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American Journal of Kidney Diseases :... Oct 2022Metabolic alkalosis is a widespread acid-base disturbance, especially in hospitalized patients. It is characterized by the primary elevation of serum bicarbonate and... (Review)
Review
Metabolic alkalosis is a widespread acid-base disturbance, especially in hospitalized patients. It is characterized by the primary elevation of serum bicarbonate and arterial pH, along with a compensatory increase in Pco consequent to adaptive hypoventilation. The pathogenesis of metabolic alkalosis involves either a loss of fixed acid or a net accumulation of bicarbonate within the extracellular fluid. The loss of acid may be via the gastrointestinal tract or the kidney, whereas the sources of excess alkali may be via oral or parenteral alkali intake. Severe metabolic alkalosis in critically ill patients-arterial blood pH of 7.55 or higher-is associated with significantly increased mortality rate. The kidney is equipped with sophisticated mechanisms to avert the generation or the persistence (maintenance) of metabolic alkalosis by enhancing bicarbonate excretion. These mechanisms include increased filtration as well as decreased absorption and enhanced secretion of bicarbonate by specialized transporters in specific nephron segments. Factors that interfere with these mechanisms will impair the ability of the kidney to eliminate excess bicarbonate, therefore promoting the generation or impairing the correction of metabolic alkalosis. These factors include volume contraction, low glomerular filtration rate, potassium deficiency, hypochloremia, aldosterone excess, and elevated arterial carbon dioxide. Major clinical states are associated with metabolic alkalosis, including vomiting, aldosterone or cortisol excess, licorice ingestion, chloruretic diuretics, excess calcium alkali ingestion, and genetic diseases such as Bartter syndrome, Gitelman syndrome, and cystic fibrosis. In this installment in the AJKD Core Curriculum in Nephrology, we will review the pathogenesis of metabolic alkalosis; appraise the precipitating events; and discuss clinical presentations, diagnoses, and treatments of metabolic alkalosis.
Topics: Aldosterone; Alkalies; Alkalosis; Bicarbonates; Calcium; Carbon Dioxide; Curriculum; Diuretics; Humans; Hydrocortisone
PubMed: 35525634
DOI: 10.1053/j.ajkd.2021.12.016 -
Clinical Journal of the American... Dec 2020Metabolic alkalosis is a very commonly encountered acid-base disorder that may be generated by a variety of exogenous and/or endogenous, pathophysiologic mechanisms.... (Review)
Review
Metabolic alkalosis is a very commonly encountered acid-base disorder that may be generated by a variety of exogenous and/or endogenous, pathophysiologic mechanisms. Multiple mechanisms are also responsible for the persistence, or maintenance, of metabolic alkalosis. Understanding these generation and maintenance mechanisms helps direct appropriate intervention and correction of this disorder. The framework utilized in this review is based on the ECF volume-centered approach popularized by Donald Seldin and Floyd Rector in the 1970s. Although many subsequent scientific discoveries have advanced our understanding of the pathophysiology of metabolic alkalosis, that framework continues to be a valuable and relatively straightforward diagnostic and therapeutic model.
Topics: Acid-Base Equilibrium; Alkalosis; Animals; Bicarbonates; Biomarkers; Chlorides; Humans; Hydrogen-Ion Concentration; Models, Biological; Prognosis
PubMed: 32586924
DOI: 10.2215/CJN.16041219 -
Clinical Journal of the American... Jan 2023Acid-base disorders are common in the intensive care unit. By utilizing a systematic approach to their diagnosis, it is easy to identify both simple and mixed...
Acid-base disorders are common in the intensive care unit. By utilizing a systematic approach to their diagnosis, it is easy to identify both simple and mixed disturbances. These disorders are divided into four major categories: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. Metabolic acidosis is subdivided into anion gap and non-gap acidosis. Distinguishing between these is helpful in establishing the cause of the acidosis. Anion gap acidosis, caused by the accumulation of organic anions from sepsis, diabetes, alcohol use, and numerous drugs and toxins, is usually present on admission to the intensive care unit. Lactic acidosis from decreased delivery or utilization of oxygen is associated with increased mortality. This is likely secondary to the disease process, as opposed to the degree of acidemia. Treatment of an anion gap acidosis is aimed at the underlying disease or removal of the toxin. The use of therapy to normalize the pH is controversial. Non-gap acidoses result from disorders of renal tubular H + transport, decreased renal ammonia secretion, gastrointestinal and kidney losses of bicarbonate, dilution of serum bicarbonate from excessive intravenous fluid administration, or addition of hydrochloric acid. Metabolic alkalosis is the most common acid-base disorder found in patients who are critically ill, and most often occurs after admission to the intensive care unit. Its etiology is most often secondary to the aggressive therapeutic interventions used to treat shock, acidemia, volume overload, severe coagulopathy, respiratory failure, and AKI. Treatment consists of volume resuscitation and repletion of potassium deficits. Aggressive lowering of the pH is usually not necessary. Respiratory disorders are caused by either decreased or increased minute ventilation. The use of permissive hypercapnia to prevent barotrauma has become the standard of care. The use of bicarbonate to correct the acidemia is not recommended. In patients at the extreme, the use of extracorporeal therapies to remove CO 2 can be considered.
