respiratory part three

why our air is different than that atmosphere

(1) It is humidified by contact with the mucous membranes, so its PH2o is more than 10 times higher than that of the inhaled air. (2) Freshly inspired air mixes with residual air left from the previous respiratory cycle, so its oxygen is diluted and it is enriched with CO2 from the residual air. (3) Alveolar air exchanges O2 and CO2 with the blood. Thus, the PO2 of alveolar air is about 65% that of inhaled air, and its PCO2 is more than 130 times higher.

Alveolar Gas Exchange Revisited

As hemoglobin loads oxygen, its affinity for H+ declines. Hydrogen ions dissociate from the hemoglobin and bind with bicarbonate ions (HCO3-) transported from the plasma into the RBCs. Chloride ions are transported back out of the RBC (a reverse chloride shift). The reaction of H+ and HCO3- reverses the hydration reaction and generates free CO2. This diffuses into the alveolus to be exhaled—as does the CO2 released from carbaminohemoglobin and CO2 gas that was dissolved in the plasma.

oxygen

As the level of HbO2 falls, hemoglobin binds more H+ (see fig. 22.24). This raises the blood pH, which inhibits respiration and counteracts the effect of low PO2. At about 10,800 feet (3,300 m), arterial PO2 falls to 60 mm Hg and the stimulatory effect of hypoxemia on the carotid bodies overrides the inhibitory effect of the pH increase. This produces heavy breathing in people who are not acclimated to high elevation. Long-term hypoxemia can lead to a condition called hypoxic drive, in which respiration is driven more by the low PO2 than by CO2 or pH. This occurs in situations such as emphysema and pneumonia, which interfere with alveolar gas exchange, and in mountain climbing of at least 2 or 3 days' duration.

increased ventilation

In contrast, increased ventilation raises the local blood PO2 and this stimulates vasodilation, increasing blood flow to that region to take advantage of the oxygen availability

membrane area

In good health, each lung has about 70 m2 of respiratory membrane available for gas exchange. Since the alveolar capillaries contain a total of only 100 mL of blood at any one time, this blood is spread very thinly. Several pulmonary diseases, however, decrease the alveolar surface area and thus lead to low blood PO2—for example, emphysema and lung cancer

hypercapnia

PCO2 greater than 43 mm Hg.

dissolved gas

The remaining 5% of the CO2 is carried in the blood as dissolved gas, like the CO2 in carbonated soft drinks and sparkling wines. The relative amounts of CO2 exchanged between the blood and alveolar air differ from the percentages just given. About 70% of the exchanged CO2 comes from carbonic acid, 23% from carbamino compounds, and 7% from the dissolved gas. That is, blood gives up the dissolved CO2 gas and CO2 from the carbamino compounds more easily than it gives up the CO2 in bicarbonate.

partial pressure gradient

Whenever air and water are in contact with each other, gases diffuse down their gradients until the partial pressure of each gas in the air is equal to its partial pressure in the water. If a gas has a greater partial pressure in the water than in the air, it diffuses into the air; the smell of chlorine near a swimming pool is evidence of this. If its partial pressure is greater in the air, it diffuses into the water.

Carbon dioxide is transported in three forms:

carbonic acid, carbamino compounds, and dissolved gas.

air

consists of about 78.6% nitrogen; 20.9% oxygen; 0.04% carbon dioxide; several quantitatively minor gases such as argon, neon, helium, methane, and ozone; and a variable amount of water vapor

ketoacidosis

excessive production of ketones, making the blood acidic

rbc

he efficiency of these processes therefore depends on how long an RBC spends in an alveolar capillary compared with how long it takes for each gas to be fully loaded or unloaded—that is, for them to reach equilibrium concentrations in the capillary blood. It takes about 0.25 second to reach equilibrium. At rest, when blood circulates at its slowest speed, an RBC takes about 0.75 second to pass through an alveolar capillary—plenty of time to pick up a maximum load of oxygen. Even in vigorous exercise, when the blood flows faster, an erythrocyte is in the alveolar capillary for about 0.3 second, which is still adequate.

