# Cystic Fibrosis Pathology > Cystic fibrosis pathology for MBBS Pathology: CFTR genetics, meconium ileus, bronchiectasis, pancreatic disease and the Indian mutation spectrum. - Canonical URL: https://prepelephant.com/topics/mbbs/pathology/cystic-fibrosis-pathology - Exam / course: MBBS · Subject: Pathology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Cystic Fibrosis Pathology", PrepElephant, https://prepelephant.com/topics/mbbs/pathology/cystic-fibrosis-pathology ## Direct answer A child who returns month after month with productive cough, failure to thrive and bulky, greasy stools has cystic fibrosis until proved otherwise: an autosomal recessive defect of the CFTR chloride channel (7q31.2) that dehydrates secretions, so mucus plugs airways, blocks pancreatic ducts and makes sweat salty. Meconium ileus in the neonate, bronchiectasis colonised by Pseudomonas by school age, pancreatic exocrine insufficiency in about 85%, and congenital bilateral absence of the vas deferens in surviving men form the classic quartet. The sweat chloride test remains the diagnostic gold standard worldwide and in India, where the disease is under-recognised and the mutation spectrum is far more heterogeneous than the textbook ΔF508 story suggests. ## What you must remember - **Gene and inheritance:** CFTR on 7q31.2, autosomal recessive; ΔF508 (a three-base deletion removing phenylalanine 508, a class II folding/trafficking defect) is the commonest mutation in Europeans, but Indian series report ΔF508 in only about 19-31% of alleles, with dozens of rare variants — genetic panels designed for Western populations miss Indian patients. - **Diagnostic threshold:** pilocarpine iontophoresis sweat chloride of 60 mmol/L or more confirms the diagnosis on two occasions; values below 40 make it unlikely, with an intermediate zone that demands repeat testing and genotyping. - **Lung disease, the killer:** dehydrated mucus with impaired mucociliary clearance leads to bronchiectasis; sequential colonisation by Staphylococcus aureus, then mucoid Pseudomonas aeruginosa, Burkholderia cepacia and Aspergillus (allergic bronchopulmonary aspergillosis); cor pulmonale eventually kills. - **Gut and pancreas:** meconium ileus (neonatal small-bowel obstruction with microcolon); distal intestinal obstruction syndrome later; pancreatic acinar destruction causing steatorrhoea and fat-soluble vitamin deficiency; focal biliary cirrhosis from bile-duct plugging; insulin-deficient diabetes as survivors age. - **Genitourinary:** congenital bilateral absence of the vas deferens causes azoospermia; some men with CBAVD and moderate CFTR variants present at infertility clinics with no lung disease — a favourite viva link. - **Why the sweat is salty:** the sweat duct normally reabsorbs chloride (with sodium following) through CFTR; the defective channel cannot reabsorb, so chloride and sodium remain in sweat — the physiological basis of every diagnostic test in the disease. - **Indian reality:** chronic cough with failure to thrive is repeatedly misattributed to tuberculosis, malnutrition or chronic diarrhoea, so diagnosis is delayed by years; cystic fibrosis must stay on the differential when anti-tubercular therapy fails a child with bronchiectasis. ## A worked diagnostic path Take a two-year-old with recurrent pneumonia, weight faltering below the third centile and stools that float and stain the toilet. Step one is the sweat chloride test, not a gene panel. If chloride is 95 mmol/L on two samples, the diagnosis is essentially made; genotyping then follows for counselling and for eligibility for CFTR modulator drugs such as ivacaftor-lumacaftor-elexacaftor, which work only for specific mutation classes. Step two quantifies organ damage: chest imaging for bronchiectasis, faecal elastase for pancreatic insufficiency, annual glucose tolerance for cystic-fibrosis-related diabetes. Step three is treatment built on physiology — airway clearance and nebulised recombinant deoxyribonucse (dornase alfa) to thin viscous sputum, pancreatic enzyme replacement with every meal, and fat-soluble vitamin supplementation. Stool microscopy for fat globules and a positive sweat test together close the case that TB workups had left open for a year. ## Where students slip Two errors recur in professional examinations. First, candidates parrot "ΔF508 is the commonest mutation" as if it were universal — in Indian genetics questions that statement earns a viva counter-question about heterogeneity, and the honest answer is that Indian alleles are scattered across rare variants, making newborn screening by mutation panels impractical. Second, students call cystic fibrosis a mucus-hypersecretion disease; it is primarily a dehydration-of-secretions disease — the chloride channel fails to secrete chloride at the apical membrane (with sodium and water following), so the mucus is inadequately hydrated, not overproduced. That distinction is exactly why CFTR modulators work and why "mucolytics alone" is an incomplete answer. ## Frequently asked questions ### Which single test confirms cystic fibrosis? Sweat chloride by pilocarpine iontophoresis, at 60 mmol/L or more on two separate occasions, remains the gold standard; genotyping confirms and classifies but does not replace it. ### Why does meconium ileus occur in neonates? Defective chloride secretion dehydrates meconium, which becomes sticky and inspissated in the terminal ileum, producing small-bowel obstruction with a unused microcolon. ### Which organisms colonise the lungs in sequence? Staphylococcus aureus comes first in infancy, followed by mucoid Pseudomonas aeruginosa, then Burkholderia cepacia; Aspergillus causes allergic bronchopulmonary disease rather than invasion. ### How common is ΔF508 in Indian patients? Only about one-fifth to one-third of Indian alleles carry ΔF508, against roughly 70% in European populations, so Indian diagnosis relies more on sweat testing than on Western mutation panels. ### Why are cystic fibrosis men infertile? Congenital bilateral absence of the vas deferens, a direct Wolffian-duct consequence of CFTR mutations, causes obstructive azoospermia with normal spermatogenesis.