Oxygen transport is tightly regulated by control of ventilation, circulation and red cell mass- it’s complicated !

This explains how vasoconstriction and vasodilation works . It is AMAZING !

This review [The oxygen trail: tissue oxygenation A T Nathan and M Singer Bloomsbury Institute of Intensive Care Medicine, University College London Medical School, London,UK] has attempted to demonstrate the complex relationship between oxygen and the body, with the obvious benefits and harm that imbalance in the supply-demand ratio can bring. The body responds to changes in this ratio by respiratory, macrovascular, microvascular, hormonal and cellular mechanisms which inter-relate in numerous ways. Increased understanding of these mechanisms will lead to more appropriate monitoring and interventions.……

Meaning of DO2: Oxygen extraction ratio (O2ER) is the ratio of oxygen consumption (VO2)  to oxygen delivery (DO2)

…....Oxygen transport is tightly regulated by control of ventilation, circulation and red cell mass.

……When whole body DO2 is compromised, flow is redistributed to organs unable to significantly increase oxygen extraction ratios to sustain activity and function. By the same virtue, flow is reduced redistribution of whole body DO2 has been shown to be a determinant of whole-body critical DO2 in a mathematical model.” The oxygen trail: tissue oxygenation A T Nathan and M Singer Bloomsbury Institute of Intensive Care Medicine, University College London Medical School, London, UK https://watermark.silverchair.com/55-1-96.pdf

Microvascular architecture

The microvasculature can be subdivided into flow controlling vessels (medium-sized arterioles) and distribution vessels (smaller arterioles) .

Most of the arteriovenous pressure gradient is dissipated at arteriolar level, though the distribution of flow within the tissues is determined by autoregulation at the level of the precapillary sphincters or precapillary arterioles. It has been suggested that arteriolar control of flow is under the regulation of sympathetic vasoconstrictor tone and regional factors , while distributive vessels are subject to metabolic autoregulation. It is the balance between sympathetic vasoconstrictor tone and metabolically regulated vasodilator tone that matches O2 supply to demand. Interstitial PO2, which is determined by the adequacy of tissue oxygenation, may be the mediator of this vasodilation by its effect on vascular smooth muscle. Cardiovascular reflexes in response to hypovolaemia may further augment the efficiency of local O, extraction. The microcirculation is also under the control of humoral factors (renin, vasopressin) and neural factors (Fig. 3). These factors assume varying significance based on the specific organ and its sensitivity.…....The oxygen trail: tissue oxygenation A T Nathan and M Singer Bloomsbury Institute of Intensive Care Medicine, University College London Medical School, London, UK https://watermark.silverchair.com/55-1-96.pdf

Oxygen Dynamics in Immune Homeostasis and Inflammation

Oxygen levels vary between 0 and 19% in healthy mammalian tissues.

The tissues closest to atmospheric oxygen levels (21.1% or 160 mmHg at sea level) are those of the upper airways (approximately 19%, 150 mmHg) (2). Lymphoid tissues are lower in oxygen; bone marrow is approximately 6.4% (50 mmHg) (2) and the spleen can range from 3 to 4% (25–35 mmHg) (3). The gastrointestinal (GI) tract, which contains upwards of 70–80% of one’s total lymphocytes (4), has an especially dynamic oxygen range (5). The lumen, with its many obligate anaerobic commensal bacteria, is close to 0% oxygen (6). The intestinal tissue, including the lamina propria where many T cells reside, is approximately 7% oxygen (58 mmHg) (2). Immune cells encounter a wide range of oxygen levels as they traffic within the human body (2). T cells begin life in the bone marrow; progenitors migrate to the thymus for development, then to the blood to either circulate through the blood or lymphatic systems or to become a tissue-resident T cell, in such various organs as the lung, skin, brain, or GI tract. A progenitor or mature T cell may be exposed an oxygen concentration between 3 and 19% oxygen. These oxygen levels can be further modulated within the cell’s microenvironment.


Carbon dioxide (CO(2)) is a physiological gas found at low levels in the atmosphere and produced in cells during the process of aerobic respiration. Consequently, the levels of CO(2) within tissues are usually significantly higher than those found externally. Shifts in tissue levels of CO(2) (leading to either hypercapnia or hypocapnia) are associated with a number of pathophysiological conditions in humans and can occur naturally in niche habitats such as those of burrowing animals. Clinical studies have indicated that such altered CO(2) levels can impact upon disease progression. Recent advances in our understanding of the biology of CO(2) has shown that like other physiological gases such as molecular oxygen (O(2)) and nitric oxide (NO), CO(2) levels can be sensed by cells resulting in the initiation of physiological and pathophysiological responses. Acute CO(2) sensing in neurons and peripheral and central chemoreceptors is important in rapidly activated responses including olfactory signalling, taste sensation and cardiorespiratory control. Furthermore, a role for CO(2) in the regulation of gene transcription has recently been identified with exposure of cells and model organisms to high CO(2) leading to suppression of genes involved in the regulation of innate immunity and inflammation. This latter, transcriptional regulatory role for CO(2), has been largely attributed to altered activity of the NF-B family of transcription factors. Here, we review our evolving understanding of how CO(2) impacts upon gene transcription. Regulation of Gene Expression by Carbon Dioxide Cormac T Taylor 1Eoin P Cummins Review J Physiol .  2011 Feb 15;589(Pt 4):797-803.  doi: 10.1113/jphysiol.2010.201467.Epub 2011 Jan 4.



The finding that sickness behavior occurs in all mammals and birds indicates that communication between the immune system and brain has been evolutionarily conserved and forms an important physiological adaptive response that favors survival of the organism during infections. The fact that cytokines act in the brain to induce physiological adaptations that promote survival has led to the hypothesis that inappropriate, prolonged activation of the innate immune system may be involved in a number of pathological disturbances in the brain, ranging from Alzheimer’s disease to stroke. Conversely, the newly-defined role of cytokines in a wide variety of systemic co-morbid conditions, ranging from chronic heart failure to obesity, may begin to explain changes in the mental state of these subjects. Indeed, the newest findings of cytokine actions in the brain offer some of the first clues about the pathophysiology of certain mental health disorders, including depression. Brain Behav Immun.  2007 Feb;21(2):153-60. doi: 10.1016/j.bbi.2006.09.006. Epub 2006 Nov 7. Twenty Years of Research on Cytokine-Induced Sickness Behavior

Robert Dantzer 1Keith W Kelley

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