membrane thickness

he respiratory membrane between the blood and alveolar air is only 0.5 µm thick in most places—much less than the 7 to 8 µm diameter of a single RBC. Thus, it presents little obstacle to diffusion. In such heart conditions as left ventricular failure, however, blood pressure builds up in the lungs and promotes capillary filtration into the connective tissues, causing the respiratory membranes to become edematous and thickened . The gases have farther to travel between blood and air, so oxygen can't get to the RBCs quickly enough to fully load their hemoglobin. Under these circumstances, blood leaving the lungs has an unusually low PO2 and high PCO2.

gas transport

is the process of carrying gases from the alveoli to the systemic tissues and vice versa. This section explains how the blood loads and transports O2 and CO2.

systemic gas exchange

is the unloading of O2 and loading of CO2 at the systemic capillaries

hydrogen ions

ltimately, pulmonary ventilation is adjusted to maintain the pH of the brain. The central chemoreceptors in the medulla oblongata mediate about 75% of the change in respiration induced by pH shifts, and yet H+ doesn't cross the blood-brain barrier very easily. However, CO2 does, and once it is in the CSF, it reacts with water to produce carbonic acid, and the carbonic acid dissociates into bicarbonate and hydrogen ions. The CSF contains relatively little protein to buffer the hydrogen ions, so most H+ remains free, andit strongly stimulates the central chemoreceptors. Hydrogen ions are also a potent stimulus to the peripheral chemoreceptors, which mediate about 25% of the respiratory response to pH changes

alkalosis

pH above 7.45

acidosis

pH below 7.35

Ventilation-perfusion coupling

refers to physiological responses that match airflow to blood flow and vice versa. These reactions of the pulmonary arteries are opposite from the reactions of systemic arteries, which dilate in response to hypoxia. Furthermore, changes in the blood flow to a region of a lung stimulate bronchoconstriction or dilation, adjusting ventilation so that air is directed to the best-perfused parts of the lung

henry's law

states that at the air-water interface, for a given temperature, the amount of gas that dissolves in the water is determined by its solubility in water and its partial pressure in the air. Thus, the greater the PO2 in the alveolar air, the more O2 the blood picks up. And since blood arriving at an alveolus has a higher PCO2 than air, it releases CO2 into the alveolar air. At the alveolus, the blood is said to unload CO2 and load O2. Each gas in a mixture behaves independently; the diffusion of one gas does not influence the diffusion of another.

deoxyhemoglobin (HHb).

whereas hemoglobin with no oxygen bound to it is

Four factors adjust the rate of oxygen unloading

Ambient PO2. temperature, ambient pH, BPg

oxygen

Arterial blood carries about 20 mL of oxygen per deciliter. About 98.5% of it is bound to hemoglobin in the RBCs and 1.5% is dissolved in the blood plasma. Hemoglobin is specialized for oxygen transport. It consists of four protein (globin) chains, each with one heme group. Each heme can bind 1 O2 to the iron atom at its center; thus, one hemoglobin molecule can carry up to 4 O2

utilization coefficient

As blood arrives at the systemic capillaries, its oxygen concentration is about 20 mL/dL and the hemoglobin is about 97% saturated. As it leaves the capillaries of a typical resting tissue, its oxygen concentration is about 15.6 mL/dL and the hemoglobin is about 75% saturated. Thus, it has given up 4.4 mL/dL—about 22% of its oxygen load.

causes of increased respiration

(1) When the brain sends motor commands to the muscles (via the lower motor neurons of the spinal cord), it also sends this information to the respiratory centers, so they increase pulmonary ventilation in anticipation of the needs of the exercising muscles. In contrast to homeostasis by negative feedback, this is considered a feed-forward mechanism, in which signals are transmitted to the effectors to produce a change in anticipation of need. (2) Exercise stimulates proprioceptors of the muscles and joints, and they transmit excitatory signals to the brainstem respiratory centers. Thus, the respiratory centers increase breathing because they are informed that the muscles have been told to move or are actually moving. The increase in pulmonary ventilation keeps blood gas values at their normal levels in spite of the elevated O2 consumption and CO2 generation by the muscles.

hypocapnia

A PCO2 less than 37 mm Hg

haldene effect

A low level of oxyhemoglobin (HbO2) enables the blood to transport more CO2. This occurs for two reasons: (1) HbO2 doesn't bind CO2 as well as deoxyhemoglobin (HHb) does. (2) HHb binds more hydrogen ions than HbO2 does, and by removing H+ from solution, HHb shifts the carbonic acid reaction (H2O + CO2 → HCO3- + H+) to the right. A high metabolic rate keeps oxyhemoglobin levels relatively low and thus allows more CO2 to be transported by these two mechanisms.

