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
How would you diagnose asthma?
- In a strongly suspected patient give a course of treatment and see if there is any improvement
- In a moderately suspected patient asses via spirometry before and after a small dose of histamine and then salbutamol.
- If there is a response- diagnosis= asthma
- No response likely differential diagnosis- SOB/ wheeze can be caused by HF/ Lung CA.
Non pharmacological method of treating asthma?
- Oxygen until saturation is 94-96%
How does the remodelling stage occur in asthma?
- Infiltration of fibroblasts
- Fibroblasts fibrose chronically inflamed tissue
- Lumen narrows and becomes less compliant
- Patient has reduced inspiratory flow rate as a result
What are the severities of asthma?
What are the factors involved in assessing asthma severity?
-
Moderate acute asthma -
- PEF 50-75% of predicted or best
- worsening symptoms
- no symptoms of severe acute asthma
-
Severe acute asthma-
- PEF 33-50% of best
- RR above or equal to 25
- HR above or equal to 110 bpm
- Difficulty completing sentences in 1 breath
-
Life threating asthma:
- PEF under 33%
- PaO2 under 8kpa
- PaCO2 normal (4- 6.0kPa)- patient is hyperventilating due to bronchoconstriction and low oxygen- blow off more CO2 despite reduced overall ventilation
- Also altered conciousness/ silent chest/ poor resp effort/ cyanosis/ arrythmia/ hypotension
-
Near fatal asthma:
- All of the above but raised PaCO2- above 6.0kPa, mechanical ventilation required
Describe the management of acute asthma
- Oxygen until sats 94-96%
-
Bronchodilators: B2 adrenergic agonists:
- Terbutaline or salbutamol
- Via inhaled nebuliser repeat 15/30 mins
- Severe cases IV salbutamol
-
Antiinflammatory agents: Corticosteroids:
- Prednisilone or hydrocortisone
- downregulate transcription of proinflammatory genes
- Continued for 5 days
-
Anticholinergics for poor bronchodilator response:
- Tiotroprium bromide or ipratroprium bromide
- Magnesium sulphate- direct bronchodilator used in acute severe asthma/life-threatening/near-fatal asthma with poor response
Asthma treatment:
When would you use magnesium sulphate?
When would you used antibiotics?
Direct bronchodilator used in acute severe asthma/ life threatening/ near fatal asthma with poor response
Antibiotics- Only in the presence of infection
Define COPD
What is it an umbrella term for?
How is it diagnosed normally?
What can support a diagnosis?
- COPD = chronic obstructive pulmonary disease. It is lung disease characterised by chronic obstruction of airflow that interferes with normal breathing and is usually irreversible.
- Umbrella term for both chronic bronchitis and emphysema.
-
Diagnosed via spirometry, supportive of diagnosis is low peak expiratory flow and classical symptoms:
- Productive cough for years preceding
- SOB/ Dysponea
Describe the pathophysiology of Chronic Bronchitis
- Exposure of cigarette smoke/ pollutants leads to irritation of bronchial airway lining
- Activation of the innate and adaptive immune systems
- Infiltration of bronchial respiratory epithelium by Neutrophils, macrophages and T lymphocytes (Th 1 and Th2).
- Release of cytokines and proinflammatory mediators (eg interleukins) and oxidative stress
- Stimulation of mucosal gland metaplasia- submucosal gland hypertrophy and increase in goblet cells
- Hypersecretion of mucus and plug formation
- Inflammatory cytokines leads to vasodilation and oedema
- oedema and mucus overproduction reduces cilia motility
- reduced clearance of mucus leads to increased susceptibility to infections
- Bronchi become clogged
- Recurrent infection leads to further inflammation
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
What three diseases does COPD encompass?
- Chronic asthma
- Chronic bronchitis- Blue bloaters
- Emphysema- Pink puffers
What three things characterise emphysema?
what three things characterise chronic bronchitis?
Emphysema:
- Small airways - lobules and alveoli
- Air space enlargement
- Alveolar wall destruction
Chronic Bronchitis:
- Affects larger airways- Bronchi and bronchioles
- Mucus gand hypertrophy and hyperplasia
- Hypersecretion of mucus
Describe the pathophysiology of Emphysema
- Exposure of cigarette smoke/ air pollutants
- Activates macrophages that normally reside in the alveolus which protect against infection
- Activated macrophages release proinflammatory cytokines
- Recruits neutrophils from the pulmonary circulation to the alveolus
- Neutrophil releases proteases- particularly elastase which breaks down elastin
- Loss of elastic recoil- air trapping and hypoventilation
- Leads to hypoxaemia and hypercapnia
- Oxidative stress due to cigarette smoke and oxygen free radicals released by inflammatory cells.
- Leads to increased apoptosis of alveolar pneumocytes.
- Inflammatory cell infiltration, release of cytokines, proteases and oxidative free radicals leads to destruction of alveolar walls and pulmonary capillaries.
- Reduction in both ventilation and perfusion leads to a matched V/Q defecit.
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
-
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
What diagnostic sign will a patient with COPD show on spirometry?
What additional investigations could be done and what could they show?
- Patient will show an decreased FEV1: FVC ratio- less than 0.7.
- In COPD both FVC and FEV1 will decrease due to increased resistance of the airways but FEV1 will decrease more
- FEV1 less than 80% of predicted
- Chest xray could also be done which could show hyperinflation
- FBC could be done- may show increased Hb (Polycythemia) as with chronic hypoxia.
Outline the management plan COPD
- SMOKING CESSATION- only way to prolong life expectancy
- Bronchodilators:
- Short acting B2 agonists- salbutamol/ terbutaline
- Short acting anticholinergic- ipratroprium bromide
- Combination therapy:
- Long acting B2 agonist- Salmeterol/ formoterol PLUS inhaled corticosteroid (Fluticasone)
- Long acting anticholinergic- Tiotroprium bromide
- Home oxygen
- Pulmonary rehabilitation programme and MDT management
- Vaccinations: Pneumoccocal (prevent community acquired pneumonia) and annual influenza.
Outline management of an acute exacerbation of COPD
- Inhaler/ nebuliser B2 agonists and anticholingergic drugs
- Oral steroid for 7 days- prednisilone
- Antibiotics for infection
- Non invasive ventilation
