Pancreatitis pathophysiology

CP-channels with smaller conductance have first been noted in the rectal gland of Squalus acanthias by ourselves and in the colonic carcinoma cell line HT29 [61,73]. Later these types of 5-15 pS CP-channels were also found in pancreatic ducts, A6-cells and many other cells [74,75]. It is now claimed that this kind of channel is much more relevant than the ICOR for the pathophysiology of cystic fibrosis [12]. 

FIGURE 20-1. Anatom ic structure of the pancreas and biliary tract. (From Berardi RR, Montgomery PA. Pancreatitis. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 722, with permission.)... 

Nearly all cells express kinin receptors that mediate the activities of both bradykinin and kallidin. The activation of these G-protein coupled receptors causes relaxation of venular smooth muscle and hypotension, increased vascular permeability, contraction of smooth muscle of the gut and airway leading to increased airway resistance, stimulation of sensory neurons, alteration of ion secretion of epithelial cells, production of nitric oxide, release of cytokines from leukocytes, and the production of eicosanoids from various cell types [11,12]. Because of this broad spectrum of activity, kinins have been implicated as an important mediator in many pathophysiologies including pain, sepsis, asthma, rheumatoid arthritis, pancreatitis, and a wide variety of other inflammatory diseases. Moreover, a recent report demonstrated that bradykinin B2 receptors on the surface of human fibroblasts were upregulated three-fold beyond normal in patients with Alzheimer s disease, implicating bradykinin as a participant in the peripheral inflammatory processes associated with that disease [13]. 

The 19th century witnessed the beginning of studies on the pathophysiology of acute pancreatitis. In 1867 Kiine isolated an enzyme catalyzing the cleavage of peptide bonds, which was later termed trypsin (1877), and a few years later Heidenhain found trypsin in pancreatic cells in the form of inactive proenzyme. 

F5. Frossard, J. L., Trypsin activation peptide (TAP) in acute pancreatitis From pathophysiology to clinical usefulness. JOP. J. Pancreas (Online) 2, 69-77 (2001). 

Solomon, T., Control of exocrine pancreatic secretion. In Pathophysiology of the Gastrointestinal Tract (L. Johnson, ed.), pp. 1173-1207. Raven, New York, 1987. 

There is epidemiologic evidence to suggest an increased prevalence of duodenal ulcers in patients with certain chronic diseases, but the pathophysiologic mechanisms of these associations are uncertain. A strong association exists in patients with systemic mastocytosis, multiple endocrine neoplasia type 1, chronic pulmonary diseases, chronic renal failure, kidney stones, hepatic cirrhosis, and ai-antitrypsin deficiency. An association may exist in patients with cystic fibrosis, chronic pancreatitis, Crohn s disease, coronary artery disease, polycythemia vera, and hyperparathyroidism. 

FIGURE 39-2. Pathophysiology of acute pancreatitis initiating and secondary events. PAF, platelet-activating factor TNF-a, tumor necrosis factor-a IL-1/J, interleukin-1 / IL-6, interleukin-6 IL-8, interleukin-8. 

Mayer J, Rau B, Gansauge F, et al. Inflammatory mediators in human acute pancreatitis Clinical and pathophysiological implications. Gut 2000 47 546-552. 

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