Exocrine function

As patients lose exocrine function of the pancreas, they have decreased ability to absorb lipids and protein ingested with normal dietary intake. Weight loss from nutritional malabsorption is a common symptom of chronic pancreatitis not often seen in acute pancreatitis. Fatty- or protein-containing stools are also common carbohydrate absorption is usually unaffected. Even though patients with chronic pancreatitis have decreased ability to absorb lipid from the gastrointestinal tract, there does not appear to be an increased incidence of fat-soluble vitamin deficiency in these patients.34... 

Negligible effects on pancreas zinc concentration and on pancreas exocrine function (Lu and Combs 1988a). 

Lowe, T.P., T.W. May, W.G. Brumbaugh, and D.A. Kane. 1985. National Contaminant Biomonitoring Program concentrations of seven elements in freshwater fish, 1978-1981. Arch. Environ. Contam. Toxicol. 14 363-388. Lu, J. and G.F. Combs, Jr. 1988a. Effects of excess dietary zinc on pancreatic exocrine function in the chick. Jour. Nutr. 118 681-689. 

Otsuki, M., Ohki, A., Okabayashi, Y., Suehiro, I., and Baba, S. (1987). Effect of synthetic protease inhibitor camostate on pancreatic exocrine function in rats. Pancreas, 2, 164-169. 

Tsuchida T, Kato T, Yamaga M, Ikebe K, Oniki Y, Irie H, Takagi K (2003) The effect of perfusion with UW solution on the skeletal muscle and vascular endothelial exocrine function in rat hindlimbs. J Surg Res 110 266-271... 

Nakamura T, Kudoh K, Takebe K, Imamura K, Terada A, Kikuchi H, Yamada N, Arai Y, Tando Y, Machida K, et al. Octreotide decreases biliary and pancreatic exocrine function, and induces steatorrhea in healthy subjects. Intern Med 1994 33(10) 593-6. 

The effects of parenteral nutrition on endocrine and exocrine functions of the pancreas have been investigated in experimental rats (906). The conclusion was that after parenteral nutrition treatment the insulin secretory... 

Fan BG, Salehi A, Sternby B, Axelson J, Lundquist I, Andren-Sandberg A, Ekelund M. Total parenteral nutrition influences both endocrine and exocrine function of rat pancreas. Pancreas 1997 15(2) 147-53. 

The cellular composition of the pancreas has been described in great detail.10,28,35 The bulk of the gland consists of acinar cells that synthesize and release pancreatic digestive enzymes (thereby providing the exocrine function). Interspersed within the acinar tissues are smaller clumps of tissue known as the islets of... 

Brugge et al. (B21) described a simple dual-isotope test for pancreatic exocrine function. They gave their patients radiolabeled [57Co]Bl2 bound to R-protein and [58Co]B12 bound to intrinsic factor if significantly less of the R-protein-bound vitamin was absorbed compared to the intrinsic-factor-bound vitamin this provided good evidence for pancreatic exocrine dysfunction. 

B21. Brugge, W. R., Goff, J. S., Allen, N. C., Podell, E. R., and Allen, R. H., Development of a dual label Schilling test for pancreatic exocrine function based on the differential absorption of cobalamin bound to intrinsic factor and R protein. Gastroenterology 78, 937-949 (1980). 

It is important to keep in mind, however, that not all patients with chronic pancreatitis develop clinical pancreatic exocrine insufficiency approximately 25% of patients still have sufficient exocrine function after 25 years of disease. On the other hand, it is also important to note that 10%-15% of patients with chronic pancreatitis have primary painless disease in these patients, pancreatic exocrine insufficiency may be the first (and possibly only) clinical manifestation. Thus, the absence of pain or a history of pancreatitis does not exclude the diagnosis (DiMagno et al., 1993). 

To be of value in routine clinical practice, any pancreatic function test is required to be not only precise and reliable, but also uncomplicated and inexpensive. However, due to the peculiarities of pancreatic anatomy and physiology, no currently available test meets all these criteria. Indeed, despite astounding developments in virtually every other diagnostic held (including pancreatic imaging), pancreatic exocrine function is estimated today by using very much the same principles and even methods as three decades ago. 

