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Cancer Metastasis Reviews Jun 2019The extracellular pH of solid tumors is unequivocally acidic due to a combination of high rates of lactic acid production (a consequence of fermentative glycolytic... (Review)
Review
The extracellular pH of solid tumors is unequivocally acidic due to a combination of high rates of lactic acid production (a consequence of fermentative glycolytic metabolism) and poor perfusion. This has been documented by us and others in a wide variety of solid tumor models, primarily using magnetic resonance spectroscopic imaging (MRSI). This acidity contributes to tumor progression by inducing genome instability, promoting local invasion and metastases, inhibiting anti-tumor immunity, and conferring resistance to chemo- and radio-therapies. Systemic buffer therapies can neutralize tumor acidity and has been shown to inhibit local invasion and metastasis and improve immune surveillance in a variety of cancer model systems. This review will revisit the causes and consequences of acidosis by summarizing strategies used by cancer cells to adapt to acidosis, and how this acidity associated with carcinogenesis, metastasis, and immune function. Finally, this review will discuss how neutralization of acidity can be used to inhibit carcinogenesis and metastasis and improve anti-cancer immunotherapy.
Topics: Acidosis; Animals; Buffers; Humans; Hydrogen-Ion Concentration; Neoplasms; Sodium Bicarbonate
PubMed: 30806853
DOI: 10.1007/s10555-019-09787-4 -
Ugeskrift For Laeger Aug 2021It is a common but flawed presumption that blood lactate reflects the lactic acid production in the body's tissues. Lactate is formed directly from pyruvate and... (Review)
Review
It is a common but flawed presumption that blood lactate reflects the lactic acid production in the body's tissues. Lactate is formed directly from pyruvate and functions to dampen reductions in intracellular pH through lactate-H+ cotransport to the extracellular space. Though this may give rise to elevated blood lactate, increased lactate production is not the cause of metabolic acidosis in such instances. "Lactic acidosis" is thus an inappropriate term as it indicates causality and in this review, we suggest that in the future, the term "hyperlactataemia-associated metabolic acidosis" should be used instead.
Topics: Acidosis; Acidosis, Lactic; Humans; Lactic Acid
PubMed: 34477100
DOI: No ID Found -
Annals of Hepatology 2022In addition to the kidneys and lungs, the liver also plays an important role in the regulation of the Acid-Base Equilibrium (ABE). The involvement of the liver in the... (Review)
Review
In addition to the kidneys and lungs, the liver also plays an important role in the regulation of the Acid-Base Equilibrium (ABE). The involvement of the liver in the regulation of ABE is crucial because of its role in lactic acid metabolism, urea production and in protein homeostasis. The main acid-base imbalance that occurs in patients with liver cirrhosis is Respiratory Alkalosis (RAlk). Due to the fact that in these patients additional pathophysiological mechanisms that affect the ABE are present, other disorders may appear which compensate or enhance the primary disorder. Conventional ABE reading models fail to identify and assess the underlying disorders in patients with liver cirrhosis. This weakness of the classical models led to the creation of new physicochemical mathematical models that take into account all the known parameters that develop and affect the ABE. In addition to the RAlk, in patients with liver cirrhosis, metabolic alkalosis (due to hypoalbuminemia), hyponatremic metabolic acidosis, hyperchloremic metabolic acidosis, lactic acidosis and metabolic alkalosis due to urea metabolism are some of the pathophysiological mechanisms that affect the ABE.
Topics: Acidosis; Alkalosis; Humans; Liver Cirrhosis; Liver Diseases; Urea
PubMed: 35074477
DOI: 10.1016/j.aohep.2022.100675 -
Clinical Journal of the American... Aug 2021Acid-related injury from chronic metabolic acidosis is recognized through growing evidence of its deleterious effects, including kidney and other organ injury.... (Review)
Review
Acid-related injury from chronic metabolic acidosis is recognized through growing evidence of its deleterious effects, including kidney and other organ injury. Progressive acid accumulation precedes the signature manifestation of chronic metabolic acidosis, decreased plasma bicarbonate concentration. Acid accumulation that is not enough to manifest as metabolic acidosis, known as eubicarbonatemic acidosis, also appears to cause kidney injury, with exacerbated progression of CKD. Chronic engagement of mechanisms to mitigate the acid challenge from Western-type diets also appears to cause kidney injury. Rather than considering chronic metabolic acidosis as the only acid-related condition requiring intervention to reduce kidney injury, this review supports consideration of acid-related injury as a continuum. This "acid stress" continuum has chronic metabolic acidosis at its most extreme end, and high-acid-producing diets at its less extreme, yet detrimental, end.
