﻿ Gas Exchange and Transport - Physiology - An Illustrated Review

Physiology - An Illustrated Review

13. Gas Exchange and Transport

13.1 Partial Pressures

In a gas mixture, each gas species exerts a pressure, the partial pressure of that gas. The sum of the partial pressures of the gases in a mixture equals the total gas pressure.

Partial pressure for an individual gas = the fraction of that gas in the gas mixture × total gas pressure

Calculation of Partial Pressure of Oxygen (Po2) in Dry Inspired Air

O2 comprises 21% of air; total gas pressure = 760 mm Hg (at sea level)

At high altitude, the Po2 is reduced because barometric pressure is lower.

Correction of Po2 for the Presence of Water Vapor

Dry air entering the lungs becomes completely saturated with water as air passes through moist airways. This displaces some of the other gases and slightly reduces their partial pressures.

Partial pressure of water vapor (PH2o) is 47 mm Hg at body temperature.

Total pressure of gases other than water = 760 mm Hg − 47 mm Hg

= 713 mm Hg

Therefore, the Po2 in warm, humidified inspired air is

13.2 Gas Exchange

Diffusion of Gases

O2 and carbon dioxide (CO2) diffuse between alveolar gas and pulmonary capillary blood according to standard physical principles (Fick’s law; see Chapter 1).

– The total amount moved per unit of time is proportional to the area available for diffusion and to the difference in partial pressure between alveolar gas and pulmonary capillary blood, and inversely proportional to the thickness of the diffusion barrier.

– Gas will diffuse from the alveoli (higher partial pressures) to the pulmonary capillaries (lower partial pressures) until they equilibrate and no partial pressure gradient exists. As a result, blood entering the pulmonary veins from the pulmonary capillaries has virtually the same partial pressures as gases in the alveoli (Fig. 13.1).

– The diffusion barrier, composed of alveolar epithelial cells (type I pneumocytes) and capillary endothelial cells, is very thin, which ensures that the diffusion distance between alveolar gas and pulmonary capillary blood is very short. This allows blood in the pulmonary capillaries to equilibrate with alveolar gas during the short time (< 1 sec) that the blood is in the capillaries.

Dry lungs and gas exchange

The epithelial cells that make up most of the alveolar wall actively reabsorb Na+ and water, thereby preventing accumulation of water in the alveoli, a situation usually referred to as “dry” lungs, although they are not literally dry. The lack of excess water prevents it from acting as an impediment to gas exchange.

Cystic fibrosis

Cystic fibrosis is an autosomal recessive disease in which there is a defect in the epithelial transport protein CFTR (cystic fibrosis transmembrane conduction regulator) found in the lungs, pancreas, liver, genital tract, intestines, nasal mucosa, and sweat glands. This alters Cl transport in and out of cells and inhibits some Na+ channels. In the lungs, Na+ and water are absorbed from secretions that then become thick and sticky. In the pancreas, secretions are thick and sticky because duct cells cannot secrete Cl via the CFTR, and water normally follows this ion movement. Sweat is salty because Cl is not being absorbed via the CFTR, so Na+ also remains in the duct lumen. Symptoms include cough, wheezing, repeated lung and sinus infections, salty taste to the skin, steatorrhea (foul-smelling, greasy stools), poor weight gain and growth, meconium ileus (in newborns), and infertility in men. Complications of this disease include bronchiectasis (abnormal dilation of the large airways), deficiency of fat-soluble vitamins (A, D, E, and K), diabetes, cirrhosis, gallstones, rectal prolapse, pancreatitis, osteoporosis, pneumothorax, cor pulmonale, and respiratory failure. Treatment involves daily physical therapy to help expectorate secretions from the lungs, antibiotics to treat lung infections, mucolytics (e.g., acetylcysteine) to decrease the viscosity of mucus, and bronchodilators.

Fig. 13.1  Alveolar gas exchange.

The capillaries surrounding an alveolus contain less gas than does the alveolus. During transit through a pulmonary capillary, blood equilibrates with alveolar gas and acquires the same partial pressures. (Pv, partial pressure of mixed venous blood; Pa, partial pressure of arterial blood; Paco2, alveolar partial pressure of CO2; Pao2, alveolar partial pressure of O2)

Limitations to the Exchange of Gases

There is an upper limit to the rate at which O2 or any other gas can be exchanged by the lungs. These limits can be divided into categories of diffusion- and perfusion-limited exchange.

