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Chapter 4
Asthma
© 2007 McGraw-Hill Higher Education. All rights reserved.
Topics
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Pathology of asthma
Lung mechanics
Gas exchange
Airflow in the lung
Convection and diffusion
Airway resistance
Breathing cycle
Pathogenesis of asthma
Bronchoactive drugs
© 2007 McGraw-Hill Higher Education. All rights reserved.
Case Study #4: Debra
• 30 yr old School teacher
• Asthma for 20 yrs
– Shortness of breath
• Particularly in
spring
–Pollen
• During exercise
• Exposure to cold
air
© 2007 McGraw-Hill Higher Education. All rights reserved.
Case Study #4: Debra
• Main complaint: SOB
– Particularly in spring
• Frequent attacks of
wheezing
– Cold air and exercise
provoke her asthma
– Stress also provokes
asthma
• Otherwise healthy
© 2007 McGraw-Hill Higher Education. All rights reserved.
Pathology
• Hypertrophied smooth muscle
– Enhanced bronchoconstriction
• Hypertrophied mucus glands
• Bronchial inflammation and edema
• Mucus plugs
• Coughed up sputum (non-purulent)
© 2007 McGraw-Hill Higher Education. All rights reserved.
Pulmonary function tests
• During an attack, all
indicesof expiratory
flow are reduced
significantly
– FEV1.0
– FEV1.0/FVC
– FEF25-75%
• FVC reduced; why?
• Usually responds well
to bronchodilator;
why?
© 2007 McGraw-Hill Higher Education. All rights reserved.
Pulmonary function in asthma
• Expiratory flow-volume loops also examined
– Flow rates are reduced in asthma and EILV and
EELV are increased
– Compare to restrictive lung disease, where EILV
and EELV are reduced
© 2007 McGraw-Hill Higher Education. All rights reserved.
Pathology
• During asthma
– Lung volume is
increased
– FRC, TLC and RV all
increased
• Due to some loss of
elastic recoil and
premature closure of
small airways
– Due to
inflammation,
edema and
increased smooth
muscle tone
© 2007 McGraw-Hill Higher Education. All rights reserved.
Gas exchange
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Arterial hypoxemia common
– Caused by VA/Q mismatching
– Caused by uneven ventilation and also uneven blood flow, which is caused by
hypoxic pulmonary vasoconstriction in regions of the lung where ventilation is
greatly reduced
Bronchodilators may improve lung function while worsening hypoxemia (relief of
VC in poorly ventilated airways)
However, the relief given (i.e. reduced perception of breathing effort) offset the drop
in PaO2 at rest
© 2007 McGraw-Hill Higher Education. All rights reserved.
Physiology & pathophysiology
• Principle of airflow
– Through tubes
• Laminar flow: low flow rates
• Transitional: as flow rates increase, at branch points,
flow is no longer linear
• High flow rates: turbulence; disorganized flow
Laminar flow:
Poiseuille’s law:
V=(pπr4)/(8nl)
P=ΔP; r=radius;
n=viscosity and
l=length
© 2007 McGraw-Hill Higher Education. All rights reserved.
Physiology & pathophysiology
• In laminar flow, the gas in the middle moves twice as fast as the average
velocity; the friction of the sides of a tube slow down flow in those regions;
flow rate is proportional to driving pressure: P=V; gas density has NO
effect under these conditions. Greater ΔP, greater V
• Turbulent flow: P=V2 in addition, gas density becomes more important
here; P1-P2 is greater for a given flow as gas density increases; or greater
ΔP necessary to achieve a given V as gas density increases
Whether flow is laminar or
not is dependent upon the
Reynolds number:
Re=(2rvd)/n
R=radius, V=velocity and
d=density, n=viscosity
Turbulence likely when #
exceeds 2000
© 2007 McGraw-Hill Higher Education. All rights reserved.
Convection and diffusion in the airways
•Convective flow and it’s attendent
turbulence occurs in the conducting
zone
•In terminal and respiratory
bronchioles gas moves primarily by
diffusion
•As the total cross sectional area
increases flow rate is reduced
•Because volume flow is the same and
the number of airways and their
combined cross-sectional area are
increased
•This is okay, because the distances are
short and the diffusive resistance is small
© 2007 McGraw-Hill Higher Education. All rights reserved.
