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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 -
American Journal of Physiology. Renal... Sep 2023The urinary potassium (K) excretion machinery is upregulated with increasing dietary K, but the role of accompanying dietary anions remains inadequately characterized....
The urinary potassium (K) excretion machinery is upregulated with increasing dietary K, but the role of accompanying dietary anions remains inadequately characterized. Poorly absorbable anions, including [Formula: see text], are thought to increase K secretion through a transepithelial voltage effect. Here, we tested if they also influence the K secretion machinery. Wild-type mice, aldosterone synthase (AS) knockout (KO) mice, or pendrin KO mice were randomized to control, high-KCl, or high-KHCO diets. The K secretory capacity was assessed in balance experiments. Protein abundance, modification, and localization of K-secretory transporters were evaluated by Western blot analysis and confocal microscopy. Feeding the high-KHCO diet increased urinary K excretion and the transtubular K gradient significantly more than the high-KCl diet, coincident with more pronounced upregulation of epithelial Na+ channels (ENaC) and renal outer medullary K (ROMK) channels and apical localization in the distal nephron. Experiments in AS KO mice revealed that the enhanced effects of [Formula: see text] were aldosterone independent. The high-KHCO diet also uniquely increased the large-conductance Ca-activated K (BK) channel β-subunit, stabilizing BKα on the apical membrane, the Cl/[Formula: see text] exchanger, pendrin, and the apical KCl cotransporter (KCC3a), all of which are expressed specifically in pendrin-positive intercalated cells. Experiments in pendrin KO mice revealed that pendrin was required to increase K excretion with the high-KHCO diet. In summary, [Formula: see text] stimulates K excretion beyond a poorly absorbable anion effect, upregulating ENaC and ROMK in principal cells and BK, pendrin, and KCC3a in pendrin-positive intercalated cells. The adaptive mechanism prevents hyperkalemia and alkalosis with the consumption of alkaline ash-rich diets but may drive K wasting and hypokalemia in alkalosis. Dietary anions profoundly impact K homeostasis. Here, we found that a K-rich diet, containing [Formula: see text] as the counteranion, enhances the electrogenic K excretory machinery, epithelial Na channels, and renal outer medullary K channels, much more than a high-KCl diet. It also uniquely induces KCC3a and pendrin, in B-intercalated cells, providing an electroneutral KHCO secretion pathway. These findings reveal new K balance mechanisms that drive adaption to alkaline and K-rich foods, which should guide new treatment strategies for K disorders.
Topics: Animals; Mice; Alkalosis; Anion Transport Proteins; Anions; Diet; Mice, Knockout; Potassium; Potassium, Dietary; Sodium; Sulfate Transporters
PubMed: 37498547
DOI: 10.1152/ajprenal.00193.2023 -
Indian Journal of Nephrology 2024Respiratory alkalosis during hemodialysis session is a rare complication. We managed two patients with severe respiratory alkalosis, a woman who developed this 75 min...
Respiratory alkalosis during hemodialysis session is a rare complication. We managed two patients with severe respiratory alkalosis, a woman who developed this 75 min after the beginning of the session and a man who developed it about 1 h before the end of the session. In both, the cause was a hypotensive episode, and both hypotension and alkalosis were successfully treated.
PubMed: 38681025
DOI: 10.4103/ijn.ijn_297_22 -
Cureus May 2024Salicylate exposure and toxicity are associated with a myriad of symptoms and signs, and a comprehensive knowledge of diagnosing and treating salicylate poisoning is...
Salicylate exposure and toxicity are associated with a myriad of symptoms and signs, and a comprehensive knowledge of diagnosing and treating salicylate poisoning is needed. Here, we present a case of a 29-year-old female with a past medical history of schizoaffective disorder and bipolar disorder with multiple suicide attempts brought to our hospital, Nassau University Medical Center, East Meadow, by the Emergency Medical Service (EMS) due to an intentional overdose of 300 pills of acetylsalicylic acid. She had mixed acid-base disturbance with respiratory alkalosis and metabolic acidosis. She was started on bicarbonate infusion in the emergency department to maintain a blood pH of 7.5 and to maintain a urine pH of more than 7.5. As her salicylate levels were 98.2 at admission with altered mental status, she was started on slow, low-efficiency hemodialysis. A few hours later, she developed a rebound increase in salicylate levels to 129, associated with a change in mental status and the patient was more confused. She was started on regular hemodialysis with improvement in mental status and elimination of salicylate steadily. Given the extensive nature of toxic effects, a patient with severe salicylate toxicity can deteriorate rapidly and can be challenging to manage. As there is no specific antidote for aspirin, the goals of therapy depend primarily on limiting the absorption of salicylate, enhancing elimination, and providing supportive care. Monitoring the acid-base status and serum salicylate levels closely and monitoring for rebound increase in salicylate levels is of paramount importance. Aggressive hydration to maintain euvolemia, alkalinization, aggressive replenishment of potassium and magnesium, activated charcoal to decrease absorption, and hemodialysis remain the cornerstones of treatment.
