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Minerva Anestesiologica Jan 2015Acidosis, hypothermia and hypocalcaemia are determinants for morbidity and mortality during massive hemorrhages. However, precise pathological mechanisms of these... (Review)
Review
Acidosis, hypothermia and hypocalcaemia are determinants for morbidity and mortality during massive hemorrhages. However, precise pathological mechanisms of these environmental factors and their potential additive or synergistic anticoagulant and/or antiplatelet effects are not fully elucidated and are at least in part controversial. Best available evidences from experimental trials indicate that acidosis and hypothermia progressively impair platelet aggregability and clot formation. Considering the cell-based model of coagulation physiology, hypothermia predominantly prolongs the initiation phase, while acidosis prolongs the propagation phase of thrombin generation. Acidosis increases fibrinogen breakdown while hypothermia impairs its synthesis. Acidosis and hypothermia have additive effects. The effect of hypocalcaemia on coagulopathy is less investigated but it appears that below the cut-off of 0.9 mmol/L, several enzymatic steps in the plasmatic coagulation system are blocked while above that cut-off effects remain without clinical sequalae. The impact of environmental factor on hemostasis is underestimated in clinical practice due to our current practice of using routine coagulation laboratory tests such as partial thromboplastin time or prothrombin time, which are performed at standardized test temperature, after pH correction, and upon recalcification. Temperature-adjustments are feasible in viscoelastic point-of-care tests such as thrombelastography and thromboelastometry which may permit quantification of hypothermia-induced coagulopathy. Rewarming hypothermic bleeding patients is highly recommended because it improves patient outcome. Despite the absence of high-quality evidence, calcium supplementation is clinical routine in bleeding management. Buffer administration may not reverse acidosis-induced coagulopathy but may be essential for the efficacy of coagulation factor concentrates such as recombinant activated factor VII.
Topics: Acidosis; Blood Coagulation Disorders; Hemorrhage; Humans; Hypocalcemia; Hypothermia
PubMed: 24608516
DOI: No ID Found -
American Journal of Physiology. Renal... Apr 2017The textbook account of whole body acid-base balance in terms of endogenous acid production, renal net acid excretion, and gastrointestinal alkali absorption, which is... (Review)
Review
The textbook account of whole body acid-base balance in terms of endogenous acid production, renal net acid excretion, and gastrointestinal alkali absorption, which is the only comprehensive model around, has never been applied in clinical practice or been formally validated. To improve understanding of acid-base modeling, we managed to write up this conventional model as an expression solely on urine chemistry. Renal net acid excretion and endogenous acid production were already formulated in terms of urine chemistry, and we could from the literature also see gastrointestinal alkali absorption in terms of urine excretions. With a few assumptions it was possible to see that this expression of net acid balance was arithmetically identical to minus urine charge, whereby under the development of acidosis, urine was predicted to acquire a net negative charge. The literature already mentions unexplained negative urine charges so we scrutinized a series of seminal papers and confirmed empirically the theoretical prediction that observed urine charge did acquire negative charge as acidosis developed. Hence, we can conclude that the conventional model is problematic since it predicts what is physiologically impossible. Therefore, we need a new model for whole body acid-base balance, which does not have impossible implications. Furthermore, new experimental studies are needed to account for charge imbalance in urine under development of acidosis.
Topics: Acid-Base Equilibrium; Acidosis; Animals; Humans; Hydrogen-Ion Concentration; Kidney; Models, Biological; Renal Elimination; Urine
PubMed: 28031171
DOI: 10.1152/ajprenal.00560.2016 -
European Journal of Medical Research May 2024The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, pCO (mmHg), sO (%) and cHb (g/dl) is a diagnostic tool for several... (Review)
Review
The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, pCO (mmHg), sO (%) and cHb (g/dl) is a diagnostic tool for several in vivo events, e.g., mortality after multiple trauma or shock, acidosis, bleeding, clotting, artificial ventilation. In everyday clinical practice a few microlitres of blood (arterial, mixed venous or venous) are sufficient for optimal diagnostics of any metabolic acidosis or alkalosis.The same applies to a therapeutic tool-then referred to as potential base excess (BEpot)-for several in vitro assessments, e.g., solutions for infusion, sodium bicarbonate, blood products, packed red blood cells, plasma. Thus, BE or BEpot has been a parameter with exceptional clinical significance since 2007.
Topics: Humans; Acidosis; Acid-Base Imbalance; Acid-Base Equilibrium; Alkalosis
PubMed: 38735983
DOI: 10.1186/s40001-024-01796-6 -
Praxis Sep 2020Lactic Acidosis and Other Misunderstandings Lactic acidosis is a frequently encountered clinical problem in intensive care medicine. Nevertheless, many of the...
