Physiological And Pathological Responses To Hypoxia And High Altitude

The appearance of photosynthetic organisms about 3 billion years ago increased the partial pressure of oxygen (PO2) in the atmosphere and enabled the evolution of organisms that use glucose and oxygen to produce ATP by oxidative phosphorylation. Hypoxia is commonly defined as the reduced availability of oxygen in the tissues produced by different causes, which include reduction of atmospheric PO2 as in high altitude, and secondary to pathological conditions such as sleep breathing and pulmonary disorders, anemia, and cardiovascular alterations leading to inadequate transport, delivery, and exchange of oxygen between capillaries and cells. Nowadays, it has been shown that hypoxia plays an important role in the genesis of several human pathologies including cardiovascular, renal, myocardial and cerebral diseases in fetal, young and adult life. Several mechanisms have evolved to maintain oxygen homeostasis. Certainly, all cells respond and adapt to hypoxia, but only a few of them can detect hypoxia and initiate a cascade of signals intended to produce a functional systemic response. In mammals, oxygen detection mechanisms have been extensively studied in erythropoietin-producing cells, chromaffin cells, bulbar and cortical neurons, pulmonary neuroepithelial cells, smooth muscle cells of pulmonary arteries, and chemoreceptor cells. While the precise mechanism underpinning oxygen, sensing is not completely known several molecular entities have been proposed as possible oxygen sensors (i.e. Hem proteins, ion channels, NADPH oxidase, mitochondrial cytochrome oxidase). Remarkably, cellular adaptation to hypoxia is mediated by the master oxygen-sensitive transcription factor, hypoxia-inducible factor-1, which can induce up-regulation of different genes to cope the cellular effects related to a decrease in oxygen levels. Short-term responses to hypoxia included mainly chemoreceptor-mediated reflex ventilatory and hemodynamic adaptations to manage the low oxygen concentration while more prolonged exposures to hypoxia can elicit more sustained physiological responses including switch from aerobic to anaerobic metabolism, vascularization, and enhancement of blood O2 carrying capacity. The focus of this research topic is to provide an up-to-date vision on the current knowledge on oxygen sensing mechanism, physiological responses to acute or chronic hypoxia and cellular/tissue/organ adaptations to hypoxic environment.

Hypoxia is a constant threat throughout life. International experts from many different fields, including clinicians, clinical researchers, and basic scientists, have contributed to this volume, presenting state-of-the-art information regarding normal and abnormal (pathophysiological) responses to hypoxia. The topics covered include visitors to high altitude, the latest developments on high-altitude cerebral and pulmonary edema, the brain in hypoxia, high-altitude headache, and similarities between ischemic and hypoxic injury to the brain. In addition topics are covered such as blood-brain barrier in hypoxia, hypoxia interactions with vascular growth, and how humans adjust to extreme hypoxia.

​ Over the last decade the science and medicine of high altitude and hypoxia adaptation has seen great advances. High Altitude: Human Adaptation to Hypoxia addresses the challenges in dealing with the changes in human physiology and the particular medical conditions that arise from exposure to high altitude. In-depth and comprehensive chapters cover both the basic science and the clinical consequences of exposure to high altitude. Genetic, cellular, organ and whole body system responses to high altitudes are covered and chapters discuss these effects on a wide range of diseases. Expert authors provide insight into the care of patients with pre-existing medical conditions that fail in some cases to adapt as well as offer insights into how high altitude research can help critically ill patients. High Altitude: Human Adaptation to Hypoxia is an important new volume that offers a window into greater understanding and more successful treatment of hypoxic human diseases.

Recently, endurance athletes and high altitude climbers have gained access to commercially available, portable normobaric hypoxic chambers. Intermittent exposures to hypoxia in these chambers may elicit adaptations similar to those observed during acclimatization to altitude. Manufactures of these systems purport that intermittent exposures may elicit adaptations similar to those observed in response to the hypoxia of high altitude, however there have been no reports in the scientific literature that ventilatory acclimatization or alterations in cerebrovascular dynamics occur following repeated episodes in the portable chambers. The main conclusions are that an intermittent normobaric hypoxic intervention, consisting of five consecutive overnight exposures to a simulated altitude of 4300m, elicits perturbations in the acute cerebrovascular and ventilatory responses to both hypoxia and hypercapnia, which are similar to changes following chronic altitude exposure. Individual variability to intermittent hypoxia may have an impact on the rate at which the process of acclimatization proceeds. The extent of physiological and symptomatic responses to intermittent hypoxia are likely to be associated with the severity of hypoxia as well as the length and number of recurrent episodes of hypoxia.

The Novartis Foundation Series is a popular collection of the proceedings from Novartis Foundation Symposia, in which groups of leading scientists from a range of topics across biology, chemistry and medicine assembled to present papers and discuss results. The Novartis Foundation, originally known as the Ciba Foundation, is well known to scientists and clinicians around the world.

This presentation describes various aspects of the regulation of tissue oxygenation, including the roles of the circulatory system, respiratory system, and blood, the carrier of oxygen within these components of the cardiorespiratory system. The respiratory system takes oxygen from the atmosphere and transports it by diffusion from the air in the alveoli to the blood flowing through the pulmonary capillaries. The cardiovascular system then moves the oxygenated blood from the heart to the microcirculation of the various organs by convection, where oxygen is released from hemoglobin in the red blood cells and moves to the parenchymal cells of each tissue by diffusion. Oxygen that has diffused into cells is then utilized in the mitochondria to produce adenosine triphosphate (ATP), the energy currency of all cells. The mitochondria are able to produce ATP until the oxygen tension or PO2 on the cell surface falls to a critical level of about 4–5 mm Hg. Thus, in order to meet the energetic needs of cells, it is important to maintain a continuous supply of oxygen to the mitochondria at or above the critical PO2 . In order to accomplish this desired outcome, the cardiorespiratory system, including the blood, must be capable of regulation to ensure survival of all tissues under a wide range of circumstances. The purpose of this presentation is to provide basic information about the operation and regulation of the cardiovascular and respiratory systems, as well as the properties of the blood and parenchymal cells, so that a fundamental understanding of the regulation of tissue oxygenation is achieved.

* Cutting-edge information on how to prevent, diagnose, and treat altitude illness and hypoxia in everyday life * Interweaves fascinating research discoveries with dramatic first-person accounts * Authored by a celebrated mountaineer and physician who pioneered research in the field From the time of his historic expedition to Nanda Devi in the high Himalaya, Charles Houston, M.D., was fascinated by the effects of altitude on the human body. Why do people get sick in the mountains? What are the symptoms of hypoxia -- lack of sufficient oxygen -- that also occurs in everyday life, sometimes chronically due to disease? How can we decrease the incidence of illness and death? This edition incorporates current research on the effects of altitude on humans, and Houston (now deceased) joined forces with an educator and a medical writer in a text made even more accessible for the average reader while retaining the depth of material of particular use to the medical community. This edition of this seminal text added chapters on vision and the eye at altitude, chronic and subacute altitude illness, and the limits to work at altitude (with implications for athletic training). It presents information on genetics and gender differences and more on flight and space travel, on understanding and treating sea-level hypoxic illnesses, and on who can (or should not) go to high altitude, and much more. With an expanded glossary of terms.