Airway & Airway Diseases Flashcards
What is an obstructive disorder? What are some example sof obstructive lung conditions?
Obstructive disorder - when there is obstruction of air flow into the airway, resulting in less inflow of gas into the alveolar space thus resulting in a reduction in gas exchange taking place
Examples include:
1. Asthma
2. Chronic Obstructive Pulmonary Disease (COPD)
3. Causing obstructive picture
a) Bronchiectasis
b) Cystic Fibrosis
What are four variables that influence airway internal diameter?
- Increased mucus production - quanitity and thickness
- Anatomical features
- Autonomic and Non-Adrenergic/Non Cholinergic (NANC) systems - constriction/dilation
- Inflammation
Outline how the autonomic and NANC nervous systems influencing constriction and dilation of airways.
- Parasympathetic activation leading to acetyl-choline release - acts on M3 muscarinic receptors - drives constriction
- Beta agonists in circulation bind to B2 adrenergic receptors - drives dilation
- Non-autonomic inputs (not really used as drug targets)- VIP and NO drive bronchodilation / Substance P and neurokinis drive bronchoconstriction
What are the main characterisitics associated with Asthma? What does the lung pathology look like?
Asthma – atopy and allergy exposure - associated with inflammatory exacerbations driven mainly by eosinophils
Asthma is reversible and biphasic (early and late response during an exacerbation)
Pathology
1. Smooth muscle thickening
2. Bronchoconstriction
3. Basement membrane thickening
4. Mucous plugging (more acute disease presentation)
What are the main characterisitics associated with COPD? What does the lung pathology look like?
COPD - emphysema (breakdown of alveoli) and chronic bronchitis (inflammation - neutrophil mediated)
Several environmental triggers - major driver is smoking
Pathology
1. Increased mucous production
2. Destruction of alveoli and connective tissue leading to collapse of conducting airways
What is cystic fibrosis? What are the associated characteristics?
Cystic fibrosis - genetic condition that arises from a mutations in both CFTR genes - codes for a pump that regulates water and Cl- flow in and out of a cell - dysfunction creates sticky thick mucus
Characteristics
- Walls become thickened
- Mucus builds up
- Dilation - bronchiectasis (abnormal dilation)
What are the three ways that lung obstruction is measured?
- Peak flow
- Spirometry
- Lung Volumes and flow
What impact does a change in vessel radius have on levels of air resistance? What implications does this have for airflow through a tube?
Small change in radius has a significant impact on airflow resistance, and thus airflow.
Outline how peak flow is used to measure lung obstruction.
Peak expiratory flow rate (PEFR) - Measures maximum speed of expiration - How fast is the air going out, indicates how fast air is going in
Crude measurement of conducting airway flow
Can aid in Asthma diagnosis/management
Excellent bedside and patient- based tool
What are FEV1 and FVC?
FEV1 - Forced expiratory volume in 1 second
FVC - Forced vital capacity – total of volume of air that can be expired
What is spirometry?
Spirometry - pulmonary function test
Two main measures
1. Forced expired volume in 1 second (FEV1)
2. Forced vital capacity (FVC) (measure ~ 6 seconds of expiration)
We compare to predicted values based on age, sex and height - Predicted values are based on population of healthy individuals
What changes are seen in FEV1 and FVC in mild and moderate lung obstruction?
Mild to moderate airway obstruction – due to asthma, COPD, CF, etc. - reduction in FEV1is seen but eventually expiration volume will catch up and reach normal FVC
Severe obstruction – significantly reduced FEV1 and FVC – reduction in lung volume - Sign of severe disease
What can the ratio of FEV1 to FVC tell us?
The ratio of FEV1 to FVC helps us to differentiate between obstruction (airflow problem) and restriction (lung volume problem)
If less than 0.7 - suggests am obstructive airways pathology - Loss of more FEV1 than FVC - mainly a reduction in airflow not volume
If more than 0.7 - suggests an restrictive airway pathology - loss of FVC more than FEV1 - mainly a lung volume problem
Note in cases of severe obstruction/disease - there is a significant loss in both FEV1 and FVC
How is spirometry used as a diagnostic tool for asthma?
