Updated: 1/15/2019

Cystic Fibrosis

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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 
      • 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
        • 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)
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)
 

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Questions (11)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.PL.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? Review Topic

QID: 106523
1

Histidine

17%

(1/6)

2

Leucine

0%

(0/6)

3

Lysine

0%

(0/6)

4

Valine

0%

(0/6)

5

Phenylalanine

67%

(4/6)

M1

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PREFERRED RESPONSE 5

(M1.PL.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? Review Topic

QID: 106514
1

Insufficient CFTR channel production

22%

(2/9)

2

Defective post-translational glycosylation of the CFTR channel

56%

(5/9)

3

Excess CFTR channel production

0%

(0/9)

4

Defective post-translational hydroxylation of the CFTR channel

22%

(2/9)

5

Defective post-translational phosphorylation of the CFTR channel

0%

(0/9)

M1

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(M1.PL.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? Review Topic

QID: 106978
1

Trinucleotide repeat expansion of CAG on chromosome 4

17%

(1/6)

2

Accumulation of glycogen in the lysosome

67%

(4/6)

3

Inability to convert carbamoyl phosphate and ornithine into citrulline

0%

(0/6)

4

Abnormal production of type IV collagen

17%

(1/6)

5

Mutated gene for mitochondrial-tRNA-Lys

0%

(0/6)

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PREFERRED RESPONSE 2
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(M1.PL.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? Review Topic

QID: 104731
1

It may result in connective tissue defects

5%

(1/19)

2

It may result in corneal vascularization

26%

(5/19)

3

It may result in the triad of confusion, ophthalmoplegia, and ataxia

5%

(1/19)

4

It may be exacerbated by excessive ingestion of raw eggs

5%

(1/19)

5

It may manifest itself as a prolonged PT

58%

(11/19)

M1

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PREFERRED RESPONSE 5

(M1.PL.79) A child with which of the following diseases would have the highest morbidity from being outside during a hot summer day? Review Topic

QID: 100882
1

Tay-Sachs disease

4%

(1/24)

2

Cystic fibrosis

75%

(18/24)

3

Cerebral palsy

0%

(0/24)

4

Down syndrome

0%

(0/24)

5

Asthma

17%

(4/24)

M1

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PREFERRED RESPONSE 2

(M1.PL.109) A 19-year-old Caucasian male underwent a bilateral lung transplant. His past medical history is significant for several severe respiratory infections. A sweat test found chloride levels of 70 mmol/L, and digital clubbing was present on physical examination. Which of the following is most likely to also be present in this patient: Review Topic

QID: 100912
1

Hypertrophic cardiomyopathy

12%

(5/42)

2

Azoospermia

67%

(28/42)

3

Ghon complex

0%

(0/42)

4

Low serum alpha1-antitrypsin levels

17%

(7/42)

5

Mitral valve prolapse

0%

(0/42)

M1

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PREFERRED RESPONSE 2

(M1.PL.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? Review Topic

QID: 100806
1

Nasal transepithelial potential difference

58%

(42/73)

2

Chest radiograph

19%

(14/73)

3

Skeletal survey

1%

(1/73)

4

Complete blood cell count

14%

(10/73)

5

Urinalysis

7%

(5/73)

M1

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PREFERRED RESPONSE 1
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