Amylase test and Acute pancreatitis

Description

Amylases are enzymes that catalyze the hydrolysis of amylopectin, amylose, glycogen, and their hydrolyzed products into simple and easily digestible sugars. Amylase is an enzyme produced in the pancreas and by the salivary glands that converts starches, glycogens, and related polysaccharides into simple and easily digested sugar. It is also present in molds, bacteria, yeasts, and plants.

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Amylase isoenzymes
Alpha amylase is of salivary origin (S-type amylase) or pancreatic origin (P-type amylase).

1. Salivary origin (S-type amylase)
2. Pancreatic origin (P-type amylase)

Salivary amylase is synthesized by parotid, sweat, and lactating mammary glands.

Pancreatic amylase is secreted by acinar cells of the pancreas and is tissue specific and more temperature labile than salivary amylase.

Separation of amylase enzyme (a protein) by slab gel electrophoresis
On agarose gel, the mobility of the less anionic isoenzyme corresponds to pancreatic amylase, while the more anionic band is salivary amylase.

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Macroamylasemia
Macroamylasemia is a condition of persistently elevated serum amylase activity with no apparent pancreatic disorder due to the formation of a large amylase-globulin complex, which is not excreted.

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Test overview
An amylase test measures the amount of this enzyme in a sample of blood taken from a vein or in a sample of urine.

1. Blood/serum amylase
2. Urine amylase

Amylase levels
Normally, only low levels of amylase are found in the blood or urine. However, if the pancreas or salivary glands become damaged or blocked, more amylase is usually released into the blood and urine. In the blood, amylase levels rise for only a short time. In the urine, amylase may remain high for several days.

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Symptoms
Almost everyone with acute pancreatitis has severe abdominal pain in the upper abdomen. The pain penetrates to the back in about 50% of people.

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Causes & pain

1. When acute pancreatitis is caused by gallstones, the pain usually starts suddenly and reaches its maximum intensity in minutes. 
2. When pancreatitis is caused by alcohol, pain typically develops over a few days. 

Whatever the cause, the pain then remains steady and severe, has a penetrating quality, and may persist for days.

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Pain & relief
Coughing, vigorous movement, and deep breathing may worsen the pain. Sitting upright and leaning forward may provide some relief. Most people feel nauseated and have to vomit, sometimes to the point of dry heaves (retching without producing any vomit). Often, even large doses of an injected opioid analgesic do not relieve pain completely.

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Breathing problems
Some people, especially those who develop acute pancreatitis because of heavy alcohol use, may never develop any symptoms other than moderate to severe pain. Other people feel terrible. They look sick and are sweaty and have a fast pulse (100 to 140 beats a minute) and shallow, rapid breathing. Rapid breathing may also occur if people have inflammation of the lungs, areas of collapsed lung tissue (atelectasis), or accumulation of fluid in the chest cavity (pleural effusion). These conditions may decrease the amount of lung tissue available to transfer oxygen from the air to the blood and can lower the oxygen levels in the blood.

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Body temperature
At first, body temperature may be normal, but it may increase in a few hours to between 100° F and 101° F (37.7° C and 38.3° C).

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Blood pressure
Blood pressure is usually low and tends to fall when the person stands, causing lightheadedness or transient loss of consciousness (TLOC) or syncope.

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Yellow sclerae
Occasionally, the whites of the eyes (sclera) become yellowish.

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Complications of acute pancreatitis

The main complications of acute pancreatitis are

1. Low blood pressure and shock
2. Damage to other organs
3. Infection of the pancreas
4. Pancreatic pseudocyst

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Pancreatic damage
Damage to the pancreas may permit activated enzymes and toxins such as cytokines to enter the bloodstream and cause low blood pressure and damage to other organs, such as the lungs and kidneys. Some people who have acute pancreatitis develop failure of other organs including the kidneys, lungs, or heart, and this failure can lead to death.

The part of the pancreas that produces hormones, especially insulin, tends not to be affected by acute pancreatitis.

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Swollen upper abdomen
In acute pancreatitis, a person may develop some swelling in the upper abdomen. This swelling may occur because the intestinal contents have stopped moving, causing the intestines to swell (a condition called ileus).

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Acute pancreatitis
In severe acute pancreatitis, parts of the pancreas may die (called necrotizing pancreatitis), and body fluid may escape into the abdominal cavity, which decreases blood volume and results in a large drop in blood pressure, possibly causing shock and organ failure. Severe acute pancreatitis can be life threatening.

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Inflammed pancreas (due to infection)
Infection of an inflamed pancreas is a risk, particularly after the first week of illness. Sometimes, a doctor suspects an infection when a person's condition worsens and a fever develops, especially if this happens after the person's first symptoms started to subside.

