pulmonary pathophysiology iain macleod, ph.d [email protected]
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Pulmonary Pathophysiology Iain MacLeod, Ph.D [email protected]. Iain MacLeod 2 November 2009. Anatomy. Areas of the lungs: Conducting zones: upper airways, trachea, bronchi, bronchioles act to filter air of pathogens/dust and to humidify - PowerPoint PPT PresentationTRANSCRIPT
Areas of the lungs:
Conducting zones: upper airways, trachea, bronchi, bronchioles
act to filter air of pathogens/dust and to humidify
contains mucous glands, ciliated cells, smooth muscle and cartilage
Transitional zone: respiratory bronchioles
Respiratory zone: alveolar ducts and alveoli
site of gas exchange
synthesizes surfactant
contains type I and II epithelial cells, macrophages and fibroblasts
Anatomy
Alveoli are small, hollow sacs that contain a cell wall that is usually one cell thick – made up
of type I alveolar cells (flat epithelial cells) – a single cell wall can separate adjacent alveoli.
In addition to type II alveolar cells, the cell wall can contain capillaries. A small volume of
interstitial fluid can separate capillaries and the alveolar cell wall, but when fluid is absent,
the capillary and cell wall can fuse – results in an extremely thin barrier between O2 / CO2
and RBCs.
The thin cell wall coupled with the extensive surface area of alveoli results in the rapid,
bulk movement of gases.
Respiratory Zone
Similar to blood, air move by bulk flow, such that it can be defined as:
F = P / R
Air flow (F) is proportional to the change in pressure, and in this scenario we are thinking in
terms of atmospheric pressure (Patm) and alveolar pressure (Palv):
F = Palv - Patm) / R
During inspiration, Palv is less than Patm so the driving force is negative and air flow moves
inward; the reverse occurs during expiration.
To change Palv the body can vary the volume of the lungs, resulting in a change in pressure
(Boyle’s law – pressure is inversely proportional to the volume)
Mechanics
Two factors determine lung volume: 1.The difference in pressure between the inside and outside of the lungs – the transpulmonary pressure (Ptp)
2.Lung compliance – the amount of expansion that they are capable of
The pressure inside the lungs is equivalent to Palv while the pressure outside equals the
pressure of the intrapleural fluid (Pip). Therefore: Ptp = Palv – Pip
By taking advantage of Boyle’s law, air can flow into the alveoli as a result of decreasing P ip.
This is achieved through the expansion of the chest wall, which as a result increases the
volume of the intrapleural space.
What happens? Pip decreases as a result, making Ptp more positive making the lungs
expand. This expansion results in decreasing Palv allowing air to flow inwards.
Mechanics
Diaphragm and inspiratory intercostal muscles contract
Thorax Expands
Pip becomes more negative
Transpulmonary pressure increases
Lungs expand
Palv becomes more subatmospheric
Air flows into alveoli
Mechanics
Diaphragm and inspiratory intercostal muscles stop contracting
Chest wall recoils inwards (due to elasticity)
Pip becomes more positive
Transpulmonary pressure decreases back to preinspiration levels
Lungs recoil - elasticity
Palv becomes greater than Patm
Air flows out of lungs
Mechanics
Lung compliance: this can be thought of as the opposite of stiffness
Compliance (CL) is defined as the magnitude of change in lung volume (VL) produced by a
given change in transpulmonary pressure (Ptp): CL = VL / Ptp
Therefore – the greater the compliance, the easier it for the lungs to expand. If compliance
is low, then a greater decrease in Pip must occur so that the lungs can expand sufficiently.
People with low lung compliance tend to have shallow, rapid breathing.
What determines lung compliance?
Mechanics
Lung compliance: this can be thought of as the opposite of stiffness
Compliance (CL) is defined as the magnitude of change in lung volume (VL) produced by a
given change in transpulmonary pressure (Ptp): CL = VL / Ptp
Therefore – the greater the compliance, the easier it for the lungs to expand. If compliance
is low, then a greater decrease in Pip must occur so that the lungs can expand sufficiently.
