Respiratory - Cystic Fibrosis (CF) Midterm Notes PDF
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University of Windsor
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These notes provide an overview of cystic fibrosis (CF), a genetic disorder affecting the function of exocrine glands, primarily impacting the lungs, pancreas, and reproductive system. The notes cover the causes, pathophysiology, and effects on various organ systems, including the respiratory and digestive tracts. They also discuss disease transmission and risk factors.
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4 1 RESPIRATORY – Cys$c Fibrosis (CF) Cys$c Fibrosis (CF) is a gene$c disorder that affects the func.on of the exocrine glands. It impacts mul.ple organs, par.cularly the lungs, pancreas, and reproduc.ve s...
4 1 RESPIRATORY – Cys$c Fibrosis (CF) Cys$c Fibrosis (CF) is a gene$c disorder that affects the func.on of the exocrine glands. It impacts mul.ple organs, par.cularly the lungs, pancreas, and reproduc.ve system. The disease is characterized by the produc.on of thick, s$cky mucus that can clog airways and other ducts within the body. 1. Most Likely Cause Cause: o Gene$c Muta$on in the CFTR Gene: Cys.c fibrosis is caused by muta.ons in the Cys$c Fibrosis Transmembrane Conductance Regulator (CFTR) gene. o Most Common Muta$on: The most common muta.on is the F508del muta$on, which results in a misfolded CFTR protein that is subsequently destroyed by the cell's quality control system. o Impact of Muta$on: The muta.on disrupts the normal func.on of the CFTR protein, which is responsible for transpor.ng chloride ions across epithelial cell membranes. o Protein Deficiency: Muta.ons in the CFTR gene lead to decreased chloride ion transport, resul.ng in thicker mucus in the lungs, pancreas, and reproduc.ve system. 2. Pathophysiology The pathophysiology of cys.c fibrosis involves dysfunc.on of the CFTR protein, which is a chloride ion channel present on the surface of epithelial cells in various organs. This dysfunc.on affects mul.ple organ systems, but the primary impact is seen in the lungs, diges$ve system, and reproduc$ve system. 1. Chloride Ion Transport Dysfunc$on: o Normally, CFTR transports chloride ions from the intracellular space to the extracellular space across the epithelial cells. o Sodium and water follow chloride ions, ensuring proper hydra.on of mucus. o In CF, the defec.ve CFTR protein fails to transport chloride ions, leading to a decrease in the movement of sodium and water. This results in the produc.on of thick, dehydrated mucus in the airways, pancreas, intes.nes, and other organs. 2. Respiratory System Effects: o Thick mucus clogs the airways, crea.ng a breeding ground for bacterial infec.ons. o Recurrent lung infec.ons (e.g., Pseudomonas aeruginosa and Staphylococcus aureus) occur, leading to chronic inflamma.on and bronchiectasis. o Inflammatory mediators like IL-8 recruit neutrophils, which release toxic mediators that damage lung.ssue, resul.ng in further airway obstruc.on and structural lung disease. 3. Diges$ve System Effects: 2 o The pancreas is unable to secrete enzymes effec.vely due to mucus blocking the pancrea.c ducts, leading to pancrea$c insufficiency and malabsorp$on of nutrients. o Intes.nal obstruc.on can occur due to the thick, s.cky mucus in the intes.nes. 4. Reproduc$ve System Effects: o Vas Deferens Blockage: In males, the vas deferens may be absent or blocked, leading to infer$lity. 3. Disease Transmission Transmission: o Cys.c fibrosis is a gene$c disorder inherited in an autosomal recessive paPern. o Both parents must be carriers of the CFTR gene muta$on for their child to inherit the disease. o Carriers (heterozygous individuals) typically do not show symptoms of CF, but they can pass the defec.ve gene to their offspring. 4. Risk Factors The primary risk factor for cys.c fibrosis is related to gene$cs. Other environmental and geographic factors can influence the severity of the disease, but they do not cause it. Non-Modifiable Risk Factors Gene$cs: Being born to parents who are carriers of the CFTR gene muta$on is the primary risk factor for cys.c fibrosis. Ethnicity: Cys.c fibrosis is most common in people of Caucasian/European descent, with about 1 in 25 being a carrier of the defec.ve gene. Environmental/Other Factors Geography: The prevalence of CF varies by geographic loca.on, being more common in popula.ons of European descent compared to popula.ons of Asian or African descent. Access to Care: Early diagnosis and access to CFTR modulator medica$ons can impact the severity of symptoms and quality of life. Summary Table Criteria Cys$c Fibrosis (CF) Most Likely Gene$c muta$on of the CFTR gene. The most common muta.on is F508del, Cause leading to a defec.ve CFTR protein. Dysfunc.on of the CFTR protein impairs chloride ion transport, resul.ng in thick, s$cky mucus in the airways, pancreas, intes.nes, and vas deferens. Pathophysiology This causes airway blockage, chronic infec.ons, pancrea.c insufficiency, and infer.lity. Autosomal recessive inheritance. A child must inherit defec.ve CFTR genes Transmission from both parents to develop CF. Non-Modifiable: Gene.cs (carrier parents), Caucasian ethnicity. Risk Factors Environmental/Other: Access to early diagnosis and CFTR modulator medica.ons affects disease outcomes. 3 Clinical Manifesta$ons Respiratory Symptoms: o Chronic cough with thick, s.cky mucus. o Recurrent respiratory infec$ons (e.g., Pseudomonas aeruginosa, Staphylococcus aureus). o Bronchiectasis and progressive lung disease. Gastrointes$nal Symptoms: o Pancrea$c insufficiency: Difficulty diges.ng food due to blocked pancrea.c ducts. o Steatorrhea (faPy stools) due to poor fat absorp.on. o Failure to thrive in infants and children due to malabsorp.on. Reproduc$ve Symptoms: o Male infer$lity due to absent or blocked vas deferens. Other Symptoms: o Salty-tas$ng skin due to abnormal sodium and chloride transport across sweat glands. Diagnosis Newborn Screening: CF is oYen detected via newborn screening. Sweat Test: Measures chloride concentra.on in sweat; CF is diagnosed if the concentra.on is greater than 60 mmol/L. Gene$c Tes$ng: Iden.fies CFTR muta.ons, such as F508del, to confirm a CF diagnosis Treatment Airway Clearance Techniques (ACTs): Includes chest physiotherapy to help clear mucus from the lungs. Medica$ons: o CFTR Modulators: Target specific CFTR muta.ons to improve protein func.on. o Mucoly$cs: Help thin and clear mucus from the lungs. o An$bio$cs: Treat and prevent lung infec.ons. o Pancrea$c Enzyme Replacement Therapy (PERT): Helps with diges.on and nutrient absorp.on. Nutri$onal Support: High-calorie, high-fat diet with fat-soluble vitamin supplementa.on. Lung Transplant: Used as a last resort for individuals with end-stage lung disease due to CF.