Gas Exchange and Transport

Site of gas exchange

• Respiratory membrane

Thickness of respiratory membrane

• 0.5 um

Respiratory membrane

• Large total surface area for exchange → 300 million alveoli

Respiratory membrane includes

• Alveolar epithelium

• Basement membrane

• Capillary endothelium

• Fluid (air-water interface)

Both carbon dioxide and oxygen are…

which lets them pass easily through what

• Lipid soluble which allows them to pass easily through both surfactant and plasma membranes

Diffusion across blood air barrier

• Diffusion of gases to/from alveolar air to/from capillary plasma

Diffusion of gas across an exchange surface is proportional to…

• Surface area

• Pressure gradient (P1-P2)

• Solubility of gas in water

Diffusion of gas across an exchange surface is inversely proportional to …

• Thickness of exchange surface

Carbon dioxide and oxygen → diffusion

• Carbon dioxide has a rate of diffusion 20 times greater than oxygen because it is much more soluble than oxygen

Dalton’s Law

• The total pressure of a mixture of gases is equal to the sum of the partial pressures (P_x) of the individual gases

P_x

• Partial pressure of gas x

• P_x = Atmospheric pressure X fractional concentration of x in the gas mixture

• P_x = P_atm X Fl_x

Composition of ambient air

• Nitrogen

  • Fraction in air % → 78

  • Partial pressure → 593

• Oxygen

  • Fraction in air % → 21

  • Partial pressure → 159

• Carbon dioxide

  • Fraction in air % → 0.03

  • Partial pressure → 0.23

• Argon

  • Fraction in air % → 0.93

  • Partial pressure → 7

• Water

  • Fraction in air % → 0

  • Partial pressure → 0

Henry’s Law

• Amount of gas dissolved in a liquid is proportional to the partial pressure of that gas

• An increase in P_x = An increase amount of x in liquid

• Not all gases are equally soluble in all liquids (CO₂ very soluble in body fluids - N₂ low solubility)

• The concentration of a gas in solution is equal to its partial pressure multiplied by its solubility in the solution

Example of Henry’s Law:

Oxygen P_O2 = 100 mmHg

Solubility coefficient = 0.003 mL O2/100 mL plasma/mmHg

• Concentration of dissolved oxygen is 0.3 mL/100 mL plasma

Composition of tracheal air

• Conducting zone: warm and humidify incoming air

• Warmed to body temperature: 37 degrees C

  • P_H2O = 47 mmHg

• P_x = (atm pressure - water vapor pressure) X fractional concentration of gas x

• P_x = (P_atm - P_H2O) X Flx

• For carbon dioxide it is assumed that the amount of inspired CO₂ is negligible

Oxygen partial pressure → composition of tracheal air

• P_O2 = (760 mmHg - 47 mmHg) X 0.21 = 150 mmHg

• The new partial pressure decreased through humidifying

Composition of alveolar air

• P_O2 of alveolar air decreases and P_CO2 of alveolar air increased (compared to tracheal air) due to mixing of inspired air with leftover air containing carbon dioxide

• Amount of Co2 inhaled is NEGLIGIBLE

O2 → 160-150-100 mmHg

CO2 → 40 mmHg

External respiration → alveoli

• Exchange at respiratory membrane:

  • Oxygen moves down its gradient FROM alveolus into plasma

  • Carbon dioxide moves down its gradient FROM plasma into alveolus

• P_a O₂ = 40 mmHg → P_v O₂ = 100 mmHg

• P_a CO₂ = 45 mmHg → P_v CO₂ = 40 mmHg

• a = arterial blood

• v = venous blood

External respiration → alveoli regulation of respiration

• Blood flow directed to alveoli with higher P_O2 (capillaries constrict when P_O2 is low)

Internal respiration → tissues

• Oxygenated blood delivered to tissues (internal respiration of cells consumes O₂ and produces CO₂)

  • Carbon dioxide moves down its gradient FROM tissues into blood

  • Oxygen moves down its gradient FROM blood into tissues

• P_a O₂ = 95 (basically 100) mmHg → P_v O₂ = 40 mmHg

• P_a CO₂ = 40 mmHg → P_v CO₂ = 45 mmHg

Internal respiration → tissue regulation of respiration

• When tissue is active:

  • Interstitial P_O2 falls, interstitial P_CO2 rises

    • Increases the difference in partial pressure between tissue and arriving blood

    • Increases rate of diffusion

Gas transport in the blood

• Diffusion moves O₂ from the alveoli to plasma (liquid) and CO₂ from plasma to alveoli

