Snapshot A 3-year-old boy with a history of recurrent pneumonia and chronic diarrhea. His mother states that he has 6-8 four smelling stools per day. PE reveals a low grade fever, scattered rhonchi over both lung fields, crepitant rales at the left lung base and dullness to percussion. Introduction Cystic fibrosis is a genetic disorder leading to excessive, viscous secretions that plug exocrine glands autosomal recessive disorder caused by mutations in CFTR gene (chloride channel) on chromosome 7 CFTR is a transmembrane cAMP-activated ion channel its normal function is to reabsorb chloride ions (lumen → cell) in sweat glands and to secrete chloride ions (cell → lumen) in other exocrine glands (e.g., pancreas and lungs) movement of chloride creates a charge gradient that induces movement of sodium ions in the same direction as chloride to mitigate the gradient movement of these ions drags solvent (water) with them 3 nucleotide deletion most common mutation is 508 Phe del result is instability of CFTR protein and premature degradation by Golgi apparatus inability to alter ionic gradients of Cl- results in mucus dehydration Affects multiple organ systems with widespread exocrine gland dysfunction pancreatic exocrine insufficiency is responsible for most of them Epidemiology most common genetic disease in the United States mostly affects Caucasians Newborn screening now routine in all states Presentation Symptoms respiratory symptoms are more prominent in adulthood recurrent pulmonary infections Pseudomonal spp and S. aureus are most common chronic sinusitis chronic, productive cough dyspnea on exertion hemoptysis gastrointestinal symptoms are more prominent in infancy chronic, frequent diarrhea greasy stool with flatulence from malabsorption secondary to pancreatic insufficiency steatorrhea can cause deficiency in fat soluble vitamins can lead to rectal prolapse meconium ileus in infants (15%) pancreatitis other symptoms calcium oxalate kidney stones secondary to fat malabosorption Physical exam failure to thrive (50%) respiratory compromise (50%) "salty taste" cyanosis digital clubbing ronchi rales hyperresonance of chest to percussion nasal polyposis Evaluation CXR hyperinflation prominent bronchovascular markings bronchiectasis with "tram tracks" and peribronchial cuffing diffuse bronciectactic changes Sweat chloride test historical diagnostic gold standard >60 mEq/L in patients <20 years old >80 mEq/L in adults Genetic testing confirms disease by identification of specific genetic mutation Immunoreactive trypsinogen assay Nasal transepithelial potential difference Pulmonary function testing often abnormal before first birthday obstructive pattern with increased lung volumes (TLC and RV) over time from air trapping and hyperinflation reduced diffusing capacity (DLCO) reduced or normal FEV1:FVC ratio given obstructive pattern with possible late restrictive features (e.g., fibrosis, tissue destruction, and/or hyperinflation) Differential Inherited immunodeficiency (SCID, CVID) Primary ciliary dyskinesia Treatment Lifestyle health maintenance nutritional counseling psychiatric/psychologic support indicated in most patients with or without mental instability up-to-date immunizations indicated in all patients Pharmacologic respiratory therapy indicated in all patients includes several components including chest physiotherapy (percussion, positive pressure, nebulizers) bronchodilators inhaled corticosteriods if asthmatic component or ABPA DNA-ase and hypertonic saline antibiotics chronic macrolide therapy common IV antibiotics for acute exacerbations anti-inflammatory agents (ibuprofen) pancreatic enzymes and fat-soluble vitamins indicated for malabsorption Operative lung and pancreas transplantation indicated for most severe, but only if patient can tolerate surgery Prognosis, Prevention, and Complications Prognosis while patients are living longer and more complete lives with modern medicine, rarely do CF patients live beyond 40 years of age without transplantation Prevention immunization for influenza and pneumococcus can prevent infections embryonic selection, although controversial, has been used by known carriers or affected couples to prevent transmission of the disease to their children Complications chronic hypoxemia and hypercapnia lead to pulmonary hypertension patients often develop cor pulmonale (RHF) Recurrent, drug-resistent bacterial or fungal pneumonias classically Pseudomonas idiopathic hyponatremia CF-related diabetes mellitus fat-soluble vitamin deficiency (low vitamin A, D, K, and E) esophageal varices biliary cirrhosis and cholelithiasis infertility (95%) absence/obliteration of the vas deferens heat exhaustion (poor sweating)
