Cystic fibrosis 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]. 

Explain the pathophysiology of cystic fibrosis (CF) and its multi-organ system involvement. 

FIGURE 13-1. Electrolyte transport in the airway epithelial cell. Ca, calcium cAMP, cyclic-3, 5 -adenosine monophosphate Cl, chloride Na, sodium K potassium. (From Milavetz G, Smith JJ. Cystic fibrosis. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 592, with permission.)... 

Gibson RL, Burns JL, Ramsey BW. State of the art pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med 2003 168 918-951. 

Bosso JA, Milavetz G. Cystic fibrosis. In DiPiro JT, et al, eds. Pharmacotherapy A Pathophysiologic Approach. 

Davis PB. Pathophysiology of the lung disease in cystic fibrosis. In Davis PB. ed. Cystic Fibrosis. New York Marcel Dekker Inc., 1993 193-218. 

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. 

Elevated levels of MMPs have been implicated in the pathophysiology of various lung diseases, including acute respiratory distress syndrome, bronchiectasis, and cystic fibrosis (V2). MMPs, EMMPRIN, and TIMPs are produced by many of the resident cells in the lung, hence complicating the analysis of their role in disease (F5, F6, FI2). Potential use of MMP inhibitors for treatment of these disorders remains to be explored. 

Plasma vitamin A and RBP levels have been investigated in patients with cystic fibrosis of the pancreas (Smith et al., 1972 Knopfle et al., 1975 Palin et al, 1979). Plasma vitamin A and RBP levels have been found to be lower than normal in patients with cystic fibrosis, despite the administration of oral vitamin A supplements adequate to maintain normal hepatic stores. In one study (Smith et al., 1972), the plasma vitamin A transport system was studied in 43 patients with cystic fibrosis receiving oral supplements of vitamin A and in 95 normal control subjects of a similar age range. The mean plasma concentrations of vitamin A and RBP were significantly lower in the patients than in the controls. Moreover, in cystic fibrosis patients each component of the transport system failed to show the normal age-related rise. It is not known whether these abnormalities of the retinol transport system are primary or secondary features of cystic fibrosis the abnormalities may, however, play a role in the pathophysiology of the disease. 

Davis PB. Clinical pathophysiology and manifestations of lung disease. In Yankaskas JR, Knowles MR eds. Cystic Fibrosis in Adults. Philadelphia Lippincott-Raven, 1999. 

Particle clearance by cough supports mucociliary clearance, especially under pathophysiological conditions of diseased lungs (60), such as chronic obstructive pulmonary disease (COPD), immotile cilia syndrome (ICS), and cystic fibrosis (CF). An increased secretion in the airways seems to be necessary. During cough, mucus is propelled toward the larynx by the very fast exhalation, with linear air... 

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