Week 5 - Asthma, Acute Lung Injury, Restrictive Disorders & Pneumoconiosis Flashcards
What is asthma?
- Chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness and cough particularly at night and/or early in the morning.
- Increased sensitivity/irritability with excess mucous in airways, no scarring.
- Mucous threads and spirals in sputum.
- Many cells play a role in the inflammatory response, in particular eosinophils, mast cells, macrophages, lymphocytes, neutrophils and epithelial cells.
- Eosinophilia (all cases of asthma characterised by hypereosinophilia - excess eosinophils in blood, sputum and bronchial epithelium microscopy).
Identify the hallmarks of asthma.
- Intermittent and reversible airway obstruction (bronchospasm. COPD irreversible - permanent due to scarring).
- Chronic bronchial inflammation.
- Bronchial smooth muscle cell hypertrophy and hyper-reactivity.
- Increased mucus secretion.
What are the 2 main types of asthma?
- Asthma may be categorised into atopic (evidence of allergen sensitisation, often in a patient with a history of allergic rhinitis, eczema) and non-atopic.
- In either type, episodes of bronchospasm can be triggered by diverse mechanisms such as respiratory infections (especially viral), environmental exposure to irritants (e.g. smoke, fumes), cold air, stress and exercise.
- Atopic - due to allergen, early age (starts by childhood), family history of other disorders e.g. eczema, skin hypersensitivity. Commonest.
- Non-atopic - no allergen identified, hypersensitivity testing negative, starts as an adult.
What are the other types of asthma?
• Other types:
- Drug induced - typically aspirin induced, increased cyclooxygenase, genetic condition (some people genetically hypersensitive to aspirin with excess secretion of cyclooxygenase - not common).
- Occupational - paints, fumes, toxic gases - repeated exposure (may have a history of asthma but it develops after continuous exposure).
- Allergic bronchopulmonary aspergillosis - patients with allergic bronchitis - may have hypersensitivity to aspergillosis (fungus) - may not be identified or grown in body/culture but show hypersensitivity to fungus.
- There is also emerging evidence for differing patterns of inflammation - eosinophilic, neutrophilic, mixed inflammatory and pauci-granulocytic.
- Different asthma types based on mucus examination (not commonly discussed) - each type has different chemical presentation and pathogenesis - increased eosinophils, increased neutrophils, mixed (both) or no WBCs.
• Asthma may also be classified according to the agents or events that trigger bronchoconstriction - asthma triggers (in all types) - infections, smoke, fumes, stress, exercise.
Explain the pathogenesis of asthma.
Atopic or extrinsic (allergen induced) :
• Genetic - atopy/type 1 hypersensitivity (genetic hypersensitivity reaction, IgE mediated).
Non-atopic or intrinsic (no allergen identified):
• Viral infections/chemical pollution etc. (not associated with atopy reactions/family history).
• Common pathogenesis in both (due to genetic atopy or viral/pollution):
- TH2 lymphocytes.
- IL4, IL5, IgE.
- Eosinophils.
- Mast cells.
- Inflammation
• Atopic: antigen → dendritic cell (APC) → TH2 cell → IL-4, IL-5, IL-13 → B lymphocyte → IgE → mast cell and eosinophils → histamine, EBP.
- IL-4 stimulates IgE production.
- IL-5 activates eosinophils.
- IL-13 stimulates mucus production and also promotes IgE production by B cells.
• Non-atopic: external agents (irritants, viral infection) → mast cell and eosinophils → histamine, EBP. (Non-atopic doesn’t need T cells → directly stimulate mast cells and eosinophils. No family history).
• Hygiene hypothesis - eradication of infections may alter immune homeostasis and promote allergic and other harmful immune responses. Due to excess hygiene.
Identify the clinical features of asthma.
- Episodic bronchospasm.
- Cough.
- Wheezing.
- Hypoxia.
- Reversible - only smooth muscle spasm and inflammation, no scarring unlike COPD. Bronchodilator helps improve the patient.
- Severe dyspnoea - difficulty lies in expiration. The patient labours to get air into the lungs and then cannot get it out, so that there is progressive hyperinflation of the lungs with air trapped distal to the bronchi, which are constricted and filled with mucus and debris.
- Attacks usually last from one to several hours and subside either spontaneously or with therapy, usually bronchodilators and corticosteroids.
Compare a normal bronchus with that in a patient with asthma.
- Accumulation of mucus in the bronchial lumen resulting from an increase in the number of mucus-secreting goblet cells in the mucosa and hypertrophy of submucosal glands.
- Intense chronic inflammation due to the recruitment of eosinophils, macrophages and other inflammatory cells.
- Basement membrane underlying the mucosal epithelium is thickened and smooth muscle cells exhibit hypertrophy and hyperplasia.