Diffusion-limited Exchange

Gas exchange may be limited by the rate at which it can diffuse across the alveolar membrane, either because of thickening of the alveolar membrane (e.g., due to fibrosis [rare]) or because the surface area available for gas exchange is reduced (e.g., in emphysema). If the surface area is reduced, pulmonary blood is constrained to flow through fewer capillaries. Consequently the blood spends less time in the capillaries, and complete equilibration of gas between alveolar air and pulmonary capillary blood will not occur.

Diffusion-limited uptake can be illustrated using carbon monoxide (CO) as an example. Because hemoglobin in red blood cells so avidly binds CO, the partial pressure of CO (Pco) in the blood remains effectively zero as CO diffuses into pulmonary capillaries. At a given alveolar Pco, the gradient remains constant during uptake, and the amount taken up is therefore purely a function of the area available for diffusion. Variations in blood flow have little influence on the diffusion of CO because all of the CO that diffuses into the blood is immediately bound to hemoglobin.

Perfusion-limited Exchange

Gas exchange of O2 or other gases (except CO) can also be limited by the rate at which the pulmonary capillary blood removes the gas. A greater rate of perfusion would lead to greater diffusion of gas.

Perfusion-limited uptake can be illustrated using nitrous oxide (N2O) as an example. N2O diffuses rapidly from alveolar gas into pulmonary capillaries and does not bind to hemoglobin; thus, the partial pressure of N2O (Pn2o) in the blood immediately rises to match its value in the alveolar gas. Diffusion in a given capillary stops before blood completes its transit through the capillary because there is no longer a gradient. Diffusion can only be increased if blood flow increases.

Diffusion hypoxia with nitrous oxide

N2O is a common inhalational anesthetic. It is administered in high concentration along with supplemental oxygen. When anesthesia is terminated, the N2O that accumulated in the body now diffuses into the alveoli. This partially displaces other gases that are there, including O2 and CO2. If the patient is breathing room air, this displacement lowers the alveolar Po2 and Pco2 and leads to a transient hypoxemia. To prevent this from occurring, the patient is temporarily given 100% O2.

Partial Pressure Changes of Oxygen and Carbon Dioxide Following Gas Exchange

Partial Pressure Changes of Oxygen

– The Po2 of humidified inspired air is 150 mm Hg.

– The Po2 of alveolar air is 100 mm Hg. This is due to the diffusion of O2 from alveolar air into pulmonary capillary blood.

– The Po2 of systemic arterial blood is 95 mm Hg. It is almost the same as the Po2 of alveolar air because the partial pressure of pulmonary capillary blood equilibrates with alveolar air. However, ~2% of the cardiac output bypasses the pulmonary circulation, which accounts for the slight discrepancy in partial pressures.

– The Po2 of venous blood is 40 mm Hg because O2 has diffused from arterial blood into the tissues.

Partial Pressure Changes of Carbon Dioxide

– The Pco2 of humidified inspired air is almost zero.

– The Pco2 of alveolar air is 40 mm Hg because CO2 from venous blood entering the pulmonary capillaries diffuses into alveolar air.

– The Pco2 of systemic arterial blood is 40 mm Hg because pulmonary capillary blood equilibrates with alveolar air.

– The Pco2 of venous blood is 46 mm Hg. It is higher than systemic arterial blood due to the diffusion of CO2 from the tissues into venous blood following cellular respiration.

Table 13.1 summarizes the partial pressure changes of O2 and CO2 following gas exchange.

13.3 Ventilation and Perfusion Ratios for Optimum Gas Exchange

Ventilation/perfusion ratio is the ratio of alveolar ventilation V to perfusion (pulmonary blood flow) Q.

– In healthy lungs, the V/Q ratio is close to 1:1, resulting in optimum gas pressures and oxygenation in systemic arterial blood.

Distribution of V/Q Ratios

There are regional differences in alveolar ventilation and blood flow in the upright individual.

