Acute Pancreatitis

ACUTE PANCREATITIS

STRUCTURES • The pancreas is situated retroperitoneally with the second part of the duodenum wrapping around the head. The tail of the pancreas lies over the spleen. • The exocrine secretion is drained by a branching system of ducts, draining into the main pancreatic duct. This usually enters the second part of the duodenum together with the common bile duct at the ampulla of Vater. There is considerable anatomical variation.

FUNCTIONS • The majority of the pancreatic cells are concerned with its exocrine function. Release of secretin from acid stimulation of the duodenum causes production of water , electrolytes and bicarbonate from the pancreas. • The endocrine function of the pancreas is served by the islets of Langerhans.Within these,most cells secrete insulin.

DEFINITIONS • Acute pancreatitis is an acute inflammatory process arising in the exocrine pancreas, with variable involvement of adjacent and remote organs. • The inflammation begins in the perilobular and peripancreatic fatty tissue, manifested 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.

• Although pancreatic function and structure eventually return to normal, the risk of recurrent attacks is nearly 50% unless the precipitating cause is removed. • Initia1 manifestations and pains of chronic pancreatitis may be indistinguishable from attacks of acute pancreatitis. And they should be treated as such.

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.

• 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 。

ETIOLOGIC ASSOCIATIONS

•ASSOCIATED FACTORS∶ • Clinical conditions, medications, and toxins are all known to precipitate acute pancreatitis. Among these, choledocholithiasis and alcohol abuse account for 70 to 80% of all cases.

• All remaining causes combined account for l0% or less of the tota1.

• Alcohol. Fully 70 to 80% of patients with chronic pancreatitis are chronic alcohol abusers. Alcoholic pancreatitis, 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 but does not alter the progression of pancreatic fibrosis and exocrine insufficiency. The mechanism of alcoho1-induced pancreatic injury remains unknown. •

• Hypertriglyceridemia: • The presence of lipemia ， with serum triglyceride 1evels ＞ 1000mg per deciliter （ 11.29mmol ／ L ）， represents a cause ， not an effect ， of pancreatitis 。 Causes include estrogen therapy, alcoholism ， intravenous lipid infusions ， and primary hyperlipidemias 。

• Multi-ply Factors∶ • Acute hypercalcemia may trigger acute pancreatitis 。 This may occur with intravenous calcium infusions and with vitamin D poisoning ． • Blunt abdominal trauma causes pancreatitis by disrupting the duct ； it is the most common cause of pancreatitis 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 are an exceeding1y rare and poorly documented cause of pancreatitis ．

CLINICAL PRESENTATIONS

• Steady ， dull ， or boring mid—epigastric pain associated with nausea and vomiting is the classic presentation of acute pancreatitis 。 The 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 shock 。

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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 are 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 two weeks after the onset, large ecchymosis rarely appear in the f1anks(Grey Turner's sign) or the umbilical area(Cullen's sign). represent blood dissecting from the • These retroperitoneal1y located pancreas along fascial planes. • Similarly, inflammatory masses, large fluid collections, or a pancreatic abscess may become palpable later in the course of the disease.

DIAGNOSIS

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The diagnosis of acute pancreatitis rests on a combination of clinical, laboratory, and radiologic findings, none of which is infallible. 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 identify a precipitating cause

LABORATORY TESTS

• Amylase. 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 specific for acute pancreatitis, but these are found in only 80 to 90% of cases. • The magnitude of the rise in serum amylase does not correlate with the severity of the attack, nor does prolonged hyperamylasemia indicate developing complications. Marked hypetriglyceridemia, sufficient to give the serum a lipemia appearance ， masks elevations in serum amylase and lipase ； dilution of these sera leads to a paradoxical rise in the reported enzyme values 。

• 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 。 • Serum amylase may be elevated in many other clinical conditions ， such as chronic pancreatitis ， perforation of viscus ， mesenteric infarction ， metabolic acidosis ； carcinoma of the pancreas ， illustrating the fact that the diagnosis of acute pancreatitis should not be based so1ely on laboratory results 。

• Lipase. • Serum lipase assays ， have similar specificity ， and sensitivity as serum amylase 。 The serum lipase tends to remain e1evated longer than amylase during the healing phase of pancreatitis.

• Combinations Tests∶

of

Serum

Enzyme

• The combination of serum amylase and lipase determinations 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 hypoalbuminemia and calcium precipitation in areas of fat necrosis. The ionized calcium concentration remains norma1, and symptoms of tetany are extremely rare;Pre-existing hypercalcemia may, however, be obscured by the ca1cium-lowering effect of pancreatitis. • Transient mi1d hyperg1ucemia is common and does not require insulin treatment.