• Limited solubility of both O₂ and CO₂

• Peripheral tissues need more O₂ and generate more CO₂ than plasma alone can absorb and transport

• CO₂ is transported via three different mechanisms

• O₂ is transported primarily by RBCs (small amount in plasma)

• RBCs remove gases from the plasma - diffusion continues

Carbon dioxide in the blood

• Physically dissolved in the plasma

  • Approximately 7% of CO₂ in blood

• Bound to hemoglobin (carbamino -hemoglobin): bound to amino groups o hemoglobin molecule

  • Approximately 23% of CO₂ in blood

• Chemically modified in the form of carbon acid

  • Approximately 70% of total CO₂ in blood

Reaction with H₂O and CO₂ and the enzyme

• This reaction is greatly accelerated by the carbonic anhydrase (CA), an enzyme present in most cells and abundant in red blood cells

Carbon dioxide exchange in tissues

• Plasma P_CO2 = 40 mmHg

• Tissue P_CO2 = 45 mmHg

• Carbon dioxide diffuses into capillary down its partial pressure gradient

• Absorbed by RBCs

• Carbaminohemoglobin (23%)

• Converted to carbonic acid (70%)

• Bicarbonate is moved into the plasma in exchange for chloride

Carbon dioxide exchange in the lung

• Alveoli P_CO2 = 40 mmHg

• Blood P_CO2 = 45 mmHg

• Carbon dioxide diffuses into alveolus down its partial pressure gradient from plasma

• RBCs release CO₂ (from two sources)

• Released from hemoglobin

• Bicarbonate moves into RBCs (chloride exchange)

• Carbonic acid converted back into CO₂

Oxygen in the blood

• Physically dissolved in the plasma

  • Approximately 2% of total oxygen in blood

  • Responsible for the partial pressure of oxygen in the blood

  • Poor solubility in plasma - inadequate to meet body’s needs

• Bound to heme group of hemoglobin

  • 98% of total oxygen in blood

  • Oxyhemoglobin

  • Does not contribute to the partial pressure of oxygen

  • Each Hb molecule has 4 heme groups and therefore can carry 4 oxygen molecules

% oxygen saturation

• % saturation of hemoglobin molecules with oxygen

• Ex: 50% saturation → 50% of heme sites occupied with oxygen

Oxygen delivery in the lungs

• Alveoli P_O2 = 100 mmHg

• Blood P_O2 = 40 mmHg

Oxygen delivery in the tissues

• Blood P_O2 = 100 mmHg

• Tissue P_O2 = 40 mmHg

Loading of oxygen on Hb helps…

• Maintain the pressure gradient for oxygen (by maintaining P_O2 in plasma)

Oxyhemoglobin - dissociation curve

• As (plasma) P_O2 rises, % saturation of hemoglobin increases

• Sigmoidal shape: cooperative binding

  • More O₂ attached, more likely for another O₂ to bind

• Oxygen loading onto one heme site facilitates loading of oxygen on remaining heme sites

Regions of oxyhemoglobin-dissociation curve

• Plateau region: oxygen loading → this is at the PO2 encountered at the lungs

• Steep region: oxygen unloading → this is at a PO2 encountered at the tissues

P50

• Pressure at which hemoglobin molecules are half saturated with oxygen

• Measure of the affinity of hemoglobin for oxygen

A higher P50 reflects…

• A decrease in affinity for hemoglobin

• Right shift

A lower P50 reflects…

• An increase in affinity for hemoglobin

• Left shift

Bohr effect

• Changes in pH shifts the curve (normal blood pH: 7.4)

• Increase in pH: shifts the curve to the left

  • P50 decreases

  • Affinity of O2 for hemoglobin increases

• Decrease in pH: shifts the curve to the right

  • P50 increases

  • Affinity of O2 for hemoglobin decreases

• Increased CO2 will increase H+ and therefore lower pH which shifts curve. H+ binds to hemoglobin which decreases the affinity of hemoglobin for oxygen

• Increased CO2 will also shift curve to right independent of pH change. Increased formation of carbaminohemoglobin which decreases affinity of hemoglobin for oxygen

Temperature - oxygen-hemoglobin curve

• Increases in temperature shifts curve to the right

• Decreases in temperature shifts curve to the left

Carbon monoxide

• Outcompetes oxygen for the heme binding sites of hemoglobin

  • 250 times greater affinity for hemoglobin than oxygen

• Carbon monoxide also shifts the oxyhemoglobin dissociation curve to the left

  • Heme groups not bound to CO will have an increased affinity for oxygen and will not give up oxygen as easily to the tissues