Gas Exchange and Alveolar Ventilation. Objectives At the end of this session students should be able...

Gas Exchange and Alveolar Ventilation

Objectives At the end of this session students should be able to 1.Define dead space, physiological and anatomical 2.Define partial pressure and fractional concentration as they apply to gases in air. 3. List the normal airway, alveolar, arterial, and mixed venous PO2 and PCO2 values. 3. List the normal arterial and mixed venous values for O2 saturation, [HCO3-], and pH.

4. Be able to estimate the alveolar oxygen partial pressure (PAO2) using the simplified form of the alveolar gas equation 5.Name the factors that affect diffusive transport of a gas between alveolar gas and pulmonary capillary blood. 6. Understand diffusion limited and perfusion limited gas exchange. 7.Define oxygen diffusing capacity.

Dead space Regions of the respiratory system that contain air but are not exchanging O2and CO2with blood are considered dead space. Anatomic dead space Airway regions that, because of inherent structure, are not capable of O2and CO2exchange with the blood. Includes the conducting zone, which ends at the level of the terminal bronchioles. The size of the anat V D in mL is approximately equal to a persons weight in pounds. ( Thus a 150-lb individual has an anatomic dead space of 150 mL.)

Alveolar dead space(alv V D ) Refers to alveoli containing air but without blood flow in the surrounding capillaries. An example is a pulmonary embolus Physiologic dead space total dead space in the lung system (anatV D +alvV D )

VENTILATION Total Ventilation/minute volume or minute ventilation total volume of air moved in or out (usually the volume expired) of the lungs per minute.

Alveolar Ventilation Represents the air delivered to the respiratory zone(include the alveoli, alveolar sacs, alveolar ducts, and respiratory bronchioles)per breath.

Increases in the Depth of Breathing: There will be equal increases in total and alveolar ventilation per breath, since dead space volume is constant Increases in the Rate of Breathing Increased rate causes increased ventilation of dead space and alveoli.

A woman has a respiratory rate of 18, a tidal volume of 350 mL, and a dead space of 100 mL. What is her alveolar ventilation? a. 4.0 L b. 4.5 L c. 5.0 L d. 5.5 L e. 6.0 L

Gas laws Boyle's law: when temperature is constant, pressure (P) and volume (V) are inversely related Dalton's law: the partial pressure of a gas in a gas mixture is the pressure that the gas would exert if it occupied the total volume of the mixture in the absence of the other components. Henry's law : that the concentration of a gas dissolved in a liquid is proportional to its partial pressure.

Henry's law is used to convert the partial pressure of gas in the liquid phase to the concentration of gas in the liquid phase (e.g., in blood). Where; C X =Concentration of dissolved gas (mL gas/100 mL blood) and not the gas present in blood in bound form like bound to hemoglobin or plasma protein. P X =Partial pressure of gas (mmHg) Solubility =Solubility of gas in blood (mL gas/100 mL blood/mmHg)

Partial pressure of a gas in inspired air

COMPOSITION OF AIR Partial pressure- gas Ambient air Humidifie d air Alveolar air Expired air P O2158mm149mm104mm120mm P CO20.3mm 40mm28mm P H2O5.7mm47mm P N2596mm563mm573mm565mm

AlveolarBlood Gas Exchange

pCO2 Factors affecting alveolar pCO2 1. Metabolic Rate

pCO2 Factors affecting alveolar pCO2 2. Alveolar Ventilation Hyperventilation inappropriately elevated level of alveolar ventilation, and pACO2 is depressed. Hypoventilation inappropriately depressed level of alveolar ventilation, and pACO2 is elevated.

pO2 Factors affecting alveolar pO2 The Alveolar Gas Equation

The Effect of pACO2 on pAO2

RESPIRATORY MEMBRANE 1)fluid lining alveolus 2)alveolar epithelium 3)epith basement membrane 4)interstitial space 5)Capillary basement membrane 6)capillary endothelial cell

alveolarblood gas transfer: Fick law of diffusion 1.Structural Features That Affect the Rate of Diffusion. A- area, T- thickness 2.Factors That Are Specific to Each Gas Present D- diffusion coefficient, P1-P2 = pressure diff