Revesibility of Spirometry
Couple the use of a bronchodilator with spirometry to see if levels can be reversed/improved - positive test = asthma
Look for a 12% change in spirometry – but usually analyze it in the context of the patients previous measurements
Can also use bronchial challenge agents (histamine) to induce bronchospasm and obstructive spirometry
Note this is possible for asthma as it is a reversible condition unlike COPD
Are our airways normally colonised by bacteria?
Yes
Upper airway is not sterile, whereas the lower airway has low levels of microorganisms
It is thought that some microorganisms constantly move down to the lower airway from the upper airways – when we have pathogenic pathogen and/or susceptible to infection moving down we are more likely to suffer from a lower respiratory tract infection
What are four factors that protect us from respiratory infections?
- Colonisation - Commensal flora and colonisation resistance
- Swallowing - Normal swallowing reflex, epiglottis
- Lung anatomy - Neurological and anatomical factors, Mucus and Ciliated epithelium, (mucociliary escalator), and Cough reflex
- Immunity (innate and adaptive)
- Soluble factors; IgA, defensins, collectins, lysozyme
- Alveolar macrophages
- B- and T-cells
When these factors are not operating adequetly, they make people susceptible to respiratory tract infections
What is the most common cause of an upper respiratory tract infection?
Most common cause – viruses – common cold– Main causal agents are the rhinoviruses, influenza A (known to cause systemic symptoms) and recently SARS-CoV2
Usually transient
May lead to complications - sinusitis, pharyngitis, otitis media, bronchitis, rarely pneumonia
Note
Respiratory Syncytial viruses - known to causes illness in children and severe illness in nursing home residents
What is pharyngitis? What are the typical causes?
Pharyngitis = sore throat
Typically viral
But could also be…
1. beta-hemolytic streptococci
2. Glandular fever Epstein Barr virus
3. Acute HIV infection
What is sinusitis? What are the most common causes?
Sinusitis - inflammation of your sinuses
- Usually viral (as per causes URI)
- Bacterial also possible - more likely if ther is unilateral pain and purulent discharge, with a fever of more than >10d or presenting acutely or with complications
- Bacteria that are most commonly associated
a) Streptococcus pneumoniae (40%),
b) Haemophilus influenzae (30-35%)
Complications - brain abscess, sinus vein thrombosis, orbital cellulitis
What is acute epiglottitis? WHat is it associated with?
Inflammation of the epiglottis
Typically associated with children - 2-4 years old who presented with fever, dysphagia, drooling and stridor
Caused by Haemophilus infuenzae type B (Hib) - rare now due to vaccinations
But can also present in immunocompromised adults
Epiglottis is swollen and extends into the airway – medical emergency and requires intubation
What are the symptoms associated with Bordatella pertussis infection?
Adults chronic cough, paroxysms of coughing and 50% post tussive (coughing) vomitting but fairly specific for pertussis infection.
Basically vomitting post coughing - think pertussis
Acellular vaccine does not give lifelong immunity – require boosting
What is croup? What are it’s associated characteristics?
Acute laryngo-treacheobronchitis - infection of the larynx, trachea and bronchi
Disease of children – 3 months to 3 years
Associated with a barking cough, hoarse voice, difficulty breathing and cold-like symptoms
Mainly due to Parainfluenza viruses, ( also RSV, IAV and other respiratory viruses)
What is bronchiolitis? What are it’s associated characteristics/symptoms?
Bronchiolitis - Infections due to respiratory syncytial virus (RSV) (80%) (rarely other viruses)
Inflammation of bronchioles and mucus production cause airway obstruction
A common chest infection that affects babies and children under 2.
Features - dry cough, increasing breathlessness, wheezing, inspiratory crackles and feedin difficulty
What is bronchitis? What are it’s symptoms, investigations and treatment?
Bronchitis is inflammation of the bronchi (large and medium-sized airways) in the lungs that causes coughing.
Aetiology: Frequently viral (May be bacterial)
May cause acute exacerbations of COPD or asthma with increased wheeze
Symptoms: cough (productive or non-productive), shortness of breath, often a wheeze, fever but no systemic signs of infection,
Investigations: Arterial blood gas/oximetry - for those with chronic lung disease and X-ray to rule out pneumonia
Treatment:
a) Usually none especially if viral, sometimes antimicrobials
b) Manage exacerbation of COPD/asthma with steroids and increased inhalers
What is bronchiectasis? What are some potential causes?
Bronchiectasis describes a permanent dilatation of the airways secondary to chronic infection or inflammation.
