**4.3 Incidence and diagnosis**

278 New Advances in the Basic and Clinical Gastroenterology

It is most frequently due to chronic pancreatitis (in adults) or cystic fibrosis (in children) (Keller & al., 2009). Other pancreatic causes include acute pancreatitis, pancreatic tumors

While protein and starch digestion are usually maintained at a normal physiological level even in severe cases of pancreatic insufficiency, lipid malabsorption becomes the overriding

Clinically evident EPI occurs only when 90% of the function is lost and the secretion of pancreatic enzymes is less than 10% of normal (Lankisch & al., 1986; Layer & al., 1986). In chronic pancreatitis, an earlier decrease of lipase secretion is observed in comparison with amylase and protease. This is due to higher susceptibility of lipase to acidic pH caused by concomitant impairment of bicarbonate secretion, higher susceptibility of lipase to proteolytic destruction during small intestinal transit, additional acidic denaturation of bile acids and marked inhibition of bile acid secretion in malabsorptive states (Keller & Layer, 2005). Hence, in case of EPI, fat malabsorption precedes malabsorption of proteins and carbohydrates and is clinically more apparent. Additionally, due to the low bicarbonate secretion, the intraduodenal pH may drop below 4 late postprandially, bile salts may precipitate which leads to a decrease in post- prandial duodenal lipid solubilisation and contribute to impaired lipolysis (Zentler-Munro & al., 1984). The increased presence of lipids and other nutrients in the distal small bowel causes significant alterations in gut motility leading to accelerated gastric emptying and intestinal transit. This results in a marked decrease in the time available for digestion and absorption of nutrients, which also contributes to the malabsorption (Layer & al. 1997). However, more than 80% of carbohydrates can be digested and absorbed in the absence of pancreatic amylase activity and the colonic flora can further metabolizes malabsorbed carbohydrates (Layer & al., 1986). By contrast, gastric lipase, the only extrapancreatic source of lipolytic activity in humans, does not compensate efficiently for pancreatic lipase deficiency although it may be elevated in patients with chronic pancreatitis compared to healthy individuals (Carrière & al., 1993b). That's why fat malabsorption remains the first problem to be considered when treating EPI.

Maldigestion of fat results in steatorrhoea. In western countries steatorrhoea is diagnosed when daily stool fat content exceeds 7 g during ingestion of a diet containing 100 g fat per day. This corresponds to a decrease of the enteral absorption rate to less than 93% (Dimagno & al., 1973). Steatorrhoea causes symptoms such as foul-smelling, voluminous, greyish, fatty stools, abdominal cramps, bloating and chronic abdominal pain (Pasquali & al., 1996). It may also cause weight loss due to the loss of the highest dietary source of calories (fat contains 38 kJ/g, carbohydrates and protein contain 17 kJ/g) (Rosenlund & al., 1974). Steatorrhoea and weight loss are the overt clinical symptoms of EPI. They usually only occur if pancreatic enzyme secretion falls below 5–10% of normal levels (Keller & al., 2009). Due to fat malabsorption fat-soluble vitamins (A, D, E and K), magnesium, calcium and essential fatty and amino–acids are insufficiently resorbed (Dutta & al., 1982; Keller & al., 2009) which results in a variety of associated complications. Deficiencies in these vitamins and

problem and causes many of the clinical symptoms and nutritional deficiencies.

and pancreatic surgery (Table 3).

**4.2 Clinical symptoms and complications** 

**4.1 Pathophysiology** 

The prevalence of EPI is increasing with the higher proportion of patients with cystic fibrosis who survive into adult life and the incidence of chronic pancreatitis, which rises in parallel with alcohol consumption. In fact, the incidence of cystic fibrosis is approximately 1 in 2500 live births. The lack of chloride secretion in the pancreatic duct is responsible for severe exocrine pancreatic insufficiency in approximately 85% of CF newborns (Levy, 2011). In case of chronic pancreatitis, an incidence of 8.2 per 100 000 population per year and a prevalence of 26.4 cases per 100 000 along with a 3.6-fold increase in mortality in patients with alcohol-induced chronic pancreatitis compared with a population without chronic pancreatitis has been signaled (Keller & al., 2009). Hence, to avoid malnutrition related morbidity and mortality, it is pivotal to start treatment as soon as EPI is diagnosed.

Several direct and indirect function tests are available for assessment of pancreatic function. Direct invasive function tests like the secretin-caerulein test are still the gold standard with highest sensitivity and specificity. However, their availability is limited to specialized centers, they are costly, time consuming and uncomfortable for the patient (Keller & al., 2009). Determination of fecal elastase is convenient and widely available but its sensitivity is low in mild to moderate cases. Moreover, due to low specificity, it is of limited value for differential diagnosis in patients with diarrhea (Dominguez-Munoz & al., 1995; Stein & al., 1996). Other non-invasive tests such as 13C-breath tests are becoming more important but are not widely established, yet (Dominguez-Munoz & al., 2007).