– Alveolar ventilation is higher at the base of the lungs than the apices because the base is more compliant and changes more in volume during each breathing cycle.

– Blood flow is very low at the apex of the lung and very high at the base due to the effects of gravity.

The differences in regional blood flow are greater than the differences in regional ventilation. This creates different V/Q ratios at various levels of the lung. Typical values are as follows:

– Apex V/Q is ~3:1.

– Middle of lungs (heart level) V/Q is ~1:1.

– Base of lungs V/Q is ~1:2.

Despite these regional differences, which are mainly attributed to gravity, the overall V/Q ratio of the lung is matched 1:1.

V/Q Mismatching

A V/Q mismatch (inequality), beyond the modest regional differences in V/Q ratio that is seen in healthy lungs due to gravity, occurs because of a lung disorder that affects normal ventilation and/or perfusion. This can be illustrated using airway obstruction and pulmonary embolism as examples.

– V/Q ratio with airway obstruction: In complete airway obstruction, perfusion is normal, but there is no ventilation.

– V/Q = 0, which is termed a shunt.

– V/Q ratio with pulmonary embolism (PE): In PE causing complete blockage of the pulmonary artery, ventilation is normal, but there is no blood flow.

– V/Q = ∞, which is termed dead space.

– Gas exchange does not occur; therefore, alveolar air has a composition closer to that of inspired air: high Po2 and low Pco2.

– Gas exchange does not occur; therefore, alveolar air has a composition closer to that of systemic venous blood: low Po2 and high Pco2.

Pulmonary embolism

Pulmonary embolism (PE) is an obstruction in the pulmonary arterial system, usually caused by blood clots from the periphery, particularly the deep veins of the legs, which are transported to the lung. Symptoms include shortness of breath (dyspnea), chest pain exacerbated by taking a deep breath or coughing, and cough +/− blood (hemoptysis). PE decreases the area available for diffusion of gases (increases dead space) and therefore causes a V/Q mismatch. In severe cases, PE can cause death due to hypoxia and cor pulmonale (right heart failure due to chronic pulmonary hypertension). Treatment involves the use of the anticoagulants (e.g., heparin and warfarin) or thrombolytics (e.g., streptokinase; not normally required). Surgical clot removal may be necessary for large pulmonary emboli.

V/Q mismatches ultimately cause reduced oxygenation of systemic arterial blood (low Po2). The lungs are able to compensate somewhat for V/Q mismatches by hypoxic vasoconstriction.

Hypoxic Vasoconstriction

If an area of the lung become hypoxic (has a low Po2), for example, due to a blocked bronchus, there is reflex vasoconstriction of pulmonary arteriolar smooth muscle. This is the opposite of the response seen in the peripheral vasculature, where hypoxia stimulates vasodilation. Hypoxic vasoconstriction increases pulmonary vascular resistance in the hypoxic region so that blood flow decreases and is diverted to other areas of the lung with higher Po2. This prevents perfusion of poorly ventilated areas of the lungs and thus optimizes the V/Q ratio and gas exchange in the rest of the lung. This mechanism is limited, and in cases of severe lung malfunction, it cannot prevent pathological V/Q mismatch. Furthermore, a low Po2 in the whole lung, as occurs at high altitude, can lead to high resistance and pulmonary hypertension in susceptible individuals.

Table 13.2 summarizes the possible causes of impairment of gas exchange.

13.4 Oxygen Transport in the Blood

Oxygen is mainly transported in the blood bound to hemoglobin. However, some is always transported as dissolved O2, which determines the Po2 of the blood.

Transport of Oxygen Bound to Hemoglobin

Hemoglobin is a metalloprotein consisting of four subunits. Each subunit contains a globular protein chain bound to a heme group. Heme is a porphyrin containing an iron atom in the ferrous state (Fe2+), which can bind an O2molecule. Thus, each hemoglobin molecule has four binding sites for O2. The fraction of the binding sites that are occupied (the percentage saturation of O2, Sao2) is mainly a function of the existing Po2, but it also depends on the structure of the protein chains and other factors.