PubMed: 38746490
DOI: 10.7759/cureus.60241 -
Thorax Oct 2023Metabolic alkalosis may lead to respiratory inhibition and increased need for ventilatory support or prolongation of weaning from ventilation for patients with chronic... (Meta-Analysis)
Meta-Analysis
Acetazolamide for metabolic alkalosis complicating respiratory failure with chronic obstructive pulmonary disease or obesity hypoventilation syndrome: a systematic review.
BACKGROUND
Metabolic alkalosis may lead to respiratory inhibition and increased need for ventilatory support or prolongation of weaning from ventilation for patients with chronic respiratory disease. Acetazolamide can reduce alkalaemia and may reduce respiratory depression.
METHODS
We searched Medline, EMBASE and CENTRAL from inception to March 2022 for randomised controlled trials comparing acetazolamide to placebo in patients with chronic obstructive pulmonary disease, obesity hypoventilation syndrome or obstructive sleep apnoea, hospitalised with acute respiratory deterioration complicated by metabolic alkalosis. The primary outcome was mortality and we pooled data using random-effects meta-analysis. Risk of bias was assessed using the Cochrane RoB 2 (Risk of Bias 2) tool, heterogeneity was assessed using the I value and χ test for heterogeneity. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology.
RESULTS
Four studies with 504 patients were included. 99% of included patients had chronic obstructive pulmonary disease. No trials recruited patients with obstructive sleep apnoea. 50% of trials recruited patients requiring mechanical ventilation. Risk of bias was overall low to some risk. There was no statistically significant difference with acetazolamide in mortality (relative risk 0.98 (95% CI 0.28 to 3.46); p=0.95; 490 participants; three studies; GRADE low certainty) or duration of ventilatory support (mean difference -0.8 days (95% CI -7.2 to 5.6); p=0.36; 427 participants; two studies; GRADE: low certainty).
CONCLUSION
Acetazolamide may have little impact on respiratory failure with metabolic alkalosis in patients with chronic respiratory diseases. However, clinically significant benefits or harms are unable to be excluded, and larger trials are required.
PROSPERO REGISTRATION NUMBER
CRD42021278757.
Topics: Humans; Acetazolamide; Obesity Hypoventilation Syndrome; Pulmonary Disease, Chronic Obstructive; Alkalosis; Respiratory Insufficiency
PubMed: 37217290
DOI: 10.1136/thorax-2023-219988 -
British Journal of Pharmacology Sep 2023Itch is associated with several pathologies and is a common drug-induced side effect. Chloroquine (CQ) is reported to induce itch by activating the Mas-related G...
BACKGROUND AND PURPOSE
Itch is associated with several pathologies and is a common drug-induced side effect. Chloroquine (CQ) is reported to induce itch by activating the Mas-related G protein-coupled receptor MrgprA3 and subsequently TRPA1. In this study, we demonstrate that CQ employs at least two MrgprA3-independent mechanisms to activate or sensitize TRPA1 and TRPV1.
EXPERIMENTAL APPROACH
Patch clamp and calcium imaging were utilized to examine effects of CQ on TRPA1 and TRPV1 expressed in HEK 293T cells.
KEY RESULTS
In calcium imaging, CQ induces a concentration-dependent but MrgprA3-independent activation of TRPA1 and TRPV1. Although CQ itself inhibits TRPA1 and TRPV1 in patch clamp recordings, co-application of CQ and ultraviolet A (UVA) light evokes membrane currents through both channels. This effect is inhibited by the reducing agent dithiothreitol (DTT) and is reduced on mutants lacking cysteine residues accounting for reactive oxygen species (ROS) sensitivity. The combination of CQ and UVA light triggers an accumulation of intracellular ROS, removes fast inactivation of voltage-gated sodium currents and activates TRPV2. On the other hand, CQ is a weak base and induces intracellular alkalosis. Intracellular alkalosis can activate TRPA1 and TRPV1, and CQ applied at alkaline pH values indeed activates both channels.
