Department of Physiology and Biophysics of the School of Medicine-University of Puerto Rico

 

 

RESPIRATORY PHYSIOLOGY
OUTLINE & OBJECTIVES

Instructor: Dr. Furilla

These notes are only an abbreviated version of the text book. Do not assume that you can study from these notes alone.
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OBJECTIVES

Lecture 1: Lung Structure, Gas Laws, Spirometry.

  • Be familiar with the structure of the lung.

  • Understand the concepts of barometric pressure, partial pressure, and the affect of altitude on these variables.

  • Understand the gas laws.

  • Learn the relationship between temperature and water vapor pressure, and the influence of water vapor on inspired air.

  • Be familiar with the solubility of gases in liquid.

  • Understand the aspects of lung volumes and spirometry.

Lecture 2: Alveolar Ventilation.

  • Understand the concept of anatomical dead space.

  • Understand physiological dead space.

  • Calculate minute ventilation, dead space ventilation, and alveolar ventilation.

  • Be able to use the alveolar ventilation equation and the alveolar gas equation.

  • Understand the difference between the respiratory quotient (RQ) and the respiratory exchange ratio (R).

  • Be able to calculate ventilation efficiency using CO2 exchange.

Lecture 3: Oxygen Transport.

  • Calculate the amount of dissolved oxygen in blood.

  • Understand the role of hemoglobin as an oxygen carrier.

  • Calculate the amount of oxygen carried by hemoglobin.

  • Become familiar with the oxygen-hemoglobin dissociation curve.

  • Understand the concept of P50 and the factors that influence it.

  • Be familiar with the difference between anemia and carbon monoxide poisoning.

  • Be able to determine the a-v O2 content difference.

Lecture 4: Carbon Dioxide Transport.

  • Be familiar with the ways that carbon dioxide is carried in blood.

  • Understand the chemical reaction between CO2 and water.

  • How does carbonic anhydrase affect CO2 transport?

  • Know the CO2 equilibrium curve and the Haldane effect.

  • What affects arterial and venous CO2 content and the a-v CO2 difference?

Lecture 5: Control of Breathing.

  • Be familiar with the brain structure responsible for controlling ventilation.

  • Know the factors that influence the acid-base status of the CSF.

  • What is the difference between acute and chronic CO2 retention?

  • Know the effect of peripheral lung receptors on the control of breathing (e.g. Hering-Breuer inflation reflex).

  • Understand the influence of carotid body chemoreceptors on ventilation.

  • How does exercise influence ventilation?

  • Know the effect of altitude on the control of breathing

  • What happens to breathing during sleep?

Lecture 6: Pulmonary Shunts.

  • What is a shunt, and what impact does shunted blood have on arterial PO2?

  • What are the sources of shunted blood?

  • Understand the shunt equation.

  • How can breathing 100% oxygen help to determine the shunt fraction?

Lecture 7: Ventilation/Perfusion imbalance.

  • Understand the interaction between ventilation (oxygen delivery) and perfusion (oxygen uptake).

  • Why does capillary PO2 depend on the V/Q ratio?

  • How does a V/Q mismatch affect the alveolar arterial PO2 difference?

  • Understand why when breathing 100% oxygen, arterial PO2 approaches alveolar PO2.

Lecture 8: Pulmonary Blood Flow & Gas Exchange.

  • Describe blood flow distribution within the lung.

  • Understand Fick's law of diffusion.

  • What factors affect gas diffusion between alveolar air and capillary blood?

  • Why is carbon monoxide a good gas to use to determine lung diffusing capacity?

  • Understand the difference between perfusion and diffusion limitations to gas exchange.

Additional objectives not covered by lecture material.

  • Be able to describe pulmonary anatomy and microstructure.

  • Understand the concept of surface tension.

  • What is the function of surfactant?

  • Be able to interpret pulmonary function tests (from the lab).

  • Understand the concepts that determine the work of breathing (from the lab).

  • Review non-respiratory functions of the lung.

INTRODUCTION TO GASES

The pressure of a gas in a container is directly proportional to the average force per unit area that gas molecules exert on the walls of the container. Pressure is generated by molecular collisions.