Topics: Acid-Base Equilibrium; Acidosis; Acids; Bicarbonates; Chronic Disease; Diet; Glomerular Filtration Rate; Humans; Kidney Diseases; Stress, Physiological
PubMed: 33741720
DOI: 10.2215/CJN.17541120 -
Journal of the American Society of... Feb 2018Metabolic acidosis is not uncommon in CKD and is linked with bone demineralization, muscle catabolism, and higher risks of CKD progression and mortality. Clinical... (Review)
Review
Metabolic acidosis is not uncommon in CKD and is linked with bone demineralization, muscle catabolism, and higher risks of CKD progression and mortality. Clinical practice guidelines recommend maintaining serum total CO at ≥22 mEq/L to help prevent these complications. Although a definitive trial testing whether correcting metabolic acidosis improves clinical outcomes has not been conducted, results from small, single-center studies support this notion. Furthermore, biologic plausibility supports the notion that a subset of patients with CKD have acid-mediated organ injury despite having a normal serum total CO and might benefit from oral alkali before overt acidosis develops. Identifying these individuals with subclinical metabolic acidosis is challenging, but recent results suggest that urinary acid excretion measurements may be helpful. The dose of alkali to provide in this setting is unknown as well. The review discusses these topics and the prevalence and risk factors of metabolic acidosis, mechanisms of acid-mediated organ injury, results from interventional studies, and potential harms of alkali therapy in CKD.
Topics: Acidosis; Acids; Alkalies; Asymptomatic Diseases; Bone Demineralization, Pathologic; Carbon Dioxide; Glomerular Filtration Rate; Humans; Renal Insufficiency, Chronic; Risk Factors; Sodium Bicarbonate
PubMed: 29030467
DOI: 10.1681/ASN.2017040422 -
Immunology Jul 2018Due to imbalances between vascularity and cellular growth patterns, the tumour microenvironment harbours multiple metabolic stressors including hypoxia and acidosis,... (Review)
Review
Due to imbalances between vascularity and cellular growth patterns, the tumour microenvironment harbours multiple metabolic stressors including hypoxia and acidosis, which have significant influences on remodelling both tumour and peritumoral tissues. These stressors are also immunosuppressive and can contribute to escape from immune surveillance. Understanding these effects and characterizing the pathways involved can identify new targets for therapy and may redefine our understanding of traditional anti-tumour therapies. In this review, the effects of hypoxia and acidosis on tumour immunity will be summarized, and how modulating these parameters and their sequelae can be a useful tool for future therapeutic interventions is discussed.
Topics: Acidosis; Animals; Humans; Hypoxia; Immune System; Immune Tolerance; Immunologic Surveillance; Immunotherapy; Neoplasms; Tumor Escape; Tumor Microenvironment
PubMed: 29485185
DOI: 10.1111/imm.12917 -
Cancer Metastasis Reviews Jun 2019The glycolytic phenotype of the Warburg effect is associated with acidification of the tumor microenvironment. In this review, we describe how acidification of the tumor... (Review)
Review
The glycolytic phenotype of the Warburg effect is associated with acidification of the tumor microenvironment. In this review, we describe how acidification of the tumor microenvironment may increase the invasive and degradative phenotype of cancer cells. As a template of an extracellular acidic microenvironment that is linked to proteolysis, we use the resorptive pit formed between osteoclasts and bone. We describe similar changes that have been observed in cancer cells in response to an acidic microenvironment and that are associated with proteolysis and invasive and metastatic phenotypes. This includes consideration of changes observed in the intracellular trafficking of vesicles, i.e., lysosomes and exosomes, and in specialized regions of the membrane, i.e., invadopodia and caveolae. Cancer-associated cells are known to affect what is generally referred to as tumor proteolysis but little direct evidence for this being regulated by acidosis; we describe potential links that should be verified.