Airway resistance and pressure cycles
• Airway resistance:
– R=(Pmouth-PA)/flow rate
– R is the ration of ΔP to V
• A: Lung volume inc during inspiration
and decreases during expiration
• B: Pleural pressure falls during insp.
And rises during expiration
– Always negative; why?
– Asymmetrical profile due to the
elastic recoil (dashed line) and
changing alveolar press. So solid
line is actual
• C: Flow rate: increases during insp and
exp; zero at transition
• D: Alveolar pressure: mirrors flow rate
© 2007 McGraw-Hill Higher Education. All rights reserved.
Sites of airway resistance
• As airways divide throughout lung,
they become more numerous and
narrow
• Where is the greatest resistance to
flow?
– As R=P/Q one might think the
small airways because of the
small radius
• No, it’s the medium sized airways;
why?
• Laminar flow in terminal airways
– P=V
• Extremely large number of small
airways
– Each airway has high
resistance, but since flow is
spread out over sooo many
airways, total resistance is small
© 2007 McGraw-Hill Higher Education. All rights reserved.
Airway resistance
• Bronchial smooth muscle
– Bronchoconstriction
• Reflexive; controlled by
Vagus n.; Ach causes
BC, sympathetic stim
causes BD
• Lung volume
– Bronchial diameter inc. as
lung vol inc.
– Below a certain vol
(closing vol.); resistance is
so high that no flow
occurs (conductance is
zero)
© 2007 McGraw-Hill Higher Education. All rights reserved.
Airway resistance
• Gas density and viscosity
effects
• Impact the Reynold’s number
and the resistance
– Flow resistance increases
during diving
• Inc. gas density (inc.
Reynold’s #)
• Helium reduces density
– Thus, these effects are
mostly in medium sized
bronchi where turbulence is
most likely and resistance is
highest and thus, can be
changed the most
© 2007 McGraw-Hill Higher Education. All rights reserved.
Uneven Ventilation
• Phases of expiration and the
gas content after single breath
of oxygen
• Phase one: rapid, pure O2 from
upper airways
• Phase 2: N2 rises rapidly,
washout of anatomic DS
• Phase 3: N2 plateaus, alveolar
gas coming out
– Slope is a measure of
ventilatory inequality
• Phase 4: onset is closing
volume of lung; end is RV
© 2007 McGraw-Hill Higher Education. All rights reserved.
Airway closure and uneven ventilation
• Uneven ventilation in the lung
– Partial obstruction of an airway
– Series inequality
• Dilation of peripheral air sacs
– Emphysema
– Collateral ventilation
• Asthma
– Slows emptying of closed units
© 2007 McGraw-Hill Higher Education. All rights reserved.
Pathogenesis of Asthma
• Airway hyperresponsiveness and
inflammation
– They are related
• Triggers
– Allergens
– Cold, dry air
– Pollution
• Chemical mediators
– Mast cells, WBCs
– Histamine, Leukotrienes (and
arachidonic acid), Bradykinin,
cytokines (interleukins)
– Prostaglandins, reactive oxygen
species, etc.
© 2007 McGraw-Hill Higher Education. All rights reserved.
Bronchoactive drugs
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Β-adrenergic agonists
– Two types of β receptors
• β1 in heart, β2 in lung
– Stimulation of β2 receptors
» Relaxes smooth muscle in bronchi
» Albuterol intermediate time course
» Salmeterol long acting
» Work through adenylate cyclase-cAMP pathway
Corticosteroids
– Inhibit inflammatory/immune response
– Enhance β-receptor expression and/or function
Methylxanthines (caffeine breakdown products)
– Theophylline or aminophylline
– Bronchodilatory and anti-inflammatory effects
Anticholinergics
– Block parasympathetic system; usu in sever COPD
Cromolyn and nedocromil
– Block inflammation, possibly through mast cell stabilizing effects
New therapies
– Leukotriene anatagonists (singulair) and 5-lipoxygenase inhibitors (perhaps more effective
with allergic asthma)
© 2007 McGraw-Hill Higher Education. All rights reserved.