or the etiology of the disease has
some influence on the frequency of this
presentation. Ninety-six percent of those
with early onset idiopathic pancreatitis
present with abdominal pain, compared
with 77% with alcohol-induced disease
and 54% with late-onset idiopathic
chronic pancreatitis.

Clinically, the patient experiences

intermittent attacks of severe pain,
often in the mid abdomen or left upper
abdomen and occasionally radiating in a
bandlike fashion or localized to the
midback. The pain may occur either after
meals or independently of meals, but it
is not fleeting or transient and tends to
last at least several hours.
Unfortunately, patients often are
symptomatic for years before the
diagnosis is established; the average
time from the onset of symptoms until a
diagnosis of chronic pancreatitis is 62
months. The delay in diagnosis is even
longer in people without alcoholism, in
whom the average time is 81 months
from the onset of symptoms to
diagnosis.
Physical Examination
In most instances, the standard physical
examination does not help to establish a
diagnosis of chronic pancreatitis;
however, a few points are noteworthy.

During an attack, patients may assume a

characteristic position in an attempt to
relieve their abdominal pain (eg, lying on
the left side, flexing the spine and
drawing the knees up toward the chest).

Occasionally, a tender fullness or mass

may be palpated in the epigastrium,
suggesting the presence of a pseudocyst
or an inflammatory mass in the
abdomen. Patients with advanced
disease (ie, patients with steatorrhea)
exhibit decreased subcutaneous fat,
temporal wasting, sunken
supraclavicular fossa, and other physical
signs of malnutrition.
Differential Diagnoses
 Ampullary Carcinoma
 Cholangitis
 Cholecystitis
 Chronic Gastritis
 Community-Acquired Pneumonia
(CAP)
 Crohn Disease
 Intestinal Perforation
 Mesenteric Artery Ischemia
 Myocardial Infarction
 Pancreatic Cancer
 Peptic Ulcer Diseases.
Laboratory analysis
Blood tests
Serum amylase and lipase levels may be
slightly elevated in chronic pancreatitis;
high levels are found only during acute
attacks of pancreatitis. In the later
stages of chronic pancreatitis, atrophy of
the pancreatic parenchyma can result in
normal serum enzyme levels because of
significant fibrosis of the pancreas,
resulting in decreased concentrations of
these enzymes within the pancreas.
Fecal tests
Because maldigestion and
malabsorption do not occur until more
than 90% of the pancreas has been
destroyed, steatorrhea is a
manifestation of advanced chronic
pancreatitis. Neither qualitative nor
quantitative fecal fat analysis can detect
early disease.
Pancreatic Function Tests
Direct tests
These tests are the most sensitive and
can be used to detect chronic
pancreatitis at its earliest stage;
however, they are somewhat invasive,
labor intensive, and expensive.
Determination in duodenal aspirates
Intubation of the duodenum usually is
performed with a Dreiling tube, which
allows for separate aspiration of the
gastric and duodenal contents. The
methodology varies depending on the
specific laboratory; however, exogenous
secretin with cholecystokinin (CCK) is
used to achieve maximal stimulation of
the pancreas. The output of pancreatic
bicarbonate, protease, amylase, and
lipase then is measured in the duodenal
aspirates.
This test currently is available only in
specialized centers. While the greatest
sensitivity can be obtained in prolonged
infusions of a secretagogue to uncover a
decreased pancreatic secretory reserve,
it is impractical for general clinical use.
Determination in pancreatic juice
This test generally is performed in
conjunction with ERCP. The pancreatic
duct is freely cannulated, an exogenous
secretagogue is administered as above,
and the pancreatic juice then is
aspirated out of the duct as it is
produced. The output of pancreatic
bicarbonate, protease, amylase, and
lipase are measured.
Indirect tests
Noninvasive tests of pancreatic function
have been developed for detecting
chronic pancreatitis. In principle, these
tests work via oral administration of a
complex substance that is hydrolyzed by
a specific pancreatic enzyme to release a
marker substance. The intestine absorbs
the marker, which then is measured in
the serum or urine. These tests are
capable of detecting moderate to severe
chronic pancreatitis. The presence of
renal, intestinal, and liver disease may
interfere with the accuracy of these
tests. Neither currently is freely available
in the United States.

Imaging tests

Imaging studies such as abdominal

radiography and CT scanning can show
inflammation or calcium deposits in the
pancreas or changes in the pancreatic
ducts. Pancreatic calcifications, often
considered pathognomonic of chronic
pancreatitis, are observed in
approximately 30% of cases.

