ACUTE PANCREATITIS

INTRODUCTION

 Acute pancreatitis is an acute inflammatory process of the pancreas. It is

usually associated with severe acute upper abdominal pain and elevated
blood levels of pancreatic enzymes. Most cases are associated with alcoholism
or gallstones, but the precise pathogenetic mechanisms are not fully
understood
 Acute pancreatitis can be suspected clinically, but requires biochemical,
radiologic, and sometimes histologic evidence to confirm the diagnosis.
Clinical, biochemical, and radiologic features need to be considered together
since none of them alone is diagnostic of acute pancreatitis
CLASSIFICATION OF ACUTE
PANCREATITIS
 The revised Atlanta classification system divides acute pancreatitis into two
broad categories:
Interstitial edematous acute pancreatitis, which is characterized by acute
inflammation of the pancreatic parenchyma and peripancreatic tissues, but
without recognizable tissue necrosis
Necrotizing acute pancreatitis, which is characterized by inflammation
associated with pancreatic parenchymal necrosis and/or peripancreatic
necrosis
 According to the severity, 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 which is characterized by transient
organ failure (resolves within 48 hours) and/or local or systemic complications
without persistent organ failure (>48 hours)
Severe acute pancreatitis which is characterized by persistent organ failure
that may involve one or multiple organs
Etiology of acute pancreatitis

 ALCOHOL — may act by increasing the synthesis of enzymes by pancreatic

acinar cells to synthesize the digestive and lysosomal enzymes that are
thought to be responsible for acute pancreatitis or over-sensitization of acini
to cholecystokinin
 SMOKING — Until recently, smoking was thought to be a risk factor due to its
association with alcohol. However, at least four large studies have suggested
that cigarette smoking is an independent risk factor for acute and chronic
pancreatitis by mechanisms that are unclear
 HYPERTRIGLYCERIDEMIA — Serum triglyceride concentrations above 1000
mg/dL (11 mmol/L) can precipitate attacks of acute pancreatitis
 HYPERCALCEMIA — Although an uncommon complication, hypercalcemia of
any cause can lead to acute pancreatitis
 INFECTIONS AND TOXINS — Pancreatitis has been associated with the
following infections, although the frequency with which these infections lead
to pancreatitis is unknown:
Viruses – Mumps, coxsackievirus, hepatitis B, cytomegalovirus, varicella-
zoster, herpes simplex, HIV
Bacteria – Mycoplasma, Legionella, Leptospira, Salmonella
Fungi – Aspergillus
Parasites – Toxoplasma, Cryptosporidium, Ascaris
 TRAUMA — Blunt or penetrating trauma can damage the pancreas, although
these injuries are uncommon due to the retroperitoneal location of the gland
 PREGNANCY — Hyperlipidemic gestational pancreatitis usually occurs only in
women with preexisting abnormalities in lipid metabolism, although it is not
clear if pregnancy increases the risk of pancreatitis in women who have
underlying hypertriglyceridemia
 DRUGS — Several different mechanisms of drug-induced pancreatitis have
been proposed. These mechanisms include immunologic reactions (eg, 6-
mercaptopurine, aminosalicylates, sulfonamides), direct toxic effect (eg,
diuretics, sulfonamides), accumulation of a toxic metabolite (valproic acid,
didanosine , pentamidine , tetracycline ), ischemia (diuretics, azathioprine ),
intravascular thrombosis (estrogen), and an increased viscosity of pancreatic
juice (diuretics and steroids)
 POST-ERCP — Asymptomatic hyperamylasemia occurs in 35 to 70 percent of
patients undergoing endoscopic retrograde cholangiopancreatography (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
 MECHANICAL AMPULLARY OBSTRUCTION — Mechanical ampullary obstruction can
be induced by gallstone and a variety of disorders
 GENETIC MUTATIONS — Several genetic mutations have been associated with
pancreatitis. Inherited forms of pancreatitis may present as recurrent acute
pancreatitis but eventually progress to chronic pancreatitis
 IDIOPATHIC — No obvious etiology is identifiable by history, laboratory tests, and
gallbladder ultrasound in up to 30 percent of patients with acute pancreatitis
 OTHER CAUSES — Another rare cause of recurrent pancreatitis is celiac disease,
where duodenal inflammation and papillary stenosis may be the mechanisms for
pancreatitis. Autoimmune pancreatitis can sometimes present as acute
pancreatitis, although the usual presentation is by weight loss, jaundice, and
pancreatic enlargement on imaging, mimicking a neoplasm
Pathogenesis of acute pancreatitis

