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      Refractory Lactic Acidosis and an Approach to its Management - A Case Report

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          Abstract

          Background

          Lactic acidosis (LA) is a complication of diseases commonly seen in intensive care patients which carries an increased risk of mortality. It is classified by its pathophysiology; Type A results from tissue hypo-perfusion and hypoxia, and Type B results from abnormal metabolic activity in the absence of hypoxia. Reports of the co-occurrence of both types have been rarely reported in the literature relating to intensive care patients. This case report describes the challenging management of a patient diagnosed with both Type A and Type B LA.

          Case presentation

          A 55-year-old female with newly diagnosed diffuse large B-cell lymphoma (DLBCL) developed hospital-acquired pneumonia, respiratory failure, shock and intra-abdominal septicaemia from a bowel perforation. Blood gases revealed a mixed picture lactic acidosis. Correction of septic shock, respiratory failure and surgical repair caused initial improvement to the lactic acidosis, but this gradually worsened in the intensive care unit. Only upon starting chemotherapy and renal replacement therapy was full resolution of the lactic acidosis achieved. The patient was discharged but succumbed to her DLBCL several months later.

          Conclusion

          Type A and Type B LA can co-occur, making management difficult. A systematic approach can help diagnose any underlying pathology and aid in early management.

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          Most cited references18

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            Akt stimulates aerobic glycolysis in cancer cells.

            Cancer cells frequently display high rates of aerobic glycolysis in comparison to their nontransformed counterparts, although the molecular basis of this phenomenon remains poorly understood. Constitutive activity of the serine/threonine kinase Akt is a common perturbation observed in malignant cells. Surprisingly, although Akt activity is sufficient to promote leukemogenesis in nontransformed hematopoietic precursors and maintenance of Akt activity was required for rapid disease progression, the expression of activated Akt did not increase the proliferation of the premalignant or malignant cells in culture. However, Akt stimulated glucose consumption in transformed cells without affecting the rate of oxidative phosphorylation. High rates of aerobic glycolysis were also identified in human glioblastoma cells possessing but not those lacking constitutive Akt activity. Akt-expressing cells were more susceptible than control cells to death after glucose withdrawal. These data suggest that activation of the Akt oncogene is sufficient to stimulate the switch to aerobic glycolysis characteristic of cancer cells and that Akt activity renders cancer cells dependent on aerobic glycolysis for continued growth and survival.
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              p53 regulates mitochondrial respiration.

              The energy that sustains cancer cells is derived preferentially from glycolysis. This metabolic change, the Warburg effect, was one of the first alterations in cancer cells recognized as conferring a survival advantage. Here, we show that p53, one of the most frequently mutated genes in cancers, modulates the balance between the utilization of respiratory and glycolytic pathways. We identify Synthesis of Cytochrome c Oxidase 2 (SCO2) as the downstream mediator of this effect in mice and human cancer cell lines. SCO2 is critical for regulating the cytochrome c oxidase (COX) complex, the major site of oxygen utilization in the eukaryotic cell. Disruption of the SCO2 gene in human cancer cells with wild-type p53 recapitulated the metabolic switch toward glycolysis that is exhibited by p53-deficient cells. That SCO2 couples p53 to mitochondrial respiration provides a possible explanation for the Warburg effect and offers new clues as to how p53 might affect aging and metabolism.
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                Author and article information

                Journal
                J Crit Care Med (Targu Mures)
                J Crit Care Med (Targu Mures)
                jccm
                jccm
                The Journal of Critical Care Medicine
                Sciendo
                2393-1809
                2393-1817
                April 2019
                13 May 2019
                : 5
                : 2
                : 60-65
                Affiliations
                [1 ]Division of Anaesthesiology , Singapore General Hospital, Singapore
                [2 ]Department of Engineering, Materials Engineering and Material-Tissue Interactions Group, University of Cambridge , Cambridge, United Kingdom
                [3 ]Department of Surgical Intensive Care , Singapore General Hospital, Singapore
                Author notes
                [* ] John Ong, Department of Engineering, Materials Engineering and Material-Tissue Interactions Group, University of Cambridge, Trumpington Street, CB2 1PZ, United Kingdom jo401@ 123456cam.ac.uk
                [#]

                Authors with shared co-first authorship.

                Article
                jccm-2019-0010
                10.2478/jccm-2019-0010
                6534942
                31161143
                ef07e255-f13f-486b-9baf-5a17d7d48179
                © 2019 Yingke He, John Ong, Sharon Ong, published by Sciendo

                This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

                History
                : 12 March 2019
                : 24 April 2019
                Page count
                Pages: 6
                Categories
                Case Report

                lactic acidosis,hyperlactatemia,critical care,intensive care

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