CONCLUSION AND IMPLICATIONS
Our data reveal novel pharmacological properties of CQ, allowing activation of TRPA1 and TRPV1 via photosensitization as well as intracellular alkalosis. These findings add more complexity to the commonly accepted dogma that CQ-induced itch is specifically mediated by MrgprA3 coupling to TRPA1.
Topics: Humans; Chloroquine; TRPA1 Cation Channel; Sensory Receptor Cells; Calcium; Reactive Oxygen Species; Pruritus; TRPV Cation Channels; Transient Receptor Potential Channels; Ganglia, Spinal
PubMed: 36928865
DOI: 10.1111/bph.16072 -
Journal of Clinical Medicine Jul 2023Autoresuscitation is a phenomenon of the heart during which it can resume its spontaneous activity and generate circulation. It was described for the first time by K.... (Review)
Review
Autoresuscitation is a phenomenon of the heart during which it can resume its spontaneous activity and generate circulation. It was described for the first time by K. Linko in 1982 as a recovery after discontinued cardiopulmonary resuscitation (CPR). J.G. Bray named the recovery from death the Lazarus phenomenon in 1993. It is based on a biblical story of Jesus' resurrection of Lazarus four days after confirmation of his death. Up to the end of 2022, 76 cases (coming from 27 countries) of spontaneous recovery after death were reported; among them, 10 occurred in children. The youngest patient was 9 months old, and the oldest was 97 years old. The longest resuscitation lasted 90 min, but the shortest was 6 min. Cardiac arrest occurred in and out of the hospital. The majority of the patients suffered from many diseases. In most cases of the Lazarus phenomenon, the observed rhythms at cardiac arrest were non-shockable (Asystole, PEA). Survival time after death ranged from minutes to hours, days, and even months. Six patients with the Lazarus phenomenon reached full recovery without neurological impairment. Some of the causes leading to autoresuscitation presented here are hyperventilation and alkalosis, auto-PEEP, delayed drug action, hypothermia, intoxication, metabolic disorders (hyperkalemia), and unobserved minimal vital signs. To avoid Lazarus Syndrome, it is recommended that the patient be monitored for 10 min after discontinuing CPR. Knowledge about this phenomenon should be disseminated in the medical community in order to improve the reporting of such cases. The probability of autoresuscitation among older people is possible.
PubMed: 37510819
DOI: 10.3390/jcm12144704 -
Neuroscience and Biobehavioral Reviews Dec 2023High Ventilation Breathwork (HVB) refers to practices employing specific volitional manipulation of breathing, with a long history of use to relieve various forms of... (Review)
Review
High Ventilation Breathwork (HVB) refers to practices employing specific volitional manipulation of breathing, with a long history of use to relieve various forms of psychological distress. This paper seeks to offer a consolidative insight into potential clinical application of HVB as a treatment of psychiatric disorders. We thus review the characteristic phenomenological and neurophysiological effects of these practices to inform their mechanism of therapeutic action, safety profiles and future clinical applications. Clinical observations and data from neurophysiological studies indicate that HVB is associated with extraordinary changes in subjective experience, as well as with profound effects on central and autonomic nervous systems functions through modulation of neurometabolic parameters and interoceptive sensory systems. This growing evidence base may guide how the phenomenological effects of HVB can be understood, and potentially harnessed in the context of such volitional perturbation of psychophysiological state. Reports of putative beneficial effects for trauma-related, affective, and somatic disorders invite further research to obtain detailed mechanistic knowledge, and rigorous clinical testing of these potential therapeutic uses.
Topics: Humans; Yoga; Respiration; Autonomic Nervous System; Mental Disorders; Psychophysiology
PubMed: 37923236
DOI: 10.1016/j.neubiorev.2023.105453 -
The Journal of Small Animal Practice Nov 2023Metabolic alkalosis, although uncommon in small animals, has been previously associated with gastrointestinal obstructions. Depending on the population and disease...
OBJECTIVES
Metabolic alkalosis, although uncommon in small animals, has been previously associated with gastrointestinal obstructions. Depending on the population and disease process evaluated, previous prevalence of metabolic alkalosis is reported as ranging from 2% to 45% in canine patients. The objective of this study was to determine the prevalence of metabolic alkalosis and other acid-base and electrolyte disorders in a cohort of dogs with a confirmed upper gastrointestinal obstruction.
MATERIALS AND METHODS
Electronic medical records were reviewed to identify dogs who presented for vomiting with evidence of an upper gastrointestinal obstruction from January 2015 to October 2021. Patients were enrolled only if a preoperative venous blood gas was obtained and analysed in house. Traditional acid-base analysis was utilised to determine an acid-base status before relieving the obstruction. When available, post-operative venous acid-base status was determined within 24 hours after surgery, and compared to preoperative results.