Lactic Acidosis and Other Misunderstandings Lactic acidosis is a frequently encountered clinical problem in intensive care medicine. Nevertheless, many of the underlying biochemical processes are insufficiently understood, which leads to various misconceptions. Physiologically, lactate is an important, continuously produced carrier of energy and by no means a metabolic 'waste product'. Lactate is the corresponding base to lactic acid and is produced directly from pyruvate. In this reaction H is consumed and therefore lactate production itself cannot be directly responsible for the simultaneously arising acidosis. An elevated lactate level allows no conclusions about the underlying pathophysiological process, and, more importantly, it is not an appropriate marker for tissue oxygenation.
Topics: Acidosis; Acidosis, Lactic; Biomarkers; Critical Care; Humans; Lactic Acid
PubMed: 32933388
DOI: 10.1024/1661-8157/a003508 -
The Veterinary Clinics of North... Apr 2022This article overviews metabolic disorders associated with renal disease. Included is a discussion of the pathophysiology, clinical signs, and treatment of... (Review)
Review
This article overviews metabolic disorders associated with renal disease. Included is a discussion of the pathophysiology, clinical signs, and treatment of hyperchloremic metabolic acidosis associated with renal tubular acidosis. Conditions affecting the central nervous system including uremic encephalopathy and hyponatremic encephalopathy secondary to renal disease are presented. Finally, a discussion of the unique features of calcium and phosphorus homeostasis in horses is provided with special emphasis on a recently described syndrome of calcinosis and calciphylaxis of unknown etiology.
Topics: Acidosis, Renal Tubular; Animals; Horse Diseases; Horses
PubMed: 35282958
DOI: 10.1016/j.cveq.2021.11.008 -
Emergency Medicine Australasia : EMA Jun 2020Diabetic ketoacidosis, a life-threatening complication of type 1 diabetes mellitus, is a common cause of presentation to EDs. Two new drug classes have been found to... (Review)
Review
Diabetic ketoacidosis, a life-threatening complication of type 1 diabetes mellitus, is a common cause of presentation to EDs. Two new drug classes have been found to cause ketoacidosis with distinctive presentations. The sodium-glucose transport protein 2 inhibitors used in the management of type 2 diabetes mellitus may present with ketoacidosis with normal glucose levels. Ketoacidosis with these medications may be prolonged and recur after initial resolution. Checkpoint inhibitors may present with fulminant diabetic ketoacidosis in individuals with previously normal glucose tolerance. Ketoacidosis may also occur as a result of starvation and alcohol excess, as well as a number of rare causes. Other causes of metabolic acidosis with both high and normal anion gap need to be considered in the differential diagnosis of ketoacidosis. Diabetic ketoacidosis may also present with biochemical changes suggestive of myocardial ischaemia and pancreatitis in the absence of these pathologies. The present paper reviews ketone body metabolism, ketone testing and the causes and differential diagnosis of ketoacidosis with particular relevance to emergency medicine.
Topics: Acidosis; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Emergency Service, Hospital; Humans; Ketosis
PubMed: 32266781
DOI: 10.1111/1742-6723.13503 -
Advances in Experimental Medicine and... 2016Hypoxia, depending upon its magnitude and circumstances, evokes a spectrum of mild to severe acid-base changes ranging from alkalosis to acidosis, which can alter many... (Review)
Review
Hypoxia, depending upon its magnitude and circumstances, evokes a spectrum of mild to severe acid-base changes ranging from alkalosis to acidosis, which can alter many responses to hypoxia at both non-genomic and genomic levels, in part via altered hypoxia-inducible factor (HIF) metabolism. Healthy people at high altitude and persons hyperventilating to non-hypoxic stimuli can become alkalotic and alkalemic with arterial pH acutely rising as high as 7.7. Hypoxia-mediated respiratory alkalosis reduces sympathetic tone, blunts hypoxic pulmonary vasoconstriction and hypoxic cerebral vasodilation, and increases hemoglobin oxygen affinity. These effects and others can be salutary or counterproductive to tissue oxygen delivery and utilization, based upon magnitude of each effect and summation. With severe hypoxia either in the setting of profound arterial hemoglobin desaturation and reduced O2 content or poor perfusion (ischemia) at the global or local level, metabolic and hypercapnic acidosis develop along with considerable lactate formation and pH falling to below 6.8. Although conventionally considered to be injurious and deleterious to cell function and survival, both acidoses may be cytoprotective by various anti-inflammatory, antioxidant, and anti-apoptotic mechanisms which limit total hypoxic or ischemic-reperfusion injury. Attempts to correct acidosis by giving bicarbonate or other alkaline agents under these circumstances ahead of or concurrent with reoxygenation efforts may be ill advised. Better understanding of this so-called "pH paradox" or permissive acidosis may offer therapeutic possibilities. Rapidly growing cancers often outstrip their vascular supply compromising both oxygen and nutrient delivery and metabolic waste disposal, thus limiting their growth and metastatic potential. However, their excessive glycolysis and lactate formation may not necessarily represent oxygen insufficiency, but rather the Warburg effect-an attempt to provide a large amount of small carbon intermediates to supply the many synthetic pathways of proliferative cell growth. In either case, there is expression and upregulation of many genes involved in acid-base homeostasis, in part by HIF-1 signaling. These include a unique isoform of carbonic anhydrase (CA-IX) and numerous membrane acid-base transporters engaged to maintain an optimal intracellular and extracellular pH for maximal growth. Inhibition of these proteins or gene suppression may have important therapeutic application in cancer chemotherapy.