Barometric pressure is measured in mmHg, and at sea level, is 760 mmHg. Because the density of molecules decreases as you ascend to higher altitude, barometric pressure also decreases. In respiratory physiology, pressures are measured relative to atmospheric pressure. Therefore, if pleural pressure is 755 mmHg and barometric pressure is 760 mmHg, we say that pleural pressure is -5 mmHg (5 mmHg below atmosphere). Because respiratory pressures are small, we usually measure pressure in cmH2O (1 mmHg = 1.36 cmH2O). Pressure is also proportional to the kinetic energy of the molecules; therefore, pressure is proportional to temperature.

  • Boyle's law: at a constant temperature and number of gas molecules, pressure is inversely proportional to volume.

  • Charles' law: at a constant pressure and number of gas molecules, volume is directly proportional to temperature.

  • Ideal gas law: PV = nRT, where P = pressure, V = volume, n = number of gas molecules, R = 0.08205 liters / ATM / ºK = 62.32 liters / mmHg / ºK, and T = temperature in ºK.

  • Dalton's law: the sum of the partial pressures of each gas species = the total pressure.

If you have a container with 50% O2 and 50% N2 at a pressure of 760 mmHg, and you now remove all of the N2 without changing the volume of the container, the total pressure depends on O2 only, and is 380 mmHg. Partial pressure = the fractional concentration of the gas species times the total pressure of the mixture (PO2 = FO2 * PB = 0.5 * 760 mmHg = 380 mmHg in this example). Because the fractional concentration of O2 in air is 0.2094, PO2 at sea level is 0.2094 * 760 mmHg, which is about 159 mmHg. Fractional concentration is %/100.

Air contains mostly N2, O2, and H2O. CO2 and other gases are in trace amounts.

Dry air contains 79.02% N2, 20.94% O2, 0.0004% CO2. In future calculations, we will consider O2 = 21% and N2 = 79%

When water is exposed to air, molecules of water leave the liquid and enter the air, producing water vapor. The vapor pressure of water = the partial pressure of water (PH2O) when there is no net movement of water between the gas and liquid phases. Water vapor depends on temperature only, and is independent of barometric pressure.

Inspired air is warmed to 37C and saturated before entering the alveoli. At 37C, the vapor pressure of water when the air is saturated is 47 mmHg at sea level or on top of Mt. Everest. Therefore, the PO2 of saturated air at 37C at sea level is (760 - 47) * 0.21, or about 149 mmHg. We call this the partial pressure of inspired oxygen (PIO2). At ½ atmosphere, PO2 of saturated air at 37C is (380 - 47) * 0.21, or about 70 mmHg. Notice that you do not divide the PO2 at sea level by 2 to calculate the PO2 at ½ atmosphere.

Gases move by convection and diffusion. Convection is the process of bulk air flow or blood flow, while diffusion is the process of molecular movement from a region of high concentration to a region of low concentration. The driving force for movement by convection or diffusion is the pressure gradient (barometric or partial pressure respectively) between the two regions.

LUNG VOLUMES

The following diagram depicts a spirogram trace with the components of Total Lung Capacity (TLC).

  • VT = Tidal Volume: the volume of air inspired and then expired during quiet (resting) breathing.

  • IRV = Inspiratory Reserve Volume: the volume of air a person can inspire above tidal volume.

  • IC = Inspiratory Capacity: the volume of air a person can inspire above the resting expiratory volume.

  • ERV = Expiratory Reserve Volume: the volume of air that a person can exhale below resting expiratory volume.

  • RV = Residual Volume: the volume of air left in the lung after maximum expiratory effort.

  • FRC = Functional Residual Capacity: the volume of air in the lung below resting expiratory volume (ERV + RV).

  • VC = Vital Capacity: the maximum volume of air that can be inspired and then expired.

  • FVC = Forced Vital Capacity: this is similar to VC, but under maximum expiratory force, the airways may close prematurely trapping more air in the alveoli so that FVC < VC.

ALVEOLAR VENTILATION

Total ventilation is a measure of the amount of air expired in one minute (VE) and is the amount of air expired in one breath (VT, tidal volume) multiplied by breathing frequency (f). The symbol for flow is an upper case V with a dot directly over over it (pronounced "Vee dot"), but the internet will not allow that symbol, so I will italicize the letter to indicate flow (V). Notice I did not write VT to represent ventilation above. We normally refer to the volume of air expired in one minute (VE) and assume it is the same as that inspired. The volume of the entire respiratory system is composed of dead space and alveoli. The volume of the nose, mouth, pharynx and tracheobronchial tree is called anatomical dead space volume (VD). It is dead because these areas are not involved in gas exchange. Gas exchange occurs from the volume of fresh air entering the alveoli (VA). The air that a person inspires and expires (VT) is distributed in these two compartments, and can be written as VT = VD + VA. Multiply all variables by breathing frequency (f) to convert to ventilation expressed in liters/minute; therefore, VE = VD + VA. Another form of dead space is referred to as physiological deadspace. Any alveolus that is not perfused is dead space because that alveolus is being ventilated, but is not involved in gas exchange. Furthermore, any alveolus that is poorly perfused has some portion of the ventilating gas that does not completely exchange with blood, and is, therefore, wasted ventilation.

