Acute pancreatitis

Acute pancreatitis or acute pancreatic necrosis is a sudden inflammation of the pancreas. Depending on its severity, it can have severe complications and high mortality despite treatment. While mild cases are often successfully treated with conservative measures, such as NPO (nil per os or nothing by mouth (NBM)) and IV fluid rehydration, severe cases may require admission to the ICU or even surgery (often requiring more than one intervention) to deal with complications of the disease process.

Symptoms and signs

The most common symptoms and signs include:

Severe epigastric pain radiating to the back

Nausea, vomiting, diarrhea and loss of appetite

Fever/chills

Hemodynamic instability, which include shock

Signs which are less common, and indicate severe disease, include:

Grey-Turner's sign (hemorrhagic discoloration of the flanks)

Cullen's sign (hemorrhagic discoloration of the umbilicus)

Grünwald sign (appearance of ecchymosis, large bruise, around the umbilicus due to local toxic lesion of the vessels)

Körte's sign (pain or resistance in the zone where the head of pancreas is located (in epigastrium, 6–7 cm above the umbilicus)

Kamenchik's sign (pain with pressure under the xiphoid process)

Mayo-Robson's sign (pain while pressing at the top of the angle lateral to the Erector spinae muscles and below the left 12th rib (left costovertebral angle (CVA)) Mayo-Robson's point - a point on border of inner 2/3 with the external 1/3 of the line that represents the bisection of the left upper abdominal quadrant, where tenderness on pressure exists in disease of the pancreas. At this point the tail of pancreas is projected on the abdominal wall.

Other conditions to consider are:

Pancreatic pseudocyst

Pancreatic dysfunction (diabetes mellitus; malabsorption due to exocrine failure)

Pancreatic cancer

Although these are common symptoms, they are not always present. Simple abdominal pain may be the sole symptom.

Causes

Most common causes

A common mnemonic for the causes of pancreatitis spells "I get smashed", an allusion to heavy drinking (one of the many causes):

I - idiopathic. Thought to be hypertensive sphincter or microlithiasis.

G - gallstone. Gallstones that travel down the common bile duct and which subsequently get stuck in the Ampulla of Vater can cause obstruction in the outflow of pancreatic juices from the pancreas into the duodenum. The backflow of these digestive juices causes lysis (dissolving) of pancreatic cells and subsequent pancreatitis.

E - ethanol (alcohol)

T - trauma

S - steroids

M - mumps (paramyxovirus) and other viruses (Epstein-Barr virus, Cytomegalovirus)

A - autoimmune disease (Polyarteritis nodosa, Systemic lupus erythematosus)

S - scorpion sting (e.g. Tityus trinitatis), also snake bites and brown recluse spider bites

H - hypercalcemia, hyperlipidemia/hypertriglyceridemia and hypothermia

E - ERCP (Endoscopic Retrograde Cholangio-Pancreatography - a procedure that combines endoscopy and fluoroscopy)

D - drugs (SAND - steroids & sulfonamides, azathioprine, NSAIDS, diuretics such as furosemide and thiazides, & didanosine) and duodenal ulcers. As an example, the U.S. Food and Drug Administration (FDA) reported in August 2008 six cases of hemorrhagic or necrotizing pancreatitis in patients taking Byetta, a diabetes medicine approved in 2005. Two patients died. The FDA previously reported 30 other cases of pancreatitis. Patients taking Byetta should promptly seek medical care if they experience unexplained severe abdominal pain with or without nausea and vomiting.

This mnemonic is also roughly arranged according to the frequency of its causes. Thus: Gallstone pancreatitis is more common than pancreatitis caused by alcohol, trauma, or steroids.

Less common causes

pancreas divisum

long common duct

carcinoma of the head of pancreas, and other cancer

ascaris blocking pancreatic outflow

chinese liver fluke

ischemia from bypass surgery

fatty necrosis

pregnancy

infections other than mumps, including varicella zoster

repeated marathon running.

cystic fibrosis

valproic acid

Anorexia or bulimia

Familial

Codeine reaction

Causes by demographic

The most common causes of pancreatitis, are as follows :

Western countries - chronic alcoholism and gallstones accounting for more than 85% of all cases

Eastern countries - gallstones

Children - trauma

Adolescents and young adults - mumps

Pathogenesis

The exocrine pancreas produces a variety of enzymes, such as proteases, lipases, and saccharidases. These enzymes contribute to food digestion by breaking down food tissues. In acute pancreatitis, the worst offender among these enzymes may well be the protease trypsinogen which converts to the active trypsin. Trypsin is most responsible for auto-digestion of the pancreas which in turn causes the pain and complications of pancreatitis.