 Alcohol-induced pancreatitis — It is unclear why alcohol-induced pancreatitis

occurs only after many years of alcohol abuse and not after a single binge in
individuals not habituated to alcohol use. However, several mechanisms have
been proposed:
Sensitization of acinar cells to CCK-induced premature activation of zymogens
Potentiation of the effect of CCK on the activation of transcription factors,
nuclear factor kB, and activating protein-1
Generation of toxic metabolites such as acetaldehyde and fatty acid ethyl esters
Sensitization of the pancreas to the toxic effects of coxsackie virus B3
Activation of pancreatic stellate cells by acetaldehyde and oxidative stress and
subsequent increased production of collagen and other matrix proteins
 Gallstone pancreatitis — Two factors have been suggested as the possible
initiating event in gallstone pancreatitis: reflux of bile into the pancreatic duct
due to transient obstruction of the ampulla during passage of gallstones, or
obstruction at the ampulla secondary to stone(s) or edema resulting from the
passage of a stone
 Hyperlipidemia-induced pancreatitis — In hyperlipidemia, free fatty acids are
released from serum triglycerides in toxic concentrations by the action of
pancreatic lipase within pancreatic capillaries
 Genetic mutations in hereditary pancreatitis — Genetic mutations leading to
premature activation of pancreatic zymogens within the pancreas has also
been proposed as the pathogenetic mechanism for the acute attacks of
pancreatitis seen in patients with hereditary pancreatitis. This may be due to
a number of genetic mutations
 Intraacinar activation of proteolytic enzymes — One of the earliest events in
different models of acute pancreatitis is blockade of secretion of pancreatic
enzymes while synthesis continues. It is becoming increasingly apparent that the
central requirement for induction of acute pancreatitis is the intraacinar
activation of these proteolytic enzymes, which ultimately leads to an
autodigestive injury to the gland
 Microcirculatory injury — The release of pancreatic enzymes damages the
vascular endothelium and the interstitium as well as the acinar cells.
Microcirculatory changes, including vasoconstriction, capillary stasis, decreased
oxygen saturation, and progressive ischemia, occur early in experimental models
of acute pancreatitis. These changes lead to increased vascular permeability and
swelling of the gland
 SYSTEMIC RESPONSE — Some patients with severe pancreatic damage develop
systemic complications including fever, acute respiratory distress syndrome
(ARDS), pleural effusions, renal failure, shock, and myocardial depression. This
systemic inflammatory response syndrome (SIRS) is probably mediated by
activated pancreatic enzymes (phospholipase, elastase, trypsin, etc) and cytokines
(tumor necrosis factor, platelet activating factor) released into the circulation
from the inflamed pancreas
 Bacterial translocation — The normal human gut prevents the translocation of
bacteria into the systemic circulation through a complex barrier that consists
of immunologic, bacteriologic, and morphologic components. During the
course of acute pancreatitis, the gut barrier is compromised, leading to
translocation of bacteria, which can result in local and systemic infection.
The breakdown in the gut barrier is thought to be a consequence of ischemia
due to hypovolemia and pancreatitis-induced gut arteriovenous shunting
CLINICAL FEATURES

 Almost all patients with acute pancreatitis have acute upper abdominal pain
at the onset. The pain is steady and may be in the mid-epigastrium, right
upper quadrant, diffuse, or, infrequently, confined to the left side
 The abdominal pain is typically accompanied (in approximately 90 percent of
patients) by nausea and vomiting, which may persist for many hours
 Restlessness
 Agitation
 Relief on bending forward are other notable symptoms
 Physical examination — Physical findings vary depending upon the severity of
an attack. Systemic features include fever, tachycardia, and, in severe cases,
shock and coma
 In mild disease, the epigastrium may be minimally tender. However, severe
episodes are often associated with abdominal distention, especially in the
epigastrium, and tenderness and guarding, which are less than expected from
the intensity of the patient's discomfort
 Respirations may be shallow due to diaphragmatic irritation from
inflammatory exudate, and dyspnea may occur if there is an associated
pleural effusion
 Ecchymotic discoloration in the flank (Grey-Turner's sign) or the periumbilical
region (Cullen's sign) occurs in 1 percent of cases but is not diagnostic. These
signs reflect intraabdominal hemorrhage and are associated with a poor
prognosis
 Obstruction of the common bile duct, due to choledocholithiasis or edema of
the head of the pancreas, can lead to jaundice
LABORATORY TESTS