FACTORS DETERMINING DIFFUSION- DIFFUSION COEFFICIENT DIFFUSION COEFFICIENT=S/MW Depends on 1) Solubility in water 2)Molecular Weight Though CO2 has greater molecular weight than O2 it is 20 times more soluble in water than O2. CO2 > O2> N2

Diffusing Capacity of the Respiratory Membrane In practice, surface area, thickness, and the diffusion coefficient can be combined to yield a constant that describes the lungs diffusing capacity (D L ) for gas. Gas flow across the barrier can then be estimated from:

DIFFUSION-LIMITED AND PERFUSION- LIMITED GAS EXCHANGE Gas exchange across the alveolar/pulmonary capillary barrier is described as either diffusion-limited or perfusion-limited. Diffusion-limited gas exchange means that the total amount of gas transported across the alveolar-capillary is limited by the diffusion process. In these cases, as long as the partial pressure gradient for the gas is maintained, diffusion will continue along the length of the capillary. The equilibrium is not achieved. Perfusion-limited gas exchange means that the total amount of gas transported across the alveolar/capillary membrane is limited by blood flow (i.e., perfusion) through the pulmonary capillaries. In perfusion-limited exchange, the pressure gradient is not maintained, and in this case, the only way to increase the amount of gas transported is by increasing blood flow. Equilibrium is achieved.

Perfusion-Limited Gas Exchange the transport of N 2 O across the alveolar/pulmonary capillary barrier P A N 2 O is constant, and PaN 2 O is assumed to be zero at the beginning of the pulmonary capillary. Thus, initially, there is a very large partial pressure gradient for N 2 O between alveolar gas and capillary blood, N 2 O rapidly diffuses into the pulmonary capillary. Because all of the N 2 2O remains free in blood, all of it creates a partial pressure. Thus, the partial pressure of N 2 O in pulmonary capillary blood increases very rapidly and is fully equilibrated with alveolar gas in the first one fifth of the capillary. Once equilibration occurs, there is no more partial pressure gradient and, therefore, no more driving force for diffusion. Net diffusion of N2O then ceases, although four fifths of the capillary still remain to be travelled by blood. O2 (under normal conditions)

Perfusion-limited O2 transport In the lungs of a normal person at rest, O2 transfer from alveolar air into pulmonary capillary blood is perfusion- limited. PAO2 is constant at 100 mm Hg. At the beginning of the capillary, PaO2 is 40 mm Hg, reflecting the composition of mixed venous blood. There is a large partial pressure gradient for O2 between alveolar air and capillary blood, which causes diffusion into the capillary. As O2 is added to pulmonary capillary blood, PaO2 increases. The gradient for diffusion is maintained initially because O2 binds to hemoglobin, which keeps the free O2 concentration in blood and the partial pressure low. Equilibration of O2 occurs about one third of the distance along the capillary, at which point PaO2 becomes equal to PAO2, and unless blood flow increases, there can be no more net diffusion of O2. Thus, under normal conditions, transport is perfusion- limited.

Diffusion-limited O2 transport In certain pathologic conditions (e.g., fibrosis) and during strenuous exercise, transfer becomes diffusion limited. Fibrosis: In fibrosis the alveolar wall thickens, increasing the diffusion distance for gases across the wall and decreasing DL which slows the rate of diffusion of O2 and prevents equilibration of O 2 between alveolar air and pulmonary capillary blood. In these cases, the partial pressure gradient for O2 is maintained along the entire length of the capillary, converting it to a diffusion-limited process (although not as extreme as in the example of CO). At the end of the pulmonary capillary, equilibration has not occurred between alveolar air and pulmonary capillary blood (PaO2 is less than PAO2), which will be reflected in a decreased PaO2 in systemic arterial blood and decreased PvO2 in mixed venous blood.

