L5 Gas exchange (in Alveoli and Tissues) and Transport

Gas exchange diagram

Lung perfused with Blood Prior to fixation - reveals capillaries

Air/Blood barrier

How do we make things move?

• Apply force

• Forces acting on gas molecules come from atmospheric pressure and heat

• If a force is greater than resistance, the object will move.

Partial pressure

• Atmospheric (Aka Barometric) pressure at sea level + 760mmHg

• O2 = 21%
  CO2 = 0.04%
  N = 78.96%
  PO2 = 760 * 0.21 = 159.6 mmHg
  PCO2 = 760 * 0.0004 = 0.3 mmHg
  PN2 = 760 × 0.7896 = 600.1 mmHg

What else other than gas is present in the air in your lungs?

• Water vapour pressure

  • In any gas mix in direct contact with water (or other aqueous solution) there is water vapour present i.e. water in gaseous form.

  • The max partial pressure of water is a function of temperature alone.

    • At 37*C PH20 = 47 mmHg

Effect of water vapour on partial pressures

PH2O is a constant at body temperature (37*C) and equal to 47 mmHg, thus in a mixture of gases saturated with water vapour

• PO2 = (P_B -- 47) * FO2

Therefore for room air humidified during inspiration

PO2 = (760 - 47) * 0,21 = 149.7 mmHg

Gas exchange in Lungs

Oxygen partial pressure gradient drives oxygen from the alveolar air into the blood.

Oxygen diffuses through alveolar wall into blood

• Rate of diffusion is related to:

  • Surface area

  • Pressure gradient

  • Solubility

  • Thickness of barrier

Fick’s law (rate of diffusion)

• There is a capillary there but no shown in diagram

• A = Area

  D = Diffusion constant
  P1-P2 = pressure difference
  T = thickness of membrane

Ventilation (V) - Perfusion (Q) matching

• Air coming in is 150

• Going down to Alveoli

• O2 is 102 and CO2 is 40

  → time to search it up in YT

O2 transport in Blood

1. Dissolved in physical solution

2. Bound to Haemoglobin (Hb)

Partial pressure of a Gas in a liquid

• Exposure of liquid to air gas dissolves in solution

• Equilibrium established when rate of entry of gas molecules into solution equal rate of exit

• Partial pressure of gas in liquid is then equal to that in the aur with which is in equilibrium.

• Total amount of Gas in solution depends on solubility of Gas in solution.

Gases in solution (Henry’s law)

• The amount of gas dissolved in a solution is directly proportional to the partial pressure of the gas in the solution

• Conc gas = S * Pgas

• Where S is constant indicating the solubility of the gas in the solution (solubility coefficient).

• S differs markedly between gases.

Partial pressure of oxygen in the lung

Atmomspheric PO2 = 160mmHg

Trachea/Bronchus/Bronchioles

• Add heat (gas expands)

• Add humidity (gas diluted)

• Some oxygen consumed by Epithelial cells

• Alveolar PO2(P_Alv) approx. 100mmHg

Dissolved O2

• Amount of O2 that can dissolve in blood is proportional to the PO2 (Henrys Law)

  • -0.003ml O2/100mL blood for each mmHg PO2

• At normal P_art O2 of 100mnnHg

  • -3ml O2/litre of blood

• At rest

  • cardiac output of 5 L/min

  • total O2 delivered to tissue 15 ml/min

  • However resting tissue O2 consumption is approximately 250 ml/min

• During exercise

  • Cardiac output of 30L/min

  • Total O2 delivered to tissue 90 ml/min

  • However exercising tissue O2 consumption is approx 3000 ml/min

Haemoglobin

• Haem is an iron-porphyrin compound

• Joined to the protein globin

• A tetramer consisting of 4 polypeptide chains

  • two alpha and two beta polypeptide chains

  • four haem groups, each bound to an alpha or beta

• Each haem group contains a porphyrin ring and a ferrous atom (Fe++) which can bind reversibly with one O2.

