Pancreatic enzyme activity

Pancreatic enzyme activity is very low in premature neonates. Lipase activity increases 20-fold in the first 9 months of life. Since concentration of bile salts is also... 

The presence or absence of pancreatic enzymes can only be satisfactorily decided by intraduodenal intubation and direct examination of samples of small intestinal contents after the administration of a suitable stimulus to pancreatic secretion (Fll). It is not sufficient to look at one enzyme only, such as trypsin, since a specific deficiency of lipase can occur (Sll). Assessment of the degree of hydrolysis of fat in the stools is quite unreliable as a guide to pancreatic enzyme activity (CIO). 

The dose of enzyme required to treat steatorrhea may vary among individuals, and the dose should be individualized to achieve optimal therapeutic effects. In addition less-than-precise enzyme extraction and inconsistent enteric-coating procedures demand careful consideration in selecting from the array of pancreatic enzyme products now available. As much as a 30-fold difference may be seen in pancreatic enzyme activity among products after being exposed to simulated gastric fluid [19]. 

Pancreatic enzyme activity may be low at birth, but enzymes such as amylase, lipase, and trypsin develop to adult levels within the first year of life. Premature infants appear to have lower amylase levels than do full-term infants. Low concentrations of pancreatic enzymes may be the reason why newborns have a decreased ability to cleave prodrug esters such as chloramphenicol palmitate. Lipid-soluble drugs may not be well absorbed by neonates because of low lipase concentrations and bile acid pool. ... 

The iso-osmolar non-ionic dimer iotrolan and the low-osmolar ionic monomer iopromide (osmolarity about twice that of the blood) have been compared in 40 patients who underwent ERCP (159). They were randomized to receive either iopromide (iodine 300 mg/ml, 770 mosmol/kg, mean dose 15 ml) or iotrolan (iodine 300 mg/ ml, 320 mosmol/kg, mean dose 12 ml). Pancreatitis after ERCP occurred in two patients given iopromide and in five given iotrolan. There were no significant differences between the groups in the time-course of changes in serum pancreatic enzyme activities, changes in acute-phase proteins, or the incidence of abdominal pain. 

Muller, D.P. and Ghale, G.K. (1982) Stability of pancreatic enzyme activities in duodenal juice after pancreatic stimulation by a test meal or exogenous hormones. Ann. 

Pancreatic enzyme activity is very low in premature neonates. Lipase activity increases 10-fold in the first nine months of life, whereas amylase activity increases 200-fold. Since concentration of bile salts is also low in neonate and infants, it is anticipated that lipid-soluble vitamins and drugs would be poorly absorbed in early infancy (9). 

Dunaif, G., and Schneeman, B. 0., 1981, The effect of dietary fiber on human pancreatic enzyme activity in vitro. Am. 0. Clin. Nutr., 34 1034-1035. 

Examination of intestinal secretions yields normal values (Friedman et al. 1960 Lamy et al. 1961 Schwartz et al. 1963). In duodenal contents pancreatic enzyme activity and concentrations of bile acids were found to be normal (Wolff 1965). 

Studies of both acute and chronic pancreatitis in humans and in animals support the hypothesis that free radicals are involved in the pathogenesis of pancreatitis. There is some conflicting data from the animal work, which may in part be due to differences in the models used. It does also indicate that free radicals are not the only factors involved and su ests that activation of pancreatic enzymes are also imprortant, particularly in the development of haemorrhagic pancreatitis (Sanfey, 1991). The findings of decreased antioxidant defences and the success of treatment reported in chronic pancreatitis with a cocktail of antioxidants and with allopurinol surest further studies are required to establish the role of antioxidants in pancreatic disease and its prevention. 

O In the Western hemisphere, acute pancreatitis is caused mainly by ethanol use/abuse and gallstones. Other common causes of acute pancreatitis include hypertriglyceridemia, endoscopic retrograde cholangiopancreatography (ERCP), and autodigestion due to early activation of pancreatic enzymes. Numerous medications have also been implicated as causes of acute pancreatitis (Table 20-1). 

