Gas Exchange Principles

Principles of Gas Exchange

• Gas exchange in the lungs happens via diffusion.
• Oxygen moves from alveoli to pulmonary blood.
• Carbon dioxide moves from blood to alveoli.

Partial Pressures of Gases

• The pressure exerted by a single gas in a gas mixture.
• Partial pressures are labeled as PO2, PCO2, PN2, etc.

Factors Affecting Partial Pressure

• Gas concentration.
• Gas solubility coefficient.

Henry's Law

• Describes the relationship between partial pressure, concentration, and solubility:
• Partial pressure equals the concentration of dissolved gas divided by the solubility coefficient.

Solubility Coefficients

• CO2: 0.57
• O2: 0.024
• CO: 0.018
• N2: 0.012
• He: 0.008

Diffusion of Gases

• Net diffusion goes from high to low partial pressure areas.
• Diffusion rate links to partial pressure difference.

Factors Affecting Net Rate of Diffusion

• Gas solubility.
• Cross-sectional area.
• Diffusion distance.
• Molecular weight of the gas.
• Temperature (usually constant in the body).

Vapor Pressure of Water

• At 37°C, it's 47 mm Hg.
• Important for calculating partial pressures of gases in humidified air.

Quantifying Net Rate of Diffusion

• Proportional to partial pressure difference.
• Affected by solubility, area, distance, and molecular weight.

Composition of Alveolar Air vs. Atmospheric Air

• Alveolar air differs due to:
  • Partial replacement by atmospheric air.
  • Oxygen absorption into blood.
  • Carbon dioxide diffusion into alveoli.
  • Humidification.

Humidification of Air

• Water vapor partial pressure at 37°C is 47 mm Hg.
• Dilutes oxygen partial pressure from 159 mm Hg to 149 mm Hg.
• Dilutes nitrogen partial pressure from 597 mm Hg to 563 mm Hg.

Alveolar Air Renewal

• Slowly renewed, about 1/7 replaced per breath.
• This slow rate prevents sudden blood gas concentration changes.

Oxygen Concentration and Partial Pressure in the Alveoli

• Controlled by:
  • Oxygen absorption rate into the blood.
  • New oxygen entry rate by ventilation.
• Alveolar PO2 maintained at 104 mm Hg through ventilation adjustment.

Effect of Alveolar Ventilation on Alveolar PO2

• Increased ventilation can increase alveolar PO2, up to 149 mm Hg with normal air at sea level.
• Higher oxygen partial pressure gases can further increase alveolar PO2.

CO2 Concentration and Partial Pressure in the Alveoli

• Carbon dioxide is constantly produced and carried to alveoli.
• Alveolar PCO2 rises with CO2 excretion and falls with alveolar ventilation.

Effects of Alveolar Ventilation and CO2 Excretion

• Normal values:
  • Alveolar ventilation: 4.2 L/min.
  • CO2 excretion: 200 ml/min.
• Under these conditions, alveolar PCO2 is 40 mm Hg.

Expired Air

• Combination of dead space air and alveolar air.
• Determined by dead space air and alveolar air amounts.
• The last portion of expired air is alveolar air.

Diffusion of Gases Through the Respiratory Membrane

• The respiratory unit includes respiratory bronchioles, alveolar ducts, atria, and alveoli.
• Respiratory membrane layers:
  • Alveolar epithelium.
  • Epithelial basement membrane.
  • Interstitial space.
  • Capillary basement membrane.
  • Capillary endothelial membrane.
• It is thin (0.2-0.6 micrometers) with a large surface area (about 70 square meters).

Structure of the Respiratory Membrane

• A layer of fluid with surfactant.
• Alveolar epithelium.
• Epithelial basement membrane.
• Interstitial space.
• Capillary basement membrane.
• Capillary endothelial membrane.

Importance of Respiratory Membrane Structure

• Thinness and large surface area for rapid gas diffusion.
• Gases are in close proximity to blood in pulmonary capillaries, easing gas exchange.

Factors Affecting Gas Diffusion Through the Respiratory Membrane

• Membrane thickness: Increased can impede gas exchange.
• Membrane surface area: Decreased area can reduce gas exchange.
• Diffusion coefficient of the gas: Solubility and molecular weight matter.
• Partial pressure difference drives gas exchange.

Diffusion Coefficient

• CO2 diffuses 20x faster than O2 due to greater solubility.
• O2 diffuses 2x faster than nitrogen.

