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Journal of the American Society of... Dec 2016Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary... (Review)
Review
Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis.
Topics: Acid-Base Imbalance; Acidosis; Bone Diseases; Calcium; Humans; Hypercalciuria; Kidney Tubules; Nephrocalcinosis
PubMed: 27468975
DOI: 10.1681/ASN.2016030305 -
Cancer Metastasis Reviews Jun 2019While cancer is commonly described as "a disease of the genes," it is also associated with massive metabolic reprogramming that is now accepted as a disease "Hallmark."... (Review)
Review
While cancer is commonly described as "a disease of the genes," it is also associated with massive metabolic reprogramming that is now accepted as a disease "Hallmark." This programming is complex and often involves metabolic cooperativity between cancer cells and their surrounding stroma. Indeed, there is emerging clinical evidence that interrupting a cancer's metabolic program can improve patients' outcomes. The most commonly observed and well-studied metabolic adaptation in cancers is the fermentation of glucose to lactic acid, even in the presence of oxygen, also known as "aerobic glycolysis" or the "Warburg Effect." Much has been written about the mechanisms of the Warburg effect, and this remains a topic of great debate. However, herein, we will focus on an important sequela of this metabolic program: the acidification of the tumor microenvironment. Rather than being an epiphenomenon, it is now appreciated that this acidosis is a key player in cancer somatic evolution and progression to malignancy. Adaptation to acidosis induces and selects for malignant behaviors, such as increased invasion and metastasis, chemoresistance, and inhibition of immune surveillance. However, the metabolic reprogramming that occurs during adaptation to acidosis also introduces therapeutic vulnerabilities. Thus, tumor acidosis is a relevant therapeutic target, and we describe herein four approaches to accomplish this: (1) neutralizing acid directly with buffers, (2) targeting metabolic vulnerabilities revealed by acidosis, (3) developing acid-activatable drugs and nanomedicines, and (4) inhibiting metabolic processes responsible for generating acids in the first place.
Topics: Acidosis; Animals; Buffers; Humans; Hydrogen-Ion Concentration; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms
PubMed: 30911978
DOI: 10.1007/s10555-019-09792-7 -
Cancer Metastasis Reviews Jun 2019Skeletal involvement is a frequent and troublesome complication in advanced cancers. In the process of tumor cells homing to the skeleton to form bone metastases (BM),... (Review)
Review
Skeletal involvement is a frequent and troublesome complication in advanced cancers. In the process of tumor cells homing to the skeleton to form bone metastases (BM), different mechanisms allow tumor cells to interact with cells of the bone microenvironment and seed in the bone tissue. Among these, tumor acidosis has been directly associated with tumor invasion and aggressiveness in several types of cancer although it has been less explored in the context of BM. In bone, the association of local acidosis and cancer invasiveness is even more important for tumor expansion since the extracellular matrix is formed by both organic and hard inorganic matrices and bone cells are used to sense protons and adapt or react to a low pH to maintain tissue homeostasis. In the BM microenvironment, increased concentration of protons may derive not only from glycolytic tumor cells but also from tumor-induced osteoclasts, the bone-resorbing cells, and may influence the progression or symptoms of BM in many different ways, by directly enhancing cancer cell motility and aggressiveness, or by modulating the functions of bone cells versus a pro-tumorigenic phenotype, or by inducing bone pain. In this review, we will describe and discuss the cause of acidosis in BM, its role in BM microenvironment, and which are the final effectors that may be targeted to treat metastatic patients.