Endoscopic retrograde
cholangiopancreatograph
y

The endoscopic retrograde

cholangiopancreatography (ERCP) test
provides the most accurate visualization
of the pancreatic ductal system and has
been regarded as the criterion standard
for diagnosing chronic pancreatitis. It
combines the use of endoscopy and
fluoroscopy to visualize and treat
problems of the biliary and pancreatic
ducts.
This endoscopic retrograde
cholangiopancreatograph
This endoscopic retrograde
cholangiopancreatography (ERCP) shows
advanced chronic pancreatitis. The
pancreatogram has blunting of the
lateral branches, dilation of the main
pancreatic duct, and filling defects
consistent with pancreatolithiasis. The
cholangiogram also shows a stenosis of
the distal bile duct and a dilated biliary
tree.
Magnetic resonance
cholangiopancreatography

MRCP provides information on the

pancreatic parenchyma and adjacent
abdominal viscera, and it uses heavily
T2-weighted images to visualize the
biliary and pancreatic ductal systems.
This procedure is relatively safe,
reasonably accurate, noninvasive, fast,
and very useful in planning surgical or
endoscopic intervention.

Endoscopic ultrasonography
The most predictive endosonographic
feature of chronic pancreatitis is the
presence of stones. Other suggestive
features include the following:
 Visible side branches
 Cysts
 Lobularity
 An irregular main pancreatic duct
 Hyperechoic foci and strands
 Dilation of the main pancreatic duct
 Hyperechoic margins of the main
pancreatic duct

Management
Treatment is typically directed at the
underlying cause of the pancreatitis and
to relieve pain and malabsorption.
Pain relief
Pancreatic enzyme supplementation
may be helpful in reducing pain. The
hypothesis is that stimulation of the
pancreas by food causes pain.
Cholecystokinin (CCK) is one of the
possible mediators of this response.
When exogenous pancreatic enzymes
are taken with a meal, CCK-releasing
factors are degraded and CCK release in
response to a meal is reduced. This
decreases pancreatic stimulation and
pain.
If conventional medical therapy is
unsuccessful and the patient has severe,
intractable pain, celiac ganglion
blockade can be considered.This
approach tries to alleviate pain by
modifying the afferent sensory nerves in
the celiac plexus, using agents that
anesthetize, reduce inflammation, or
destroy the nerve fibers.

Endoscopic therapy aimed at

decompressing an obstructed pancreatic
duct can be associated with pain relief in
some patients. The rationale for this
approach is based on the hypothesis that
ductal hypertension due to strictures of
the main pancreatic duct leads to pain.

Surgery

The choice of operation depends on the

clinical problem and the preoperative
assessment of the abnormality. In
general, the approach aims either to
improve pancreatic duct drainage or to
resect the diseased organ. Data suggest
that surgical drainage of the pancreatic
duct is more effective than endoscopic
drainage in patients with obstruction of
the pancreatic duct due to chronic
pancreatitis.
In patients with a dilated pancreatic
duct, a Roux-en-Y side-to-side
pancreaticojejunostomy is indicated. If
the disease is limited to the head of the
pancreas, a Whipple operation
(pancreaticoduodenectomy) can
produce good results.
Medication
 Analgesics
- Acetaminophen
 Opioid Analgesics
- Hydrocodone and acetaminophen
- Acetaminophen with codeine
- Tramadol
 Nonsteroidal Anti-inflammatory
drug
 - Naproxen
- Diclofenac
- Ketorolac
- Ibuprofen
- Celecoxib
 Hormones
- Octereotide
 Antidepressant’s ,TCAs
- Amitryptyline
- Clomipramine
- Doxepin
- Nortriptyline
- Desipramine
 Pancreatic Enzyme Supplements
- Pancrealipase
Reference
Kaufman M, Singh G, Das S, et al.
Efficacy of endoscopic ultrasound-
guided celiac plexus block and celiac
plexus neurolysis for managing
abdominal pain associated with chronic
pancreatitis and pancreatic cancer. J
Clin Gastroenterol. 2010 Feb.
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Gadroy FX, Ponchon T, Roda R, et al.
Endoscopic treatment of chronic
pancreatitis: long-term results.
Gastrointest Endosc. Apr 2006.
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Cahen DL, Gouma DJ, Nio Y, et al.
Endoscopic versus surgical drainage of
the pancreatic duct in chronic
pancreatitis. N Engl J Med. 2007 Feb 15.
356(7):676-84. [Medline].
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guidelines for chronic pancreatitis 2015.
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Malfertheiner P. A proposal for a new
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pancreatitis. BMC Gastroenterol. 2009
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