A 55-year-old man comes to the emergency department due to several weeks of productive cough with occasional hemoptysis, weight loss, and low-grade fever. He has lost 7 kg (15.4 lb) over the past 3 months. Medical history is significant for type 2 diabetes mellitus and chronic kidney disease, and the patient works as a prison guard. Temperature is 37.8 C (100 F), blood pressure is 110/70 mm Hg, pulse is 78/min, and respirations are 18/min. Chest x-ray reveals a right apical lung infiltrate and cavitary lesion. He is placed in respiratory isolation, and appropriate empiric therapy is started. The cavitary lesions seen in this patient most likely formed through which of the following pathogenic mechanisms?

Question

A 55-year-old man comes to the emergency department due to several weeks of productive cough with occasional hemoptysis, weight loss, and low-grade fever.  He has lost 7 kg (15.4 lb) over the past 3 months.  Medical history is significant for type 2 diabetes mellitus and chronic kidney disease, and the patient works as a prison guard.  Temperature is 37.8 C (100 F), blood pressure is 110/70 mm Hg, pulse is 78/min, and respirations are 18/min.  Chest x-ray reveals a right apical lung infiltrate and cavitary lesion.  He is placed in respiratory isolation, and appropriate empiric therapy is started.  The cavitary lesions seen in this patient most likely formed through which of the following pathogenic mechanisms?

Quizplus · Accepted Answer

11ec160b_3a22_c0ae_9249_a33f1964ac72_MD0001_00 This patient has a productive cough, hemoptysis, fever, and weight loss with an apical cavitary lung lesion, findings characteristic of active tuberculosis. Mycobacterium tuberculosis is an acid-fast bacillus that replicates within the alveoli. The bacteria are phagocytized by alveolar macrophages, which are initially unable to destroy the pathogen due to microbial adaptations that inhibit the formation of an effective phagolysosome. However, in the weeks after the initial infection, antigen presenting cells (eg, macrophages, dendritic cells) display mycobacterial antigens to naïve CD4⁺ T lymphocytes in regional lymph nodes, which subsequently differentiate into T helper type 1 (Th1) cells that secrete interferon-gamma. Interferon-gamma activates macrophages, leading to the formation of fully acidified phagolysosomes capable of destroying intracellular mycobacteria. Activated macrophages also aggregate and differentiate into epithelioid histiocytes and multinucleated giant cells, which surround extracellular mycobacteria within granulomas. The release of proteases, nitric oxide, and reactive oxygen species by these cells helps contain the infection. However, these compounds also cause extensive collateral tissue damage and can result in the formation of cavitary lung lesions. (Choice B) M tuberculosis produces trehalose dimycolate (cord factor), which inhibits phagolysosome maturation and may contribute to the formation of caseating granulomas. However, cord factor does not directly cause the tissue necrosis associated with cavitary lesions; the release of digestive enzymes by activated macrophages lining the granuloma drives caseation and cavitation. (Choice C) Lobar pneumonia is characterized by the initial accumulation of an abundant proteinaceous exudate within the alveoli, followed by hepatization of the affected lobe. Lobar pneumonia is typically caused by pathogens such as Streptococcus pneumoniae. However, lobar pneumonia presents acutely, not slowly, over several weeks. (Choice D) Intraalveolar mycobacteria do not directly cause cavitary lesions. Activated macrophages that surround the extracellular mycobacteria are primarily responsible for the tissue damage that leads to cavitation. (Choice E) Obliterative lower airway inflammation can occur as a feature of cryptogenic organizing pneumonia. In this condition, inflammation causes the proliferation of granulation tissue, which obstructs small bronchioles and leads to alveolar consolidation. However, apical cavitary lesions and hemoptysis are uncommon. Educational objective: Control of Mycobacterium tuberculosis infection is mediated primarily by activated macrophages, which surround extracellular mycobacteria and wall them off within granulomas. The release of digestive enzymes by these cells not only helps control the infection, but also leads to damage of the surrounding tissue and the formation of cavitary lung lesions. __________ References: The tuberculous granuloma: an unsuccessful host defence mechanism providing a safety shelter for the bacteria? (http://www.ncbi.nlm.nih.gov/pubmed/22811737) Macrophages and control of granulomatous inflammation in tuberculosis. (http://www.ncbi.nlm.nih.gov/pubmed/21430653)

A 55-Year-Old Man Comes to the Emergency Department Due to Several