L57 – Pathology of Small Airway Obstruction

Question 1

Compare the cause and effects between small airway pathologies and large airway pathologies?

Answer 1

Small airway = Functional impairment, Generalized, diffuse

Large airway = Not functional impairment, Regional

Question 2

Airflow obstruction belongs to small or large airway pathologies?

Answer 2

Small

Question 3

Infection, collapse and atelectasis belongs to small or large airway pathologies?

Answer 3

Large

Question 4

When does large airway pathologies become functional impairments?

Answer 4

When pathology affects lobe of lung supplied by a large bronchi

Question 5

What is acinus in lungs?

Answer 5

The ending of a tiny airway in the lung, where the alveoli (air sacs) are located.

Question 6

What structures are included in small airways?

Answer 6

 Terminal bronchioles
 Respiratory bronchioles (gas exchange starts)
 Alveolar duct
 Alveoli

Question 7

What is the definition of asthma?

Answer 7

Proxysmal (episodic) narrowing of airways

reversible spontaneously or with treatment

Question 8

What increase in FEV1/FVC post-bronchodilator is considered effective treatment of asthama?

Answer 8

at least 15% increase

Question 9

What is the reduction of FEV1/FVC in asthma?

Answer 9

less than 70%

but threshold is age dependent

Question 10

Is asthma a small airway disease or a large one?

Answer 10

Small

Due to reduction in airflow from airway narrowing

Question 11

What is extrinsic asthma caused by?

Answer 11

Type I HS triggered by allergen inhalation

Question 12

What is the action of extrinsic asthma? (from allergen to production of mediators)

Answer 12

Inspire foreign Ag (e.g. allergen) > binds to IgE antibodies on submucosal mast cells > mast cells
degranulate > release chemical mediators

Question 13

What 2 conditions can aggrevate asthma?

Answer 13

Air pollution

Upper respiratory tract infection

Question 14

What are the 3 major effects of mast cell degranulation in extrinsic asthma?

Answer 14

1. Mucus hypersecretion
2. Bronchospasm/ bronchoconstriction
3. Vascular dilatation > edema

Question 15

What chemical mediators are released in extrinsic asthma mast cell degranulation?

Answer 15

histamine, leukotrienes, eosinophil chemotactic factor

Question 16

Explain the pathology of Airway inflammation?

Answer 16

Histamine > submucosal vessels dilate > proteins and plasma leak into interstitial space + congestion of RBC > Oedema and swelling

Question 17

Explain the pathology of Mucus plugs?

Answer 17

Histamine + leukotrienes > stimulate goblet cells at respiratory epithelium > mucus hypersecretion > Mucus plug

Question 18

Explain the pathology of bronchospasm/ ‘ thick muscle coat’ ?

Answer 18

Histamine, leukotrienes > stimulate airway smooth muscle contraction > bronchospasm / bronchoconstriction

Question 19

How does asthma affect V Q?

Answer 19

Narrow lumen of airway increases Raw > affect ventilation, not perfusion

Question 20

Does asthma affect exhalation or inhalation?

Answer 20

Exhalation:
expiration = passive process: depends on elastic recoil

Increase Raw means air cannot escape > cause air-trapping in lungs and hyperinflation

Question 21

Why is asthma not affected by inspiration?

Answer 21

active effort: builds up suction pressure by muscles > air can still go into lungs

Question 22

In CXR of asthma patient, what are the changes?

Answer 22

Due to hyperinflation of lungs:
Elongated, narrowed heart / cardiac shadow

Horizontal ribs

Suppressed diaphragm

Question 23

When does asthma attack subside spontaneously?

Answer 23

when allergen is removed

Question 24

What are the functional volume changes in asthma? (tidal, VC, Residual)

Answer 24

Decrease Tidal volume, Vital capacity

Increase residual lung volume

Question 25

What are the clinical features of asthma?

Answer 25

 Shortness of breath, difficulty in breathing  Long expiration phase + high-pitched wheezing (turbulent airflow hit on narrow airways)  Episodic attacks with recovery in-between (paroxysmal, reversible)

Question 26

On a volume flow graph, what is the change in the expiratory phase curve in asthma?

Answer 26

Change from concave to convex

Question 27

What are the spirometry changes in asthma? (FEV, FVC, ratio)

Answer 27

Dis-proportionally reduced FEV1 FVC also reduced but not as much as FEV1 FEV1/FVC becomes <70% predicted

Question 28

What are the 2 types of asthma? What are their triggers?

Answer 28

Extrinsic - triggered by allergens in environment Intrinsic - etiology is unknown/ not always due to antigen

Question 29

Name some causes of intrinsic asthma?

