Methyldopa

Definition

Pancreatitis is an inflammation of the pancreas, an organ that is important in digestion. Pancreatitis can be acute (beginning suddenly, usually with the patient recovering fully) or chronic (progressing slowly with continued, permanent injury to the pancreas).

Description

The pancreas is located in the midline of the back of the abdomen, closely associated with the liver, stomach, and duodenum (the first part of the small intestine). The pancreas is considered a gland. A gland is an organ whose primary function is to produce chemicals that pass either into the main blood circulation (called an endocrine function), or pass into another organ (called an exocrine function). The pancreas is unusual because it has both endocrine and exocrine functions. Its endocrine function produces three hormones. Two of these hormones, insulin and glucagon, are central to the processing of sugars in the diet (carbohydrate metabolism or breakdown). The third hormone produced by the endocrine cells of the pancreas affects gastrointestinal functioning. This hormone is called vasoactive intestinal polypeptide (VIP). The pancreas' exocrine function produces a variety of digestive enzymes (trypsin, chymotrypsin, lipase, and amylase, among others). These enzymes are passed into the duodenum through a channel called the pancreatic duct. In the duodenum, the enzymes begin the process of breaking down a variety of food components, including, proteins, fats, and starches.

Acute pancreatitis occurs when the pancreas suddenly becomes inflamed but improves. Patients recover fully from the disease, and in almost 90% of cases the symptoms disappear within about a week after treatment. The pancreas returns to its normal architecture and functioning after healing from the illness. After an attack of acute pancreatitis, tissue and cells of the pancreas return to normal. With chronic pancreatitis, damage to the pancreas occurs slowly over time. Symptoms may be persistent or sporadic, but the condition does not disappear and the pancreas is permanently impaired. Pancreatic tissue is damaged, and the tissue and cells function poorly.

Causes & symptoms

There are a number of causes of acute pancreatitis. The most common, however, are gallbladder disease and alcoholism. These two diseases are responsible for more than 80% of all hospitalizations for acute pancreatitis. Other factors in the development of pancreatitis include:

• Certain drugs
• Infections
• Structural problems of the pancreatic duct and bile ducts (channels leading from the gallbladder to the duodenum)
• Injury to the abdomen resulting in injury to the pancreas (including injuries occurring during surgery)
• Abnormally high levels of circulating fats in the bloodstream
• Malfunction of the parathyroid gland, with high blood levels of calcium
• Complications from kidney transplants
• A hereditary tendency toward pancreatitis.

Pancreatitis caused by drugs accounts for about 5% of all cases. Some drugs that are definitely related to pancreatitis include:

• Azathioprine, 6-mercaptopurine (Imuran)
• Dideoxyinosine (Videx)
• Estrogens (birth control pills)
• Furosemide (Lasix)
• Pentamidine (NebuPent)
• Sulfonamides (Urobak, Azulfidine)
• Tetracycline
• Thiazide diuretics (Diuril, Enduron)
• Valproic acid (Depakote).

Some drugs that are probably related to pancreatitis include:

• Acetaminophen (Tylenol)
• Angiotensin-converting enzyme (ACE) inhibitors (Capoten, Vasotec)
• Erythromycin
• Methyldopa (Aldomet)
• Metronidazole (Flagyl, Protostat)
• Nitrofurantoin (Furadantin, Furan)
• Nonsteroidal anti-inflammatory drugs (NSAIDs) (Aleve, Naprosyn, Motrin)
• Salicylates (aspirin).

All of these causes of pancreatitis seem to have a similar mechanism in common. Under normal circumstances, many of the extremely potent enzymes produced by the pancreas are not active until they are passed into the duodenum, where contact with certain other chemicals allow them to function. In pancreatitis, something allows these enzymes to become prematurely activated, so that they actually begin their digestive functions within the pancreas. The pancreas, in essence, begins digesting itself. A cycle of inflammation begins, including swelling and loss of function. Digestion of the blood vessels in the pancreas results in bleeding. Other active pancreatic chemicals cause blood vessels to become leaky, and fluid begins leaking out of the normal circulation into the abdominal cavity. The activated enzymes also gain access to the bloodstream through leaky, eroded blood vessels, and begin circulating throughout the body.

