Lipase

Lipases are enzymes that hydrolyze glycerol esters with long-chain fatty acids. Pancreatic lipase is a single-chain glycoprotein with a molecular weight of 48 kDa. The con centration of lipase in the pancreas is 5000-fold higher than in other tissues, and the concentration gradient between pancreas and serum is ∼20,000-fold. Most of the lipase activity in serum comes from pancreatic acinar cells, but a small amount is also secreted by gastric, pulmonary, and intestinal mucosa. Lipase is a molecule small enough to be freely filtered through the glomerulus. It is totally reabsorbed by the renal tubules and is therefore not detectable in the urine.

 Clinical Significance

Serum lipase measurement represents the recommended laboratory test for the diagnosis of acute pancreatitis. The clinical sensitivity is 80–100% depending on the selected decision level and the clinical specificity of 80–100% depending on the population to which the test is applied. After an attack of acute pancreatitis, serum lipase activity increases within 4–8 hours, peaks after ∼24 hours, and values return to basal levels within 7–14 days. Increases between 2 and 50 times the URL have been reported, but it is important to remember that the magnitude of the increase in lipase activity is not necessarily proportional to the severity of the attack.

Acute pancreatitis is sometimes difficult to diagnose because it must be differentiated from other serious intra- abdominal disorders with similar clinical findings, such as perforated gastric or duodenal ulcer or intestinal obstruction. In the differential diagnosis, increased serum lipase concentrations >3 times the URL, in the absence of renal insufficiency, is a more specific diagnostic finding than increased serum α-amylase activity. In addition, lipase concentrations remain increased longer than α-amylase concentrations, which is another advantage in patients with delayed clinical presentation. Therefore, it is recommended that lipase should replace α-amylase determination as to the first diagnostic step for acute pancreatitis in a clinical emergency; on the other hand, simultaneous measurement of both enzymes is not warranted.

In subjects with reduced glomerular filtration rate, serum lipase activity is increased. Therefore, caution should be paid in the interpretation of increased lipase values in the presence of renal disease.

Reference Intervals

Among the most clinically essential enzymes, lipase is the only one whose measurement (and consequently the result) is method dependent. The reference intervals of lipase are, therefore, method dependent. For methods based on the use of diglycerides as a substrate, the suggested URL is 45 U/L, whereas the method using methylresorufin as a substrate has an URL of 64 U/L. There are no differences related to gender or age.

 Amylase (Pancreatic)

The α-amylases are enzymes of the class of hydrolases that catalyze the hydrolysis of 1,4-α-glucosidic bonds present in polysaccharides (amylose, amylopectin, and glycogen). Amylases present physiologically in human plasma are small molecules with molecular weights ranging from 54 to 62 kDa. The enzyme is therefore small enough to pass freely through renal glomeruli, and amylase is the only plasma enzyme physiologically found in urine.

Amylases are present in numerous organs and tissues. The highest concentration is observed in the salivary glands, which secrete a potent amylase (the S form) to initiate the hydrolysis of starch when the food is still in the mouth and esophagus. In the pancreas, the enzyme (the P form) is synthesized by the acinar cells and is then secreted into the intestinal tract by the pancreatic ductal system. Amylase activity is also found in sperm, testes, ovaries, fallopian tubes, striated muscles, lungs, and adipose tissue. The enzyme physiologically present in serum and urine is predominantly of pancreatic and salivary origin. These isoenzymes are the products of two closely related loci present on chromosome 1. Amylase isoenzymes also undergo posttranslational modifications of deamidation, glycosylation, and deglycosylation to form several isoforms.

Clinical Significance

 Plasma amylase activity is physiologically low and constant, and it increases markedly in acute pancreatitis and salivary gland inflammation. However, the specificity of amylase determination for the diagnosis of acute pancreatitis is low (20–60%, depending on the type of patient population studied), because increased values are also found in numerous other acute intra-abdominal disorders and in various extra- pancreatic conditions. The lack of specificity of total amylase measurement has shifted clinical interest to the direct measurement of pancreatic amylase. Applying the best decisional cut-off (an activity of three times the URL) and measuring the enzyme only under clinical conditions of diagnostic suspicion, the specificity of pancreatic amylase for the diagnosis of acute pancreatitis is >90%. However, it must be remembered that biliary tract diseases, such as acute cholecystitis, and various intra-abdominal events cause an increase in serum pancreatic amylase activity of up to four times the URL and sometimes even higher.

In renal insufficiency, serum amylase activity is increased in proportion to the degree of renal impairment. Hyperamylasemia also occurs in multiple myeloma, pulmonary neoplastic diseases, and serous and mixed ovarian carcinomas, with increases even >50 times the URL. In 1% of the population, the presence of macroamylases, which can cause hyperamylasemia, can be detected in the serum. These macroamylases are complexes composed of amylase (S-type amylase) and IgG or IgA. These macroamylases cannot be filtered by renal glomeruli because of their large size (>200 kDa) and are thus retained in plasma, where their presence, typically stable over time, can increase measurable amylase activity by two to eight times the URL. No clinical significance is associated with this biological manifestation.

Reference Intervals

In apparently healthy adults, pancreatic amylase accounts for ∼40–50% of total serum amylase activity. The reference interval is 13–51 U/L. The activity of the pancreatic form is not demonstrable in the serum of most children <6 months of age, then slowly increasing to adult concentrations around 5 years of age; this reflects postnatal development of the exocrine pancreatic function. Consequently, the use of this enzyme for the diagnosis of suspected acute pancreatitis in young children should be avoided .