Sweat chloride in cystic fibrosis –
Correct Answer: Increased
Description: Ans. is 'b' i.e., Increased CYSTIC FIBROSISo Cystic fibrosis is an inherited disease of the mucus and sweat glands,o Cystic fibrosis follows on autosomal recessive transmission,o There is a defect in ion transport of epithelial cells that affects fluid secretion inExocrine glands (pancreas)Epithelial lining of respiratory, gastrointestinal and reproductive tract Pathophysiologyo In normal duct epithelia, chloride is transported by plasma membrane channels (chloride channels)o The primary defect in cystic fibrosis results from abnormal function of an epithelial chloride channel protein encoded by the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7q 31.2.o Protein encoded by CFTR is a chloride channel through which chloride passes - In cystic fibrosis activity of chloride channel is decreased.o Along with chloride channel, CFTR can regulate other channel also, for example epithelial sodium channels (ENaC). ENaC is inhibited by normally functioning CFTR; hence, in cystic fibrosis, ENaC activity increases, markedly augmenting sodium uptake across the apical membrane (especially in respiratory and gastrointestinal system).Normal CFTR gene productDef ective (mutated) CFTR gene product in cystic fibrosis||1. Induce Cl conductance through itself (chloride channel)1. Reduced or lost Cl- conductance1. Inhibits Na+ conductance through ENaC2. Augmented sodium uptake across apical membrane Clinical features of CFo Functions of CFTR are tissue specific, i.e. its functions signify whether the epithelium is secretory (secrete Cl" into lumen) or absorptive (reabsorb Cl- from lumen),o Therefore clinical features are tissue specific:1. Respiratory tracto Respiratory epithelium is secretory, i.e. there is active secretion of Cl-,o CFTR mutation in cystic fibrosis results in loss or reduction of chloride secretion in lumen.o Active luminal sodium absorption is also increased (due to loss of inhibition of ENaC activity)o Both these decreased Cl- secretion and increased Na+ absorption from lumen) lead to increased passive water reabsorption (As you all know diffusion of water occurs from high osmolar to low osmolar concentration area),o This results in accumulation of dehydraded hyperconcentrated viscid secretion in respiratory lumen and defective mucociliary clearance - obstruction and recurrent respiratory tract infection; and bronchiectasis.2. Intestineo Similar to respiratory epithelium, intestinal epithelium is secretory and in CF there is defective Cl- secretion and enhanced Na+ absorption from lumen - Increased passive reabsorption of water from lumen,o This results in accumulation of dehydrated desciated intraluminal contents - obstruction of small and large intestine.3. Pancreaso The absence of CFTR Cl- channel in the apical membrane of pancreatic ductal epithelium limits the function of an apical membrane Cl- -HCHO3 exchanger to secrete bicarbonate and Na+ (by a passive process) into the duct.o The failure to secrete bicarbonate and Na+ leads to retention of enzyme in the pancreas and ultimately destruction of all pancreatic tissues due to pancreatitis.4. Hepatobiliary systemo Similar to respiratory and intestinal epithelium, defective biliar Cl- and water secretion causes thickened biliary secretions - biliary cirrhosis, cholecystitis, cholelithiasis.5. Sweat glandso In contrast to respiratory and intestinal epithelium, sweat gland duct epithelium is absorptive, i.e. function of normal CFTR in the sweat gland ducts is to reabsorb Cl- ions and Na+ from lumen,o Therefore, in the sweat ducts, loss of CFTR function leads to decreased reabsorption of NaCl - Hypertonic sweat with increased Na+ and Cl- in sweat.
Category:
Pathology
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