Pancreatic exocrine insufficiency

Cystic fibrosis (CF) is a recessive genetic disorder prevalent among whites in North America and certain parts of northern Europe. It is characterized by chronic bacterial infections of the airways and sinuses, fat maldigestion due to pancreatic exocrine insufficiency, infertility in males due to abnormal development of the vas deferens, and elevated levels of chloride in sweat (> 60 mmol/L). 

Pancreatic exocrine insufficiency with nutrient maldigestion as described in the case report is both a classical complication and a defining leading symptom of chronic pancreatitis. Therefore, taking a careful history provides the key for the diagnosis. 

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). 

Pancreatic function tests are therefore indicated if and when one or more of the following aspects need be clarified Is a symptom or sign caused by pancreatic exocrine insufficiency Has pancreatic exocrine insufficiency developed in the course of chronic pancreatitis Does a patient require enzyme supplementation treatment ... 

Pancreatic exocrine insufficiency Decreased intraluminal fat digestion Chronic pancreatitis Cystic fibrosis... 

Nutrient maldigestion due to pancreatic exocrine insufficiency is a classical complication of chronic pancreatitis. In most cases, it occurs... 

Steatorrhea, the clinical result of insufficient intraluminal lipid hydrolysis, is the most important digestive malfunction in pancreatic exocrine insufficiency. As a rule, concomitant malabsorption of the lipid-soluble vitamins A, D, E, and K must be suspected in these patients. Naturally, potential differential diagnoses have to be considered in patients who present with steatorrhea (Table 26-1). The pivotal role of fat malabsorption in chronic pancreatitis is due to several interacting mechanisms ... 

Figure 26-3. Patients with severe pancreatic exocrine insufficiency (n = 14, mean + SE) show marked alterations of gastrointestinal functions with shortened small bowel transit time, 90% gastric emptying time, and duration of the fed pattern. These alterations are corrected by enzyme replacement therapy ( P <. 05 vs. controls, P <. 05 vs. placebo) (Layer et al., 1997).

In addition to steatorrhea and nutritional deficiencies, patients with pancreatic exocrine insufficiency also develop symptoms such as postprandial pain, cramps, bloating, and distention. These are caused by profound alterations of upper gastrointestinal secretory and motor functions in response to increased nutrient delivery to the distal small intestine, particularly the ileum. In the first 5-10 years of chronic pancreatitis, overt malabsorption is usually neither detected nor a major clinical problem, although enzyme output may decrease by 60%-90%. Still, there is evidence that, even in the early stages of chronic pancreatitis, the site of maximal nutrient digestion and absorption is shifted from the duodenum to the more distal small intestine. 

Although all pancreatic enzymes are inactivated during intestinal transit, fecal outputs of several enzymes correlate with pancreatic enzyme secretion. Fecal chymotrypsin activity, which is comparatively stable in the lumen as well as in extracorporal fecal samples, can be measured by a commercially available photometric test kit. When performed on three consecutive days, this test detects severe pancreatic exocrine insufficiency, but sensitivity and specificity are low in mild-to-moderate cases. In addition, the test does not differentiate between porcine and human chymotrypsin, so that pan-creatin supplements need to be discontinued 5 days prior to the test. For this reason, however, the test is able to monitor a patient s compliance in severe pancreatic insufficiency appar-endy refractory to enzyme treatment. Patients... 

Fecal elastase 1 concentration can be measured by an ELISA test kit using an antibody specific for the human enzyme pancreatin supplements do not interfere with this pancreatic function test and need not be discontinued. Although measurement of fecal elastase 1 excretion appears to be somewhat more sensitive than fecal chymotrypsin, its specificity and positive predictive value are similarly low, and falsepositive results can be expected in patients with intestinal diseases. Conversely, mild-to-moderate stages of pancreatic exocrine insufficiency cannot be diagnosed reliably. 

The test is valid for diagnosing severe pancreatic exocrine insufficiency but has the sensitivity limitations described above with respect to detecting mild impairment of pancreatic function. Conversely, despite the inclusion of the control test, false-positive results may occur in patients with intestinal and biliary diseases, as well as following gastric resection or Yen-Roux procedures. In the latter patients, intraluminal lack of pancreatic enzymes (despite normal secretory... 

Direct tests of secretory function such as fecal chymotrypsin and elastase 1 are the tests of first choice if the main diagnostic goal consists of noninvasive confirmation of chronic pancreatitis. Indirect tests may be preferred, however, if the main goal is to verify maldigestion (which needs not be due to loss of pancreatic secretory capacity) or to optimize enzyme treatment. For patients for whom noninvasive direct or indirect tests are negative or equivocal and diagnosis or exclusion of pancreatic exocrine insufficiency appears relevant, the invasive secretin-cerulein (SC) test should be considered. 

Figure 26-6. Therapeutic algorithm in pancreatic exocrine insufficiency.

Why is steatorrhea the most important digestive malfunction in pancreatic exocrine insufficiency in chronic pancreatitis ... 

Gregory, P.C., Tabeling, R., Fassmann, C. and Kamphues, J. (2002) Therapy of pancreatic exocrine insufficiency new experimental data. In Chronic pancreatitis Novel concepts in biology and therapy (Buckler,... 

CP is an inflammatory condition that usually results in functional and structural damage to the pancreas. In most patients CP is progressive and loss of pancreatic function is irreversible. Permanent destruction of pancreatic tissue usually leads to exocrine and endocrine insufficiency. Cystic fibrosis may be associated with pancreatic exocrine insufficiency in children and is discussed in Chap. 30. 

S. M. Griffin, D. Alderson, and J. R. Famdon. Acid resistant lipase as replacement therapy in chronic pancreatic exocrine insufficiency a study in dogs. Gut 30 1012 (1989). 

Bentiromide, a para-aminobenzoic acid (PABA) derivative (500 mg dose p.o.), is used as a screening test for pancreatic exocrine insufficiency. Following oral administration, bentiromide is cleaved by the pancreatic enzyme chymotrypsin, causing the release of PABA. 

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