Hemoglobin–Oxygen Dissociation Curve (Fig. 13.2)

– The hemoglobin–O2 dissociation curve is a plot of hemoglobin–oxygen saturation as a function of Po2. When one hemoglobin subunit binds an O2 molecule, this increases the affinity of the other subunits for O2, resulting in a sigmoid–shaped relation between Po2 and Sao2.

– Normal hemoglobin is 50% saturated at a Po2 of 26 mm Hg, 75% saturated at a Po2 of 40 mm Hg, (the Po2 of mixed venous blood), 90% saturated at a Po2 of 60 mm Hg, and 100% saturated at 95 mm Hg (the Po2 of systemic arterial blood).

– Because hemoglobin is > 90% saturated at all values of arterial Po2 > 60 mm Hg, people with healthy lungs can tolerate a wide range of inspired Po2 values without difficulty. Furthermore, raising arterial Po2 by breathing air enriched with O2 adds little additional O2 content to the blood. However, the situation is quite different for people with lung pathology, for whom supplemental O2 is of great benefit.

Note: Fetal hemoglobin (Hb F) has a slightly higher affinity for O2 than does the adult form (Hb A) because it binds 2,3-diphosphoglycerate (2,3-DPG) less avidly. Hb F is 50% saturated at a Po2 of 19 mm Hg. This facilitates the uptake of O2 by the fetus at the relatively low values of Po2 that exist in the placenta.

Methemoglobinemia

Methemoglobinemia is a condition in which there are higher levels of methemoglobin in the blood than normal. Methemoglobin is formed when the heme moiety contains iron in the ferric state (Fe3+) rather than the ferrous state (Fe2+). This may occur when red blood cells are exposed to exogenous oxidizing drugs and their metabolites. Methemoglobin does not bind O2, so people with this condition will show signs of hypoxia, including shortness of breath (dyspnea), dizziness, cyanosis, fatigue, and mental changes. Treatment includes the administration of methylene blue, a substance that is able to reduce iron in hemoglobin to its normal, oxygen-carrying state, and supplemental O2.

Shifts in the Hemoglobin–Oxygen Dissociation Curve

The affinity of hemoglobin for O2 is somewhat dependent on conditions. A decrease in affinity (meaning it requires a higher Po2 to reach a given level of saturation) is called a “shift to the right” of the hemoglobin–O2 dissociation curve, whereas an increase in affinity is a “shift to the left” (Fig. 13.3).

– A right shift facilitates the unloading of O2 in peripheral tissues. Conditions favoring a shift to the right (high temperature, low pH, and high Pco2) exist in exercising muscle. Unloading more O2 raises local Po2 and drives O2diffusion into nearby tissues. In muscle, this benefits oxidative metabolism. A shift to the right also occurs when there is increased levels of 2,3-DPG in the blood at high altitude.

Fig. 13.2  Hemoglobin–O2 dissociation curve.

Fig. 13.3  Shifts in the hemoglobin–O2 dissociation curve.

The O2 dissociation curve is shifted to the right (green line) indicates a decrease in affinity of hemoglobin for O2 and therefore an increase in O2 unloading in peripheral tissues. The curve is shifted to the left (blue line) when there is an increase in the affinity of hemoglobin for O2 and reduced O2unloading into peripheral tissues. (DPG, 2,3-diphosphoglycerate.)

– A left shift reduces the unloading of O2 in peripheral tissues. It occurs with decreased temperatures, high pH, low high Pco2, and decreased 2,3-DPG levels.

Carbon monoxide poisoning

CO is an odorless, tasteless gas that can poison an individual without the person being aware. CO binds to the same sites on hemoglobin as O2, but ~200 times more avidly. When CO binds to hemoglobin, the binding sites are no longer available to load O2 even if alveolar Po2 is normal. Thus, delivery of O2 to the tissues is greatly reduced. CO poisoning can be treated with hyperbaric O2. By greatly raising arterial Po2, the dissolved O2 level increases so much that the dissolved component, normally trivial, is high enough to help oxygenate body tissues. The high Po2 also raises the rate at which the residual CO dissociates from hemoglobin.

Hypoxia and Hypoxemia

– Hypoxia is a general term meaning low delivery of O2 to tissues. It may occur in local tissue sites as a result of vascular occlusion or in the whole body at high altitude or in conditions of impaired ventilation or low cardiac output.

