Indicators of histohypoxia

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Abstract
Cellular tissue damage due to inadequate oxygen supply is frequently encountered in the critically ill patient and can be the end result of a number of conditions. The eventual disruption to the normal processes required for the cell to survive can be due either to the hypoxic state per se or by damage caused during reperfusion of the tissue. Blood gas analysis is commonly used as a macro indicator of oxygen supply, state of art blood gas analysers provide information for oxygen tension (pO2), haemoglobin oxygen saturation (SO2) and concentration (THb), ideally, in arterial and mixed venous blood. The concurrent measurement of carbon dioxide tension (pCO2) and pH will allow the calculation of variables which assist in differentiating between respiratory and non-respiratory conditions. Measurement of cardiac output and clinical assessment of the patients' oxygen requirements will complete the macro picture of supply and demand and although computed indicators of hypoxia have been improved in recent years (1, 2) the definitive diagnosis of histohypoxia requires the measurement of the cellular and subcellular products of metabolic processes that are present when an inappropriate concentration of oxygen has been experienced. However, increases, for example, in blood lactate concentration can occur when an ischaemic area is reperfused and it is argued conversely, that the absence of hyperlactataemia in conditions such as acute respiratory distress syndrome does not necessarily preclude delivery dependence of oxygen consumption with the attendant potential for tissue hypoxia (3). Nevertheless there is general agreement that blood lactate levels can serve as a reliable clinical guide to therapy (4). The laboratory measurement of the metabolic products that accumulate when cellular oxygen supply is limited has become far less labour intensive and with the development of increasingly sophisticated instrumentation, these analytes can be available in small to medium hospital laboratories as well as the larger units. The relatively rapid and accurate analysis of metabolites that accumulate in hypoxic states has allowed us to measure concentrations of blood lactate, pyruvate, β-hydroxybutyrate and acetoacetate and calculate the lactate/pyruvate ratio and β-hydroxybutyrate/acetoacetate ratio. These measurements and ratios can then be compared with the non invasive macro blood gas indicators in order to determine their effectiveness as additional “routine” investigations and to indicate how each of the variables contributes to the eventual diagnosis. The parameters used in this study are as follows: Oxygen tension - pO2, Haemoglobin oxygen saturation - SaO2 Haemoglobin concentration - THb Hydrogen ion concentration as - pH Concentration of extractable oxygen - Cx Oxygen extraction tension - px Conditional extraction at an assumed pvO2 = 30 mmHg - C(a-30)O2 Lactate and pyruvate β-hydroxybutyrate and acetoacetate