There are a wide variety of causes are listed below:
a) Congenital; Cystic fibrosis (most common cause in the pediatric population), ciliary dysfunction, hypogammaglobulinemia
b) Post-infectious; TB, suppurative pneumonia, measles , whooping cough
c) Other; Foreign body
What are the symptoms and observations upon examination of bronchiectasis?
Symptoms
1. Chronic cough
2. Copius sputum
3. Recurrent pneumonia
4. Weight loss
On examination (O/N):
1. Clubbing
2. Coarse ‘wet’ crackles
Can be complicated by haemoptysis
What is pneumonia?
Pneumonia is the inflammation of the parenchyma of the lung.
In pneumonia, the air sacs (i.e. alveoli) become filled with microorganisms and inflammatory cells leading to poor lung function with features of cough, fever, and shortness of breath.
What are the top five most common organisms that cause pneumonia?
- Streptococcus pneumoniae (40%) – most common
- Mycoplasma pneumoniae (~10% peaks in epidemic seasons)
- Chlamydophila pneumoniae (~10%)
- Legionella pneumophila and other spp (<5%)
- Haemophilus influenzae (<5%)
What people are at risk of pneumonia infection?
- Infants and the elderly
- COPD and certain other chronic lung diseases
- Immunocompromised
- Nursing home residents
- Impaired swallow (neurological conditions etc.)
- Diabetes
- Congestive heart disease
- Alcoholics and drug users
How can pneumonia be categorised based on the source of infection?
- Community Acquired Pneumonia (CAP) - majority of patients develop pneumonia within the community, i.e. outside of hospital
- Hospital-acquired pneumonia - Patients who develop pneumonia within hospitals (occuring 48 hours or more after admission) are said to have hospital-acquired pneumonia
The distinction is important as the causative organisms vary and hence first-line antibiotic guidelines are also different.
What are some three key decisions that need to be made with a pneumonia diagnosis?
- Does the patient need antimicrobials?
- How sick is the patient?Should they be managed in hospital?
- Is there an alternative diagnosis;
- Heart failure
- Pulmonary embolus
- Cancer
- TB
- Interstitial lung disease
What treatment should be used for pneumonia?
Prompt but appropriate initiation of antimicrobials; ideally establish diagnosis and start treatment ≤4h - Use narrowest spectrum to stop spread of resistance
Mild severity pneumonia in community
Oral antimicrobial e.g amoxicillin for short duration
Severe
Intravenous antimicrobial often in combinations e.g co-amoxiclav + oral clarithromycin
Duration 7d mild-moderate
7-10d severe
14-21d S. aureus, Gram-negative bacteria, and Legionella sp (associated with water cooling towers/showers)
What are the signs and symptoms associated with pneumonia?
Symptoms
1. cough
2. sputum
3. dyspnoea
4. chest pain: may be pleuritic
5. fever
Signs
1. Signs of systemic inflammatory response - fever and tachycardia
2. Reduced oxygen saturations
3. Auscultation: reduced breath sounds and bronchial breathing
What is tuberculosis? Suspectible groups?
Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis that most commonly affects the lungs.
Specific epidemiological groups
1. Exposed to a case
2. Born in country of high incidence
3. Homeless, alcoholic, HIV infection, anti-TNF treatment
What are the clinical features and radiological appearances for TB?
Clinical features;
1. Cough, hemoptysis (more common), shortness of breath
2. Weight loss, fever and night sweats
3. Swollen lymph nodes or other extrapulmonary features
Multiple radiological appearances:
1. Upper lobe disease with cavities - Upper lobe think TB!
2. Pleural disease
3. Multiple tiny nodules (‘miliary’),
4. Lymphadenopathy in chest
Failure to resolve with routine antibiotics also suggestive
What is needed for a TB diagnosis and how is it treated?
TB diagnosis - Culture in special media e.g. Mycobacteria growth indicator tube (MGIT) and use of a special stain (Special stain Ziehl-Neelsen)
Also possible to use PCR
Treatment
What is needed for a TB diagnosis and how is it treated?
TB diagnosis - Culture in special media e.g. Mycobacteria growth indicator tube (MGIT) and use of a special stain (Special stain Ziehl-Neelsen)
Also possible to use PCR
Treatment - prolonged (6 months or longer)
Use of multiple drugs to avoid resistance
1. Isoniazid
2. Rifampicin
3. Pyrazinamide
4. Ethambutol
Three examples of conditions that predispose people to airway infection?
