Pulmonary Infections & TB Pathology

Lung infections are a perennial NEET PG favourite, blending morphology, microbiology, and immunology. This note distils tuberculosis (primary vs secondary, the named foci, and tissue patterns), the four classic stages of lobar pneumonia, bronchopneumonia, and lung abscess into exam-ready frameworks.

Tuberculosis: the core concept

Tuberculosis (TB) is a chronic granulomatous infection caused by Mycobacterium tuberculosis, an aerobic, acid-fast bacillus (AFB) with a waxy mycolic-acid-rich wall. The organism is an obligate aerobe, which explains its predilection for the well-oxygenated apices in post-primary disease. Tissue damage in TB is driven not by bacterial toxins but by the host type IV (delayed-type) hypersensitivity response — caseating granuloma formation is an immunological event.

The hallmark lesion is the tubercle: a granuloma with central caseous necrosis surrounded by epithelioid macrophages, Langhans giant cells (horseshoe/peripheral arrangement of nuclei), and a rim of lymphocytes and fibroblasts.

High-yield: Caseous (caseating) granuloma = TB until proven otherwise. Caseous necrosis is a combination of coagulative + liquefactive necrosis; grossly cheese-like, microscopically amorphous granular eosinophilic debris with loss of cellular outlines.

Cell biology you must know

• Epithelioid cells = activated macrophages with abundant pink cytoplasm, modified to resemble epithelium.
• Langhans giant cells = fused epithelioid macrophages with peripheral horseshoe nuclei (distinct from foreign-body giant cells with haphazard nuclei, and Touton/Reed-Sternberg cells).
• Granuloma formation requires CD4+ Th1 cells secreting IFN-γ, which activates macrophages; TNF-α maintains the granuloma. This is why anti-TNF biologics (infliximab) reactivate latent TB.

Primary vs secondary (post-primary) TB

Primary TB is infection in a previously unexposed, unsensitised host (classically a child). Secondary TB arises in a previously sensitised host — usually reactivation of dormant bacilli, occasionally reinfection.

Feature	Primary TB	Secondary (post-primary) TB
Host	Non-immune, first exposure	Previously sensitised
Typical site	Subpleural lower part of upper lobe / upper part of lower lobe (best-ventilated)	Apex of upper lobe (apico-posterior)
Characteristic lesion	Ghon focus → Ghon complex	Apical fibrocaseous lesion / cavity
Hypersensitivity	Develops during this phase	Already present (brisk)
Lymph node involvement	Marked hilar/mediastinal lymphadenopathy	Usually minimal
Cavitation	Rare	Common
Outcome	Usually heals (fibrosis/calcification); may progress	Cavitation, fibrosis, dissemination

Named foci — the most-tested table

Eponym	What it is	Location/Timing
Ghon focus	Initial subpleural parenchymal caseous lesion of primary TB	Lower upper lobe / upper lower lobe, near fissure
Ghon complex	Ghon focus + draining lymphangitis + hilar/tracheobronchial lymphadenitis	Primary TB triad
Ranke complex	Calcified/fibrosed healed Ghon complex (radiologically visible)	Healed primary TB
Simon focus	Apical focus from haematogenous seeding during primary TB; later reactivates	Apex; nidus for secondary TB
Assmann focus	Early secondary (reactivation) infraclavicular apical lesion	Subclavicular, secondary TB
Rasmussen aneurysm	Pseudoaneurysm of pulmonary artery branch in a TB cavity wall → haemoptysis	Within chronic cavity
Puhl lesion	Apical reinfection focus (less commonly asked)	Apex

High-yield: Ghon focus = primary; Simon focus = apical seed during primary that reactivates; Assmann focus = early secondary. A classic stem describes calcified hilar node + peripheral calcified parenchymal scar = Ranke complex (healed primary TB).

Sequence of primary TB: Inhalation of bacilli → Ghon focus (subpleural) → lymphatic spread → Ghon complex → healing by fibrosis + calcification → Ranke complex (or progression/dissemination if immunity fails).

Patterns / spread of pulmonary TB

1. Progressive primary TB — failure to contain infection (infants, HIV, malnutrition); the Ghon focus enlarges, caseates, and may cavitate.
2. Cavitary secondary TB — liquefied caseum is coughed out via a bronchus leaving a cavity; high bacillary load, highly infectious.
3. Miliary TB — haematogenous dissemination producing innumerable 1–2 mm (millet-seed) yellow-white nodules. "Miliary" implies blood-borne spread to lungs, liver, spleen, bone marrow, meninges, etc. Caused by erosion into a pulmonary vein (systemic miliary) or lymphatics draining into venous system (pulmonary miliary).
4. Tuberculous bronchopneumonia — endobronchial spread of liquefied caseum producing patchy consolidation.
5. Tuberculous ARDS / diffuse alveolar damage — overwhelming infection.
6. Endobronchial, endotracheal, laryngeal TB — from infected sputum.
7. Tuberculous pleuritis / empyema and fibrocaseous cavitary disease with healing fibrosis.

