TB Overview and Pathogenesis

Overview

This lecture covers the epidemiology, pathophysiology, diagnosis, and treatment of tuberculosis (TB), focusing on the disease process, immune response, diagnostic methods, and drug-resistant strains.

Epidemiology & Transmission

• TB is caused by Mycobacterium tuberculosis and infects about two billion people worldwide.
• The majority of infected individuals have latent TB with no symptoms due to immune system containment.
• TB is transmitted via inhalation and primarily affects the lungs.

Microbiology & Pathogenesis

• Mycobacterium tuberculosis is a strict aerobe with a waxy, mycolic acid-rich cell wall, making it acid-fast.
• The bacterium survives inside macrophages by preventing phagosome-lysosome fusion.
• Primary TB develops after inhalation and initial immune response, usually with mild or no symptoms.
• Granulomas form around infection sites, leading to caseous necrosis (cheese-like tissue death) and Ghon focus.
• Spread to hilar lymph nodes forms a Ghon complex; calcification leads to a Ranke complex.
• Bacteria may remain dormant and reactivate if the immune system weakens, especially in the upper lobes of the lungs.

Clinical Manifestations & Complications

• Reactivation TB can cavitate and spread within lungs (bronchopneumonia) or systemically (miliary TB).
• Extrapulmonary TB can affect kidneys (sterile pyuria), brain (meningitis), spine (Pott disease), adrenal glands (Addison’s disease), liver (hepatitis), and neck lymph nodes (scrofula).

Diagnosis

• Tuberculin skin test (PPD/Mantoux) or IGRA blood test detects TB exposure but cannot distinguish active from latent TB.
• Chest X-ray is used to identify signs of active TB disease.
• Sputum or bronchoalveolar lavage samples are examined by staining, culture, and PCR for Mycobacterium tuberculosis.

Treatment & Drug Resistance

• Latent TB is typically treated with isoniazid for 9 months.
• Active TB requires combination antibiotics (isoniazid, rifampin, ethambutol, pyrazinamide) for several months.
• Multi-drug resistant (MDR-TB) and extremely drug-resistant (XDR-TB) strains require special regimens.
• Pretomanid, bedaquiline, and linezolid combination is effective for XDR-TB.
• Directly observed therapy (DOT) is used to ensure medication adherence.
• Patients are isolated until non-infectious; visitors use N-95 masks.

Key Terms & Definitions

• Latent TB — TB infection without symptoms, bacteria are dormant.
• Active TB — TB infection with symptoms, bacteria are multiplying and potentially contagious.
• Granuloma — Immune cell cluster that walls off TB bacteria.
• Caseous necrosis — Cheese-like dead tissue within granuloma.
• Ghon focus — Primary lung lesion of TB infection.
• Ghon complex — Ghon focus plus affected lymph node.
• Ranke complex — Calcified Ghon complex seen on X-ray.
• Miliary TB — Disseminated TB infection involving multiple organs.
• MDR-TB/XDR-TB — TB resistant to multiple or extensive antibiotics.
• DOT (Directly Observed Therapy) — Healthcare personnel observe patients taking medication.

Action Items / Next Steps

• Review TB pathogenesis and immune response.
• Memorize key diagnostic methods and treatment regimens.
• Study differences between latent and active TB.
• Prepare for questions on drug-resistant TB and extrapulmonary complications.