Carbamino compounds

About 5% binds to the amino groups of plasma proteins and hemoglobin to form this, chiefly carbaminohemoglobin (HbCO2). The reaction with hemoglobin can be symbolized Hb + CO2 → HbCO2. Carbon dioxide does not compete with oxygen because CO2 and O2 bind to different sites on the hemoglobin molecule—oxygen to the heme moiety and CO2 to the polypeptide chains. Hemoglobin can therefore transport both O2 and CO2 simultaneously. As we will see, however, each gas somewhat inhibits transport of the other.

carbonic acid

About 90% of the CO2 is hydrated (reacts with water) to form carbonic acid, which then dissociates into bicarbonate and hydrogen ions: CO2 + H2O → H2CO3 → HCO3- + H+. More will be said about this reaction shortly.

ambient pH

Active tissues also generate extra CO2, which raises the H+ concentration and lowers the pH of the blood. Hydrogen ions weaken the bond between hemoglobin and oxygen and thereby promote oxygen unloading—a phenomenon called the Bohr28 effect. This can be seen in the oxyhemoglobin dissociation curve, where a drop in pH shifts the curve to the right (fig. 22.26b). The effect is less pronounced at the high PO2 present in the lungs, so pH has relatively little effect on pulmonary oxygen loading. In the systemic capillaries, however, PO2 is lower and the Bohr effect is more pronounced.

carbon dioxide loading

Aerobic respiration produces a molecule of CO2 for every molecule of O2 it consumes. The tissue fluid therefore contains a relatively high PCO2 and there is typically a CO2 gradient of 46 → 40 mm Hg from tissue fluid to blood. Consequently, CO2 diffuses into the bloodstream, where it is carried in the three forms already noted. Most of it reacts with water to produce bicarbonate ions (HCO3-) and hydrogen ions (H+). This reaction occurs slowly in the blood plasma but much faster in the RBCs, where it is catalyzed by the enzyme carbonic anhydrase. An antiport called the chloride-bicarbonate exchanger then pumps most of the HCO3- out of the RBC in exchange for Cl- from the blood plasma. This exchange is called the chloride shift. Most of the H+ binds to hemoglobin or oxyhemoglobin, which thus buffers the intracellular pH.

co2

Although the arterial PCO2 has a strong influence on respiration, we have seen that it is mostly an indirect one, mediated through its effects on the pH of the CSF. Yet the experimental evidence described earlier shows that CO2 has some effect even when pH remains stable. At the beginning of exercise, the rising blood CO2 level may directly stimulate the peripheral chemoreceptors and trigger an increase in ventilation more quickly than the central chemoreceptors do.

BPG

Erythrocytes have no mitochondria and meet their energy needs solely by anaerobic fermentation. One of their metabolic intermediates is bisphosphoglycerate (BPG), which binds to hemoglobin and promotes oxygen unloading. An elevated body temperature (as in fever) stimulates BPG synthesis, as do thyroxine, growth hormone, testosterone, and epinephrine. All of these hormones thus promote oxygen unloading to the tissues.

poor ventilation

For example, if part of a lung were poorly ventilated because of tissue destruction or an airway obstruction, it would be pointless to direct much blood to that tissue. Poor ventilation leads to a low PO2 in that region of the lung. This stimulates local vasoconstriction, rerouting the blood to better-ventilated areas of the lung where it can pick up more oxygen

alveolar gas exchange.

