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Intrapartum Fetal Surveillance
Published in Gowri Dorairajan, Management of Normal and High Risk Labour During Childbirth, 2022
Unlike adults, the fetus cannot protect the myocardium from hypoxic injury by increasing the rate and depth of respiration. As the stroke volume cannot be increased, the increase in cardiac output in the fetus is mainly by the increase in the heart rate. This redistribution of fetal circulation and the increase in cardiac output to avoid the injury from hypoxia of the central organ may result in rapid myocardial hypoxia and acidosis, resulting in bradycardia. Hypoxia thus can result in acidosis and low intracellular pH, which can compromise cellular function and cell death. Fetuses respond by reducing the activity and reducing the heart rate leading to less demand of oxygen by myocardial fibres. The reduced rate will in turn increase oxygenation by increasing the diastolic filling of the coronary circulation. Once the oxygenation is restored, the fetus will recover the heart rate to baseline or even higher, due to the catecholamine release during hypoxic stress.1
Basic Concepts of Acid–Base Physiology
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Intracellular pH is finely regulated to enable optimal functioning of enzyme systems. This is achieved by the extrusion of protons through the membrane by the Na+/H+ antiport (or counter-transport) system (H+ ions move in the direction opposite to the Na+ ion gradient) and intracellular buffering by intracellular proteins.
Chemical Exchange Saturation Transfer and Amide Proton Transfer Imaging
Published in Shoogo Ueno, Bioimaging, 2020
Finally, as previously mentioned, the APTWSI can be affected by the local pH and temperature through alterations in the proton exchange rate. Studies have shown that in many tumor types, the intracellular pH is higher than that in normal brain tissue [64]. Because the amide proton exchange rate is base catalyzed in the physiological pH range, the exchange rate increases as pH increases, thus increasing the APT contrast. Nevertheless, pH has not been considered a major source of increased APTWSI in malignant tumors. These should be recognized as possible confounding factors of the interpretation of APT imaging results.
High-throughput screening in multicellular spheroids for target discovery in the tumor microenvironment
Published in Expert Opinion on Drug Discovery, 2020
Blaise Calpe, Werner J. Kovacs
Intracellular pH homeostasis is crucial for the maintenance of cellular metabolism and signaling. High glycolytic flux in cancer cells leads to acidification of the milieu as a result of lactate secretion while intracellular pH (pHi) becomes more alkaline [71]. Importantly, this reverse pH gradient is thought to contribute to drug resistance and metastasis [72]. Several pH-sensitive fluorescent dyes have been developed, the most widely used being derivatives of fluorescein and benzoxanthene [73]. These dyes can be utilized to measure the pH of the extracellular milieu [74] and are compatible with MTS [75]. On the other hand, genetically encoded pH-sensitive sensors are better suited for intracellular pH measurement. Tantama et al. developed pHRed, a genetically encoded pH sensor engineered by mutagenesis of the red fluorescent protein mKeima and the first ratiometric single-protein red fluorescent sensor of pH [76]. The pHRed ratio response is insensitive to oxidative stress (H2O2), temperature (21–37°C), and different ion concentrations (K+, Na+, Cl−, Mg2+, Ca2+, HCO3−) [76]. pHRed also allows the simultaneous imaging of intracellular ATP and pH because of its spectral compatibility with the GFP-based ATP sensor Perceval [77]. Shirmanova and colleagues successfully used the stably expressed fluorescent pH-sensitive ratiometric (dual-excitation) indicator SypHer2 [78] to image intracellular pH in MTS and xenografts [79].
Novel approaches for designing drugs that interfere with pH regulation
Published in Expert Opinion on Drug Discovery, 2019
Emanuela Berrino, Claudiu T. Supuran
In physiological systems, the pH of extracellular compartments ranges between 7.35 and 7.45, whereas the intracellular pH values are slightly lower (i.e. 6.8–7.2) [1]. Such values vary according to the considered cell type as well as their physiologic/pathologic status. Different pH values are characteristic for diverse intracellular organelles, which in turn are able to independently control their pH in order to allow them to exert their physiological functions (e.g. the mitochondria have a slightly alkaline pH, of around 8) [1]. As any other physiological parameter, the pH is kept constant through a dynamic equilibrium, since protons are continuously produced and consumed. For example, glycolysis generates H+ ions, whereas creatine phosphate hydrolysis requires H+ ions in order to occur, just to mention two essential metabolic pathways [2]. To preserve the pH homeostasy, such processes are tightly controlled in all organisms and all types of tissues/cells [1,2].
Approach to the patient presenting with metabolic acidosis
Published in Acta Clinica Belgica, 2019
Jill Vanmassenhove, Norbert Lameire
The metabolism of fat and carbohydrates results in large amounts of CO2. Although CO2 is not an acid, it can combine with water to form H2CO3. The accumulation of volatile or carbonic acids is prevented through removal of CO2 by ventilation, preventing H+ accumulation. For the greater part, Western diets will impose a net acid load of 50–100 meq/day to the body. The dietary acid load is primarily due to the generation of H2SO4 from the metabolism of sulphur-containing amino acids besides incomplete oxidation of fat and carbohydrates also producing a net H+ load. Large fluctuations in H+ concentration (and thus pH) would be incompatible with life and thus the regulation of extra- and intracellular pH is vital for the preservation of normal cellular function and life in general. The protons delivered to the body by means of non-volatile acids (50–100 meq/day) are immediately buffered in the plasma by the bicarbonate buffer system (see equation).