Partial Pressure Difference

• Determines net direction and rate.
• Higher partial pressure in alveoli pushes gas into the blood.

Diffusing Capacity of the Respiratory Membrane

• Volume of gas diffusing per minute per mm Hg partial pressure difference.
• For O2, it's 21 ml/min/mm Hg at rest, 65 ml/min/mm Hg during exercise.

Increased Oxygen Diffusing Capacity During Exercise

• Due to opened dormant capillaries increasing surface area.
• Better ventilation-perfusion matching.

Ventilation-Perfusion Ratio (VA/Q)

• Measures alveolar ventilation relative to blood flow.
• Normal VA/Q is essential for efficient gas exchange.
• Abnormal VA/Q leads to impaired gas exchange and respiratory distress.

Effects of Abnormal VA/Q Ratios

• VA/Q = 0 (no ventilation): alveolar gas pressures equilibrate with venous blood.
• VA/Q = infinity (no blood flow): alveolar gas pressures equal inspired air.
• Abnormal VA/Q causes physiological shunt (VA/Q < normal) or dead space (VA/Q > normal).

Physiological Shunt and Dead Space

• Shunt: blood flows through poorly ventilated alveoli, causing inadequate oxygenation.
• Dead space: ventilation exceeds blood flow, causing wasted ventilation.
• Both decrease gas exchange effectiveness.

Abnormalities in VA/Q in Lung Disease

• COPD causes abnormal VA/Q leading to impaired gas exchange.
• COPD presents physiological shunt and dead space.

Transport of Oxygen from the Lungs to the Body Tissues

• Oxygen diffuses into pulmonary capillary blood because alveolar PO2 (104 mm Hg) exceeds venous blood PO2 (40 mm Hg).
• Blood PO2 quickly rises and becomes saturated with O2.

Uptake of Oxygen by the Pulmonary Blood during Exercise

• Increased cardiac output needs more oxygen.
• Blood can still fully oxygenate due to increased diffusing capacity, even with less time in capillaries.

Transport of Oxygen in the Arterial Blood

• 98% of blood to left atrium is oxygenated, 2% bypasses gas exchange (shunt flow).
• Blood PO2 entering left heart/aorta is around 95 mm Hg.

Diffusion of Oxygen from the Peripheral Capillaries into the Tissue Fluid

• Oxygen diffuses into tissues as capillary blood PO2 (95 mm Hg) exceeds interstitial fluid PO2 (40 mm Hg).
• Blood PO2 leaving tissue capillaries/entering systemic veins is around 40 mm Hg.

Factors Affecting Interstitial Fluid PO2

• Increased blood flow raises PO2.
• Increased tissue metabolism lowers PO2.

Diffusion of Oxygen from the Peripheral Capillaries to the Tissue Cells

• Oxygen moves from capillaries to tissue cells.
• Intracellular PO2 ranges from 5-40 mm Hg (average 23 mm Hg).

Diffusion of Carbon Dioxide

• Carbon dioxide moves from tissue cells into capillaries, then from pulmonary capillaries into alveoli.
• CO2 diffuses 20x faster than O2.
• CO2 diffusion requires smaller pressure differences than O2.

PCO2 Pressures

• Intracellular: 46 mm Hg; interstitial: 45 mm Hg.
• Arterial blood entering tissues: 40 mm Hg; venous blood leaving tissues: 45 mm Hg.
• Pulmonary capillary blood: 45 mm Hg; alveolar air: 40 mm Hg.

Factors Affecting Interstitial PCO2

• Decreased blood flow increases PCO2.
• Increased tissue metabolism increases PCO2.

Oxygen Binding with Hemoglobin

• 97% of O2 is transported bound to hemoglobin, the other 3% dissolves in plasma/blood cells.
• Oxygen binds in lungs and releases in tissues due to pressure changes.

Oxygen-Hemoglobin Dissociation Curve

• Shows the relationship between PO2 and hemoglobin saturation.
• Normal arterial blood PO2 is 95 mm Hg, with 97% hemoglobin saturation.
• Normal venous blood PO2 is 40 mm Hg, with 75% hemoglobin saturation.

Amount of Oxygen Released from Hemoglobin

• Normal conditions release 5 ml of O2 per 100 ml of blood flow.
• During exercise, this can increase to 15 ml per 100 ml of blood flow.