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Pancreatic pseudocyst
A pancreatic pseudocyst is a collection of pancreatic enzymes, fluid, and tissue debris that sometimes forms in and around the pancreas. The pseudocyst goes away spontaneously in some people. In other people, the pseudocyst does not go away and can become infected.

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Diagnosis
Blood tests
Imaging tests

Characteristic abdominal pain leads a doctor to suspect acute pancreatitis, especially in a person who has gallbladder disease or who drinks a lot of alcohol. During the examination, a doctor often notes that the abdomen is tender and the abdominal wall muscles may be rigid. When listening to the abdomen with a stethoscope, a doctor may hear few or no bowel (intestinal) sounds.

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Blood tests
No single blood test proves the diagnosis of acute pancreatitis, but certain tests suggest it. Blood levels of two enzymes produced by the pancreas—amylase and lipase—usually increase on the first day of the illness but return to normal in 3 to 7 days. If the person has had other flare-ups (bouts or attacks) of pancreatitis, however, the levels of these enzymes may not increase significantly, because so much of the pancreas may have been destroyed that few cells are left to release the enzymes.

The white blood cell count and blood urea nitrogen level (marker of kidney function) are usually increased.

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Imaging tests
X-rays of the abdomen may show dilated loops of intestine or, rarely, one or more gallstones. Chest x-rays may reveal areas of collapsed lung tissue or an accumulation of fluid in the chest cavity.

An ultrasound of the abdomen may show gallstones in the gallbladder or sometimes in the common bile duct and also may detect swelling of the pancreas.

A computed tomography (CT) scan is particularly useful in detecting inflammation of the pancreas and is used in people with severe acute pancreatitis. Because the images are so clear, a CT scan helps a doctor make a precise diagnosis and identify complications of pancreatitis.

Magnetic resonance cholangiopancreatography (MRCP), a special magnetic resonance imaging (MRI) test, may also be done to show the pancreatic- duct and bile duct and to determine if there is any dilation, blockage, or narrowing of the ducts.

Endoscopic retrograde cholangiopancreatography allows doctors to view the bile duct and pancreatic duct. During this test, doctors are able to remove from the bile duct gallstones that are causing a blockage.

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Other tests
If doctors suspect that there is an infection, they may withdraw a sample of infected material from the pancreas by inserting a needle through the skin into the fluid collection.

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Prognosis
In acute pancreatitis, a CT scan helps determine the outlook or prognosis. If the scan indicates that the pancreas is only mildly swollen, the prognosis is excellent. If the scan shows large areas of destroyed pancreas, the prognosis is usually poor.

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Scoring (arbitrary)
A number of scoring systems help doctors predict the severity of acute pancreatitis, which can help them better manage the person. These scoring systems may include information such as age, medical history, physical examination findings, laboratory tests, and CT scan results.

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Death
When acute pancreatitis is mild, the death rate is about 5% or less. However, in pancreatitis with severe damage, or when the inflammation is not confined to the pancreas, the death rate can be much higher. Death during the first several days of acute pancreatitis is usually caused by failure of the heart, lungs, or kidneys. Death after the first week is usually caused by pancreatic infection or by a pseudocyst that bleeds or ruptures.

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Treatment

1. Fasting
2. Fluids by vein
3. Pain relief
4. Measures to support nutrition
5. Sometimes endoscopy or surgery

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Treatment
Treatment of mild acute pancreatitis usually involves short-term hospitalization where fluids are given by vein (intravenously / i.v.), analgesics are given for pain relief, and the person fasts to try to rest the pancreas. A low-fat, soft diet is usually started soon after admission if there is no nausea, vomiting, or severe pain.

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Intravenous fluids
People with moderate to severe acute pancreatitis need to be hospitalized for a longer period of time and are given intravenous fluids. They must initially avoid food and liquids, because eating and drinking stimulate the pancreas. Symptoms such as pain and nausea are controlled with drugs given intravenously. Doctors may give antibiotics if these people show any signs of infection.

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People with severe acute pancreatitis are admitted to an intensive care unit (ICU), where vital signs (pulse, blood pressure, and rate of breathing) and urine production can be monitored continuously.

Blood samples are repeatedly drawn to monitor various components of the blood, including the following:

1. Hematocrit (Hct), 
2. Blood sugar (glucose) levels, 
3. Electrolyte levels, 
4. White blood cell (WBC) count, and 
5. Blood urea nitrogen (BUN) levels or Urea levels.*

*Urea analysis is performed nowadays, where urea nitrogen is measured and multiplied by 2 and reported as urea levels.

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Nasogastric tube

A tube may be inserted through the nose and into the stomach (nasogastric tube) to remove fluid and air, particularly if nausea and vomiting persist and ileus is present.