Pain is a major symptom in pancreatitis. The pain is usually quite intense and steady, located in the upper right hand corner of the abdomen, and often described as "boring." This pain is also often felt all the way through to the patient's back. The patient's breathing may become quite shallow because deeper breathing tends to cause more pain. Relief of pain by sitting up and bending forward is characteristic of pancreatic pain. Nausea and vomiting, and abdominal swelling are all common as well. A patient will often have a slight fever, with an increased heart rate and low blood pressure.

Classic signs of shock may appear in more severely ill patients. Shock is a very serious syndrome that occurs when the volume (quantity) of fluid in the blood is very low. In shock, a patient's arms and legs become extremely cold, the blood pressure drops dangerously low, the heart rate is quite fast, and the patient may begin to experience changes in mental status.

In very severe cases of pancreatitis (called necrotizing pancreatitis), the pancreatic tissue begins to die, and bleeding increases. Due to the bleeding into the abdomen, two distinctive signs may be noted in patients with necrotizing pancreatitis. Turner's sign is a reddish-purple or greenish-brown color to the flank area (the area between the ribs and the hip bone). Cullen's sign is a bluish color around the navel.

Some of the complications of pancreatitis are due to shock. When shock occurs, all of body's major organs are deprived of blood (and, therefore, oxygen), resulting in damage. Kidney, respiratory, and heart failure are serious risks of shock. The pancreatic enzymes that have begun circulating throughout the body (as well as various poisons created by the abnormal digestion of the pancreas by those enzymes) have severe effects on the major body systems. Any number of complications can occur, including damage to the heart, lungs, kidneys, lining of the gastrointestinal tract, liver, eyes, bones, and skin. As the pancreatic enzymes work on blood vessels surrounding the pancreas, and even blood vessels located at a distance, the risk of blood clots increases. These blood clots complicate the situation by blocking blood flow in the vessels. When blood flow is blocked, the supply of oxygen is decreased to various organs and the organ can be damaged.

The pancreas may develop additional problems, even after the pancreatitis decreases. When the entire organ becomes swollen and suffers extensive cell death (pancreatic necrosis), the pancreas becomes extremely susceptible to serious infection. A local collection of pus (called a pancreatic abscess) may develop several weeks after the illness subsides, and may result in increased fever and a return of pain. Another late complication of pancreatitis, occurring several weeks after the illness begins, is called a pancreatic pseudocyst. This occurs when dead pancreatic tissue, blood, white blood cells, enzymes, and fluid leaked from the circulatory system accumulate. In an attempt to enclose and organize this abnormal accumulation, a kind of wall forms from the dead tissue and the growing scar tissue in the area. Pseudocysts cause additional abdominal pain by putting pressure on and displacing pancreatic tissue (resulting in more pancreatic damage). Pseudocysts also press on other nearby structures in the gastrointestinal tract, causing more disruption of function. Pseudocysts are life-threatening when they become infected (abscess) and when they rupture. Simple rupture of a pseudocyst causes death 14% of the time. Rupture complicated by bleeding causes death 60% of the time.

As the pancreatic tissue is increasingly destroyed in chronic pancreatitis, many digestive functions become disturbed. The quantity of hormones and enzymes normally produced by the pancreas begins to seriously decrease. Decreases in the production of enzymes result in the inability to appropriately digest food. Fat digestion, in particular, is impaired. A patient's stools become greasy as fats are passed out of the body. The inability to digest and use proteins results in smaller muscles (wasting) and weakness. The inability to digest and use the nutrients in food leads to malnutrition, and a generally weakened condition. As the disease progresses, permanent injury to the pancreas can lead to diabetes.

Diagnosis

Diagnosis of pancreatitis can be made very early in the disease by noting high levels of pancreatic enzymes circulating in the blood (amylase and lipase). Later in the disease, and in chronic pancreatitis, these enzyme levels will no longer be elevated. Because of this fact, and because increased amylase and lipase can also occur in other diseases, the discovery of such elevations are helpful but not mandatory in the diagnosis of pancreatitis. Other abnormalities in the blood may also point to pancreatitis, including increased white blood cells (occurring with inflammation and/or infection), changes due to dehydration from fluid loss, and abnormalities in the blood concentration of calcium, magnesium, sodium, potassium, bicarbonate, and sugars.