Carbon dioxide is a useful variable to measure because all CO2 produced must be eliminated by ventilation alone. Therefore, in the steady state, CO2 expired = CO2 produced, and because CO2 expired must have come from the alveolar air, VCO2 = VA * FACO2 = VE * FECO2, where FACO2 = the fractional concentration of CO2 in the alveolar air and FECO2 = the fractional concentration of mixed expired CO2. Therefore, FACO2 = VCO2 / VA (VCO2 is STPD and VA is BTPS). The partial pressure of CO2 in the alveolar air PACO2 = FACO2 * (PB - 47) = (VCO2 / VA) * (PB - 47). To convert the units to the same conditions (convert VA to BTPS), we can reduce the equation to PACO2 = (VCO2 / VA) * K, where K is 863 mmHg. This relationship is called the alveolar ventilation equation. Remember to convert all flows to the same units (either ml/min or liters/min). Because alveolar ventilation is determined by PACO2, then if PACO2 is less than normal (40 mmHg) the individual is hyperventilating. This is important. Increasing total ventilation does not equal hyperventilation. An exercising person that is maintaining alveolar and arterial PCO2 at a normal level is not hyperventilating even if breathing is heavy. Increased total ventilation in the absence of hyperventilation is called hyperpnea.

Metabolism is the process that consumes oxygen, and as a by-product, produces carbon dioxide. The ratio of CO2 produced to O2 consumed is called the respiratory quotient (RQ), and RQ depends on the type of fuel supplied. If carbohydrates are the substrate, RQ = 1; whereas, when fats are used, RQ = 0.7, for proteins, RQ = 0.8. Cells, however, do not rely on a single substrate, so that on average, RQ is about 0.8. Oxygen and carbon dioxide are also exchanged between the alveoli and capillaries. This exchange ratio is called R. In the steady state, R = RQ, but transiently, they can be different. If a person hyperventilates, R will rise as more CO2 is eliminated from blood. Oxygen uptake, however changes only slightly because of the low solubility of O2 in plasma and the nearly saturated hemoglobin; therefore, the ratio VCO2 / VO2 increases during the period of hyperventilation. Eventually, R must equal RQ, but now at a lower alveolar and arterial PCO2.

The level of alveolar oxygen is also the result of a balance between O2 delivery to the alveoli and O2 uptake by the perfusing blood. Oxygen delivery depends on alveolar ventilation and the level of O2 in the inspired air; whereas, O2 uptake by the blood depends on tissue oxygen consumption. Therefore, VO2 = VA * (FIO2 - FAO2) or FIO2 - FAO2 = VO2 / VA, and PIO2 - PAO2 = (VO2 / VA) * (PB - 47). If R = 1, then PIO2 - PAO2 = PACO2. R rarely equals 1, so PIO2 - PAO2 = PACO2 / R, and in an ideal lung, PACO2 = PaCO2 so that PIO2 - PAO2 = PaCO2 / R, where PACO2 refers to alveolar CO2 and PaCO2 refers to arterial CO2. This relationship is called the alveolar gas equation. If PIO2 is 149 mmHg, PaCO2 is 40 mmHg, and R is 0.8, then using the alveolar gas equation, PAO2 = 99 mmHg.

