Physiology and function in obstructive lung disease

Question 1

What is an obstructive disorder?

Answer 1

• Narrowing of airway (increased resistance)
• Reduced inflow of gas
• Reduced inflation of alveolus

Question 2

Examples of obstructive lung diseases

Answer 2

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)
• Causing obstructive picture (Bronchiectasis, cystic fibrosis)

Question 3

What are the factors affecting airway internal diameter?

Answer 3

• Increased mucus production
• Anatomical features
• Autonomic and Non-Adrenergic/ Non-Cholinergic (NANC) systems
• Inflammation

Question 4

What does the airway surface liquid layer compromise of?

Answer 4

mucus layer (comprised of gel-forming mucins, MUC5AC and MUC5B) and the PCL (liquid filled domain), from fixed human bronchial
epithelial
PCL within cilia (low-viscosity periciliary gel layer)

Question 5

How does mucous clearance occur?

Answer 5

The airways are covered by a layer of fluid and mucus that is constantly being propelled by cilia from the distal to proximal lung airways
The viscoelastic mucus layer is composed of secreted mucus glycoproteins (termed mucins) in addition to several secreted products.

Question 6

What are the differences between large and small airways?

Answer 6

Larger: contain cartilage, relatively rigid
Smaller: no cartilage, susceptible to collapse

Question 7

What are bronchioles?

Answer 7

Bronchioles are small airways, up to 1 or 2 mm in diameter, without cartilage or submucosal glands
respiratory bronchioles are distinguished from the terminal bronchioles by the alveolar sacs in their walls.

Question 8

How do autonomic nervous systems interact with airway smooth muscle?

Answer 8

Parasympathetic vagus nerve- Acetyl choline- M3 muscarinic receptor= constriction of airway smooth muscle
Antigen in circulation- ACh- beta 2 adrenergic receptors= dilation

Question 9

How do NANC NS interact with airway smooth muscle?

Answer 9

VIP and NO= bronchodilation

substance P and neurokinins= bronchoconstriction

Question 10

How are asthma and COPD different in host factors?

Answer 10

A: Atopy, Sex, Low birth weight
COPD: Alpha-1 antitrypsin deficiency, low birth weight, family history, genetic predisposition

Question 11

How are asthma and COPD different in environmental factors?

Answer 11

A: allergen exposure, occupational sensitizers, respiratory infections
COPD: smoking, occupational exposure, pollution, low SES status

Question 12

How are asthma and COPD different in mechanism?

Answer 12

A: mast cells degranulate to release histamine leukotrienes and prostaglandins for bronchoconstriction of smooth muscle, inflammation (eosinophils) and antibody production (chemokines and interleukins= B cells)
COPD: mucous hyper secretion (macrophage chemokines, monocytes, neutrophil proteases), alveolar wall destruction (macrophage proteases, T cells), fibrosis (TGF beta and fibroblasts)

Question 13

What are the reasons for airway narrowing in asthma?

Answer 13

• Smooth muscle thickening
• Bronchoconstriction
• Basement membrane thickening
• Mucous plugging

Question 14

What happens in COPD?

Answer 14

• Increased mucous production

- Destruction of alveoli and connective tissue leading to collapse of conducting airways

Question 15

What is Cystic Fibrosis?

Answer 15

CF is an autosomal recessive genetic disease. CFTR encodes its protein, a chloride and bicarbonate ion channel present on cell membranes. It is a multi-system disease affecting the GI tract, liver, reproductive system, but death is principally related to airways inflammation and infection leading to respiratory failure, which occurs from childhood. Whilst median predicted survival is 47 years of age, the median age of death in 2017 was only 31.

Question 16

How do we measure obstruction?

Answer 16

• Peak flow
• Spirometry
• Lung volumes and flow

Question 17

What are the factors determining airway resistance and flow?

Answer 17

-Airflow
-Upstream pressure
-Downstream
Airflow= (upstream pressure-downstream pressure)/resistance
Airflow= volume of gas per unit time

Question 18

How do we calculate resistance?

Answer 18

Resistance= 8/pie x viscosity x length/(radius)^4

So small decrease in radius= big increase in resistance= reduces flow

Question 19

What is Peak expiratory flow rate (PEFR)?

Answer 19

• Measures maximum speed of expiration
• Crude measurement of conducting airway flow
• Can aid in asthma diagnosis/ management
• Excellent bedside and patient based tool

Question 20

How do we measure airflow?

Answer 20

How much can the patient exhale in a given time compared with how much they can exhale altogether

Question 21

How do we use spirometry?

Answer 21

• Forced expired volume in 1 second (FEV1)
• Forced vital capacity (FVC)
• We compare to predicted values based on age, sex and height
• Predicted values based on population of healthy individuals

Question 22

What is the Global Lung initiative?

Answer 22

Set up in 2008 to standardize the predicted values for spirometry
Online data tool for interpretation

Question 23

How do we use the ratio of FEV1 to FVC?

Answer 23

• Useful to differentiate between obstructive and restriction
• If less than 0.7 then suggests obstructive airways pathology
• In mild obstruction biggest impact on FEV1
• In severe obstruction also lose FVC

Question 24

What is the effect of mild/moderate airway obstruction on lung volumes?

Answer 24

• TLC remains in normal range
• Airway narrowing and collapse leads to gas trapping
• RV increased above normal range (gas trapping)
• RV/TLC ratio increased above normal

Question 25

What is the effect of severe airway obstruction on lung volumes?

Answer 25

- TLC increased above normal range due to destruction of lung tissue - VC decreased - Extensive airway narrowing and collapse leads to gas trapping - RV substantially increased above normal range - FVC decreased due to loss of elastic recoil - RV/TLC ratio increased above normal

Question 26

How can the reversibility of spirometry be used?

Answer 26

- Used as a diagnostic test in asthma (following bronchodilator) - Asthma reversible vs COPD fixed airways obstruction - Can also use bronchial challenge agents (histamine) to induce bronchospasm and obstructive spirometry