- Immunosuppression - disease or drug induced
- Macrophage dysfunction
- Pulmonary oedema
What is bronchitis? What are it’s associated features?
Bronchitis - Inflammation of bronchi
May also involve larynx and trachea - laryngotracheobronchitis
Causes:
Often viral
May be bacterial e.g. H influenzae - common in COPD
Acute exacerbations of ‘chronic bronchitis’ are common
What is bronchiolitis? What are it’s associated features?
Bronchiolitis - Inflammation of bronchioles
Primary bronchiolitis
a) Usually in children
b) Respiratory syncytial virus (RSV)
c) Tachypnoea and dyspnoea
Rare in adults – normally would result in pneumonia
Also commonly seen as a feature of chronic bronchitis
Rare types
a) Follicular bronchiolitis
b) Bronchiolitis obliterans
What is a localised airway obstruction?
Localised Airway obstruction - is a localised blockage of respiration in the airway that hinders the free flow of air.
Can be caused by:
1. Lesion outside the wall e.g. large lymph node
2. Lesion in the wall e.g. tumour
3. Lesion in the lumen e.g. foreign body
Causes distal collapse or over-inflation (one-way valve)
Can give a normal pulmonary function tests
Localized airway obstruction normally presents with pneumonia
Obstruction lesion, if present for long enough, can result in Bronchiectasis (destruction of airway)
What are diffuse obstructive airways diseases? What are the characteristics? What are some examples?
Obstructive Airways Disease can be reversible and intermittent OR Irreversible and persistent
Centred on bronchi and bronchioles - many different airways can be involved, hence diffuse
Pulmonary function tests ‘obstructive’
a) Reduced vital capacity (VC)
b) Reduced FEV1 / FVC ratio
c) Reduced peak expiratory flow rate
Examples
1. Chronic bronchitis
2. Emphysema
3. Asthma
4. Bronchiectasis - not included in the UK
5. COPD
How do you define chronic bronchitis? What is its aetiology? What are some clinical features?
Clinical definition - Cough and sputum for 3 months in 2 consecutive years
Aetiology - pollution, smoking (mainly)
Clinical picture:
1. Middle-aged heavy smokers
2. Recurrent low-grade bronchial infections (exacerbations) - H. influenzae, S. pneumoniae, viruses
3. Airway obstruction may be partially reversible
How does chronic bronchitis disease progress?
Progression of disease
1. Hypercapnia - elevated CO2
2. Hypoxia - Low O2
3. Pulmonary hypertension - right side of the heart has to work extra hard
4. ‘Cor pulmonale’ - right ventricular failure
Later stages associated with increased fluid retention.
What does the pathology of chronic bronchitis look like?
Pathology
1. Respiratory bronchiolitis
2. Centrilobar emphysema
3. Mucus hypersecretion
4. Chronic bronchial inflammation - Squamous metaplasia, increased risk of malignancy
‘Blue Bloater’
What is emphysema?
Anatomical definition - Irreversible dilatation of acinar spaces (alveolar space) with destruction of walls (loss of elasticity)
Definition extends to respiratory bronchioles
Associated with loss of surface area for gas exchange
What are the four different types of emphysema? What are they associated with?
- Centrilobular Emphysema - associated with smoking, coal workers, upper lobes, respiratory bronchiolitis often present
- Panlobular Emphysema - usually lower lobes, lungs overdistended, associated with alpha-1-antitrypsin deficiency, accelerated in smokers with this deficiency
- Paraseptal - Distension adjacent to pleural surfaces and may be associated with scarring
- Irregular - Associated with scarring and overlap with paraseptal emphysema
Others -
- Bullous: distended areas >10mm - pop leading to pneuomothorax
- Interstitial
What are the clinical features of emphysema?
Clinical features
1. Hyperventilation
2. Normal pO2, pCO2
3. Weight loss
4. Right ventricular failure
Often co-existing chronic bronchitis, in which case clinical features are mixed
‘Pink puffer’
What is Chronic Obstructive Pulmonary disease (COPD)?
COPD - A combination of the features of chronic bronchitis and emphysema - leads to symptoms associated with airway obstruction and loss of surface area for gas exchange.