High-yield: Miliary lesions are 1–2 mm; "miliary" derives from milium (millet seed). Systemic miliary TB follows entry into the pulmonary vein (left heart → systemic circulation).

Extrapulmonary eponyms worth a line

• Pott disease — TB spondylitis (vertebral, classically thoracolumbar) → gibbus deformity, cold (psoas) abscess.
• Scrofula — tuberculous cervical lymphadenitis.
• Weigert / endarteritis obliterans — vascular changes around TB lesions limiting spread.

Investigations & diagnosis of choice

• Sputum AFB smear (Ziehl–Neelsen / ZN stain) — bacilli stain bright red against a blue background; carbol fuchsin + acid-alcohol decolourisation. Detection threshold ~10,000 bacilli/mL (low sensitivity). Auramine-rhodamine fluorescent stain is more sensitive for screening.
• CBNAAT / GeneXpert MTB/RIF — current first-line rapid test: detects M. tuberculosis DNA and rifampicin resistance within hours. NAAT is the investigation of choice for rapid confirmation.
• Culture (Löwenstein–Jensen / liquid MGIT) — gold standard; LJ medium takes 4–8 weeks (slow grower), liquid culture faster; allows drug-susceptibility testing.
• Mantoux/TST and IGRA (QuantiFERON) — detect infection/exposure, not active disease; cannot distinguish latent from active. IGRA is unaffected by prior BCG.
• Histopathology — caseating epithelioid granuloma with Langhans giant cells.

High-yield: ZN stain = AFB demonstration; LJ culture = gold standard but slow; CBNAAT/GeneXpert = rapid first-line that also flags rifampicin resistance. Granuloma + caseation on biopsy is strongly suggestive.

Lobar pneumonia — the four classic stages

Lobar pneumonia is acute exudative consolidation of a large portion or an entire lobe, classically due to Streptococcus pneumoniae (>90%; also Klebsiella in alcoholics/diabetics → "currant-jelly" sputum, bulging fissure). It evolves through four sequential stages, an absolute NEET PG favourite.

Stage	Timing	Gross	Microscopy
1. Congestion	Day 1–2	Heavy, red, boggy, wet lung	Vascular engorgement, intra-alveolar serous fluid, few neutrophils, many bacteria
2. Red hepatization	Day 3–4	Red, firm, liver-like, airless	Alveoli packed with RBCs, neutrophils, fibrin; congested capillaries
3. Grey hepatization	Day 5–7	Dry, grey-brown, firm	RBCs lyse; persistent fibrinosuppurative exudate (fibrin + neutrophils), bacteria disappear
4. Resolution	Day 8+	Lung returns to normal	Enzymatic digestion of exudate → granular debris resorbed / coughed up / phagocytosed; macrophages predominate

Flow: Congestion → Red hepatization → Grey hepatization → Resolution

High-yield: Red hepatization = RBCs + neutrophils + fibrin (red, liver-like). Grey hepatization = RBCs degraded, fibrinopurulent exudate (grey). The colour change is due to disintegration of red cells. Resolution is driven by macrophages.

Mnemonic for stages: "Children Read Good Rhymes" = Congestion → Red hep → Grey hep → Resolution.

Complications of lobar pneumonia: abscess (esp. type 3 pneumococcus, Klebsiella, Staph), empyema, organisation (carnification — fibrous conversion of exudate into solid tissue), and bacteraemic dissemination (meningitis, endocarditis, arthritis).

Bronchopneumonia (lobular pneumonia)

Patchy, multifocal, often bilateral basal consolidation centred on bronchioles, common at extremes of age and as a terminal event in debilitated patients.

Feature	Lobar pneumonia	Bronchopneumonia
Distribution	One/contiguous lobe, uniform	Patchy, multilobar, often bilateral basal
Centred on	Alveoli (lobar)	Bronchioles, spreading to adjacent alveoli
Age	Healthy adults 20–50	Infants, elderly, debilitated
Organism	S. pneumoniae, Klebsiella	Staph, Strep, H. influenzae, Pseudomonas, coliforms
Stages	Four classic stages	No defined stages; suppurative foci of varied age
Pleura	Often fibrinous pleuritis	Less often

High-yield: Bronchopneumonia is bronchiolocentric and patchy; lobar pneumonia is alveolocentric and uniform with the four stages. Klebsiella causes lobar pneumonia with abscess, bulging fissure, and currant-jelly (red-brown mucoid) sputum.

Lung abscess

A localised area of suppurative necrosis producing a cavity, usually following aspiration (the single most common cause), pneumonia (esp. S. aureus, Klebsiella, type 3 pneumococcus), bronchial obstruction (tumour), septic emboli, or haematogenous spread.

