Central chemoreceptors that monitor cerebrospinal fluid will stimulate an increase in ventilation

Chemoreceptors detect the levels of carbon dioxide in the blood by monitoring the concentrations of hydrogen ions in the blood.

Learning Objectives

Describe the role of chemoreceptors in the regulation of breathing

hypoxia: A system-wide deficiency in the levels of oxygen that reach the tissues.
central chemoreceptors: Located within the medulla, they are sensitive to the pH of their environment.
peripheral chemoreceptors: The aoritic and carotid bodies, which act principally to detect variation of the oxygen concentration in the arterial blood, also monitor arterial carbon dioxide and pH.

Chemoreceptor regulation of breathing is a form of negative feedback. The goal of this system is to keep the pH of the blood stream within normal neutral ranges, around 7.35.

A chemoreceptor, also known as chemosensor, is a sensory receptor that transduces a chemical signal into an action potential. The action potential is sent along nerve pathways to parts of the brain, which are the integrating centers for this type of feedback. There are many types of chemoreceptors in the body, but only a few of them are involved in respiration.

The respiratory chemoreceptors work by sensing the pH of their environment through the concentration of hydrogen ions. Because most carbon dioxide is converted to carbonic acid (and bicarbonate ) in the bloodstream, chemoreceptors are able to use blood pH as a way to measure the carbon dioxide levels of the bloodstream.

The main chemoreceptors involved in respiratory feedback are:

Central chemoreceptors: These are located on the ventrolateral surface of medulla oblongata and detect changes in the pH of spinal fluid. They can be desensitized over time from chronic hypoxia (oxygen deficiency) and increased carbon dioxide.
Peripheral chemoreceptors: These include the aortic body, which detects changes in blood oxygen and carbon dioxide, but not pH, and the carotid body which detects all three. They do not desensitize, and have less of an impact on the respiratory rate compared to the central chemoreceptors.

Negative feedback responses have three main components: the sensor, the integrating sensor, and the effector. For the respiratory rate, the chemoreceptors are the sensors for blood pH, the medulla and pons form the integrating center, and the respiratory muscles are the effector.

Consider a case in which a person is hyperventilating from an anxiety attack. Their increased ventilation rate will remove too much carbon dioxide from their body. Without that carbon dioxide, there will be less carbonic acid in blood, so the concentration of hydrogen ions decreases and the pH of the blood rises, causing alkalosis.

In response, the chemoreceptors detect this change, and send a signal to the medulla, which signals the respiratory muscles to decrease the ventilation rate so carbon dioxide levels and pH can return to normal levels.

There are several other examples in which chemoreceptor feedback applies. A person with severe diarrhea loses a lot of bicarbonate in the intestinal tract, which decreases bicarbonate levels in the plasma. As bicarbonate levels decrease while hydrogen ion concentrations stays the same, blood pH will decrease (as bicarbonate is a buffer) and become more acidic.

In cases of acidosis, feedback will increase ventilation to remove more carbon dioxide to reduce the hydrogen ion concentration. Conversely, vomiting removes hydrogen ions from the body (as the stomach contents are acidic), which will cause decreased ventilation to correct alkalosis.

Chemoreceptor feedback also adjusts for oxygen levels to prevent hypoxia, though only the peripheral chemoreceptors sense oxygen levels. In cases where oxygen intake is too low, feedback increases ventilation to increase oxygen intake.

A more detailed example would be that if a person breathes through a long tube (such as a snorkeling mask) and has increased amounts of dead space, feedback will increase ventilation.

Respiratory feedback: The chemoreceptors are the sensors for blood pH, the medulla and pons form the integrating center, and the respiratory muscles are the effector.