X rays or ultrasound examination of the abdomen may reveal gallstones, perhaps responsible for blocking the pancreatic duct. The gastrointestinal tract will show signs of inactivity (ileus) due to the presence of pancreatitis. Chest x rays may reveal abnormalities due to air trapping from shallow breathing, or due to lung complications from the circulating pancreatic enzyme irritants. Computed tomography scans (CT scans) of the abdomen may reveal the inflammation and fluid accumulation of pancreatitis, and may also be useful when complications like an abscess or a pseudocyst are suspected.

In the case of chronic pancreatitis, a number of blood tests will reveal the loss of pancreatic function that occurs over time. Blood sugar (glucose) levels will rise, eventually reaching the levels present in diabetes. The levels of various pancreatic enzymes will fall, as the organ is increasingly destroyed and replaced by non-functioning scar tissue. Calcification of the pancreas can also be seen on x rays. Endoscopic retrograde cholangiopancreatography (ERCP) may be used to diagnose chronic pancreatitis in severe cases. In this procedure, the doctor uses a medical instrument fitted with a fiber-optic camera to inspect the pancreas. A magnified image of the area is shown on a television screen viewed by the doctor. Many endoscopes also allow the doctor to retrieve a small sample (biopsy) of pancreatic tissue to examine under a microscope. A contrast product may also be used for radiographic examination of the area.

Treatment

Treatment of pancreatitis involves quickly and sufficiently replacing lost fluids by giving the patient new fluids through a needle inserted in a vein (intravenous or IV fluids). These IV solutions need to contain appropriate amounts of salts, sugars, and sometimes even proteins, in order to correct the patient's disturbances in blood chemistry. Pain is treated with a variety of medications. In order to decrease pancreatic function (and decrease the discharge of more potentially harmful enzymes into the bloodstream), the patient is not allowed to eat. A thin, flexible tube (nasogastric tube) may be inserted through the patient's nose and down into his or her stomach. The nasogastric tube can empty the stomach of fluid and air, which may accumulate due to the inactivity of the gastrointestinal tract. Oxygen may need to be administered by nasal prongs or by a mask.

The patient will need careful monitoring in order to identify complications that may develop. Infections (often occurring in cases of necrotizing pancreatitis, abscesses, and pseudocysts) will require antibiotics through the IV. Severe necrotizing pancreatitis may require surgery to remove part of the dying pancreas. A pancreatic abscess can be drained by a needle inserted through the abdomen and into the collection of pus (percutaneous needle aspiration). If this is not sufficient, an abscess may also require surgical removal. Pancreatic pseudocysts may shrink on their own (in 25-40% of cases) or may continue to expand, requiring needle aspiration or surgery. When diagnostic exams reveal the presence of gallstones, surgery may be necessary for their removal. When a patient is extremely ill from pancreatitis, however, such surgery may need to be delayed until any infection is treated, and the patient's condition stabilizes.

Because chronic pancreatitis often includes repeated flares of acute pancreatitis, the same kinds of basic treatment are necessary. Patients cannot take solids or fluids by mouth. They receive IV replacement fluids, receive pain medication, and are monitored for complications. Treatment of chronic pancreatitis caused by alcohol consumption requires that the patient stop drinking alcohol entirely. As chronic pancreatitis continues and insulin levels drop, a patient may require insulin injections in order to be able to process sugars in his or her diet. Pancreatic enzymes can be replaced with oral medicines, and patients sometimes have to take as many as eight pills with each meal. As the pancreas is progressively destroyed, some patients stop feeling the abdominal pain that was initially so severe. Others continue to have constant abdominal pain, and may even require a surgical procedure for relief. Drugs can be used to reduce the pain, but when narcotics are used for pain relief there is danger of the patient becoming addicted.

Prognosis

A number of systems have been developed to help determine the prognosis of an individual with pancreatitis. A very basic evaluation of a patient will allow some prediction to be made based on the presence of dying pancreatic tissue (necrosis) and bleeding. When necrosis and bleeding are present, as many as 50% of patients may die.

