Metabolic acidosis inhibits hypothalamic warm-sensitive receptors: a potential causative factor in heat stroke

ثبت نشده
چکیده

THE PREOPTIC AREA and anterior hypothalamus (POAH) is regarded as the primary site for thermoreception in the mammalian brain. Peripheral thermal afferents synapse on temperature-sensitive neurons in the POAH. The POAH, in particular, contains a high concentration of warm-sensitive neurons, which are proposed to activate heat-loss responses while inhibiting heat-production. Accordingly, electrical stimulation or localized warming of the POAH decreases core temperature, whereas lesioning or localized cooling of the POAH increases core temperature (2, 3). Core body temperature is maintained constant around a “set point” by the neural control and integration of various physiological reflexes (autonomic, endocrine, cardiorespiratory, and motor) and behavioral responses. Because of the number of organ systems utilized to maintain body temperature, and the variety of autonomic and behavioral functions that are regulated by the hypothalamus, it is not surprising that thermosensitive neurons in the hypothalamus are sensitive to multiple types of stimuli, including hyperosmolarity, hyperglycemia, sex steroids (4), and, as reported in this issue of the Journal of Applied Physiology, cellular acidosis (11). Wright and Boulant (11) have tested and proven the hypothesis that warm-sensitive neurons in the POAH are inhibited by hypercapnic acidosis. Conversely, temperature-insensitive neurons are unresponsive to hypercapnic acidosis. The significance of this finding is twofold. First, the authors have clarified a discrepancy in the literature regarding the effects of hypercapnia on thermosensitive neurons (6, 9); as reported here, under in vitro conditions, the primary effect of hypercapnic acidosis is to reduce activity of warm-sensitive neurons in the POAH. Second, this finding supports the new hypothesis that inhibition of warm-sensitive neurons in the POAH during cellular acidosis may disrupt normal heat loss mechanisms. This, in turn, could contribute to thermoregulatory dysfunction that causes core hyperthermia during respiratory acidosis (8). Molecular CO2 or hypercapnia per se is not the critical stimulus, however. The authors (11) have shown that the inhibitory effect of hypercapnic acidosis on warm-sensitive neurons occurs by a mechanism that is dependent on extracellular pH (pHe). This conclusion was based on their findings that the inhibitory effect of hypercapnic acidosis (1PCO2, 2pHe, unchanged HCO3 ) on firing rate was mimicked by isocapnic acidosis (unchanged PCO2,2pHe,2HCO3 ) but not isohydric hypercapnia (1PCO2, unchanged pHe,1HCO3 ). All three acid-base manipulations would have likely caused a significant decrease in intracellular pH (pHi) (7). Thus it seems likely that decreased pHe is the critical stimulus causing inhibition of neuronal activity. Given the importance of pH in the inhibitory mechanism they have reported, it is tempting to speculate that metabolic acidosis (i.e., isocapnic acidosis: unchanged PCO2, 2pHe, 2HCO3 , 2pHi) may be an important factor contributing to the occurrence of heat stroke. Metabolic acidosis is a wellknown predictor of heat exhaustion and heat stroke, and it has been attributed to the failure of multiple organ systems (1, 10). The present study (11), however, supports the exciting hypothesis that metabolic acidosis in and of itself can induce central hyperthermia by inhibition of heat loss mechanisms that are controlled by the POAH, resulting in heat stroke (5). Future studies, therefore, will want to address several questions that have been raised by the work of Wright and Boulant (11). Do metabolic disturbances in acid-base balance alter various behavioral and physiological mechanisms of thermoregulation? For example, are there differences in the effects of hypercapnic acidosis or metabolic acidosis on evaporative heat loss versus increased skin blood flow? At the cellular level, does acidosis alter the warm sensitivity of individual hypothalamic neurons? If so, what are the effects of pH on ionic currents and synaptic mechanisms that underlie neuronal thermosensitivity? Moreover, are temperature-induced changes in pH an important aspect of the thermosensing mechanism? If the above hypothesis is true, then one would predict that warm sensitivity of hypothalamic neurons and thus heat loss responses will be reduced during acidosis.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Metabolic acidosis inhibits hypothalamic warm-sensitive receptors: a potential causative factor in heat stroke.

THE PREOPTIC AREA and anterior hypothalamus (POAH) is regarded as the primary site for thermoreception in the mammalian brain. Peripheral thermal afferents synapse on temperature-sensitive neurons in the POAH. The POAH, in particular, contains a high concentration of warm-sensitive neurons, which are proposed to activate heat-loss responses while inhibiting heat-production. Accordingly, electri...

متن کامل

Carbon dioxide and pH effects on temperature-sensitive and -insensitive hypothalamic neurons.

The preoptic-anterior hypothalamus (POAH) controls body temperature, and thermoregulatory responses are impaired during hypercapnia. If increased CO(2) or its accompanying acidosis inhibits warm-sensitive POAH neurons, this could provide an explanation for thermoregulatory impairment during hypercapnia. To test this possibility, extracellular electrophysiological recordings determined the effec...

متن کامل

A Case of Multiple Organ Failure due to Heat Stoke Following a Warm Bath

Heat stroke is a potentially fatal disorder that's caused by an extreme elevation in body temperature. We report here an unusual case of multiple organ failure that was caused by classical, nonexertional heat stroke due to taking a warm bath at home. A 68 year old diabetic man was hospitalized for loss of consciousness. He was presumed to have been in a warm bath for 3 hrs and his body temperat...

متن کامل

Neuronal basis of Hammel's model for set-point thermoregulation.

In 1965, H. T. Hammel proposed a neuronal model to explain set-point thermoregulation. His model was based on a synaptic network encompassing four different types of hypothalamic neurons: i.e., warm-sensitive and temperature-insensitive neurons and heat loss and heat production effector neurons. Although some modifications to this model are suggested, recent electrophysiological and morphologic...

متن کامل

Invited Review HIGHLIGHTED TOPIC A Physiological Systems Approach to Human and Mammalian Thermoregulation Neuronal basis of Hammel’s model for set-point thermoregulation

Boulant, Jack A. Neuronal basis of Hammel’s model for set-point thermoregulation. J Appl Physiol 100: 1347–1354, 2006; doi:10.1152/japplphysiol.01064.2005.—In 1965, H. T. Hammel proposed a neuronal model to explain set-point thermoregulation. His model was based on a synaptic network encompassing four different types of hypothalamic neurons: i.e., warm-sensitive and temperature-insensitive neur...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2007