Histopathology

The acute pancreatitis (acute hemorrhagic pancreatic necrosis) is characterized by acute inflammation and necrosis of pancreas parenchyma, focal enzymic necrosis of pancreatic fat and vessel necrosis - hemorrhage. These are produced by intrapancreatic activation of pancreatic enzymes. Lipase activation produces the necrosis of fat tissue in pancreatic interstitium and peripancreatic spaces. Necrotic fat cells appear as shadows, contours of cells, lacking the nucleus, pink, finely granular cytoplasm. It is possible to find calcium precipitates (hematoxylinophilic). Digestion of vascular walls results in thrombosis and hemorrhage. Inflammatory infiltrate is rich in neutrophils.

Investigations and diagnosis

Blood Investigations - Full blood count, Renal function tests, Liver Function, serum calcium, serum amylase and lipase, Arterial blood gas, Trypsin-Selective Test

Imaging - Chest Xray (for exclusion of perforated viscus), Abdominal Xrays (for detection of "sentinel loop" dilated duodenum sign, and gallstones which are radioopaque in 10%) and CT abdomen

Amylase and lipase, serum calcium, glycosuria

* Elevated serum AMYLASE and LIPASE levels, in combination with severe abdominal pain, often trigger the initial diagnosis of acute pancreatitis.

Serum lipase rises 4 to 8 hours from the onset of symptoms and normalizes within 7 to 14 days after treatment.

Serum amylase may be normal (in 10% of cases) for cases of acute or chronic pancreatitis (depleted acinar cell mass) and hypertriglyceridemia.

Reasons for false positive elevated serum amylase include salivary gland disease (elevated salivary amylase) and macroamylasemia.

If the lipase level is about 2.5 to 3 times that of amylase, it is an indication of pancreatitis due to alcohol.

*DECREASED serum Calcium

*Glycosuria

Regarding selection on these tests, two practice guidelines state:

: "It is usually not necessary to measure both serum amylase and lipase. Serum lipase may be preferable because it remains normal in some nonpancreatic conditions that increase serum amylase including macroamylasemia, parotitis, and some carcinomas. In general, serum lipase is thought to be more sensitive and specific than serum amylase in the diagnosis of acute pancreatitis"

: "Although amylase is widely available and provides acceptable accuracy of diagnosis, where lipase is available it is preferred for the diagnosis of acute pancreatitis (recommendation grade A)"

Most (PMID 15943725, PMID 11552931, PMID 2580467, PMID 2466075, PMID 9436862), but not all (PMID 11156345, PMID 8945483) individual studies support the superiority of the lipase. In one large study, there were no patients with pancreatitis who had an elevated amylase with a normal lipase. Another study found that the amylase could add diagnostic value to the lipase, but only if the results of the two tests were combined with a discriminant function equation.

Computed tomography

Regarding the need for computed tomography, practice guidelines state:

: 2006: "Many patients with acute pancreatitis do not require a CT scan at admission or at any time during the hospitalization. For example,a CT scan is usually not essential in patients with recurrent mild pancreatitis caused by alcohol. A reasonable indication for a CT scan at admission (but not necessarily a CT with IV contrast) is to distinguish acute pancreatitis from another serious intra-abdominal condition, such as a perforated ulcer." magnetic resonance imaging (MRI) has become increasingly valuable as a tool for the visualization of the pancreas, particularly of pancreatic fluid collections and necrotized debris. Additional utility of MRI includes its indication for imaging of patients with an allergy to CT's contrast material, and an overall greater sensitivity to hemorrhage, vascular complications, pseudoaneurysms, and venous thrombosis.

Another advantage of MRI is its utilization of magnetic resonance cholangiopancreatography (MRCP) sequences. MRCP provides useful information regarding the etiology of acute pancreatitis, i.e., the presence of tiny biliary stones (choledocholithiasis or cholelithiasis) and duct anomalies.

