Pancreatitis


Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types, acute pancreatitis and chronic pancreatitis. Signs and symptoms of pancreatitis include pain in the upper abdomen, nausea, and vomiting. The pain often goes into the back and is usually severe. In acute pancreatitis, a fever may occur; symptoms typically resolve in a few days. In chronic pancreatitis, weight loss, fatty stool, and diarrhea may occur. Complications may include infection, bleeding, diabetes mellitus, or problems with other organs.
The two most common causes of acute pancreatitis are a gallstone blocking the common bile duct after the pancreatic duct has joined; and heavy alcohol use. Other causes include direct trauma, certain medications, infections such as mumps, and tumors. Chronic pancreatitis may develop as a result of acute pancreatitis. It is most commonly due to many years of heavy alcohol use. Other causes include high levels of blood fats, high blood calcium, some medications, and certain genetic disorders, such as cystic fibrosis, among others. Smoking increases the risk of both acute and chronic pancreatitis. Diagnosis of acute pancreatitis is based on a threefold increase in the blood of either amylase or lipase. In chronic pancreatitis, these tests may be normal. Medical imaging such as ultrasound and CT scan may also be useful.
Acute pancreatitis is usually treated with intravenous fluids, pain medication, and sometimes antibiotics. For patients with severe pancreatitis who cannot tolerate normal oral food consumption, a nasogastric tube is placed in the stomach. A procedure known as an endoscopic retrograde cholangiopancreatography may be done to examine the distal common bile duct and remove a gallstone if present. In those with gallstones the gallbladder is often also removed. In chronic pancreatitis, in addition to the above, temporary feeding through a nasogastric tube may be used to provide adequate nutrition. Long-term dietary changes and pancreatic enzyme replacement may be required. Occasionally, surgery is done to remove parts of the pancreas.
Globally, in 2015 about 8.9 million cases of pancreatitis occurred. This resulted in 132,700 deaths, up from 83,000 deaths in 1990. Acute pancreatitis occurs in about 30 per 100,000 people a year. New cases of chronic pancreatitis develop in about 8 per 100,000 people a year and currently affect about 50 per 100,000 people in the United States. It is more common in men than women. Often chronic pancreatitis starts between the ages of 30 and 40 and is rare in children. Acute pancreatitis was first described on autopsy in 1882 while chronic pancreatitis was first described in 1946.

Signs and symptoms

The most common symptoms of pancreatitis are severe upper abdominal or left upper quadrant burning pain radiating to the back, nausea, and vomiting that is worse with eating. The physical examination will vary depending on severity and presence of internal bleeding. Blood pressure may be elevated by pain or decreased by dehydration or bleeding. Heart and respiratory rates are often elevated. The abdomen is usually tender but to a lesser degree than the pain itself. As is common in abdominal disease, bowel sounds may be reduced from reflex bowel paralysis. Fever or jaundice may be present. Chronic pancreatitis can lead to diabetes or pancreatic cancer. Unexplained weight loss may occur from a lack of pancreatic enzymes hindering digestion.

Complications

Early complications include shock, infection, systemic inflammatory response syndrome, low blood calcium, high blood glucose, and dehydration. Blood loss, dehydration, and fluid leaking into the abdominal cavity can lead to kidney failure. Respiratory complications are often severe. Pleural effusion is usually present. Shallow breathing from pain can lead to lung collapse. Pancreatic enzymes may attack the lungs, causing inflammation. Severe inflammation can lead to intra-abdominal hypertension and abdominal compartment syndrome, further impairing renal and respiratory function and potentially requiring management with an open abdomen to relieve the pressure.
Late complications include recurrent pancreatitis and the development of pancreatic pseudocysts—collections of pancreatic secretions that have been walled off by scar tissue. These may cause pain, become infected, rupture and bleed, block the bile duct and cause jaundice, or migrate around the abdomen. Acute necrotizing pancreatitis can lead to a pancreatic abscess, a collection of pus caused by necrosis, liquefaction, and infection. This happens in approximately 3% of cases or almost 60% of cases involving more than two pseudocysts and gas in the pancreas.

