Cuerpo carotídeo: un enfoque anatómico y fisiológico / Carotid body: an anatomical and physiological approach

Resumen:Este trabajo describe la presencia del cuerpo carotídeo y su relación con el seno carotídeo. Además, se presenta una revisión bibliográfica de la historia, anatomía y fisiologia del órgano y su importancia como quimioreceptor del cuerpo humano.

Abstract:This work describes the presence of carotid body and its relationship to the carotid sinus. In addition, a literature review of the history, anatomy and physiology of the body and its importance as chemoreceptory the human body is presented.

Los baroquimiorreceptores carotídeos: órganos blanco de la hipertensión arterial / Carotid barochemoreceptors: target organs of arterial hypertension

El cuerpo carotídeo (CC) es el principal quimiorreceptor arterial periférico, capaz de sensar los cambios en la PaO2, la PaCO2 y de pH y transducirlos en señales nerviosas reguladoras de respuestas ventilatorias, circulatorias y endócrinas, que permiten una adaptación a la hipoxemia, la acidosis y la hipercapnia. El seno carotídeo, ubicado próximo al CC, con función barorreceptora, genera respuestas cardiovasculares que descienden la tensión arterial (TA). Ambas estructuras son inervadas por el nervio del seno carotídeo (NSC), que a su vez se proyecta al núcleo del tracto solitario (NTS), y se relacionan íntimamente entre sí y reciben la denominación de baroquimiorreceptores. Últimamente estos órganos se han considerado claves en la regulación de respuestas cardiorrespiratorias homeostáticas que podrían estar íntimamente relacionadas con el desarrollo y el mantenimiento de la hipertensión arterial (HTA). Existe escasa información sobre los cambios estructurales que ocurren en estos órganos durante la HTA y/o como consecuencia de ella. Nuestro planteo es que los baroquimiorreceptores carotídeos representarían un nuevo “órgano blanco” de la HTA. En diversos estudios realizados en seres humanos y en modelos de hipertensión sistólica en animales observamos un daño severo en el CC que se correlacionó significativamente con la elevación de la TA. A su vez, considerando que el sistema renina-angiotensina-aldosterona (SRAA) tendría un papel significativo en la fisiopatología del daño observado, demostramos que el ramipril, versus el atenolol, ejerce un efecto protector sobre el CC más allá de la mera reducción de la TA. Incluso el losartán mostró dicho efecto protector, aun cuando los animales utilizados en los modelos fueron normotensos. Nuestros hallazgos indican que el CC se comporta como un órgano blanco de la HTA y que la activación de un SRAA local sería responsable de los cambios morfológicos y funcionales observados.

The carotid body (CB) is the main peripheral arterial chemoreceptor, able to sense changes in PaO2, PaCO2 and pH, and translate them into nervous signals that regulate ventilating, circulating and endocrine responses which allow adaptation to hypoxemia, acidosis, and hypercapnia. The carotid sinus, located next to the CB, with a baroreceptor function, generates cardiovascular responses that decrease arterial hypertension. Both structures are innervated by the carotid sinus nerve (CSN), which is projected to the solitary tract nucleus (STN), closely inter-related and called barochemoreceptors. Lately, these organs have been considered key in the regulation of homeostatic cardiorespiratory responses that could be intimately related to the development and maintenance of arterial hypertension (AHT). There is scant information on the structural changes that occur in these organs during AHT and/or as its consequence. Our hypothesis is that carotid barochemoreceptors would be a new “target organ” of the AHT. In several studies performed in humans and in models of systolic hypertension in animals we observed a severe damage in the CB which was significantly correlated with elevation of the AT. Hence, considering that the renin-angiotensin-aldosterone system(RAAS) would play a significant role in the pathophysiology of the observed injury, we showed that ramipril versus atenolol has a protective effect on the CB further to the mere decrease of the AT. Even though the animal models used had normal pressure, losartan showed this protective effect. Our findings indicate that the CB behaves as a target organ in AHT and the activation of a local RAAS would be responsible for the morphological and functional changes that were observed.

How the carotid body works: Different strategies and preparations to solve different problems

This is a review of the different experimental approaches developed to solve the problems in our progress towards a comprehensive understanding of how arterial chemoreceptors operate. An analysis is performed of the bases, advantages and limits of the following preparations: studies of ventilatory reflexes originated from carotid bodies (CBs) in the entire animal; recordings of CB chemosensory discharges in situ; CB preparations perfused in situ; CB explants in oculo; CB explants in ovo; CB preparations incubated in vitro; CB preparations superfused in vitro; CB preparations perfused and superfused in vitro; CB tissue slices in vitro; cells acutely dissociated from CBs; CB cells in tissue culture; petrosal ganglia superfused in vitro; petrosal ganglion cells in tissue culture; and co-cultures of CB and sensory ganglion cells. A brief historical account is given of the passage from one preparation to the next one. Emphasis is placed on personal experience with the different preparations whenever possible. Examples are given of the importance of selecting the appropriate experimental preparation for solving each particular theoretical problem. In fact, brilliant ideas on how the CB works have been unproductive until finding the adequate experimental approach to explore the validity of such ideas.

