Pulmonary TB Flashcards
PULMONARY TUBERCULOSIS
• Estimated 1/3 of world population infected with TB; Majority of cases in Africa and Asia (India
and China); Coinfection with HIV remains a major problem because of heavy healthy burden and growing incidence of drug resistant strains and high mortality of both disease
• Responsible for 1.4 million deaths in 2010; 25% of which are HIV coinfected individuals
• Four main Mycobacteria species together called Mycobacterium tuberculosis complex (MTb);
Mycobacterium tuberculosis, bovis, africanum and microti
o Obligate aerobes and facultative intracellular pathogens; infects mononuclear
phagocytes (e.g. Macrophages); Slow growing generation time of 12-18 hours
o High lipid content of cell wall; Relatively impermeable, stains weakly with Gram;
When stained with Dye and Phenol, and washed with Acid organic solvents they resist
decolourisation = Acid-fast Bacilli
At Risk Population
Immigrants from affected areas, Elderly and Immunosuppressed,
Diabetics, Alcoholics and Homeless`
Pathogenesis of Tuberculosis
• Airborne infection spread via respiratory droplets; Only a small number required to develop
infection but not all infected develop active disease
• Development of disease depends on many factors including contact with high-risk groups,
immune deficiency (E.g. HIV, Immunosuppressant therapy, CKD and DM, Malnutrition)
• Primary Tuberculosis – First infection with MTb; Alveolar macrophages ingest bacteria and
proliferation occurs intracellularly resulting in release of Neutrophil Chemokines and
Cytokines; Inflammatory infiltrate reaches Lungs and Hilar Lymph Nodes
• Macrophages present antigen to T cells to develop Cell-mediated Immunity, resulting in
delayed Hypersensitivity-like reaction causing Tissue Necrosis and Granuloma formation
• Granuloma consists of central Necrosis (Caseation) surrounded by Macrophage-derived
Epithelioid cells and multinucleated Langhans’ Giant Cells; Lymphocytes also present
o Initial focus of disease is termed Ghon focus; seen on CXR as small Calcified nodule
often within midzone near the Hilum; Focus can also develop within regional draining
lymph node (Primary complex of Ranke)
• Some caseated areas heal completely while many become calcified; Some Calcified nodules
contain bacteria which are contained by the Immune System and Hypoxic, Acidic environment
of the Granuloma, and are capable of lying dormant for years
o Upon initial contact <5% of people develop active disease; 10% within 1yr
Latent Infection
Bacilli present in Ghon focus Sputum and culture negative Tuberculin positive CXR normal (small calcified Ghon focus) Asymptomatic Not infectious to others
Active Disease
Bacilli in tissues/secretions
MTb cultured from sputum and infected tissue
Tuberculin usually positive and can ulcerate
Consolidation, Cavitation, Pulmonary Effusion
Night sweats, Fevers, Weight loss, Cough
Infectious if bacilli present in Sputum
Latent Tuberculosis
Immune system contains the infection in majority of people and patient
develops Cell-mediated Immune memory to bacteria
Reactivation Tuberculosis
Majority of TB cases due to Reactivation of Latent infection;
Usually many years from initial contact; HIV patients with newly acquired TB is also common
Presentation of Tuberculosis
Pulmonary, Pleural, Laryngeal, Miliary, CNS,
and Lymph Node presentations in either
primary or reactivation TB; Extrapulmonary
involvement far less common, usually seen
only in regions of high endemicity
Pulmonary TB
Productive cough, Haemoptysis with systemic symptoms of Weight Loss, Fevers, Sweats (End of day and throughout night); Laryngeal involvement results in Hoarseness and severe Cough; Pleura involvement results in Pleuritic pain ▪ CXR – Consolidation ± Cavitation, Pleural Effusion or Mediastinum thickening/widening due to Hilar/Paratracheal Adenopathy
Lymph Node TB
– Extrathoracic nodes more commonly involved than
Intrathoracic/Mediastinal; presents as firm, non-tender enlargement of Cervical and
Supraclavicular nodes; Node becomes necrotic centrally and can liquefy and become
fluctuant if peripheral
▪ Overlying skin indurated; Sinus tract formation with purulent discharge but
characteristically no erythema occurs (Cold Abscess Formation)
▪ CT imaging reveals necrotic centre
Miliary TB
Haematogenous spread to multiple sites including CNS (20% of cases); Systemic upset with Respiratory symptoms in majority; Microabscesses in Liver and Spleen resulting in deranged LFTs or Cholestasis with GI symptoms ▪ CXR – Multiple nodules that appear like Millet seeds o Other forms of TB include Gastrointestinal, TB of Bone/Spine, Skin, Pericardium and CNS TB • Substantial effort to obtain tissue/fluid for MCS; Tissue samples for histopathology
Microbiological Diagnosis of Tuberculosis
• Auramine-Rhodamine Fluorescence microscopy (Bacilli appears yellow-orange) staining more
sensitive but less specific than Ziehl-Neelsen
• Liquid/Broth culture in addition to solid media (Lowenstein-Jensen or Middlebrook); Liquid
culture in the presence of anti-Mycobacterial drugs establishes drug sensitivity in 3 weeks
• Microscope observation of Drug Sensitivity (MODS) assay compares growth of wells in liquid
media with different drugs; Inexpensive but labour intensive and operator dependent
• Nucleic Acid Amplification – Useful for differentiating MTb from Non-TB Mycobacteria (NTM);
Also detects dead organisms; Useful for CNS TB and identifying drug resistance
Management of Tuberculosis
• Fully sensitive TB patients requires 6 months; CNS TB requires at least 12 months
• Corticosteroids for CNS and Pericardial Disease to reduce long term complications
• Direct Observed Therapy (DOT) – Treatment supervised by healthcare professional or family
member; Majority of relapsed disease/treatment failure due to lack of adherence,
interrupted treatment or incorrect treatment
o Dosing frequency may be reduced to 3 times a week; Success rate comparable to
standard unsupervised daily therapy
Drug Regimen for Active Tuberculosis
Initial 2 months Rifampicin (inhibit DNA dependent RNA polymerase) Isoniazid (against bacterial cell wall) Ethambutol (against bacterial cell wall) Pyrazinamide (only used in combination, lowers bacterial pH) Further 4 months 10 months + Steroids if CNS Rifampicin Isoniazid
Rifampicin
Induction of Liver Enzymes (concomitant drugs less effective); Stopped if
Bilirubin elevated or Transferases are >3× elevated; Stains body secretions pink
o Oral Contraception not effective so alternative birth control required
o Rifabutin – Used for prophylaxis against MAI in HIV patients with CD4 <200/mm3