Increasing breathing frequency will increase VE, VD, and VA (the VD/VT ratio remains constant); whereas, increasing tidal volume will increase only VE and VA (the VD/VT ratio decreases). At high lung volumes, however, anatomical dead space ventilation will increase because airway diameter increases. Calculating physiological dead space ventilation is more complicated because the dead space is not anatomically identifiable. Ventilation inefficiency, however, can be estimated by the effect on CO2 exchange. If we assume there are three types of alveoli, ideal alveoli in which PACO2 = PaCO2, unperfused alveoli which contribute no CO2 to the expired gas and poorly perfused alveoli in which there is incomplete CO2 exchange, then the total expired volume of CO2 comes from the effective alveoli or partially effective alveoli: VCO2 = VE * FECO2 = (VE - VD) * FACO2. Algebraic manipulation of this relationship yields VD * FACO2 = VE * FACO2 - VE * FECO2. and the wasted fraction, VD/VT = (FACO2 - FECO2) / FACO2 = (PACO2 - PECO2) / PACO2. As before, we can substitute PaCO2 for PACO2 if there is no significant shunt (see Shunts). Because this relationship depends on expired, alveolar, or arterial CO2 and not anatomical volumes, physiological or effective dead space volume and ventilation can be calculated. Dead space and alveolar ventilation can be found in the respiratory simulations.

BLOOD GAS TRANSPORT

Oxygen Transport: The amount of any gas that dissolves in blood is directly proportional to the partial pressure of the gas and the solubility of the gas. Therefore, CO2 = SO2 * PO2, where CO2 is the content of oxygen (not carbon dioxide), SO2 is the solubility of oxygen, and PO2 is the partial pressure of oxygen (Henry's law). At 37C, the solubility of O2 is 0.003 ml O2 / 100 ml blood / mmHg. The content of O2 dissolved in blood = 0.003 * PO2. If plasma PO2 is 100 mmHg (approximately normal arterial blood), the amount of O2 dissolved is 0.3 ml. This small amount of oxygen will not sustain normal human metabolism. another method is needed to transport oxygen to tissues in sufficient quantity to meet metabolic demands. The molecule hemoglobin (Hb) meets this requirement. Each molecule of hemoglobin can carry 4 molecules of O2. In respiratory physiology, there is a long history of measuring the volume of oxygen in blood in ml O2 / 100 ml blood. Fully saturated hemoglobin can carry approximately 1.36 ml O2 / g Hb, and normal human blood contains about 15 g Hb / 100 ml blood. Multiplying these two constants yields 20.4 ml O2 / 100 ml blood (left figure below). Because blood is almost fully saturated at a PO2 of 100 (dotted line in the right figure below), there are about 20 ml O2 / 100 ml of normal arterial blood, which is considerably more than the 0.3 ml dissolved in plasma.

The relative hemoglobin-oxygen affinity is represented by the P50 (dashed line in the right figure above). The P50 is defined as the partial pressure of O2 required to achieve 50% hemoglobin saturation, and is normally about 26 or 27 mmHg. If the P50 is low, hemoglobin has a higher affinity for oxygen (binds more easily), and the dissociation curve shifts to the left. A right shift (high P50) indicates a lower affinity for oxygen. There are several factors that influence P50. As [H+] increases (low pH), O2 affinity decrease (right shift) because hydrogen ions bind to the imidazole group of the amino acid histidine. Carbon dioxide also produces a low affinity (right shift) for two reasons. First, CO2 binds to the N-terminal valines of the alpha and beta chains of hemoglobin, and second, because increasing CO2 causes an increase in hydrogen ions. This relationship was first described by Christian Bohr in 1904 and is known as the Bohr Effect. Increasing temperature will also decrease the affinity for O2. Finally, 2,3-diphosphoglycerate (DPG) reduces the affinity for O2 by binding to the beta chains in the central cavity of hemoglobin. Increasing DPG also reduces the CO2 Bohr effect because of competition at the beta chains. The position of the dissociation curve is a balance between the need to load O2 at the lung and the need to unload O2 at the tissues. Ideally, a high affinity is preferable when blood enters the lung to load oxygen, and a low affinity is preferable when blood enters the tissues to unload oxygen. To a small extent, this occurs because as CO2 leaves the blood and pH rises in lung capillaries, there is a slight left shift in the dissociation curve, facilitating O2 loading, and as CO2 enters the capillary blood at the tissues, there is a slight right shift in the dissociation curve, facilitating O2 unloading. Hemoglobin in normal concentration can carry slightly more than 20 ml O2 / 100 ml blood. However, this capacity can be reduced by anemia or the addition of carbon monoxide (CO to the blood). Carbon monoxide and O2 bind reversibly to the same site on the hemoglobin molecule. The affinity for CO, however, is about 250 times greater than for O2, making it extremely difficult to bind O2 to hemoglobin during CO poisoning. Severe CO poisoning may require breathing 100% O2 in a hyperbaric chamber to hasten the washout of CO. Anemia is the reduction of hemoglobin concentration either pathologically or through hemorrhage.

