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Pharmacology & Therapeutics Jul 2023Sensing acidosis is an important somatosensory function in responses to ischemia, inflammation, and metabolic alteration. Accumulating evidence has shown that acidosis... (Review)
Review
Sensing acidosis is an important somatosensory function in responses to ischemia, inflammation, and metabolic alteration. Accumulating evidence has shown that acidosis is an effective factor for pain induction and that many intractable chronic pain diseases are associated with acidosis signaling. Various receptors have been known to detect extracellular acidosis and all express in the somatosensory neurons, such as acid sensing ion channels (ASIC), transient receptor potential (TRP) channels and proton-sensing G-protein coupled receptors. In addition to sense noxious acidic stimulation, these proton-sensing receptors also play a vital role in pain processing. For example, ASICs and TRPs are involved in not only nociceptive activation but also anti-nociceptive effects as well as some other non-nociceptive pathways. Herein, we review recent progress in probing the roles of proton-sensing receptors in preclinical pain research and their clinical relevance. We also propose a new concept of sngception to address the specific somatosensory function of acid sensation. This review aims to connect these acid-sensing receptors with basic pain research and clinical pain diseases, thus helping with better understanding the acid-related pain pathogenesis and their potential therapeutic roles via the mechanism of acid-mediated antinociception.
Topics: Humans; Chronic Pain; Protons; Acid Sensing Ion Channels; Signal Transduction; Acidosis
PubMed: 37210007
DOI: 10.1016/j.pharmthera.2023.108444 -
The Journal of Trauma and Acute Care... Mar 2020
Review
Topics: Acidosis; Blood Coagulation Disorders; Blood Transfusion; Humans; Hypocalcemia; Hypothermia; Shock, Traumatic
PubMed: 31876689
DOI: 10.1097/TA.0000000000002570 -
Heart & Lung : the Journal of Critical... 2022Current guidelines suggest the use of isotonic saline (IS) infusion as the preferred resuscitation fluid in the management of diabetic ketoacidosis (DKA). However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Current guidelines suggest the use of isotonic saline (IS) infusion as the preferred resuscitation fluid in the management of diabetic ketoacidosis (DKA). However, balanced electrolyte solutions (BES) have been proposed as an alternative due to a lower propensity to cause hyperchloremic metabolic acidosis. Evidence regarding the use of BES in DKA remains limited.
OBJECTIVES
To determine if the use of BES in fluid resuscitation leads to faster resolution of DKA compared to IS.
METHODS
The study involves a comprehensive search of literature from PubMed, Cochrane CENTRAL, Google Scholar, and Science Direct of clinical trials addressing the use of BES vs IS in fluid resuscitation in DKA. The time to resolution of DKA was examined as the primary endpoint. Pooled hazard ratios (HR) and Mean Difference (MD) in hours with their 95% confidence intervals (CI) were calculated using a random-effects model.
RESULTS
The literature search included 464 studies that were screened individually. A total of 9 studies were identified but 6 studies were excluded due to irrelevance in the outcome of interest and target population. The pooled hazard ratio HR significantly revealed 1.46 [1.10 to 1.94] (p = 0.009) with 12% heterogeneity while MD was -3.02 (95% CI -6.78-0.74; p = 0.12) with heterogeneity of 85%.
CONCLUSION
Considering the evidence from pooled small randomized trials with moderate overall certainty of evidence, the use of BES in DKA was associated with faster rates of DKA resolution compared to IS.
Topics: Acidosis; Adult; Diabetes Mellitus; Diabetic Ketoacidosis; Electrolytes; Fluid Therapy; Humans; Resuscitation
PubMed: 35358905
DOI: 10.1016/j.hrtlng.2022.03.014 -
Advances in Chronic Kidney Disease Jul 2022The various mechanisms responsible for the development of metabolic acidosis are briefly reviewed, and the metabolic acidoses are categorized both by mechanism and by... (Review)
Review
The various mechanisms responsible for the development of metabolic acidosis are briefly reviewed, and the metabolic acidoses are categorized both by mechanism and by the presence or absence of an increased anion gap. When a diagnosis of metabolic acidosis is established, it becomes imperative to identify the primary causative etiology as quickly as possible. This is often readily apparent from the history and physical exam (ie, diabetic ketoacidosis when the glucose is very high in a patient with diabetes mellitus; lactic acidosis in a patient with sepsis and hypotension, etc.). However, when the etiology is not obvious, it is very helpful to determine if the metabolic acidosis is of the hyperchloremic or high-anion-gap type (or a combination of both). Once this categorization has been established, a stepwise consideration of each of the potential causative etiologies will usually direct the clinician to order the appropriate diagnostic studies.