People with low lung compliance tend to have shallow, rapid breathing.
What determines lung compliance? Elasticity of the connective tissue and surface tension.
Mechanics
Surface Tension:
The surface of alveolar cells is moist creating surface tension (think of two glass slides with
water in between them that are difficult to prise apart). If this attractive force wasn’t
countered, it would require extreme effort to expand the lungs and the would collapse.
Recall that type II alveolar cells are found in the cell wall – these cells release surfactant.
This lipid / protein mixture vastly reduces the attractive forces and increases lung
compliance.
Vitally important in premature neonates – infant respiratory distress syndrome
Mechanics
Recall that flow is dependent not only on a change in pressure but also the resistance.
Factors that determine resistance are similar to those of blood flow: tube length, radius and interactions between molecules. Like the circulatory system, airway resistance is inversely proportional to the radius (Poiseuille’s law):
F = ∆P r4 L8
With the main point being that halving the radius results in 16-fold increase in resistance
(decrease in flow).
There is usually little airflow resistance such that small changes in pressure are the main
driving force behind large flows of air - however, it has a detrimental effect when
increased.
what’s the average change in pressure (Palv - Patm) during a normal breath?
Resistance
Recall that flow is dependent not only on a change in pressure but also the resistance.
Factors that determine resistance are similar to those of blood flow: tube length, radius and interactions between molecules. Like the circulatory system, airway resistance is inversely proportional to the radius (Poiseuille’s law):
F = ∆P r4 L8
With the main point being that halving the radius results in 16-fold increase in resistance
(decrease in flow).
There is usually little airflow resistance such that small changes in pressure are the main
driving force behind large flows of air - however, it has a detrimental effect when
increased.
what’s the average change in pressure (Palv - Patm) during a normal breath?
1 mmHg
Resistance
Asthma – how does this disease process help us understand the impact of resistance?
Resistance - Pathologies
Asthma – how does this disease process help us understand the impact of resistance?
A pathology that results from chronic inflammation of the bronchi. Inflammatory mediators
stimulate bronchoconstriction – reduced tube radius = increased restriction.
How is it treated?
Resistance - Pathologies
Asthma – how does this disease process help us understand the impact of resistance?
A pathology that results from chronic inflammation of the bronchi. Inflammatory mediators
stimulate bronchoconstriction – reduced tube radius = increased restriction.
How is it treated?
Chronic Obstructive Pulmonary Disease – emphysema and chronic bronchitis
Both diseases have the same etiology – they are caused by smoking. Chronic bronchitis is
characterized by excessive mucus production and chronic inflammation of the bronchi.
Emphysema is characterized by an increase in pulmonary compliance – why would this be
an issue?
Similar to chronic bronchitis, toxin-induced inflammation, this time in the alveoli, leads to
cell death.
Resistance - Pathologies
O2 has to get from the alveoli into the capillaries, from there to metabolically active
tissues, into the extracellular fluid & across the plasma membrane; CO2 does it in reverse
Generally speaking, in a steady state, the volume of O2 added to the blood is the same as
the volume of O2 consumed by tissues, with the reverse being true for CO2.
Gases are usually discussed in terms of partial pressure. For example: at sea level,
atmospheric pressure is 760mmHg, but this accounts for all the gases found in the
atmosphere. If we wish to think about O2 alone then we discuss it’s partial pressure. As
oxygen makes up 21% of the atmosphere then it’s partial pressure (PO2) is 21% of
760mmHg = 160mmHg.
Partial pressures are important for understanding the exchanges of gases
Exchange of Gases
Similar to the bulk movement of air from high to low pressure, dissolved gases in a liquid
behave in a similar manner.
Alveolar gas pressures are PO2 = 105 mmHg and PCO2 = 40 mmHg, whereas the atmospheric
partial pressures are 160 mmHg and 0 mmHg, respectively.
