The pancreas is an organ located in the upper abdomen, behind the stomach and next to the spleen. It is connected by a duct to the small intestine. The pancreas is responsible for the production of insulin, which regulates blood sugar (endocrine function), and enzymes that digest carbohydrates, fat, and protein (exocrine function). Digestive enzymes are made in the pancreas, but, to prevent them from digesting the pancreas, they are not activated until they enter the small intestine. When the pancreas becomes inflamed, however, these enzymes are activated prematurely and begin to digest the pancreas itself. Damage to the pancreas attracts cells of the immune system, causing further pancreatic injury. Pancreatitis is classified as acute (an episode or “attack” of inflammation), or chronic (permanent damage to the pancreas resulting from repeated or unresolving inflammation).
Persons with acute pancreatitis typically present with the abrupt onset of constant pain in the epigastrium (the mid-upper portion of the abdomen), with radiation of the pain to the back. The pain is often described as a severe and “penetrating” pain that is improved by leaning forward and worsened by lying down. Eating exacerbates the pain. Nausea and vomiting frequently occur with the attack, as may fever.
Diagnosis
The diagnosis of acute pancreatitis is made by evaluation of the patient’s symptoms (described above), physical examination, and blood tests.(1-3) Radiologic tests may be helpful in determining the cause and assessing the severity of the pancreatitis.
The physical examination in a person with acute pancreatitis is notable for tenderness in the epigastrium. The abdomen is often distended with decreased bowel sounds, indicating that the bowel is inactive because it is adjacent to the inflamed pancreas. Patients may have a fever and, if the pancreatitis is severe, low blood pressure and an elevated heart rate, indicating shock.
Several blood tests can be helpful in the diagnosis of pancreatitis. The most important are amylase and lipase, which are enzymes made by the pancreas and normally detected in the blood in small amounts. In acute pancreatitis, large amounts of amylase and lipase are released into the blood, and elevated levels of amylase and lipase are a hallmark of acute pancreatitis. The white blood cell count and C-reactive protein (CRP), markers of inflammation, are also elevated. When acute pancreatitis is caused by a gallstone, blood tests that reflect liver injury may be elevated.
For many patients with acute pancreatitis, radiologic imaging is not necessary. There are several instances, however, when imaging can be helpful (Figures 1 and 2). An abdominal ultrasound can be used to detect gallstones (a common cause of acute pancreatitis) and determine whether the duct connecting the pancreas and the small intestine is dilated, indicating blockage. In patients with severe acute pancreatitis a computed tomography (CT) scan can be used to detect pancreatic “necrosis” (dead pancreatic tissue) or fluid collections around the pancreas, which indicate a poor prognosis (Figure 3).
Other medical conditions may cause symptoms and findings similar to those of acute pancreatitis. These include peptic ulcer disease, biliary pain from gallstones, and inflammation of the gallbladder (cholecystitis). In addition, obstruction of the small intestine or decreased blood flow to the bowel (“mesenteric ischemia”) can cause abdominal pain, nausea, and vomiting. Conditions outside of the gastrointestinal tract, including acute myocardial infarction (heart attack) and a ruptured aortic aneurysm (a “blowout” of the aorta) or aortic dissection (tear of the aorta), can also present similarly to acute pancreatitis.
Causes
Gallstones and alcohol are the two most common causes of acute pancreatitis. Gallstones are formed in the gallbladder and can travel into the bile duct, which connects the liver to the small intestine. The pancreatic duct joins the bile duct just before the entry into the small intestine. Occasionally, stones can become lodged in the bile duct, leading to obstruction. When this occurs, bile and pancreatic enzymes back up into the pancreas, causing inflammation and damage.
Gallstone pancreatitis can be distinguished from other causes of acute pancreatitis by several characteristics. Blood tests often show not only inflammation of the pancreas, but also inflammation of the liver, since the blocked bile duct can lead to liver injury. In addition, ultrasound of the abdomen can identify gallstones and can show a blocked, and therefore dilated, bile duct.
Alcohol stimulates excess levels of pancreatic enzymes that injure the pancreas, leading to pancreatitis. Alcohol often leads to chronic pancreatitis as well as to attacks of acute pancreatitis (see below).
