A mother brings her 6-month-old daughter to the HCP for evaluation of possible colic. The mother says the baby has had many episodes of crying after eating and, despite having a good appetite, is not gaining weight. The mother says the baby's belly "gets all swollen sometimes." The mother says the baby tastes "salty" when the mother kisses the baby. Further work up reveals a diagnosis of cystic fibrosis. The mother relates that her 23-month-old son has had multiple episodes of "chest congestion" and was hospitalized once for pneumonia. The mother wants to know what cystic fibrosis is and she also wants to know if she should have any more children.

 

 

• Why the patient is presenting with the specific symptoms described.
• The physiologic response to the stimulus presented in the scenario and why you think this response occurred.
• The cells that are involved in this process.
• How another characteristic (e.g., gender, genetics) would change your response.

 

Cystic fibrosis is a disease wherein there is a mutation (absence of single phenylalanine) in encoding the cystic fibrosis transmembrane regulator (CFTR). The CFTR protein is a membrane transporter that is responsible for maintaining the balance in the airways. A defect in the CFTR protein leads to defects in chloride transport particular in the lungs, exocrine glands, sweat ducts, and pancreas.

It is important to note that the functions of CFTR are tissue specific thus the impact of the mutation is also expected to be tissue-specific. The primary function of CFTR in the sweat gland ducts is reabsorption of luminal chloride ions and increase sodium reabsorption through the epithelial sodium channel (ENaC) (epithelial cells are highly involved in this mechanism). Therefore, the functional loss of the CFTR would lead to a decreased reabsorption of sodium chloride (salt) which would lead to having hypertonic salty secretions, thus, salty sweat. All the while in the respiratory and gastrointestinal epithelium, CFTR is important for chloride secretion in the lumen. Mutations would lead to a total loss or reduced chloride secretion and increase sodium absorption of in the lumen. Since water follows the direction of sodium, water reabsorption is also expected thus lowering the water content of the surface fluid of the mucosal cells resulting to a dehydrated mucus that could lead to a defecting mucociliary action thus making it hard to expectorate and the concentrated mucus could accumulate leading to congestion and ultimately airway obstruction thus increased predisposition to recurrent respiratory infections. The increase in water reabsorption would also be the reason behind the swelling. CFTR is also responsible for regulating transport of bicarbonate ions. In normal tissues, alkaline fluids are secreted. However, if there is a defective CFTR then there is a marked loss of bicarbonate hence acidic fluids are secreted. The increased acidity of the environment could lead to pancreatic insufficiency that could have caused weight loss since a decrease in function of the pancreas means there's a decrease in enzymes that are need for the absorption of nutrients.

Cystic fibrosis is an autosomal recessive disease which means that only when both parents carry the defective gene will the disease manifest. If both parents have the disease, the likelihood of having a child with the disease is 100%. If either of the parents have the active disease while the other is just a carrier, the probability is at 50%. If neither have an active disease but both carries the defective gene, there is 25% probability. However, mutations on the CF gene may also vary in severity hence they may not all present with the same phenotype. Some may be a mild mutation thus only manifesting a mild phenotype which is very much compatible with life. Some may be severe mutations and presents as the classic cystic fibrosis with the complete absence of the CFTR protein.

Cystic fibrosis and its severity is now also known to be heavily influence by environmental modifiers as well as other genetic modifiers in which they are able to modify the occurence and severity of organ-specific manifestations.

• In genetics, polymorphisms in genes modulating neutrophilic function in bacterial infections may act as a modifier for severity of pulmonary disease in cystic fibrosis.
• In the environment, presence of Pseudomonas aeruginosa that could infect the respiratory system may increase the severity of respiratory manifestations of cystic fibrosis. Other factors that may influence the severity of pulmonary disease would include concurrent infection and virulence of pathogens, and even exposure to tobacco and allergens affecting the respiratory system.

Step-by-step explanation

Some add'l information you might need:

Cystic Fibrosis is a disease that affects the respiratory, primarily the lungs, and digestive systems. It's hereditary wherein the defect is in the CF gene on chromosome 7 that encodes for cystic fibrosis transmembrane regulator (CFTR). It affects fluid secretion and in many individuals, it can lead to abnormally viscous secretions that could obstruct organ passages which may manifest as chronic lung disease secondary to recurrent infections, steatorrhea, pancreatic insufficiency, hepatic cirrhosis, malnutrition, intestinal obstruction and male infertility.

CFTR regulates multiple channels and cellular processes of which include outward (to airways) chloride channels, inward potassium channels, gap junctions, epithelial sodium channel (ENaC), and other processes involved in mucus secretion and ATP transport. Among these, ENaC is said to have pathophysiologic relevance on cystic fibrosis. It is responsible for sodium uptake from the lumen making the lumen hypotonic. ENaC is inhibited in a normal state by CFTR.

While in cystic fibrosis, activity of ENaC is increased which would increases sodium uptake from the apical membrane, however in sweat ducts, ENaC activity decreases hence the luminal fluid becomes hypertonic and thus results to high sodium chloride in sweat.

Due to the increased predisposition to respiratory infections, there is also higher susceptibility to Pseudomonas aeruginosa pneumonia which may be harder to treat because of the bacteria's characteristic enabling it to harness an antibiotic resistance.

Chloride and sodium channel regulated by CFTR:

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