ACUTE PANCREATITIS

• DEFINITIONS:
• Acute pancreatitis is an acute inflammatory plocess with variable involvement of
adjacent and remote organs. Although pancreatic function and structure even.tually
return to normal, the risk of recurrent attacks is nearly 50% unless the precipitating
cause is removed. Initia1 manifestations and exacerbations of chronic pancreatitis
may be indistinguishable from attacks of acute pancreatitis. And they should be
treated as such. The inflammation.begins in the perilobular and peripancreatic fatty
tissue, rnanifested by edema and spotty fat necrosis.The disease may progress to the
peripheral acinar ce1ls, pancreatic ducts, blood vessels, and bordering organs. In
severe cases; patchy areas of the pancreatic parenchyma become necrotic.
• PATHOGENESIS:
• Premature activation of zymogens and the escape of activated enzymes
from acinar cells and pancreatic ducts set the stage for the .autodigestive
process that represents acute pancreatitis. Proteases released into the b1ood
are inactivated by circulating inhibitors. Based on clinical and experimental
observations, several mechanisms have been proposed to initiate acute
pancreatitis. Among these, ref1ux of duodenal contents or bile into the
pancreatic duct is no longer considered to play a role. Obstruction of the
pancreatic duct near the ampulla of Vater remains a plausible mechanism
that may explain many, although not all, episodes of acute pancreatitis 。
• ASSOCIATED FACTORS∶
• Clinical conditions, medications, and toxins know.
to precipitate acute pancreatitis are 1isted in
Tab1e .Among these, choledocholithiasis and
ethanol abuse account for 70 to 80% of all cases.
The number attr.ibuted to the idiopathic type varies
with the clinician′s astuteness in identifying one of
the factors listed. All remaining causes combined
account for l0% or less of the tota1.
 ETIOLOGIC
ASSOCIATIONS
• Alcohol.
• Fully 70 to 80% of patients with chronic pancreatitis are chronic alcohol
abusers. Alcoholic pancreaitits, even when if presents as.an. acute episode, is
a chronic, progressive disease. Typically, the initial symptoms appear at ages
35 to 45, but some patients may experience their first attack before age 25.
Alcoho1ic liver disease develops in 40 to 50% of patients and frequently
becomes manifest 5 to 10 years after the onset of pancreatitis. Alcohol
abstinence offers moderate and unpredictable benefits in terms of pain relief
and 1ater development of diabetes mellitus but does not alter the progression
of pancreatic f1brosis and exocrine insufficiency. The mechanism of
alcoho1-induced pancreatic injury remains unknown.
• Drug-induced Pancreatitis:
• This comp1ication characteristically occurs within
the first 2 months of exposure: it is not dose related
and the pancreatitis usually is mild. Most commonly
implicated are azathioprine/6-mercaptopurine,
valproic acid in chi1dren, su1fir-containing
diuretics.
• Hypcrtriglyceridemia:
• The presence of lipemia ， with serum triglyceride
1evels ＞ 1000mg per deciliter （ 11.29mmol ／
L ）， represcnts a cause ， not an effect ， of
pancreatitis 。 Causes include estrogen therapy,
alcoholism ， intravenous lipid infusions ， and
primary hyperlipidemias 。
• Misce11aneous Factors∶
• Acute hypercalcemia rnay trigger acute pancreatitis 。 This may occur with intravenous
calcium infusions and with vitamin D poisoning ． Blunt abdominal trauma causes pancrcatitis
by disrupting the duct ； it is the most common cause of pancrcatitis in children 。
Postoperative pancreatitis may follow intra- and extra-abdomina1 surgery and carries a high
mortality rate of 25 to 50 ％。 Pancreatitis following endoscopic retrograde
cholangiopancreatography （ ERCP ） is usually mild unless it is complicated by duodena1
perforation during endoscopic sphincterotomy 。 Pancreatic infections arc an exceeding1y
rare and poorly documented cause of pancreat1tls ．
• CLINICAL PRESENTATION∶
• Steady ， dull ， or boring mid—epigastric pain associatcd with nausea and
vomiting is the classic prescntation of acute pancrcatitis 。 Thc pain reaches
peak intensity within15 minutes to 1 hour from onset ， in contrast to the
more abrupt onset of pain with a perforated viscus 。 It radiates straight to
the midline of the lower thoracic vertebral region in about 50 ％ of patients
and is usually worse in the supine position. Painless acute pancreatitis is
very rare but carries a grave prognosis because the patients frequently present
in shlock 。
• Initial physical examination reveals mild fever and tachycardia ；
hypotension is present in 30 to 40% of patients 。 There is marked
tenderness to deep palpation of the upper abdomen ， but signs of
peritoneal irritation such as abdominal wall rigidity and rebound
tenderness are absent 。 Bowel sounds arc diminished ； paralytic
ileus with abdominal distention may develop during the first few
days, signifying extension of the inflammatory process into the small
intestinal and colonic mesentery.