 A number of biochemical tests have been used in the diagnosis of acute

pancreatitis. These can be broadly classified as serum or urinary levels of
pancreatic digestive enzymes, serum or urinary levels of nonenzymatic
pancreatic secretions, and immune/nonspecific markers of inflammation
 Pancreatic enzymes — 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. As a
result, digestive enzymes leak out of acinar cells through the basolateral
membrane to the interstitial space and then the systemic circulation:
Serum amylase — Serum amylase is the most frequently ordered test to
diagnose acute pancreatitis. It rises within 6 to 12 hours of onset, and is
cleared fairly rapidly from the blood (half-life approximately 10 hours). In
uncomplicated attacks, serum amylase is usually elevated for three to five days
 Urine amylase — Hyperamylasuria occurs in acute pancreatitis because the
normal 3 percent amylase-to-creatinine clearance ratio (ACCR), which
indicates that approximately 3 percent of filtered amylase is excreted,
increases to approximately 10 percent . However, other than to diagnose ,
urinary amylase and the ACCR offer no advantage over routine serum amylase
Serum lipase — Because lipase measurements have been difficult to perform
and lacked precision, they have been less frequently ordered than serum
amylase. Lipase measurement is more specific than serum amylase and
urinary total amylase in diagnostic accuracy both on day one and day three
 Since activation of trypsin is likely an early event in the pathogenesis of acute
pancreatitis, trypsinogen activation peptide (TAP) may be useful in detection
of early acute pancreatitis
 Markers of immune activation/nonspecific markers — Serum markers of
immune activation may be useful in predicting a severe outcome of acute
pancreatitis. These include IL-6, IL-8, IL-10, TNF, PMN elastase, and C-
reactive protein
 Other tests include CBC, UECr, RBS, Blood Gas Analysis
RADIOLOGIC FEATURES

 Important radiologic features may be seen on a plain film of the abdomen,

chest radiograph, and spiral (helical) CT scan. Abdominal ultrasound also can
provide useful information but is often limited technically. Endoscopic
ultrasound may become useful to document the presence of gallstones within
the common bile duct
 The role of MRI is being increasingly recognized in acute pancreatitis to
detect pancreatic necrosis, differentiate fluid collections from areas of
pancreatic necrosis, and to detect common bile duct stones using magnetic
resonance cholangiopancreatography (MRCP)
 Abdominal plain film — In the setting of acute abdominal pain, an abdominal
plain film helps to exclude other causes of abdominal pain such as obstruction
and bowel perforation. The radiographic findings in acute pancreatitis range
from unremarkable in mild disease to localized ileus of a segment of small
intestine ("sentinel loop") or the "colon cutoff sign" in more severe disease
 The latter reflects a paucity of air in the colon distal to the splenic flexure
due to functional spasm of the descending colon secondary to spread of
pancreatic inflammation to that area
 A ground glass appearance may indicate ascites
 Chest film — Approximately one-third of patients with acute pancreatitis
have abnormalities visible on the chest roentgenogram such as elevation of a
hemidiaphragm, pleural effusions, basal atelectasis, pulmonary infiltrates, or
acute respiratory distress syndrome. Left-sided or bilateral pleural effusions
suggest increased risk of complications
 Abdominal ultrasound — A diffusely enlarged, hypoechoic pancreas is the
classic ultrasonographic image of acute pancreatitis; it can also detect
gallstones in the gallbladder. Ultrasound is ideal to image the gallbladder and
biliary tree and can be used in mild, uncomplicated cases of acute
pancreatitis. It cannot clearly delineate extrapancreatic spread of pancreatic
inflammation or identify necrosis within the pancreas; these important
findings are best seen by contrast enhanced CT scan
 CT scan — CT scan is the most important imaging test for the diagnosis of
acute pancreatitis and its intraabdominal complications and also for
assessment of severity. Patients with clinical and biochemical features of
acute pancreatitis who do not improve with initial conservative therapy or
who are suspected of having complications or other diagnoses should undergo
CT scan of the abdomen
 Magnetic resonance imaging — MRI and MRCP are being increasingly used in
the diagnosis and management of acute pancreatitis. Magnetic resonance
cholangiopancreatography, both enhanced and non-enhanced, has a strong
correlation with contrast-enhanced CT in acute pancreatitis. The advantages
of MRI over CT include: lower risk of nephrotoxicity from gadolinium in
patients without underlying renal disease, ability of MRI to better categorize
fluid collections as acute fluid collections, necrosis, abscess, hemorrhage, and
pseudocyst, and the greater sensitivity of MRI to detect mild acute
pancreatitis compared with CT
 In addition, unlike CT, MRCP delineates the pancreatic and bile ducts better,
and MRCP is comparable to ERCP for the detection of choledocholithiasis
Treatment of acute pancreatitis