Utilization Coefficient

• Percentage of blood that releases O2 in tissue capillaries.
• Normal value is 25%, increasing to 75-85% during exercise.

Hemoglobin as a Tissue Oxygen Buffer

• Helps maintain constant PO2 in tissues (15-40 mm Hg).
• Allows a consistent O2 supply despite atmospheric changes.

Factors that Shift the Oxygen-Hemoglobin Dissociation Curve

• Changes in pH, CO2, temperature, and BPG.
• Right shift reduces affinity, left shift increases affinity.

Increased Delivery of Oxygen to Tissues

• Increased carbon dioxide and hydrogen ions shift the oxygen-hemoglobin dissociation curve to the right, this is called the Bohr effect.
• This shift enhances the release of oxygen from hemoglobin in the tissues.

Factors that Shift the Oxygen-Hemoglobin Dissociation Curve

• Increased CO2 concentration.
• Increased hydrogen ion concentration (decrease in pH).
• Increased temperature.
• Increased 2,3-biphosphoglycerate (BPG) concentration.

Effect of BPG on Oxygen Delivery

• BPG shifts the curve to the right, allowing for more oxygen released at higher PO2 levels.
• Elevated BPG helps adjust to hypoxia, especially with poor tissue blood flow.

Effect of Exercise on Oxygen Delivery

• During exercise, more CO2, hydrogen ions, and temperature shift the curve to the right.
• This shift allows for increased oxygen delivery to muscle fibers.

Metabolic Use of Oxygen by Cells

• Intracellular PO2 required for normal cellular metabolism is very low (above 1 mm Hg).
• Oxygen usage rate is managed by ADP concentration in the cells.
• Oxygen delivery can be limited by diffusion and blood flow.

Transport of Oxygen in the Dissolved State

• A small portion of oxygen is transported in the dissolved state (about 3% of total oxygen transported).
• During strenuous exercise, the relative quantity of oxygen transported in the dissolved state decreases.

Combination of Hemoglobin with Carbon Monoxide

• Carbon monoxide (CO) binds to hemoglobin with high affinity, displacing oxygen and reducing oxygen delivery to tissues.
• CO poisoning can be lethal due to its high affinity for hemoglobin and lack of obvious signs of hypoxemia.

Transport of Carbon Dioxide in the Blood

• Carbon dioxide (CO2) is transported in the blood mainly in the form of bicarbonate ions (HCO3-), which accounts for about 70% of CO2 transport.
• CO2 is transported in the blood in several forms, including dissolved CO2, bicarbonate ions, and carbaminohemoglobin.
• CO2 transport is essential for maintaining acid-base balance in the body fluids.

Transport of Carbon Dioxide in the Form of Bicarbonate Ion

• Carbon dioxide (CO2) is transported in the blood mainly in the form of bicarbonate ions (HCO3-), which accounts for about 70% of CO2 transport.
• CO2 reacts with water to form carbonic acid (H2CO3), catalyzed by the enzyme carbonic anhydrase.
• CO2 + H2O → H2CO3 (carbonic acid) then H2CO3 → H+ (hydrogen ions) + HCO3- (bicarbonate ions)

Role of Carbonic Anhydrase

• Carbonic anhydrase accelerates the reaction between CO2 and water, allowing for rapid formation of bicarbonate ions.
• Inhibition of carbonic anhydrase (e.g., by acetazolamide) impairs CO2 transport.

Transport of CO2 in Combination with Hemoglobin and Plasma Proteins

• CO2 also reacts with hemoglobin and plasma proteins to form carbaminohemoglobin (CO2Hgb).
• This reaction accounts for about 20-30% of CO2 transport.

Carbon Dioxide Dissociation Curve

• The curve depicts the relationship between blood CO2 content and PCO2.
• The normal blood PCO2 range is between 40 mm Hg (arterial) and 45 mm Hg (venous).

Haldane Effect

• Binding of oxygen to hemoglobin displaces CO2 from the blood, increasing CO2 transport.
• The Haldane effect results from the increased acidity of hemoglobin when oxygen binds, which displaces CO2 from carbaminohemoglobin and bicarbonate ions.

Respiratory Exchange Ratio

• The ratio of CO2 output to O2 uptake is called the respiratory exchange ratio (R).
• R varies depending on metabolic conditions, with a normal value of around 0.825 for a person on a balanced diet.