Most patients exhibit a mixture of features
Typically assessed using pulmonary function tests - FEV1/FVC < 0.7 for diagnosis and % predicted FEV1 to assess severity
Presentation
1. Smoking, air pollution and alpha-1 antitrypsin deficiency
2. Breathless (dyspnoea) - upon exercise? upon rest?
3. Recurrent chest infections - exacerbations
4. Productive cough (due to mucus build-up)
5. Wheeze
How does COPD appear on X-rays?
Main abnormalities visible:
1. Flattening of the diaghragm
2. Translucent lung fields (blacker than normal)
How does the macroscopic appearance of the lung change in COPD?
The main abnormalities are:
1. Distended air spaces
2. More prominent in the lower lobe
3. The lung has a rather ‘flaccid’ appearance (rather than fibrotic)
What lung abnormality defines the emphysema component of COPD?
Acinar wall destruction
How is the diagnosis of COPD performed?
Diagnosis based on FEV1/FVC < 0.7 (airflow limitation)
Severity assessed by percent predicted post- bronchodilator FEV1
GOLD criteria (global initiative for chronic obstructive lung disease)
FEV1 ≥ 80 – mild
FEV1 50– 79 – moderate
FEV1 30 – 49 – severe
FEV1 < 30 – very severe
What are the microscope changes seen in COPD?
Outline how the destruction of alveolar walls, ultimately leads to pulmonary hypertension?
- Destruction of alveolar walls leads to loss of surface area for gas exchange
- Increased respiratory drive compensates for the drop in pO2
- pCO2 may be low due to the high respiratory rate
- In some cases, respiratory drive may fall, with tolerance of a low pO2 and elevation of pCO2 - adapts to lower pO2/ high pCO2
- Pulmonary vasoconstriction (due to hypoxia) and destruction of pulmonary vasculature lead to pulmonary hypertension
What is the eventual consequence of chronic pulmonary hypertension?
Right Ventricular Failure
Associated with…
1. Ankle swelling - odema
2. Hepatic congestion
a) Pain
b) Abnormal liver function tests
c) ‘Nutmeg’ liver
What is asthma? What are five different aetiological causes?
Definition - Reversible wheezy dyspnoea
Related to the irritability of the bronchial tree – asthma is an exacerbation of the normal
Five categories
1. Atopic – related to allergy
2. Non-atopic
3. Aspirin-induced
4. Occupational – wood workers lung
5. Allergic bronchopulmonary aspergillosis (ABPA) – fungus – difficult to treat without making the diagnosis
What is atopic asthma?
Atopic Asthma - Associated with allergy
Triggered by a variety of factors: Dust, pollen, house dust mite, etc.
Often associated with eczema and hay fever
Bronchoconstriction mediated by a type I hypersensitivity reaction
What pathological process take place in atopic asthma?
Hypersensitivity reaction leads to:
1. Bronchial obstruction with distal overinflation or collapse
2. Mucus plugging of bronchi
3. Bronchial inflammation
4. Mucous gland hypertrophy
5. Bronchial wall smooth muscle hypertrophy
6. Thickening of bronchial basement membranes
Outline the mechanism that drives the asthmatic reaction?
- Antigen enters - binds to IgE
- IgE binds to mast cells - priming them
- Upon secondary exposure, the antigen binds to the anitbody on the mast cell - driving degranulation
- Release of mediators - Histmaine, SRS-A, ECF-A and pAF
- Results in bronchoconstriction, mucus hypersecretion and oedema
What are non-atopic asthma, aspirin induced asthma, occupational asthma and allergic bronchopulmonary aspergillosis? What are they associated with?
- Non-atopic asthma - asthma that is not related to an allergen
Associated with…
1. Recurrent infections
2. Not immunologically mediated
3. Skin testing negative
- Aspirin-induced Asthma - Associated with recurrent rhinitis, nasal polyps and urticaria (raised itchy rashes)- mechanism unclear
- Occupational asthma - hypersensitivity related to allergens inhaled at work
- Allergic Bronchopulmonary Aspergillosis - Specific allergic response to the spores of Aspergillus fumigatus - Mucus plugs common, associated with bronchiectasis - mixture of type 1 and 3 hypersensitivity
Is sudden death due to asthma possible?
