Respiratory Infections

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Respiratory Infections
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Respiratory tract defences

• Ventilatory flow
• Cough
• Mucociliary clearance mechanisms
• Mucosal immune system

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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

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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)

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Acute epiglottitis

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

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Pneumonia

• Infection of pulmonary parenchyma with
  consolidation

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Pneumonia

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

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Classification of Pneumonia

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

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Pathological description of pneumonia
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Organisms

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

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Lobar Pneumonia

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

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Clinical Setting

• Usually community acquired
• Classically in otherwise healthy young adults

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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

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Macroscopic pathology

• Heavy lung
• Congestion
• Red hepatisation
• Grey hepatisation
• Resolution
• The classical pathway

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Lobar pneumonia (upper lobe grey hepatisation),
terminal meningitis
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Pneumonia fibrinopurulent exudate in alveoli
(grossly red hepatisation)
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Pneumonia neutrophil and macrophage exudate
(grossly grey hepatisation)
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Complications

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

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Pneumonia fibrous organisation
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Bronchopneumonia

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

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Bronchopneumonia
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Bronchopneumonia

• The consolidation is patchy and not confined by
  lobar architecture

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Clinical Context

• Complication of viral infection (influenza)
• Aspiration of gastric contents
• Cardiac failure
• COPD

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Organisms

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

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Complications

• Organisation
• Abscess
• Bronchiectasis
• Empyema

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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

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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)

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Diagnosis

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

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Immunosuppressed patient fatal haemorrhage into
Aspergillus-containing cavity
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HIV-positive patient CMV (cytomegalovirus) and
pulmonary oedema on transbronchial biopsy.
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Special stain also shows Pneumocystis
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Tuberculosis

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

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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)

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Tuberculosis (pathogenesis of clinical disease)

1. Virulence of organisms
2. Hypersensitivity vs. immunity
3. Tissue destruction and necrosis

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Mycobacterial virulence

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

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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

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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

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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

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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

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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

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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

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Primary TB Ghon Focus
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Secondary TB

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

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Granulomatous inflammation with caseous necrosis
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Acid fast stain spot the organism (a red
snapper)!
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Complications

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

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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

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Secondary TB rapid death due to miliary disease
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Miliary white foci blood spread to lower lobe
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Galloping consumption TB bronchopneumonia
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Decreased immunity many more organisms on acid
fast stain
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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

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Lung Abscess

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

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Lung abscess

• Organisms
• Staphylococcus
• Anaerobes
• Gram negatives
• Clinical contexts
• Aspiration
• Following pneumonia
• Fungal infection
• Bronchiectasis
• Embolic

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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

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Bronchiectasis (2)

• Affects lower lobes preferentially
• Chronic recurring infection sometimes leads to
  finger clubbing

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Complications of bronchiectasis

• Pneumonia
• Abscess
• Septicaemia
• Empyema
• Metastatic abscess
• Amyloidosis

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Bronchiectasis with chronic suppuration
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Bronchiectasis
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Bronchiectasis distal to an obstructing tumour