Ventilation and diffusion

Question 1

Learning outcomes

Answer 1

• Define the term “partial pressure“ and know how to calculate a gas partial pressure
• Explain what factors determine how much gas dissolves in a liquid
• Explain what factors affect the diffusion of gases across the air-blood barrier, and the consequences of such factors on arterial blood gases
• State the normal partial pressures of nitrogen, oxygen, carbon dioxide and water vapour in atmospheric air and alveolar air (in mmHg and kPa)
• Describe the processes involved in an oxygen molecule moving from alveolar air to the blood
• Describe the processes involved in a carbon dioxide molecule moving from blood to the alveolar air
• State how different disease states can affect the diffusion of O2 and CO2 across the alveolar barrier
• Describe how altitude affects PO2
• Describe the effects of high pressure on blood gases

Question 2

Discuss the conducting airways

Answer 2

• The conducting airways
– Cartilage, few smooth muscles
– Collapse rare

• Respiratory bronchioles & alveolar ducts
– No cartilage, lots of smooth muscle
– Susceptible to collapse during expiration

• Anatomical Dead Space – 150mls
– Up to generation 17

• Humans have ~ 300 million alveoli and cross sectional area increases from 2.5cm2 at trachea to around 100m2

Question 3

What are the primary functions of the respiratory and cardiovascular systems

Answer 3

• One of the primary functions of the cardiovascular systems is to transport O2 from the lungs to all tissues in the body
• And CO2 from the tissues to the lungs
• The lungs expire this CO2 to the atmosphere
• Both gases move by diffusion down their concentration gradients

Question 4

What is Dalton’s law of partial pressures?

Answer 4

• “Total pressure (PTotal) of a mixture of gases is the sum of their individual partial pressures (Px)”
• Atmospheric Pressure (PB) at sea level is 760mmHg or 101.325 kPa

• Nitrogen (PN2): 78.09% x 760 mmHg = 593.48 mmHg
• Oxygen (PO2): 20.95% x 760 mmHg = 159.22 mmHg
• Carbon dioxide (PCO2): 0.030% x 760 mmHg = 0.23 mmHg
Argon (P ): 0.930% x 760 mmHg = 7.07 mmHg

• If atmospheric pressure changes then partial pressure changes
• If proportion of gas changes its partial pressure changes

Question 5

What is Henry’s Law

Answer 5

• States that the concentration of O2 dissolved in water ([O2]dis) is proportional to the Partial pressure (PO2) in the gas phase
[O2]dis = s x PO2
where s = solubility of O2 in water

For blood plasma s = 0.0013 mM/mmHg at 37oC, so

[O2]dis = 0.0013 x 100 mmHg = 0.13 mM (arterial blood) 
[O2]dis = 0.0013 x 40 mmHg = 0.05 mM (mixed venous blood)

• CO2 is the most soluble, O2 is about 1/20th as soluble and N2 is barely soluble at atmospheric pressure

Question 6

Discuss alveolar gas composition

Answer 6

• Alveolar air is warmed and humidified

• Nitrogen (PN2): 78.09% x (760 – 47) mmHg = 556.78 mmHg
• Oxygen (PO2): 20.95% x (760 – 47) mmHg = 149.37 mmHg
• Carbon dioxide (PCO2): 0.030% x (760 – 47) mmHg = 0.21 mmHg
• Argon (P ): 0.930% x (760 – 47) mmHg = 6.63 mmHg

• O2 in lungs is actually lower (104 mmHg), CO2 is higher (40 mmHg) and water vapour is higher (as a consequence of this N2 is lower)
• Why?
– alveolar air is made up of ‘fresh air’ plus the air that remains in the lungs after the last breath

Question 7

Discuss gas exchange between alveolar and blood

Answer 7

• O2 has to:
– dissolve in an aqueous layer
– diffuse across the membranes
– enter the blood

Flow = (∆P x A x D) / T

• Rate of diffusion is proportional to
– Partial pressure difference (∆P)
– Surface area (A)
– Solubility (D, diffusion coefficient)
– molecular mass (D, diffusion coefficient)
– Inversely proportional to tissue thickness (T)

