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M. Tuberculosis are acid fast. Other acid fast bacilli include –

  1. Nocardia,                  
  2. Rhodococcus,                
  3. Legionella,            
  4. Isospora,      
  5. cryptosporidium.
  6. lepra bacilli        
  7. Cryptococcus 

Infectivity (in decreasing order)

Cavitary lesion, endobronchial/ laryngeal tuberculosis > smear negative > culture negative > extra pulmonary


Important Points: Pathogenesis

2 – 4 weeks after infection two host response develop –       

  1. Tissue damaging response – Result of delayed type hypersensitivity reaction to bacillary antigen. It destroys non activated macrophages that contain multiplying bacilli.
  2. Macrophage – activating response – It results in the activation of macrophages that are capable of killing and digesting tubercle bacilli. 

Extra Edge: Pathology

  1. Ghon focus – It is a subpleural focus usually at the lower border of upper lobe or upper border of lower lobe. It is infraclavicular in location (AIIMS Nov 09).
  2. Ghon’s complex – Combination of Ghon’s focus and the draining lymph nodes.
  3. Ghon’s lesion – Calcified parenchymal nodule on chest x- ray.    
  4. Ranke’s complex – Calcified parenchymal nodule + calcified hilar node.
  5. Simon Focus – Present in apical or post. segment of upper lobe
  6. Rich Focus – Present in meninges.
  7. Assmann Focus - Present in apical. Segment of upper lobe (AIIMS Nov 09) It is infraclavicular 
Primary TB—Simon focus (apex lesion with primary elsewhere in body)
Secondary  TB—Supraclavicular (Puhls lesion), Infraclavicular (Assman focus)


  1. In young children with a positive tuberculin test extensive physical changes were found in the chest, consisting of an impaired percussion note with diminished or tubular breathing, mostly localized in the upper lobe, especially on the right side. Rales were only rarely heard.
  2. The most striking feature being that in the majority of cases the physical signs, after remaining unchanged for some months, completely disappeared.
  3. The extensive physical changes appearing on the skiagram as a dense diffuse shadow were not due to specific tuberculous tissue changes.
  4. They suggested that these pathological alterations were a reaction in the adjacent lung tissue to toxins produced by a tuberculous focus. If the activity of the focus ceased these alterations might completely disappear.
  5. The infiltration should be put on the same level with the perifocal inflammation (Tendeloo) which may occur in the proximity of any inflammatory focus (e.g. the inflammatory swelling round a boil). 

Primary disease – First time infection with tubercle bacilli


In few patients, the initial infection progresses and manifests as –

  1. Rupture into pleural space causing pleural effusion
  2. Extensive caseous pneumonia
  3. Enlargement of LN → bronchial obstruction
  4. Rupture of TB focus into a bronchus leading to endobronchial TB.
  5. Rupture into a pulm blood vessel causes hematogenous spread
  6. Manifestations of hypersensitivity reactions
    1. Erythema nodosum
    2. Phlyctenular conjunctivitis

Primary tuberculosis

  1. It is the first infection with tubercle bacilli in individuals who have not been previously exposed to the organism
  2. Seen in children
  3. Primary complex is characteristic
Extra Edge :

Unilateral hilar lymphadenopathy as part of the primary complex is a characteristic feature of primary tuberculosis (LQ 2012)


Primary (Ghon) complex

  1. Unilateral enlarged hilar lymph nodes
  2. Ghon focus: Epithelioid cell granulomatous inflammation (Consolidation) at site of parenchymal infection. Usually small and subpleural most commonly located under pleura in lower part of upper lobe.
  3. Usually a symptomatic or manifested by a mild flu like illness at time of tuberculin conversion.
  4. Fibrocaseous lesion are characteristic in primary TB.
  5. Phlyctenular conjunctivitis is a feature of primary TB

Important Points:

  1. Pleural effusion is common in primary TB
    Pleural effusion is found in upto 2/3 of cases of primary TB and results from penetration of bacilli into the pleural space from an adjacent subpleural focus.
  2. Cavitation is not a feature of primary TB but it is a feature of secondary TB (Robbins) 

Important Points: Effects of primary tuberculosis

  1. Tuberculin positivity.
  2. Partial immunity to tuberculosis: individual requires a higher dose to be reinfected by tubercle bacilli.
  3. Presence of dormant tubercle bacilli.
  4. Lesions heal by fibrosis and may calcify.
  5. Radiological evidence of healed primary infection may or may not be present. 