A number of medications may cause acute pancreatitis. Those most frequently implicated include aminosalicylates (anti-inflammatory agents), L-asparaginase (an anti-cancer agent), azathioprine (an immunosuppressant agent), didanosine (an antiviral agent), estrogen, and furosemide (a diuretic). Other medications have been reported to cause acute pancreatitis, but these associations are less certain.
Acute Pancreatitis
SymptomsPersons with acute pancreatitis typically present with the abrupt onset of constant pain in the epigastrium (the mid-upper portion of the abdomen), with radiation of the pain to the back. The pain is often described as a severe and “penetrating” pain that is improved by leaning forward and worsened by lying down. Eating exacerbates the pain. Nausea and vomiting frequently occur with the attack, as may fever.
Diagnosis
The diagnosis of acute pancreatitis is made by evaluation of the patient’s symptoms (described above), physical examination, and blood tests.(1-3) Radiologic tests may be helpful in determining the cause and assessing the severity of the pancreatitis.
The physical examination in a person with acute pancreatitis is notable for tenderness in the epigastrium. The abdomen is often distended with decreased bowel sounds, indicating that the bowel is inactive because it is adjacent to the inflamed pancreas. Patients may have a fever and, if the pancreatitis is severe, low blood pressure and an elevated heart rate, indicating shock.
Several blood tests can be helpful in the diagnosis of pancreatitis. The most important are amylase and lipase, which are enzymes made by the pancreas and normally detected in the blood in small amounts. In acute pancreatitis, large amounts of amylase and lipase are released into the blood, and elevated levels of amylase and lipase are a hallmark of acute pancreatitis. The white blood cell count and C-reactive protein (CRP), markers of inflammation, are also elevated. When acute pancreatitis is caused by a gallstone, blood tests that reflect liver injury may be elevated.
For many patients with acute pancreatitis, radiologic imaging is not necessary. There are several instances, however, when imaging can be helpful (Figures 1 and 2). An abdominal ultrasound can be used to detect gallstones (a common cause of acute pancreatitis) and determine whether the duct connecting the pancreas and the small intestine is dilated, indicating blockage. In patients with severe acute pancreatitis a computed tomography (CT) scan can be used to detect pancreatic “necrosis” (dead pancreatic tissue) or fluid collections around the pancreas, which indicate a poor prognosis (Figure 3).
Other medical conditions may cause symptoms and findings similar to those of acute pancreatitis. These include peptic ulcer disease, biliary pain from gallstones, and inflammation of the gallbladder (cholecystitis). In addition, obstruction of the small intestine or decreased blood flow to the bowel (“mesenteric ischemia”) can cause abdominal pain, nausea, and vomiting. Conditions outside of the gastrointestinal tract, including acute myocardial infarction (heart attack) and a ruptured aortic aneurysm (a “blowout” of the aorta) or aortic dissection (tear of the aorta), can also present similarly to acute pancreatitis.
Causes
Gallstones and alcohol are the two most common causes of acute pancreatitis. Gallstones are formed in the gallbladder and can travel into the bile duct, which connects the liver to the small intestine. The pancreatic duct joins the bile duct just before the entry into the small intestine. Occasionally, stones can become lodged in the bile duct, leading to obstruction. When this occurs, bile and pancreatic enzymes back up into the pancreas, causing inflammation and damage.
Gallstone pancreatitis can be distinguished from other causes of acute pancreatitis by several characteristics. Blood tests often show not only inflammation of the pancreas, but also inflammation of the liver, since the blocked bile duct can lead to liver injury. In addition, ultrasound of the abdomen can identify gallstones and can show a blocked, and therefore dilated, bile duct.
Alcohol stimulates excess levels of pancreatic enzymes that injure the pancreas, leading to pancreatitis. Alcohol often leads to chronic pancreatitis as well as to attacks of acute pancreatitis (see below).
A number of medications may cause acute pancreatitis. Those most frequently implicated include aminosalicylates (anti-inflammatory agents), L-asparaginase (an anti-cancer agent), azathioprine (an immunosuppressant agent), didanosine (an antiviral agent), estrogen, and furosemide (a diuretic). Other medications have been reported to cause acute pancreatitis, but these associations are less certain.
Elevated blood levels of triglycerides (a chemical form of fat in the blood) can cause acute pancreatitis when the level exceeds 1000 mg/dL. Levels this high can be seen in patients with familial syndromes such as hyperlipidemia type 5.
