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Biology of Disease
CH0576
Respiratory Disorders I
Dr Suad Awad
[email protected]
Room A305 Ellison’s- Ext 3816
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Lecture Objectives
* Identify lung volumes & capacities
* Explain effect of relevant pressures in pulmonary
ventilation
* Discuss causes and consequence of Pneumothorax
* Explain the aetiology of obstructive lung disease
* Discuss causes and pathological features of Asthma
* Explain the basis of pulmonary compliance
* Discribe pathological features of
Respiratory Distress Syndrome
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Lecture Outline
* Spirometry: Lung Volumes & Capacities
* Pneumothorax
* Resistance to Airflow
* Chronic Obstructive Lung Diseases:
Asthma
* Pulmonary Compliance:
Respiratory Distress Syndrome
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Lung Volumes & Capacities
Classic Spirometer
Spirometry: Measure
air
entering or leaving
lung
Change in Lung
Volume
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Fig 26-1A- Boron
Lung Volumes & Capacities
Inspiration: Upward deflection,
Expiration: Downward deflection
TV= Tidal volume
IRV= Inspiratory Reserve
Volume
Max volume inhaled at end
of quiet inspiration
ERV= Expiratory Reserve
Volume
Max volume expired at end
of quiet expiration
RV= Residual Volume
Air remaining in lung
after max exp effort
Fig 26-1B- Boron
RV= Can not be measured
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by a Spirometer
Lung Volumes & Capacities
TLC= Total Lung Capacity
Sum of all 4 volumes
FRC= Functional Residual
capacity
Sum of ERV + RV
Air remaining after
quiet expiration
IC= Inspiratory Capacity
Sum of IRV + TV
max inspired volume
after a quiet expiration
VC= Vital Capacity
Sum of IRV + TV + ERV
max inspired achievable
tidal volume
Fig 26-1B- Boron
Any capacity that includes
the RV can not be measured6
by a Spirometer
Lung Volumes & Capacities
FEV1
Forced Expiratory Volume in
One Second
~ 80% VC in Healthy Young
Adults
Affected in Pulmonary
Disorders with increased
Airway resistance
Eg Asthma
Fig 26-1B- Boron
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Lung Volumes & Capacities
Volumes & Capacities
Typical Ranges
(L)
IRV (Inspiratory Reserve Volume)
TV (Tidal Volume)
1.9- 2.5
0.4- 0.5
ERV (Expiratory Reserve Volume)
RV (Residual Volume)
TLC (Total Lung Capacity)
1.1- 1.5
1.5- 1.9
4.9- 6.4
IC (Inspiratory Capacity)
2.3- 3.0
FRC (Functional Residual Capacity)
VC (Vital Capacity)
2.6- 3.4
3.4- 4.5
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Spirometry: FEV1/VC ratio
• FEV1 This is the forced expiratory volume in one
second. It reflects airway narrowing and is
relatively independent of effort
• FVC = the forced vital capacity
Normally FEV1 = 70%-80% of the FVC
FEV1 and FVC used to differentiate between
Obstructive and Restrictive patterns of lung disease
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Peak Flow Metre
• Peak Expiratory Flow Rate (PEFR) is defined
as the highest air flow (Vol/time) achieved at the
mouth during a forced expiration
• It is a measure of the existence and severity of
airflow obstruction
• The PEFR obtained by a patient is compared to
that of a normative standard (use height, age,
gender). It is calculated as % of the expected
PEFR.
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Peak Flow Meter
Measured by modern Spirometry: Next Lecture
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FRC
Functional Residual Capacity
Volume of air remaining in the lungs at the end of a quiet
expiration
Determined by the lung and chest wall
elastic recoils
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Factors affecting Ispiratory & Expiratory
Reserve Volumes
* Current Volume
The greater the current volume, the less are the
reserve volumes
* Lung Compliance
A measure of how easy to inflate the lungs
* Muscle Strength
* Comfort
* Posture
Problems with innervation - muscle weakness
Pain (injury) limit desire or ability to make insp efforts
Recumbent position = IRV falls- Difficult for diaphragm to
move abdominal contents
* Flexibility of Skeleton
Arthritis, Kyphoscoliosis = Reduce IRV
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Important Pressures in Pulmonary
Ventilation
* Atmospheric Pressure - Barometric pressure
* Intra-alveolar Pressure - Pressure within the
alveoli
Fluctuates during breathing cycle: -ve inspiration, +ve expiration
* Intrapleural Pressure - Pressure inside the
thoracic cavity
Less than Barometric P (-ve)
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Pneumothorax
• Occurs when the Intrapleural Pressure
equilibrates with atmospheric P.