Sudden death due to asthma is possible but rare – extreme mucus plugging and diffuse bronchoconstriction
What are different interventions/therapies that can be used to help the following features of asthma?
a) Mucus Plugging
b) Bronchoconstriction
c) Bronchial oedema and inflammatory cell infiltration
d) Smooth muscles hyperthrophy/basement membrane thickening
What is bronchiectasis?
Permanent dilatation of bronchi and bronchioles
Typically affects the 2nd to 8th order of segmental bronchi.
Due to a combination of obstruction and inflammation (usually infection).
May be localised or diffuse, depending on cause
What are the clinical features of bronchiectasis?
Clinical features
1. Chronic cough productive of copious sputum
2. Finger clubbing
Complications
- Spread of infection - Pneumonia, Empyema, Septicaemia, Meningitis, Metastatic abscesses e.g. brain
- Amyloidosis
- Respiratory failure
What are the mechanical and immunlogical defences present in the lungs?
Mechanical
1. Ciliated epithelium
2. Mucus
3. Cough
Immunological
1. IgA & antimicrobials in mucus
2. Resident alveolar macrophages & dendritic cells
3. Innate / adaptive immune responses
What does the lung parenchyma refer to?
The parts of the lungs involved in gas transfer including the alveoli, interstitium, blood vessels, bronchi and bronchioles.
What are 6 categories of pneumonia with regards to the source of infection? Why is it important to differentiate?
Categories
1. Community acquired
2. Hospital acquired
3. Health care associated
4. Aspiration associated
5. Immunocompromised host
6. Necrotising / abscess formation
Source of pneumonia is important as it will inform the whether and the type of antibiotic
Note pneumonia can be caused by a range of bacteria, viruses and fungi
What are the five cardinal signs of inflammation?
- Heat
- Redness
- Swelling
- Pain
- Loss of function
What are the two principal cellular responses to pneumonia?
Neutrophils
1. Chemotaxis - move to infection site
2. Degranulation
3. Reactive oxygen species
4. Extracellular traps
5. Phagocytosis
Macrophages
1. Cytokine & chemokines
2. Phagocytosis (bacteria & dead cells)
3. Antimicrobial peptides
4. Resolution
What are the common organisms that causes community and hospital acquired pneumonia?
Community acquired
1. Streptococcal pneumoniae
2. Haemophilus influenzae
3. Moraxella catarrhalis
4. Staphylococcus aureus
Hospital acquired / Health care associated
1. Gram-negative rods, Enterobacteriaceae, Pseudomonas
2. Staphylococcus aureus (usually methicillin-resistant)
What are the clinical presentations of pneumonia?
Clinical Presentation:
- Cough
- Sputum
- Pyrexia
- Pleuritic chest pain
- Haemoptysis
- Dyspnoea
- Hypoxia
What are two types of pneumonia based on symptomology
Bronchopneumonia
- Most common pattern
- Patchy & diffuse consolidated areas of acute suppurative inflammation
- Often elderly with risk factors - Cancer, heart failure, renal failure, stroke, COPD
Lobar pneumonia
- Rust coloured sputum
- S. pneumoniae
- Consolidation of a large portion of a lobe or of an entire lobe
What are the general and local risk factors associated with pneumonia?
General factors
1. Chronic diseases
2. Immunologic deficiency
3. Immunosuppressive agents
4. Leukopaenia - decreased number of leukocytes
Local factors
1. Loss or suppression of the cough reflex - drugs
2. Injury to the mucociliary apparatus - viruses, gases
3. Accumulation of secretions - CF, obstruction (tumour)
4. Impaired alveolar macrophages function – alcohol, tobacco
5. Pulmonary congestion and oedema
What are the local and systemic complications associated with pneumonia?
Local
1. Abscess formation - pus accumulation
2. Parapneumonic effusion - presence of exudate in pleural cavity
3. Empyema - pus accumulation in pleural cavity
Systemic
1. Sepsis
2. Acute respiratory distress syndrome - fluid build up in lungs
3. Multi-organ failure - Liver / renal /cardiac etc.
4. Cancer?
What is Acute respiratory distress syndrome (ARDS)?
Acute respiratory distress syndrome (ARDS) is caused by the increased permeability of alveolar capillaries leading to fluid accumulation in the alveoli, i.e. non-cardiogenic pulmonary oedema.