Causes

About 80 percent of pancreatitis cases are caused by gallstones or alcohol. Choledocholithiasis are the single most common cause of acute pancreatitis, and alcoholism is the single most common cause of chronic pancreatitis. Serum triglyceride levels greater than 1000 mg/dL is another cause.
The mnemonic "GET SMASHED" is often used to help clinicians and medical students remember the common causes of pancreatitis: Gallstones, Ethanol, Trauma, Steroids, Mumps, Autoimmune, Scorpion sting, Hyperlipidemia, hypothermia or hyperparathyroidism, ERCP, Drugs.

Medications

There are seven classes of medications associated with acute pancreatitis: statins, ACE inhibitors, oral contraceptives/hormone replacement therapy, diuretics, antiretroviral therapy, valproic acid, and oral hypoglycemic agents. Mechanisms of these drugs causing pancreatitis are not known exactly, but it is possible that statins have direct toxic effect on the pancreas or through the long-term accumulation of toxic metabolites. Meanwhile, ACE inhibitors cause angioedema of the pancreas through the accumulation of bradykinin. Birth control pills and HRT cause arterial thrombosis of the pancreas through the accumulation of fat. Diuretics such as furosemide have a direct toxic effect on the pancreas. Meanwhile, thiazide diuretics cause hypertriglyceridemia and hypercalcemia, where the latter is the risk factor for pancreatic stones.
HIV infection itself can cause a person to be more likely to get pancreatitis. Meanwhile, antiretroviral drugs may cause metabolic disturbances such as hyperglycemia and hypercholesterolemia, which predisposes to pancreatitis. Valproic acid may have direct toxic effect on the pancreas. Various oral hypoglycemic agents are associated with pancreatitis including metformin, but glucagon-like peptide-1 mimetics such as exenatide are more strongly associated with pancreatitis by promoting inflammation in combination with a high-fat diet.
Atypical antipsychotics such as clozapine, risperidone, and olanzapine can also cause pancreatitis.

Infection

A number of infectious agents have been recognized as causes of pancreatitis including:
Other common causes include trauma, autoimmune disease, high blood calcium, hypothermia, and endoscopic retrograde cholangiopancreatography. Pancreas divisum is a common congenital malformation of the pancreas that may underlie some recurrent cases. Diabetes mellitus type 2 is associated with a 2.8-fold higher risk.
Less common causes include pancreatic cancer, pancreatic duct stones, vasculitis, and porphyria—particularly acute intermittent porphyria and erythropoietic protoporphyria.
There is an inherited form that results in the activation of trypsinogen within the pancreas, leading to autodigestion. Involved genes may include trypsin 1, which codes for trypsinogen, SPINK1, which codes for a trypsin inhibitor, or cystic fibrosis transmembrane conductance regulator.

Diagnosis

The differential diagnosis for pancreatitis includes but is not limited to cholecystitis, choledocholithiasis, perforated peptic ulcer, bowel infarction, small bowel obstruction, hepatitis, and mesenteric ischemia.
Diagnosis requires 2 of the 3 following criteria:
Amylase and lipase are 2 enzymes produced by the pancreas. Elevations in lipase are generally considered a better indicator for pancreatitis as it has greater specificity and has a longer half life. However, both enzymes can be elevated in other disease states. In chronic pancreatitis, the fecal pancreatic elastase-1 test is a marker of exocrine pancreatic function. Additional tests that may be useful in evaluating chronic pancreatitis include hemoglobin A1C, immunoglobulin G4, rheumatoid factor, and anti-nuclear antibody.
For imaging, abdominal ultrasound is convenient, simple, non-invasive, and inexpensive. It is more sensitive and specific for pancreatitis from gallstones than other imaging modalities. However, in 25–35% of patients the view of the pancreas can be obstructed by bowel gas making it difficult to evaluate.
A contrast-enhanced CT scan is usually performed more than 48 hours after the onset of pain to evaluate for pancreatic necrosis and extrapancreatic fluid as well as predict the severity of the disease. CT scanning earlier can be falsely reassuring.
ERCP or an endoscopic ultrasound can also be used if a biliary cause for pancreatitis is suspected.