1. Dr. Thomas Hillen: Please sit on your hands for the next thirty minutes. We’ll take you out for coffee later if you listen

2. A Carbon Dioxide Driven Model for the Alveolar Lung PIMS Summer School May 14, 2004 James Bailey Appalachian State University Sean Laverty Millersville University

3. Problem Statement Build a simple model of the breathing process, describing the concentration of oxygen within the lung during regular breathing. Consider the following: -Different breathing mechanisms -Environmental conditions -Presence of toxic chemicals

4. Biological Background Discussion of: Respiration and Circulation Constraints on Systems Ventilation

5. Respiration and Circulation Respiration – Function: To provide oxygen [O 2 ] to the blood and remove excess carbon dioxide [CO 2 ] from the blood Circulation – Function: A system responsible for transporting materials throughout the body via blood and respiratory pigments

6. Constraints of diffusion Diffusion is extremely slow! While it works for unicellular organisms, it does not provide sufficient O 2 to larger organisms A breath-taking example: A one centimeter organism with a 100ml O 2 /kg/hr demand [less than half that of a resting human] would need an atmospheric pressure of 25 atms to rely on diffusion

7. Ventilation The process beginning with the movement of atmospheric air into the alveoli, where gas exchange occurs, and the expulsion of the air from the body To depend on gas exchange by diffusion, the human lung contains roughly 300 million individual alveoli with a total surface area of nearly seventy square meters

8. Capillary-Alveolar Transport The flow of gas by diffusion depends on: -the diffusion coefficient – which itself depends on the size and solubility of the gas molecules -the alveolar surface area through which diffusion occurs -the length of the path to the alveoli -the partial pressure gradient across the membrane.

9. Properties of Capillary Diffusion Where: - A is the capillary cross-sectional area - L is the capillary length - v is the blood velocity - u is the gas concentration - p is the capillary surface area - q(x,t) is the flux per unit area across the capillary wall - Q is the total flux across the capillary wall - σ is the solubility of the gas in blood - P gi is the partial pressure of the gas in its respective location - D s is the diffusion coefficient of the gas

10. The Gas Exchange Model: [The Mackey-Glass Equation] Where: - x is the partial pressure of blood CO 2 - λ is the rate of production of CO 2 - α assumes that change in x varies linearly with the concentration -V’ is the ventilation rate described by the Hill equation

11. The Hill Equation Where: - V m is the maximum tidal volume per breath - θ influences the rate of breathing - n influences the maximum CO 2 level

12. The Oxygen Concentration Equation: [The Bailey-Laverty Equation] Where: - P bO 2 is the partial pressure of blood O 2 -P iO 2 is the partial pressure of inspired O 2

13. Ventilation-Perfusion Ratio: For Hypo- and Hyperventilation R relates the volume of CO 2 eliminated from the blood to the oxygen uptake through the lungs, and is equal to V’/Q as defined above

14. Hold your breath, we’re almost there...

15. Figures to Follow Rapid Breathing -Blood Level Carbon Dioxide -Blood Level Oxygen Blood Level Gases with Increasing Metabolic Rate -Carbon Dioxide -Oxygen Blood Level Oxygen with Increasing Altitude -With No Exertion -With Exertion Presence of Environmental Toxins

24. Suggestions for Further Study Incorporate complexities which arise from the branching structure of the lung - Our model assumes that the flow of the gas through the lung, and the flow of blood through capillary mesh surrounding the alveoli are both constant - The model should incorporate pulmonary branch diameters, branching angles, and gravitational angles and the corresponding effects on the flow and distribution of gas

26. Suggestions for Further Study Incorporate complexities which arise from environmental variations - This model ignores variations in partial pressures of inspired inert gases - The model ignores changes in humidity of inspired air -The model ignores molecular mass and atomic structure of inspired gases and the effects on deposition

27. Acknowledgements Project Advisor - Dr. Thomas Hillen PIMS Participant Professors Laboratory Assistants Keener and Sneyd PIMS Participant Students