Answer 29

``` Aspirin exercise cold air viral infection stress ```

Question 30

Compare the onset between extrinsic and instrinsic asthma?

Answer 30

Extrinsic = childhood onset, familial, Well-controlled childhood asthma = subside in adolescence Intrinsic = adult onset, usually not fully reversible

Question 31

Is COPD a small or large airway disease?

Answer 31

Small >> chronic AIRFLOW obstruction

Question 32

What are some alternative terms for COPD?

Answer 32

Alternative terms:  Chronic obstructive airway disease (COAD)  Chronic obstructive lung disease (COLD)  Chronic obstructive respiratory disease (CORD)

Question 33

Name the most important factor in the etiology of COPD and other contributing factors?

Answer 33

Most important inducing factor (80%-95%) = tobacco ``` Other contributing factors:  Occupational  Air pollution = co-factor (increases risk, duration of hospital stay)  Genetics = susceptibility factors ```

Question 34

What are the 2 clinical entities of COPD?

Answer 34

Chronic bronchitis | Emphysema

Question 35

What is the clinical definition of Chronic Bronchitis?

Answer 35

chronic productive cough with mucoid sputum, at least 3 months per year for 2 consecutive years in absence of other lung diseases that can account for the symptom

Question 36

How does Tobacco cause activation of inflammatory cells?

Answer 36

Tobacco / cigarette smoke / irritant gas >> contain ROS or induce ROS production > Activate NFκB > express inflammatory mediators and chemotaxis > attract inflammatory cells to airway

Question 37

What inflammatory cells are involved in chronic bronchitis?

Answer 37

activated macrophages, neutrophils, | lymphocytes

Question 38

What are the 4 pathological conditions in chronic bronchitis?

Answer 38

Affect airway: 1) Induce mucus thickening 2) Peribronchiolar fibrosis 3) Chronic inflammation Affect airSPACE 4) Proteolytic enzyme > emphysema

Question 39

What causes increased mucus accumulation in COPD patients? What are the results?

Answer 39

Impaired ciliary clearance > mucus plugs + cough and mucoid sputum + prone to lung infection

Question 40

What are the long term effects of chronic bronchitis?

Answer 40

Overall: narrow obstruction of small airways due to: 1) non-reversible bronchoconstriction 2) Chronic inflammation causing slowly progressive peribronchial/ peribronchiolar fibrosis

Question 41

What is the definition of emphysema?

Answer 41

permanent destruction of alveolar wall / interstitial septum between alveolar airspace permanent enlargement of airspaces beyond terminal bronchioles

Question 42

The balance of which enzymes determine the progression of emphysema?

Answer 42

imbalance between protease, anti-protease

Question 43

How does smoking increase the level of proteases whilst decrease level of Anti-proteases?

Answer 43

Toxins in smoke neutralize and decrease level of anti-protease Smoke causes activation of inflammatory cells and ROS > neutrophils (PMN) and macrophages release proteolytic enzymes > increase protease level

Question 44

What are the results of proteolytic enzymes released in lung tissue?

Answer 44

 Apoptosis of alveolar tissue cells  Degradation/ uncontrolled proteolysis of elastic tissue in extracellular matrix

Question 45

How does Alpha 1 anti-trypsin deficiency cause an imbalance in proteases?

Answer 45

Congenital deficiency of anti- proteases >> causes emphysema even without smoking ... etc

Question 46

Which parts of lung lobules are involved in centriacinar (centrilobular) emphysema? How about panacinar (panlobular) emphysema?

Answer 46

Centriacinar= happens first, Involve alveoli at centre of lobules Panacinar = advanced cases involve entire lung lobule

Question 47

Describe how alveolar tissue lose function in emphysema? (2)

Answer 47

1) Loss of surface area for gas exchange 2) Proteases break down connective tissue > loss of lung recoil, respiratory bronchioles not supported by radial traction > early small airway closure during expiration and air-trapping

Question 48

a-1 antitrypsin deficiency is related to which type of emphysema?

Answer 48

Panacinar (panlobular) emphysema

Question 49

What is the gross morphology of lungs with emphysema?

Answer 49

pale, soft, expanded pale due to loss of capillaries Expanded due to air-trapping

Question 50

Compare chronic bronchitis and emphysema. Which one is defined clinically, which on pathologically?

Answer 50

Clinically defines = chronic bronchitis Pathologically defined = emphysema

Question 51

Compare chronic bronchitis and emphysema. Which one affects airspace, which one airway?

Answer 51

Airway affected = chronic bronchitis Airspace affected = emphysema

Question 52

What induces Acute exacerbation of emphysema ?

Answer 52

upper respiratory tract / bronchial infections, air pollution, irritant gas, dusts

Question 53

Can COPD symptoms be stopped by smoking cessation?

Answer 53

 Not completely stopped by smoking-cessation > progressive disease  Deteriorates (does not recover)

Question 54

What are 4 long term complications of COPD?

Answer 54

1) Chronic persistent hypoxia 2) Pulmonary hypertension > irreversible pulmonary artery narrowing due to chronic alveolar hypoxia 3) Cor pulmonale - Right heart failure due to primary lung disease 4) Polycythaemia - Increased RBC production under chronic hypoxia for compensation of low PaO2

Question 55

How is COPD asociated with lung cancer?

Answer 55

Smoking > inflammation > release of ROS/ RNS, inflammatory mediators and growth factors can cause: 1) chronic inflammation leading to COPD 2) DNA damage, mutation and Cancer

Question 56

Compare asthma with COPD: | What is the etiology?

Answer 56

``` Asthma = allergy COPD = smoking mostly ```

Question 57

Compare asthma with COPD: | What is the disease pattern?

Answer 57

``` Asthma = reversible COPD = non-reversible ```

Question 58

What are some acute complications of severe asthma and COPD exacerbations?

Answer 58

Pneumothorax Superimposed bacterial infection (pneumonia) Acute respiratory failure (type II ventilation failure)

Question 59

What are some common clinical features of asthma and COPD?

Answer 59

Prolonged expiration Expiratory wheeze due to turbulent flow in narrow airways Cough, sputum, shortness of breath

Question 60

The symptoms and sings, pathophysiological effects and acute complications appear common in small airway diseases. What pathology is not common?

Answer 60

Different long term complications