Topics: Acidosis; Acids; Alkalies; Altitude; Exercise; Humans; Hypoxia; Neoplasms
PubMed: 27343105
DOI: 10.1007/978-1-4899-7678-9_21 -
Advances in Chronic Kidney Disease Sep 2017Subjects with CKD and reduced glomerular filtration rate are at risk for chronic metabolic acidosis, and CKD is its most common cause. Untreated metabolic acidosis, even... (Review)
Review
Subjects with CKD and reduced glomerular filtration rate are at risk for chronic metabolic acidosis, and CKD is its most common cause. Untreated metabolic acidosis, even in its mildest forms, is associated with increased mortality and morbidity and should therefore be treated. If reduced glomerular filtration rate or the tubule abnormality causing chronic metabolic acidosis cannot be corrected, it is typically treated with dietary acid (H) reduction using Na-based alkali, usually NaHCO. Dietary H reduction can also be accomplished with the addition of base-producing foods such as fruits and vegetables and limiting intake of H-producing foods like animal-sourced protein. The optimal dose of Na-based alkali that prevents the untoward effects of metabolic acidosis while minimizing adverse effects and the appropriate combination of this traditional therapy with dietary strategies remain to be determined by ongoing studies. Recent emerging evidence supports a phenomenon of H retention, which precedes the development of metabolic acidosis by plasma acid-base parameters, but further studies will be needed to determine how best to identify patients with this phenomenon and whether they too should be treated with dietary H reduction.
Topics: Acid-Base Equilibrium; Acidosis; Acidosis, Renal Tubular; Animals; Bicarbonates; Diet; Dietary Proteins; Fruit; Glomerular Filtration Rate; Humans; Renal Insufficiency, Chronic; Sodium Bicarbonate; Vegetables
PubMed: 29031356
DOI: 10.1053/j.ackd.2017.06.006 -
Biochemical Society Transactions Feb 2023Chronic kidney disease (CKD) is characterized by progressive reduction in kidney function and treatments aiming at stabilizing or slowing its progression may avoid or... (Review)
Review
Chronic kidney disease (CKD) is characterized by progressive reduction in kidney function and treatments aiming at stabilizing or slowing its progression may avoid or delay the necessity of kidney replacement therapy and the increased mortality associated with reduced kidney function. Metabolic acidosis, and less severe stages of the acid stress continuum, are common consequences of CKD and some interventional studies support that its correction slows the progression to end-stage kidney disease. This correction can be achieved with mineral alkali in the form of bicarbonate or citrate salts, ingestion of diets with fewer acid-producing food components or more base-producing food components, or a pharmacological approach. In this mini-review article, we summarize the potential mechanisms involved in the beneficial effects of alkali therapy. We also discuss the perspectives in the field and challenges that must be overcome to advance our understanding of such mechanisms.
Topics: Humans; Alkalies; Disease Progression; Renal Insufficiency, Chronic; Acidosis; Diet
PubMed: 36744634
DOI: 10.1042/BST20220690 -
American Journal of Kidney Diseases :... Feb 2020Alkali therapy for certain organic acidoses remains a topic of ongoing controversy, but little attention has been given to a related medical controversy, namely the... (Review)
Review
Alkali therapy for certain organic acidoses remains a topic of ongoing controversy, but little attention has been given to a related medical controversy, namely the prescription of alkali for respiratory acidosis. We first describe the determinants of carbon dioxide retention in the 2 types of respiratory failure; hypercapnic respiratory failure and hypoxemic respiratory failure with coexisting hypercapnia. We then highlight the deleterious consequences of severe acidemia for several organ systems, particularly the cardiovascular and central nervous systems. We argue that alkali therapy is not indicated for respiratory acidosis as a simple acid-base disturbance. Notwithstanding, we recommend prescription of alkali for severe acidemia caused by mixed acidosis (ie, combined respiratory and metabolic acidosis) or permissive hypercapnia. We examine the utility of alkali therapy in various clinical scenarios incorporating respiratory acidosis. We conclude that controlled studies will be required to test the impact of alkali therapy on clinical outcomes of these clinical settings. Such studies should also examine the optimal mode of administering alkali (amount, rate, and tonicity) and the blood pH to be targeted. The development of new buffers should be explored, especially systems that do not generate carbon dioxide or even consume it.
Topics: Acid-Base Equilibrium; Acidosis, Respiratory; Alkalies; Carbon Dioxide; Humans; Treatment Outcome
PubMed: 31473018
DOI: 10.1053/j.ajkd.2019.05.029