Physiological comparison of hemorrhagic shock and (Formula presented.)O 2 max: A conceptual framework for defining the limitation of oxygen delivery

Victor A. Convertino, Kristen R. Lye, Natalie J. Koons, Michael Joseph Joyner

Research output: Contribution to journalReview article

2 Scopus citations


Based on evidence extracted from a cross-sectional review of the literature, we sought to advance a novel conceptual framework that the physiology of hemorrhagic shock from exsanguination and maximal oxygen uptake ((Formula presented.) O 2 max), induced by physical exercise, shares key common features. As such, this review focuses on the notion that intolerance to inadequate oxygen delivery (DO 2 ) resulting from associated states of hypovolemia appears to be a common physiological link that “connects” hemorrhagic shock to the physiology that limits maximal aerobic capacity. Our approach focuses on the similarities in a complex cascade of cardiopulmonary, metabolic and autonomic compensatory responses during hemorrhage and maximal physical exertion that ultimately function to avoid critical levels of DO 2 (DO 2crit ) and are manifested by elevation in blood lactate levels. We introduce a paradigm of absolute (i.e. hemorrhage) versus relative (i.e. exercise) hypovolemia as a primary physiological factor that contributes to reaching DO 2crit , and define the concept of “O 2 deficit” to replace the clinical concept of O 2 debt. Using the peer-reviewed literature, we provide human data obtained from patients who suffered hemorrhagic shock from severe blood loss and compare it to healthy subjects who performed maximal exercise. We include a novel conceptual framework of the continuum of metabolic relationship between DO 2 and (Formula presented.) O 2 that is manifested as the final step during both progressive blood loss leading to hemorrhagic shock and at (Formula presented.) O 2 max. We present evidence to support the contribution of utilizing “O 2 extraction reserve” as the initial mechanism for developing an O 2 deficit, and the notion of individual variability in compensatory responses. In the absence of reversing inadequate DO 2 , an increased reliance on O 2 extraction reserve, cellular anaerobic glycolysis, and phosphocreatine stores to supplement the energy required by the tissues for normal function will deplete a finite capacity for compensation. In the end, acidity reflected by a blood pH ≤ ∼7.0 leads to disturbance of normal cell functioning of metabolic machinery manifested by irreversible shock in the case of hemorrhage or physical exhaustion when (Formula presented.) O 2 max is reached. Impact statement: Disturbance of normal homeostasis occurs when oxygen delivery and energy stores to the body’s tissues fail to meet the energy requirement of cells. The work submitted in this review is important because it advances the understanding of inadequate oxygen delivery as it relates to early diagnosis and treatment of circulatory shock and its relationship to disturbance of normal functioning of cellular metabolism in life-threatening conditions of hemorrhage. We explored data from the clinical and exercise literature to construct for the first time a conceptual framework for defining the limitation of inadequate delivery of oxygen by comparing the physiology of hemorrhagic shock caused by severe blood loss to maximal oxygen uptake induced by intense physical exercise. We also provide a translational framework in which understanding the fundamental relationship between the body’s reserve to compensate for conditions of inadequate oxygen delivery as a limiting factor to (Formula presented.) O 2 max helps to re-evaluate paradigms of triage for improved monitoring of accurate resuscitation in patients suffering from hemorrhagic shock.

Original languageEnglish (US)
JournalExperimental Biology and Medicine
StatePublished - Jan 1 2019



  • blood lactate
  • blood pH
  • compensatory reserve
  • Oxygen deficit
  • oxygen extraction reserve

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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