• One to twq weeks after the onset, large ecchymoses rarely
appear in the f1anks(Grey Turner's sign) or the umbilical
area(Cullen's sign). these represent blood dissecting from
the retroperitoneal1y located pancreas along fascial
planes. Sirnilarly, inflammatory masses, large fluid
collections, or a pancreatic abscess may become palpable
later in the course of the disease.
• DIAGNOSIS:
• The diagnosii of acute pancreatitis rests on a
combination of clinical, laboratory, and radiologic
f1ndings, none of which is infallib]e. The goals of
diagnostic studies are
• (1) to exc1ude other acute conditions that may
require urgent surgical management;
• (2) to assess the prognosis;
• (3) to detect local and systemic complications early;
• (4) to identifv a precipitating cause
• Laboratory Tests:
• Anylase.
• Total serum amylase activity is the test most frequently used to diagnose acute
pancreatitis. The, level rises 2 to l2 hours after onset of symptoms and remains
e1evated for 3 to 5 days in most cases. Va1ues>5 times the upper limit of normal
are highly specif1c for acute pancreatitis, but these are found in only 80 to 90% of
cases. The magnitude of the rise in serum anylase does not correlate with the
severity of the attack, nor. does prolonged hyperamylasemia indicate developing
complications. Marked hypetriglyceridemia, sufficient to givc thc scrum a lipemic
appearance ， masks elevations in serum amylase and lipase ； dilution of these
sera lead to a paradoxical rise in the reported enzyme valucs 。 Separation of total
serum amylase into its pancreatic
• 〔 P 〕 and salivary （ S ） isoenzymes and measurements of urinary amylase
output add 1ittle to the diagnostic information 。 The amylase － creatinine
clearance ratio （ ACR ）（ the ratio of amylase concentration in urine over
p1asma ， divided by the corresponding values for creatinine ） is useful in
diagnosing asymptomatic macroamylasemia only when aggregates of circulating
amylase escape glomerular infiltration and the ACR is abnormally low 。 Serum
amylase may be elevated in many other clicinal conditions ， such as chronic
pancrcatitis ， perforation of viscus ， mesemteric inforction ， metabolic
acidosis ； carcinoma of the pancreas ， illustrating the fact that the diagnosis of
acute pancrcatitis should not be based so1ely ， on laboratory results 。
• Lipase.
• Serum lipase assays ， have similar
specifcity ， and sensitieity as serum
amylase 。 The serum lipase tends to remain
e1evated longer than amylase during the healing
phase of pancreatitis.
• Combinations of Serum Enzyme Tests∶
• The combination of serum amylase and lipase
determunations is more accurate than either test
alone 。 The diagnostic accuracy can be
improved further by ca1culating cut-off values
that lie above the upper limit of normal.
• Other B1ood Tests:
• .Leukocytosis. of up to 25000 cells per cubic mi1limeter is present in 80% of
patients. Hypocalcemia occurs in up to 30% of patients due to a combination
of hypoabuminemia and calcium precipitation in areas of .fat necrosis. The
ionized calcium concentration remains norma1, and symptoms of tetany are
extremely rare;Prc-exiting hypercalcemia may, however, be obscured by the
ca1cium-lowering effect of pancreatitis. Transient mi1d hyperg1ycemia is
common and does not require insulin treatment.
• Serum triglyceride leve1s should be obtained in all liver disease
or to the pancreatic inf1ammation itself patients because of their
etiologic imp1icatiots and to help interpret unexpectedly normal
serum amy1ase andl.lipase levels. Elevated alanine
aminotransferase (ALT) and a1kaline phosphatase (ALP) va1ues
suggest ga1lstone-associated pancreatitis. The serum aspartate.
aminotarnsferase (AST) is elevated in approximately 50% of
patients owing to alcoho1ic
• Abdominal Ultrasonography(US) and Computed
Tomography(CT) Scan.
