Week 2- Obstructive Airway Diseases (asthma And COPD) Flashcards
Define asthma
Asthma is defined as recurrent and reversible airways obstruction characterised by wheeze, SOB and nocturnal cough. Severe attack’s cause hypoxaemia and are life threatening.
What is the aetiology of asthma?
Genetic factors Environmental factors Acute triggers- allergens
Give examples of the factors involved in the aetiology of asthma
Genetics Acute triggers: dust/ mould/pollen/pet hair Environmental factors: Cold air Exercise Emotion Drugs Viral infections Atmospheric pollution Occupational sensitisers- wood/latex/dust Irritant vapours- cigarette fumes/ perfume
What are the two types of asthma? Outline their differences
Extrinsic/ atopic: Typical onset childhood
Associated with atopy- genetic predisposition to amount an exaggerated inappropriate immune response to an allergen, associated with hay fever and eczema.
Has both sensitisation and effector phases
Intrinsic/ non atopic:
Typical onset middle age
Often after an upper respiratory infection
No personal or family history of asthma or atopy
Give three things asthma is characterised by
- Reversible airways obstruction
- Bronchial hyper responsiveness
- Airways inflammation
Describe the histological changes seen in an asthmatic bronchus
- Mucus plug formation formed by an increase in the number of goblet cells and submucosal gland hypertrophy.
- Loss of and damage to the respiratory epithelium, exposure of nerve fibres
- Basement Membrane thickening
- Bronchial smooth muscle hypertrophy and hyperplasia
- Chronic inflammation with infiltration of macrophages/ eosinophils/ neutrophils/ mast cells/ Th2 cells in the lamina propria
Describe the early phase of asthma development
- Exposure to an allergen
- Presentation of the allergen by an antigen presenting cell/APC
- APC activates Th2 cells which start to produce inflammatory cytokines (IL3/5)
- Inflammatory cytokines attracts other inflammatory cells by chemotaxis, especially eosinophils which are stimulated to activate/ differentiate and start releasing these granule contents.
- Eosinophils release leukotrienes- potent bronchoconstrictors and lipid signalling molecule
- Eosinophils release toxic granule proteins which damage respiratory epithelium and expose nerve fibres leading to airways hyperresponsiveness.
- Inflammatory cytokine release from Th2 cell stimulates B plasma cells to make and release IgE.
- Cytokines from Th2 cell also stimulate mast cells to express IgE receptors on their surface
- Next exposure to allergen causes IgE crosslinking and degranulation of mast cells
- Mast cells release leukotrienes and histamine- potent bronchoconstrictors.
What happens in atopic asthma that produces a specific response?
- In atopic/ extrinsic asthma B cells produce allergen specific IgE
- This means upon next exposure of this allergen there will be a specific response to that allergen by crosslinking of IgE on mast cells and degranulation
Give two powerful bronchoconstrictors
- Leukotrienes
- Histamine
What cell does a mast cell come from?
- A mast cell is an immature form of basophil and only matures once it reaches its tissue site
Describe the late phase of asthma development and chronic remodelling
- Progressing inflammatory reaction set up by early phase inflammatory cell infilitration and production of proinflammatory cytokines (IL’s)
- Continued infiltration by Th2 cells/ eosinophils by chemotaxis
- Eosinophil release of leukotriene and toxic granular proteins
- Damage to respiratory epithelium and exposure of sensory and cholinergic fibres. These sensory nerves can be activated by inflammatory mediators leading to cholinergic reflex- SMC contraction. =Bronchial hyperresponsivenness.
- Growth factor release from inflammatory cells leads to smooth muscle cell hypertrophy and hyperplasia
- Stimulates increase in number of goblet cells and submucosal gland hyperplasia- increase in mucus production and formation of mucus plug.
- BM thickening
- Rexposure to allergen and crosslinking of IgE on mast cells releasing histamine/leukotriene leads to bronchoconstriction and increased vascular permeability.
- Increased vascular permeability leads to oedema.
Is chronic airways remodelling in asthma reversible?
- No, once the chronic inflammatory changes have occured this is irreversible.
What investigation allows you to swiftly assess severity of asthma?
Peak flow
Describe signs and symptoms of asthma
- Chronic inflammatory condition with acute exacerbations - “Asthma Attack” after trigger
- Diurnal variation- often worse at night/ morning dipping with improvement throughout the day
- Cough
- Wheeze - expiratory due to turbulent flow via reduce lumen
- Tight chest
- SOB
- Closely associated with atopy- hayfever/ ecezma/ hives/allergic rhinitis
Describe signs of an acute asthma exacerbation/ attack
- Difficultly completing sentences in 1 breath
- Wheeze/ Cough/ SOB/ Chest tightness
- Tachypnoea
- Tachycardia
- Accessory muscle use
- Reduced breath sounds when severe
What are the cardinal symptoms for COPD?
What are less common symptoms?
- Dysponea / SOB
- Chronic Cough
- Sputum production
- Frequent infective exacerbations with purulent sputum
- Respiratory failure signs (hypoxia and hypercapnia)
Less common symptoms:
- Chest tightness
- Wheeze
What are the risk factors for COPD?
- Smoking (95% cases) and cannabis smoking
- Genetics ( not all smokers develop COPD)- alpha 1 anti trypsin deficiency
- Recurrent lung infections
- Air pollution
- Low birth weight
- Low socioeconomic status
Outline the gross pathology of Chronic Bronchitis- The Blue Bloater
How can this affect the cardiovascular system?
- Exposure to smoking/ pollutants activates the immune system
- Invasion by macrophages, T lymphocytes and neutrophils, production of proinflammatory cytokines
- Stimulation of mucosal gland hypertrophy and hyperplasia
- Increase in goblet cell number and secretions
- Mucus hypersecretion
- Cytokines increase vasodilation and oedema
- Both oedema and mucus reduce cilia motility- reduced mucus clearance
- Increased infections and inflammation leads to:
- Bronchoconstriction and airways obstruction
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Airways obstruction leads to hypoventilation of alveoli:
- Reduced PAO2 in alveolus and increased PACO2 in alveolus. Therefore increases PaCO2 and decreases PaO2 (hypercapnia and hypoxaemia).
- Hypercapnia leads to respiratory acidosis
- Hypoxaemia can lead to polycythemia (increased Hb) - leads to Cyanosis- BLUE Bloater
- Hypoxaemia in alveolus initiates hypoxic pulmonary vasoconstriction - shunt to better ventilated alveoli
- Increase in pulmonary vascular resistance can back blood up into the right side of the heart
- R sided hypertrophy (Cor pulmonale) and heart failure
- Reduced venous return to the left side of the heart
- Reduced left ventricular output leading to activation of the RAAS system
- Fluid retention and exacerbation of oedema - BLOATER
Outline the gross pathology of emphysema/ Pink puffer
What clinical signs does this show as?
- Exposure to smoke/ pollution—> activation of macrophages within alveolus
- Activated macrophages releases proteases and cytokines—> recruitment of neutrophils
- Neutrophils release elastase–> destruction elastin—> loss elastic recoil –> air trapping and hyperinflation and hypoventilation
- Hypoventilation—> increased CO2 (hypercapnia) decreased O2 (hypoxia)
- Hyperinflation—> barrel chest–> increased effort to breathe
- Effort to breathe—> cachexia, dysponea, use of accessory muscles
- Destruction of alveolar walls and pulmonary capillaries by proteases—> reduced perfusion
- Matched defecit in V/Q
