Amylase and Lipase

Amylase and lipase are digestive enzymes released from the pancreas into the blood when acinar cells are injured or ductal outflow is blocked. Serum lipase is more specific and stays raised longer. Amylase is also made in the salivary glands and several other tissues, so it is less specific. Both are measured by enzymatic colorimetric methods on serum or heparin plasma, and the main use is the diagnosis of acute pancreatitis.

Acute pancreatitis is diagnosed when at least 2 of 3 features are present: characteristic upper abdominal pain, lipase or amylase over 3 times the upper reference limit, and characteristic imaging findings. Lipase alone is sufficient as the enzyme test, and measuring both adds little.

Acute pancreatitis affects about 30 to 40 people in 100 000 each year. Gallstones and alcohol cause most cases. About 80% of attacks are mild. Overall mortality is about 2 to 5%, and 20 to 40% when organ failure persists or necrosis becomes infected.

Indications. Acute upper abdominal pain radiating to the back, persistent vomiting, suspected pancreatitis after ERCP, hypertriglyceridaemia or hypercalcaemia with abdominal pain, unexplained abdominal pain in a patient on drugs known to injure the pancreas, parotid swelling, and unexplained raised amylase.

Specimen. Serum or heparin plasma. EDTA and citrate chelate the calcium needed by amylase and give falsely low results, so they must not be used. Samples are stable for days at 2 to 8 °C. Saliva or sweat contamination can raise amylase.

Adult reference ranges are method specific. Local laboratory ranges take precedence.

Serum lipase. Pancreatic triacylglycerol lipase, which digests dietary fat. Range: up to about 60 U/L, with some methods up to about 160 U/L.

Raised:

• acute pancreatitis, acute on chronic pancreatitis
• pancreatic cancer and obstruction
• kidney failure
• bowel obstruction or ischaemia
• perforated peptic ulcer
• cholecystitis
• diabetic ketoacidosis
• HIV infection
• macrolipasaemia
• drugs (GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors can raise it without pancreatitis)

Lowered: advanced chronic pancreatitis and pancreatic destruction, without clinical use as a test.

Lipase rises within 4 to 8 hours of onset, peaks at about 24 hours and stays raised for 8 to 14 days. Sensitivity for acute pancreatitis is about 90 to 100% in the first 24 to 48 hours. A value over 3 times the upper limit supports the diagnosis, and the height of the value does not predict severity.

Serum amylase. Enzyme that digests starch, made by the pancreas (P-type) and salivary glands (S-type). Range: about 30 to 110 U/L.

Raised:

• acute pancreatitis
• salivary disease (mumps, parotitis, stones, head and neck surgery, bulimia, alcohol)
• macroamylasaemia
• kidney failure
• bowel obstruction, ischaemia or perforation
• ruptured ectopic pregnancy
• diabetic ketoacidosis
• burns
• ovarian and lung cancer
• cholecystitis
• post-ERCP states, and drugs

Lowered: advanced chronic pancreatitis, pancreatic insufficiency, cystic fibrosis, and in vitro suppression with severe hypertriglyceridaemia.

Amylase rises within 2 to 12 hours, peaks at 12 to 72 hours and returns to normal in 3 to 5 days, so a late presenter can have a normal value. A raised amylase with a normal lipase points to a non-pancreatic source, usually salivary or macroamylase.

Amylase isoenzymes and macroamylase. Isoenzyme assays separate pancreatic from salivary amylase. Macroamylase is amylase bound to an immunoglobulin, which is too large for the kidney to clear, so serum amylase is persistently raised with no disease and with a low urinary amylase. The amylase to creatinine clearance ratio is under 1% in macroamylasaemia, against 2 to 5% normally, and it is raised in acute pancreatitis.

Causes of acute pancreatitis.

• Gallstones and microlithiasis, the commonest cause. An ALT over 150 U/L (3 times the upper limit) in the first 48 hours makes a biliary cause likely.
• Alcohol, usually after years of heavy intake.
• Hypertriglyceridaemia, usually with triglycerides over 10 mmol/L (about 885 mg/dL). Amylase may be normal.
• Hypercalcaemia, notably in primary hyperparathyroidism.
• Drugs: azathioprine, valproate, didanosine, asparaginase, thiazides, oestrogens, tetracyclines, mesalazine, and GLP-1 receptor agonists.
• Post-ERCP, abdominal trauma, autoimmune (IgG4-related) disease, infection (mumps, Ascaris, HIV, cytomegalovirus), genetic variants (PRSS1, SPINK1, CFTR), pancreas divisum, and scorpion venom in some regions.

Severity. Classified as mild, moderately severe and severe, by the presence and duration of organ failure (over 48 hours defines severe disease). Features that predict severity at admission include persistent systemic inflammatory response, raised urea or haematocrit, obesity, older age, and a CRP over 150 mg/L at 48 hours.

Enzyme rises without pancreatitis. After ERCP, enzymes over 3 times the upper limit are common and need pain to count as pancreatitis. In kidney failure, amylase and lipase rise to 2 to 3 times the upper limit from reduced clearance.

Critical values and findings needing immediate action.

• Lipase or amylase over 3 times the upper limit with severe pain, persistent vomiting, hypotension, tachycardia or low urine output.
• Pancreatitis with jaundice, fever and rigors, which indicates cholangitis and needs urgent drainage.
• Pancreatitis with triglycerides over 10 mmol/L, calcium under 2.0 mmol/L, or ketoacidosis.
• Pancreatitis with hypoxia, rising creatinine or confusion, which indicates organ failure and needs critical care.
• Raised enzymes with peritonism, which suggests perforation or ischaemia.

Interferences and pitfalls.

• A late presentation gives a normal amylase after 3 to 5 days, and lipase can also normalise after 8 to 14 days.
• Severe hypertriglyceridaemia can give a falsely normal amylase by assay interference.
• Chronic pancreatitis with burnt out parenchyma releases little enzyme in an acute attack.
• Macroamylase and macrolipase cause persistent raised results without disease.
• Haemolysed or lipaemic samples distort some assays.
• Different methods give different ranges, and results are not interchangeable.
• Enzyme concentration does not correlate with severity and is not used for monitoring.

Special groups.

• Neonates and infants: amylase is very low at birth and reaches adult values by about 1 year.
• Children: trauma, viral infection, gallstones, drugs and genetic causes are the main causes of pancreatitis.
• Pregnancy: gallstones and hypertriglyceridaemia are leading causes, and hyperemesis can raise salivary amylase.
• Older adults: gallstones and pancreatic cancer are more frequent, and pain can be atypical.
• Regions: ascariasis and scorpion envenomation cause pancreatitis in some areas.

Follow up tests. ALT, bilirubin, ALP and GGT, calcium, triglycerides, glucose, CRP, full blood count, urea and creatinine, lactate, blood gas, abdominal ultrasound, contrast CT of the abdomen at 72 hours or later when complications are suspected, MR cholangiopancreatography, endoscopic ultrasound, IgG4, faecal elastase, genetic testing, amylase to creatinine clearance ratio, isoenzyme analysis.