Respiratory Infections Dr Mulazim Hussain Bukhari.
-
Upload
allan-russell -
Category
Documents
-
view
220 -
download
3
Transcript of Respiratory Infections Dr Mulazim Hussain Bukhari.
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
11
23
33
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