As a result lungs collapse - inherent elastic recoil
• Traumatic Pneumothorax - caused by
the chest wall being punctured
• Spontaneous Pneumothorax 1. Due to a hole in the wall of the lung
2. Congenital defect in connective tissue in
alveolar wall
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Pneumothorax
Traumatic
COLLAPSED
LUNG
Spontaneous
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Pneumothorax
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Factors Influencing Airflow Through
the Lung
Airflow (F) depends on:
1. Pressure Gradient PDifference between atmospheric pressure
and intra-alveolar pressure.
2. Resistance of Airways (R)Determined by the radii of the airways
F is inversely related to R
F = P/R
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Resistance to Airflow
F = P/R
• Main determinant of resistance to airflow (R)
is the RADIUS of the conducting airways
• In the healthy lung the radius is relatively large
and so R is low
• The airways normally offer such a low resistance
that only small pressure gradients are needed for
adequate airflow into the lung
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Adjustment of Airway Size
• Normally modest changes in airway size, to meet
the body’s needs, are achieved through the
AUTONOMIC nervous system
• In quiet respiration Parasympathetic
stimulation promotes bronchiolar smooth muscle
contraction causing Bronchoconstriction
Maintains muscle tone in airways
• Sympathetic stimulation brings about
Bronchodilation by bronchiolar smooth
muscle, Decreasing airway resistance during
exercise, fight or flight situations
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Pulmonary Diseases Associated
with Narrowing of the Airways
• Increased Resistance is an extremely
important impediment to airflow when airways
become narrowed due to disease:
CHRONIC OBSTRUCTIVE PULMONARY
DISEASE (COPD)
• COPD is a group of lung diseases including Chronic Bronchitis, Asthma and Emphysema
• COPD is characterised by Increased Airway
Resistance
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Chronic Obstructive Pulmonary Disease
* Sufferers have to work harder to breathe
• F = P/R
When resistance is increased, a larger pressure
gradient is needed to maintain a normal airflow.
e.g. If resistance is doubled by narrowing of airway
lumens, P must be doubled through increased
respiratory muscle workload
• Expiration is more difficult to accomplish than
inspiration giving rise to the characteristic
‘WHEEZE’ as air is forced out of narrow airway
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Chronic Obstructive Lung Diseases (COPDs)
Aetiology:
• Group of diseases in which there is a chronic
limitation to airflow
• Flow is reduced for one of two reasons:
1. Narrowing of the Airways causing increased
resistance - Asthma, Chronic Bronchitis
2. Loss of Elastic Recoil - Reduction
in the outflow pressure - Emphysema
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Asthma
• Asthma is the Greek word for ‘Breathless’ or
‘to breathe opened mouthed’
• It is caused by Chronic Inflammatory Responses
in the airways
• This leads to REVERSIBLE airway obstruction.
• It is characterised by breathlessness and
wheezing
caused by generalised narrowing of
intrapulmonary airways
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Causes of Asthma
Asthma is a heterogeneous disease triggered by
a variety of inciting agents (Genetic + Environ)
• Extrinsic Factors
Caused by Type I hypersensitivity reactions on
exposure to extrinsic allergen (pollen, perfume,
dust mite, others?)
• Intrinsic Factors
Non-immune trigger mechanism e.g.
hormonal, stress, exercise
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Asthma
There are three main features of asthma:
Remember: (F = P/R)
1. Muscle Spasm – Bronchospasm (Narrowing of
airway lumen- increased airway R)
2. Mucus Plugging- (air trapping in distal
bronchioles- increased RV, and relevant volume &
capacities; eg? )
3. Mucosal Oedema- (Narrowing of lumen- increased
R- increased pressure- increased work for
respiratory muscles)
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Pathological Features of Asthma
* Mucosal Oedema
- Inflammatory cell infiltration (Eosinophils 5%-50%)
- Basement membrane thickening
- Goblet cell and submucosal gland hyperplasia
- Hypertrophy and hyperplasia of the smooth muscle
in the bronchial wall
These events lead to - Airway Obstruction
Bronchial Muscle Constriction
Airway Congestion
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Early
phase
response in
asthma
Dust mite, pollen
Other??
