The Hemoglobin System

Adair, G. S.

doi:10.1016/s0021-9258(18)85018-9

“…A hypoxic cellular environment is caused by hypoxaemia, which is a reduction in arterial blood oxygen partial pressure (PaO 2 ) and haemoglobin-bound oxygen saturation (SaO 2 ) that results in inadequate oxygen delivery to tissues. Hypoxaemia is characterised by a sigmoidal relationship between PaO 2 and SaO 2 , which occurs when breathing atmospheric PO 2 below 149 mmHg (Adair, 1925;Lambertsen et al, 1952; Figure 1). In a resting, healthy individual at sea-level, an SaO 2 is ~97-99% and remains relatively stable until PaO 2 declines below ~80 mmHg (Collins et al, 2015).…”

Section: Hypoxiamentioning

confidence: 99%

Hypoxic Hypoxia and Brain Function in Military Aviation: Basic Physiology and Applied Perspectives

Shaw

¹

,

Cabre²

2021

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Acute hypobaric hypoxia (HH) is a major physiological threat during high-altitude flight and operations. In military aviation, although hypoxia-related fatalities are rare, incidences are common and are likely underreported. Hypoxia is a reduction in oxygen availability, which can impair brain function and performance of operational and safety-critical tasks. HH occurs at high altitude, due to the reduction in atmospheric oxygen pressure. This physiological state is also partially simulated in normobaric environments for training and research, by reducing the fraction of inspired oxygen to achieve comparable tissue oxygen saturation [normobaric hypoxia (NH)]. Hypoxia can occur in susceptible individuals below 10,000 ft (3,048 m) in unpressurised aircrafts and at higher altitudes in pressurised environments when life support systems malfunction or due to improper equipment use. Between 10,000 ft and 15,000 ft (4,572 m), brain function is mildly impaired and hypoxic symptoms are common, although both are often difficult to accurately quantify, which may partly be due to the effects of hypocapnia. Above 15,000 ft, brain function exponentially deteriorates with increasing altitude until loss of consciousness. The period of effective and safe performance of operational tasks following exposure to hypoxia is termed the time-of-useful-consciousness (TUC). Recovery of brain function following hypoxia may also lag beyond arterial reoxygenation and could be exacerbated by repeated hypoxic exposures or hyperoxic recovery. This review provides an overview of the basic physiology and implications of hypoxia for military aviation and discusses the utility of hypoxia recognition training.

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“…3, where the n value of the ferricyanide-ferrocyanide system in this same experiment is 1 and compares excellently with the slope calculated from other data utilizing this system (Barnard, 1931). We do not, at this time, consider the value of n in this particular oxidation-reduction titration as fortifying Adair's (1925) hypothesis as to the oxygenation of hemoglobin any more than in 1928, when we first measured and secured the value of n = 1 in the electrochemical equation was it considered an objection to the theory of Hill (1910). Conant and McGrew (1929), from whose paper it is inferred that the electrometric measurements of n in the oxidation-reduction equation (HbO,)n --K' assigned to n in the former case a value of 2 as determined by Conant and Scott (1928).…”

Section: Resultsmentioning

confidence: 84%

The Effect of Cyanide and of Variation in Alkalinity on the Oxidation-Reduction Potential of the Hemoglobin-Methemoglobin System

Barnard

¹

1933

Journal of General Physiology

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Since Ray Lankester (1869) studied the effects of cyanogen upon hemoglobin, numerous divergent reports, relative to compounds of cyanide with the blood pigment have appeared in the literature. These reports may now be interpreted in light of recent investigations on the physical chemistry of the hemoglobin molecule. For instance, that Hoppe-Seyler (1868) obtained a crystalline reaction product of hemoglobin and cyanide we neither doubt, nor explain as did Gamgee (1898) on a basis of inadequate separation. Hemoglobin has many basic groups functioning throughout the pH range over which cyanion is bound and there are reasons for assuming the existence of ferrous and ferric hemoglobin cyanides of varying composition; cyanide being linked to one or more of the basic groups of the globin radicle, as any protein may combine with acidic radicles.In this study we are more interested in the nature of cyanide linkages with the prosthetic groups of hemoglobin derivatives. The conclusions of Warburg (1923), in which he ascribes the r61e of respiratory catalyst to the hematin-hemochromogen system; the wide distribution of this system in nature (Keilin, 1925), and the poisonous effects of cyanide ion upon the system (Warburg, 1923; Dixon and Elliot, 1929, direct our attention to the possible modes of combination of cyanide ion with the constituents of the system. A compound of cyanide and hematin has been prepared by Ziemke and Miller (1901), who found its spectroscopic bands to be similar in position to those of cyanmethemoglobin. Anson and Mirsky (1928) describe two compounds of "recluced heine" with cyanide. A crystalline compound of cyanide and

