Acute Pancreatitis

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

Ultrasonography(US) • Abdominal Tomography(CT) Scan. •

and

Computed

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. Gramnegative 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.