Respiratory System
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Lung Volumes and Ventilation
Minute ventilation
• Volume of an inspired or expired air per minute
• = tidal volume (VT) x respiratory rate
Dead space ventilation
• The portion of minute ventilation that fails to reach the area of the lungs involved in gas exchange
• Anatomic dead space(VD) is the volume of gas that occupies the conducting zone of
respiratory system (plus the accessory tubings), which does not participate in gas exchange
• Alveolar dead space :- some alveoli do not receive any blood flow
Alveolar ventilation
• Volume of gas that reaches the alveolar portion for the exchange of O2 and CO2
• = (VT – VD) x respiratory rate
• Adequate alveolar ventilation is critical because it determines the PAO2 and PACO2
PACO2 and PaCO2
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• Are essentially equal because of the high diffusibility of CO2
• Are determined by the ratio of the rate of CO2 production to alveolar ventilation
• Normal values = 40 + 4 mmHg (36–44 mmHg)
• Hyperventilation (constant VCO2) Æ hypocapnia Æ respiratory alkalosis
• Hypoventilation (constant VCO2) Æ hypercapnia Æ respiratory acidosis
Static Mechanics of Breathing
Generation of a pressure gradient between atmosphere and alveoli
Air moves from a region of higher pressure to one of lower pressure
Intra-alveolar pressure (Palv)
• Inspiration: Palv < Patm
• Passive expansion of alveoli response to an increased distending pressure across the alveolar
wall generated by contraction of muscles of inspiration
• Expiration: Palv > Patm
Intrapleural pressure or intrathoracic pressue (Pel)
• Pressure in the space between the visceral and parietal pleura is normally subatmospheric
• Caused by the mechanical interaction between the lung and the chest wall
• There is normally no gas in the intrapleural space
• Lung is held against the chest wall by the thin layer of serous intrapleural liquid (~8mL)
Transmural pressure (PTM)
• The pressure across the wall; PTM = Pin – Pout
• Positive transmural pressure (Pin > Pout) Æ force expanding a structure
• Negative transmural pressure (Pin < Pout) Æ force deflating a structure
• Transpulmonary pressure = alveolar-distending pressure = Palv – Ppl
• Transpulmonary pressure is same as alveolar elastic recoil pressure (Pel), but different
direction
• Alveolar pressure (Palv) = intrapleural pressure (Ppl) + alveolar elastic recoil pressure (Pel)
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Elastic Resistance
• Elasticity = ability to return to its original configuration
• Compliance = change in volume divided by change in pressure (ΔV/ΔP)
• Elastic recoil of the lung Æ inward to smaller volume
ƒ Collagen, elastin, fibrous tissue in pulmonary parenchyma
ƒ Surface tension at the air-liquid interface in the alveoli
• Elastic recoil of the chest wall Æ spring outward to larger volume
Surface tension
• Generated by cohesive forces between the molecules of the liquid that balance within the
liquid phase Æ cause a liquid to shrink to form the smallest possible surface area
• Laplace Law
• Small bubble generates a larger pressure, it blows up the large bubble
• Pulmonary surfactant produced by type II alveolar epithelial cells helps equalize alveolar
pressure through out the lung and to stabilize alveoli by decreasing surface tension
Decreased lung compliance
• Fibrosis :- sequelae from lung injury (ARDS), autoimmune disease
• Atelectasis or collapsed alveoli from IRDS/ARDS
• air, excess fluid, blood in the pleural space
Increased lung compliance
• pulmonary emphysema (destroying alveolar septal tissue)
• aging
Decreased chest wall compliance
• obesity
• kyphoscoliosis
• non-functioning diaphragm
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Dynamic Mechanics of Breathing
Airway Resistance :- Frictional Resistance of the airways to the flow of air
Pressure
=
Flow x
Resistance
Poiseuille Law
• R = resistance, η = viscosity of fluid, l = length of tube, r = radius of tube
Determinants of cross-sectional area of the airway
• Airway structure
• Bronchial smooth muscle tone
• Lung volume
• Elastic recoil of the lung
Dynamic compression of airways
• Forced expiratory effort generates positive intrapleural pressure
• Palv is higher than Ppl because Palv = Ppl + Pel
• During forced expiration, there is a point along the airways where pressure inside the airways
is just equal to the pressure outside the airway Æ transmural pressure = 0, but above this
point is negative, so airway will collapse if cartilaginous support or alveolar septal traction is
insufficient to keep it open
• In healthy subject, airway closure can be demonstrated at low lung volume, but the closing
