3.2　Pathophysiology

In chronic pancreatitis pancreatic exocrine insufficiency develops as a consequence of progressive inflammatory destruction of pancreatic tissue leading to reduced synthesis and secretion of bicarbonate and particularly pancreatic enzymes during meals.It is reported that in patients with chronic pancreatitis，pancreatic exocrine function is reduced by around 50-80%compared with healthy controls.On the other hand，80-90%of chronic pancreatitis patients show some degree of pancreatic exocrine insufficiency（Keller and Layer 2005）.In the majority of patients，that is in about 65-75%，morphologic alterations and functional impairment develop in parallel.Still，in rare cases，histologically proven chronic pancreatitis with pancreatic exocrine insufficiency can be present without visible morphologic alterations，even when using endoscopic ultrasound（Chowdhury et al.2005；Conwell et al.2007）.

Due to the large reserve capacity of the pancreas，clinically overt malabsorption rarely occurs before pancreatic function is impaired more than 90%（DiMagno et al.1973）.Once this stage has been reached，marked reduction of enzyme output to less than 5%of normal has been shown to be associated with an about 40%malabsorption rate from a readily digestible lowcalorie meal（Layer et al.1997）.(https://www.daowen.com)

In alcoholic chronic pancreatitis，development of steatorrhea as a sign of overt malabsorption usually takes 10-20 years after diagnosis（Layer et al.1994）.Still，a minority of chronic pancreatitis patients—about 10%—may initially present with symptoms of maldigestion due to advanced pancreatic exocrine insufficiency（Layer et al.1994）.The risk of pancreatic exocrine insufficiency appears to be influenced by the aetiology of chronic pancreatitis.Different natural courses suggest that，compared with alcoholic and“late onset”idiopathic chronic pancreatitis，maldigestion may present later in“early onset”idiopathic chronic pancreatitis and hereditary disease，although hardly any study has directly compared the degree of exocrine insufficiency in patients with varying etiologies（Keller and Layer 2005；Layer et al.1994；Hoffmeister et al.2012）.Smoking has an independent negative impact on pancreatic exocrine function（Luaces-Regueira et al.2014；Rebours et al.2012）.

With regard to different macronutrients，lipid malabsorption with steatorrhea usually occurs earlier and is more severe than malabsorption of other nutrients.This is due to a combination of pathomechanisms that preferentially impair secretion and intraluminal availability of pancreatic lipase:lipase secretion decreases earlier compared with that of amylase and proteases as it is highly susceptible to pH and proteolytic destruction（Keller and Layer 2005；DiMagno et al.1975）.Moreover，in humans only gastric lipase can serve as an extrapancreatic source of lipolytic activity.Although it may be elevated，it does not compensate for pancreatic lipase deficiency（Carriere et al.1993）.In contrast，even after almost complete inactivation of pancreatic amylase activity，more than 80%of complex carbohydrates can be digested and absorbed（Layer et al.1986），and the colonic flora can further metabolize malabsorbed carbohydrates leading to production of short chain fatty acids.These can be absorbed by the colon and thereby contribute to the overall caloric supply.