Gas Exchange Notes

NOTES NOTES GAS EXCHANGE GAS EXCHANGE & LAWS ▪ Diffusion of oxygen (O2), carbon dioxide (CO2) in lungs, peripheral tissues ▪ Alveolar O2 from inhaled gas → pulmonary capillary blood → circulation → tissue capillaries → cells ▪ CO2 from cells → tissue capillaries → circulation → pulmonary capillary blood → CO2 for exhalation from alveoli ▪ Gas exchange, gas behavior in solution is governed by fundamental physical gas properties → represented by gas laws FORMS OF GAS IN SOLUTION Dissolved gas ▪ All gas in solution are to some extent carried in a freely dissolved form ▪ For given partial pressure, the higher the solubility of a gas, the higher the concentration in solution ▪ In solution only dissolved gas molecules contribute to partial pressure ▪ Of the gases inspired as air, only nitrogen is exclusively carried in dissolved form Bound gas ▪ O2, CO2, CO are bound to proteins in blood ▪ O2, CO2, CO can all bind to hemoglobin ▪ CO2 also binds to plasma proteins Chemically modified gas ▪ The ready back and forth conversion of CO2 to bicarbonate (HCO3-) in presence of enzyme carbonic anhydrase allows CO2 to contribute to gas equilibria despite chemical conversion ▪ Majority of CO2 in blood carried as HCO3- IDEAL (GENERAL) GAS LAW osms.it/ideal-gas-law ▪ Relates multiple variables to describe state of a hypothetical “ideal gas” under various conditions ▫ Ideal gas: theoretical gas composed of many randomly moving point particles whose only interactions are perfectly elastic collisions ▫ All gas laws can be derived from general gas law ▪ PV = nRT ▫ P = Pressure (millimeters of mercury (mmHg) ▫ V = Volume (liters (L) ▫ n = Moles (mol) ▫ R = Gas constant (8.314 J/mol) ▫ T = Temperature (Kelvin [K]) ▪ In gas phase: body temperature, pressure (BTPS) used ▫ T = 37°C/98.6°F/310K ▫ P = Ambient pressure ▫ Gas is saturated with water vapor (47mmHg) ▪ In liquid phase/solution: standard temperature, pressure (STPD) used ▫ T = 0°C/32°F/273K ▫ P = 760mmHg ▫ Dry gas (no humidity) ▪ Ideal gas law can be used to interconvert between properties of same gas under BTPS, STPD conditions ▫ E.g. gas volume (V1) at BTPS → gas volume at STPD (V2) OSMOSIS.ORG 603

V2 = V1 × T1 P1 − Pw1 × T2 P2 − Pw2 V2 = V1 × 273 760 − 47 × 310 760 − 0 V2 = V1 × 0.826 BOYLE'S LAW osms.it/Boyles-law ▪ Describes how pressure of gas ↑ as container volume ↓ ▪ P1V1 = P2V2 ▪ For gas at given temperature, the product of pressure, volume is constant ▪ Inspiration → diaphragm contraction → ↑ lung volume ▪ If PV constant + lung volume ↑ → pressure ↓ ▪ Pressure ↓ → disequilibrium between room, lung air pressures → air fills lungs to equalize pressure DALTON'S LAW osms.it/Daltons-law ▪ Total pressure exerted by gaseous mixture = sum of all partial pressures of gases in mixture → partial pressure of gas in gaseous mixture = pressure exerted by that gas if it occupied total volume of container ▪ Px = PB x F ▫ Px = partial pressure of gas (mmHg) ▫ PB = barometric pressure (mmHg) ▫ F = fractional concentration of gas (no unit) ▪ Partial pressure = total pressure X fractional concentration of dry gas ▪ For humidified gases 604 OSMOSIS.ORG ▫ Px = (PB - PH2O) x F ▫ PH2O = Water vapor pressure at 37°C/98.6°F (47mmHg) ▫ If the sum of partial pressures in a mixture = total pressure of mixture → barometric pressure (PB) is sum of the partial pressures of O2, CO2, N2 (nitrogen), and H2O ▫ At barometric pressure (760 mmHg) composition of humidified air is O2, 21%; N2, 79%; CO2, 0% ▫ Within airways, air is humidified thus water vapor pressure is obligatory = to 47mmHg at 37°C/98.6°F