Topics: Acidosis; Animals; Bone Neoplasms; Breast Neoplasms; Female; Humans; Tumor Microenvironment
PubMed: 30825056
DOI: 10.1007/s10555-019-09790-9 -
Cancer Metastasis Reviews Jun 2019The microenvironment of solid tumors is often acidic due to poor vascular perfusion, regional hypoxia, and increased glycolytic activity of tumor cells. Although... (Review)
Review
The microenvironment of solid tumors is often acidic due to poor vascular perfusion, regional hypoxia, and increased glycolytic activity of tumor cells. Although acidosis is harmful to most types of cells, tumor cells seem well adapted to such harsh conditions. Moreover, overwhelming evidence indicates that tumor cells are more invasive and more aggressive in acidic conditions by a cascade of cell signaling and upregulation of oncogenic gene expression. Therefore, how extracellular acidic signals are transduced to the cytoplasm and then into the nucleus is an interesting topic to many cancer researchers. In this review, we update on the recent advances in acidosis-induced tumorigenesis through the acid-sensing ion channels (ASICs) and activation of cell signaling.
Topics: Acidosis; Carcinogenesis; Humans; Hydrogen-Ion Concentration; NF-kappa B; Neoplasms; Proto-Oncogene Proteins c-akt; Signal Transduction; Tumor Microenvironment
PubMed: 30729352
DOI: 10.1007/s10555-019-09785-6 -
The Veterinary Clinics of North... Mar 2017Metabolic acidosis results from an increase in the concentration of a strong anion. Metabolic acidosis is divided into hyperchloremic metabolic acidosis and high anion... (Review)
Review
Metabolic acidosis results from an increase in the concentration of a strong anion. Metabolic acidosis is divided into hyperchloremic metabolic acidosis and high anion gap acidosis based on the changes in the anion gap. Hyperchloremic metabolic acidosis is the result of chloride retention, excessive loss of sodium relative to chloride, or excessive gain of chloride relative to sodium. Clinical signs are related to the underlying disease that accompanies the metabolic acidosis. Treatment of hyperchloremic acidosis is based on addressing the underlying disease process.
Topics: Acid-Base Equilibrium; Acidosis; Animals; Chlorides; Renal Insufficiency, Chronic
PubMed: 28017409
DOI: 10.1016/j.cvsm.2016.11.001 -
Jornal Brasileiro de Nefrologia 2017Metabolic acidosis is highly prevalent in hemodialysis patients. The disorder is associated with increased mortality and its deleterious effects are already present in... (Review)
Review
Metabolic acidosis is highly prevalent in hemodialysis patients. The disorder is associated with increased mortality and its deleterious effects are already present in the predialysis phase of chronic kidney disease. Metabolic acidosis has been linked to progression of chronic kidney disease, changes in protein and glucose metabolism, bone and muscle disorders and cardiovascular disease. At present, the control of metabolic acidosis in hemodialysis is mainly focused on the supply of bicarbonate during dialysis session, but further studies are needed to set the optimum target serum bicarbonate and the best concentration of the bicarbonate dialysate. The present study reviews pathophysiological and epidemiological aspects of metabolic acidosis in hemodialysis patients and also addresses its adverse effects and treatment.
Topics: Acidosis; Humans; Kidney Failure, Chronic; Renal Dialysis
PubMed: 29044339
DOI: 10.5935/0101-2800.20170053 -
Obstetrics and Gynecology May 2021Although acetaminophen is commonly used in pregnancy, it can deplete glutathione concentrations and cause accumulation of 5-oxoproline, with subsequent metabolic...
BACKGROUND
Although acetaminophen is commonly used in pregnancy, it can deplete glutathione concentrations and cause accumulation of 5-oxoproline, with subsequent metabolic acidosis.
CASE
A malnourished 25-year-old woman, G2P1001, with chronic acetaminophen use presented with abdominal pain and high anion gap metabolic acidosis. After ruling out other potential causes, her urine 5-oxoproline level was found to be elevated. She received N-acetylcysteine, with resolution of the acidosis.
CONCLUSION
Those who care for pregnant patients should remain alert to 5-oxoprolinemia as a cause of metabolic acidosis during pregnancy. Care must be taken when using acetaminophen in states of malnutrition. N-acetylcysteine seems to be an effective antidote.