volume may occur at higher lung volume in patients with emphysema
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Measurement
Obstructive
Restrictive
FVC (L)
↓
↓
FEV1 (L)
↓
↓
FEV1/FVC (%)
Normal (N) to ↓
N to ↑
FEF25-75 (L/sec)
N to ↓
↓
Peak expiratory flow (L/sec)
N to ↓
↓
FEF50 (L/sec)
N to ↓
↓
Slope of Flow-volume curve
↓
↑
Maximal voluntary ventilation (L/min)
N to ↓
↓
TLC (L)
N to ↑
↓
RV (L)
↑
↓
RV/TLC (%)
N
↑
Work of breathing
• Work required to move the lung and chest wall to let the air in
o The pressure expanding the respiratory system is stored temporarily in elastic tissues and
then dissipated in driving expiratory flow
• Patients with restrictive diseases tend to breath with a rapid, shallow pattern
• Patients with obstructive diseases tend to adopt a slower breathing pattern with large tidal
volume
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Mechanisms of airway narrowing in asthma
Airway smooth muscle contraction and mucus hypersecretion
Æ narrows airway lumen and increases airway resistance
Airway wall cellular infiltration and edma AND smooth muscle hyperplasia/hypertrophy
Æ increased airway wall thickness
COPD = chronic bronchitis + emphysema
Chronic bronchitis
• Goblet cell metaplasia (a change from ciliated airway epithelium into mucus-secreting cell)
• Airway smooth muscle hypertrophy/hyperplasia
• Excess mucus, edema, inflammatory cell infiltration at airway wall
Emphysema
• Chronic inflammation and destruction of alveolar space with coalescence into larger alveolar
space
• Loss of alveolar attachments with airway distortion and narrowing in COPD
• Elastolysis Æ loss of elastin Æ decreased elastic lung recoil Æ decreased driving pressure
for expiratory airflow from alveoli to mouth
• Air trapping Æ increased lung volume Æ increased antero-posterior diameter of chest wall
Æ limited respiratory excursion of the diaphragm
• Reduced alveolar-capillary surface area
• Ventilation/perfusion inequality
o Perfusion of poorly-ventilated areas Æ reduction in arterial oxygenation
o Overventilation of poorly perfused areas Æ increased dead space ventilation Æ impaired
CO2 excretion
Gas Exchange
Partial Pressure = total pressure X fractional concentration
= (PB – PH2O) X Fx
PB = 760 mmHg at sea level, PH2O = 47 mmHg, FIO2 = 0.21
In dry inspired air at sea level, PIO2 = 760 X 0.21 = 160 mmHg
In humidified tracheal air at 37C, PIO2 = (760-47) X 0.21 = 713 X 0.21 = 150 mmHg
Alveolar oxygen tension is calculated by means of the alveolar gas equation
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PAO2 = (PB – 47) X FIO2 – PACO2/R
R = respiratory quotient = ratio of CO2 production to oxygen consumption = 0.8
At sea level, PAO2 = (760 – 47) X 0.21 – (40/0.8) = 100 mmHg
A-aDO2
PaCO2
Decreased PIO2
Alveolar hypoventilation
Ventilation-perfusion
mismatch
Shunt
Normal
Normal
Increased
Decreased
Increased
Increased
Increased
Diffusion abnormality
Increased
Decreased to
normal
Decreased to
normal
Significant
response to
supplemental O2
Yes
Yes
Yes
Present at rest
No
Yes
Yes
Not usually,
unless severe
Yes
Yes
Yes
Gas Transport
Oxygen dissolves in the plasma of the pulmonary capillaries after diffusing across the alveolar
capillary membrane
From the plasma, oxygen diffuses into the red blood cell, where it combines reversibly with the iron
atoms of hemoglobin and converts deoxyhemoglobin into oxyhemoglobin
1 gram of hemoglobin can combine with 1.35 mL of O2
Solubility coefficient of O2 :- 1 mmHg PO2 can dissolved and generate 0.003 mL of O2/ 100 mL
blood
+ dissolved O2 in blood
Oxygen content = O2 bound to Hb
+ 0.003 X PO2
= 1.35 X [Hb] X SO2
Oxygen hemoglobin dissociation curve
Arterial oxygen tension 100 mmHg, arterial oxygen saturation 97 %
Mixed venous oxygen tension 40 mmHg, mixed venous oxygen saturation 75%
Unloading (dissociation) zone
Loading (association) zone
• Steep portion of the curve
• Plateau portion of the curve
• Occurs below 60 mmHg of PO2
• Occurs above 60 mmHg of PO2
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Hemoglobin affinity for oxygen
• Is inversely related to P50
• Increased Hb affinity Æ ↓ P50
• ↓ H+, ↓ 2,3-diphosphoglycerate, ↓ PCO2, ↓ temperature Æ increased Hb affinity
• Decreased Hb affinity Æ ↑ P50
• ↑ H+, ↑ 2,3-DPG, ↑ PCO2, ↑ temperature Æ decreased Hb affinity
Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS)
Injury to alveolar-capillary membrane Æ permeability pulmonary edema
Injury to alveolar epithelial type 2 Æ reduction of pulmonary surfactant Æ atelectasis
Æ right-to-left shunt Æ hypoxemia with unresponsiveness to oxygen therapy
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Solutions
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