A 2720-g (6-lb) female newborn delivered at 35 weeks’ gestation starts vomiting and becomes inconsolable 48 hours after birth. The newborn has not passed her first stool yet. Examination shows abdominal distention and high-pitched bowel sounds. A water-soluble contrast enema study shows microcolon. Serum studies show increased levels of immunoreactive trypsinogen. Which of the following is the most likely additional laboratory finding?

Increased sodium concentration in sweat

Decreased hydrogen ion concentration in renal collecting duct

Increased chloride concentration in alveolar fluid

Increased bicarbonate concentration in pancreatic secretions

Increased serum calcium concentration

A 14-year-old boy is brought to the physician by his parents for a follow-up examination. Since early childhood, he has had recurrent respiratory infections that cause him to miss several weeks of school each year. Last month, he had received treatment for his seventh episode of sinusitis this year. He has always had bulky, foul-smelling, oily stools that are now increasing in frequency. His parents are concerned that he is too thin and not gaining weight appropriately. He has a good appetite and eats a variety of foods. He is in the 10th percentile for height and the 5th percentile for weight. Examination of the nasal cavity shows multiple nasal polyps. The lung fields are clear upon auscultation. Further evaluation is most likely to show which of the following?

Positive methacholine challenge test

Anti-tissue transglutaminase antibodies

A 7-year-old girl is brought by her parents to her pediatrician's office for a persistent cough observed over the past month. She was diagnosed with cystic fibrosis 2 years ago and has been receiving chest physiotherapy regularly and the flu vaccine yearly. Her parents tell the pediatrician that their daughter has been coughing day and night for the past month, and produces thick, purulent, foul-smelling sputum. They are concerned because this is the first time such an episode has occurred. She has not had a fever, chills or any other flu-like symptoms. On examination, her blood pressure is 100/60 mm Hg, the pulse is 82/min, and the respiratory rate is 16/min. Breath sounds are reduced over the lower lung fields along with a presence of expiratory wheezing. Her sputum culture comes back positive for an aerobic, non-lactose fermenting, oxidase-positive, gram-negative bacillus. Which of the following prophylactic regimes should be considered after treating this patient for her current symptoms?

Oral trimethoprim-sulfamethoxazole

Oral amoxicillin/clavulanic acid

An 11-month-old boy is brought to a pediatrician by his parents with a recurrent cough, which he has had since the age of 2 months. He has required 3 hospitalizations for severe wheezing episodes. His mother also mentions that he often has diarrhea. The boy’s detailed history reveals that he required hospitalization for meconium ileus during the neonatal period. Upon physical examination, his temperature is 37.0°C (98.6ºF), pulse rate is 104/min, respiratory rate is 40/min, and blood pressure is 55/33 mm Hg. An examination of the boy’s respiratory system reveals the presence of bilateral wheezing and scattered crepitations. An examination of his cardiovascular system does not reveal any abnormality. His length is 67.3 cm (26.5 in) and weight is 15 kg (33 lbs). His sweat chloride level is 74 mmol/L. His genetic evaluation confirms that he has an autosomal recessive disorder resulting in a dysfunctional membrane-bound protein. Which of the following best describes the mechanism associated with the most common mutation that causes this disorder?

Defective maturation and early degradation of the protein

Decreased chloride transport through the protein

Disordered regulation of the protein

Decreased transcription of the protein due to splicing defect

Complete absence of the protein

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 AUTOSOMAL RECESSIVE mode of inheritance as the disorder experienced by this patient?

Accumulation of glycogen in the lysosome

Abnormal production of type IV collagen

Trinucleotide repeat expansion of CAG on chromosome 4

Mutated gene for mitochondrial-tRNA-Lys

Inability to convert carbamoyl phosphate and ornithine into citrulline

A 4-year-old girl is brought to the physician by her parents because she is severely underweight. She is easily fatigued and has difficulty keeping up with other children at her daycare. She has a good appetite and eats 3 full meals a day. She has 4 to 5 bowel movements daily with bulky, foul-smelling stools that float. She has had recurrent episodes of sinusitis since infancy. Her parents report that she recently started to snore during her sleep. She is at the 15th percentile for height and 3rd percentile for weight. Her vital signs are within normal limits. Examination shows pale conjunctivae. A few scattered expiratory crackles are heard in the thorax. There is abdominal distention. Which of the following is the most likely underlying cause of this patient's failure to thrive?

Exocrine pancreatic insufficiency

T. whippelii infiltration of intestinal villi

Impaired intestinal amino acid transport

Small intestine bacterial overgrowth

Intestinal inflammatory reaction to gluten

A 10-year-old girl is admitted to the medical floor for a respiratory infection. The patient lives in a foster home and has been admitted many times. Since birth, the patient has had repeated episodes of pain/pressure over her frontal sinuses and a chronic cough that produces mucus. She was recently treated with amoxicillin for an infection. The patient is in the 25th percentile for height and weight which has been constant since birth. Her guardians state that the patient has normal bowel movements and has been gaining weight appropriately. The patient has a history of tricuspid stenosis. She also recently had magnetic resonance imaging (MRI) of her chest which demonstrated dilation of her airways. Her temperature is 99.5°F (37.5°C), blood pressure is 90/58 mmHg, pulse is 120/min, respirations are 18/min, and oxygen saturation is 94% on room air. Physical exam is notable for bruises along the patient's shins which the guardians state are from playing soccer. The rest of the exam is deferred because the patient starts crying. Which of the following findings is associated with this patient's most likely underlying diagnosis?

