A 45-year-old man comes to the office due to progressive dyspnea on exertion and cough for the past several weeks. He has had no fever, chills, chest pain, or leg swelling. The patient is a former smoker with 5-pack-year history. Temperature is 37.2 C (99 F), blood pressure is 120/70 mm Hg, pulse is 82/min, and respirations are 16/min. The patient is hypoxemic at rest, with an oxygen saturation of 88% on room air. Jugular venous pressure is normal. Lung auscultation shows scattered crackles. Heart sounds are normal. Chest x-ray reveals bilateral midalveolar and lower alveolar opacities. Transbronchial lung biopsy reveals lipoproteinaceous material that is positive on periodic acid-Schiff stain and fills up the terminal bronchioles and alveoli. Electron microscopy of the substance shows lamellar bodies. Impaired function of which of the following most likely caused excessive accumulation of the substance in this patient's alveoli?

Question

A 45-year-old man comes to the office due to progressive dyspnea on exertion and cough for the past several weeks.  He has had no fever, chills, chest pain, or leg swelling.  The patient is a former smoker with 5-pack-year history.  Temperature is 37.2 C (99 F), blood pressure is 120/70 mm Hg, pulse is 82/min, and respirations are 16/min.  The patient is hypoxemic at rest, with an oxygen saturation of 88% on room air.  Jugular venous pressure is normal.  Lung auscultation shows scattered crackles.  Heart sounds are normal.  Chest x-ray reveals bilateral midalveolar and lower alveolar opacities.  Transbronchial lung biopsy reveals lipoproteinaceous material that is positive on periodic acid-Schiff stain and fills up the terminal bronchioles and alveoli.  Electron microscopy of the substance shows lamellar bodies.  Impaired function of which of the following most likely caused excessive accumulation of the substance in this patient's alveoli?

Quizplus · Accepted Answer

11ec160b_3b46_a6ad_9249_07c999fd3342_MD0001_00 This patient's presentation is consistent with pulmonary alveolar proteinosis (PAP), a rare condition characterized by progressive respiratory dysfunction due to the accumulation of surfactant debris within alveolar spaces. Surfactant is a lipoproteinaceous material that appears pink with periodic acid-Schiff staining; it forms concentrically laminated structures (ie, lamellar bodies) that can be seen on electron microscopy. PAP is caused by an imbalance between surfactant production and clearance. In healthy lungs, surfactant is secreted by type 2 pneumocytes and eventually cleared by alveolar macrophages. In PAP, surfactant removal is impaired due to compromised alveolar macrophage function (eg, usually because of defects in granulocyte-monocyte colony-stimulating factor [GM-CSF] signaling). Treatment involves therapeutic whole-lung lavage to wash away surfactant and inhaled GM-CSF replacement therapy. (Choice B) Ciliated epithelial cells line the conducting airways and are responsible for mucociliary escalator function, a key process in airway clearance. Primary ciliary dyskinesia (eg, Kartagener syndrome) is characterized by impaired ciliary function and leads to mucostasis, recurrent pneumonia, and bronchiectasis. (Choice C) Club cells (bronchiolar cells) are located at the bronchoalveolar alveolar junction and protect and repair the distal airway (terminal bronchioles). Club cell dysfunction has been implicated in the pathogenesis of COPD. (Choice D) Fibroblasts produce and maintain the connective tissue matrix of the lung, lending structural support and elasticity. Loss of fibroblast function contributes to degenerative airspace dilation in emphysema. (Choice E) Type 1 pneumocytes form the alveolar gas-exchanging surface. Rapid destruction and loss of type 1 pneumocytes occurs in early acute lung injury. It does not result in the abnormal accumulation of surfactant products. Educational objective: Pulmonary alveolar proteinosis is a rare condition characterized by progressive respiratory dysfunction due to the accumulation of surfactant (periodic acid-Schiff positive material forming lamellar bodies) within the alveolar spaces. The condition occurs most often due to the impaired clearance of surfactant by alveolar macrophages (eg, decreased granulocyte-monocyte colony-stimulating factor signaling).

A 45-Year-Old Man Comes to the Office Due to Progressive