Chapter 70 Respiratory Physiology: Gas Exchange HENRY'S LAW osms.it/Henrys-law ▪ For concentrations of dissolved gases ▪ When gas is in contact with liquid → gas dissolves in proportion to its partial pressure → greater concentration of a particular gas, in gas phase → more dissolves into solution at faster rate ▫ Cx = Px x Solubility ▫ Cx = concentration of dissolved gas (mL gas / 100mL blood) ▫ Concentration of gas in solution only applies to dissolved gas that is free in solution ▫ Concentration of gas in solution does not include any gas that is presently bound to any other dissolved substances (e.g. plasma proteins/ hemoglobin) ▫ Px = partial pressure of gas (mmHg) ▫ Solubility = solubility of gas in blood (mL gas / 100mL blood per mmHg) ▪ Henry’s law governs gases dissolved within solution (e.g. O2, CO2 dissolved in blood) ▪ To calculate gas concentration in liquid phase ▫ Partial pressure of gas in gas phase → partial pressure in liquid phase → concentration in liquid ▫ Partial pressure of gas in liquid phase (at equilibrium) = partial pressure of gas in gaseous phase ▫ If alveolar air has PO2 of 100mmHg → PO2 of capillary blood that equilibrates with alveolar air = 100mmHg HYPERBARIC CHAMBERS ▪ Hyperbaric chambers employ Henry’s law ▫ Contain O2 gas pressurized to above 1 atm → greater than normal amounts of O2 forced into the blood of the enclosed individual ▫ Used to treat carbon monoxide poisoning, gas gangrene due to anaerobic organisms (cannot live in presence of high concentrations of O2), improve oxygenation of skin grafts, etc. FICK'S LAWS OF DIFFUSION osms.it/Ficks-law-of-diffusion ▪ Describes diffusion of gases Vx = DAΔP Δx ▫ Vx = volume of gas transferred per unit time ▫ D = gas diffusion coefficient ▫ A = surface area ▫ ΔP = partial pressure difference of gas ▫ Δx = membrane thickness ▪ Driving force of gas diffusion is difference in partial pressures of gas (ΔP) across membrane (not the concentration difference) ▫ If PO2 of alveolar air = 100mmHg ▫ PO2 of mixed venous blood entering pulmonary capillary = 40mmHg ▫ Driving force across membrane is 60mmHg (100mmHg - 40mmHg) ▪ Diffusion coefficient of gas (D) is a combination of usual diffusion coefficient (dependent on molecular weight) and gas solubility ▪ Diffusion coefficient dramatically affects OSMOSIS.ORG 605

diffusion rate, e.g. diffusion coefficient for CO2 is approximately 20x greater than that of O2 → for a given partial pressure difference CO2 would diffuse across the same membrane 20x faster than O2 LUNG DIFFUSION CAPACITY (DL) ▪ A functional measurement which takes into account ▫ Diffusion coefficient of gas used ▫ Membrane surface area ▫ Membrane thickness ▫ Time required for gas to combine with proteins in pulmonary capillary blood (e.g. hemoglobin) ▪ Measured using carbon monoxide (CO) → CO transfer across alveolar-capillary barrier exclusively limited by diffusion process ▪ Lung diffusion capacity of carbon monoxide (DLCO) is measured using a single breath ▫ Individual breathes a mixture of gases with a low CO concentration → rate of CO disappearance is predictable in different disease states ▫ Emphysema → destruction of alveoli → decreased surface area for gas exchange → decreased DLCO ▫ Fibrosis/pulmonary edema → increase in membrane thickness (via fluid accumulation in the case of edema) → decreased DLCO ▫ Anemia → reduced hemoglobin → reduced protein binding in a given time period → decreased DLCO ▫ Exercise → increased utilization of lung capacity, increased recruitment of pulmonary capillaries → increased DLCO GRAHAM'S LAW osms.it/Grahams-law ▪ Diffusion rate of gas through porous membranes varies inversely with the square root of its density ▪ To compare rate of effusion (movement through porous membrane) of two gases → velocity of molecules determine the rate of spread ▪ Kinetic temperature in kelvin of a gas is directly proportional to average kinetic energy of gas molecules → at the same temperature, molecule of heavier gas will have a slower velocity than those of lighter gas 606 OSMOSIS.ORG ▫ Kinetic energy = ½mv2 ▫ ½m1v12 = ½m2v22 ▫ v12 / v22 = m2 / m1 ▫ v1 / v2 = √(m2 / m1) ▫ Which can be rewritten to give Graham’s law Rate1 = Rate2 M2 M1