What would lead to a drop in alveolar PO2?
Exchange of Gases
Similar to the bulk movement of air from high to low pressure, dissolved gases in a liquid
behave in a similar manner.
Alveolar gas pressures are PO2 = 105 mmHg and PCO2 = 40 mmHg, whereas the atmospheric
partial pressures are 160 mmHg and 0 mmHg, respectively.
What would lead to a drop in alveolar PO2?
High altitude = lower atmospheric PO2
Decreased ventilation
Exercise - Increased demand for O2 from tissues
Exchange of Gases
Exchange of Gases
Venous Blood Arterial Blood Alveoli Atmosphere
PO2 40 mmHg 100 mmHg 105 mmHg 160 mmHg
PCO2 46 mmHg 40 mmHg 40 mmHg 0.3 mmHg
You should be able to recognise that as venous blood reaches the pulmonary capillaries,
the differences in partial pressure for O2 and CO2 between the blood and alveoli will result
in an exchange of both gases.
Why isn’t all the CO2 removed?
Hypoxemia – decreased arterial PO2
Hypoventilation: can result from a defect anywhere in the stimulation of respiratory muscles, from the
controlling centres of the medulla down to the muscles themselves.
occlusion of the upper airway / thoracic cages injuries
hypoxemia by hypoventilation is accompanied by a rise in arterial PCO2
Hypoxemia – decreased arterial PO2
Hypoventilation: can result from a defect anywhere in the stimulation of respiratory muscles, from the
controlling centres of the medulla down to the muscles themselves.
occlusion of the upper airway / thoracic cages injuries
hypoxemia by hypoventilation is accompanied by a rise in arterial PCO2
Diffusion Impairment: either a thickening of the alveolar cell well and / or a decrease in surface are
leads to impairment of equilibria between arterial and alveolar PO2
PaCO2 is either normal or reduced (if ventilation is increased to offset hypoxemia)
Hypoxemia – decreased arterial PO2
Hypoventilation: can result from a defect anywhere in the stimulation of respiratory muscles, from the
controlling centres of the medulla down to the muscles themselves.
occlusion of the upper airway / thoracic cages injuries
hypoxemia by hypoventilation is accompanied by a rise in arterial PCO2
Diffusion Impairment: either a thickening of the alveolar cell well and / or a decrease in surface are
leads to impairment of equilibria between arterial and alveolar PO2
PaCO2 is either normal or reduced (if ventilation is increased to offset hypoxemia)
Shunt: an anatomical abnormality that allowed mixed venous blood to by-pass ventilation and
enter
arterial blood.
can also occur when blood passes through alveoli that are unventilated thus the blood in
the
capillaries does not become perfused
PaCO2 is normal due to increased ventilation to counteract hypoxemia
Hypoxemia – decreased arterial PO2
Hypoventilation: can result from a defect anywhere in the stimulation of respiratory muscles, from the
controlling centres of the medulla down to the muscles themselves.
occlusion of the upper airway / thoracic cages injuries
hypoxemia by hypoventilation is accompanied by a rise in arterial PCO2
Diffusion Impairment: either a thickening of the alveolar cell well and / or a decrease in surface are
leads to impairment of equilibria between arterial and alveolar PO2
PaCO2 is either normal or reduced (if ventilation is increased to offset hypoxemia)
Shunt: an anatomical abnormality that allowed mixed venous blood to by-pass ventilation and
enter
arterial blood.
can also occur when blood passes through alveoli that are unventilated thus the blood in
the
capillaries does not become perfused
PaCO2 is normal due to increased ventilation to counteract hypoxemia
Ventilation-Perfusion most common cause of hypoxemia – found in lung diseases such as COPD – ie. an increase
Inequality: in dead space. Ventilation is the same but perfusion (gas exchange) is impaired.
PaCO2 is increased or normal if increased ventilation is possible