• In deoxyHB, globin chains are tightly bound (electrostatic bonds) in a tense conformation (T) relatively low affinity for O2

• Binding of O2 breaks these bonds, exposes remaining O2 binding sites leading to a relaxed conformation (R)

• R conformation has an affinity for O2 which is approximately 500 times that of T conformation

Oxygen capacity

Max amount of O2 that can be combined with the Hb is called the O2 capacity

• 1.39ml O2/g Hb

• 15g of Hb/100ml normal blood

• O2 capacity is about (15×1.49)

• 20.8ml O2/100ml b

O2 delivery - normal resting state

• Consider normal Hb15g/100ml blood, then arterial concentration of O2.

  (1.39 × 15) + 0.003*PO2

• Giving 20.853ml O2/100ml blood

• At normal cardiac output of 5 L/min, this gives O2 delivery to the tissues of approximately 1042 ml/min

• Resting tissue O2 requirement approximately 250 ml/min

• Large reserve

The problem of ‘‘designing’’ Hb

• In the lung a molecule with a very high affinity for O2 is best to ensure maximum O2 loading

• But in the tissues optimum molecule has a low affinity for O2 to allow maximum unloading

• Make a molecule that change its behaviour

Oxygen Dissociation Curve

• O2 forms an easily reversible combination with haemoglobin in RBC

  O2 + Hb → ← HbO2

Advantages of O2 dissociation curve

• Flat upper portion

  • Even if PO2 in alveolar gas falls, loading of O2 not greatly affected

• Steep lower portion

  • Peripheral tissues can withdraw large amounts of O2 for only a small drop in capillary PO2

  • Maintenance of blood PO2 assists diffusion of O2 into tissue cell

Going from a high to low concentration of O2 is what’s happening in the diagram.

O2 unloading tissues

• In tissues O2, unloading from Hb promoted by

  • decreased PO2

  • increased diphosphoglycerate (DPG) in RBC → by-product of metabolism

  • increased PCO2

  • increased H+

  • increased temperature

    • Denatures bond between Hb and O2

  When compared to the alveoli i.e. more unloading of O2 at a give PO2

• These conditions exemplified by exercising muscle

Co2 transport in Blood

• CO2 transported in three forms

  • Dissolved CO2

  • HCO3

  • In combination with proteins as Carbamino compounds

Dissolved CO2

• CO2 in solution according to Henry’s law

• Solubility coefficient for O2 is 0.00314

• Solubility coefficient for CO2 is 0.0746

• CO2 is approximately 24 times more soluble than O2

• 10% of CO2 excreted in the lung is carried in mixed venous blood in dissolved form.

CO2 as Bicarbonate

• More acidic if you hold your breath…

CO2 transported as Bicarbonate

• First reaction is very slow in plasm but rapid when catalysed by carbonic anhydrase (CA) in RBC

• Endothelium of pulmonary circulation has CA

• Dissociation of H2CO3 is rapid in the absence of enzyme

• 60% of CO2 excreted in the lung carried in mixed venous blood as HCO3

CO2 as Carbamino Compounds

• Blood proteins that bind CO2 are called carbamino compounds

• Globin portion of Hb most important protein (>95% of protein in RBC)

• Many CO2 molecules can bind to a single Hb molecule

• Hb.NH2 + CO2 ←→ Hb.NHCOOH

• Reversibly produces carbaminohaemoglobin

• Rapid reaction in the absence of enzyme

• 30% of CO2 excreted in the lung carried in mixed venous blood as carbamino form

Forms in which CO2 transported

In arterial blood

• 5% carried as dissolved CO2

• 90% carried as HCO3

• 5% carried as carbamino

Of the CO2 that is excreted into lung

• 10% carried as dissolved CO2

• 60% carried as HCO2

• 30% carried as carbamino

Hb-O2 Dissociation Curve

• Amount of O2 carried by increases rapidly up to about 50mmHg

• Curve becomes flatter after that

Summary of Effects in Tissues

Summary of Effects in Lungs