Chapter 70 Respiratory Physiology: Gas Exchange GAS EXCHANGE IN THE LUNGS osms.it/gas-exchange-in-lungs PULMONARY GAS EXCHANGE ▪ AKA external respiration ▪ Pulmonary capillaries perfused with blood from right heart (deoxygenated) ▪ Gas exchange occurs between pulmonary capillary, alveolar gas ▫ Room air → inspired air → humidified tracheal air → alveoli ▫ O2 diffuses from alveolar gas → pulmonary capillary blood ▫ CO2 diffuses from pulmonary capillary blood → alveolar gas ▫ Blood exits the lungs → left heart → systemic circulation Dry inspired air ▪ PO2 is approximately 160mmHg ▫ Barometric pressure x fractional concentration of O2 (21%) ▫ PO2 = 760mmHg x 0.21 ▫ Assume no CO2 in dry inspired air Humidified tracheal air ▪ PO2 of humidified tracheal air is 150mmHg ▫ Air is fully saturated with water vapor → “dilution” of partial pressures → calculations must correct for water vapor pressure (subtracted from barometric pressure) ▫ At 37°C/98.6°F, PH2O is 47mmHg ▫ PO2 = (760mmHg − 47mmHg) x 0.21 ▫ Assume no CO2 in humidified inspired air Alveolar air ▪ Pressures of alveolar gas designated “PA” ▪ Alveolar gas exchange in lungs sees a drop in O2 partial pressure, increase in CO2 partial pressure ▪ PAO2 = 100mmHg ▪ PACO2 = 40mmHg ▪ Amount of these gases entering/leaving alveoli correspond to physiological body needs (i.e. O2 consumption, CO2 production) Pulmonary capillaries ▪ Blood entering pulmonary capillaries is mixed venous blood ▪ Tissues (metabolic activity alters composition of blood) → venous vasculature → right heart → pulmonary circulation ▪ PO2 = 40mmHg ▪ PCO2 = 46mmHg Systemic arterial blood (oxygenated) ▪ Gas partial pressures of systemic arterial blood designated “Pa” ▪ In a healthy individual, diffusion of gas across alveolar, capillary membrane is so rapid that we can assume equilibrium is achieved between alveolar gases, pulmonary capillaries → PO2 and PCO2 of blood leaving pulmonary capillaries = alveolar air ▪ PAO2 = PaO2 = 100mmHg ▪ PACO2 = PaCO2 = 40mmHg ▪ This blood enters systemic circulation to eventually return to lungs Physiological shunt ▪ Small fraction of pulmonary blood flow bypasses alveoli → physiological shunt → blood not arterialized → systemic blood has slightly lower PO2 than alveolar air ▪ Shunting occurs due to ▫ Coronary venous blood, drains directly into left ventricle ▫ Bronchial blood flow ▪ Shunting may be increased in various pathologies → ventilation-perfusion defects/mismatches ▪ As shunt size increases → alveolar gas, pulmonary capillary blood do not equilibrate → blood is not fully arterialized ▪ A-a difference: difference in PO2 between alveolar gas (A), systemic arterial blood (a) ▫ Physiological shunting → negligible/ small differences ▫ Pathology → notably increased difference OSMOSIS.ORG 607

FACTORS AFFECTING EXTERNAL RESPIRATION Thickness of respiratory membrane ▪ In healthy lungs, respiratory membrane → 0.5–1 micrometer thick ▪ Presence of small amounts of fluid (left heart failure, pneumonia) → significant loss of efficiency, equilibration time dramatically increases → the 0.75 seconds blood cells spend in transit through pulmonary circulation may not be sufficient Surface area of respiratory membrane ▪ Greater surface area of respiratory membrane → greater amount of gas exchange ▪ Healthy adult male lungs have surface area of 90m2 ▪ Pulmonary diseases (e.g. emphysema) → walls of alveoli break down → alveolar chambers enlarge → loss of surface area ▪ Tumors/pneumonia → prevent gas from occupying all available lung → loss of surface area Partial pressure gradients and gas solubilities ▪ Partial pressures of O2, CO2 drive diffusion of these gases across respiratory membrane ▪ Steep O2 partial pressure gradient exists ▫ PO2 of deoxygenated blood in pulmonary arteries = 40mmHg ▫ PO2 of 104mmHg in alveoli ▫ O2 diffuses rapidly from alveoli into pulmonary capillary blood ▪ O2 equilibrium (PO2 of 104mmHg on both sides of respiratory membrane) occurs in around 0.25 seconds of transit through lungs (about ⅓ of the time available) ▪ CO2 has smaller gradient → 5mmHg (45mmHg vs 40mmHg), although pressure gradient for O2 is much steeper than for CO2, CO2 is 20x more soluble in plasma, alveolar fluid than O2 → equal amounts of gas exchanged Ventilation-perfusion coupling ▪ Ventilation: amount of gas reaching alveoli ▪ Perfusion: amount of blood flow in pulmonary capillaries ▪ These are regulated by local autoregulatory 608 OSMOSIS.ORG ▪ ▪ ▪ ▪ mechanisms → continuously respond to local conditions → some control in blood flow around lungs Arteriolar diameter controlled by PO2 ▫ If alveolar ventilation is inadequate → blood taking O2 away faster than ventilation can replenish it → low local PO2 → terminal arteriole restriction → blood redirected to respiratory areas with high PO2, oxygen pickup more efficient ▫ In alveoli where ventilation is maximal → high PO2 → pulmonary arteriole dilation → blood flow into pulmonary arterioles increases ▫ Pulmonary vascular muscle autoregulation is opposite of that in systemic circulation Bronchiolar diameter controlled by PCO2 ▫ Bronchioles connecting areas where PACO2 high → dilation → allows CO2 to be eliminated from body ▫ Those with low CO2 → constrict Independent autoregulation of arterioles, bronchioles → matched perfusion, ventilation Ventilation-perfusion matching is imperfect ▫ Gravity → regional variation in blood, air flow (apices have greater ventilation but lesser perfusion, bases have greater perfusion, lesser ventilation) ▫ Occasionally alveolar ducts may be plugged with mucus → unventilated areas INTERNAL RESPIRATION ▪ Capillary gas exchange in body tissue ▪ Partial pressures, diffusion gradients are reversed from lungs however physical laws governing the exchanges remain identical ▪ Cells in body continuously use O2, produce CO2 ▫ PO2 always lower in tissue than arterial blood (40mmHg vs 100mmHg) → O2 moves rapidly from blood → tissues until equilibrated ▫ CO2 moves rapidly down its pressure gradient (PCO2 of 40mmHg in fresh blood arriving at capillary beds beds vs. PCO2 of 45mmHg in tissues) → venous blood → right heart

