Comparative Literature
Topic: Cystic Fibrosis
Introduction
Cystic Fibrosis (CF) according to Cohen 2004, is the most common fatal hereditary disease amongst children and adults. It is an autosomal recessive disorder, and most carriers of the gene are asymptomatic. The flawed gene that causes CF affects the glandular secretions by altering chloride transport across cell membranes. Thickening of bronchial secretions leads to infection and other respiratory disorders. Other mucus secreting glands, sweat glands, and glands of the pancreas are also involved, causing electrolyte imbalance and digestive disturbance. Pathophysiology:
Cystic fibrosis is caused by defects in the cystic fibrosis gene, which codes for a protein trans-membrane conductance regulator (CFTR) that functions as a chloride channel and is regulated by cyclic adenosine monophosphate (cAMP). Mutations in the CFTR gene result in abnormalities of cAMP-regulated chloride transport across epithelial cells on mucosal surfaces.
Six classes of defects resulting from CFTR mutations have been described and are as follows: 1. Complete absence of CFTR protein synthesis 2. Defective protein maturation and early degradation (caused by the most common mutation, 3. Disordered regulation (diminished ATP binding and hydrolysis) 4. Defective chloride conductance or channel gating 5. Diminished transcription due to promoter or splicing abnormality 6. Accelerated channel turnover from the cell surface
CFTR mutations have poor penetrance. This means that the genotype does not predict the pattern or severity of disease. Defective CFTR results in decreased secretion of chloride and increased reabsorption of sodium and water across epithelial cells. The resultant reduced height of epithelial lining fluid and decreased hydration of mucus results in mucus that is stickier to bacteria, which promotes infection and inflammation. Secretions in the respiratory tract, pancreas, GI tract, sweat glands,
Introduction
Cystic Fibrosis (CF) according to Cohen 2004, is the most common fatal hereditary disease amongst children and adults. It is an autosomal recessive disorder, and most carriers of the gene are asymptomatic. The flawed gene that causes CF affects the glandular secretions by altering chloride transport across cell membranes. Thickening of bronchial secretions leads to infection and other respiratory disorders. Other mucus secreting glands, sweat glands, and glands of the pancreas are also involved, causing electrolyte imbalance and digestive disturbance. Pathophysiology:
Cystic fibrosis is caused by defects in the cystic fibrosis gene, which codes for a protein trans-membrane conductance regulator (CFTR) that functions as a chloride channel and is regulated by cyclic adenosine monophosphate (cAMP). Mutations in the CFTR gene result in abnormalities of cAMP-regulated chloride transport across epithelial cells on mucosal surfaces.
Six classes of defects resulting from CFTR mutations have been described and are as follows: 1. Complete absence of CFTR protein synthesis 2. Defective protein maturation and early degradation (caused by the most common mutation, 3. Disordered regulation (diminished ATP binding and hydrolysis) 4. Defective chloride conductance or channel gating 5. Diminished transcription due to promoter or splicing abnormality 6. Accelerated channel turnover from the cell surface
CFTR mutations have poor penetrance. This means that the genotype does not predict the pattern or severity of disease. Defective CFTR results in decreased secretion of chloride and increased reabsorption of sodium and water across epithelial cells. The resultant reduced height of epithelial lining fluid and decreased hydration of mucus results in mucus that is stickier to bacteria, which promotes infection and inflammation. Secretions in the respiratory tract, pancreas, GI tract, sweat glands,
References: Cohen, B. J. (2004). Respiration. Medical Terminology (Fourth Edition ed., pp. 261-263). 530 Walnut St Philadelphia, PA 19106: Lippincott Williams & Wilkins. Medscape: Medscape Access. (n.d.). Medscape: Medscape Access. Retrieved October 25, 2012, from http://emedicine.medscape.com/article/1001602-overview#a0104 Cystic fibrosis: Symptoms - MayoClinic.com. (n.d.). Mayo Clinic. Retrieved November 2, 2012, from http://www.mayoclinic.com/health/cystic-fibrosis/DS00287/DSECTION=symptoms