Topics: Acetaminophen; Acidosis; Adult; Diagnosis, Differential; Female; Humans; Malnutrition; Poisoning; Pregnancy; Pregnancy Complications; Prenatal Diagnosis
PubMed: 33831932
DOI: 10.1097/AOG.0000000000004351 -
Advances in Chronic Kidney Disease Jul 2022
Topics: Acidosis; Humans
PubMed: 36175069
DOI: 10.1053/j.ackd.2022.07.008 -
The American Journal of Emergency... Nov 2023Acidosis has been reported to cause ST-segment elevation. We presented a woman with a history of rectal adenocarcinoma experienced cardiac arrest during the...
Acidosis has been reported to cause ST-segment elevation. We presented a woman with a history of rectal adenocarcinoma experienced cardiac arrest during the contrast-enhanced computed tomography examination. When spontaneous circulation returned, arterial blood gas revealed she had severe respiratory acidosis, and bedside electrocardiogram showed ST-segment elevation in anterior precordial leads. Emergent coronary angiography was normal. Echocardiography revealed no abnormality of cardiac cavity size, segmental wall motion, or pericardial echo. Carcinoma metastasis in the peritoneal cavity and lungs was detected on the contrast-enhanced computed tomography scan while the heart was not involved. The ST-segment regressed and the respiratory acidosis was corrected after she received mechanical ventilation which strongly suggested the association between acidosis and the electrocardiogram changes.
Topics: Female; Humans; Acidosis, Respiratory; Electrocardiography; Arrhythmias, Cardiac; Coronary Angiography; Acidosis; Pericardium
PubMed: 37230846
DOI: 10.1016/j.ajem.2023.05.013 -
The American Journal of Emergency... Nov 2020Acidosis, a part of the lethal trauma triad, occurs frequently after major combat trauma. Tris-hydroxymethyl aminomethane (THAM) has been used to effectively treat...
BACKGROUND
Acidosis, a part of the lethal trauma triad, occurs frequently after major combat trauma. Tris-hydroxymethyl aminomethane (THAM) has been used to effectively treat acidosis in injured casualties. No research has been conducted assessing the safety of THAM in the military combat setting. We sought to describe the US military experience with THAM administration to battlefield injury subjects.
METHODS
We conducted a retrospective descriptive cohort study reviewing the trauma data from the Department of Defense Trauma Registry. US military personnel with an injury severity score greater than 15, between September 2001 and December 2014, were analyzed. Our primary outcome was the 30-day all-cause mortality among cohort treated with THAM versus those who were not. Differences between the cohort were examined using a student t-test (continuous variables), Wilcoxon Rank Sum test (ordinal variables), and chi-squared test (nominal variables).
RESULTS
4558 subjects met the inclusion criteria. 69 received THAM and 4489 did not. Casualties receiving THAM had higher mean ISS scores (33 vs. 27, p < 0.001), and required significantly higher amounts of packed red blood cells (RBCs, 37 vs. 10, p < 0.001). THAM cohort had longer ventilator and intensive care unit (ICU) days with an overall lower survival to hospital discharge. On univariable analysis, THAM was associated with lower odds of survival (OR 0.18, 95% CI 0.11-0.31) but on multivariable analysis, when controlling for confounders, THAM use was not associated with a worse odds of survival (OR 0.83, 95% CI 0.21-3.24).
CONCLUSIONS
Within our combat trauma population, we were unable to detect worse 30 day mortality associated with THAM administration. Prospective investigations are needed to validate its use in critically injured combat casualties.
Topics: Acidosis; Acrylamides; Adult; Afghan Campaign 2001-; Case-Control Studies; Female; Humans; Injury Severity Score; Iraq War, 2003-2011; Male; Military Personnel; Registries; Retrospective Studies; United States; Wounds and Injuries
PubMed: 31924438
DOI: 10.1016/j.ajem.2019.11.026