A simplified bedside approach to acid–base: fluid physiology utilizing classical and physicochemical approaches

Hughes, Ryan; Brain, Matthew

doi:10.1016/j.mpaic.2013.07.013

Cited by 9 publications

(8 citation statements)

References 3 publications

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“…Stewart ( Stewart, 1983 ; Hughes and Brain, 2013 ) has suggested an insightful approach to understanding acid-base changes in biological systems. In this system, intracellular [H + ] is determined by CO 2 tension, the balance of concentrations of the strongly dissociated ions (the strong ion difference [SID]), and the requirement for electroneutrality.…”

Section: Introductionmentioning

confidence: 99%

Control of Cerebral Blood Flow by Blood Gases

2021

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Cerebrovascular reactivity can be measured as the cerebrovascular flow response to a hypercapnic challenge. The many faceted responses of cerebral blood flow to combinations of blood gas challenges are mediated by its vasculature’s smooth muscle and can be comprehensively described by a simple mathematical model. The model accounts for the blood flow during hypoxia, anemia, hypocapnia, and hypercapnia. The main hypothetical basis of the model is that these various challenges, singly or in combination, act via a common regulatory pathway: the regulation of intracellular hydrogen ion concentration. This regulation is achieved by membrane transport of strongly dissociated ions to control their intracellular concentrations. The model assumes that smooth muscle vasoconstriction and vasodilation and hence cerebral blood flow, are proportional to the intracellular hydrogen ion concentration. Model predictions of the cerebral blood flow responses to hypoxia, anemia, hypocapnia, and hypercapnia match the form of observed responses, providing some confidence that the theories on which the model is based have some merit.

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Section: Introductionmentioning

confidence: 99%

Control of Cerebral Blood Flow by Blood Gases

2021

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“…The major complexity of this model lies in the carriage of O 2 and CO 2 in blood. The CO 2 dissociation curves were derived from the Stewart approach to acid base regulation (Hughes & Brain, ), details of which are to be found in Duffin (), and the O 2 dissociation curves from relationships derived from in vivo measurements described in Balaban et al . ().…”

Section: Methodsmentioning

confidence: 99%

A mathematical model of cerebral blood flow control in anaemia and hypoxia

Duffin

Hare

Fisher

2020

The Journal of Physiology

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Key points The control of cerebral blood flow in hypoxia, anaemia and hypocapnia is reviewed with an emphasis on the links between cerebral blood flow and possible stimuli. A mathematical model is developed to examine the changes in the partial pressure of oxygen in brain tissue associated with changes in cerebral blood flow regulation produced by carbon dioxide, anaemia and hypoxia. The model demonstrates that hypoxia, anaemia and hypocapnia, alone or in combination, produce varying degrees of cerebral hypoxia, an effect exacerbated when blood flow regulation is impaired. The suitability of brain hypoxia as a common regulator of cerebral blood flow in hypoxia and anaemia was explored, although we failed to find support for this hypothesis. Rather, cerebral blood flow appears to be related to arterial oxygen concentration in both anaemia and hypoxia. Abstract A mathematical model is developed to examine the changes in the partial pressure of oxygen in brain tissue associated with changes in cerebral blood flow regulation produced by carbon dioxide, anaemia and hypoxia. The model simulation assesses the physiological plausibility of some currently hypothesized cerebral blood flow control mechanisms in hypoxia and anaemia, and also examines the impact of anaemia and hypoxia on brain hypoxia. In addition, carbon dioxide is examined for its impact on brain hypoxia in the context of concomitant changes associated with anaemia and hypoxia. The model calculations are based on a single compartment of brain tissue with constant metabolism and perfusion pressure, as well as previously developed equations describing oxygen and carbon dioxide carriage in blood. Experimental data are used to develop the control equations for cerebral blood flow regulation. The interactive model illustrates that there are clear interactions of anaemia, hypoxia and carbon dioxide in the determination of cerebral blood flow and brain tissue oxygen tension. In both anaemia and hypoxia, cerebral blood flow increases to maintain oxygen delivery, with brain hypoxia increasing when cerebral blood flow control mechanisms are impaired. Hypocapnia superimposes its effects, increasing brain hypoxia. Hypoxia, anaemia and hypocapnia, alone or in combination, produce varying degrees of cerebral hypoxia, and this effect is exacerbated when blood flow regulation is degraded by conditions that negatively impact cerebrovascular control. Differences in brain hypoxia in anaemia and hypoxia suggest that brain oxygen tension is not a plausible sensor for cerebral blood flow control.

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“…The model assumes that intracellular [H + ] is regulated to support the activity of proteins and enzymes (Boron, 2004) by adjusting the difference in the intracellular concentration of strongly dissociated ions [strong ion difference (SID)] as described by Stewart (1983) and elaborated upon by Jennings (1994). I suggest that the adjustment of intracellular [SID] requires membrane transporters of strongly dissociated ions (Hughes & Brain, 2013) dependent on an energy metabolism involving O 2 . As a result, a failure to supply sufficient O 2 causes [H + ] regulation to fail; subsequently, cytosolic [H + ] increases and the resulting transmitter release stimulates carotid sinus afferents.…”

Section: Methodsmentioning

confidence: 99%

Fail‐safe aspects of oxygen supply

Duffin

2020

The Journal of Physiology

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Key points A fall in oxygen supply releases a remedial response that is otherwise prevented when the oxygen supply is sufficient; for example, the remedial function of HIF‐1α is released when oxygen levels fall. Concept: the physiological responses initiated when oxygen supply is compromised operate in a fail‐safe manner. This concept is applied to two cases: the control of cerebral blood flow, and the detection of hypoxia by the carotid body. The fail‐safe oxygen supply concept was tested with simple computer simulations to demonstrate its function and verify the ability to reproduce measured data. The computer model reproduced published observations, suggesting that the fail‐safe concept can be considered as a principle that provides novel insight into the physiology of oxygen supply in these cases. Abstract An engineered fail‐safe system automatically prevents or mitigates the consequences of a system failure. This operational concept can be applied both to the delivery of oxygen to the brain during hypoxia and anaemia, and to the carotid body response to hypoxia and hypercapnia. I aimed to develop simple mathematical models of these fail‐safe processes and examine their ability to replicate experimental observations. The intent is to demonstrate the validity of applying the fail‐safe concept, not to reveal the details of the physiology involved. The model calculations are based on a single compartment of the relevant tissue in each case that is challenged with a decrease in oxygen supply. The model equation parameters were adjusted to reproduce experimental observations. The fail‐safe model of cerebral blood flow control yielded results similar in form to published experimental observations of the cerebral blood flow responses to hypoxia and anaemia. The fail‐safe model of carotid body glomus cell control of intracellular hydrogen ion concentration also yielded results similar in form to observations of carotid sinus nerve responses to hypoxia and hypercapnia. The ability of these simple models to simulate experimental observations demonstrates the applicability of the fail‐safe concept to oxygen delivery. I suggest that a fail‐safe view of oxygen delivery provides novel physiological insight.

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A simplified bedside approach to acid–base: fluid physiology utilizing classical and physicochemical approaches

Cited by 9 publications

References 3 publications

Control of Cerebral Blood Flow by Blood Gases

Control of Cerebral Blood Flow by Blood Gases

A mathematical model of cerebral blood flow control in anaemia and hypoxia

Fail‐safe aspects of oxygen supply

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