Final common pathway for many conditions
Clinical features are typically of an acute onset and severe:
1. Dyspnoea
2. Elevated respiratory rate
3. Bilateral lung crackles
4. Low oxygen saturations
Clinical diagnosis
1. Hypoxia (PaO2/FiO2 ≤ 300mmHg )
2. Non-cardiogenic pulmonary oedema
What are some direct and indirect causes of ARDS?
Causes
Direct – pneumonia, aspiration, hyperoxia, ventilation
Indirect – sepsis, trauma, pancreatitis, acute hepatic failure
What is TB? What are the two stages of infection? What are the predisposing factors for TB?
TB - Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis that most commonly affects the lungs.
Most common cause of granulomatous inflammation in the world
Stages
1. Primary TB - A non-immune host who is exposed to M. tuberculosis may develop a primary infection of the lungs - forms Gohn complex (Ghon focus and hilar lymph nodes) - normally cleared in healthy individuals.
2. Secodnary TB - reactivation of latent TB
Predisposing factors
1. Alcoholism
2. Diabetes mellitus
3. HIV / AIDS
4. Some ethnic groups
What are the treatments/preventions used for TB?
- Drugs – antibiotic therapy - isoniazid and rifampicin, pyrazinamide and ethambutol - e.g. all four for 2 months, followed by single antibiotic use for 3-6 months
- Prevention e.g. BCG vaccination
Outline the development/progression of primary tuberculosis?
First 3-4 weeks
1. M. TB infects and multiplies within alveolar macrophages (naive, unable to kill) - secrete IFN causing increased recruitment to form local granuloma (necrosis in the middle)
2. Bacterium resides in phagosomes &
carried to regional lymph nodes, from there to circulation
3-8 weeks
1. Onset of cellular immunity & delayed hypersensitivity
2. Activated lymphocytes further activate macrophages to kill
3. Primary infection arrested in most immunocompetent people
4. Few bacilli may survive dormant
Visible features - Hilar lymph node and Subpleural lesion - Known as Ghon complex
What happens if the immune system is unable to arrest the primary TB infection?
Infection not arrested - minority of people - Infants, children, immunocompromised
Two outcomes
-
Tuberculous bronchopneumonia
- Infection spreads via bronchi
- Results in diffuse bronchopneumonia
- Well developed granulomas do not form -
Miliary Tuberculosis
- Infection spreads via blood-stream
- Scattered TB across lung parenchyma
- Spread to multiple organs - lungs, liver, spleen, kidneys, meninges, brain
What is secondary tuberculosis?
Secondary Tuberculosis - Also termed ‘Post-primary’ TB
Reactivation of old, often subclinical infection
More damage due to hypersensitivity
1. Apical region of lung
2. Tubercules develop locally, enlarge and merge
3. Erode into bronchus and cavities develop
4. May progress to tuberculous bronchopneumonia
What is a granuloma?
A granuloma is an aggregation of macrophages that forms in response to chronic inflammation.
This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate
What is another important cause granulomatous pulmonary inflammation?
Sarcoidosis - autoimmune disease
What are key features of fibrotic interstial lung disease?
Fibrotic interstial lung disease
- Restrictive chronic lung disease
- Symptoms - Dyspnoea, (cough), tachypnoea, crepitations, cyanosis (late stage)
- Pulmonary function tests - Reduced transfer factor and total lung capacity - reduced gas transfer and capacity
- Honeycomb/Ground glass changes in lower zones on x-ray - BIG YES to fibrosis
Association with righ side heart failure - oedema
What are the three different type of fibrotic lung diease?
- Idiopathic pulmonary fibrosis - high level of mortality when compared to other types, pathogenesis is unknown (genetic causes, fibroblast changes and immune cell involvement), lung surrounded by fibrosis tissue = restriction
- Autoimmune - hypersensitivity pneumonitis - in resposne to foreign antigens
- External agent - e.g. asbestos (occupational lung disease) - pleural plaques, pulmonary fibrosis, different cancers - other triggers Silica, coal dust, berrylium
Summary of parenchymal lung disease.
Acute inflammation
1. Pneumonia - Neutrophils & macrophages
2. ARDS & COVID
Granulomatous inflammation
- Tuberculosis
- Host pathogen interactions
Fibrosing lung diseases
- Defective repair mechanisms
- Failure of clearance
