Central and peripheral chemoreceptors

Most metabolic acid-base disorders develop slowly, within hours in diabetic ketoacidosis and months or even years in chronic renal disease. The respiratory system responds immediately to a change in acid-base status, but several hours maybe required for the response to become maximal. The maximum response is not attained until both the central and peripheral chemoreceptors are fully stimulated. For example, in the early stages of metabolic acidosis, plasma pH decreases, but because H ions equilibrate rather slowly across the blood-brain barrier, the pH in CSF remains nearly normal. However, because peripheral chemoreceptors are stimulated by the decreased plasma pH, hyperventilation occurs, and plasma PCO2 decreases. When this occurs, the PCO2 of the CSF decreases immediately because CO2 equilibrates rapidly across the blood-brain barrier, leading to a rise in the pH of the CSF. This will inhibit the central chemoreceptors. But as plasma bicarbonate gradually falls because of acidosis, bicarbonate concentration and pH in the CSF wih also fall over several hours. At this point, stimulation of respiration becomes maximal as both the central and peripheral chemoreceptors are maximally stimulated. 

CO2/H+ homeostasis Role of central and peripheral chemoreceptors in adult mammals... 

The respiratory response to metabolic alkalosis is hypoventilation, which resnlts in an increased PaC02. Respiratory compensation is initiated within honrs when the central and peripheral chemoreceptors sense an increase in pH. The PaC02 increases 6 to 7 mm Hg for each 10-mEq/L increase in bicarbonate, np to a PaC02 of abont 50 to 60 mm Hg (see Table 51M) before hypoxia sensors react to prevent fnrther hypoventilation. If the PaC02 is normal or less than normal, one shonld consider the presence of a snperimposed respiratory alkalosis, which may be secondary to fever, gram-negative sepsis, or pain. 

Figure 1). The disturbances (e.g., changes in the chemical composition of inspired air or changes in metabolic activity) produce changes in the controlled system (the gas exchange and transport components of the respiratory and circulatory system) which in turn produce changes in the controlled variables (arterial p02> Pco2> [H+], and CSF [H+] ). The deviation of the controlled variables from their reference values is sensed at various points (the central and peripheral chemoreceptors), and this signal is transmitted to the controller (the respiratory center in the brain) where it induces a change in the manipulated variables (ventilation, cardiac output, and blood distribution).

Heeringa,)., Berkenbosch, A., de Goede,). et al. 1979. Relative contribution of central and peripheral chemoreceptors to the ventilatory response to CO2 during hyperoxia. Respir. Physiol. 37 365. 

Low doses of nicotine stimulate respiration through activation of chemoreceptors in the aortic arch and carotid bodies, while high doses directly stimulate the respiratory centers. In toxic doses, nicotine depresses respiration by inhibiting the respiratory centers in the brainstem and by a complex action at the receptors at the neuromuscular junction of the respiratory muscles. At these neuromuscular receptors, nicotine appears to occupy the receptors, and the end plate is depolarized. After this, the muscle accommodates and relaxes. These central and peripheral effects paralyze the respiratory muscles. 

The vagus nerve is a major connection between central and peripheral components. It contains both afferent (80%) and efferent (20%) pathways from and to the upper GIT. These include both cholinergic and non-cholinergic nerve fibres the non-cholinergic neurones may have serotonin as transmitter. Two types of vagal afferent receptors are involved in the emetic response (1) mechanoreceptors, iocated in the muscular wall of the distal stomach and proximal duodenum, which are activated by distension or contraction of the gut wall and (2) chemoreceptors located in the gut mucosa of the upper small bowel. These monitor the... 

The antiemetic properties of metoclopramide appear to be a result of its antagonism of central and peripheral dopamine receptors. Dopamine produces nausea and vomiting by stimulation of the medullary chemoreceptor trigger zone (CTZ), and metoclopramide blocks stimulation of the CTZ by agents like levodopa or apomorphine that are known to increase dopamine levels or to possess dopaminelike effects. Metoclopramide also inhibits the central and peripheral effects of apomorphine and abolishes the slowing of gastric emptying caused by apomorphine. 

Perphenazine is thought to exert its antipsychotic effects by postsynaptic blockade of CNS dopamine receptors, thus inhibiting dopamine-mediated effects. The antiemetic effects of perphenazine are attributed to dopamine-receptor blockade in the medullary chemoreceptor trigger zone. Perphenazine has many other central and peripheral effects it produces both alpha and ganglionic blockade and counteracts histamine- and serotonin-mediated functions. It produces... 