SM spasm followed
By inflammation
Lamina propria
Histamine induces
SM contraction
Through H1 Rs
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Late phase
response in
asthma
Eosinophill
Infiltration,
(MBP, ECP)
Loss of Epithelial
Cells
Increased mucus
secretion
Edema
SM
Hypersensitivity
(histamine),
Infiltration of
Basophils &
Neutrophils
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Pathological Features of Asthma
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Bronchioles in Asthma
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Features of Asthma in Status
Asthmatics
• Lungs are Overdistended - Due to trapped air
• May be small areas of Atelectasis
• The most striking feature is the blocking of
bronchi and bronchioles with thick mucus plugs
• The mucus plugs contain
- Whorls of shed epithelium
- Eosinophils
- Charcot - Leyden Crystals
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Charcot Leyden Crystals
Crystallised
Lysophospolipase
Enzyme produced
By Eosinophils
Up to 50 m
length
Normally colourless
Stains reddish by
trichrome
Indicative of a disease involving eosinophilic inflammation
& proliferation
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Asthma - Clinical Course
• Severe Dyspnoea with wheezing
• Hyperinflation of lungs, with air trapped distal
to the bronchi which are constricted and full
of mucus (which volumes & capacities are affected?)
• This leads to Hypercapnia, acidosis and hypoxia
• Asthma tends to be severely debilitating rather
than lethal
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COMPLIANCE
• A factor influencing the pressure gradient P in
the lung is the ELASTIC behaviour of the lung
• This affects alveolar and lung volume,
and therefore the pressure gradient needed to inflate lung
• COMPLIANCE refers to how much effort is
required to stretch or distend the lungs
• Specifically Compliance is a measure of the
change in lung volume due to a given
change in transmural pressure
(The Force That Stretches the Lung)
C = V/ P
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COMPLIANCE
• A HIGHLY compliant lung stretches further for
a given increase in pressure than does a LESS
compliant lung (eg inflating a very flexible Vs stiff balloon)
• A LESS compliant lung will require MORE
Effort (P) to produce a given degree of inflation
• A POORLY compliant lung is referred to as a
‘STIFF LUNG’
• Compliance is reduced in pulmonary diseases
e.g. FIBROSIS of the lung
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Factors Affecting Pulmonary Compliance
Pulmonary compliance depends on various factors:
1. Highly Elastic Connective Tissue
2. Alveolar Surface Tension:- due to a
thin liquid film lining each alveolus.
It resists any force that increases
surface area (thus OPPOSES expansion)
3. Pulmonary Surfactant:- Surface Active Agent - detergent !
produced by TYPE II alveolar cells, decreases surface
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tension (70 dynes/cm Vs 25 dynes/cm)
Pulmonary Compliance
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Effect of Pulmonary Surfactant
• It REDUCES the surface tension and
contributes to lung stability
• It acts by interspersing water molecules
lining the alveolus, which reduces surface tension
Benefits of Reducing Surface Tension:
a) Increases pulmonary compliance - thus reducing
the effort needed to inflate the lungs
b) It stabilises the alveoli so they do not collapse at
end of expiration
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Newborn Respiratory Distress Syndrome
• Surfactant produced by 34th wk gestation
* Premature infants- Deficiency in lung surfactant
leads to Newborn Respiratory Distress Syndrome
• Very strenuous inspiratory efforts are required to
overcome the high surface tension in the alveoli
The lungs are Poorly Compliant
• It may require transmural pressure gradients of
20-30 mm Hg (normally 4-6 mm Hg) to overcome
the tendency of the lungs to collapse
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NEWBORN RDS
• The problem is compounded as the newborn’s
muscles are still very weak
• Deficiency in surfactant leads to alveolar
instability and severe respiratory failure
• Life threatening condition
• Newborn RDS can be treated by:
a) Artificially increasing atmospheric pressure
b) Treating with exogenous surfactant
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Useful Textbooks
Rhoades & Bell, 3rd ed. Medical Physiology:
Principles of Clinical Medicine. LWW
Boron & Boulpeap, 2nd ed. Medical Physiology:
Saunders
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