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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 preexisting 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
M bovis
M leprae
M kansasii
M marinum
M scrofulaceum
M avium
intracellulare
M ulcerans
M fortuitum
M chelonae
No
Human
No
Human, cattle
No
Humn
Rarely
Water, cattle
Rarely
Fish, water
Possibly
Soil, water
Possibly
Soil, water, birds
No
Unknown
Yes
Soil, water, animals
Yes
Soil, water, animals
CLASSIFICATION OF MYCOBACTERIA
ASSOCIATED WITH HUMAN DISEASE
Mycobacterium
Clinical significance
Pigmentation
Growth
M Tuberculosis , M bovis
M ulcerans
Strict pathogens
No
No
M leprae
Strict pathogen
-
-
M marinum , kansasii
Runyon Group 2
Usually pathogenic
Photochromogens
slow
M scrofulaceum
Rarely pathogenic
Scotochromogens slow
Unclassified
Runyon Group 1
Runyon Group 3
M avium intracellulare
Pathogenic in
No
immunocompromised
slow
Rarely pathogenic
‘rapid’
Runyon Group 4
M fortuitum, M chelonae
No
MYCOBACTERIUM
• Aerobic bacilli
–non spore forming
non motile
• Cell wall
–rich in lipids
• Acid-fast bacilli
• Very slow growing
Mycobacterium tuberculosis
•
•
•
•
•
•
•
•
Causes tuberculosis
Classic human disease
Pathogenesis
Transmission
Clinical presentations
Diagnosis
Treatment
Prevention
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 TUBERCULOSIS
Chest x-ray / positive skin test
Mycobacterial virulence
• Related to ability to resist phagocytosis.
• Surface LAM antigen stimulates host
tumour necrosis factor (TNF) a 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 nonspecific inflammation
with developing
granulomas in nodes
In secondary there are
primed T cells which
stimulate a localised
granulomatous response
CLINICAL PRESENTATION
Pulmonary tuberculosis
HEALS
Primary complex
Asymptomatic
Acute pulmonary disease
Systemic spread
Aymptomatic /symptomatic
LATER DISEASE
Renal / CNS etc
REACTIVATION
Post-primary
tuberculosis
MILIARY TUBERCULOSIS
Pulmonary
meningitis
DIAGNOSIS
Pulmonary tuberculosis
1
HEALS
1 Primary complex
Asymptomatic
2
3
Acute pulmonary disease
Systemic spread
Aymptomatic /symptomatic
LATER DISEASE
3 Renal / CNS etc
REACTIVATION
Post-primary
tuberculosis
MILIARY TUBERCULOSIS
Pulmonary
3
meningitis
DIAGNOSIS
1. Evidence of infection
a. Chest x-ray - hilar lymphadenopathy
calcification of primary focus/LN
b. Delayed hypersensitivity response to purified protein
derivative (PPD) MANTOUX /HEAF TEST
2. Evidence of active disease
a. Sputum for AFB
positive
3. Evidence of active disease
a. Indirect evidence of infection
b. Direct evidence of infection
c. Histo-pathological evidence
(Mantoux)
PCR / culture
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 antituberculous drugs
• Improved social conditions
- housing /nutrition
• Case detection & treatment
• Contact tracing
• Evidence of infection / disease
• Treatment of infected / diseased contacts
ROLE OF IMMUNIZATION
BCG (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