DNP 649 Module 1 Cell Physiology Case Study: Cystic Fibrosis Example

From Gene to Salty Skin: A Cell Physiology Case Study of Cystic Fibrosis in an Infant

Student Name

Edson College of Nursing and Health Innovation, Arizona State University

DNP 649: Advanced Physiology

Instructor Name

Month Day, Year

From Gene to Salty Skin: A Cell Physiology Case Study of Cystic Fibrosis in an Infant

Case

A 4-month-old boy has poor weight gain despite feeding well, frequent greasy stools and a persistent cough. His parents say he tastes salty when they kiss him. His newborn screen showed an elevated immunoreactive trypsinogen. A sweat chloride test measures 78 mmol/L. Genetic testing shows two copies of the F508del variant in the CFTR gene.

1. Interpreting the Data

Sweat chloride of 78 mmol/L. A sweat chloride of 60 mmol/L or higher is consistent with cystic fibrosis in a child with a positive newborn screen, and a value below 30 makes it unlikely (Farrell et al., 2017). Together with two disease-causing variants, the diagnosis is confirmed.

Elevated immunoreactive trypsinogen. Trypsinogen leaks into the blood when pancreatic ducts are obstructed, which is why it is used as a newborn screen.

Greasy stools and poor weight gain. These point to pancreatic insufficiency: digestive enzymes cannot reach the intestine, so fat and protein are malabsorbed.

2. From Gene to Protein: Genetic Control and Quality Control

The CFTR gene on chromosome 7 codes for the cystic fibrosis transmembrane conductance regulator. Following the pathway of transcription, mRNA processing and translation on ribosomes of the rough endoplasmic reticulum (Hall & Hall, 2026), the protein is made and must fold correctly before it moves through the Golgi apparatus to the cell membrane. The F508del variant deletes a single amino acid, phenylalanine at position 508. The protein misfolds, the endoplasmic reticulum's quality control system recognizes it as abnormal, and most of it is tagged and degraded in proteasomes instead of reaching the membrane (Elborn, 2016). This is a trafficking defect: the gene is transcribed, but the protein rarely arrives where it is needed.

3. From Protein to Membrane: Transport Across the Cell Membrane

CFTR is an anion channel in the apical membrane of epithelial cells, opened by ATP binding and phosphorylation by protein kinase A. It lets chloride and bicarbonate move down their electrochemical gradients. Because water follows solute movement by osmosis, chloride secretion through CFTR draws water onto the epithelial surface. Without functioning CFTR, chloride secretion falls, sodium absorption through epithelial sodium channels continues unchecked and water is pulled back into the cells.

4. From Membrane to Organ: Explaining His Symptoms

Airways. The thin layer of surface liquid that lets cilia beat becomes dehydrated, mucus becomes thick and sticky and mucociliary clearance fails. Bacteria remain in the airway, leading to inflammation and infection, which explains his cough.

Pancreas. Reduced chloride and bicarbonate secretion leaves pancreatic secretions thick and acidic, so ducts plug, enzymes cannot reach the intestine and the gland is gradually damaged. This explains his greasy stools and poor weight gain.

Sweat glands. Here the defect works in reverse. The sweat duct depends on CFTR to pull chloride back out of the sweat on its way to the skin. Without it, chloride and sodium stay in the sweat, which is why his skin tastes salty and why the sweat test works.

5. Treating the Protein, Not Only the Symptoms

Because the defect lies in a protein, drugs called CFTR modulators can partly correct it. Correctors help the misfolded protein fold and reach the membrane, and potentiators keep the channel open longer. In a trial of 403 patients aged 12 and older with at least one F508del variant, the triple combination elexacaftor-tezacaftor-ivacaftor improved lung function, measured as percent predicted FEV1, by about 14 points over 24 weeks, brought 63% fewer pulmonary exacerbations and dropped sweat chloride by nearly 42 mmol/L relative to placebo (Middleton et al., 2019). The fall in sweat chloride shows the drug working at the level of the membrane transport this case describes. For this infant, care now centers on pancreatic enzyme replacement, nutrition and airway clearance, with modulator eligibility reviewed by his CF center as age approvals change.

References

Elborn, J. S. (2016). Cystic fibrosis. The Lancet, 388(10059), 2519-2531. https://doi.org/10.1016/S0140-6736(16)00576-6

Farrell, P. M., White, T. B., Ren, C. L., Hempstead, S. E., Accurso, F., Derichs, N., Howenstine, M., McColley, S. A., Rock, M., Rosenfeld, M., Sermet-Gaudelus, I., Southern, K. W., Marshall, B. C., & Sosnay, P. R. (2017). Diagnosis of cystic fibrosis: Consensus guidelines from the Cystic Fibrosis Foundation. Journal of Pediatrics, 181S, S4-S15. https://doi.org/10.1016/j.jpeds.2016.09.064

Hall, J. E., & Hall, M. E. (2026). Guyton and Hall textbook of medical physiology (15th ed.). Elsevier.

Middleton, P. G., Mall, M. A., Dřevínek, P., Lands, L. C., McKone, E. F., Polineni, D., Ramsey, B. W., Taylor-Cousar, J. L., Tullis, E., Vermeulen, F., Marigowda, G., McKee, C. M., Moskowitz, S. M., Nair, N., Savage, J., Simard, C., Tian, S., Waltz, D., Xuan, F., ... Jain, R. (2019). Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele. New England Journal of Medicine, 381(19), 1809-1819. https://doi.org/10.1056/NEJMoa1908639