Hallmarks indicating Hypersensitivity to mycobacteria in primary pulmonary TB.

  1. Erythema nodosum
  2. Phlyctenular conjunctivitis 

Post Primary disease/Adult type/ reactivation/ Secondary –

  1. Apical and post segment of the upper lobe
  2. Superior segment of the lower lobes
  3. Caseous material contains 1 x 104 bacilli /gm
  4. Cavity contain 1 x 109 bacilli
  5. The classical "galloping consumption" of the past, others undergo a process of spontaneous remission    or proceed along a chronic, progressively debilitating course ("consumption"). 

Complications of Post Primary disease

  1. Pleural effusion                                        
  2. Empyema                    
  3. Resp failure                                            
  4. Hyponatremia due to SIADH            
  5. Scar carcinoma                                       
  6. Hemoptysis
  7. Poncet’s disease               
  8. Pneumothorax
  9. Aspergilloma                           
  10. Pott’s disease
  11. Fibrosis                                  
  12. Skin – erythema nodosum
  13. Eye - Phlyctenular conjunctivitis

Important Points:


Poncet's disease, is a reactive symmetric form of polyarthritis that affects persons with visceral or disseminated tuberculosis. No mycobacteria are found in the joints, and symptoms resolve with antituberculous therapy.


Miliary tuberculosis

  1. This is produced by acute dissemination of bacilli via blood resulting in the appearance of discrete nodular shadows of size 2mm..
  2. Choroid tubercles on fundus examination in children.
  3. Sputum negative in 80% of cases.
  4. Anemia, leukopenia may be there. 

Important Points:

  1. Miliary TB may occur following primary infection and secondary reactivation
  2. Sputum microscopy is usually negative
  3. Mantoux test is negative in 20-30% of patients with Miliary TB
  4. Liver, kidney and spleen are common sites of involvement along with other sites.

Cryptic miliary tuberculosis  

  1. Seen in elderly, chronic course.
  2. No choroid tubercles.
  3. Tuberculin test negative. CXR normal (size of tubercles <0.5mm) 

Non – reactive miliary tuberculosis

  1. Acute septicemic form.
  2. Pancytopenia.
  3. Rapidly fatal.
  4. Multiple necrotic non – granulomatous, (non – reactive) lesions.

Important Points:


Pulmonary tuberculosis is known to leave behind a lot of devastations even after complete biological cure of the disease. These may be classified as

  1. Parenchymal; tuberculoma, cavity, aspergilloma and carcinoma.
  2. Airway lesions; broncholithiasis, bronchial stenosis and bronchiectasis.
  3. Vascular; pulmonary and bronchial arteritis, and Rasmussen's aneurysm.
  4. Mediastinal; lymph node calcification, esophagobronchial and mediastinal fistulae, fibrosing mediastinitis and constrictive pericarditis.
  5. Pleural; chronic empyema, fibrothorax, bronchopleural fistula and pneumothorax.
  6. Chest wall lesions. Rasmussen's Aneurysm is a very rare sequelae of Pulmonary Tuberculosis

Extra Edge  Physical finding in Lung disease

  1. Cavernous breathing: It is heard when the bronchial tubes communicate with cavities in the lungs. (LQ 2012)
  2. Whispered pectoriloquy refers to an increased loudness of whispering noted during auscultation with a stethoscope on the lung fields on a patient's back. It is heard in the presence of lung consolidation
  3. Bronchophony. In bronchophony, the patient says “ninety-six” while listening over the lung fields: the sound will be louder in areas where consolidation is present.
  4. Egophony is an increased resonance of voice sounds heard when auscultating the lungs, often caused by lung consolidationfibrosis, Above the level of pleural effusion. It results in a high-pitched nasal or bleating quality in the affected person's voice

HIV associated TB – –(MCQ, UPSC 2008) (Ref. Hari. 18th ed., Pg- 1355)