O2 diffusion along the length of the pulmonary capillary in normal persons and persons with fibrosis. A, at sea level and B, at high altitude.

O2 transport at high altitude Ascent to high altitude alters some aspects of the O2 equilibration process. At high altitude, barometric pressure is reduced, and with the same fraction of O2 in inspired air, the partial pressure of O2 in alveolar gas also will be reduced. PAO2 is reduced to 50 mm Hg, compared the normal value of 100 mm Hg. Mixed venous PO2 is 25 mm Hg (as opposed to the normal value of 40 mm Hg). Therefore, at high altitude, the partial pressure gradient for O2 is greatly reduced compared with sea level. Even at the beginning of the pulmonary capillary, the gradient is only 25 mm Hg (50 mm Hg - 25 mmHg) instead of the normal gradient at sea level of 60 mm Hg (100 mm Hg - 40 mm Hg). This reduction of the partial pressure gradient means that diffusion of O2 will be reduced, equilibration will occur more slowly along the capillary, complete equilibration will be achieved at a later point along the capillary (two-thirds of the capillary length at altitude, compared with one third of the length at sea level). The final equilibrated value for PaO2 is only 50mmHg because PAO2 is only 50 mm Hg (it is impossible for the equilibrated value to be higher than 50 mm Hg). The equilibration of O2 at high altitude is exaggerated in a person with fibrosis. Pulmonary capillary blood does not equilibrate even by the end of the capillary, resulting in values for PaO2 as low as 30 mm Hg, which will seriously hamper O2 delivery to the tissues.

Examples Diffusion-Limited Gas Exchange the transport of CO across the alveolar/pulmonary capillary barrier net diffusion of CO into the pulmonary capillary depends on the magnitude of the partial pressure gradient, is maintained because CO is bound to hemoglobin in capillary blood. Recall that only free, dissolved gas causes a partial pressure. Thus, CO does not equilibrate by the end of the capillary. In fact, if the capillary were longer, net diffusion would continue indefinitely, or until equilibration occurred. the transport of O2 during strenuous exercise and in pathologic conditions such as emphysema and fibrosis.

Carbon Monoxide: A Gas that is Always Diffusion Limited measuring the volume of carbon monoxide absorbed in a short period and dividing this by the alveolar carbon monoxide partial pressure, one can determine accurately the carbon monoxide diffusing capacity.

11. A patient inspired a gas mixture containing a trace amount of carbon monoxide and then held his breath for 10 sec. During breath holding, the alveolar PCO averaged 0.5 mm Hg and CO uptake was 10 mL/min. What is his pulmonary diffusing capacity (DLCO)? (A) 2.0 mL/min per mm Hg (B) 5.0 mL/min per mm Hg (C) 10 mL/min per mm Hg (D) 20 mL/min per mm Hg (E) 200 mL/min per mm Hg

Transport of Oxygen and carbon dioxide

Learning objectives At the end of this session students should be able to Define oxygen partial pressure (tension), oxygen content, and percent hemoglobin saturation as they pertain to blood. Interpret an oxyhemoglobin dissociation curve (hemoglobin oxygen equilibrium curve)

Learning objectives Show how the oxyhemoglobin dissociation curve is affected by changes in blood temperature, pH, PCO2, and 2,3-DPG. List the forms in which carbon dioxide is carried in the blood. Identify the percentage of total CO2 transported as each form. Interpret the carbon dioxide dissociation curves for oxy- and deoxyhemoglobin. Describe the interplay between CO2 and O2 binding on hemoglobin that causes the Haldane effect.

Pulse oximetry Hb changes color from dark blue to bright red when O 2 binds, which makes it possible to monitor arterial O 2 -saturation levels using noninvasive pulse oximetry. A light-emitting probe is attached to a finger or ear, then the relative amounts of saturated and desaturated Hb is calculated from the amount of light absorbed at 660 nm and 940 nm, respectively.