Chapter 70 Respiratory Physiology: Gas Exchange ▪ Gas exchange at tissue level driven by partial pressures, occurs via simple diffusion DIFFUSION-LIMITED & PERFUSIONLIMITED GAS EXCHANGE osms.it/diffusion-limited-perfusion-limited-gas-exchange Diffusion-limited gas exchange ▪ Diffusion is limiting factor determining total amount of gas transported across alveolarcapillary barrier ▪ As long as partial pressure gradient is maintained, diffusion continues ▫ Gas readily diffuses across permeable membrane ▫ Blood flow away from alveoli/chemical binding → partial pressure of gas on systemic end does not rise → partial pressure maintenance ▫ Given a sufficiently long capillary bed diffusion will continue along entire length as equilibrium is not achieved ▪ Examples include ▫ CO across alveolar-pulmonary capillary barrier ▫ Oxygen during strenuous exercise/ emphysema/fibrosis Perfusion-limited gas exchange ▪ Perfusion (blood flow) is the limiting factor determining total amount of gas transported across alveolar-capillary barrier ▪ Increasing blood flow → increasing amount gas transported; examples include ▫ Nitrous oxide (N2O): not bound in blood → entirely free in solution; PAN2O is constant, PaN2O = zero at start of capillary → initial large A-a difference → because no N2O binds to any other components of blood, all of it remains free in solution → partial pressure builds rapidly → rapid equilibration, most of capillary length does not participate in gas exchange; new blood must be supplied to partake in further gas exchange with alveolar N2O → “perfusion-limited gas exchange” ▫ O2 at rest ▫ CO2 Limitations of O2 transport ▪ Under physiological conditions O2 transport into pulmonary capillaries → perfusionlimited ▪ Diseased or abnormal conditions → diffusion-limited ▪ Perfusion-limited O2 transport ▫ PAO2 is constant = 100mmHg ▫ At beginning of capillary PaO2 = 40mmHg (mixed venous blood) → large partial pressure gradient → drives diffusion ▫ As O2 diffuses into pulmonary capillary blood → increase in PaO2 ▫ Hemoglobin binds O2 → resists increase in PaO2 → initially gradient is maintained; eventually equilibrium is achieved → perfusion-limitation ▫ Therefore pulmonary blood flow determines net O2 transfer (changes in pulmonary blood flow will affect net O2 transfer) Diffusion-limited O2 transport ▪ Fibrosis → thickening of alveolar walls → increased diffusion distance for O2 (decreases DL) → slowed rate of diffusion → prevents equilibration → partial pressure gradient maintained along length of capillary ▪ Increasing capillary length allows for more time for equilibrium to occur → diffusionlimitation OSMOSIS.ORG 609

O2 transport at high altitude ▪ High altitude reduces barometric pressure → reduced partial pressures ▪ Reductions in PaO2 → reduce oxygen amount available to diffuse into blood → reduced rate of equilibration at capillary → more time required for gas exchange, lower peak oxygen concentration reached once equilibrated 610 OSMOSIS.ORG