Hemorrhage is a leading cause of death following traumatic injuries in the United States. Much of the previous work in assessing the physiology and pathophysiology underlying blood loss has focused on descriptive measures of hemodynamic responses such as blood pressure, cardiac output, stroke volume, heart rate, and vascular resistance as indicators of changes in organ perfusion. More recent work has shifted the focus toward understanding mechanisms of compensation for reduced systemic delivery and cellular utilization of oxygen as a more comprehensive approach to understanding the complex physiologic changes that occur following and during blood loss. In this article, we begin with applying dimensional analysis for comparison of animal models, and progress to descriptions of various physiological consequences of hemorrhage. We then introduce the complementary side of compensation by detailing the complexity and integration of various compensatory mechanisms that are activated from the initiation of hemorrhage and serve to maintain adequate vital organ perfusion and hemodynamic stability in the scenario of reduced systemic delivery of oxygen until the onset of hemodynamic decompensation. New data are introduced that challenge legacy concepts related to mechanisms that underlie baroreflex functions and provide novel insights into the measurement of the integrated response of compensation to central hypovolemia known as the compensatory reserve. The impact of demographic and environmental factors on tolerance to hemorrhage is also reviewed. Finally, we describe how understanding the physiology of compensation can be translated to applications for early assessment of the clinical status and accurate triage of hypovolemic and hypotensive patients. © 2021 American Physiological Society. Compr Physiol 11:1531-1574, 2021.
Copyright © 2021 American Physiological Society. All rights reserved.