Respiratory Infections

Dr Mulazim Hussain Bukhari

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)

MYCOBACTERIA ASSOCIATED WITH HUMAN DISEASE

Mycobacterium Environmental contaminant Reservoir

M tuberculosis No Human

M bovis No Human, cattle

M leprae No Humn

M kansasii Rarely Water, cattle

M marinum Rarely Fish, water

M scrofulaceum Possibly Soil, water

M avium intracellulare

Possibly Soil, water, birds

M ulcerans No Unknown

M fortuitum Yes Soil, water, animals

M chelonae Yes Soil, water, animals

CLASSIFICATION OF MYCOBACTERIA ASSOCIATED WITH HUMAN DISEASE

Mycobacterium Clinical significance Pigmentation Growth

Unclassified

M Tuberculosis , M bovis

M ulcerans

Strict pathogens No No

M leprae Strict pathogen - -

Runyon Group 1

M marinum , kansasii

Runyon Group 2

Usually pathogenic Photochromogens slow

M scrofulaceum Rarely pathogenic Scotochromogens slow

Runyon Group 3

M avium intracellulare Pathogenic in immunocompromised

No slow

Runyon Group 4

M fortuitum, M chelonae Rarely pathogenic No ‘rapid’

MYCOBACTERIUM

• Aerobic bacilli –non spore forming non motile

• Cell wall –rich in lipids

• Acid-fast bacilli

• Very slow growing

• Causes tuberculosis• Classic human disease• Pathogenesis• Transmission• Clinical presentations• Diagnosis• Treatment• Prevention

Mycobacterium tuberculosis

Tuberculosis (pathogenesis of clinical disease)

1. Virulence of organisms

2. Hypersensitivity vs. immunity

3. Tissue destruction and necrosis

Pathogenesis• Inhaled aerosols

Engulfed by alveolar macrophages Bacilli replicate Macrophages die

• Infected macrophages migrate local lymph nodes• Develop Ghon’s focus Primary complex• Cell mediated immune response

stops cycle of destruction and spread• Viable but non replicating bacilli present in macrophages

EVIDENCE OF INFECTION WITH M TUBERCULOSISChest x-ray / positive skin test

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

CLINICAL PRESENTATION

Pulmonary tuberculosisPulmonary tuberculosis

Primary complexAsymptomaticHEALS

REACTIVATIONPost-primary tuberculosis

Acute pulmonary diseaseSystemic spread

Aymptomatic /symptomatic

LATER DISEASERenal / CNS etc

MILIARY TUBERCULOSISPulmonarymeningitis

DIAGNOSIS

Pulmonary tuberculosisPulmonary tuberculosis

Primary complexAsymptomaticHEALS

REACTIVATIONPost-primary tuberculosis

Acute pulmonary diseaseSystemic spread

Aymptomatic /symptomatic

LATER DISEASERenal / CNS etc

MILIARY TUBERCULOSISPulmonarymeningitis

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1. Evidence of infectiona. Chest x-ray - hilar lymphadenopathy

calcification of primary focus/LNb. Delayed hypersensitivity response to purified protein

derivative (PPD) MANTOUX /HEAF TEST

2. Evidence of active diseasea. Sputum for AFB positive

3. Evidence of active diseasea. Indirect evidence of infection (Mantoux)

b. Direct evidence of infection PCR / culture

c. Histo-pathological evidence

DIAGNOSIS

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

TREATMENT

• Anti-tuberculous drugs– INAH– Rifampicin– Ethambutol– Pyrazinamide

• DOT • Multi-drug resistant tuberculosis

PREVENTION

• Incidence declined before availability of anti-tuberculous drugs

• Improved social conditions - housing /nutrition• Case detection & treatment• Contact tracing• Evidence of infection / disease• Treatment of infected / diseased contacts

ROLE OF IMMUNIZATIONBCG (bacillus Calmette Guerin)

ROLE OF IMMUNIZATIONBCG (bacillus Calmette Guerin)

Bronchiectasis• Bronchiectasis is a chronic lung disease that is

characterized by permanent dilatation of the bronchi and fibrosis of the lung.

• It is defined as the pathological, irreversible dilation of bronchi , due to destruction of the bronchilal walls and their supporting tissues

• It is highly associated with chronic bacterial infection

• Often looked at, as the final common pathway of many injurious processes

Cont.

• Bronchiectasis , although uncommon,bears the potential to cause severe illness , including repeated respiratory infections , disabling cough, purulent sputum, shortness of breath,

• chest pain and occasionally hemoptysis, with significant impact on the health and the quality of life of the affected person

Causes of 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• Affects lower lobes preferentially• Chronic recurring infection sometimes leads to

finger clubbing

NCI

Clubbing is not a feature of COPD alone. If clubbing is found, search for lung cancer.

Cont.

• Repeated or prolonged episodes of pneumonitis, • Inhaled foreign objects or • Neoplasms have been known to cause

bronchiectasis. • When the bronchiectatic process involves most or

all of the bronchial tree, whether in one or both lungs, it is believed to be genetic or developmental in origin

Types of Bronchiectasis

• Bronchiectasis means irreversible dilation and distortion of the bronchi and bronchioles.

• Pathologically, bronchiectasis can be divided into four types

Cylindrical Bronchiectasis

• The first type, cylindrical bronchiectasis, is characterized by uniform dilatation of bronchi, that extends into the lung periphery, without tapering.

• Tubular bronchiectasis is simply the absence of normal bronchial tapering and is usually a manifestation of severe chronic bronchitis rather than of true bronchial wall destruction

Bronciectasis

Cylindrical Forma

uniform dilatation of bronchi, that extends into the lung periphery, without tapering.

Varicose Bronchiectasis

• The second type is called varicose bronchiectasis and is characterized by irregular and beaded outline of bronchi, with alternating areas of constriction and dilatation.

Saccular Bronchiectasis.

• The third type is called cystic or saccular bronchiectasis and is the most severe form of the disease.

• The bronchi dilate, forming large cysts, which are usually filled with air and fluid.

• Saccular bronchiectasis is the classic advanced form characterized by irregular dilatations and narrowing.

• The term cystic is used when the dilatations are especially large and numerous

Bronchiectasis

Saccular Form

The bronchi dilate, forming large cysts, which are usually filled with air and fluid.

Follicular Bronchiectasis

• The fourth type of bronchiectasis is called follicular and is characterized by extensive lymphoid nodules within the bronchial walls.

• It usually occurs following childhood infections

Complications of bronchiectasis

• Pneumonia

• Abscess

• Septicaemia

• Empyema

• “Metastatic” abscess

• Amyloidosis

Bronchiectasis with chronic suppuration

Bronchiectasis

Bronchiectasis distal to an obstructing tumour