Elevated blood levels of calcium, often caused by hyperparathyroidism (an overactive parathyroid gland), can result in acute pancreatitis. High levels of calcium may activate trypsinogen, an enzyme in the pancreas, to cause pancreatic damage. In addition, calcium may deposit in the pancreatic duct, causing obstruction and back-up of enzymes in the pancreas.
Abdominal trauma following a motor vehicle collision, fall, or assault can lead to pancreatic injury and pancreatitis. A second type of trauma can be induced by endoscopic retrograde cholangiopancreatography (ERCP), a procedure in which a camera at the end of a scope is inserted through the mouth into the small intestine and dye is injected via a catheter to visualize the pancreatic and bile ducts. Instrumenting the pancreas with this scope can cause inflammation resulting in pancreatitis.
While rare, a number of infections have been associated with acute pancreatitis. These include infections caused by human immunodeficiency virus (HIV), hepatitis B virus, Coxsackie A virus, and mumps virus, and by the organisms that cause tuberculosis, mycoplasma, toxoplasmosis, leptospirosis, salmonellosis, and legionella infection.
Finally, several congenital or acquired abnormalities can cause obstruction to pancreatic drainage. These include pancreatic divisum (a divided pancreatic duct), choledochal (bile duct) cysts, benign or cancerous strictures (narrowing of the duct), or cancerous masses. Thickened pancreatic secretions, as occur in cystic fibrosis, can obstruct the outflow of pancreatic enzymes from the pancreatic duct and rarely lead to pancreatitis, in addition to causing insufficient delivery of pancreatic enzymes to the small intestine.
Treatment
Patients with acute pancreatitis are generally hospitalized and prescribed nothing by mouth in order to rest the pancreas. Fasting allows the pancreas to take a break from secreting digestive enzymes. If fasting is prolonged, nutrition can be provided via a tube inserted through the nose into the intestine beyond the pancreas; this prevents food in the small intestine from activating enzymes from the pancreas, thereby worsening pancreatitis. Intravenous fluids are necessary to counteract the fluid losses that occur from vomiting, fever, and leakage of fluid out of the abdominal blood vessels adjacent to the pancreas (“third spacing”). Pain from acute pancreatitis can be severe and often requires control with intravenous or intramuscular narcotics.
For certain causes of acute pancreatitis, specific treatments are prescribed. In gallstone pancreatitis, ERCP can be a valuable tool to remove stones that have lodged in the bile duct and cause obstruction to bile flow, often resulting in jaundice or infection of the bile (cholangitis).
In pancreatitis from elevated blood triglyceride levels, fasting alone can reduce blood triglyceride levels significantly; medication to lower blood triglyceride levels may be prescribed when the patient resumes oral feedings. Reduction of elevated blood glucose levels can also reduce the level of triglyceride levels in the blood. If these measures do not decrease triglycerides, plasmapheresis, a technique by which triglycerides are filtered from the blood, can be undertaken.
Prognosis
Several scoring systems have been developed to predict the severity of an attack of pancreatitis. Ranson’s criteria, first developed in 1974, take into account clinical signs and laboratory values to predict the severity of pancreatitis. Criteria used include a patient’s age, white blood cell count, blood aspartate aminotransferase level (a marker of liver injury), and lactate dehydrogenase level (a marker of tissue injury). Calculating the full Ranson score requires values recorded when the patient first presents for medical care and additional laboratory results 48 hours later. These criteria include the hematocrit value (red blood cell level), serum calcium level, partial pressure of oxygen in the blood, amount of fluid that has leaked into the abdomen (fluid sequestration), base deficit (reflecting the amount of acid in the blood), and blood urea nitrogen level (a measure of kidney function).
A second scoring system, the Acute Physiology and Chronic Health Evaluation (APACHE), has an advantage over Ranson’s criteria in that it can be fully calculated at the time of admission to the hospital. This scoring system includes variables such as age and blood tests, similar to Ranson’s criteria, and also takes into account a patient’s previous medical conditions and vital signs.
Complications
Severe pancreatitis results not only in damage to the pancreas, but also, in some cases, in harm to other organs, leading to multi-system organ failure. The lungs in particular are sensitive to pancreatic inflammation, and severe lung inflammation (acute respiratory distress syndrome) may result in the need for mechanical ventilation. In addition, shock, gastrointestinal bleeding, and acute kidney failure can develop. When these complications occur, intensive care is often required, along with medications to support blood pressure.
