Measurement of Exocrine Pancreatic Secretion in Humans

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Various measurement strategies have been developed to determine secretory function both for understanding normal physiology and determining the effects of disease states of the pancreas on secretory function [158172]. These measurements of secretory function are divided into two groups: the direct measurements and the indirect measurements. Direct measurements of pancreatic secretory function involve collection of pancreatic secretions in the duodenum either without stimulation of the pancreas or after intravenous administration of a secretagogue or a combination of secretagogues combined with measurements of the ions and digestive enzymes in the secretions. Indirect measurements of pancreatic secretory function include the measurement of pancreatic enzymes in duodenal samples after nutrient ingestion, the measurement of products of digestive enzyme action on ingested substrates, and the measurement of pancreatic enzymes in the stool.

Which measurement to use depends on the physiologic or clinical question under consideration. A key point that has to be considered for any measurement strategy is that the exocrine pancreas has a large functional reserve. That is, the capacity for digestion is about 10 times of what is needed for complete digestion and absorption of a meal. Nutrient loss in the stool does not occur unless the functional capacity of the exocrine pancreas is less than 5% to 10% of normal as measured by CCK-stimulation of digestive enzyme secretion into the duodenum (a direct measurement technique) [126]. Thus, the indirect measurements that depend on the conversion of an ingested substrate to a measurable product will be insensitive to the changes in function that may occur in a disease state. Thus, the direct measurement of duodenal digestive enzymes, ions and water after the intravenous administration of pancreatic secretagogues provides the greatest sensitivity.

Direct measurements of pancreatic exocrine secretion are the most versatile for determining physiology during both interdigestive state and after administration of secretin, CCK or the two combined. The combination provides the complete information for both the acinar and ductular cell secretions. For this measurement, tubes are placed through the nose or mouth into both the stomach and duodenum for collection of secretions. The gastric tube is used to remove gastric secretions that would prevent the ability to measure water and bicarbonate secretion from the pancreas. The duodenal tube is used for collection of pancreatic secretions as well as delivering a nonabsorbable marker that can be used to determine the portion of the pancreatic secretions collected. For example, the use of a nonabsorbable marker, such as cobalamin or polyethylene glycol (PEG), allows the quantitation of secretions without the need for complete aspiration of secretions [161].

The direct measurements of pancreatic exocrine function are based on the principle that maximal water, bicarbonate and enzyme secretion are related to the functional mass of the pancreas [158, 159]. The intravenous administration of secretin, with volume and sodium bicarbonate measurement, provides information about the ductal function of the pancreas in normal states as well as various disease states. The intravenous administration of CCK and the measurement of digestive enzyme secretion have been used to successfully measure acinar cell function. Because the combination of secretin and CCK administration provides stimulation of both functional units of the exocrine pancreas, this combination is most commonly used [158, 159, 161166]. CCK is best delivered by constant intravenous infusion. For measurements of maximal ductal secretion rates, synthetic secretin (SecroFlo, Repligen, Needham, MA) at a dose of 0.2 μg/kg injected over 1 minute is used. For maximal acinar secretion, synthetic CCK-octapeptide (carboxy-terminal octapeptide of CCK; Squibb, Princeton, NJ) at a dose of 40 ng/kg/h is used. Collections are made by aspiration of duodenal contents. Measurements, corrected for percentage recovery of the nonabsorbable marker, are made for fluid volume; bicarbonate and protein concentrations and the activity of various digestive enzymes (i.e., amylase, trypsin, chymotrypsin and lipase) [162].

More recently, a direct measurement method has been developed using endoscopy, and a short collection period has been described. An endoscopy which contains aspirating channels is passed into the duodenum [168172]. Then, secretin, CCK or the combination of the two is administered intravenously, and pancreatic secretions are collected via the endoscope tip with its aspiration channel positioned in the duodenum.

The classic indirect measurement of pancreatic function with ingestion of a meal is the “Lundh Test Meal [160].” In the original description, the subject ingests a 300-mL liquid test meal composed of dried milk, vegetable oil and dextrose (6% fat, 5% protein and 15% carbohydrate). Samples are aspirated from the duodenum at intervals for measurement of digestive enzymes. The results of this type of measurement are dependent on the entire physiologic system, including the various sensory inputs during the different phases of the meal, the neurohumoral transmission systems and the pancreatic responses to the neurohumoral system. Thus, pancreatic enzyme secretory responses will be influenced by disorders of sensory organs, mucosal diseases of the upper intestine and alterations in the anatomy of the upper gastrointestinal tract. Comparisons of the results of the Lundh test meal (or variations of this meal) with those of direct measurement of pancreatic function can be used to show the influence of these factors on the pancreatic response [161].

There are several testing systems designed to measure of products of digestive enzyme action on ingested substrates. The most specific one is the measurement of stool triglyceride (also called stool fat or steatorrhea). Steatorrhea occurs when meal-stimulated pancreatic lipase output drops to less than 5% to 10% of normal [126]. For this measurement, the stools of the subject are collected for 72 h while he/she is ingesting a diet adequate in fat intake (70 to 100 g/day). Normally, 7% or less of ingested fat appears in the stool. A simple qualitative microscopic examination of a single stool for oil is almost as sensitive as quantitative measurements for fat [161]. Of note, this measurement is only useful in determining large losses of pancreatic function or significant alterations in anatomy or mucosal function because of the great amount of reserve of exocrine pancreatic function.

Several other indirect measurement systems have been designed that rely on digestive enzyme action on synthetic ingested substrates [161]. The substrates are acted upon by specific digestive enzymes, such as chymotrypsin and carboxylesterase, creating products that are measured in the urine, blood or breath. Again, because of the large functional reserve of the exocrine pancreas, these measurements are only able to determine large decreases in pancreatic secretory output. Finally, measurement of select pancreatic digestive enzymes, including chymotrypsin and elastase 1 in the stool, have been used to determine exocrine pancreatic insufficiency in patients with cystic fibrosis and chronic pancreatitis [173, 174].