RESULTS
A total of 115 dogs were included in the study. Twenty-five out of 115 (22%) dogs displayed either a simple metabolic alkalosis or a mixed acid-base disturbance before surgery. Twenty-seven out of 115 dogs (37%) had a normal acid-base status at entry. Seventy-one dogs had pre- and post-operative venous blood gas results available. Metabolic alkalosis was resolved in nearly all patients post-operatively, with no patients displaying a simple metabolic alkalosis. A mixed metabolic acidosis and respiratory alkalosis was the most common condition post-operatively, found in 25 of 71 (35%) dogs. Severe derangements of electrolytes were infrequent preoperatively (3/115; 2.6%). A majority of patients in this study exhibited hypokalaemia (64.4%), hypochloraemia (72.8%) and hyponatraemia (77.4%) on preoperative venous blood gases. Venous pH, P CO , bicarbonate and base excess were significantly higher preoperatively when compared to the post-operative results.
CLINICAL SIGNIFICANCE
This study found the prevalence of pre-operative metabolic alkalosis in dogs with a documented upper gastrointestinal obstruction to be lower than previously reported. Surgical or endoscopic alleviation of the upper gastrointestinal obstruction resulted in resolution of metabolic alkalosis in nearly all patients.
Topics: Humans; Dogs; Animals; Alkalosis; Acid-Base Imbalance; Acidosis; Electrolytes; Intestinal Obstruction; Hydrogen-Ion Concentration; Acid-Base Equilibrium; Dog Diseases
PubMed: 37565533
DOI: 10.1111/jsap.13656 -
The Journal of Physiology Aug 2023The interoceptive homeostatic mechanism that controls breathing, blood gases and acid-base balance in response to changes in CO /H is exquisitely sensitive, with...
The interoceptive homeostatic mechanism that controls breathing, blood gases and acid-base balance in response to changes in CO /H is exquisitely sensitive, with convergent roles proposed for chemosensory brainstem neurons in the retrotrapezoid nucleus (RTN) and their supporting glial cells. For astrocytes, a central role for NBCe1, a Na -HCO cotransporter encoded by Slc4a4, has been envisaged in multiple mechanistic models (i.e. underlying enhanced CO -induced local extracellular acidification or purinergic signalling). We tested these NBCe1-centric models by using conditional knockout mice in which Slc4a4 was deleted from astrocytes. In GFAP-Cre;Slc4a4 mice we found diminished expression of Slc4a4 in RTN astrocytes by comparison to control littermates, and a concomitant reduction in NBCe1-mediated current. Despite disrupted NBCe1 function in RTN-adjacent astrocytes from these conditional knockout mice, CO -induced activation of RTN neurons or astrocytes in vitro and in vivo, and CO -stimulated breathing, were indistinguishable from NBCe1-intact littermates; hypoxia-stimulated breathing and sighs were likewise unaffected. We obtained a more widespread deletion of NBCe1 in brainstem astrocytes by using tamoxifen-treated Aldh1l1-Cre/ERT2;Slc4a4 mice. Again, there was no difference in effects of CO or hypoxia on breathing or on neuron/astrocyte activation in NBCe1-deleted mice. These data indicate that astrocytic NBCe1 is not required for the respiratory responses to these chemoreceptor stimuli in mice, and that any physiologically relevant astrocytic contributions must involve NBCe1-independent mechanisms. KEY POINTS: The electrogenic NBCe1 transporter is proposed to mediate local astrocytic CO /H+ sensing that enables excitatory modulation of nearby retrotrapezoid nucleus (RTN) neurons to support chemosensory control of breathing. We used two different Cre mouse lines for cell-specific and/or temporally regulated deletion of the NBCe1 gene (Slc4a4) in astrocytes to test this hypothesis. In both mouse lines, Slc4a4 was depleted from RTN-associated astrocytes but CO -induced Fos expression (i.e. cell activation) in RTN neurons and local astrocytes was intact. Likewise, respiratory chemoreflexes evoked by changes in CO or O were unaffected by loss of astrocytic Slc4a4. These data do not support the previously proposed role for NBCe1 in respiratory chemosensitivity mediated by astrocytes.
Topics: Animals; Mice; Astrocytes; Carbon Dioxide; Chemoreceptor Cells; Ions; Mice, Knockout; Sodium-Bicarbonate Symporters; Symporters
PubMed: 37384821
DOI: 10.1113/JP284960