More elaborate systems have been created to help determine the prognosis of patients with pancreatitis. The most commonly used system identifies 11 different signs (Ranson's signs) that can be used to determine the severity of the disease. The first five categories are evaluated when the patient is admitted to the hospital:

• Age over 55 years
• Blood sugar level over 200 mg/Dl
• Serum lactic dehydrogenase over 350 IU/L (increased with increased breakdown of blood, as would occur with internal bleeding, and with heart or liver damage)
• AST over 250 µ (a measure of liver function, as well as a gauge of damage to the heart, muscle, brain, and kidney)
• White blood count over 16,000 µL

The next six of Ranson's signs are reviewed 48 hours after admission to the hospital. These are:

• Greater than 10% decrease in hematocrit (a measure of red blood cell volume)
• Increase in BUN greater than 5 mg/dL (blood urea nitrogen, an indicator of kidney function)
• Blood calcium less than 8 mg/dL
• PaO2 less than 60 mm Hg (a measure of oxygen in the blood)
• Base deficit greater than 4 mEg/L (a measure of change in the normal acidity of the blood)
• Fluid sequestration greater than 6 litres (an estimation of the quantity of fluid that has leaked out of the blood circulation and into other body spaces).

Once a doctor determines how many of Ranson's signs are present and gives the patient a score, the doctor can better predict the risk of death. The more signs present, the greater the chance of death. A patient with less than three positive Ranson's signs has a less than 5% chance of dying. A patient with three to four positive Ranson's signs has a 15-20% chance of dying.

The results of a CT scan can also be used to predict the severity of pancreatitis. Slight swelling of the pancreas indicates mild illness. Significant swelling, especially with evidence of destruction of the pancreas and/or fluid build-up in the abdominal cavity, indicates more severe illness. With severe illness, there is a worse prognosis.

Prevention

Alcoholism is essentially the only preventable cause of pancreatitis. Patients with chronic pancreatitis must stop drinking alcohol entirely. The drugs that cause or may cause pancreatitis should also be avoided.

Key Terms

Abscess

A pocket of infection; pus.

Acute

Of short and sharp course. Illnesses that are acute appear quickly and can be serious or life-threatening. The illness ends and the patient usually recovers fully.

Chronic

Of long duration and slow progression. Illnesses that are chronic develop slowly over time, and do not end. Symptoms may be continual or intermittent, but the patient usually has the condition for life.

Diabetes

A disease characterized by an inability to process sugars in the diet, due to a decrease in or total absence of insulin production. May require injections of insulin before meals to aid in the metabolism of sugars.

Duodenum

The first section of the small intestine that receives partly digested material from the stomach.

Endocrine

A system of organs that produces chemicals that go into the bloodstream to reach other organs whose functioning they affect.

Enzyme

A chemical that speeds up or makes a particular chemical reaction more efficient. In the digestive system, enzymes are involved in breaking down large food molecules into smaller molecules that can be processed and utilized by the body.

Exocrine

A system of organs that produces chemicals that go through a duct (or tube) to reach other organs whose functioning they affect.

Gland

Collections of tissue that produce chemicals needed for chemical reactions elsewhere in the body.

Hormone

A chemical produced in one part of the body that travels to another part of the body in order to exert an effect.

Further Reading

For Your Information

Books

• Greenberger, Norton J., Phillip P. Toskes, and Kurt J. Isselbacher. "Acute and Chronic Pancreatitis." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998, pp. 1741-1751.

  Periodicals

• Amann, Stephen, et al. "Pancreatitis: Diagnostic and Therapeutic Interventions." Patient Care 31, no. 11 (June 15, 1997): 200+.
• Apte, Minoti V., et al. "Alcohol-Related Pancreatic Damage: Mechanisms and Treatment." Alcohol Health and Research World 21, no. 1 (Winter 1997): 13+.
• Baillie, John. "Treatment of Acute Biliary Pancreatitis." The New England Journal of Medicine 336, no. 4 (January 23, 1997): 286+.
• Meissner, Judith E. "Caring for Patients with Pancreatitis." Nursing 27, no. 10 (October 1997): 50+.
• Ruth-Sahd, Lisa A. "Acute Pancreatitis: How to Stop This Pathologic Process Before Systemic Complications Occur." American Journal of Nursing 96, no. 6 (June 1996): 38+.
• Steer, Michael L., et al. "Chronic Pancreatitis." The New England Journal of Medicine 332, no. 22 (June 1, 1995): 1482+.

  Organizations

• National Digestive Diseases Information Clearinghouse. 2 Information Way, Bethesda, MD 20892-3570.

Gale Encyclopedia of Medicine. Gale Research, 1999.