Carbon Dioxide Transport: Carbon dioxide is carried in blood in three forms. The amount of CO2 dissolved in blood follows the same laws of solubility as other gases, and = 0.072 * PCO2. This amount, however, represents only 6% of the total CO2 carried in arterial blood. CO2 also reversibly combines with hemoglobin by binding to the amino terminus of the alpha and beta chains. Under normal conditions, this represents about 4% of total CO2 carriage in blood. The amount of CO2 carried as carbamino compounds is inversely related to the amount of O2 bound to hemoglobin even though these two molecules do not bind to the same site. Desaturated hemoglobin carries more carbon dioxide than fully saturated hemoglobin. This dependence of CO2 content on O2 is called the Haldane effect. By far, the majority of CO2 is carried in the form of bicarbonate. The enzyme carbonic anhydrase catalyzes the reaction of CO2 with H2O to form carbonic acid (H2CO3). Carbonic acid then dissociates into H+ and HCO3-. Even though CO2 has no hydrogen ions to liberate, it is considered an acid because the product of the final step is H+. This will be discussed further in the acid-base section of the course. The partial pressure of arterial CO2 is virtually identical to PACO2, and is a balance between CO2 production from metabolism and CO2 elimination through ventilation. Arterial CO2 content is determined by PaCO2 and the CO2 equilibrium curve. Mixed venous CO2 content depends on the balance between CO2 production (VCO2), the CO2 equilibrium curve, and cardiac output (Q). Remember, the removal of O2 from hemoglobin in the tissue capillaries promotes CO2 binding. Under normal conditions, the arterio-venous (a-v) O2 content difference is 5 ml O2 / 100 ml blood. Therefore, if RQ is 0.8, the a-v CO2 content difference is 5 * 0.8 = 4 ml CO2 / 100 ml blood. Oxygen and carbon dioxide transport can be found in the respiratory simulations.

SHUNTS AND V/Q INEQUALITY

Shunt: Up until this point we have been discussing ideal lungs in which partial pressures of arterial blood gases are virtually identical to alveolar gases. In a normal healthy individual, arterial and alveolar gases are close, but not exactly the same. In disease conditions, the values can deviate greatly. A shunt is the mixing of deoxygenated blood from systemic veins with oxygenated blood coming from pulmonary capillaries. There are many sources of shunted blood. One is the Thebesian circulation which perfuses the left ventricle and empties directly into the left ventricle without passing through the lung. Lung tissue itself must be perfused (bronchial circulation), and this blood empties into pulmonary veins, mixing with pulmonary capillary blood. This mixing occurs even in normal healthy individuals. Perfusing collapsed alveoli (atelectasis) will result in no gas exchange and that blood will mix with pulmonary capillary blood from normal healthy tissue. A congenital defect may produce a right to left shunt through holes in the atria or ventricles. If we know the shunt fraction (QS) and total pulmonary blood flow (QT) we can calculate the content of oxygen in arterial blood. QS/QT = (CCO2 - CaO2) / (CCO2 - CVO2), where CCO2 is the content of oxygen in the normal pulmonary capillary blood, CaO2 is arterial content and CVO2 is mixed venous content. If the shunt fraction is not known, we can calculate the shunt by giving the subject 100% O2 to breathe (FIO2 = 1). At sea level, the maximum PAO2 will be 673 mmHg when FIO2 = 1, (760 - 40 - 47). Can you recall from where the 40 and 47 came? This only works for FIO2 = 1 because, as we will see later, V/Q heterogeneity can produce a reduction in PaO2 which cannot be distinguished from a shunt unless FIO2 = 1. A handy clinical approximation is to administer 100% O2 and measure the A-a O2 difference. Each 1% shunt will produce about 20 mmHg difference. If Alveolar PO2 is 670 mmHg and arterial PO2 is 470 mmHg, there is approximately a 10% shunt (see figure below).

Important Point: A small shunt fraction (i.e. a small reduction in O2 content as seen in the figure above) can have a dramatic effect on reducing arterial PO2. Review the Shunt model in the respiratory simulations.