For oxygen to get into the blood, it must dissolve in this water and pass through the respiratory membrane separating the air from the bloodstream. For carbon dioxide to leave the blood, it must pass the other way and diffuse out of the water film into the alveolar air. This back-and-forth traffic of O2 and CO2 across the respiratory membrane is called this.

solubility of the gases

Gases differ in their ability to dissolve in water. Carbon dioxide is about 20 times as soluble as oxygen, and oxygen is about twice as soluble as nitrogen. Even though the pressure gradient of O2 is much greater than that of CO2 across the respiratory membrane, equal amounts of the two gases are exchanged because CO2 is so much more soluble and diffuses more rapidly.

oxyhemoglobin (HbO2)

If one or more molecules of O2 are bound to hemoglobin, the compound is called,

ambient PO2

Since an active tissue consumes oxygen rapidly, the PO2 of its tissue fluid remains low. From the oxyhemoglobin dissociation curve you can see that at a low PO2, HbO2 releases more oxygen.

Pressure gradients of the gases.

The PO2 is about 104 mm Hg in alveolar air and 40 mm Hg in blood arriving at an alveolus. Oxygen therefore diffuses from the air into the blood, where it reaches a PO2 of 104 mm Hg. Before the blood leaves the lung, however, this drops to about 95 mm Hg. This oxygen dilution occurs because the pulmonary veins anastomose with the bronchial veins in the lungs, so there is some mixing of the oxygen-rich pulmonary blood with the oxygen-poor systemic blood. Even though the blood is 100% saturated with oxygen as it leaves the alveolar capillaries, it is virtually impossible for it to remain 100% saturated by the time it leaves the lungs. At high elevations, the partial pressures of all atmospheric gases are lower.Thus, there is a very steep gradient of PO2 from alveolus to blood and diffusion into the blood is accelerated.

venous reserve

The oxygen remaining in the blood after it passes through the capillary bed provides a venous reserve of oxygen, which can sustain life for 4 to 5 minutes even in the event of respiratory arrest. At rest, the circulatory system releases oxygen to the tissues at an overall rate of about 250 mL/min

oxyhemoglobin dissociation curve

The relationship between hemoglobin saturation and ambient PO2 At low PO2, the curve rises slowly; then there is a rapid increase in oxygen loading as PO2 rises farther. This reflects the way hemoglobin loads oxygen. When the first heme group binds O2, hemoglobin changes shape in a way that facilitates uptake of the second O2 by another heme group. This, in turn, promotes the uptake of the third and then the fourth O2—hence the rapidly rising midportion of the curve. At high PO2 levels, the curve levels off because the hemoglobin approaches 100% saturation and cannot load much more oxygen.

summary

Ventilation is adjusted to maintain arterial pH at about 7.40 and arterial PCO2 at about 40 mm Hg. This automatically ensures that the blood is at least 97% saturated with O2 as well. Under ordinary circumstances, arterial PO2 has relatively little effect on respiration. When it drops below 60 mm Hg, however, it excites the peripheral chemoreceptors and stimulates an increase in ventilation. This can be significant at high elevations and in certain lung diseases. The increase in respiration during exercise results from the expected or actual activity of the muscles, not from any change in blood gas pressures or pH.

oxygen unloading

When H+ binds to oxyhemoglobin (HbO2), it reduces the affinity of hemoglobin for O2 and tends to make hemoglobin release it. Oxygen consumption by respiring tissues keeps the PO2 of tissue fluid relatively low, so there is typically a pressure gradient of 95 → 40 mm Hg of oxygen from the arterial blood to the tissue fluid. Thus, the liberated oxygen—along with some that was carried as dissolved gas in the plasma—diffuses from the blood into the tissue fluid

hemoglobin

When hemoglobin is 100% saturated, every molecule of it carries 4 O2; if it is 75% saturated, there is an average of 3 O2 per hemoglobin molecule; if it is 50% saturated, there is an average of 2 O2 per hemoglobin; and so forth. The poisonous effect of carbon monoxide stems from its competition for the O2 binding site

temperature

When temperature rises, the oxyhemoglobin dissociation curve shifts to the right. in other words, elevated temperature promotes oxygen unloading. Active tissues are warmer than less active ones and thus extract more oxygen from the blood passing through them.