Topics: Acidosis; Animals; Humans; Neoplasms; Proteolysis; Tumor Microenvironment
PubMed: 31069574
DOI: 10.1007/s10555-019-09796-3 -
Journal of Animal Science Aug 2020Acute and subacute ruminal acidosis (SARA) are common nutritional problems in both beef and dairy cattle. Therefore, the objective of this review is to describe how... (Review)
Review
Acute and subacute ruminal acidosis (SARA) are common nutritional problems in both beef and dairy cattle. Therefore, the objective of this review is to describe how ruminal Gram-negative bacteria could contribute to the pathogenesis of ruminal acidoses, by releasing lipopolysaccharides (LPS; a component of their cell wall) in the ruminal fluid. When cattle consume excessive amounts of highly fermentable carbohydrates without prior adaptation, normal fermentation become disrupted. The fermentation of these carbohydrates quickly decreases ruminal pH due to the accumulation of short-chain fatty acids and lactate in the rumen. As a consequence, ruminal epithelium may be damaged and tissue function could be impaired, leading to a possible translocation of pathogenic substances from the rumen into the bloodstream. Such changes in fermentation are followed by an increase in Gram-positive bacteria while Gram-negative bacteria decrease. The lyses of Gram-negative bacteria during ruminal acidosis increase LPS concentration in the ruminal fluid. Because LPS is a highly proinflammatory endotoxin in the circulatory system, past studies have raised concerns regarding ruminal LPS contribution to the pathogenesis of ruminal acidosis. Although animals that undergo these disorders do not always have an immune response, recent studies showed that different Gram-negative bacteria have different LPS composition and toxicity, which may explain the differences in immune response. Given the diversity of Gram-negative bacteria in the rumen, evaluating the changes in the bacterial community during ruminal acidosis could be used as a way to identify which Gram-negative bacteria are associated with LPS release in the rumen. By identifying and targeting ruminal bacteria with possible pathogenic LPS, nutritional strategies could be created to overcome, or at least minimize, ruminal acidosis.
Topics: Acidosis; Animals; Cattle; Cattle Diseases; Diet; Epithelium; Fatty Acids, Volatile; Fermentation; Gram-Negative Bacteria; Hydrogen-Ion Concentration; Lipopolysaccharides; Rumen
PubMed: 32761212
DOI: 10.1093/jas/skaa248 -
Ugeskrift For Laeger Jun 2019Alcoholic ketoacidosis is a relatively rare condition, which may have a lethal outcome if left untreated. This review covers definition, pathophysiology, clinical... (Review)
Review
Alcoholic ketoacidosis is a relatively rare condition, which may have a lethal outcome if left untreated. This review covers definition, pathophysiology, clinical manifestations, diagnostic approach and treatment. Usually, patients respond well and quickly to treatment, if it is started early in the course. Thus, mortality can be significantly reduced.
Topics: Acidosis; Alcoholism; Diabetic Ketoacidosis; Humans; Ketosis; Rare Diseases
PubMed: 31267934
DOI: No ID Found -
Journal of the American Society of... May 2021Two papers, one in 1986 and another one in 1988, reported a strong inverse correlation between urinary anion gap (UAG) and urine ammonia excretion (UNH) in patients with... (Review)
Review
Two papers, one in 1986 and another one in 1988, reported a strong inverse correlation between urinary anion gap (UAG) and urine ammonia excretion (UNH) in patients with metabolic acidosis and postulated that UAG could be used as an indirect measure of UNH This postulation has persisted until now and is widely accepted. In this review, we discuss factors regulating UAG and examine published evidence to uncover errors in the postulate and the design of the original studies. The essential fact is that, in the steady state, UAG reflects intake of Na, K, and Cl. Discrepancy between intake and urinary output of these electrolytes (, UAG) indicates selective extrarenal loss of these electrolytes or nonsteady state. UNH excretion, which depends, in the absence of renal dysfunction, mainly on the daily acid load, has no consistent relationship to UAG either theoretically or in reality. Any correlation between UAG and UNH, when observed, was a fortuitous correlation and cannot be extrapolated to other situations. Furthermore, the normal value of UAG has greatly increased over the past few decades, mainly due to increases in dietary intake of potassium and widespread use of sodium salts with anions other than chloride as food additives. The higher normal values of UAG must be taken into consideration in interpreting UAG.
Topics: Acid-Base Equilibrium; Acidosis; Ammonia; Humans
PubMed: 33769949
DOI: 10.1681/ASN.2020101509