• These two imaging modalities play important and
complementary roles in diagnosing and managing acute
pancreatitis. US is the method of choice for detecting
cholelithiasis and for determining the diameter of the
extrahepatic and intrahepatic bile ducts. Di1atation of these
ducts suggests recent or persisting impaction of a.stone jn the
distal common bile duct or the ampulla of Vater. US also very
accurate1y detects acute
• cholecysitis. The CT scan is the primary modality for assessing the extent and
local,complications of pancreatitis. It is far superior to US in this regard. The
examination shou1d be performed with. rapid intravenous bo1us injection of
contrast .material (dynamic CT scan). It revea1s extension of peripancreatic
inflammation, involvement of adjacent organs,venous thrombosis(splenic
vein) , and f1uid co1lections. Most important, pancreatic necrosis can be
identif1ed and quantitated by the lack of contrast enhancement following the
bolus injection. The abdominal CT soan. may be normal, however, in about 1
0% of patients with ear1y, mi1d pancreatitis.
• Differentia1 Diagnosis∶
• There is no sing1e absolute criterioh for the diagnosis of acutc
pancrcatitis 。 The differential diagnosis shou1d focus on other conditions
presenting with acute upper abdominal pain which require specif1c
therapy 。 Υhese include perforated peptic ulcer ， acute cholecystitis ，
and mesenteric vascular occlusion ， A ga11stone impacted in the ampulla
of Vater may not only delay the resolution of bi1iary pancrcatitis but a1so
cause combination of positive US f1ndings
CLINICAL COURSE AND
THERAPY
• （ gallstones or bile duct dila1ation ） with a positive
biochemical score is indicative of this situation 。
• A positive score consists of three or more of the fo1Iowing
tests exceeding the stated limit
• （ 1 ） alkalinephosphatase ＞ ULN （ upper limit of
normal ）；
• （ 2 ） total bilirubin ＞ ULN ；
• （ 3 ） gamma glutamyltransfcrase ＞ 2× ULN ； （ 4 ）
ALT ＞ 1.5×ULN ；
• （ 5 ） ALT ／ ASΥ ＞ 1.0
CLINICAL COURSE
AND THERAPY
• Mild Pancreatitis.
• Mi1d acute pancreatitis is defined by the absence of systemic
and local complications. About 80% of patients belongs to this
category and require<1 week of hospitalization. Treatment
consists of general supportive care and close monitoring for
signs of systemic. complications; local complications tend to
manifest during the second and third week of illness. There is no
evidence. that any medication is specif1cal1y bencf1cial. The
intravascular volume def1cit may exceed 30%
• due to peripancreati9 fluid sequestration and vometing.
Volume restoratin must be rapid and eff1cient in order
to maintain regularly monitored urine output ob40 ml
per hour. The patient receives nothing by mouth, with
the goal>al of resting the pancreas. Nasogastric
aspiration is indicated in t1le presence of vomiting or
developing ileus; it need. not be initiated routine1y.
The patient should receive suff1cient analgesic
medications to alleviate pain.
• Systemic Complications
• Most systemic complications occur during the f1rst week of illness. They are
treated by standard medica1 measures. Close patient monitoring is the key to their
timely recognition. Circulatory shock arises by a combination. fo volume depletion
and a hyperdynamic circu1atory ' state with decreased peripheral vascular
resistance. The management incldes transfer to an ICU, volume replacement, and
vasopressor substances. The occurrence of shock is frequently followed by
panc1eatic necrosis. Acute. renal failure may be caused by circu1atory shock
• and a selective increase in renal vascular. resistance. The
treatment is that of acute tubular necrosis. arising in any
setting. The 1eading catlse of respiratory insuff1ciency
during acute pancreaitits is the adult respiratory distress
syndrome(ARDS), a1tnough respiratory depress1on
caused by opiate medictltions, p1eural effusions, invlves
damage to the pulm onary surfactant layer by circulating
phospholipase A and free fatty acids. Sepsis is most
commonly caused b$ infection of the bile bucts, of areas
of pancreatic necrosis, or of peripancreatic f1uid
collections.
LOCAL COMPLICATIONS
• Aacending cholangitis and severe bi1iary pancreatitis
present over1apping features and may coexist. Gram-
negative becteremia and spiking fevers are more
common w1th infection of the biliary tract, whereas
hyperbilirubinemia may be mild or absent in oth
situations. Appropriate antibiotic therapy should be
instituted.
• Pancreatic Necrosis ：
• Pahcreatic necrosis(PN) is found by dynamic CT scanning in
approximately 80% of patients( L6% of the tota1) with cIinically
severe disease, usually during the second or third week of illness.
