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Tuberculosis (TB)

Clinical Overview: Pathology, Features, Diagnosis & Management

Pathology and Pathogenesis

Tuberculosis is caused by infection with Mycobacterium tuberculosis (MTB).

Transmission & Initial Reaction

M. tuberculosis is spread by the inhalation of aerosolised droplet nuclei from other infected patients. Once inhaled, the organisms lodge in the alveoli and initiate the recruitment of macrophages and lymphocytes. Macrophages undergo transformation into epithelioid and Langhans cells, which aggregate with the lymphocytes to form the classical tuberculous granuloma.

Primary Lesions

• Ghon Focus: Numerous granulomas aggregate to form a primary lesion. This is a pale yellow, caseous nodule, usually a few millimetres to 1–2cm in diameter, characteristically situated in the periphery of the lung.
• Primary Complex of Ranke: Spread of organisms to the hilar lymph nodes is followed by a similar pathological reaction. The combination of the primary lesion and regional lymph nodes is referred to as the 'primary complex of Ranke'.

Dissemination

Lymphatic or haematogenous spread may occur before containment is established. This seeds secondary foci in other organs, including lymph nodes, serous membranes, meninges, bones, liver, kidneys, and lungs, which may lie dormant for years.

Clinical Features: Pulmonary Disease

Primary Pulmonary TB

Primary TB refers to the infection of a previously uninfected (tuberculin-negative) individual. A few patients develop a self-limiting febrile illness, but clinical disease occurs only if there is a hypersensitivity reaction or progressive infection.

Miliary TB

Blood-borne dissemination gives rise to miliary TB. It may present acutely but is more frequently characterised by 2–3 weeks of fever, night sweats, anorexia, weight loss, and a dry cough. Hepatosplenomegaly may develop, and the presence of a headache may indicate coexistent tuberculous meningitis.

Radiological Appearance: Classical appearances on chest X-ray are of fine 1–2 mm lesions ('millet seed') distributed throughout the lung fields.

Post-primary Pulmonary TB

Post-primary disease refers to exogenous ('new' infection) or endogenous (reactivation of a dormant primary lesion) infection in a person who has been sensitised by earlier exposure.

• Location: Most frequently pulmonary, characteristically occurring in the apex of an upper lobe, where the oxygen tension favours survival of the strictly aerobic organism.
• Onset: Usually insidious, developing slowly over several weeks.
• Radiology: Ill-defined opacification in one or both of the upper lobes. As progression occurs, consolidation, collapse, and cavitation develop. The presence of a miliary pattern or cavitation favours active disease.

Clinical Presentations

Common presentations of pulmonary tuberculosis include:

• Chronic cough, often with haemoptysis
• Pyrexia of unknown origin
• Unresolved pneumonia
• Exudative pleural effusion
• Weight loss, general debility
• Spontaneous pneumothorax
• Asymptomatic (diagnosis on chest X-ray)

Investigations & Diagnosis

The presence of an otherwise unexplained cough for more than 3 weeks, particularly in regions where TB is prevalent, or typical chest X-ray or CT changes should prompt further investigation.

Specimens Required

• Sputum: Preferably three early morning samples (induced with nebulised hypertonic saline if patient is not expectorating).
• Lavage: Bronchoalveolar lavage (BAL) (mainly used for children).

Diagnostic Tests

• Microscopy: Auramine fluorescence or Ziehl–Neelsen staining.
• Culture: Solid media (typically between 4 and 6 weeks) and liquid media (typically around 2 weeks).
• Fluid Analysis: Pleural fluid adenosine deaminase.
• Therapeutic Trial: Response to empirical antituberculous drugs.

Baseline Blood Tests

C-reactive protein, urea and electrolytes, liver function tests.

Management

Chemotherapy Principles

The treatment of TB is based on the principle of an initial intensive phase to reduce the bacterial population rapidly, followed by a continuation phase to destroy any remaining bacteria.

Standard Regimen

• Duration: 6 months total treatment.
• Core Drugs: Isoniazid and Rifampicin.
• Intensive Phase (First 2 months): Supplemented with Pyrazinamide and Ethambutol.

Fixed-dose tablets combining two, three, or four drugs are preferred.

Infectiousness: Where drug resistance is not anticipated, patients can be assumed to be non-infectious after 2 weeks of appropriate therapy.

Medical Information Summary based on provided lecture notes.