Humoral Control of respiration

Humoral control refers to those factors in the body fluids that influence ventilation like CO₂, O₂ and H⁺.

• Their concentrations in the blood affect alveolar ventilation in several ways:
  1. Carbon dioxide increase causes alveolar ventilation to increase; its decrease causes alveolar ventilation to decrease.
  2. H⁺ increase causes alveolar ventilation to increase; its decrease causes alveolar ventilation to decrease.
  3. Oxygen decrease causes alveolar ventila­ tion to increase; its increase causes alveolar ventilation to decrease.

The respiratory system functions to bring in O₂ and eliminate CO₂ from the body. This function is assisted by specialized receptors called chemoreceptors that monitor the levels of CO₂, O₂ and H⁺, and then send such information to the respiratory center.

These chemoreceptors are located in several loca­tions. There are central chemoreceptors found in the medulla oblongata that respond to changes in cerebro­spinal fluid H⁺ and PCO₂. Because of the much greater diffusibility of carbon dioxide, as com­pared with H⁺, it is distributed more quickly from the blood to the interstitial fluid of the medulla and to the cerebrospinal fluid than hydrogen ions.

The H⁺ concentration of the interstitial fluid of the brain stem is the deciding stimulus for respiratory drive. The influence of CO₂ is exerted by its conversion to H⁺ through the hydration reaction.

Peripheral chemoreceptors include the aortic bodies and carotid bodies whose removal eliminates a respiratory response to hypoxia.

The aortic bodies are a cluster of chemoreceptors in the aortic arch; the carotid bodies are oval nodules in the wall of the left and right common carotid arteries, where they bifurcate into the internal and external carotid arteries.

Axons from the chemoreceptors in the aortic bodies are part of the vagus nerve (cranial nerve X), whereas those of the carotid bodies project in the glossopharyngeal nerves (cranial nerve IX).

The levels of CO₂ and H⁺ are highly correlated.

Throughout the body, CO₂ is quickly converted to car­bonic acid catalyzed by the enzyme carbonic anhy­drase. Carbonic acid dissociates into HC0₃^– and H⁺. Therefore, increase in PCO₂ lead to increases in H+ while decreases in CO₂ lead to decreases in H⁺. As a result, has a large affect on respiration, whereas P O₂ affects respiration only if its levels change substantially.

Increases in arterial blood CO₂, called hypercapnia, cause an increase in H⁺. This has a particularly large effect on central chemoreceptors since there is little protein within the cerebrospinal fluid to buffer the H⁺. Activation of the central chemoreceptors causes increased respiration rate, possibly causing hyperven­tilation. Conversely, low arterial blood CO₂, called hypocapnia, inhibits respiration. Large drops in arte­rial PO₂ increase ventilation by stimulating peripheral chemoreceptors.

Influences of PO2 in ventilation rate

The influence of oxygen is transmitted from the carotid and aortic bodies to the respiratory center. The carotid and aortic body receptors also respond to carbon dioxide and hydrogen ion concentration, but the effectiveness of the carotid and aortic body response to carbon dioxide and hydrogen ions is far less than the response from the brain stem.

Thus, the carotid and aortic bodies are considered to be the most influential for the regulation of oxygen. These bodies are distinct structures with an abun­dant blood supply located just outside the aortic arch, at the division of the carotid arter­ies. They respond to changes in the PO₂ (arterial) of blood.

Blood with reduced amounts of hemo­globin, and consequently less oxygen, has the same PO₂ as blood with normal hemoglobin and oxygen, and thus no ventilation response would be elicited because there is no change in PO_2.

In anemia ventilation might be increased, not because of less oxygen, but because of greater H+ concentration caused by reduced buffering associated with the hemoglobin decrease. In the case of carbon monoxide poisoning and lack of oxygen carried by hemoglobin, ventilation is not increased, not only because the PO2 is normal, but also because there is adequate hemoglobin present for buffering hydrogen ions.

Arterial blood PO2 must be in the range of 30 to 60 mm Hg for the respiratory center to receive stimulation to ventilation from the carotid and aortic bodies. At this stage hemoglobin is still about 90% saturated with oxygen at a PO2 of 60 mm Hg.

Also, the slowing effect of an increased arterial PO2 would not normally be observed in animals breathing atmospheric air because the arterial PO2 seldom increases above 100 mm Hg.

The slowing is noted in anesthetized animals breathing an oxygen-enriched atmosphere, in which the arterial PO2 could increase to 350 to 400 mm Hg.

The regulation of ventilation by oxygen is not ordinarily thought to be important. There is usually no problem in maintaining arterial blood PO2 in the range of 80 to 100 mm Hg, and it is not advantageous to have it higher than 100 mm Hg because hemoglobin is almost saturated at that partial pressure.

Ventilation could even be reduced to about 50% of normal and hemoglobin still would be considerably saturated. The most important chemical factor in the regula­tion of ventilation is the concentration of carbon dioxide; relatively small changes can have an effect.

The regulation of ventilation by oxygen becomes more important in such conditions as pneumonia and pulmonary edema, in which gases are not diffused as readily through the respiratory membrane.

Decreased diffusion is more noticeable for oxygen than for carbon dioxide because of the smaller diffusion coefficient for oxygen. Hyperventilation caused by oxygen lack can therefore reduce the carbon dioxide concentration (because CO2 readily diffuses) and thus reduced formation of hydrogen ions , so that they become inef­fective in stimulating increased ventilation.

The oxygen deficiency mechanism (originat­ing from the carotid and aortic bodies) con­tinues to function and provides the drive to increase ventilation.