V/Q Ratio: Another method of increasing the A-a O2 difference, producing hypoxemia is through a ventilation-perfusion heterogeneity (sometimes called inequality or mismatch). The rate at which O2 is taken up by the blood is determined by the rate at which it is supplied (ventilation) and the rate at which it is removed (perfusion). If the ventilation/perfusion (V/Q) ratio is 1 then you have perfect matching. Normally the V/Q ratio is closer to 0.8. If ventilation and perfusion of each alveolus are matched, capillary PO2 will reach equilibrium with alveolar PO2 and there will be no alveolar arterial PO2 difference. If, however, ventilation to an alveolus were to decrease with no change in perfusion, the higher rate of perfusion relative to ventilation would reduce alveolar PO2 more rapidly, which in turn would reduce end-capillary PO2. A reduction in PO2 would reduce end-capillary O2 content. Eventually a steady state would be reached with the outcome being end-capillary hypoxemia and an increased A-a O2 difference. This alveolus has a low V/Q ratio. Hyperperfusion of a normally ventilated alveolus would have the same effect. Hypoperfusion or hyperventilation of that alveolus would result in an increase in end-capillary PO2 because the V/Q ratio is high. The important point here is that it is the ratio of ventilation to perfusion that determines the PO2 of the blood leaving the alveolus for a given PIO2. Administering 100% O2 would eventually raise alveolar PO2 to 673 mmHg even in hypoventilated alveoli, so that end-capillary PO2 in all alveoli would also be 673 mmHg, and there would be no A-a O2 difference. This cannot occur when there is a true shunt (some blood experiencing no gas exchange). Therefore, if there is an A-a O2 difference when FIO2 = 1, there must be a shunt. There is a two compartment model in the respiratory simulations for practice.

Regional Gas Exchange in the Lung: Even in normal healthy individuals there is a V/Q heterogeneity. This heterogeneity is produced by an uneven distribution of ventilation and perfusion among regions of the lung. Ventilation is greater in the lower (caudal) region of the lung than in the upper (cranial) region. Blood flow is also greater in the caudal compared with the cranial region of the lung. (See the text for more discussion of regional distribution). Because ventilation and perfusion have changed in the same direction, you might expect that the V/Q ratio in these regions has not changed. However, blood flow variations in the lung are greater than the variations in ventilation, so that the V/Q ratio varies as you move from the top to bottom of the lung (see figure below).

Modified from West, J.B., Ventilation/Blood Flow and Gas Exchange, Oxford, 1977.

PULMONARY GAS EXCHANGE

The exchange of gases between the alveolar air and the capillary blood occurs by passive diffusion. Fick's law of diffusion can be simplified as follows: gas flow (Vgas) is proportional to the gas partial pressure difference between the alveolus and the blood (P1 - P2) divided by the resistance to flow (R). Other factors, such as diffusion distance and the diffusion coefficient, can be combined into a single constant K because these are not likely to change in an individual over the short term. The expression then can be written Vgas = K * (P1 - P2) / R. This general principle applies to any variable that is moving from one position to another. That is, to move anything requires a force and that movement will experience resistance. This applies to heat flow, blood flow, gas flow, ion flow, electron flow in a wire, or even sliding a chair across the floor. You may remember ohms law E = I * R or I = E / R. Electron flow (I) requires a potential difference (E) and is opposed by the resistance (R) in a conductor. If you understand and remember only one equation in physiology it probably should be Fick's law of diffusion.

Under normal resting conditions, blood is in contact with an alveolus for about 0.75 seconds. Also in normal resting individuals, O2 reaches equilibrium between capillary blood and alveolar air in about 0.25 seconds. If the O2 pressure gradient decreases (left figure below) or the diffusion resistance increases (right figure below), the movement of O2 from alveolus to blood will slow. Remember Fick's law: decreasing the pressure gradient (hypoxia) will reduce the rate of movement of O2 into the blood, and increasing resistance (low diffusing capacity) will decrease the rate of O2 uptake by the blood. In addition, under hypoxic conditions, desaturated hemoglobin will bind oxygen, inhibiting the rise in capillary PO2. If the time to reach equilibrium is greater than the transit time for blood, arterial hypoxemia will be the result. It should also be intuitive that decreasing the transit time by increasing perfusion (e.g. exercise) may result in blood that has not had time to equilibrate with the alveolar air, producing arterial hypoxemia.

The figures show how capillary PO2 changes with time between the entry of blood (capillary PO2 = mixed venous PO2) and the exit of blood (capillary PO2 = or approaches alveolar PO2).

CONTROL OF BREATHING

This link takes you to an outline of control of breathing, sleep, and breathing in special environments.

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