Outline the immediate and late phase of asthma.
- Immediate: on re-exposure to antigen, the immediate reaction is triggered by antigen-induced cross-linking of IgE bound to IgE receptors on mast cells in the airways. These cells release preformed mediators. Collectively, either directly or through neuronal reflexes, the mediators induce bronchospasm, increase vascular permeability and mucus production and recruit additional mediator-releasing cells from the blood.
- Late: the arrival of recruited leukocytes (neutrophils, eosinophils, basophils, lymphocytes and monocytes) signals the initiation of the last phase of asthma and a fresh round of mediator release from leukocytes, endothelium and epithelial cells. Factors, particularly from eosinophils (e.g. major basic protein, eosinophil cationic protein) also cause damage to the epithelium, IgE.
Describe the morphology of asthma.
Gross:
• Inflammed thick bronchi.
• Mucous plugs.
Microscopy: • Excess mucous. • Goblet cell hyperplasia. • Inflammation with plenty of eosinophils. • Smooth muscle hyperplasia. • Mucous gland hyperplasia.
Note: microscopy similar to chronic brochitis except there are plenty of eosinophils in asthma (only neutrophils in CB).
Describe the sputum microscopy in asthma.
- Charcot-Leyeden crystals (eosinophil protein) - eosinophil basic protein which is apart of eosinophil granules → form big crystals in sputum which can be seen under microscopy.
- Curschmann spirals (mucous + epithelium) - long threads of mucus with epithelium inside.
Outline status asthmaticus.
- Persisting severe exacerbation of asthmatic attack, no response to therapy (usually asthmatic attacks are short in duration, respond to therapy).
- Severe hypoxia, hypercapnia (CO2 retention) and acidosis. May be fatal.
- Hyperinflation of lungs (lungs hyperinflated as bronchi are constricted, alveoli retain the air - cannot push it out).
- Triggered by excess mucus plugging the major bronchi. Thick mucus totally blocking → does not respond to therapy.
Asthma summary.
- Reversible bronchoconstriction - due to external stimuli.
- Atopic asthma - TH2 and IgE (IgE mediated type 1 hypersensitivity).
- Non-atopic asthma - viral infections and pollutants (also remember drug induced/exercise induced asthma).
- Eosinophils are key inflammatory cells (difference from COPD). Eosinophil products such as major basic proteins are responsible for airway damage.
- Airway inflammation, hypertrophy of bronchial mucous glands and smooth muscle.
- Airway remodelling adds an irreversible component to obstructive disease (sub-basment membrane thickening and hypertrophy of bronchial glands and smooth muscle adds an irreversible component to obstructive disease. It is reversible but gradually over many years of asthma → reversibility reduces because of mucus glands and smooth muscle hypertrophy. Over the years, reversibility becomes less).
Outline restrictive lung disorders.
- AKA infiltrative lung disorders.
- Reduced expansion of lung due to diffuse fibrosis (stiff lung - lung becomes hard instead of being elastic normally).
- FEV, FVC both low (lung cannot expand) so FEV1:FVC ratio ~normal (slightly abnormal but not significant).
- TLC decreased.
- Either because chest wall becomes stiff or lung tissue itself becomes scarred (fibrosis) - chest wall/lungs cannot expand → restrictive.
Identify the types of restrictive lung disorders.
A. Intrinsic lung disorders (common, seen clinically):
• Diffuse fibrosis, pneumoconiosis and sarcoidosis.
• Tuberculosis and other interstitial pneumonia.
B. Extrinsic disorders (chest wall):
• Scoliosis, kyphosis, gross obesity, Pickwick syndrome.
• Pleurisy, rib fracture etc.
C. Neuromuscular disorders:
• Paralysis of the diaphragm, myasthenia gravis, poliomyelitis.
• Generalised weakness - malnutrition.
Describe the pathogenesis of restrictive lung disorders.
- Particles of 1-5ų* (> harmless) - usually caused by particles 1-5ų - smaller are easily removed (not much damage) and larger do not get deposited in terminal alveoli.
- Common particles - carbon, silica* (most common) and asbestos*
- Lung injury (inhaled agents, dusts, blood-borne toxins, unknown antigens).
- Stimulation of lymphocytes and macrophages.
- Produce interstitial inflammation and fibrosis.
- Results in stiff lung (restrictive).
- Tobacco and TB* - patients with restrictive disorders who also smoke → more damage. Increased damage to the lung stimulates reactivation of TB - susceptibility to TB increases.
• Lung injury → activates macrophages → oxidants/proteases → damage epithelium (type 1 pneumocytes) → type 2 pneumocytes increase in response → secrete fibroblast growth factors → fibrosis → leads to damaged alveoli with excess fibrosis.
See diagram*