Release of active pancreatic enzymes directly causes local or distant tissue damage. Trypsin digests cell membranes and leads to the activation of other pancreatic enzymes. Lipase damages fat cells, producing noxious substances that cause further pancreatic and peripancreatic injury. 

Oral pancreatic enzyme supplements are available as powders, uncoated or coated tablets, capsules, enteric-coated spheres and microspheres, or enteric-coated microtablets encased in a cellulose or gelatin capsule (Table 28-2). Microencapsulated enteric-coated products are not superior to recommended doses of conventional non-enteric-coated enzyme preparations. The quantity of active lipase delivered to the duodenum appears to be a more important determinant in pancreatic enzyme replacement therapy than the dosage form. GI side effects appear to be dose related but occur less frequently with enteric-coated products. 

Pancreatic enemies (B) from slaughtered animals are used to relieve excretory insufficiency of the pancreas ( disrupted digestion of fats steatorrhea, inter alia). Normally, secretion of pancreatic enzymes is activated by cholecystokinin ancreozymin, the en-terohormone that is released into blood from the duodenal mucosa upon contact with chyme. With oral administration of pancreatic enzymes, allowance must be made for their partial inactivation by gastric acid (the lipases, particularly). Therefore, they are administered in acid-resistant dosage forms. 

Various pancreatic enzymes hydrolyze lipids, including lipase with its auxiliary protein colipase (see p. 270), phospholipase A2, and sterol esterase. Bile salts activate the lipidcleaving enzymes through micelle formation (see below). 

Opiates can effect serum levels of enzymes and other substances whose homeostatic control depends on clearance through the liver (F8, G12, M15, N4, S19). In one reported case, the aspartate aminotransferase was within normal limits before the administration of codeine, but within 2 hours after the drug, the enzyme activity had risen to two times the normal value by 8 hours to eight times the normal activity, and within 24 hours it had returned to normal (F8). Increases in transaminase to levels 5-85 times the control value have been reported in 6 of 16 patients with disease of the biliary tree following the administration of codeine phosphate (2 grains) (B7, F8). Gross has shown that morphine, codeine, or mepheridine administration produce elevations of serum amylase or lipase (G12). These elevations have been attributed to constriction of the sphincter of Oddi and increased intraductal pressure on the pancreatic duct (G12, N4). 

Gastrointestinal enzyme activities tend to be lower in the newborn than in the adult. Activities of -amylase and other pancreatic enzymes in the duodenum are low in infants up to 4 months of age. Neonates also have low concentrations of bile acids and lipase, which may decrease the absorption of lipid-soluble drugs. 

Exocrine pancreatic insufficiency is most commonly caused by cystic fibrosis, chronic pancreatitis, or pancreatic resection. When secretion of pancreatic enzymes falls below 10% of normal, fat and protein digestion is impaired and can lead to steatorrhea, azotorrhea, vitamin malabsorption, and weight loss. Pancreatic enzyme supplements, which contain a mixture of amylase, lipase, and proteases, are the mainstay of treatment for pancreatic enzyme insufficiency. Two major types of preparations in use are pancreatin and pancrelipase. Pancreatin is an alcohol-derived extract of hog pancreas with relatively low concentrations of lipase and proteolytic enzymes, whereas pancrelipase is an enriched preparation. On a per-weight basis, pancrelipase has approximately 12 times the lipolytic activity and more than 4 times the proteolytic activity of pancreatin. Consequently, pancreatin is no longer in common clinical use. Only pancrelipase is discussed here. 

Pancreatic enzyme supplements are well tolerated. The capsules should be swallowed, not chewed, because pancreatic enzymes may cause oropharyngeal mucositis. Excessive doses may cause diarrhea and abdominal pain. The high purine content of pancreas extracts may lead to hyperuricosuria and renal stones. Several cases of colonic strictures were reported in patients with cystic fibrosis who received high doses of pancrelipase with high lipase activity. These high-dose formulations have since been removed from the market. 

In addition to LPL, human milk contains a bile salts-activated lipase, which probably contributes to the metabolism of lipids by breast-fed babies who have limited pancreatic lipase activity. Bovine milk and milks from other dairy animals do not contain this enzyme. 

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