• Elevation of serum triglyceride leve1s should be obtained in all patients with liver disease or to the pancreatic inf1ammation itself because of their etiologic imp1ications and to help interpret unexpectedly normal serum amy1ase and lipase levels. • Elevated alanine aminotransferase (ALT) and a1kaline phosphatase (ALP) va1ues suggest ga1lstone-associated pancreatitis. The serum aspartate aminotransferase (AST) is elevated in approximately 50% of patients owing to alcoho1ic abuse.

• A positive score consists of three or more of the fo1lowing tests exceeding the stated limit: （ 1 ） alkaline phosphatase ＞ ULN （ upper limit of normal ）； •（ 2 ） total bilirubin ＞ ULN ； （ gallstones or bile duct dilatation with a positive biochemical score is indicative of this situation) •（ 3 ） gamma glutamyltransferase ＞ 2× ULN ； •（ 4 ） ALT ＞ 1.5×ULN ； •（ 5 ） ALT ／ AST ＞ 1.0

• 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 in the distal common bile duct or the ampulla of Vater. • US also very accurate1y detects acute cholecystitis.

• 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). • The CT scan revea1s extension of peripancreatic inflammation, involvement of adjacent organs,venous thrombosis(splenic vein) , and f1uid co1lections. Most importantly, pancreatic necrosis can be identified and quantitated by the lack of contrast enhancement following the bolus injection. • The abdominal CT scan may be normal, however, in about 10% of patients with ear1y, mi1d pancreatitis.

• Differentia1 Diagnosis∶ • There is no sing1e absolute criterion for the diagnosis of acute pancreatitis 。 The differential diagnosis shou1d focus on other conditions presenting with acute upper abdominal pain which require specific therapy 。 • These 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 pancreatitis but a1so cause combination of positive US findings.

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 specifical1y beneficial.

• The intravascular volume deficit may exceed 30% due to peripancreatic fluid sequestration and vomiting. Volume restoration must be rapid and efficient in order to maintain regularly monitored urine output of 40 ml per hour. • The patient receives nothing by mouth, with the goal of resting the pancreas. Nasogastric aspiration is indicated in the presence of vomiting or developing ileus; this need not be initiated routine1y. • The patient should receive sufficient analgesic medications to alleviate pain.

• Systemic Complications •

Most systemic complications occur during the first week of illness. They are treated by standard medica1 measures. Close patient monitoring is the key to their timely recognition.

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1.Circulatory shock arises by a combination of volume depletion and a hyperdynamic circu1atory state with decreased peripheral vascular resistance. The management includes transfer to an ICU, volume replacement, and vasopressor substances. The occurrence of shock is frequently followed by pancreatic necrosis.

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2. 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.

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3.The 1eading cause of respiratory insufficiency during acute pancreatitis is the adult respiratory distress syndrome(ARDS). A1though respiratory depression caused by opiate medications, p1eural effusions, involves damage to the pulmonary surfactant layer by circulating phospholipase A and free fatty acids.

• 4. Sepsis is most commonly caused by infection of the bile

ducts, of areas of pancreatic necrosis, or of peripancreatic f1uid collections .

• 5. Ascending cholangitis and severe bi1iary pancreatitis present over1apping features and may coexist. Gramnegative bacteremia and spiking fevers are more common with infection of the biliary tract, whereas hyperbilirubinemia may be mild or absent in this situations. Appropriate antibiotic therapy should be instituted.

LOCAL COMPLICATIONS

• Pancreatic Necrosis (or abscess) ： • Pancreatic necrosis(PN) is found by dynamic CT scanning in approximately 80% of patients with clinically severe disease ( 6% of the tota1), 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 patients with PN depend crucia1ly on the presence of necrotic tissue. This question should be answered by fineneedle 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 final results of bacterial cu1tures. • Antibiotics with high penetration into pancreatic tissue 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 fistula formation. •The management of patients with sterile PN remains controversial.

• Fluid Collections ： • These occur within or around the pancreas is 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 abscesses contain 1iquid pus and may be considered to represent infected fluid collections. • Pancreatic ascites reflects involvement of peritoneal surfaces by the inf1ammatory process and, rarely, the rupture of a pancreatic duct with pancreatic juice entering into the peritoneal cavity.

• BLEEDING: • There are several causes of b1eeding during acute pancreatitis. • Hemorrhage may occur into necrotic intrapancreatic and peripancreatic tissue and into f1uid co1lections. • Brisk hemorrhage 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. Diffuse mucosa1 bleeding from antrum and duodenum is common but rarely severe.

• Final1y, 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 complication leads to gastric fundic varices.

PREVENTING RECURRENCES

• The search for the precipitating cause begins during the acute attack. • Serum calcium and triglyceride leve1s are determined. • An abdominal US examination is performed routinely. If gallstones are detected, the patient should undergo early cholecystectomy, preferably before discharge from the hospital. The absence of choledocholithiasis must be ascertained before or during this surgical procedure • At this stage, approximately 20% of patients are assumed to have idiopathic pancreatitis.

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