QUESTIONS 1 of 12 1 2 3 4 5 6 7 8 9 10 11 12 Previous Next Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.PL.15.72) A 1-year-old child who was born outside of the United States is brought to a pediatrician for the first time because she is not gaining weight. Upon questioning, the pediatrician learns that the child has had frequent pulmonary infections since birth, and on exam the pediatrician appreciates several nasal polyps. Genetic testing is subsequently ordered to confirm the suspected diagnosis. Testing is most likely to show absence of which of the following amino acids from the protein involved in this child's condition? QID: 106523 Type & Select Correct Answer 1 Histidine 4% (3/74) 2 Leucine 8% (6/74) 3 Lysine 5% (4/74) 4 Valine 1% (1/74) 5 Phenylalanine 74% (55/74) M 1 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 5 Review Tested Concept Review Full Topic (M1.PL.15.72) A newborn is found to have cystic fibrosis during routine newborn screening. The parents, both biochemists, are curious about the biochemical basis of their newborn's condition. The pediatrician explains that the mutation causing cystic fibrosis affects the CFTR gene which codes for the CFTR channel. Which of the following correctly describes the pathogenesis of the most common CFTR mutation? QID: 106514 Type & Select Correct Answer 1 Insufficient CFTR channel production 10% (9/91) 2 Defective post-translational glycosylation of the CFTR channel 59% (54/91) 3 Excess CFTR channel production 0% (0/91) 4 Defective post-translational hydroxylation of the CFTR channel 11% (10/91) 5 Defective post-translational phosphorylation of the CFTR channel 19% (17/91) M 1 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review Tested Concept Review Full Topic (M1.PL.14.91) A 27-year-old female presents to general medical clinic for a routine checkup. She has a genetic disease marked by a mutation in a chloride transporter. She has a history of chronic bronchitis. She has a brother with a similar history of infections as well as infertility. Which of the following is most likely true regarding a potential vitamin deficiency complication secondary to this patient's chronic illness? QID: 104731 Type & Select Correct Answer 1 It may result in wound healing defects 18% (16/90) 2 It may result in corneal vascularization 17% (15/90) 3 It may result in the triad of confusion, ophthalmoplegia, and ataxia 11% (10/90) 4 It may be exacerbated by excessive ingestion of raw eggs 4% (4/90) 5 It may manifest itself as a prolonged PT 47% (42/90) M 4 Question Complexity D Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 5 Review Tested Concept Review Full Topic (M1.PL.14.0) A 1-year-old male with a history of recurrent pseudomonal respiratory infections and steatorrhea presents to the pediatrician for a sweat test. The results demonstrate a chloride concentration of 70 mEq/L (nl < 40 mEq/L). Which of the following defects has a similar mode of inheritance as the disorder experienced by this patient? QID: 106978 Type & Select Correct Answer 1 Trinucleotide repeat expansion of CAG on chromosome 4 10% (8/83) 2 Accumulation of glycogen in the lysosome 48% (40/83) 3 Inability to convert carbamoyl phosphate and ornithine into citrulline 16% (13/83) 4 Abnormal production of type IV collagen 13% (11/83) 5 Mutated gene for mitochondrial-tRNA-Lys 7% (6/83) M 1 Question Complexity D Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.PL.13.79) A child with which of the following diseases would have the highest morbidity from being outside during a hot summer day? QID: 100882 Type & Select Correct Answer 1 Tay-Sachs disease 1% (1/85) 2 Cystic fibrosis 81% (69/85) 3 Cerebral palsy 0% (0/85) 4 Down syndrome 0% (0/85) 5 Asthma 15% (13/85) M 4 Question Complexity E Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review Tested Concept Review Full Topic (M1.PL.13.3) A 4-year-old Caucasian girl previously diagnosed with asthma presents with recurrent sinusitis, otitis media, and clubbing of the nail bed. Family history is significant for a distant cousin with cystic fibrosis. A "sweat test" is performed and comes back normal. What additional diagnostic test would be helpful in establishing a diagnosis? QID: 100806 Type & Select Correct Answer 1 Nasal transepithelial potential difference 61% (85/139) 2 Chest radiograph 17% (23/139) 3 Skeletal survey 1% (2/139) 4 Complete blood cell count 11% (15/139) 5 Urinalysis 9% (13/139) M 2 Question Complexity E Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK
All Videos (1) Login to View Community Videos Login to View Community Videos Peribronchial cuffing Keshav Mudgal Respiratory - Cystic Fibrosis D 11/5/2015 82 views 4.7 (3) Respiratory | Cystic Fibrosis Respiratory - Cystic Fibrosis Listen Now 14:33 min 7/5/2021 78 plays 5.0 (1)