The Respiratory System

1. The Respiratory System Gas Exchange

2. Behavior of Gases • PV = nRT • Where P = pressure • V= volume • n = the number of moles of gas • R = the universal gas constant (22.4 liters/mole deg. Atm) • T = temperature in deg. Kelvin

3. Partial Pressure • The total pressure of a gas mixture is the sum of the partial pressures of its constituents, so • The partial pressure of a single gas is determined by multiplying the % of that gas by the total pressure.

4. Gas composition of clean dry air at sea level (PT = 760 mmHg)

5. Water vapor is an important respiratory gas • As air passes through the airway, it is warmed and becomes saturated with water vapor • At 37o and 1 atm, the partial pressure of water vapor is 47 mmHg. • Addition of water vapor diminishes the partial pressures of all the other gases, compared to dry air

6. Gases in solution • In a gas-water equilibrium, the partial pressure of gas in solution becomes equal to the partial pressure of the gas in the gas phase, BUT • The concentration of gas in solution does not become equal to the concentration in the gas phase; instead, the concentration is determined by the partial pressure multiplied by the solubility coefficient and the temperature.

7. The solubility coefficients and diffusion coefficients of oxygen and carbon dioxide differ greatly • The solubility of CO2 in plasma at 37o is about 21X that of oxygen • The diffusion coefficient for CO2 in plasma at 37o is about 20X that of oxygen • These facts will have large implications for gas exchange in the lungs and gas transport in the blood

8. Gas compositions of alveolar air and pulmonary blood Systemic arterial blood – generally has equilibrated with alveolar gas Mixed systemic venous blood

9. Forms of gas in bloodstream

10. Oxygen transport

11. Oxygen transport by Hemoglobin (Hb) and Myoglobin (Mb) • Evolution of O2 transport proteins necessitated by the poor solubility of O2 in water • Hb is a tetramer composed (after birth) of two alpha globin chains and two beta globin chains = 4 binding O2 binding sites – the binding sites exhibit cooperativity • Mb is an intracellular transport protein composed of a single globin chain = 1 binding site, so no cooperativity

12. The Hb-O2 dissociation curve % saturation

13. Implications of the Hb-O2 dissociation curve • Hb is about 98% saturated at the PO2 of systemic arterial blood. • Normal variations in the PO2 of alveolar gas have little effect on the O2 content of arterial blood • On average, about ¼ of the total O2 carried by arterial blood is delivered to the tissues in each pass through the systemic loop. • Individual organs and tissues can extract more or less than ¼ of the oxygen, depending on their metabolic rate and other factors.

14. Five factors can modulate the amount of O2 unloaded • 1. the PO2 of the tissue itself • 2. increased temperature • 3. decreased pH (called the Bohr effect) • 4. increased PCO2 • 5. increased plasma levels of 2,3 diphosphoglycerate (2,3 DPG) • The last four factors act by shifting the rising part of the curve to the right, causing more O2 to be unloaded at any tissue PO2.

15. Right shifting the curve increases unloading, without affecting loading

16. The route for oxygen from lungs to mitochondria Alveolar gas diffusion Hemoglobin binding, convective transport in bloodstream Capillary RBCs diffusion Interstitial fluid diffusion Cytoplasm Facilitated diffusion (Mb) mitochondria

17. Carbon Dioxide Transport

18. Plasma CO2 exists in equilibrium with its other chemical forms • CO2+H2O H2CO3 H+ + HCO3- Carbonic anhydrase • Ka = [H+][HCO3-]/[H2CO3] = [H+][HCO3-]/[CO2][H2O]

19. Plasma pH is described by the Henderson-Hasselbalch equation • H-H eq describes the equilibrium state of the buffer system normal arterial value is 24 mEq/L • pH = 6.1 + log [HCO3-]/0.03PCO2 Solubility Coefficient of CO2 Normal arterial value is 40 mmHg pKa of H2CO3

20. Facts • The bicarbonate buffer system with a pKa of 6.1 is, from a chemist’s point of view, a crummy choice for an arterial plasma pH of 7.4 – but we never run out of the ingredients! • The buffer system is “open” – so plasma PCO2 is set by alveolar PCO2

21. CO2 transport by Hb • No transport protein is really needed for CO2,because it is so water-soluble – but to a limited extent, Hb is also a CO2 transport protein because of the formation of carbaminoHb. • CarbaminoHb has a lower affinity for O2 than Hb (remember, binding CO2 causes the Hb dissociation curve to shift to the right) – so when a RBC passes through a systemic capillary, formation of carbaminoHb forces additional O2 to be unloaded.

22. Hb buffering, carbonic anhydrase and the chloride shift facilitate CO2 loading • Hb is a buffer – but both deoxyHb and carbaminoHb are even better buffers than Hb • When CO2 diffuses into a RBC, it rapidly dissociates (catalyzed by carbonic anhydrase), releasing some H+, which is accepted by the Hb. • This leaves HCO3-, which would build up in the RBC and cause the process to grind to a halt, except for a process called the chloride shift, in which HCO3- is transported out of the RBC in exchange for Cl- by an anion exchanger in the plasma membrane.

23. CO2 unloading in pulmonary capillaries is the reverse of CO2 loading in pulmonary capillaries • Each RBC spends less than 1 second in a pulmonary capillary – so it is remarkable that gas equilibrium can be attained in so short a time. • Because of the short time scale, the carbonic anhydrase in RBCs is especially important for this process.