• Anaerobes (Bacteroides, Fusobacterium, Peptostreptococcus, Prevotella) — commonest organisms; from oral cavity → foul-smelling/putrid sputum.
• Location depends on posture: aspiration in the supine/recumbent position favours the posterior segment of right upper lobe and superior (apical) segment of right lower lobe — the right main bronchus is wider, shorter, more vertical.
• Microscopy: central pus, fibrous wall; chronicity → squamous metaplasia of lining.
• Complications: empyema, bronchopleural fistula, massive haemoptysis, secondary (AA) amyloidosis with chronicity, brain abscess from septic emboli.

High-yield: Aspiration lung abscess most often lodges in the right lung (posterior segment upper lobe / superior segment lower lobe) because of the more vertical right main bronchus.

Atypical & special infections (quick hits)

• Primary atypical (interstitial) pneumonia — Mycoplasma pneumoniae (commonest), Chlamydophila, viruses; interstitial mononuclear inflammation, sparse alveolar exudate, walking pneumonia; cold-agglutinin positive.
• Legionella — water/AC sources; needs buffered charcoal yeast extract (BCYE) culture; silver stain; SIADH/hyponatraemia, diarrhoea.
• Klebsiella — alcoholics, currant-jelly sputum, upper-lobe abscess.
• Aspergillus — colonises old TB cavity → aspergilloma (fungus ball/mycetoma) with air-crescent / Monod sign; acute-angle septate hyphae.
• Pneumocystis jirovecii — HIV (CD4 <200); foamy/frothy intra-alveolar exudate, cysts on GMS/silver stain, ground-glass on CT.

Key differentials of a caseating/cavitary lung lesion

• Caseating granuloma: TB (commonest). Non-caseating granuloma: sarcoidosis (Schaumann/asteroid bodies, non-caseating, ACE↑), berylliosis, Crohn.
• Cavity: TB, lung abscess, cavitating squamous cell carcinoma, Klebsiella, Staph, fungal (aspergilloma), GPA (Wegener — necrotising granulomatous vasculitis, c-ANCA/PR3).
• Apical fibrocavitary disease: secondary TB vs chronic histoplasmosis vs ankylosing spondylitis apical fibrosis.

Recently asked / exam angle

• Match the eponym to the focus: Ghon (primary, subpleural), Simon (apical seed, reactivates), Assmann (early secondary), Ranke (calcified healed primary), Rasmussen (aneurysm in cavity → haemoptysis). Frequently tested as a one-line stem.
• Caseous necrosis identified as combined coagulative + liquefactive; Langhans giant cell with peripheral horseshoe nuclei.
• Stage of lobar pneumonia from a histology/gross description — "grey, dry, firm with fibrinopurulent exudate and lysed RBCs" = grey hepatization; "alveoli full of RBCs, fibrin, neutrophils, liver-like" = red hepatization.
• Site of aspiration abscess = right posterior upper / superior lower lobe segment.
• Type IV hypersensitivity as the mechanism of tissue damage in TB; granuloma cytokines IFN-γ, TNF-α.
• CBNAAT/GeneXpert as first-line rapid test detecting rifampicin resistance; LJ culture as gold standard.
• Miliary TB lesion size 1–2 mm; spread via pulmonary vein/lymphatics.
• Image-based: air-crescent sign = aspergilloma in old TB cavity.

Rapid revision

1. Ghon complex = Ghon focus + lymphangitis + hilar lymphadenitis (primary TB).
2. Ranke complex = calcified/healed Ghon complex.
3. Simon focus = apical haematogenous seed during primary TB that later reactivates → secondary TB.
4. Assmann focus = early secondary (reactivation) infraclavicular apical lesion.
5. Rasmussen aneurysm = pulmonary artery pseudoaneurysm in a TB cavity → haemoptysis.
6. TB tissue damage = type IV hypersensitivity; granuloma needs IFN-γ (Th1) and TNF-α; anti-TNF drugs reactivate TB.
7. Langhans giant cell = peripheral horseshoe nuclei; epithelioid cells = activated macrophages; caseation = coagulative + liquefactive necrosis.
8. Lobar pneumonia stages: Congestion → Red hepatization → Grey hepatization → Resolution ("Children Read Good Rhymes"); resolution driven by macrophages.
9. Red hep = RBC+fibrin+neutrophils (red, liver-like); grey hep = lysed RBCs + fibrinopurulent exudate (grey).
10. Bronchopneumonia = patchy, bilateral basal, bronchiolocentric; lobar = uniform, alveolocentric. Klebsiella → currant-jelly sputum, bulging fissure, abscess.
11. Aspiration lung abscess → right lung posterior upper / superior lower segment; anaerobes → foul sputum; chronic → AA amyloidosis.
12. CBNAAT/GeneXpert = rapid first-line (+ rifampicin resistance); LJ culture = gold standard; ZN stain = AFB red on blue; aspergilloma = air-crescent sign.