Figure 26-5. Principle of the 13C-mixed triglyceride breath test. Absorption of 13C-mixed triglycerides requires prior hydrolysis by pancreatic lipase (1), which leads to production of free fatty acids (stearic acid) and monoacylglycerol [2-(l-13C)octanoylglycerol]. These metabolites are incorporated into micelles, absorbed, and transported to the liver (2). Further degradation by hepatic enzymes and P-oxidation results in formation of 13C02, which is absorbed into the bloodstream, transported to the lung, and exhaled (3). Thus, exhalation of 13C02 reflects intestinal lipolysis and is a marker of pancreatic exocrine function.

Diarrhea may cause acidosis as a result of loss of Na, Kfi and HCOJ. One of the primary exocrine functions of the pancreas is production of HCOs to neutralize gastric contents on entry into the duodenum. If the water, K", and HCO7 in the intestine are not reabsorbed, a hypokalemic, normal anion gap metabolic acidosis will develop. The resulting hyperchloremia is due to the replacement of lost bicarbonate with Cr to maintain electrical balance. 

Chronic pancreatitis is defined by irreversible pancreatic damage with histological evidence of inflammation and fibrosis leading to destruction of both endocrine and exocrine function. There are many causes of chronic pancreatitis but the major histological features are similar... 

The predominant exocrine functions of the pancreas are the production and secretion of pancreatic juice, which is rich in enzymes and bicarbonate. Normal pancreatic juice is colorless and odorless it has a pH of 8.0 to 8.3 and a specific gravity of 1.007 to 1.042. The total 24-hour secretion volume may be as high as 3000 mL. ... 

A number of laboratory tests are available to measure exocrine function in the investigation of pancreatic insufficiency (most commonly caused by cystic fibrosis in children and chronic pancreatitis in adults). Tests fall into two categories, invasive and noninvasive. Invasive tests require GI, intubation to collect pancreatic samples noninvasive tests (or tubeless tests ) were developed to avoid intubation, which is uncomfortable for the patient, time-consuming, and therefore expensive. Noninvasive tests are simpler and cheaper to perform, but in general they lack the sensitivity and specificity of the invasive tests, particularly for the diagnosis of mild pancreatic insufficiency. It is important to recognize that biochemical tests have a limited clinical application in the diagnosis of pancreatic disease because of either the complexity of the invasive tests or the inadequate... 

TABLE 48-7 Summary of Invasive Tests of Pancreatic Exocrine Function... 

Cade A, Walters MP, McGinley N, Firth J, Brownlee KG, Conway SP, Littlewood JM. Evaluation of fecal pancreatic elastase-1 as a measure of pancreatic exocrine function in children with cystic fibrosis. Pediatr Puhnonol 2000 29 172-6. 

Cole SG, Rossi S, Stern A, Hofmann AF. Cholesteryl octanoate breath test—preliminary studies on a new noninvasive test of human pancreatic exocrine function. Gastroenterology 1987 93 1372-80,... 

Czako L, Endes J, Takacs T, Boda K, Lonovics J. Evaluation of pancreatic exocrine function by secretin-enhanced magnetic resonance cholangiopancreatography. Pancreas 2001 23 323-8. 

It is now well established that the MCI receptor mainly expressed in melanocytes and leukocytes plays a key role in skin pigmentation and inflammatory response (136, 137). The MC2 receptor is expressed only in the adrenal gland and mediates glucocorticoneogen-esis (123). The MC3 and MC4 receptors are both found in the brain, the MC3 receptor is found in the arcuate nucleus and the nucleus of the solitary tract, whereas the MC4 receptor is mainly found in the hypothalamus (138). Finally, the MC5 receptor is involved in exocrine functions and is localized predominantly in the sebaceous glands (139). The complex role of the melanotropins and the MC receptors, in controlling various physiological functions, has made it difficult to draw simple correlations between these receptors and the... 

---