• Surface area of lungs is large 50 -100 m2
• Large number of alveoli (~500 million)
• Thickness is small (0.2 – 0.5 μm)
• Concentration gradient is large
– PO2 alveolar air is 100 mmHg
– PO2 of venous blood is 40 mmHg, so diffusion rapid
• Molecular mass insignificant, but solubility very important, with CO2 diffusing 20 x more rapidly than O2
• At rest, takes about 0.75 - 1 second for blood to pass through pulmonary capillaries
• O2 equilibrium only takes about 0.25 s (so not normally diffusion-limited)
• In exercise, capillary transit time can be reduced to as little as 0.3 s (so now diffusion-limited)

• CO2 moves in the other direction, from blood capillary into alveoli
• Smaller concentration gradient
– alveolar PCO2 is 40 mmHg
– venous PCO2 is 45 mmHg
• However, greater solubility, so CO2 diffusing 20 x more rapidly than O2
• Same amount of gas moves

Question 8

Discuss diffusion limitations of gas exchange

Answer 8

• Flow = (∆P x A x D) / T

• In oedema, T (thickness of barrier) increases
• Transit time through capillary may not be sufficient to complete full gas exchange
– gas exchange reduced
– More marked effect on O2 than CO2, due to greater solubility of CO2
• In emphysema, A reduced (breakdown of tissue and alveolar sacs)
– Gas exchange reduced
• In pulmonary fibrosis, T increased (deposition of fibrotic tissue) – Gas exchange reduced
• Mucus, inflammation of airway, tumours, reduce gas entry – Gas exchange reduced

Question 9

Discuss the impact of altitude on ventilation

Answer 9

• At altitude, atmospheric pressure is reduced
• Hence, PO2 is reduced

• Denver, Colorado, 1620m (5300 ft)
above sea level
– PB is 632 mmHg (down from 760 mmHg)
– Inspired PO2 – 125 mmHg (down from 149 mmHg)
– Alveolar PO2 – 84 mmHg (down from 104 mmHg)
– Alveolar PCO2 – 34 mmHg (down from 40 mmHg)

Question 10

Discuss physiological adaptations to altitude

Answer 10

• Acute
– Hypoxia sensed by peripheral
chemoreceptors
– Ventilatory drive increases initially but blunted by central chemoreceptors that respond to decreased PaCO2 due to increased ventilation
– CO increases due to suppression of cardioinhibitory centre

• Adaptive
– Central chemoreceptors adapt so
ventilation rate continues to increase
– PaCO2 drops leading to respiratory alkalosis, kidneys compensate by reducing acid excretion blood pH normalises
– Alkalosis stimulates 2,3 DPG production – leads to rightward shift of O2 dissociation curve

• Acclimation
– Blood
– Erythropoietin release stimulated
– Hb conc. increases to 200 g/L from 150 g/L
– Vasculature
– Hypoxia stimulates angiogenesis
– Capillary density increases throughout body
– Cardiopulmonary system
– Vascular and ventricular remodelling
– Smooth muscle growth increase vascular wall thickness
– Right ventricle hypertrophies

Question 11

Discuss diving and ventilation

Answer 11

Atmospheric pressure increases by 760 mmHg (1 atmosphere) every 10 m depth
Effects of Depth
– Increase in partial pressure, N2 and O2 dissolve into blood at lethal excess
– Volume decrease

Gas toxicity
– N2 narcosis – partial pressure of N2 (40m and below) rises and starts to dissolve in body tissues
– O2 poisoning – again tightly regulated at sea level and system essentially saturated
– At high pressure O2 dissolves in blood in excess of the buffering capacity of Hb
– Heliox – N2 replaced by helium and percentage of O2 tailored to reduce harm
– He less readily dissolves in body tissues and less narcotic.

Question 12

Summary

Answer 12

• O2 and CO2 exchange occurs by diffusion , driven by partial pressures gradients for both gases
• O2 has limited water solubility
• CO2 is 20 x more soluble than O2 in blood
• Atmospheric pressure decreases with altitude above sea level
• PO2 also decreases causing hypoxia
• Diving increases partial pressure of inspired gases
• O2 and N2 become potentially toxic as dissolve into tissues at depth