Carotid Body

Description

The carotid body (CB) comprises chemoreceptors and their supporting cells at the bifurcation of the carotid artery. It functions to detect oxygen and carbon dioxide partial pressures as well as changes in pH, glucose, and temperature.
From the available literature, the CB was first reported in 1743 in a dissertation from the lab of the famous German physiologist, Albrecht von Haller. In 1938, Corneille Heymans received the Nobel Prize in Physiology or Medicine for his discovery of the role carotid and aortic mechanisms played in cardiopulmonary control. Heymans’ work owed a great debt to the pioneering histological work of Fernando De Castro who knew the difference between the CB and carotid sinus before the Heymans’ group (1).
The CB is sometimes confused with the carotid sinus, located at the base of the internal carotid artery; this latter structure is the principal detector and regulator of BP in mammals.
The CB, however, is arguably the most important interoreceptor in humans.

Physiology Principles

In human subjects, the CB is football-shaped with a volume of ~12 mm³. The human CB weighs ~14 mg but has an enormous blood flow, the highest of any organ measured.
The CB "tastes" the blood; that is, it is sensitive to qualitative changes in arterial blood composition.
- When PaO₂ or glucose drops, carbon dioxide tension (PaCO₂) or hydrogen ion rises. The neurotransmitter-containing chemosensitive glomus cells in the CB become depolarized and extracellular calcium rises in these cells. This provokes the release of excitatory (acetylcholine, adenosine triphosphate [ATP]) and inhibitory (dopamine) transmitters.
- Serotonin and GABA, slower acting agents, are subsequently released (2). These neurotransmitters cross a synaptic-like cleft between the glomus cell and the abutting sensory afferent neuron, a branch of the glossopharyngeal nerve to bind to appropriate receptors.
- The afferent neurons have their cell bodies in the petrosal ganglion and insert into nucleus tractus solitarii in the medulla.
- The neurotransmitters also bind to autoreceptors on the glomus cells to promote or attenuate further release of the agents.
Stimulation of the CB initiates an impressive array of systemic reflex responses.
- Pulmonary
  - Increase in tidal volume
  - Increase in respiratory frequency
  - Increase in FRC (a static lung volume)
  - Increase in airway resistance
  - Increase in secretions
  - Decrease in pulmonary vascular resistance.
- Cardiovascular
  - Increase in sympathetic nerve output leading to tachycardia after an initial brief bradycardia
  - Peripheral vasoconstriction
  - Some of the cardiovascular responses are modified by the stimulated lung receptors due to the hyperpnea (increase in depth and rate of respiration).
- Endocrine
  - Release of some adrenal medullary contents as well as 17-OH corticosteroids
  - Increase in plasma renin
- Renal. CB stimulation increases renal sodium and water excretion in normoxic mammals. Bilateral CB denervation abolishes the natriuresis (3).

Anatomy

Located bilaterally at the bifurcations of the common carotid arteries into their external and internal branches.

Physiology/Pathophysiology

Respiratory concerns
- Obstructive sleep apnea (OSA). This condition, which affects over 11 million Americans including children, results from the relaxing and collapse of the upper airway muscles during sleep.
  - Since metabolism continues, oxygen is consumed and PaO₂ falls. Likewise CO₂ is produced and PaCO₂ rises.
  - This modest form of asphyxia strongly stimulates the CBs first; this provokes a minimal arousal and taking in of a breath. The stimulus to the CB also provokes a significant increase in sympathetic nervous system (SNS) output. This is not attenuated by input from the stretch receptors in the lung since the subject is apneic.
  - As a consequence of the increased SNS output, heart rate and contractility increase as well as vascular resistance in some beds. This results in an increase in BP, a very undesirable consequence for subjects who have suffered a previous stroke. BP never returns to normal. The nocturnal hypertension frequently carries over into the daylight hours.
  - Episodes of OSA can occur as frequently as 30–40 times per hour.
  - Hypoxia also increases pulmonary arterial pressure by local mechanisms; this is somewhat attenuated by CB stimulation.
- Sudden infant death syndrome. Though this condition has been greatly reduced by proper positioning of the infant during sleep, the CBs are still thought to function as above in the periodic apneas observed in children throughout their first year of postnatal life as their respiratory control system undergoes development.
Cardiovascular concerns
- Chronic heart failure. As the population ages, the occurrence of heart failure (HF) is on the rise. In the US, almost 5 million people experience this condition with about 20% mortality within 1 year and about 50% mortality within 5 years (4,5).
  - Recent research using the rabbit as an animal model has illustrated that the CB plays a key role in CHF (6). Heart failure results in decreased blood flow in the common carotid artery with a resultant decrease in blood flow to the CB. The rabbits demonstrated an increase in CB neural output and renal sympathetic nerve activity.
  - Decreased blood flow reduces sheer stress on the endothelial cells in the CB vasculature. This factor initiates a cascade of events that reduces nitric oxide synthase (nNOS) activity and NO in the CB. NO is a well-known attenuator of CB neural output (7,8). When an adenovirus was loaded with the gene for nNOS and injected into the CBs of the HF rabbits, CB neural output as well as SNS output were reduced (9).
  - Modest exercise, which increases blood flow, also reduced CB neural output.