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Parenteral nutrition
People with moderate to severe acute pancreatitis are often given nutrition via a thin plastic tube that is inserted through the nose and down through the stomach into the small intestine (tube feeding). Less often, people are given intravenous feeding.

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Other
For people with a drop in blood pressure or who are in shock, blood volume is carefully maintained with intravenous fluids and drugs and heart function is closely monitored. Some people need supplemental oxygen, and the most seriously ill require a ventilator (a machine that helps air get in and out of the lungs).

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Pancreatitis due to gallstones
When acute pancreatitis results from gallstones, treatment depends on the severity. Although more than 80% of people with gallstone pancreatitis pass the stone spontaneously, ERCP with stone removal is usually needed for people who do not improve because they have a stone they cannot pass. At some point, the gallbladder is usually removed but if the pancreatitis is severe, removal of the gallbladder can usually be delayed until symptoms subside.

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Pseudocysts & drainage
Pseudocysts that have rapidly grown larger or are causing pain or other symptoms are usually drained. Depending on its location and other factors, a pseudocyst can be drained by doing a surgical procedure, or by placing a drainage tube (catheter) into the pseudocyst. The catheter can be placed using an endoscope or by inserting the catheter directly through the skin into the pseudocyst. The catheter allows the pseudocyst to drain for several weeks.

An infection is treated with antibiotics, and may require removal of infected and dead tissue endoscopically or surgically.

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Indications/Applications
Most elevations in serum amylase are due to increased rates of amylase entry into the blood stream, decreased rates of clearance or both. The test is primarily used, in conjunction with a lipase test, to help diagnose and monitor acute pancreatitis and other pancreatic disorders. Serum amylase increases in 6-48 hrs of onset of acute pancreatitis but not in proportion to the severity of the disease and activity returns to normal in 3-5 days. Urine amylase increases in proportion to serum amylase and remains elevated for several days after serum amylase has been normalized. The ratio of amylase urinary clearance to creatinine clearance can be used in the diagnosis of acute and relapsing pancreatitis.

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Other uses of serum amylase test
Serum amylase levels can also be elevated in pancreatic cancers, although a bit too late to be diagnostically useful; however, the results can assist in monitoring treatment of pancreatic cancers. Other conditions in which determination of serum amylase is useful is to determine the effects of the removal of gallstones, and swelling and inflammation of the salivary/parotid glands.

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Indications for testing are as follows:

• Severe abdominal pain
• Fever
• Loss of appetite (LOA)
• Nausea

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Causes
The most common causes (more than 70% of cases) of acute pancreatitis are

1. Gallstones
2. Heavy alcohol intake
3. Other causes

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Gallstones
Gallstones cause about 40% of cases of acute pancreatitis. Gallstones are collections of solid material in the gallbladder. These stones sometimes pass into and block the duct that the gallbladder shares with the pancreas (called the common bile duct).

Normally, the pancreas secretes pancreatic fluid through the pancreatic duct into the first part of the small intestine (duodenum). This pancreatic fluid contains digestive enzymes that help digest food. If a gallstone becomes stuck in the sphincter of Oddi (the opening where the pancreatic duct empties into the duodenum), pancreatic fluid stops flowing. Usually, the blockage is temporary and causes limited damage, which is soon repaired. But if the blockage remains, the enzymes collect in the pancreas and begin to digest the cells of the pancreas, causing severe inflammation.

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Alcohol
Alcohol use causes about 30% of cases of acute pancreatitis and usually occurs only after heavy alcohol use. The risk of developing pancreatitis increases with increasing amounts of alcohol (4 to 7 drinks per day in men and 3 or more drinks per day in women). How alcohol causes pancreatitis is not fully understood. One theory is that alcohol is converted into toxic chemicals in the pancreas that cause damage. Another theory is that alcohol may cause the small ductules in the pancreas that drain into the pancreatic duct to clog, eventually causing acute pancreatitis.

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Other causes
For some people, acute pancreatitis is hereditary. Gene mutations that predispose people to developing acute pancreatitis have been identified. People who have cystic fibrosis or carry the cystic fibrosis genes have an increased risk of developing acute as well as chronic pancreatitis.

Many drugs can irritate the pancreas. Usually, the inflammation resolves when the drugs are stopped.

Viruses can cause pancreatitis, which is usually short-lived.