Pancreatic necrosis is a complication of severe acute pancreatitis that may occur one to two weeks after a patient first comes to medical attention. Necrosis occurs when pancreatic inflammation becomes so severe that portions of the pancreas are permanently destroyed. In the most severe cases, the dead tissue becomes infected. Pancreatic necrosis is suspected when a patient has unresolving or worsening abdominal pain, fever, or an elevated white blood cell count. Diagnosis is based on findings of a CT scan of the pancreas following intravenous infusion of a contrast (dye) agent. Definitive evidence of infected pancreatic necrosis requires a fine-needle aspiration of the area of necrosis in the pancreas. Treatment of infected pancreatic necrosis involves antibiotics and surgery to remove (“debride”) the infected area of the pancreas. Even with appropriate treatment, infected pancreatic necrosis has a high mortality rate. Patients with pancreatic necrosis that is uninfected may be managed medically without the need for surgery; surgery can be undertaken if medical management does not lead to improvement.
A pseudocyst is a late complication of acute pancreatitis. A pseudocyst is a cavity in the pancreas (it looks like a cyst) that results from the action of pancreatic enzymes that leak into the pancreas because of a disruption in the pancreatic duct. These collections can be asymptomatic or can cause abdominal pain, bowel obstruction, intestinal bleeding, or infection. When these conditions occur, drainage or surgical resection of the pseudocyst is necessary.
As is discussed in the next section, acute pancreatitis, especially when recurrent, can lead to chronic pancreatitis.
Chronic Pancreatitis
Chronic pancreatitis is the result of recurrent bouts of inflammation that lead to permanent damage and scarring of the pancreas. The exocrine and endocrine cells of the pancreas as well as the pancreatic duct can be damaged.Symptoms
Chronic pancreatitis often presents with recurrent bouts of upper abdominal pain associated with loss of appetite, nausea, and vomiting. The pain can be unrelenting, and associated with weight loss. Intestinal malabsorption of nutrients such as protein and fat can occur in patients with chronic pancreatitis as a result of reduced production of pancreatic enzymes. The inability to digest fat leads to chronic diarrhea with stools that are bulky, greasy, and floating (steatorrhea).
The pancreas serves an important role in the regulation of blood sugar levels by making insulin. When the pancreas is severely and chronically damaged, its ability to make insulin can be compromised or completely eliminated. Thus, diabetes mellitus can occur and may be difficult to control.
Diagnosis
As in acute pancreatitis, the pancreatic enzymes amylase and lipase can be elevated during acute flares of chronic pancreatitis. However, with chronic pancreatitis the blood levels of these enzymes may remain normal, even during acute flares. For patients with diarrhea or weight loss, stool may be collected to measure the fat content, which is increased in pancreatic insufficiency.
ERCP or a radiologic test known as magnetic resonance cholangiopancreatography (MRCP) can be a valuable tool for evaluating both the pancreas and its ducts for evidence of chronic pancreatitis. CT scanning may also demonstrate changes of chronic pancreatitis including a dilated pancreatic duct as well as calcifications in the pancreas. In some centers, endoscopic ultrasound, a technique in which an ultrasound probe is introduced via the mouth into the intestine, can be used to visualize the pancreas and demonstrate changes of chronic pancreatitis. (4)
Causes
Several of the causes of acute pancreatitis can also cause chronic pancreatitis. These include chronic alcohol use and, rarely, recurrent obstruction from a gallstone or stricture. A mnemonic for remembering the various causes of chronic pancreatitis is TIGAR-O:
- T is for toxic causes, including alcohol, toxins from kidney failure, and elevated calcium levels. Chronic, heavy alcohol use accounts for the majority of cases of chronic pancreatitis. However, only a small proportion of heavy alcohol drinkers will develop pancreatitis.
- I is for idiopathic, meaning no cause can be determined.
- G is for genetic, including mutations of genes that code for trypsinogen, the cystic fibrosis transmembrane regulator protein (the protein that is abnormal in patients with cystic fibrosis), and another protein known as the serine protease inhibitor Kazal type 1 or “SPINK.” These gene mutations place patients at increased risk of developing chronic pancreatitis.