Perioperative Relevance

Effect of sedation on the CB
- Many drugs used in anesthesia depress regulation of breathing during acute hypoxia, among which are propofol, halogenated inhaled general anesthetics, and neuromuscular blocking agents.
- In a recent study of human CBs, mechanisms behind this action were studied (5). and though many of the elements operating to depress ventilation and hypoxia-induced increases in CB neural output in animal models were the same in humans, not all of the implicated nonhuman elements could be found in human CBs. The authors speculate that in humans, propofol acts on the GABA_A receptor in the CB, while inhaled halogenated anesthetics were found to target both K⁺ channels and neuronal acetylcholine receptors (nAChRs). Human CB nAChRs having the 3, 7, and 2 subunits would also be blocked by atracurium and vecuronium.

References ⬆ ⬇

DeCastro F. The discovery of sensory nature of the carotid bodies – Invited article. Adv Exptl Med Biol. 2009;648:1–18.
Nurse C. Neurotransmission and neuromodulation in the chemosensory carotid body. Auton Neurosc Bas Clin. 2005;120:1–9.
Fitzgerald RS , Shirahata M. Systemic responses elicited by stimulating the carotid body: Primary and secondary mechanisms. In: The Carotid Body Chemoreceptors, Ed. Gonzalez C. Heidelberg, Germany, Springer, 1997, pp. 171–191.
Paterson DJ. Targeting arterial chemoreceptor over-activity in heart failure with a gas. Circ Res. 2005;97:1–6.
Fagerlund M , Kahlin J , Ebberyd A , et al. The human carotid body – Expression of oxygen sensing and signaling genes of relevance for anesthesia. Anesthesiol. 2010;113:1270–1279.
Ding Y , Li YL , Schultz H. Role of blood flow in carotid body chemoreflex function in heart failure. J Physiol. 2011;589:245–257.
Wang ZZ , Stensaas L , Bredt D , et al. Mechanisms of carotid body inhibition. Adv Exptl Med Biol. 1994;360:229–235.
Fitzgerald RS , Shirahata M , Chang I , et al. L-arginine's effect on the hypoxia-induced release of acetylcholine from the in vitro cat carotid body. Respir Physiol Neurobiol. 2005;147:11–17.
Schultz H , Li YL. Carotid body function in heart failure. Respir Physiol Neurobiol. 2007;157:171–185.
Heath D , Smith P. Diseases of the human carotid body. London, Springer-Verlag, 1992, pp. 88–89.

Additional Reading ⬆ ⬇

See Also (Topic, Algorithm, Electronic Media Element)

Clinical Pearls ⬆ ⬇

Aging has an effect on the human CB: In three groups of adults with mean ages of 26, 52, and 79, the mean cross-sectional area of the CB (mm²) was 2.71, 3.12, and 4.42 respectively. But the mean percent of type I cell tissue was 45, 39, and 29. This suggests that the reflex responses to CB stimulation by hypoxia, hypercapnia, and hypoglycemia would become less as one ages.
A further consequence of aging is the diffuse infiltration of lymphocytes. In a group of 38 male and 37 female subjects, only 2 of 18 subjects under 50 years of age exhibited this phenomenon, while 32 of the 57 subjects greater than 50 years showed it.
The CB is affected by COPD. There is usually an accompanying right ventricular hypertrophy that is associated with alveolar hypoxia, hypercarbia, and muscularization of pulmonary arterioles. In emphysematous patients presenting without right ventricular hypertrophy, the mean weight of the combined CBs was 32.4 mg. In the presence of hypertrophy, the mean weight of the combined CBs was 56.2 mg.
In asthma, one might expect enlarged CBs due to the mild hypoxemia resulting from bronchospasm and mucus secretion. Stimulated CBs normally provoke contraction of airways smooth muscle. However, in asthmatic subjects who had undergone CB removal, the structures were not enlarged. But the proportion of sustentacular cells had doubled in the asthmatics compared to controls. and of the two types of type I (chief) cells, the dark type had increased from ~28% of all type I cells in the normal CBs to 43% in the asthmatics. This suggests the possibility of an abnormal CB sensitivity (10).
A commonly used neuromuscular blocker during anesthesia, vecuronium has been shown in rats to decrease the neural output from the CB. It is believed that halothane, enflurane, and isoflurane prolong the effects of vecuronium, and this would suggest that the CB would remain hyporesponsive.

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Basics ⬇

References ⬆ ⬇

Additional Reading ⬆ ⬇

Clinical Pearls ⬆ ⬇

Author(s) ⬆