The basis, cause, treatment and current research on Cystic Fibrosis

8/13/2019 The basis, cause, treatment and current research on Cystic Fibrosis

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The McGraw-Hill Companies.All Rights Reserved.

CHAPTER 37

CHANIN C. WRIGHT AND YOLANDA Y. VERA

Cystic Fibrosis


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FIGURE 37-1. Mechanism of underlying elevated sodium chloride levels in the sweat of patients with

cystic fibrosis. Sweat ducts (panel A) in patients with cystic fibrosis differ from those in people without

the disease in the ability to reabsorb chloride before the emergence of sweat on the surface of the

skin. A major pathway for Clabsorption is through CFTR, situated within luminal plasma membranes

of cells lining the duct (i.e., on the apical, or mucosal, cell surface) (panel B). Diminished chloride

reabsorption in the setting of continued sodium uptake leads to an elevated transepithelial potentialdifference across the wall of the sweat duct, and the lumen becomes more negatively charged

because of a failure to reabsorb chloride (panel C). The result is that total sodium chloride flux is

markedly decreased, leading to increased salt content. The thickness of the arrows corresponds to the

degree of movement of ions.10(Rowe SM, Miller S, Sorscher EJ.

Cystic fibrosis. N Engl J Med 2005;352(19):1992-2001.

Copyright 2005 Massachusetts Medical Society. All rights reserved.)


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FIGURE 37-2. Mechanism Extrusion of mucus secretion

onto the epithelial surface of airways in cystic fibrosis.

Panel A shows a schematic of the surface epithelium and

supporting glandular structure of the human airway. Inpanel B, the submucosal glands of a patient with cystic

fibrosis are filled with mucus, and mucopurulent debris

overlies the airway surfaces, essentially burying the

epithelium. Panel C is a higher-magnification view of a

mucus plug tightly adhering to the airway surface, with

arrows indicating the interface between infected and

inflamed secretions and the underlying epithelium to which

the secretions adhere. (Both panels B and C were stainedwith hematoxylin and eosin, with the colors modified to

highlight structures.) Infected secretions obstruct airways

and, over time, dramatically disrupt the normal architecture

of the lung. In panel D, CFTR is expressed in surface

epithelium and serous cells at the base of submucosal

glands in a porcine lung sample, as shown by the dark

staining, signifying binding by CFTR antibodies toepithelial structures (aminoethylcarbazole detection of

horseradish peroxidase with hematoxylin counterstain)10.

(Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J

Med 2005;352(19):1992-2001. Copyright 2005

Massachusetts Medical Society. All rights reserved.)


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FIGURE 37-1. Cystic Fibrosis Foundation Diagnosis Criteria

and Clinical Presentation


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FIGURE 37-3. Classic and nonclassic

cystic fibrosis. The findings in classic

cystic fibrosis are shown on the left-hand

side, and those of nonclassic cystic

fibrosis on the right-hand side. Patients

with nonclassic cystic fibrosis have better

nutritional status and better overall

survival. Although the lung disease is

variable, patients with nonclassic cystic

fibrosis usually have late-onset or more

slowly progressive lung disease. Sweat-

gland function, as evidenced by the sweat

chloride test, is abnormal but not to the

extent noted in classic cystic fibrosis.

Pancreatitis may occur in patients withnonclassic disease. However, chronic

sinusitis and obstructive azoospermia

occur in both groups of patients. On the

basis of these findings, one can infer that

mutations in CTFR, perhaps coupled with

other genetic or environmental factors,

may confer a predisposition to sinusitis,

pancreatitis, or congenital bilateral

absence of the vas deferens(azoospermia) in the general population.16

(Knowles MR, Durie PR. What is cystic

fibrosis? N Engl J Med 2002;347(6):439-

442. Copyright 2002 Massachusetts

Medical Society. All rights reserved.)


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FIGURE 37-3.

Classic The CF

diagnostic process for

screened newborns.3

(Reprinted from JPediatr, Vol. 153(2),

Farrell PM,

Rosenstein BJ, White

TB, et al. Guidelines

for the diagnosis of

cystic fibrosis in

newborns through

older adults: Cystic

Fibrosis Foundation

Consensus Report,

pages S4-14,

Copyright 2008,

with permission from

Elsevier.)


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TABLE 37-2. Cystic Fibrosis Foundation Nutritional Assessment Parameters

and Recommendations


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TABLE 37-3. Pancreatic Enzyme Supplements


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TABLE 37-4. Airway Clearance Therapies


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TABLE 37-5. Airway Anti-microbial agents utilized in CF

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The basis, cause, treatment and current research on Cystic Fibrosis