One way in which breathing is controlled is through feedback by chemoreceptors. There are two kinds of respiratory chemoreceptors: arterial chemoreceptors, which monitor and respond to changes in the partial pressure of oxygen and carbon dioxide in the arterial blood, and central chemoreceptors in the brain, which respond to changes in the partial pressure of carbon dioxide in their immediate environment. Ventilation levels behave as if they were regulated to maintain a constant level of carbon dioxide partial pressure and to ensure adequate oxygen levels in the arterial blood. Increased activity of chemoreceptors caused by hypoxia or an increase in the partial pressure of carbon dioxide augments both the rate and depth of breathing, which restores partial pressures of oxygen and carbon dioxide to their usual levels. On the other hand, too much ventilation depresses the partial pressure of carbon dioxide, which leads to a reduction in chemoreceptor activity and a diminution of ventilation. During sleep and anesthesia, lowering carbon dioxide levels three to four millimetres of mercury below values occurring during wakefulness can cause a total cessation of breathing (apnea).

Hypoxia, or the reduction of oxygen supply to tissues to below physiological levels (produced, for example, by a trip to high altitudes), stimulates the carotid and aortic bodies, the principal arterial chemoreceptors. The two carotid bodies are small organs located in the neck at the bifurcation of each of the two common carotid arteries into the internal and external carotid arteries. This organ is extraordinarily well perfused and responds to changes in the partial pressure of oxygen in the arterial blood flowing through it rather than to the oxygen content of that blood (the amount of oxygen chemically combined with hemoglobin). The sensory nerve from the carotid body increases its firing rate hyperbolically as the partial pressure of oxygen falls. In addition to responding to hypoxia, the carotid body increases its activity linearly as the partial pressure of carbon dioxide in arterial blood is raised. This arterial blood parameter rises and falls as air enters and leaves the lungs, and the carotid body senses these fluctuations, responding more to rapid than to slow changes in the partial pressure of carbon dioxide. Larger oscillations in the partial pressure of carbon dioxide occur with breathing as metabolic rate is increased. The amplitude of these fluctuations, as reflected in the size of carotid body signals, may be used by the brain to detect changes in the metabolic rate and to produce appropriate adjustment in ventilation.

The carotid body communicates with medullary respiratory neurons through sensory fibres that travel with the carotid sinus nerve, a branch of the glossopharyngeal nerve. Microscopically, the carotid body consists of two different types of cells. The type I cells are arranged in groups and are surrounded by type II cells. The type II cells are generally not thought to have a direct role in chemoreception. Fine sensory nerve fibres are found in juxtaposition to type I cells, which, unlike type II cells, contain electron-dense vesicles. Acetylcholine, catecholamines, and neuropeptides such as enkephalins, vasoactive intestinal polypeptide, and substance P, are located within the vesicles. It is thought that hypoxia and hypercapnia (excessive carbon dioxide in the blood) cause the release of one or more of these neuroactive substances from the type I cells, which then act on the sensory nerve. It is possible to interfere independently with the responses of the carotid body to carbon dioxide and oxygen, which suggests that the same mechanisms are not used to sense or transmit changes in oxygen or carbon dioxide. The aortic bodies located near the arch of the aorta also respond to acute changes in the partial pressure of oxygen, but less well than the carotid body responds to changes in the partial pressure of carbon dioxide. The aortic bodies are responsible for many of the cardiovascular effects of hypoxia.

Carbon dioxide is one of the most powerful stimulants of breathing. As the partial pressure of carbon dioxide in arterial blood rises, ventilation increases nearly linearly. Ventilation normally increases by two to four litres per minute with each one millimetre of mercury increase in the partial pressure of carbon dioxide. Carbon dioxide increases the acidity of the fluid surrounding the cells but also easily passes into cells and thus can make the interior of cells more acid. It is not clear whether the receptors respond to the intracellular or extracellular effects of carbon dioxide or acidity.

Even if both the carotid and aortic bodies are removed, inhaling gases that contain carbon dioxide stimulates breathing. This observation shows that there must be additional receptors that respond to changes in the partial pressure of carbon dioxide. Current thinking places these receptors near the undersurface (ventral part) of the medulla. However, microscopic examination has not conclusively identified specific chemoreceptor cells in this region. The same areas of the ventral medulla also contain vasomotor neurons that are concerned with the regulation of blood pressure. Some investigators suspect that respiratory responses produced at the ventral medullary surface are direct and are caused by interference with excitatory and inhibitory inputs to respiration from these vasomotor neurons. They further suspect that respiratory chemoreceptors that respond to carbon dioxide are more diffusely distributed in the brain.