 Most attacks of acute pancreatitis are mild with recovery occurring within five to
seven days. Death is unusual in such patients. In contrast, severe necrotizing
pancreatitis is associated with a high rate of complications and significant
mortality
 Treatment is aimed at correcting any underlying predisposing factors and at the
pancreatic inflammation itself
 SUPPORTIVE CARE — Mild acute pancreatitis is treated with supportive care
including pain control, intravenous fluids, and correction of electrolyte and
metabolic abnormalities. The majority of patients require no further therapy,
and recover and eat within three to seven days
 In severe acute pancreatitis, intensive care unit monitoring and support of
pulmonary, renal, circulatory, and hepatobiliary function may minimize systemic
sequelae
SUPPORTIVE CARE

 Vital signs and urine output should be monitored every few hours in the first
24 to 48 hours. Patients with severe pancreatitis will need ongoing monitoring
for other complications that might arise
 Sustained hypoxemia, hypotension refractory to a bolus of IV fluids, and
possibly renal insufficiency that does not respond to a fluid bolus warrant
prompt transfer to an intensive care unit for close monitoring
 The importance of fluid replacement in the initial stages has been accepted
as standard of care. Fluid replacement is important because patients with
necrotizing pancreatitis develop vascular leak syndrome. Inadequate
hydration can lead to hypotension and acute tubular necrosis. In addition,
fluid depletion damages pancreatic microcirculation and results in further
pancreatic necrosis
 Oxygen saturation needs to be assessed routinely and supplemental oxygen
administered to maintain arterial oxygen saturation of greater than 95
percent. Blood gas analysis should be done if oxygen saturation is less than 95
percent or if clinical situation demands. Hypoxia may be due to splinting,
atelectasis, pleural effusions, opening of intrapulmonary shunts, or acute
respiratory distress syndrome (ARDS). Persistent or progressive hypoxia may
require mechanical ventilation
 Electrolytes should be monitored in patients with acute pancreatitis based on
disease severity. Hypocalcemia should be corrected if ionized calcium is low
or if there are signs of neuromuscular instability (Chvostek’s or Trousseau’s
sign). Low magnesium levels may cause hypocalcemia and should be
corrected
 Serum glucose levels should be carefully monitored hourly in patients with
severe pancreatitis and sliding scale insulin should be used to keep blood
sugar levels under good control. Hyperglycemia may result from parenteral
nutritional therapy, decreased insulin release, increased gluconeogenesis, and
decreased glucose utilization, and may increase the risk of secondary
pancreatic infections
 Deep vein thrombosis prophylaxis should be considered in bedridden patients
PAIN MANAGEMENT
 Abdominal pain is often the dominant symptom. Patients with hypovolemia
from vascular leak and hemoconcentration may have ischemic pain. Markers of
ischemia include metabolic acidosis and elevated serum lactate. Uncontrolled
pain can contribute to the hemodynamic instability
 Attention to adequate fluid resuscitation should be the first priority in
addressing severe abdominal pain
 Adequate pain control requires the use of intravenous opiates, usually in the
form of a patient controlled analgesia pump. Hydromorphone or fentanyl
(intravenous) may be used for pain relief in acute pancreatitis. Fentanyl is
being increasingly used due to its better safety profile, especially in renal
impairment
 Meperidine has been favored over morphine for analgesia in pancreatitis
because studies showed that morphine caused an increase in sphincter of Oddi
pressure
NUTRITION

 Patients with mild pancreatitis can often be managed with intravenous

hydration alone since recovery often occurs rapidly, allowing patients to
resume an oral diet within a week. Nutritional support is often required in
patients with severe pancreatitis
 Nutritional support should be provided to those who are unlikely to resume
oral intake for more than five to seven days. Nasojejunal tube feeding (using
an elemental or semi-elemental formula) is preferred to total parenteral
nutrition
 Early enteral nutrition (24 to 48 hours) should be initiated upon transfer to an
intensive care unit, development of organ dysfunction, or systemic
inflammatory response syndrome (SIRS) persisting for 48 hours if severe acute
pancreatitis is confirme
 Initiation of oral feeding — When to begin oral feedings depends on the
severity of the pancreatitis:
In mild pancreatitis, in the absence of ileus, nausea or vomiting, oral feeds can be
initiated as soon as the pain starts improving and narcotic requirements are
decreasing. This usually occurs 24 to 48 hours after the onset of pancreatitis.
Traditionally, patients have been advanced from a clear liquid diet to solid food
as tolerated
In moderate to severe pancreatitis, oral feeding is frequently not tolerated due to
postprandial pain, nausea, or vomiting, probably related to gastroduodenal
inflammation and/or extrinsic compression from fluid collections leading to
gastric outlet obstruction. Patients are generally placed on enteral or parenteral
feeding as discussed above. When the local complications start improving, oral
feeds are initiated and advanced as tolerated
INFECTION

