A 44-year-old man presented with cough, breathlessness, night sweats and fever for 4 weeks. He recently developed blood in his sputum. Examination found a temperature of 37.8°C with no other abnormalities. Tests found elevated ESR and CRP, and a strongly positive Mantoux test. Chest X-ray showed haziness in the upper and middle lobes bilaterally. Sputum was positive for acid-fast bacilli and culture grew Mycobacterium tuberculosis. The patient was diagnosed with pulmonary tuberculosis and started on anti-tuberculosis treatment. His sputum became negative and chest X-ray improved, and he was discharged on ongoing treatment.

1. Pulmonary Tuberculosis

2. Theme: Hemoptysis

3. Theme: Hemoptysis
Case Scenario:
A 44-year-old man presented in the pulmonary clinic complaining of cough,
breathlessness, night sweats and low grade fever from last four weeks. Now he
had small amount of blood in the sputum from few days. He also had lost 2kg
weight during this illness.
Clinical examination:
Temperature 37.8°C with no evidence of anaemia, clubbing and edema.
Chest auscultation; crepitation's audible in the lung apices
Lab investigations:
Haemoglobin and white cell count were normal.
ESR 70mm / hour
C-Reactive protein 231 mg/l (normal below 3mg/L)

4. Cont…..
Mantoux test: strongly positive
Chest X-ray: bilateral upper and middle-lobe haziness
Sputum Smear: positive for acid-fast bacilli
Culture: reported Mycobacterium tuberculosis
Diagnosis: Pulmonary tuberculosis
Treatment: Started anti tuberculous treatment (isoniazid
and rifampicin for 6 months, together with pyrazinamide for
the first 2 months)
Progress: sputum became negative and chest X-ray much
improved
Discharged: on ATT with regular follow up till full recovery

5. Learning Objectives
List the causative agents of pulmonary tuberculosis
Identify routes of infection of pulmonary TB
Explain the pathogenesis of Tuberculosis
Classify pulmonary TB into; primary and secondary subtypes
Identify components of primary complex of TB
Know causes of secondary TB and list its complications
Identify sites and morphology of secondary TB
Correlate pathogenesis of TB with clinical presentation

6. Tuberculosis (TB)
Communicable disease
Chronic granulomatous inflammation with caseation necrosis leads to
destruction of tissue or organs
Epidemiology:
WHO reported; 1.7 billion individual infected worldwide with 8-10 million new
cases and 1.5 million deaths per year
TB flourishes under conditions of poverty, crowding and chronic debilitating
illness

7. Etiology and Routes of Transmission
M. tuberculosis hominis; most cases of pulmonary TB; transmission
usually direct, by inhalation of airborne organisms in aerosols or by
exposure to contaminated secretions of infected individuals with active
pulmonary disease
Mycobacterium bovis; Oropharyngeal and intestinal TB contracted by
drinking milk contaminated with Mycobacterium bovis
Mycobacterium avium complex; much less virulent than M. tuberculosis,
causes disease in immunocompromised individuals, in about 10% - 30% of
AIDS patients and atypical mycobacteria in HIV infected cases

8. Spread of Tuberculosis
Local spread
Macrophages carrying M. bacilli into surrounding tissues
Lymphatic spread
Into the regional lymph nodes
Hematogenous spread
Tuberculous bacteremia producing miliary tuberculosis involving multiple organs
By natural passages
Transbronchial spread to adjacent lung segments and from lung lesions into pleura
Swallowing of infected sputum into intestinal tract
Tuberculous salpingitis into peritoneal cavity

9. Types of Tuberculosis (TB)
Pulmonary TB
Primary and Secondary Pulmonary TB
Progressive primary and secondary TB
Miliary TB
Progressive primary and secondary TB may lead to miliary TB which may be;
Pulmonary and Extra-pulmonary Miliary TB
Isolated organ TB
Involves ; intestine, lymph node, bone, skin, meninges, brain, kidney,
adrenals, testis, epididymis, ovaries, fallopian tubes and endometrium

10. Pathogenesis
Bacilli entry into alveolar macrophages
After inhalation of coughed out infectious aerosol bacilli engulfed by alveolar
macrophages - Internalization
Replication in macrophages
In earliest phase of primary TB (first 3 weeks) in non-sensitized patient,
bacillary proliferation within alveolar macrophages and air spaces leads to
bacteremia and seeding of bacilli to multiple sites
Development of cell-mediated immunity
Approximately 3 weeks after exposure, processed mycobacterial antigens
by alveolar macrophages and dendritic cells reach the draining lymph nodes
and is presented to T cells.
Meanwhile IL-12 secreted by alveolar macrophage than generate CD4+T
cells (TH1 subset) which secrete IFN-γ

11. Cont …….
T cell–mediated macrophage activation and killing of bacteria
IFN-γ, secreted from TH1 cells activate macrophages to release;
Tumor necrosis factor (TNF): which recruit monocytes at site of infection
Inducible nitric oxide synthase (iNOS): raises nitric oxide(NO) levels to
create reactive nitrogen species, important in killing of bacilli
Anti-microbial peptides (defensins): toxic to bacilli
Granulomatous inflammation and tissue damage
Under the influence of IFN-γ, monocytes differentiate into “epithelioid
histiocytes” and some multinucleated giant cells to form granulomas to halt
infection, before significant tissue destruction, but in immune deficits
individuals infection progresses to caseation necrosis and tissue damage

