Respiratory Infections

Respiratory tract defences

Ventilatory flow Cough Mucociliary clearance mechanisms Mucosal immune system

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

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)

Acute epiglottitis

H. influenza type B Another cause of

acute severe airway compromise in childhood

Pneumonia

Infection of pulmonary parenchyma with consolidation

Pneumonia

Gr. “disease of the lungs” Infection involving the distal airspaces

usually with inflammatory exudation (“localised oedema”).

Fluid filled spaces lead to consolidation

Classification of Pneumonia

By clinical setting (e.g. community acquired pneumonia)

By organism (mycoplasma, pneumococcal etc)

By morphology (lobar pneumonia, bronchopneumonia)

Pathological description of pneumonia

Organisms

Viruses – influenza, parainfluenza, measles, varicella-zoster, respiratory syncytial virus (RSV). Common, often self limiting but can be complicated

Bacteria Chlamydia, mycoplasma Fungi

Lobar Pneumonia

Confluent consolidation involving a complete lung lobe

Most often due to Streptococcus pneumoniae (pneumococcus)

Can be seen with other organisms (Klebsiella, Legionella)

Clinical Setting

Usually community acquired Classically in otherwise healthy young

adults

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

Macroscopic pathology

Heavy lung Congestion Red hepatisation Grey hepatisation Resolution

The classical pathway

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

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

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

Complications

Organisation (fibrous scarring) Abscess Bronchiectasis Empyema (pus in the pleural cavity)

Pneumonia – fibrous organisation

Bronchopneumonia

Infection starting in airways and spreading to adjacent alveolar lung

Most often seen in the context of pre-existing disease

Bronchopneumonia

Bronchopneumonia

The consolidation is patchy and not confined by lobar architecture

Clinical Context

Complication of viral infection (influenza)

Aspiration of gastric contents Cardiac failure COPD

Organisms

More varied – Strep. Pneumoniae, Haemophilus influenza, Staphylococcus, anaerobes, coliforms

Clinical context may help. Staph/anaerobes/coliforms seen in aspiration

Complications

Organisation Abscess Bronchiectasis Empyema

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

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)

Diagnosis

High index of suspicion Teamwork (physician, microbiologist,

pathologist) Broncho-alveolar lavage Biopsy (with lots of special stains!)

Immunosuppressed patient – fatal haemorrhage into Aspergillus-containing cavity

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

Special stain also shows Pneumocystis

Tuberculosis

22 million active cases in the world 1.7 million deaths each year (most

common fatal organism) Incidence has increased with HIV

pandemic

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)

Tuberculosis (pathogenesis of clinical disease)

1. Virulence of organisms

2. Hypersensitivity vs. immunity

3. Tissue destruction and necrosis

Mycobacterial virulence

Related to ability to resist phagocytosis.

Surface LAM antigen stimulates host tumour necrosis factor (TNF) production (fever, constitutional symptoms)

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

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

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

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

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

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

Primary TB – Ghon Focus

Secondary TB

Necrosis Fibrosis Cavitation T cell response: CD4

(helper) enhance killing. CD8 (cytotoxic) kill infected cells giving necrosis

Granulomatous inflammation with caseous necrosis

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

Complications

Local spread (pleura, lung)

Blood spread. Miliary TB or “end-organ” disease (kidney, adrenal etc.)

Swallowed - intestines

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

Secondary TB – rapid death due to miliary disease

Miliary white foci – blood spread to lower lobe

“Galloping consumption” – TB bronchopneumonia

Decreased immunity – many more organisms on acid fast stain

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

Lung Abscess

Localised collection of pus. Central tissue destruction. Lined by granulation tissue/fibrosis (attempted healing)

Tumour-like Chronic malaise and fever

Lung abscess

Organisms: Staphylococcus Anaerobes Gram negatives

Clinical contexts: Aspiration Following pneumonia Fungal infection Bronchiectasis Embolic

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

Bronchiectasis (2)

Affects lower lobes preferentially Chronic recurring infection sometimes

leads to finger clubbing

Complications of bronchiectasis

Pneumonia Abscess Septicaemia Empyema “Metastatic” abscess Amyloidosis

Bronchiectasis with chronic suppuration

Bronchiectasis

Bronchiectasis distal to an obstructing tumour