 The occurrence of pancreatic infection is a leading cause of morbidity and

mortality in acute necrotizing pancreatitis. Approximately one-third of
patients with pancreatic necrosis develop infected necrosis
 The important organisms causing infection in necrotizing pancreatitis are
predominantly gut-derived, including Escherichia coli, Pseudomonas,
Klebsiella, and Enterococcus
 Prophylactic antibiotics — we initiate antimicrobial therapy with imipenem/
meropenem and continue it for 7 to 10 days if there is necrotizing
pancreatitis (involving more than approximately 30 percent of the pancreas).
Because of the risk of fungal superinfection, antibiotics should be stopped
after 7 to 10 days unless infection is documented
 Percutaneous CT-guided aspiration — CT-guided percutaneous aspiration with
Gram's stain and culture is recommended when infected pancreatic necrosis is
suspected (clinical instability or sepsis physiology, increasing white blood cell
count, fevers). Sterile necrosis does not usually require antibiotics and acute
fluid collections do not require therapy in the absence of infection or
obstruction of a surrounding hollow viscus
 Necrosectomy — Indications for necrosectomy include infected pancreatic
necrosis and sterile symptomatic pancreatic necrosis with abdominal pain
preventing oral intake. Surgical debridement of pancreatic necrosis
(necrosectomy) can be accomplished by open surgery or a minimally invasive
approach (endoscopic or percutaneous radiologic)
TREATMENT OF ASSOCIATED CONDITIONS

 In addition to the above treatment for pancreatic inflammation, treatment of

acute pancreatitis is aimed at correcting any underlying predisposing factors,
such as gallstones and hypertriglyceridemia, and treating complications such
as splenic vein thrombosis and abdominal compartment syndrome
COMPLICATIONS

 Splenic vein thrombosis — Splenic vein thrombosis is seen on imaging in up to

19 percent of patients with acute pancreatitis
 Treatment should focus on the underlying pancreatitis since the effective
treatment may be associated with spontaneous resolution of the thrombosis.
Anticoagulation may be needed if there is extension of the clot into the portal
or superior mesenteric vein resulting in hepatic decompensation or
compromise of bowel perfusion
 However, this needs to be considered along with the theoretical possibility of
hemorrhage into pancreatic necrosis or fluid collections
 Abdominal compartment syndrome — Patients with severe pancreatitis are at
increased risk for intraabdominal hypertension and abdominal compartment
syndrome. Factors that can contribute to abdominal compartment syndrome
in patients with acute pancreatitis include tissue edema from aggressive fluid
resuscitation, peripancreatic inflammation, ascites, and ileus
 Abdominal compartment syndrome is a life threatening complication that
results in visceral organ ischemia and tissue necrosis. Abdominal
compartment syndrome occurs when intra-abdominal pressure rises above 21
mmHg. Patients in the ICU should be monitored for potential abdominal
compartment syndrome with serial measures of urinary bladder pressures
 If abdominal compartment syndrome is confirmed, either percutaneous
catheter-based or surgical decompression is indicated
 In patients with severe pancreatitis who require surgical decompression, this
typically requires midline laparotomy. Following decompressive laparotomy,
temporary abdominal closure is used until the need for an open abdomen has
resolved. The abdomen is then closed primarily, functionally, or using skin
grafts
INCIDENCE AND MORTALITY

 Accurate assessment of the incidence and mortality of acute pancreatitis is

difficult as mild pancreatitis may be subclinical and deaths may occur before
the diagnosis is made in severe and fulminant attacks
 The reported annual incidence of acute pancreatitis has ranged from 4.9 to
35 per 100,000 population. Acute pancreatitis is a leading cause of
hospitalization in the United States
 The incidence of acute pancreatitis is increasing in many European and
Scandinavian countries due to increased alcohol consumption and better
diagnostic capability
The end

 Thank you all