The blood of a normal person contains about 15 grams of hemoglobin in each 100 milliliters of blood, and each gram of hemoglobin can bind with a maximum of 1.34 milliliters of oxygen. There-fore, 15 times 1.34 equals 20.1 On average, the 15 grams of hemoglobin in 100 milliliters of blood can combine with a total of almost exactly 20 milliliters of oxygen if the hemoglobin is 100 per cent saturated On passing through the tissue capillaries, this amount is reduced, on average, to 14.4 milliliters (Po2of 40 mm Hg, 75 per cent saturated hemoglobin). Thus, under normal conditions, about 5milliliters of oxygen are transported from the lungs to the tissues by each 100 milliliters of blood flow.

Aerobic metabolism generates CO 2 and causes tissue Pco 2 to rise. CO 2 binds to terminal globin amino groups and decreases Hbs O 2 affinity. The HbO 2 dissociation curve shifts to the right, and O 2 is unloaded. CO 2 also dissolves in water to yield free acid, which promotes further O 2 unloading via the Bohr effect

CO poisoning

CO decreases O 2 bound to hemoglobin and also causes a left shift of the O 2 -hemoglobin dissociation curve. CO binds to hemoglobin with an affinity that is 250 times that of O 2 to form carboxyhemoglobin. the presence of CO decreases the number of O 2 -binding sites available on hemoglobin. Reduces O 2 content of blood and O 2 delivery to tissues

Use the following diagram of oxyhemoglobin saturation curves

What is the P50of the oxyhemoglobin curve labeled A in the diagram? a. 80 mmHg b. 60 mmHg c. 40 mmHg d. 30 mmHg e. 20 mmHg Which of the following conditions is most likely to shift the above oxyhemoglobin curve from A to B? a. Increased temperature b. Exercise c. Acclimatization to high altitude d. Hyperventilation e. Metabolic acidosis

Which of the following conditions causes a decrease in arterial O2 saturation without a decrease in O2tension? a. Anemia b. Carbon monoxide poisoning c. A low V/Q ratio d. Hypoventilation e. Right-to-left shunt

Which one of the above oxyhemoglobin saturation curves was obtained from fetal blood? a. A b. B c. C d. D e. E

Which one of the above oxyhemoglobin saturation curves was obtained from blood exposed to carbon monoxide? a. A b. B c. C d. D e. E

Transport of Carbon dioxide Dissolved Carbon Dioxide 5% of the total CO2 content of blood Carbon dioxide is 20 times more soluble in blood than oxygen is. Carbamino Compound Carbon dioxide reacts with terminal amine groups of proteins(Hb) to form carbamino compounds. The protein involved appears to be almost exclusively hemoglobin and this binding is responsible for Bohr effect. Reversly, O2 bound to Hb changes its affinity for CO2, such that when less O2 is bound, the affinity of hemoglobin for CO2 increases called the Haldane effect. About 5% of the total CO2 is carried as carbamino compounds. The attachment sites that bind CO2 are different from the sites that bind O2.

Bicarbonate About 90% of the CO2 is carried as plasma bicarbonate. In order to convert CO2 into bicarbonate or the reverse, carbonic anhydrase (CA) enzyme must be present. Plasma contains no carbonic anhydrase; therefore, there can be no significant conversion of CO2 to HCO3- in this compartment.

All of the reactions described here occur in reverse in the lungs. H+ is released from its buffering sites on deoxyhemoglobin, HCO3 - enters the red blood cells in exchange for Cl-. H+ and HCO3- combine to form H2CO3, and H2CO3 dissociates into CO2 and H2O. The regenerated CO2 and H2O are expired by the lungs

Gas Exchange and Alveolar Ventilation. Objectives At the end of this session students should be able...

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