  1. TB has rapidly progressive & fatal course in HIV positive pts.
  2. HIV increase reactivation of latent infection
  3. Extrapulmonary tuberculosis is more common
  4. Little or no cavitation , CXR may be Normal
  5. Intrathoracic lymphadenopathy more common
  6. Diffuse interstitial / miliary infiltrates.
  7. Sputum smear positivity is less so best diagnosed by sputum Culture. Multi drug resistance is common.
  8. Mtx test is negative
  9. IRIS – Immune reconstitution inflammatory syndrome. (Paradoxical reactions – Exacerbations in sign symptom, lab or radiographic manifestations of tuberculosis with administration of HAART regimen)  
    1. The clinical course is characterized by marked cervical and mediastinal adenopathy accompanied by fever and weight loss during simultaneous treatment of TB and HIV disease.
    2. The paradoxical reaction is attributed to partial immune reconstitution related to highly effective antiretroviral therapy.
    3. Antiretroviral therapy (ART) initiation in HIV-infected patients leads to recovery of CD4+T cell numbers and restoration of protective immune responses against a wide variety of pathogens, resulting in reduction in the frequency of opportunistic infections and prolonged survival.
    4. However, in a subset of patients, dysregulated immune response after initiation of ART leads to the phenomenon of immune reconstitution inflammatory syndrome (IRIS).
    5. The hallmark of the syndrome is paradoxical worsening of an existing infection or disease process or appearance of a new infection/disease process soon after initiation of therapy.
    6. Majority of patients with IRIS have a self-limiting disease course.
    7. ART is usually continued and treatment for the associated condition optimized.
  10. Rifampicin can induce metabolism of protease inhibitors so according to RNTCP 2010 guidelines , if patient is taking HAART then replace rifampicin with rifabutin.
  11. Thiacetazone is contraindicated because it causes severe exfoliative dermatitis (FAQ). 



Tuberculin test

False negative tuberculin test –

  1. Measles
  2. AIDS
  3. Lymphomas, Leukemia
  4. Sarcoidosis
  5. Protein malnutrition
  6. Miliary tuberculosis,
  7. TBM
  8. Immunosuppressive drugs
  9. Newborn & elderly
  10. Live viral vaccinations
  11. Defective cell mediated immunity

Important Points: - Other tests in TB

  1. Chest x – ray
  2. Sputum smear – At least 2 samples
    1. Zeil – Nelson technique – when bacilli are numerous
    2. Auramine – rhodamine stain – when bacilli are less
    3. Carbol fuchsin stain.
  3. Sputum culture – May take 12 weeks to positive, Löffler’s medium
  4. ELISA for IgG Antibodies

Recent Advances  New technique in diagnoses of TB (Ref. Hari. 18th ed., Pg- 1351)

  1. Advanced microscopy with help of fluorescent light (LED microcopy)
  2. IF – γ release assay (PNQ) – including, TB QuantiFERON Gold, T-spot TB
  3. BACTEC radiometric method – 14c labelled palmitic acid can detect growth in 5 – 8 days
  4. It is the only method to detect live bacilli
  5. DNA probe – with in hours
  6. PCR
  7. Nucleic Acid Amplification Test (NAAT)
  8. XPERT – MDR – RIF : It is a new test to detect mycobacterium along with testing for resistance to rifampicin.

Important Points

  1. Drugs acting in acid medium – Pyrazinamide (Intracellular org)
  2. Drugs acting in Alkaline medium – Streptomycin (Extracellular org)
  3. Drugs acting in both medium – INH, Rifampicin
  4. Drugs acting on persisters – Rifampicin
  5. Drugs crossing blood brain barrier – INH, Rifampicin, pyrazinamide
Extra Edge:

Streptomycin does not cross BBB so it is not given in TBM  


Important Points: - Management


First line -


Drugs Side effects
INH Hepatitis, B6 deficiency, Neuropathy, psychosis, agranulocytosis
Rifampicin Hepatitis, orange urine, , flu like syndrome inactivates oral contraceptives, thrombocytopenia.
Ethambutol Optic neuritis, colour blindness
Pyrazinamide Hepatitis, arthralgias, hyperuricemia
Streptomycin Renal toxicity, otic toxicity


Second line drugs                                              

  1. Thiacetazone
  2. Capreomycin
  3. PAS
  4. Ethionamide
  5. Kanamycin
  6. Ciprofloxacin
  7. Cycloserine
  8. Amikacin
  9. Streptomycin

Note: In Harrison 18th edition streptomycin has been included as second line drug .