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“…(y/[ 1 -y\) against log10 p Actually, as Adair (1925) and many subsequent observers have noted, such plots are sigmoid rather than linear. The data of the present paper, since they include far more accurate observation at the two ends of the curve than have hitherto been available, should be particularly effective for confirming the sigmoid character of these log-log plots.…”

Section: -2/mentioning

confidence: 96%

“…equation (1) of the present paper). In his pioneer paper on the intermediate compound theory, Adair (1925) considered several special forms of the general equation but did not feel able to follow up any of them in detail. Subsequently Forbes & Roughton (1931), Pauling (1935, Wyman and his colleagues (Wyman 1948;Allen, Guthrie & Wyman 1950;Wyman & Allen 1951) and Roughton (1949) have developed par ticular hypotheses as to the relationships between the constants K x, K % , K 3 and K4.…”

Section: -2/mentioning

confidence: 99%

The determination of the individual equilibrium constants of the four intermediate reactions between oxygen and sheep haemoglobin

1955

Proc. R. Soc. Lond. B

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It is now generally accepted that the equilibrium between oxygen (or carbon monoxide) and mammalian haemoglobin is expressible in terms of four intermediate reactions Hb 4 + O 2 ⇌ Hb 4 O 2 (equilibrium constant K 1 ), Hb 4 O 2 + O 2 ⇌ Hb 4 O 4 ( K 2 ), Hb 4 O 4 + O 2 ⇌ Hb 4 O 6 ( K 3 ) and Hb 4 O 6 + O 2 ⇌ Hb 4 O 6 ( K 4 ), as Adair first suggested about 30 years ago. Hitherto, experimental data on the oxyhaemoglobin dissociation curve have not been precise enough to permit the direct determination of the equilibrium constants, K 1 to K 4 , of the intermediate reactions. Recently, however, the accuracy of the observations at the top and at the bottom ends of the dissociation curve has been improved about 10-fold, i.e. to within ±0.05% saturation. From such measurements—together with 2- to 3-fold more accurate data over the main part of the curve—it has now proved possible to evaluate directly, by standard statistical procedure, the values of K 1 (± ca . 5%), K 2 ( ± ca . 25%), K 3 ( ± ca . 33%) and K 4 (± ca . 13.7%) for sheep haemoglobin solutions at alkaline pH (9.1). Unfortunately, it is not yet feasible to extend the attack fully to haemoglobin solutions at neutral pH, since the method for obtaining highly accurate data at the top of the dissociation curve breaks down at this pH. For 3 to 4% solutions of sheep haemoglobin at pH 9.1, K 1 , K 2 and K 3 are found to be of the same order, whereas K 4 is from 10 to 20 times greater, thus pointing to some marked internal change in the sheep haemoglobin molecule after three molecules of oxygen have combined therewith. From the effect of temperature on K 1 and K 4 , values are derived for the heats of all the intermediate reactions and for the entropies, Δ S 1 and Δ S 4 , of the first and last of the intermediate reactions. There are appreciable differences between the heats of the intermediate reactions, contrary to the old view that these heats are all equal. Preliminary, but very rough, data are also given on the effect of pH and dilution. In the discussion it is shown that the new and more accurate data on the dissociation curve are incompatible with previous special theories of the oxygen-haemoglobin equilibrium, which had been based on, and checked by, conventional but less accurate experimental data. Wyman’s recent symmetry theory is a striking example in the latter category and hence is given detailed consideration. The kinetic implications of the higher value of K 4 are briefly considered. It appears that the responsibility therefore is about equally borne by the relative increase in k' 4 , the velocity constant of the combination Hb 4 O 6 + O 2 → Hb 4 O 8 , and by the relative decrease in k 4 , the velocity constant of the dissociation Hb 4 O 8 → Hb 4 O 6 + O 2 .

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The Hemoglobin System

Cited by 783 publications

References 13 publications

Hypoxic Hypoxia and Brain Function in Military Aviation: Basic Physiology and Applied Perspectives

Hypoxic Hypoxia and Brain Function in Military Aviation: Basic Physiology and Applied Perspectives

The Effect of Cyanide and of Variation in Alkalinity on the Oxidation-Reduction Potential of the Hemoglobin-Methemoglobin System

The determination of the individual equilibrium constants of the four intermediate reactions between oxygen and sheep haemoglobin

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