Topics: Acid-Base Imbalance; Acidosis; Anions; Glucose; Humans; Physical Examination
PubMed: 36175073
DOI: 10.1053/j.ackd.2022.07.004 -
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 -
The Veterinary Clinics of North... Jul 2023Beef cattle are less prone to metabolic diseases as compared with dairy cattle; however, there are disease entities of concern in feedlot and cow-calf beef cattle... (Review)
Review
Beef cattle are less prone to metabolic diseases as compared with dairy cattle; however, there are disease entities of concern in feedlot and cow-calf beef cattle operations. In one study, a prevalence of 2% was found for ruminant acidosis in a feedlot; however, there is little prevalence information published with regard to metabolic diseases in beef cattle.1 Metabolic diseases covered in this article are hypomagnesemia, ruminal acidosis, and all of the common sequelae, polioencephalomalacia, manganese deficiency, and protein-energy malnutrition (PEM).
Topics: Female; Cattle; Animals; Cattle Diseases; Metabolic Diseases; Acidosis
PubMed: 37032297
DOI: 10.1016/j.cvfa.2023.02.011 -
Journal of the American Society of... Mar 2024Metabolic acidosis is a common complication of CKD and is associated with more rapid decline of kidney function, but well-powered controlled randomized trials testing... (Randomized Controlled Trial)
Randomized Controlled Trial
SIGNIFICANCE STATEMENT
Metabolic acidosis is a common complication of CKD and is associated with more rapid decline of kidney function, but well-powered controlled randomized trials testing the effect of treating metabolic acidosis on slowing CKD progression have not been conducted. The VALOR-CKD study randomized 1480 individuals with CKD and metabolic acidosis, across 320 sites to placebo or veverimer (a novel hydrochloric acid binder). The findings did not demonstrate the efficacy of veverimer in slowing CKD progression, but the difference in serum bicarbonate between placebo and drug arms was only approximately 1 mEq/L. Veverimer was safe and well tolerated.
BACKGROUND
Metabolic acidosis is common in CKD, but whether its treatment slows CKD progression is unknown. Veverimer, a novel hydrochloric acid binder that removes acid from the gastrointestinal tract, leads to an increase in serum bicarbonate.
METHODS
In a phase 3, double-blind, placebo-controlled trial, patients with CKD (eGFR of 20-40 ml/min per 1.73 m 2 ) and metabolic acidosis (serum bicarbonate of 12-20 mEq/L) from 35 countries were randomized to veverimer or placebo. The primary outcome was the composite end point of CKD progression, defined as the development of ESKD (kidney transplantation or maintenance dialysis), a sustained decline in eGFR of ≥40% from baseline, or death due to kidney failure.
RESULTS
The mean (±SD) baseline eGFR was 29.2±6.3 ml/min per 1.73 m 2 , and serum bicarbonate was 17.5±1.4 mEq/L; this increased to 23.4±2.0 mEq/L after the active treatment run-in. After randomized withdrawal, the mean serum bicarbonate was 22.0±3.0 mEq/L and 20.9±3.3 mEq/L in the veverimer and placebo groups at month 3, and this approximately 1 mEq/L difference remained stable for the first 24 months. A primary end point event occurred in 149/741 and 148/739 patients in the veverimer and placebo groups, respectively (hazard ratio, 0.99; 95% confidence interval, 0.8 to 1.2; P = 0.90). Serious and overall adverse event incidence did not differ between the groups.
CONCLUSIONS
Among patients with CKD and metabolic acidosis, treatment with veverimer did not slow CKD progression. The lower than expected bicarbonate separation may have hindered the ability to test the hypothesis.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
VALOR-CKD, NCT03710291 .
Topics: Humans; Bicarbonates; Hydrochloric Acid; Acidosis; Renal Insufficiency, Chronic; Polymers
PubMed: 38261535
DOI: 10.1681/ASN.0000000000000292 -
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 -
Best Practice & Research. Clinical... Dec 2015Cardiac arrest (CA) often results in hemodynamic and metabolic compromise with associated poor prognosis. Therapeutic hypothermia (TH) has become the standard of care... (Review)
Review
Cardiac arrest (CA) often results in hemodynamic and metabolic compromise with associated poor prognosis. Therapeutic hypothermia (TH) has become the standard of care for CA survivors, decreasing reperfusion injury and intercellular acid-base disturbances, with improved neurologic outcomes. These benefits are realized despite a mild acidosis that can potentially occur during TH. By contrast, the severity of acidosis after return of spontaneous circulation (ROSC) must be monitored carefully and managed appropriately. Bicarbonate should be used only in case of severe acidosis and as a continuous infusion. The blood gas samples are usually warmed to 37 °C before analysis; hence, it is worth noting that the blood gas values are temperature dependent. Therefore, a calculated correction for values may be necessary.
Topics: Acid-Base Equilibrium; Acid-Base Imbalance; Acidosis; Heart Arrest; Humans; Hydrogen-Ion Concentration; Hypothermia, Induced
PubMed: 26670817
DOI: 10.1016/j.bpa.2015.09.005