12. Natural History and Pathogenesis of Primary Pulmonary TB
A- Inhalation of virulent M. tuberculosis results the development of cell-mediated immunity to the organism
B- Initiation and consequences of cell mediated immunity to the organism, accompanied by a positive tuberculin test
Langhans
Giant Cell Epithelioid Cell

14. Primary Pulmonary TB
Inhaled bacilli implant in distal air spaces of lower part of upper lobe or in the
upper part of lower lobe of lung typically in the sub-plural region
During the development of sensitization, 1 to 1.5cm gray-white inflammatory
lesion appears in the sub-plural region called Ghon focus, in majority it
shows central caseation necrosis
Tubercle bacilli, either free or within phagocytes, travel via lymphatic vessels
to hilar lymph nodes, which often caseate, this combination of sub-plural and
lymph node lesion is called the Ghon complex
Lymphatic and hematogenous spread to other parts of the body also occurs
during the first few weeks but due to development of cell-mediated immunity
this infection is controlled in approximately 95% of the cases

15. Primary Pulmonary TB
Fibro calcified Ghon complex
detectable as a Ranke complex
on chest radiograph)
Subpleural grey white tubercle (Ghon focus)
Ghon focus+ Hilar lymphadenopathy = Ghon Complex

16. Outcome of Primary Pulmonary TB
Depends on the balance of immunity to tissue destruction
Healing with Fibrosis:
In 95% cases cell mediated immunity  healing in 3 weeks with fibrosis 
calcification
Progressive Primary Pulmonary TB:
Cavitary tuberculosis
Tuberculous bronchopneumonia
Miliary pulmonary TB via hematogenous spread to lungs and other organs

17. Secondary Pulmonary TB
Initial lesion; lung apex a small focus of consolidation less than 2 cm in
diameter, within 1 to 2 cm of the apical pleura (Simon focus)
Grossly; sharply circumscribed, firm, gray-white to yellow areas with
variable amount of central caseation and peripheral fibrosis.
Favorable cases, the initial parenchymal focus get fibrocalcifed
Progressive lesions cavitation is common

18. Secondary Pulmonary TB
X-ray chest shows cavityUpper parts of both lungs shows cheesy-white areas of
caseation and multiple areas of softening and cavitation

19. Microscopy
Active lesions; caseating and non-
caseating epithelioid granulomas
Components of caseating granulomas
Central caseation necrosis
Surrounded by epithelioid cells
Langhans multinucleated giant cells
Circumferential collar of lymphocytes
Enclosing rim of fibroblasts(old lesions)
TB bacilli demonstrated by Z-N staining,
but not in late fibrocalcified stages

20. Outcome of Secondary Pulmonary TB
Secondary pulmonary TB may heal with fibrosis either spontaneously or
after therapy, or may progress and extend into;
Progressive Pulmonary TB
Pulmonary or Systemic Miliary TB
Amyloidosis delayed effect of chronic TB

21. Progressive Pulmonary TB
Apical lesion enlarges and erode
bronchus with evacuation of necrotic
material in its lumen
Cavity lined by caseous material is left
behind, walled off by fibrous tissue
Cavity remain intact or collapse and
become fibrotic
Erosion of blood vessels - hemoptysis
Sputum positive for TB bacilli

22. Miliary Pulmonary TB
Inadequate treatment or poor host defenses
Infection spread by direct extension and through
Airways and lympho-vascular channels
Small 1-2 mm (millet seed) sized yellow-white
areas of consolidation scattered throughout lung
parenchyma
Miliary pulmonary disease pleural effusion,
empyema or obliterative fibrous pleuritis
Mantoux test is frequently negative

23. Systemic Miliary TB
Occurs when the tubercle bacilli
disseminate hematogenously
throughout the body
Organs most commonly involved are
liver, bone marrow, spleen, adrenal
glands, meninges, kidneys, fallopian
tubes, and epididymis
Miliary TB of the spleen, cut surface
shows numerous gray-white granulomas

24. Isolated-organ TB
May appear in any one of the organs or tissues by hematogenous route;
Meninges (tuberculous meningitis), Brain (tuberculoma)
Kidneys (renal tuberculosis)
Adrenal glands (Addison disease)
Bones (osteomyelitis)
Vertebrae (Pott disease), clinically paraspinal “cold” abscesses
Genital TB (endometritis, salpingitis and epididymitis)
Intestinal TB particularly ileoceacal, ingestion of contaminated milk or by
swallowing coughed up infective material in advanced cases of secondary TB
Tuberculous Lymphadenitis usually in the cervical region (“scrofula”)

25. Screening methods
Mantoux test
Based on intra dermal injection of Tuberculin -
Purified Protein Derivative (PPD) used to detect
active or latent infection (primary method)
Gamma Interferon Release Assay (IGRA)
In vitro blood tests of cell-mediated immune
response; they measure T-cell release of IFN-γ
following stimulation by antigens specific to the
M. tuberculosis complex (with the exception of
BCG sub strains) used for latent infection