Topics: Humans; Bicarbonates; Critical Illness; Acidosis; Acid-Base Equilibrium; Acid-Base Imbalance; Alkalosis
PubMed: 35998977
DOI: 10.2215/CJN.04500422 -
International Journal of Nephrology and... 2018Bartter syndrome is an inherited renal tubular disorder caused by a defective salt reabsorption in the thick ascending limb of loop of Henle, resulting in salt wasting,... (Review)
Review
Bartter syndrome is an inherited renal tubular disorder caused by a defective salt reabsorption in the thick ascending limb of loop of Henle, resulting in salt wasting, hypokalemia, and metabolic alkalosis. Mutations of several genes encoding the transporters and channels involved in salt reabsorption in the thick ascending limb cause different types of Bartter syndrome. A poor phenotype-genotype relationship due to the interaction with other cotransporters and different degrees of compensation through alternative pathways is currently reported. However, phenotypic identification still remains the first step to guide the suspicion of Bartter syndrome. Given the rarity of the syndrome, and the lack of genetic characterization in most cases, limited clinical evidence for treatment is available and the therapy is based mainly on the comprehension of renal physiology and relies on the physician's personal experiences. A better understanding of the mutated channels and transporters could possibly generate targets for specific treatment in the future, also encompassing drugs aiming to correct deficiencies in folding or plasma membrane expression of the mutated proteins.
PubMed: 30519073
DOI: 10.2147/IJNRD.S155397 -
Nefrologia : Publicacion Oficial de La... 2016Hyperchloremia is a common electrolyte disorder that is associated with a diverse group of clinical conditions. The kidney plays an important role in the regulation of... (Review)
Review
Hyperchloremia is a common electrolyte disorder that is associated with a diverse group of clinical conditions. The kidney plays an important role in the regulation of chloride concentration through a variety of transporters that are present along the nephron. Nevertheless, hyperchloremia can occur when water losses exceed sodium and chloride losses, when the capacity to handle excessive chloride is overwhelmed, or when the serum bicarbonate is low with a concomitant rise in chloride as occurs with a normal anion gap metabolic acidosis or respiratory alkalosis. The varied nature of the underlying causes of the hyperchloremia will, to a large extent, determine how to treat this electrolyte disturbance.
Topics: Acid-Base Equilibrium; Acidosis; Alkalosis, Respiratory; Bicarbonates; Cell Membrane Permeability; Chlorides; Formates; Humans; Ion Transport; Kidney Tubules, Proximal; Membrane Transport Proteins; Natriuresis; Nephrons; Oxalates; Water-Electrolyte Imbalance
PubMed: 27267918
DOI: 10.1016/j.nefro.2016.04.001 -
Kidney International Feb 2021Bartter syndrome is a rare inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism with hypokalemic and hypochloremic metabolic...
Diagnosis and management of Bartter syndrome: executive summary of the consensus and recommendations from the European Rare Kidney Disease Reference Network Working Group for Tubular Disorders.
Bartter syndrome is a rare inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism with hypokalemic and hypochloremic metabolic alkalosis and low to normal blood pressure. The primary pathogenic mechanism is defective salt reabsorption predominantly in the thick ascending limb of the loop of Henle. There is significant variability in the clinical expression of the disease, which is genetically heterogenous with 5 different genes described to date. Despite considerable phenotypic overlap, correlations of specific clinical characteristics with the underlying molecular defects have been demonstrated, generating gene-specific phenotypes. As with many other rare disease conditions, there is a paucity of clinical studies that could guide diagnosis and therapeutic interventions. In this expert consensus document, the authors have summarized the currently available knowledge and propose clinical indicators to assess and improve quality of care.
Topics: Alkalosis; Bartter Syndrome; Consensus; Humans; Hypokalemia; Rare Diseases
PubMed: 33509356
DOI: 10.1016/j.kint.2020.10.035