– Hypoxemia is a more specific term meaning low Po2 in arterial blood. It may occur due to hypoventilation, low inspired Po2, diffusion impairment, V/Q mismatch, or a right-to-left shunt.

Comparing Causes of Hypoxemia: A-a Gradient

An A-a gradient refers to the difference between average alveolar Po2 (PAo2) and arterial Po2 (Pao2), as expressed by

A-a gradient = PAO2 − Pao2

– It can be used as a tool to analyze causes of hypoxemia.

– Alveolar Po2 can be assessed by sampling exhaled gas at the end of expiration (after dead space gas has been washed out).

– There is always a small A-a gradient of ~5 mm Hg, due to the shunting of pulmonary blood flow and to the small gravitational V/Q mismatch in the lungs.

– An increased A-a gradient (> 5 mm Hg) indicates that inspired air is reaching alveoli that are not transferring O2 to the blood. This may occur due to an impairment of diffusion (e.g., fibrosis or emphysema), V/Q mismatch, or right-to-left shunt.

Table 13.3 compares the causes of hypoxemia.

13.5 Carbon Dioxide Transport in Blood

CO2 is mainly transported in blood in the form of bicarbonate (HCO3). It is also transported as dissolved CO2 (5%) or carbaminohemoglobin (5%). The content of CO2 (the sum of its concentration in all forms) is ~2.5 times the content of O2.

Transport of Carbon Dioxide as Bicarbonate

CO2 is produced by tissues as a result of aerobic respiration. It freely diffuses into red blood cells and is then transported in blood by the following steps (Fig. 13.4):

– CO2 combines with H2O within red blood cells to form carbonic acid (H2CO3). This is catalyzed by carbonic anhydrase. H2CO3 dissociates into H+ and HCO3.

– Much of the HCO3 moves into the plasma via an antiporter in exchange for Cl (the “chlo-ride shift”). Plasma, as well as the red blood cells, is therefore a vehicle for the transportation of CO2 to the lungs.

– The H+ produced is largely buffered by hemoglobin. Removal of O2 from the blood by uptake into tissues increases the amount of CO2 that can be converted to HCO3 because deoxygenated hemoglobin is a better buffer than oxygenated hemoglobin. In addition, deoxygenated hemoglobin binds more carbamino-CO2 than oxygenated hemoglobin.

– In the lungs, the reverse of the process described above occurs: HCO3 enters red blood cells in exchange for Cl, and HCO3 binds to H+ to form H2CO3. H2CO3 then breaks down to form CO2 and H2O, and CO2 is expired.

Fig. 13.4  CO2 transport in blood.

CO2 is an end product of energy metabolism (1). It enters red blood cells, where it combines with H2O to form H+ and HCO3 (2). This is catalyzed by carbonic anhydrase. HCO3 leaves red blood cells via an HCO3/Cl antiporter (3). CO2 also forms carbaminohemoglobin within red blood cells (4). H+ ions liberated in the formation of HCO3 and carbaminohemoglobin are buffered by hemoglobin (Hb) (5). In the lung, these reactions proceed in the opposite direction, and CO2 diffuses from red blood cells into the alveoli.

The Carbon Dioxide Dissociation Curve

The CO2 dissociation curve is the relationship between CO2 concentration in the blood and Pco2 (Fig. 13.5).

– It is nearly linear over Pco2 values between normal venous blood (~46 mm Hg) and normal arterial blood (~40 mm Hg), as compared with the highly nonlinear hemoglobin–O2 dissociation curve in the normal physiological range.

Fig. 13.5  CO2 dissociation curve.

Increasing Pco2 increases total co2 concentration. Because O2 binding to hemoglobin decreases its capacity to bind CO2, the total CO2 concentration at any given Pco2 is somewhat lower at high O2 saturation (red curve) than at a lower O2 saturation (purple curve). The co2 concentration values in normal arterial and mixed venous blood are indicated at points a and v, respectively. The normal range of co2 dissociation is determined by connecting these two points by a line called “physiologic co2 dissociation curve”.

﻿
﻿
If you find an error or have any questions, please email us at admin@doctorlib.info. Thank you!