Pulmonary Tuberculosis

Detailed Overview

Tuberculosis remains one of the top infectious disease killers worldwide, transmitting via inhalation of aerosolized droplet nuclei. Once inhaled, alveolar macrophages ingest the bacilli, which evade destruction and multiply, forming a Ghon focus. Cell-mediated immunity halts the infection in most individuals, resulting in latent TB infection (LTBI). However, roughly 5-10% of infected individuals will develop active TB, often due to immunocompromise (e.g., HIV, TNF-alpha inhibitors), malnutrition, or aging, leading to classic symptoms of chronic cough, hemoptysis, and cavitary lung lesions.

Epidemiology & Demographics

In 2021, approximately 10.6 million people fell ill with TB globally, with 1.6 million deaths. Incidence is highest in South-East Asia, Africa, and the Western Pacific. Male to female ratio is ~1.5:1. HIV co-infection occurs in about 8% of incident cases.

Etiological Mechanism

The sole causative agent is Mycobacterium tuberculosis, a slow-growing, obligate aerobic, acid-fast bacillus (AFB) characterized by a lipid-rich cell wall containing mycolic acids.

Primary Causes

Mycobacterium tuberculosis infection

• Immunocompromise: HIV infection is the strongest risk factor, increasing active TB risk by 20-fold. Other states include organ transplantation and biologic therapy (infliximab).
• Overcrowded Living Conditions: Prisons, homeless shelters, and refugee camps facilitate airborne transmission.
• Substance Abuse: Alcoholism and IV drug use are strongly correlated with higher rates of infection and progression to active disease.

Inhalation of M. tuberculosis droplet nuclei leads to phagocytosis by alveolar macrophages. The bacilli prevent phagolysosome fusion through sulfatides and cord factor, multiplying intracellularly. A Th1-mediated immune response ensues, secreting IFN-gamma which activates macrophages to form epithelioid cells and multinucleated Langhans giant cells, enclosing the bacilli in a granuloma (tubercle) with a caseous, necrotic center. In active pulmonary TB, caseous material liquefies and empties into the bronchial tree, creating cavities and allowing for aerogenic spread.

Characteristic Clinical Presentation

• Chronic Productive Cough: Lasting > 3 weeks, initially non-productive but progressing to purulent sputum.
• Hemoptysis: Coughing up blood, indicative of tissue necrosis and cavitary erosion into blood vessels.
• Night Sweats: Drenching nocturnal diaphoresis associated with afternoon fevers.

Physical Examination Signs

• Apical Rales/Crackles
• Cachexia

• Massive Hemoptysis: Rupture of a Rasmussen aneurysm (pulmonary artery branch within a cavity).
• Bronchopleural Fistula: Erosion of a cavity into the pleural space leading to empyema and pneumothorax.

Diagnostic Criteria & Guidelines

Confirmed by isolation of M. tuberculosis complex from respiratory secretions via culture or Nucleic Acid Amplification Test (NAAT/Xpert MTB/RIF). AFB smear provides presumptive evidence.

Differential Diagnosis

• Pneumonia
• Lung Cancer
• Nontuberculous Mycobacterial (NTM) Infection

Laboratory Tests & Biomarkers

• Sputum AFB Smear: Positive for acid-fast bacilli on Ziehl-Neelsen stain.
• Xpert MTB/RIF Assay: Positive for M. tuberculosis DNA and detects rifampin resistance.

Imaging Modalities & Findings

• Chest X-Ray:
• CT Chest:

• Latent TB Infection (LTBI)
  Patient is infected but asymptomatic; normal chest X-ray, negative sputum, but positive IGRA/TST.
• Active Pulmonary TB
  Symptomatic, positive sputum AFB, chest X-ray showing infiltrates or cavities, infectious.

Second-Line & Adjunctive Therapy

For Multi-Drug Resistant TB (MDR-TB): Regimens including Bedaquiline 400 mg daily for 2 weeks then 200 mg 3x/week, Linezolid 600 mg daily, Levofloxacin 750 mg daily, and Clofazimine for 6-9 months.

Surgical & Procedural Management

Rarely indicated today, but lobectomy/pneumonectomy may be considered for localized multidrug-resistant disease or massive refractory hemoptysis.

Recommended Lifestyle Changes

• Strict airborne isolation during the infectious phase.
• High-protein, high-calorie diet to reverse cachexia.

Patient Counseling & Advice

Emphasize absolute adherence to the full 6-month treatment course to prevent relapse and development of drug-resistant TB. Warn about rifampin turning urine and tears red-orange.

Follow-Up & Monitoring Schedule

Monthly sputum smears and cultures until two consecutive cultures are negative. Baseline and monthly hepatic panels (AST, ALT, Bilirubin) to monitor for drug-induced hepatotoxicity.

Preventive Strategies

BCG vaccination in endemic countries. Treatment of LTBI with Isoniazid 300 mg daily for 9 months or Isoniazid+Rifapentine weekly for 3 months to prevent progression to active TB.

Excellent if fully susceptible and patient is adherent to therapy (cure rates >95%). Untreated active TB has a 50% mortality rate within 5 years.