Chemical and electric transmission in the carotid body chemoreceptor complex

Carotid body chemoreceptors are complex secondary receptors. There are chemical and electric connections between glomus cells (GC/GC) and between glomus cells and carotid nerve endings (GC/NE). Chemical secretion of glomus cells is accompanied by GC/GC uncoupling. Chemical GC/NE transmission is facilitated by concomitant electric coupling. Chronic hypoxia reduces GC/GC coupling but increases G/NE coupling. Therefore, carotid body chemoreceptors use chemical and electric transmission mechanisms to trigger and change the sensory discharge in the carotid nerve.

Time structure, temporal correlation and coherence of chemosensory impulses propagated through both carotid nerves in cats

In spontaneously breathing, pentobarbitone anesthetized cats, we recorded simultaneously the impulses in the chemosensory fibers of both carotid (sinus) nerves, to analyze the correlations between the frequencies of chemosensory discharges (f chi) and their activation ({df chi/dt}a) and deactivation ({df chi/dt}d) rates. We studied the chemosensory responses to brief exposures to hypoxia (100 percent N2; 5-s and 10-s) and hyperoxia (100 percent O2; 30-s), and intravenous injections of excitatory (NaCN 0.2-100 micrograms/kg) and inhibitory (dopamine hydrochloride 0.02-20 micrograms/kg) chemoreceptor agents. Hypoxia increased f chi, with a high temporal correlation between frequency levels in both nerves. Prolonging hypoxic stimulation increased {df chi/dt}d, with preservation of {df chi/dt}a. Hyperoxic exposure produced highly correlated decreases in f chi in both nerves, but reduced correlation in df chi/dt. Increasing doses of NaCN produced analogous increments in f chi, df chi/dt and their correlations, the {df chi/dt}a/{df chi/dt}d ratio remaining constant along all the experimental range, except in one animal in which the ratio increased in both nerves alike. Dopamine reduced f chi bilaterally, with chemosensory silencing being reached with doses of about 0.2-0.5 microgram/kg, the correlations between f chi's of both nerves remaining constant within the range analyzed. Maximal {df chi/dt}d was not affected along the range of dopamine doses, except in one animal in which it increased in both nerves. It is concluded that both carotid nerves convey similar quantitative information to the brain stem. Thus, the carotid nerves constitute either cooperative inputs or redundant afferences contributing to a high safety factor

Phrenic nerve activity during artificial ventilation at different body temperatures and its relationships with carotid chemosensory activity

While the chemoreceptor discharges of carotid bodies in vitro are highly dependent on temperature, these chemoreceptors in situ contribute only moderately to the ventilatory adjustment to changing body temperature (Tb), probably because of the concomitant and reverse changes in natural chemoreceptor stimuli in closed-loop preparations. Accordingly, we studied the frequency of carotid chemosensory discharge (fx) and the phrenic integrated electroneurogram (IENGph) in pentobarbitone anesthetized cats, paralyzed with alcuronium and artificially ventilated, at three steady-state levels of Tb (35.5, 37.5 and 40.2 C) modifying the frequency and volume of ventilator to ontain...

Carotid body chemoreception: the importance of CO2-HCO3- and carbonic anhydrase. (review)

The current hypotheses of carotid body (CB) chemoreception regard the glomus cells as the initial site of stimulus transduction. The consensus is that the transduction of chemical stimulus is coupled with the release of transmitter(s) from the glomus cells, which in turn generates action potentials in the afferent nerve terminals. Carbonic anhydrase (CA) is present in the glomus cells of the CB. Inhibition of CA activity in the CB in situ reduces the carotid chemosensory responses to CO2 and to O2, suggesting a common mechanism of chemosensing for both stimuli. However, CA inhibitors also block the red blood cell enzyme. Thus, the CO2 hydration reaction does not come to completion within the transit time of the blood from the lung to the CB. A steady-state reaction is not reached until later and so the PCO2 and pH levels in arterial blood samples are not the same as those sensed by the CB. Experiments in vitro using cat CB perfused and superfused with cell-free solutions, which had been pre-equilibrated with respiratory gases, strongly support the proposition that the CA activity in CB cells is essential for the speed and amplitude of the initial response to CO2 and for its subsequent adaptation. The immediate response to hypoxia also is delayed, but the late steady-state was less dependent on CA activity. In the nominal absence of CO2-HCO3- from the perfusate, hypoxic chemoreception persisted and its magnitude is not affected by CA inhibition, except for a delay which may be due to the initial alkaline pH of the glomus cells. Recent experiments performed in isolated glomus cells and in the whole CB show that hypoxia does not modify significantly the intracellular pH. By its simple catalytic function, CA can speed up the approach of the CO2 hydration reaction to equilibrium. However, CA may also contribute in the steady-state to the regulation of pHi by providing a continuous supply of H+ and HCO3-. Furthermore, CA performs a facilitatory role in the physiological chemosensory responses to CO2 and O2 in the presence of extracellular CO2-HCO3-. This role is likely to be related to the ion exchanger function and then to pHi regulation in the chemoreceptor cells