PN, However, is present in approximately 40% of patients within 4
days of symptom onset. It fo11ows that PN resolves without
incident in nearly 60% of patients who develop it. Therapy and
prognosis of the severely ill patient with PN depend crucia1ly on
the presence of necrotic tissue. This question should be answered
by fine-needle aspiration of necrotic areas under CT guidance
before the patient leaves the CT suite. A Gram stain of the aspirate
is>95% accurate in predicting the f1nal results of bacterial
• cu1tures. The bacteria represent enteric f1ord that gained access to mesenteric
hymphatics by trans1ocating lcross the colonic mucosa. Antibiotics with high
pene1ration into pancreatic t1ssue include the fluroquinolones, imipen/cilastatin,
and, metronidazole. The morta1ity of patients with infected PN treated
conservatively is 60 to l00%. Immediately removing necrotic tissue
(necrosectomy), combined with continued 1avage of the necrotic space, lowers
the morality to about 20%. The patients frequently require re-operation. for
continuing necrosis and other local complications, such as bleeding and f1stula
formation. The management of patients with sterile PN remains controversial.
• Fluid Collections ：
• these occur within or around the pancreas in up to 50%, of patients with severe
pancreatitis. The majority resolve spontaneous1y; collections that persist for>6
weeks develop a wall of granulation tissue and are then called pseudocysts .
Collections that continue to expends or. become infected require drainage.
Pancreatic abscesset contain 1iquid pus and may be considered to represcnt
in1ected fluid colletions. Pancreatic ascites reflects involvement of perioneal
surfaces by the inf1ammatory process and, rarely, the rupture of a pancreatic
duct with pancreatic juice entering into the peritoneal cavity.
• There are several causes of b1eeding during acute
pancreatitis. Hemorrhage may occur into necrotic
intrapancreatic and peripancreatic tissue and into f1uid
co1lections. Brisk hemorrhege occurs with erosion of
the splenic or gastroduodenal arteries. At times, the
blood gains access to a disrupted pancreatic duct and
empties into the duodenum. Diffube mucosa1 blecding
from antrum and duodcnum is common but rarcly
severe. Final1y, bleeding may signal perforation of
peripancrcatic inflammation into any portion of the
gastrointestinal tract from esophagus to colon.The
spleen may becorne involved by direct extension of the
inflammatory process or, secondarily, by splenic vein
thrombosis. The latter complication leads to gastric
fundic varices.
 PREVENTING
RECURRENCES
• The search for the precipitating cause begins during the acute
attack. Serum calcium and triglyceride levc1s are determined
and the medication list is reviewed for drugs listed in Tabe.
An abdominal US examination is performed routinely. If
gallstones are detected, the patient should undergo
earlycholecystectomy, preferably before discharge form the
hospital. The absence of choledocholithiasis must be
ascertained before or during this surgical procedure, At this
stage, approximately 20% of patinets are assumed to have
idiopathic pancreatitis.
• Fluid Collections ：
• These occur within or around the pancreas in up to 50% of patients with
severe pancreatitis. The majority reso1ve spontaneously; collections that
persist for>6 weeks develop a wal1 of granulation tissue and are then
called pseudocysts. Collections that continue to expends or become
infected require drainage. Pancreatic abscesses contain liquid pus and may
be considered to represent infected f1uid colletions. Pancreatic ascites
reflects involvement of perioneal surfaces by the inf1ammatory process
and, rarely, the rupture of a pancreatic duct with pancreatic juice entering
into the peritoneal cavity. There are several causes of bleeding
• during acute pancreatitis. Hemorrhage may occur into necrotic intrapancreatic and
peripancreatic tissue and into f1uid col1ections. Brisk hemorrhege occurs with erosion of the
splenic or gastroduodenal areries. At times, the blood gains access to a disrupted pancreatic
duct and empties into the duodenum. Diffuse mucosal bleeding from antrum and duodenum is
common but rarely severe. Finally, bleeding may signal perforation of peripancreatic
inflammation into any portion of the gastrointestinal tract from esophagus to colon. The
spleen may become involved by direct extension of the inflammatory process or, secondarily,
by splenic vein thrombosis. The latter comp1ication leads to gastric fundic varices.
 PREVENTING
RECURRENCES
• The search for the precipitating cause begins during the acute attack. Serum
calcium and triglyceride levels are determined and the medication list is
rcviewed for drugs listed in Table ． An abdominal US examination is
performed routinely. If gallstones are detected, the patient shou1d undergo
earlycholecystectomy, preferably before discharge form the hospital. The
absence of,cho]edocholithiasis must be aceHained before or durlng thls
surglcal procedure, At this stage, approx1mately, 20% of patinets..are
assumed to have idiopathic pancreatitis.