Endoscopic ultrasound

Classification by severity

Progression of pathophysiology

Acute pancreatitis patients recover in maximum cases. Some may develop abscess, pseudocyst or duodenal obstruction. In 5 percent cases, it may result in ARDS(acute respiratory distress syndrome), DIC(disseminated intravascular coagulation), etc. Acute pancreatitis can be further divided into mild and severe pancreatitis. Mostly the Atlanta classification (1992) is used. In severe pancreatitis serious amount of necrosis determine the further clinical outcome. About 20% of the acute pancreatitis are severe with a mortality of about 20%. This is an important classification as severe pancreatitis will need intensive care therapy whereas mild pancreatitis can be treated on the common ward.

Necrosis will be followed by a systemic inflammatory response syndrome (SIRS) and will determine the immediate clinical course. The further clinical course is then determined by bacterial infection. SIRS is the cause of bacterial (Gram negative) translocation from the patients colon.

There are several ways to help distinguish between these two forms. One is the above mentioned Ranson Score.

Prognostic indices

In predicting the prognosis, there are several scoring indices that have been used as predictors of survival. Two such scoring systems are the Ranson criteria and APACHE II (Acute Physiology and Chronic Health Evaluation) indices. Most, but not all studies report that the Apache score may be more accurate. In the negative study of the Apache II,

Ranson Score

Ranson criteria is a clinical prediction rule for predicting the severity of acute pancreatitis. It was introduced in 1974.[1]

At admission

age in years > 55 years

white blood cell count > 16000 cells/mm3

blood glucose > 10 mmol/L (> 200 mg/dL)

serum AST > 250 IU/L

serum LDH > 350 IU/L

At 48 hours

Calcium (serum calcium < 2.0 mmol/L (< 8.0 mg/dL)

Hematocrit fall > 10%

Oxygen (hypoxemia PO2 < 60 mmHg)

BUN increased by 1.8 or more mmol/L (5 or more mg/dL) after IV fluid hydration

Base deficit (negative base excess) > 4 mEq/L

Sequestration of fluids > 6 L

The criteria for point assignment is that a certain breakpoint be met at anytime during that 48 hour period, so that in some situations it can be calculated shortly after admission. It is applicable to both gallstone and alcoholic pancreatitis.

Alternatively, pancreatitis can be diagnosed by meeting any of the following:[2]

Ranson's score

Ranson's score of ≥ 8 Organ failure Substantial pancreatic necrosis (at least 30% glandular necrosis according to contrast-enhanced CT)

Interpretation If the score ≥ 3, severe pancreatitis likely. If the score < 3, severe pancreatitis is unlikely Or

Score 0 to 2 : 2% mortality Score 3 to 4 : 15% mortality Score 5 to 6 : 40% mortality Score 7 to 8 : 100% mortality

Mnemonic for memorizing Ranson's criteria At admission: "GA LAW" (glucose, age, LDH, AST, WBC count) At 48 hours: "C Hobbs" (i.e. Calvin and Hobbes): (calcium, hematocrit, O2, BUN, Base deficit, sequestration (of fluid) greater than 6 L (see: fluid balance)

APACHE

"Acute Physiology And Chronic Health Evaluation" (APACHE II) score > 8 points predicts 11% to 18% mortality the Computed Tomography Severity Index (CTSI) is a grading system used to determine the severity of acute pancreatitis. The numerical CTSI has a maximum of ten points, and is the sum of the Balthazar grade points and pancreatic necrosis grade points:

Balthazar Grade

Necrosis Score

CTSI's staging of acute pancreatitis severity has been shown by a number of studies to provide more accurate assessment than APACHE II, Ranson, and C-reactive protein (CRP) level. However, a few studies indicate that CTSI is not significantly associated with the prognosis of hospitalization in patients with pancreatic necrosis, nor is it an accurate predictor of AP severity.

Treatment

Pain control

Originally it was thought that analgesia should not be provided by morphine because it may cause spasm of the sphincter of Oddi and worsen the pain, so the drug of choice was meperidine. However, due to lack of efficacy and risk of toxicity of meperidine, more recent studies have found morphine the analgesic of choice. Meperidine may still be used by some practitioners in more minor cases, or where morphine is contraindicated.

Bowel rest

In the management of acute pancreatitis, the treatment is to stop feeding the patient, giving him or her nothing by mouth, giving intravenous fluids to prevent dehydration, and sufficient pain control. As the pancreas is stimulated to secrete enzymes by the presence of food in the stomach, having no food pass through the system allows the pancreas to rest. Approximately 20% of patients have a relapse of pain during acute pancreatitis. Approximately 75% of relapses occur within 48 hours of oral refeeding.