Contribution of carotid body chemoreceptors and carotid sinus baroreceptors to the ventilatory and circulatory reflexes produced by common carotid occlusion

En 16 gatos adultos anestesiados con pentobarbitoma y con respiración espontânea, se estuddió los efectos tobaritona y con respiración espontánea, se estudió los efectos evocados por oclusiones de las carótidas comunes de 1 minuto de duración. Las oclusiones unilaterales provocaron caidas de la presión intrasinusal ipsilateral y alzas de la presión arterial sistémica (a 111.5% de la basal). Las oclusiones bilaterales produjeron caidas más pronunciadas de la presión intrasinusal y alzas mayores de la presión arterial sistémica (a 137.5% de la basal), esta vez acompañadas de taquicardia e hiperventilación alveolar y pulmonar. El volumen minuto ciclo a ciclo aumentó (máxima promedio 144.7% de la basal), siendo mayor la contribución del alza del volumen corriente que la del incremento en frecuencia respiratoria. La hiperventilación máxima se relacionó en forma inversa y no lineal a la presión intrasinusal mínima alcanzada al inicio de la oclusión; después la hiperventilación se atenúa a medida que la presión intrasinusal se recupera parcialmente. La barodenervación selectiva de los senos carotídeos redujo las respuestas presoras a las oclusiones bilaterales, sin afectar las respuestas ventilatorias. En gatos con senos carotídeos con inervación intacta o barodenervación, las oclusiones bilaterales realizadas durante ventilación con O2 100% no modificaron las caídas de la presión intrasinusal ni las alzas presoras, pero disminuyeron y retardarón o incluso abolieron las respuestas ventilatorias. La naturaleza refeja de los cambios circulatorios y respiratorios provocados por oclusión carotidea se demostró por su desaparición luego de la sección de ambos nervios carotídeos (sinusales de Hering). Los resultados obtenidos indican que mientras la excitación quimiosensorial es la principal responsable de la respuesta ventilatoria a la oclusión carotídea, la desactivación barosensorial contribuê mayormente a la respuesta circulatoria a dicha maniobra

Carotid body chemoreceptor excitation produced by carotid occlusión

En 20 gatos adultos anestesiados con pentobarbitona, se registró la actividad eléctrica aferente del nervio carotídeo (sinusal). La oclusión de la arteria carótida común ipsilateral disminuyó la presión intrasinusal a 15-100 torr (dependiendo de la presión previa) y silenció la descarga barosensorial. En gatos que respiraban aire y con presión arterial media bajo 125 torr, la oclusión ipsilateral produjo aumento de la frecuencia de descarga quimiosensorial, de aparición rápida (latencia = 4 s), que alcanzó el máximo a los 30 s y después se mantuvo a un nivel submáximo de descarga (80-90% de la frecuencia máxima) al menos por 10 minutos. La oclusión carotídea ipsilateral practicada a estos mismos gatos mientras respiraban 100% O2 produjo excitación quimiosensorial de comienzo más tardío (latencia = 20 s) y menor magnitud (30-40% de la frecuencia máxima en normoxia). La oclusión carotídea ipsilateral practicada cuando la presión arterial media estaba sobre 130 torr sólo aumentó transitoriamente la frecuencia quimiosensorial o suprimió su fluctuación ventilatoria. La oclusión carotídea bilateral redujo pronunciadamente la presión intrasinusal y aumentó considerablemente la frecuencia quimiosensorial. La aplicación de estímulos químicos (inhalación de 100% N2 por 5-10 s, inyección i.v. de NaCN) durante las oclusiones carotídeas aumentó más aún la frecuencia de descarga quimiosensorial, indicando que el flujo sanguíneo a través del cuerpo carotídeo no estaba detenido. Se concluye que la oclusión carotídea puede provocar excitación quimiosensorial, cuya magnitud depende de la duración de la maniobra y condiciones circulatorias y ventilatorias prevalentes. Se sugiere que la excitación quimiosensorial podría interactuar con la desactivación barosensorial en la generación de los cambios reflejos evocados por oclusión carotídea