- A is for autoimmune pancreatitis, which can present as acute pancreatitis, chronic pancreatitis, or a pancreatic mass. Autoimmune pancreatitis is a disease in which the body produces antibodies against the pancreas, targeting it for attack by the body’s immune system and resulting in chronic pancreatitis.
- R is for recurrent acute pancreatitis, which ultimately can lead to chronic pancreatitis.
- O is for obstruction, most commonly from a stone, stricture, or tumor. (5)
Treatment
Medical Management
Once permanent damage to the pancreas has occurred, it cannot be reversed, and treatment focuses on controlling symptoms. Maldigestion is treated with replacement of pancreatic digestive enzymes, which are taken by mouth with meals to breakdown dietary fats and proteins, thereby improving digestion, decreasing diarrhea, and reversing weight loss. Pancreatic enzymes must be given with each meal and should be taken with a medication that suppresses gastric acid secretion for maximal efficacy, such as a histamine blocker or proton pump inhibitor.
Diabetes mellitus is generally treated with the use of blood sugar-modifying medications. Typically, pancreatitis-induced diabetes requires the use of insulin, rather than an oral medication, to control blood sugar adequately.
The pain of chronic pancreatitis is difficult to treat and can be debilitating, limiting a person’s ability to function normally.(6) Pancreatic enzyme replacement, as described above, has not been found to be effective in treating the pain of chronic pancreatitis. Nonsteroidal anti-inflammatory medications and tricyclic antidepressants can be used to treat acute pain flares and may need to be taken long term. Narcotics should be limited to treatment of acute flares; chronic use may result in addiction.
Patients with chronic pancreatitis are at increased risk of pancreatic cancer. Approximately 5% of patients with chronic pancreatitis will develop pancreatic cancer over a 20-year period. As yet, no screening modality is recommended for early detection of pancreatic cancer in these patients.
Procedures
Procedural and surgical management of chronic pancreatitis may play a role in selected cases. ERCP with placement of a stent (hollow tube) can be used to treat duct strictures, thereby relieving obstruction. Celiac plexus block, an endoscopic procedure in which corticosteroids or alcohol is injected into the nerves supplying the pancreas, can control pain in some patients.(7) Surgical resection of severely damaged portions of the pancreas (and even the entire pancreas) may be recommended in some cases but is not guaranteed to relieve chronic pain. Surgical options also include drainage procedures, in which a narrowed or blocked pancreatic duct is opened, and deenervation procedures are undertaken, in which the nerves supplying the pancreas are severed. (8)
Figure 1: Abdominal CT scan showing a normal pancreas. The normal pancreas is lobular.
Figure 2: Abdominal CT scan showing mild pancreatitis. Note that the lobulations seen in the normal pancreas and in Figure 1 are absent and the pancreas is swollen.
Figure 3: Abdominal CT Scan revealing pancreatic necrosis. Note the large fluid collection in the pancreas. Image courtesy of Dr. Joe Simeone.
References
1. Forsmark CE, Baillie J. AGA Institute technical review on acute pancreatitis. Gastroenterology. 2007;132(5):2022-44.2. Whitcomb DC. Clinical practice. Acute pancreatitis. N Engl J Med. 2006;354(20):2142-50.
3. Frossard JL, Steer ML, Pastor CM. Acute pancreatitis. Lancet. 2008;371(9607):143-52.
4. Witt H, Apte MV, Keim V, Wilson JS. Chronic pancreatitis: challenges and advances in pathogenesis, genetics, diagnosis, and therapy. Gastroenterology. 2007;132(4):1557-73.
5. Etemad B, Whitcomb DC. Chronic pancreatitis: diagnosis, classification, and new genetic developments. Gastroenterology. 2001;120(3):682-707.
6. Sakorafas GH, Tsiotou AG, Peros G. Mechanisms and natural history of pain in chronic pancreatitis: a surgical perspective. J Clin Gastroenterol. 2007;41(7):689-99.
7. Gress F, Schmitt C, Sherman S, Ikenberry S, Lehman G. A prospective randomized comparison of endoscopic ultrasound- and computed tomography-guided celiac plexus block for managing chronic pancreatitis pain. Am J Gastroenterol. 1999;94(4):900-5.
8. Gourgiotis S, Germanos S, Ridolfini MP. Surgical management of chronic pancreatitis. Hepatobiliary Pancreat Dis Int. 2007;6(2):121-33.
Brandyn Griffiths
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Great Article!
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