26. Natural History and Spectrum of TB
C/F
May be asymptomatic
Low grade afternoon fever
Night sweats
Chronic productive cough
Hemoptysis
Anemia
Weight loss

27. Laboratory Diagnosis
Raised ESR and CRP levels
Sputum smears for acid-fast
bacilli (AFB)
AFB culture the most specific
test for TB

28. Nontuberculous Mycobacteria
Mycobacterium avium-intracellulare (or M. avium complex) ,
M. kansasii, and M. abscessus
Most commonly cause; chronic localized pulmonary disease like; upper-lobe
cavitary lesion, mimicking TB (especially in chronic smokers and alcoholics)
COPD, cystic fibrosis and pneumoconiosis
In immunosuppressed (primarily HIV positive) individuals M. avium complex
infection manifest as a symptomatic disseminated disease (fever, night
sweats, weight loss)
In AIDS patients CD4+ T cell counts fall below 100 cells/μL
disseminated M. avium complex infection occurs and tissue
examination reveal foamy macrophages “stuffed” with atypical
mycobacteria without any granulomas

29. Pulmonary: Fungal Infections
Immunocompetent individuals
Histoplasmosis
Coccidiodomycosis
Blastomycosis
(all are diamorphic fungi)
Clinically may manifests as:
Acute primary pulmonary infection
Chronic granulomatous pulmonary disease
(with or without caseation necrosis)
Disseminated miliary disease Macrophages loaded with yeast
form of H. Capsulatum, appear
black with silver stain

30. Pulmonary Fungal Opportunistic Infections
Immunocompromised individuals
• Candidiasis
• Cryptococcosis
• Mucormycosis
• Aspergillosis
• Pneumocystis (carinii) jiroveci
Candidiasis :
Common superficial mucosal infection
Maybe invasive in patients having ; AIDS, renal
transplant, neutropenia, heart valvular diseases
Findings include abscesses in kidney, lungs, heart,
Brain and GIT.
Fungal lung abscess-Candia

31. Pulmonary Fungal Opportunistic Infections
Mucormycosis:
Immunocompromised host, specially in diabetics
Mucor having non-septate hyphae
Frequently infects sinuses, oral cavity, brain & lung
Angioinvasive, hyphae growing in and around blood
vessels causing ischemia
Cryptococcosis :
Minimal inflammation, usually in lung, may spread to
meninges

32. Pulmonary Fungal Opportunistic Infections
Aspergillosis: Infection by aspergillus, septate branching
hyphae at acute angles, stain black with GMS
Aspergilloma (fungus ball): fungus grows in existing
cavities like tuberculous cavities, bronchiectasis,
paranasal sinus and intracranial
Invasive pulmonary aspergillosis: In immunocompromised,
produces multifocal necrotizing pneumonia or may be
angioinvasive vasculitis, occlusion and infarction or
generalized dissemination
Allergic bronchopulmonary aspergillosis: Patients with
asthma or hypersensitivity pneumonitis, these patients have
Ig E antibodies with peripheral eosinophilia

33. Pulmonary Opportunistic Fungal Infections
Pneumocystis (carinii) jiroveci pneumonia
In AIDS patients, often with CMV infection
Clinical features: fever, dry cough, dyspnea & hypoxia
Radiology: bilateral & basal infiltrates
Pathology
Septa are thickened by edema and mononuclear
infiltrate
Intra-alveolar foamy pink exudate (Cotton candy)
Encysted or trophozoite forms in exudate
Diagnosis: Organism best demonstrated in
bronchioalveolar lavage or in transbronchial
biopsy cup shaped round cysts GMS positive
GMS +

34. Pneumonia in Immunocompromised
Bacterial Infections: by P. aeruginosa, typical or atypical mycobacterium
spp. (M. avium and M. hominis) common in AIDS patient) atypical
microgranulomas with minimal caseation
Viral Infections: by cytomegalovirus (CMV) and herpesvirus by
transplacental spread , in organ transplanted and AIDS patients.
Produces necrotizing interstitial pneumonia with intracellular inclusions, may
progress to acute respiratory distress syndrome (ARDS)
Fungal infections: by Pneumocytis jiroveci, Aspergillosis, Candidiasis and
Cryptococcus neoformans

35. OSPE

36. Primary Pulmonary TB

37. Pulmonary Chronic Granulomatous Inflammation

38. Caseating Granulomatous Inflammation

39. Acid Fast Tuberculous Bacilli

40. Secondary Pulmonary TB

41. Progressive Pulmonary TB

42. Pulmonary Milliary TB

43. Aspergilloma Lung

44. Lung Abscess Candida

45. KEY QUESTIONS
What are the modes of transmission of T.B.?
What are causative agents of Tuberculosis?
Mention the differences between primary & secondary pulmonary TB?
Identify classic clinical features of active pulmonary TB ?

46. References
• Robbins Basic Pathology 10th edition 2017, Chapter 13 Lung, Pages
526-37
• www.Webpathology.com