Flashcards in L57 – Pathology of Small Airway Obstruction Deck (60):
Compare the cause and effects between small airway pathologies and large airway pathologies?
Small airway = Functional impairment, Generalized, diffuse
Large airway = Not functional impairment, Regional
Airflow obstruction belongs to small or large airway pathologies?
Infection, collapse and atelectasis belongs to small or large airway pathologies?
When does large airway pathologies become functional impairments?
When pathology affects lobe of lung supplied by a large bronchi
What is acinus in lungs?
The ending of a tiny airway in the lung, where the alveoli (air sacs) are located.
What structures are included in small airways?
Respiratory bronchioles (gas exchange starts)
What is the definition of asthma?
Proxysmal (episodic) narrowing of airways
reversible spontaneously or with treatment
What increase in FEV1/FVC post-bronchodilator is considered effective treatment of asthama?
at least 15% increase
What is the reduction of FEV1/FVC in asthma?
less than 70%
but threshold is age dependent
Is asthma a small airway disease or a large one?
Due to reduction in airflow from airway narrowing
What is extrinsic asthma caused by?
Type I HS triggered by allergen inhalation
What is the action of extrinsic asthma? (from allergen to production of mediators)
Inspire foreign Ag (e.g. allergen) > binds to IgE antibodies on submucosal mast cells > mast cells
degranulate > release chemical mediators
What 2 conditions can aggrevate asthma?
Upper respiratory tract infection
What are the 3 major effects of mast cell degranulation in extrinsic asthma?
1. Mucus hypersecretion
2. Bronchospasm/ bronchoconstriction
3. Vascular dilatation > edema
What chemical mediators are released in extrinsic asthma mast cell degranulation?
histamine, leukotrienes, eosinophil chemotactic factor
Explain the pathology of Airway inflammation?
Histamine > submucosal vessels dilate > proteins and plasma leak into interstitial space + congestion of RBC > Oedema and swelling
Explain the pathology of Mucus plugs?
Histamine + leukotrienes > stimulate goblet cells at respiratory epithelium > mucus hypersecretion > Mucus plug
Explain the pathology of bronchospasm/ ' thick muscle coat' ?
Histamine, leukotrienes > stimulate airway smooth muscle contraction > bronchospasm / bronchoconstriction
How does asthma affect V Q?
Narrow lumen of airway increases Raw > affect ventilation, not perfusion
Does asthma affect exhalation or inhalation?
expiration = passive process: depends on elastic recoil
Increase Raw means air cannot escape > cause air-trapping in lungs and hyperinflation
Why is asthma not affected by inspiration?
active effort: builds up suction pressure by muscles > air can still go into lungs
In CXR of asthma patient, what are the changes?
Due to hyperinflation of lungs:
Elongated, narrowed heart / cardiac shadow
When does asthma attack subside spontaneously?
when allergen is removed
What are the functional volume changes in asthma? (tidal, VC, Residual)
Decrease Tidal volume, Vital capacity
Increase residual lung volume
What are the clinical features of asthma?
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)
On a volume flow graph, what is the change in the expiratory phase curve in asthma?
Change from concave to convex
What are the spirometry changes in asthma? (FEV, FVC, ratio)
Dis-proportionally reduced FEV1
FVC also reduced but not as much as FEV1
FEV1/FVC becomes <70% predicted
What are the 2 types of asthma? What are their triggers?
Extrinsic - triggered by allergens in environment
Intrinsic - etiology is unknown/ not always due to antigen
Name some causes of intrinsic asthma?
Compare the onset between extrinsic and instrinsic asthma?
Extrinsic = childhood onset, familial, Well-controlled childhood asthma = subside in adolescence
Intrinsic = adult onset, usually not fully reversible
Is COPD a small or large airway disease?
Small >> chronic AIRFLOW obstruction
What are some alternative terms for COPD?
Chronic obstructive airway disease (COAD)
Chronic obstructive lung disease (COLD)
Chronic obstructive respiratory disease (CORD)
Name the most important factor in the etiology of COPD and other contributing factors?
Most important inducing factor (80%-95%) = tobacco
Other contributing factors:
Air pollution = co-factor (increases risk, duration of
Genetics = susceptibility factors
What are the 2 clinical entities of COPD?
What is the clinical definition of Chronic Bronchitis?
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
How does Tobacco cause activation of inflammatory cells?
Tobacco / cigarette smoke / irritant gas >> contain ROS or induce ROS production > Activate NFκB > express inflammatory mediators and chemotaxis > attract inflammatory cells to airway
What inflammatory cells are involved in chronic bronchitis?
activated macrophages, neutrophils,
What are the 4 pathological conditions in chronic bronchitis?
1) Induce mucus thickening
2) Peribronchiolar fibrosis
3) Chronic inflammation
4) Proteolytic enzyme > emphysema
What causes increased mucus accumulation in COPD patients? What are the results?
Impaired ciliary clearance
> mucus plugs + cough and mucoid sputum + prone to lung infection
What are the long term effects of chronic bronchitis?
Overall: narrow obstruction of small airways due to:
1) non-reversible bronchoconstriction
2) Chronic inflammation causing slowly progressive peribronchial/ peribronchiolar fibrosis
What is the definition of emphysema?
permanent destruction of alveolar wall / interstitial septum between alveolar airspace
permanent enlargement of airspaces beyond terminal bronchioles
The balance of which enzymes determine the progression of emphysema?
imbalance between protease, anti-protease
How does smoking increase the level of proteases whilst decrease level of Anti-proteases?
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
What are the results of proteolytic enzymes released in lung tissue?
Apoptosis of alveolar tissue cells
Degradation/ uncontrolled proteolysis of elastic tissue in extracellular matrix
How does Alpha 1 anti-trypsin deficiency cause an imbalance in proteases?
Congenital deficiency of anti- proteases >> causes emphysema even without smoking ... etc
Which parts of lung lobules are involved in centriacinar (centrilobular) emphysema? How about panacinar (panlobular) emphysema?
Centriacinar= happens first, Involve alveoli at centre of lobules
Panacinar = advanced cases involve entire lung lobule
Describe how alveolar tissue lose function in emphysema? (2)
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
a-1 antitrypsin deficiency is related to which type of emphysema?
Panacinar (panlobular) emphysema
What is the gross morphology of lungs with emphysema?
pale, soft, expanded
pale due to loss of capillaries
Expanded due to air-trapping
Compare chronic bronchitis and emphysema. Which one is defined clinically, which on pathologically?
Clinically defines = chronic bronchitis
Pathologically defined = emphysema
Compare chronic bronchitis and emphysema. Which one affects airspace, which one airway?
Airway affected = chronic bronchitis
Airspace affected = emphysema
What induces Acute exacerbation of emphysema ?
upper respiratory tract / bronchial infections, air pollution, irritant gas, dusts
Can COPD symptoms be stopped by smoking cessation?
Not completely stopped by smoking-cessation > progressive disease
Deteriorates (does not recover)
What are 4 long term complications of COPD?
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
How is COPD asociated with lung cancer?
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
Compare asthma with COPD:
What is the etiology?
Asthma = allergy
COPD = smoking mostly
Compare asthma with COPD:
What is the disease pattern?
Asthma = reversible
COPD = non-reversible
What are some acute complications of severe asthma and COPD exacerbations?
Superimposed bacterial infection (pneumonia)
Acute respiratory failure (type II ventilation failure)
What are some common clinical features of asthma and COPD?
Expiratory wheeze due to turbulent flow in narrow airways
Cough, sputum, shortness of breath