Increased chloride in the patient's sweat

Social withdrawal and avoidance of eye contact

Repeat sinus infections secondary to seasonal allergies

Diastolic murmur best heard along the right lower sternal border

A 2-year-old boy is brought to the physician because of a productive cough for 5 days. He has a history of recurrent lower respiratory tract infections and sinusitis treated with oral antibiotics. He frequently has loose stools that do not flush easily. He was born at 37 weeks' gestation and the neonatal period was complicated by meconium ileus. His immunizations are up-to-date. He is at the 15th percentile for height and at the 5th percentile for weight. His temperature is 37.1°C (98.8°F), pulse is 98/min, and respirations are 38/min. Pulse oximetry on room air shows an oxygen saturation of 95%. Examination shows bilateral nasal polyps. There are scattered inspiratory crackles heard in the thorax. Further evaluation of this patient is most likely to show which of the following?

Decreased residual volume on spirometry

Cytoplasmic anti-neutrophil cytoplasmic antibodies

Glutamic acid decarboxylase antibodies

Cystic fibrosis for USMLE Step 1: High-Yield Pediatrics Lessons

Genetics & Pathophysiology - The Salty Secret

Genetics: Autosomal recessive inheritance.
- Gene: CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) on chromosome 7q31.2.
- Most common mutation: ΔF508 (a Class II folding defect).
Pathophysiology: Defective chloride ion ($Cl^-$) transport across epithelial cells.
- Leads to thick, dehydrated, viscous secretions in lungs, pancreas, intestines, and biliary tract.
- In sweat ducts, impaired $Cl^-$ reabsorption results in high sweat chloride.

⭐ The sweat chloride test is the gold standard for diagnosis; a value > 60 mEq/L is diagnostic.

Ion and water movement in airway epithelium

Clinical Features - A Multi-System Mayhem

Respiratory Tract
- Recurrent & chronic sinopulmonary infections (Early S. aureus, later Pseudomonas aeruginosa).
- Chronic, productive cough; bronchiectasis; nasal polyposis.
- Allergic Bronchopulmonary Aspergillosis (ABPA) complication.
Gastrointestinal & Pancreatic
- Newborn: Meconium ileus (~20% of cases).
- Pancreas: Exocrine insufficiency (~85%) → malabsorption, steatorrhea, failure to thrive.
- Deficiency of fat-soluble vitamins (A, D, E, K).
- Distal Intestinal Obstruction Syndrome (DIOS), rectal prolapse.
Sweat Glands
- Excessive salt in sweat (“salty kiss”); basis for sweat chloride test.
Reproductive
- Males: Infertility (>95%) due to congenital bilateral absence of the vas deferens (CBAVD).
Other
- Digital clubbing.

⭐ Exam Favourite: Meconium ileus in a term infant is virtually diagnostic of Cystic Fibrosis.

Cystic Fibrosis: Multi-system Effects & Genetic Modifiers

Diagnosis - The Chloride Conundrum

Screening: Newborn screening (NBS) with ↑ Immunoreactive Trypsinogen (IRT).
Gold Standard: Quantitative Pilocarpine Iontophoresis (Sweat Chloride Test).
- Sweat Chloride > 60 mEq/L on 2 occasions is diagnostic.
- 30-59 mEq/L is intermediate; requires repeat testing or further workup.
- < 30 mEq/L makes CF unlikely.

Sweat Chloride Test Procedure for Cystic Fibrosis

⭐ Exam Favourite: Diagnosis requires identifying two CF-causing mutations in the CFTR gene. The most common mutation worldwide is ΔF508 (delta-F508).

Management - The Damage Control

Airway Clearance
- Chest physiotherapy & postural drainage
- Mucolytics: Dornase alfa (rhDNase), nebulized hypertonic saline (3-7%)
- Bronchodilators
Infection & Inflammation Control
- Long-term Azithromycin (anti-inflammatory/biofilm)
- Inhaled antibiotics for chronic Pseudomonas: Tobramycin, Aztreonam
Nutritional Support
- High-calorie, high-protein, high-fat diet
- Pancreatic enzyme replacement therapy (PERT)
- Fat-soluble vitamin (A, D, E, K) supplementation

⭐ Ivacaftor is a CFTR potentiator that improves function of the G551D mutation by increasing the channel's opening time.

CF lung inflammation: Untreated vs. CFTR modulators

High‑Yield Points - ⚡ Biggest Takeaways

Autosomal recessive disorder from CFTR gene mutation; ΔF508 is the most common.

Gold standard diagnosis is the sweat chloride test (value > 60 mEq/L).

Pancreatic insufficiency is the most common GI manifestation, leading to steatorrhea.

Chronic pulmonary infection with Pseudomonas aeruginosa is a hallmark of advanced disease.

Meconium ileus in a newborn is highly suggestive.

Nearly all males exhibit azoospermia due to congenital bilateral absence of the vas deferens.

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Cystic fibrosis