An increase in arterial PC02 results in marked stimulation of the central chemoreceptors. In fact, this is the most important factor in regulation of ventilation. It is well known that it is impossible to hold one s breath indefinitely. As carbon dioxide accumulates in the arterial blood, the excitatory input to the respiratory center from the central chemoreceptors overrides the voluntary inhibitory input and breathing resumes. Furthermore, this occurs well before the arterial P02 falls low enough to stimulate the peripheral chemoreceptors. 

Chemoreceptor response to increased arterial hydrogen ion concentration. An increase in arterial hydrogen ion concentration, or a decrease in arterial pH, stimulates the peripheral chemoreceptors and enhances ventilation. This response is important in maintaining acid-base balance. For example, under conditions of metabolic acidosis, caused by the accumulation of acids in the blood, the enhanced ventilation eliminates carbon dioxide and thus reduces the concentration of H+ ions in the blood. Metabolic acidosis may occur in patients with uncontrolled diabetes mellitus or when tissues become hypoxic and produce lactic acid. An increase in arterial hydrogen ion concentration has no effect on the central chemoreceptors. Hydrogen ions are unable to cross the blood-brain barrier. 

Mechanism of Action An antiemetic that blocks serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone. Therapeutic Effect Prevents nausea and vomiting. 

Mechanism of Action Aphenothiazinethat acts centrally to inhibit or block dopamine receptors in the chemoreceptor trigger zone and peripherally to block the vagus nerve in the GI tract. Therapeutic Effect Relieves nausea and vomiting and improves psychotic conditions. 

Most older typical antipsychotic drugs, with the exception of thioridazine, have a strong antiemetic effect. This action is due to dopamine-receptor blockade, both centrally (in the chemoreceptor trigger zone of the medulla) and peripherally (on receptors in the stomach). Some drugs, such as prochlorperazine and benzquinamide, are promoted solely as antiemetics. 

Adiponitrile s mechanism of toxicity is similar to cyanide because it can potentially liberate cyanide in the body spontaneously. It forms a stable complex with ferric iron in the cytochrome oxidase enzymes, thereby inhibiting cellular respiration. Cyanide affects primarily the central nervous system (CNS), producing early stimulation followed by depression. It initially stimulates the peripheral chemoreceptors (causing increased respiration) and the carotid bodies (thereby slowing the heart). Early CNS, respiratory, and myocardial depression result in decreased oxygenation of the blood and decreased cardiac output. These effects produce both stagnation and hypoxemic hypoxia in addition to cytotoxic hypoxia from inhibition of mitochondrial cytochrome oxidase. 

The reverse is true when a patient with metabolic acidosis is treated with HCOT When the pH in plasma increases as the result of HCOj administration, stimulation of the peripheral chemoreceptors returns to normal. However, because of the slow equilibration of HCOj between plasma and CSF, the central chemoreceptors continue to be stimulated, and the patient continues to hyperventilate, even when the blood pH has returned to normal. Respiration does not return to normal until normal acid-base balance in the CSF of the brain is restored. 

Abstract CO2 and H are metabolic end-products, which are produced continuously and excreted steadily to maintain steady-state concentrations of CO2/H+ in the body, primarily by the chemoreceptors. To help maintain an adequate speed of reaction compatible with life, these reactions are enhanced by carbonic anhydrase (CA) present in the chemoreceptor cells. The role of chemoreceptors in H homeostasis is the focus of this chapter. The peripheral chemoreceptors very readily sense CO2/H and stimulate ventilation in order to enhance CO2 exhalation. Central chemoreceptors are stimulated similarly but slowly, also resulting in increased ventilation. Altogether, this phase, assisted by respiration alone, can be defined as the acute response. However, the H left behind is excreted by the renal system, rather slowly (chronic phase) without any direct intervention by the chemoreceptors. Thus, respiratory and renal systems are integrated in the long run to maintain ( XT/H homeostasis. 

A decrease in PaC02 may occur in patients with cardiogenic, hypovolemic, or septic shock because oxygen delivery to the carotid and aortic chemoreceptors is reduced. This relative deficit in Pa02 stimulates an increase in ventilation. The hyperventilation in sepsis is also mediated via a central mechanism. Hyperventilation-induced respiratory alkalosis with an elevation in cardiac index and hypotension without peripheral vasoconstriction may therefore be an early sign of sepsis. 

Ondansetron is not a dopamine-receptor antagonist. Becanse serotonin receptors of the 5-HT3 type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone, it is not certain if ondansetron s antiemetic action is mediated centrally, peripherally, or in both sites (see Fignre 73). 

In general, the principal function of the central chemoreceptors is to guard the [H+] of CSF which bathes the central nervous system while the principal function of the peripheral chemoreceptors is to regulate po2 and, under extreme conditions, the pco2 and [H+] of systemic arterial blood (25). 

The two major peripheral chemoreceptors are the carotid and the aortic bodies. The central chemoreceptors are probably localized close to the respiratory center in the medulla. 

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