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SOME CAUSES OF ACUTE PANCREATITIS

1. Gallstones
2. Heavy alcohol use
3. Drugs such as angiotensin-converting enzyme (ACE) inhibitors, azathioprine, furosemide, 6-mercaptopurine, pentamidine, sulfa drugs, and valproate
4. Estrogen use in women with high levels of lipids in the blood
5. High levels of calcium in the blood (which may be caused by hyperparathyroidism)
6. Viruses such as mumps, coxsackie B virus, and cytomegalovirus
7. High levels of triglycerides in the blood (hypertriglyceridemia)
8. Damage to the pancreas caused by surgery or endoscopy (such as endoscopic retrograde cholangiopancreatography [ERCP])
9. Damage to the pancreas caused by blunt or penetrating injuries
10. Cancer of the pancreas, or other blockages of the pancreatic duct
11. Hereditary pancreatitis, including a small percentage of people with cystic fibrosis or cystic fibrosis genes
12. Cigarette smoking
13. Kidney transplantation
14. Pregnancy (rare)
15. Tropical pancreatitis

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Biochemical markers for acute pancreatitis

Serum amylase & serum lipase tests
Serum amylase and lipase are common tests obtained as biochemical markers for acute pancreatitis.

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Blood collection and test panels

The 2 tests for amylase are serum and urine.
For both tests, patient should not drink alcohol for 24 hours before the test.

For the blood test, patients should not eat or drink anything except water for 2 hours before the test.

For the urine test, patients should drink enough fluids during the 24-hour test to avoid dehydration. In this test, patients should check with their physician about any medications being taken. Timed urine specimens can be obtained for urinary amylase and normalized to creatinine content.

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How to Prepare for Amylase Test

To prepare for an amylase test:

1. Do not drink alcohol for 24 hours before the test.
2. For a blood test for amylase, do not eat or drink anything except water for at least 2 hours before having the test.
3. For a 24-hour urine test for amylase, be sure to drink enough fluids during the test to prevent dehydration.

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Methods
Blood is collected into a vacuum tube via venipuncture (ie blood is obtained from a vein in the arm).

For urine, a patient urinates into a small container and then transfers the sample to a lab-provided larger container with a small amount of preservative.

Plasma samples that have been anticoagulated with citrate or oxalate should be avoided because amylase is a calcium-containing enzyme and false low levels can be obtained with such specimens.

Notes regarding these methods are as follows:

Keep container refrigerated.
Do not touch inside of container or drop any foreign matter into it.

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Test panels

Related tests are as follows:

1. Lipase test
2. Urinalysis
3. Urine creatinine/clearance
4. Isoamylase fractionation

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LABORATORY TEST & FINDINGS

Set up for manual serum amylase test

Reference range
Each lab has its own reference ranges for the tests that it offers.

The reference range for amylase is as follows:

Serum test: Normal is 40-140 U/L
Urine Test: Normal is 24-400 U/L

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Interpretation of serum amylase levels

Conditions associated with high amylase levels are as follows:

1. Peptic ulcers
2. Intestinal obstruction
3. Pancreatic duct obstruction
4. Cancer
5. Gallbladder attacks
6. Mesenteric thrombosis
7. Postoperative abdominal surgery
8. Mumps
9. Macroamylasemia
10. Tubal pregnancy

Conditions associated with low amylase levels are as follows:

1. Liver damage
2. Cystic fibrosis
3. Pancreatic cancer
4. Toxemia of pregnancy

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Pancreatic enzymes and products

Early in the course of acute pancreatitis, there is a breakdown in the synthesis-secretion coupling of pancreatic digestive enzymes; synthesis continues while there is a blockade of secretion. As a result, digestive enzymes leak out of acinar cells through the basolateral membrane to the interstitial space and then enter the systemic circulation.

Serum amylase
Serum amylase rises within 6 to 12 hours of the onset of acute pancreatitis. Amylase has a short half-life of approximately 10 hours and in uncomplicated attacks returns to normal within three to five days. Serum amylase elevation of greater than three times the upper limit of normal has a sensitivity for the diagnosis of acute pancreatitis of 67% to 83% and a specificity of 85% to 98%.

However, elevations in serum amylase to more than three times the upper limit of normal may not be seen in approximately 20% of patients with alcoholic pancreatitis due to the inability of the parenchyma to produce amylase, and in 50% of patients with hypertriglyceridaemia-associated pancreatitis as triglycerides interfere with the amylase assay. Given the short half-life of amylase, the diagnosis of acute pancreatitis may be missed in patients who present >24 hours after the onset of pancreatitis. In addition, elevations in serum amylase are not specific for acute pancreatitis and may be seen in other conditions.

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Sensitivity & specificity of amylase & lipase tests for pancreatitis
The sensitivity and specificity of amylase and lipase for pancreatitis depend upon the threshold for an abnormal result. Higher thresholds are associated with better specificity but lower sensitivity. Several studies suggest that lipase may be more specific than amylase in the diagnosis of acute pancreatitis. A lipase level of three times the upper limit of normal is approximately 98% specific for acute pancreatitis.

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Acknowledgement
Text and content are adapted from Up-To-Date and many test methods by various vendors, and made easy for small group discussion (SGD) for Phase I teaching-learning sessions.