Tuberculosis

TB Pathophysiology - The Ghon Show

• Primary TB: Occurs on first exposure. Organisms implant in subpleural airspaces of the mid-to-lower lobes.
• Pathogenesis: Mediated by Th1 cells activating macrophages via IFN-γ. Activated macrophages form epithelioid histiocytes and Langhans giant cells, leading to caseating necrosis.
• Ghon Focus: The initial parenchymal granuloma.
• Ghon Complex: Ghon focus + associated hilar lymph node granuloma. Usually contains the infection in immunocompetent hosts.

⭐ A Ghon complex that has undergone subsequent fibrosis and calcification is known as a Ranke complex, indicating healed primary TB.

TB Clinical Forms - Consumption's Comeback

• Primary TB: Usually asymptomatic. Ghon complex (calcified lung focus + hilar node) → Ranke complex.
• Latent TB (LTBI): Contained, non-infectious. Positive TST/IGRA, negative CXR, no symptoms.
• Reactivation (Secondary) TB: Symptomatic disease from LTBI, often in immunosuppressed (HIV, TNF-α inhibitors).
  • Symptoms: "Consumption" (fever, night sweats, weight loss), cough, hemoptysis.
  • Location: Apical/posterior upper lobes (high O₂).
• Extrapulmonary/Miliary:
  • Pott's Disease: Vertebral body destruction.
  • Scrofula: Cervical lymphadenitis.
  • Miliary: Hematogenous spread; "millet-seed" CXR.

⭐ Reactivation TB classically presents with cavitary lesions in the lung apices, a high-oxygen environment where M. tuberculosis thrives.

TB Diagnosis - Spotting the Intruder

• Latent TB Screening:

  • Tuberculin Skin Test (TST/PPD): Positive if induration is:
    • ≥5 mm: HIV+, recent contacts, fibrotic changes on CXR.
    • ≥10 mm: Recent immigrants, IVDU, high-risk settings.
    • ≥15 mm: No known risk factors.
  • Interferon-Gamma Release Assays (IGRAs): Blood test, preferred if BCG vaccinated.

• Active TB Diagnosis:

  • Sputum Analysis: 3 samples; AFB smear (Ziehl-Neelsen), NAAT, and culture (gold standard).
  • Chest X-ray: Look for upper lobe cavitations, Ghon complex, or miliary pattern.

⭐ High-Yield: IGRAs (like QuantiFERON-Gold) are more specific than TST in patients who have received the BCG vaccine, avoiding false-positive results.

TB Treatment - RIPE for the Picking

📌 RIPE Mnemonic for standard 6-month regimen.

• Rifampin: Red-orange body fluids (tears, urine); potent CYP450 inducer.
• Isoniazid (INH): Peripheral neuropathy, hepatotoxicity. Requires B6.
• Pyrazinamide (PZA): Hyperuricemia (can precipitate gout), hepatotoxicity.
• Ethambutol: Eye issues (optic neuritis, red-green color blindness).

⭐ Always co-administer Pyridoxine (Vitamin B6) with Isoniazid to prevent peripheral neuropathy.

High‑Yield Points - ⚡ Biggest Takeaways

• Primary TB is often asymptomatic, forming a Ghon complex; reactivation classically occurs in the lung apices.
• Suspect extrapulmonary TB in vertebral pain (Pott's disease) or cervical lymphadenitis (scrofula).
• Screen for latent TB with PPD or IGRA; diagnose active disease with sputum AFB smear and culture.
• Standard therapy for active TB is RIPE: Rifampin, Isoniazid, Pyrazinamide, Ethambutol.
• Key side effects: Isoniazid causes hepatotoxicity and neuropathy (give B6); Ethambutol causes optic neuritis.