The incidence of relapse after oral refeeding may be reduced by post-pyloric enteral rather than parenteral feeding prior to oral refeeding. However, the one study in the meta-analysis that used a quinolone, and a subsequent randomized controlled trial that studied ciprofloxacin were both negative.

Carbapenems

An early randomized controlled trial of imipenem 0.5 gram intravenously every eight hours for two weeks showed a reduction in from pancreatic sepsis from 30% to 12%.

Another randomized controlled trial with patients who had at least 50% pancreatic necrosis found a benefit from imipenem compared to pefloxacin with a reduction in infected necrosis from 34% to 20%

A subsequent randomized controlled trial that used meropenem 1 gram intravenously every 8 hours for 7 to 21 days stated no benefit; however, 28% of patients in the group subsequently required open antibiotic treatment vs. 46% in the placebo group. In addition, the control group had only 18% incidence of peripancreatic infections and less biliary pancreatitis that the treatment group (44% versus 24%).

Summary

In summary, the role of antibiotics is controversial. One recent expert opinion (prior to the last negative trial of meropenem

ERCP

Early ERCP (endoscopic retrograde cholangiopancreatography), performed within 24 to 72 hours of presentation, is known to reduce morbidity and mortality. The indications for early ERCP are as follows :

Clinical deterioration or lack of improvement after 24 hours

Detection of common bile duct stones or dilated intrahepatic or extrahepatic ducts on CT abdomen

The disadvantages of ERCP are as follows :

ERCP precipitates pancreatitis, and can introduce infection to sterile pancreatitis

The inherent risks of ERCP i.e. bleeding

It is worth noting that ERCP itself can be a cause of pancreatitis.

Surgery

Surgery is indicated for (i) infected pancreatic necrosis and (ii) diagnostic uncertainty and (iii) complications. The most common cause of death in acute pancreatitis is secondary infection. Infection is diagnosed based on 2 criteria

Gas bubbles on CT scan (present in 20 to 50% of infected necrosis)

Positive bacterial culture on FNA (fine needle aspiration, usually CT or US guided) of the pancreas.

Surgical options for infected necrosis include:

Minimally invasive management - necrosectomy through small incision in skin (left flank) or stomach

Conventional management - necrosectomy with simple drainage

Closed management - necrosectomy with closed continuous postoperative lavage

Open management - necrosectomy with planned staged reoperations at definite intervals (up to 20+ reoperations in some cases)

Other measures

Pancreatic enzyme inhibitors are not proven to work. The use of octreotide has not been shown to improve outcome.

Complications

Complications can be systemic or locoregional.

Systemic complications include ARDS, multiple organ dysfunction syndrome, DIC, hypocalcemia (from fat saponification), hyperglycemia and insulin dependent diabetes mellitus (from pancreatic insulin producing beta cell damage)

Locoregional complications include pancreatic pseudocyst and phlegmon / abscess formation, splenic artery pseudoaneurysms, hemorrhage from erosions into splenic artery and vein, thrombosis of the splenic vein, superior mesenteric vein and portal veins (in descending order of frequency), duodenal obstruction, common bile duct obstruction, progression to chronic pancreatitis

Epidemiology

Annual incidence in the U.S. is 18 per 100,000 population. In a European cross-sectional study, incidence of acute pancreatits increased from 12.4 to 15.9 per 100,000 annually from 1985 to 1995; however, mortality remained stable as a result of better outcomes. Another study showed a lower incidence of 9.8 per 100,000 but a similar worsening trend (increasing from 4.9 in 1963-74) over time.

See also

Chronic pancreatitis

References

External links

VIDEO: Complications of Acute Pancreatitis: Management and Outcomes, Mark Malangoni, MD, speaks at the University of Wisconsin School of Medicine and Public Health (2007)

Medical Information and Treatment of Acute Pancreatitis

Mechanisms of Disease: Etiology and Pathophysiology of Acute Pancreatitis

Pathology Atlas image.

Acute Pancreatitis PrimeHealthChannel

Category:Medical emergencies Category:Disorders of gallbladder, biliary tract and pancreas Category:Surgery Category:Inflammations