Pathophysiology of Asthma and COPD Flashcards
Describe the pathophysiology of asthma with the following in mind:
a. Bronchoconstriction
b. Mucus Hypersecretion
c. Vasodilation
d. Hypertrophy/plasia
a. There is epithelial fragility in the airways of asthmatics. This exposes sensory nerves which can get stimulated by mediators such as bradykinin to cause a cholinergic reflex. Parasympathetic activation causes constriction of airway smooth muscle cells and therefore bronchoconstriction.
b. Similarly the parasympathetic activation can cause mucus secretion and hypersecretion upon frequent activation leading to excessive mucus
c. Histamine causes vasodilation of vessels and also makes capillaries more permeable. This leads to angiogenesis and oedema.
d. As time goes on, mediators like growth factors and chemokines are released. The GF causes hyperplasia of the basement membrane and glands (goblet cells). The chemokines attract fibroblasts and lead to a bit of fibrosis in the airways
Describe the pathophysiology of COPD in regards to:
a. Chronic bronchitis
b. Emphysema
c. Chronic bronchiolitis
a. Smoking activates alveolar macrophages. They release MCP-1 which attracts more macrophages locally. These macrophages may be more activated. They also release chemo-tactic factors (IL-8, LTB4) which attract neutrophils. The neutrophils release oxidants and protease (e.g. elastase) which leads to mucus hypersecretion through epidermal growth factor.
b. The chemotactic factors from the alveolar macrophages attract cytotoxic T-lymphocytes which lead to alveolar destruction
c. Smoking causes damage to the epithelial cells leading to the release of TGF-B which attracts fibroblasts leading to fibrosis and small airway disease
Describe five effects of reactive oxygen species and their effect in COPD.
- Decrease anti-protease activity leading to increased proteolysis
- Increased mucus secretion
- Release isoprostanes which cause plasma leak and bronchoconstriction
- Cause plasma leak
- Increased gene expression of inflammatory markers (IL-8 and TNF-a) leading to increased neutrophil recruitment and activaiton
Describe the relationship between:
a. Proteases and protease inhibtors
b. Oxidants and anti-oxidants
c. Oxidants and protease inhibitors
a. Inhibitors inhibit proteases
b. Anti-oxidants keep oxidants from leading to mucus hypersecretion and alveolar destruction (chronic bronchitis and emphysema)
c. Oxidants can downregulate protease inhibitors leading to more mucus hypersecretion and alveolar destruction (chronic bronchitis and emphysema)
Why is there an increase in lung elastase in respiratory disease (COPD)?
Smoking leads to macrophage activation
CXCL8 and LTB4 released to attract neutrophils
Neutrophils release oxidants and proteases like elastase
Compare the vagal tone of the airways of a healthy patient and patient with COPD.
Healthy patient has some vagal tone to allow actin-myosin heads to be readily contractable. In COPD, the nicotine in the cigarette can cause an agonist effect on M2 nicotinic receptors leading to a bit more vagal tone.
Describe the effects of Anti-cholinergics on the airways of patients with COPD.
Due to the constricting effects of nicotine on nicotinic muscarinic receptors, anti-cholinergics cause a marked dilation of airways and relief of symptoms in COPD patients. It is also worth noting that the mediators released in COPD (IL-8, TNF-a) are not bronchoconstrictors (i.e. on Beta receptors).
Describe the effects of B2 agonists on the airways of asthmatics
The mediators released by mast cells and eosinophils (histamine, IL-4, IL-5, LTC4, LTD4) are all bronchoconstrictors (act on Beta receptors) therefore, B2 agonists can reverse the constriction and relieve symptoms
Name the parts of a spirometry trace
True or False:
a. COPD involves narrowing of the airways
b. Asthma involves narrowing of the airways
a. True - COPD patients have airway narrowing that is persistent or fixed and usually progressive, causing obstruction of bronchial airflow
b. True - Asthma patients have widespread airflow limitation which changes in intensity over short periods of time. generall worse at night and early morning. Airflow limitation can be provoked, usually responsive to treatment
Describe what you would see in results for asthma patient doing a:
a. Spirometry
b. Flow-volume loop
a. Spirometry: reduced FEV1 and FEV1/FVC
b. Concaving of the expiratory curve
These changes may be partly or completely reversed by a bronchodilator
Describe the use of flow-volume loops & spirometry and diffusion capacity tests in providing detail about the patient’s COPD.
Flow-volume loops/spirometry - looks at airways only and can tell us if COPD is associated with chronic bronchitis
Diffusion Capacity Test (TLCO/KCO) - looks at how the lungs are working in gas exchange and can tell us if COPD is associated with emphysema.
Describe how hyperinflation occurs in COPD.
- Emphysema
- Less traction on airways from parenchyma
- ↑airway resistance
- Less traction on airways from parenchyma
- Chronic bronchitis
- ↑Mucus, ↑Narrowing
- ↑airway resistance
- ↑Mucus, ↑Narrowing
- Small airways disease
- ↑Fibrosis and ↑narrowing
- ↑collapse and gas trapping
- ↑Fibrosis and ↑narrowing
- Gas trapping -> ↑RV -> ?↑FRC
Describe the GOLD guidelines on the classification of COPD Severity based on post-bronchodilator FEV1
GOLD 1 (Mild): FEV1 ≥ 80% pred
GOLD 2 (Moderate): 50% ≤ FEV1 < 80%
GOLD 3 (severe): 30% ≤ FEV1 < 50% pred
GOLD 4 (very severe): FEV1 < 30%
Describe the KCO you would expect in a patient with:
a. Asthma
b. COPD
a. KCO usually not affected as gas exchange can still happen. However, if airway obstruction is severe there can be hypoxaemia and respiratory acidosis
b. COPD with emphysema will see a reduced KCO as there is decrease in efficiency of gas exchange (increased airspace) and increased diffusion distance (small airway disease - fobrotic walls)
