Acute pancreatitis is a rapidly-onset inflammation of the pancreas. Depending on its severity, it can have severe complications and high mortality despite treatment. While mild cases settle with conservative measures or endoscopy, severe cases require surgery (often more than one intervention) to contain the disease process.

Epidemiology

• Annual incidence in the US is 17 per 100,000 population. [1]
• Prevalence in the US is 80,000 cases per year.

Features

Common symptoms include:

• Severe abdominal pain often radiating through to the back.
• Nausea, vomiting and loss of appetite.
• Fever
• Shock, hemodynamic instability

Common signs include

• Grey Turner sign (hemorrhagic discoloration of the flanks), Cullen sign (hemorrhagic discoloration of the umbilicus)

• Recovery may be followed by development of pancreatic pseudocyst , pancreatic dysfunction (malabsorption due to exocrine failure) or diabetes mellitus.

Causes

• Gallstones;
• Alcohol;
• Trauma;
• Steroid use;
• Mumps;
• Autoimmune disease;
• Scorpion venom;
• Hypercalcaemia;
• Hypertriglyceridemia;
• ERCP (a form of endoscopy);
• Drugs
• Duodenal ulcer;
• Fat necrosis ;
• Pregnancy;
• Idiopathic or unknown.

The most common causes of pancreatitis, is 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

Other causes include trauma (as from a steering wheel in an automobile accident), infection (the mumps virus being the most common), drugs (the diuretics furosemide and thiazides, and some antiretrovirals are common causes, as well as azathioprine and morphine), and cancer.

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.

A common mnemonic for the causes of pancreatitis is: "I GET SMASHED"

• I - idiopathic
• G - gallstone
• E - ethanol
• T - trauma
• S - steroids
• M - mumps (paramyxovirus) and other viruses (EBV, CMV)
• A - autoimmune (PAN, SLE)
• S - scorpion sting / snake bite
• H - hypercalcemia, hyperlipidemia and hypothermia
• E - ERCP
• D - drugs (SAND - steroids & sulphonamides, azathioprine, NSAIDS, diuretics such as furosemide and thiazides, & didanosine) and duodenal ulcers

Rare causes or attributable factors include pancreas divisum, long common duct, carcinoma of the head of pancreas, ascaris blocking pancreatic outflow, ischemia from bypass surgery

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 which is most responsible for auto-digestion of the pancreas which 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 vessels 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. Photos at: Atlas of Pathology

Investigations

• Blood Investigations - Full blood count, Renal function tests, Liver Function, serum calcium, serum amylase and lipase, Arterial blood gas
• 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 amylase rises 2 to 12 hours from the onset of symptoms, and normalises within 1 week
• Serum lipase rises 4 to 8 hours from the onset of symptoms and normalises within 8 to 14 days.
• Serum amylase may be normal (in 10 % of cases) for cases of acute on chronic pancreatitis (depleted acinar cell mass) and hypertriglyceridemia
• Reasons for false positive elevated serum amylase include salivary gland disease (elevated salivary amylase) and macroamylasemia

CT abdomen

CT abdomen should not be performed before the 1st 48 hours of onset of symptoms as early CT (<48 h) may result in equivocal or normal findings.

CT Findings can be classified into the following categories for easy recall :

• Intrapancreatic - diffuse or segmental enlargement, edema, gas bubbles, pancreatic pseudocysts and phlegmons/abscesses (which present 4 to 6 wks after initial onset)
• Peripancreatic / extrapancreatic - irregular pancreatic outline, obliterated peripancreatic fat, retroperitoneal edema, fluid in the lessar sac, fluid in the left anterior pararenal space
• Locoregional - Gerota's fascia sign (thickening of inflamed Gerota's fascia, which becomes visible), pancreatic ascites, pleural effusion (seen on basal cuts of the pleural cavity), adynamic ileus,

Balthazar Scoring for the Grading of Acute Pancreatitis

• Grade A - normal CT
• Grade B - focal or diffuse enlargement of the pancreas
• Grade C - pancreatic gland abnormalities and peripancreatic inflammation
• Grade D - fluid collection in a single location
• Grade E - two or more collections and/or gas bubbles in or adjacent to pancreas

Prognostic indices

Important biochemical markers for pancreatitis are serum amylase and lipase levels. Amylase and lipase levels can rise to more than a hundred times normal levels in cases of acute pancreatitis.

In addition, in predicting the prognosis, there are several scoring indices that have been used as predictors of survival. Two such scoring systems are the Ranson and APACHE (Acute Physiology, Age and Chronic Health Evaluation) II indices.

Ranson's Criteria on Admission :

• age greater than 55 years
• a white blood cell count of > 16,000/µL
• blood glucose > 11 mmol/L (>200 mg/dL)
• serum LDH > 400 IU/L
• serum AST >250 IU/L

Ranson's Criteria after 48 hours of admission :

• fall in hematocrit by more than 10 percent
• fluid sequestration of > 6 L
• hypocalcemia (serum calcium < 1.0 mmol/L (<8.0 mg/dL)
• hypoxemia (P_O2 < 80 mmHg
• increase in BUN to >1.98 mmol/L (>5 mg/dL) after IV fluid hydration
• hypoalbuminemia (albuminm <32 g/L (<3.2 g/dL) in the first 48 hours of admission
• base deficit of >4

The prognostic implications of Ranson's criteria are as follows :

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

Acute physiology and chronic health evaluation (APACHE II) score > 12 points

• hemorrhagic peritoneal fluid
• obesity
• indicators of organ failure
• hypotension (SBP <90 mmHG) or tachycardia > 130 beat/min
• P_O2 <60 mmHg
• Oliguria (<50 mL?h) or increasing BUN and creatinine
• serum calcium < 1.90 mmol/L (<8.0 mg/dL) or serum albumin <33 g/L (<3.2.g/dL)>

Classification by severity

Acute pancreatitis can be further divided in 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 pancreatits will need intensive care therapy whereas mild pancreatits can be treated on the common ward.

Necrosis will be followed by an systemic inflammation response syndrom (SIRS) and will determine the immediate clinical course. The further clinical course is then determined by bacterial infection. SIRS is the cause bacterial translocation from the patients colon.

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

Treatment

• Antibiotics for infected necrosis and severe pancreatitis improves outcome. The drug of choice is imipenem.
• Supportive for shock.
• Pain relief

The following have no role in the management of acute pancreatitis

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

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. 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.

Recently, there has been a shift in the management paradigm from TPN (total parenteral nutrition) to early enteral feeding. The advantage of enteral feeding is that it is more physiological, prevents gut mucosal atrophy, and is free from the side effects of TPN.

ERCP

Early ERCP (endoscopic retrograde cholangiopancreatography), performed within 24 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 commonest 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:

• Conventional management - necrosectomy with simple drainage
• Closed management - necrosectomy with closed continuous lavage
• Open management - necrosectomy with planned staged reoperations at definite intervals (up to 7 reoperations in some cases)

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 phelgmon / 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

See also

• Chronic pancreatitis