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 Secondary
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

51. “Galloping consumption” – TB bronchopneumonia

52. Decreased immunity – many more organisms on acid fast stain

53. Why does disease reactivate?
Decreased T-cell function
age
coincident disease (HIV)
immunosuppressive therapy (steroids, cancer chemotherapy)
Reinfection at high dose or with more virulent organism

54. Lung Abscess
Localised collection of pus. Central tissue destruction. Lined by granulation tissue/fibrosis (attempted healing)
Tumour-like
Chronic malaise and fever

55. Lung abscess Organisms: Clinical contexts: Staphylococcus Anaerobes
Gram negatives
Clinical contexts:
Aspiration
Following pneumonia
Fungal infection
Bronchiectasis
Embolic

56. Bronchiectasis Abnormal fixed dilatation of the bronchi
Usually due to fibrous scarring following infection (pneumonia, tuberculosis, cystic fibrosis)
Also seen with chronic obstruction (tumour)
Dilated airways accumulate purulent secretions

57. Bronchiectasis (2) Affects lower lobes preferentially
Chronic recurring infection sometimes leads to finger clubbing

58. Complications of bronchiectasis
Pneumonia
Abscess
Septicaemia
Empyema
“Metastatic” abscess
Amyloidosis

59. Bronchiectasis with chronic suppuration

60. Bronchiectasis

61. Bronchiectasis distal to an obstructing tumour