Week 2- Obstructive Airway Diseases (asthma And COPD) Flashcards
1
Q
Define asthma
A
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.
2
Q
What is the aetiology of asthma?
A
Genetic factors Environmental factors Acute triggers- allergens
3
Q
Give examples of the factors involved in the aetiology of asthma
A
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
4
Q
What are the two types of asthma? Outline their differences
A
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
5
Q
Give three things asthma is characterised by
A
- Reversible airways obstruction
- Bronchial hyper responsiveness
- Airways inflammation
6
Q
Describe the histological changes seen in an asthmatic bronchus
A
- 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
7
Q
Describe the early phase of asthma development
A
- 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.
8
Q
What happens in atopic asthma that produces a specific response?
A
- 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
9
Q
Give two powerful bronchoconstrictors
A
- Leukotrienes
- Histamine
10
Q
What cell does a mast cell come from?
A
- A mast cell is an immature form of basophil and only matures once it reaches its tissue site
11
Q
Describe the late phase of asthma development and chronic remodelling
A
- 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.
12
Q
Is chronic airways remodelling in asthma reversible?
A
- No, once the chronic inflammatory changes have occured this is irreversible.
13
Q
What investigation allows you to swiftly assess severity of asthma?
A
Peak flow
14
Q
Describe signs and symptoms of asthma
A
- 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
15
Q
Describe signs of an acute asthma exacerbation/ attack
A
- Difficultly completing sentences in 1 breath
- Wheeze/ Cough/ SOB/ Chest tightness
- Tachypnoea
- Tachycardia
- Accessory muscle use
- Reduced breath sounds when severe
16
Q
How would you diagnose asthma?
A
- 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.
17
Q
Non pharmacological method of treating asthma?
A
- Oxygen until saturation is 94-96%
18
Q
How does the remodelling stage occur in asthma?
A
- Infiltration of fibroblasts
- Fibroblasts fibrose chronically inflamed tissue
- Lumen narrows and becomes less compliant
- Patient has reduced inspiratory flow rate as a result
19
Q
What are the severities of asthma?
What are the factors involved in assessing asthma severity?
A
-
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
20
Q
Describe the management of acute asthma
A
- 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
21
Q
Asthma treatment:
When would you use magnesium sulphate?
When would you used antibiotics?
A
Direct bronchodilator used in acute severe asthma/ life threatening/ near fatal asthma with poor response
Antibiotics- Only in the presence of infection
22
Q
Define COPD
What is it an umbrella term for?
How is it diagnosed normally?
What can support a diagnosis?
A
- 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
23
Q
Describe the pathophysiology of Chronic Bronchitis
A
- 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
24
Q
What are the cardinal symptoms for COPD?
What are less common symptoms?
A
- Dysponea / SOB
- Chronic Cough
- Sputum production
- Frequent infective exacerbations with purulent sputum
- Respiratory failure signs (hypoxia and hypercapnia)
Less common symptoms:
- Chest tightness
- Wheeze
25
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
26
What three diseases does COPD encompass?
1. Chronic asthma
2. Chronic bronchitis- Blue bloaters
3. Emphysema- Pink puffers
27
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
28
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.**
29
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**
30
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
31
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.**
32
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.
33
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