Recent Advances: - Newer drugs

  1. Rifabutin   
  2. Rifapentene          
  3. Linezolid
  4. Amoxiclav combination
  5. Ofloxacin
  6. Clarithromycin               
  7. Azithromycin
  8. Clofazimine 

Recent Advances (Ref. Hari. 18th ed., pg - 1352): Moxifloxacin and Gatifloxacin are in late-phase clinical development as 4-month treatment-shortening regimens for drug-susceptible TB.


Recent Advances


XDR TB (extensive drug resistance strain) – MDR TB + resistance to fluoroquinolones and one or more of the injectable drugs amikacin, kanamycin or capreomycin.


Multi Drug Resistant TB

MDR-TB is defined by the presence of resistance to both Rifampicin and isoniazid with or without other resistance.


MDR TB should be considered in patients with:

  1. Previous drug treatment for TB
  2. Contact with a case of known MDRTB
  3. HIV infection
  4. Failure of clinical response on treatment
  5. Prolonged sputum smear or culture positive while on treatment (smear positivity at 4 months or culture positivity at 5 months) 

Sources of Bleeding in Hemoptysis

  1. Bronchial Arteries: Most common source of Bleeding in Hemoptysis (>90% cases)              
  2. Pulmonary Arteries:  Uncommon source of bleeding in hemoptysis (<10% cases) 

Hemoptysis in TB

Sources of Bleeding in Hemoptysis
  1. Bronchial Arteries: Most common source of Bleeding in Hemoptysis (>90% cases)        
  2. Pulmonary Arteries:  Uncommon source of bleeding in hemoptysis (<10% cases)

Causes of hemoptysis in TB

  1. Rupture of dilated vessel in a cavity (Rasmussen’s aneurysm) (AIIMS May 2008) It is of pulmonary artery in origin. (Ref. Hari. 18th ed., Pg - 1345)
  2. Erosion of vessel
  3. Aspergilloma formation in an old cavity 

Important Points: Commonest source of hemoptysis in TB is from rupture of bronchial artery.(LQ 2012)

Hemodynamics of Hemoptysis
  1. Large volume hemoptysis, referred to as massive hemoptysis, is variably defined as hemoptysis of greater than 200-600 cc in 24h. Massive hemoptysis should be considered a medical emergency.
  2. Shock index = Heart rate / Systolic BP. (AIIMS May 2014)
  3. Normal is 0.5 to 0.6 but in any hypovolemic shock (Which may occur in severe hemoptysis also), the index increases and  may go upto 1.
  4. Increased shock index is a good parameter to know about hypovolumic shock.
Extra Edge - Treatment of TB in special situation:
  1. Pregnancy with TB =  H, R, E (S and Z are contraindicated)
  2. Jaundice with TB =  S, E (H, R, Z are contraindicated)
  3. CRF with TB = R full dose, H half dose daily, E half dose twice a week only.

(S and Z are contra indicated in end stage renal failure).


Note: In mild to moderate renal failure, H, R, Z may be given in the usual doses (Ref. Hari. 18th ed., Pg - 1356


Extra Edge - Indications of Corticosteroids in TB –
  1. TBM                          
  2. Addison’s crisis      
  3. Seriously ill pt. before chemotherapy is effective
  4. Pericardial, pleural effusions      
  5. Genitourinary TB   
  6. Choroid retinitis


Extra Edge – Indication of Higher dose of Pyridoxine in TB
  1. Alcoholics          
  2. Malnutrition
  3. Pregnant /lactating mother   
  4. CRF       
  5. Diabetes      
  6. HIV, AIDS


Extra Edge - Indications of Surgery in TB
  1. Massive hemoptysis
  2. Empyema  chest tube.       
  3. MDR TB with localized disease

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