Respiratory Infections

1. Respiratory Infections

2. Respiratory tract defences • Ventilatory flow • Cough • Mucociliary clearance mechanisms • Mucosal immune system

3. Upper respiratory tract infections • Rhinitis • Rhinovirus, coronavirus, influenza/parainfluenza • Non-infective (allergic) rhinitis has similar symptoms (related to asthma) • Sinusitis • Otitis media Latter 2 have a risk of bacterial superinfection, mastoiditis, meningitis, brain abscess

4. Laryngitis • Most commonly upper respiratory viruses • Diphtheria • C. diphtheriae produces a cytotoxic exotoxin causing tissue necrosis at site of infection with associated acute inflammation. Membrane may narrow airway and/or slough off (asphyxiation)

6. Acute epiglottitis • H. influenza type B • Another cause of acute severe airway compromise in childhood

7. Pneumonia • Infection of pulmonary parenchyma with consolidation

8. Pneumonia • Gr. “disease of the lungs” • Infection involving the distal airspaces usually with inflammatory exudation (“localised oedema”). • Fluid filled spaces lead to consolidation

9. Classification of Pneumonia • By clinical setting (e.g. community acquired pneumonia) • By organism (mycoplasma, pneumococcal etc) • By morphology (lobar pneumonia, bronchopneumonia)

10. Pathological description of pneumonia

11. Organisms • Viruses – influenza, parainfluenza, measles, varicella-zoster, respiratory syncytial virus (RSV). Common, often self limiting but can be complicated • Bacteria • Chlamydia, mycoplasma • Fungi

12. Lobar Pneumonia • Confluent consolidation involving a complete lung lobe • Most often due to Streptococcus pneumoniae (pneumococcus) • Can be seen with other organisms (Klebsiella, Legionella)

13. Clinical Setting • Usually community acquired • Classically in otherwise healthy young adults

14. Pathology • A classical acute inflammatory response • Exudation of fibrin-rich fluid • Neutrophil infiltration • Macrophage infiltration • Resolution • Immune system plays a part antibodies lead to opsonisation, phagocytosis of bacteria

15. Macroscopic pathology • Heavy lung • Congestion • Red hepatisation • Grey hepatisation • Resolution The classical pathway

16. Lobar pneumonia (upper lobe – grey hepatisation), terminal meningitis

17. Pneumonia – fibrinopurulent exudate in alveoli (grossly “red hepatisation”)

18. Pneumonia – neutrophil and macrophage exudate (grossly “grey hepatisation”)

19. Complications • Organisation (fibrous scarring) • Abscess • Bronchiectasis • Empyema (pus in the pleural cavity)

20. Pneumonia – fibrous organisation

21. Bronchopneumonia • Infection starting in airways and spreading to adjacent alveolar lung • Most often seen in the context of pre-existing disease

22. Bronchopneumonia

23. Bronchopneumonia • The consolidation is patchy and not confined by lobar architecture

24. Clinical Context • Complication of viral infection (influenza) • Aspiration of gastric contents • Cardiac failure • COPD

25. Organisms • More varied – Strep. Pneumoniae, Haemophilus influenza, Staphylococcus, anaerobes, coliforms • Clinical context may help. Staph/anaerobes/coliforms seen in aspiration

26. Complications • Organisation • Abscess • Bronchiectasis • Empyema

27. Viral pneumonia • Gives a pattern of acute injury similar to adult respiratory distress syndrome (ARDS) • Acute inflammatory infiltration less obvious • Viral inclusions sometimes seen in epithelial cells

28. The immunocompromised host • Virulent infection with common organism (e.g. TB) – the African pattern • Infection with opportunistic pathogen • virus (cytomegalovirus - CMV) • bacteria (Mycobacterium avium intracellulare) • fungi (aspergillus, candida, pneumocystis) • protozoa (cryptosporidia, toxoplasma)

29. Diagnosis • High index of suspicion • Teamwork (physician, microbiologist, pathologist) • Broncho-alveolar lavage • Biopsy (with lots of special stains!)

30. Immunosuppressed patient – fatal haemorrhage into Aspergillus-containing cavity

31. HIV-positive patient CMV (cytomegalovirus) and “pulmonary oedema” on transbronchial biopsy….

32. Special stain also shows Pneumocystis

33. Tuberculosis • 22 million active cases in the world • 1.7 million deaths each year (most common fatal organism) • Incidence has increased with HIV pandemic

34. Tuberculosis • Mycobacterial infection • Chronic infection described in many body sites – lung, gut, kidneys, lymph nodes, skin…. • Pathology characterised by delayed (type IV) hypersensitivity (granulomas with necrosis)

35. Tuberculosis (pathogenesis of clinical disease) • Virulence of organisms • Hypersensitivity vs. immunity • Tissue destruction and necrosis

36. Mycobacterial virulence • Related to ability to resist phagocytosis. • Surface LAM antigen stimulates host tumour necrosis factor (TNF) a production (fever, constitutional symptoms)

37. Organisms • M. tuberculosis/M.bovis main pathogens in man • Others cause atypical infection especially in immunocompromised host. Pathogenicity due to ability; • to avoid phagocytosis • to stimulate a host T-cell response

38. Immunity and Hypersensitivity • T-cell response to organism enhances macrophage ability to kill mycobacteria • this ability constitutes immunity • T-cell response causes granulomatous inflammation, tissue necrosis and scarring • this is hypersensitivity (type IV) • Commonly both processes occur together

39. Pathology of Tuberculosis (1) • Primary TB (1st exposure) • inhaled organism phagocytosed and carried to hilar lymph nodes. Immune activation (few weeks) leads to a granulomatous response in nodes (and also in lung) usually with killing of organism. • in a few cases infection is overwhelming and spreads

40. Pathology of Tuberculosis (2) • Secondary TB • reinfection or reactivation of disease in a person with some immunity • disease tends initially to remain localised, often in apices of lung. • can progress to spread by airways and/or bloodstream

41. Tissue changes in TB • Primary • Small focus (Ghon focus) in periphery of mid zone of lung • Large hilar nodes (granulomatous) • Secondary • Fibrosing and cavitating apical lesion (cancer an important differential diagnosis

42. Primary and secondary TB • In primary the site of infection shows non-specific inflammation with developing granulomas in nodes • In secondary there are primed T cells which stimulate a localised granulomatous response

43. Primary TB – Ghon Focus

44. Secondary TB • Necrosis • Fibrosis • Cavitation T cell response: CD4 (helper) enhance killing. CD8 (cytotoxic) kill infected cells giving necrosis

45. Granulomatous inflammation with caseous necrosis

46. Acid fast stain – spot the organism (a red snapper)!

47. Complications • Local spread (pleura, lung) • Blood spread. Miliary TB or “end-organ” disease (kidney, adrenal etc.) • Swallowed - intestines

48. The host-organism balance • Not all infected get clinical disease • Organisms frequently persist following resolution of clinical disease • Any diminished host resistance can reactivate (thus 33% of HIV positive are co-infected with TB

49. Secondary TB – rapid death due to miliary disease

50. Miliary white foci – blood spread to lower lobe