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American Journal of Kidney Diseases :... Sep 2023The respiratory system plays an integral part in maintaining acid-base homeostasis. Normal ventilation participates in the maintenance of an open buffer system, allowing... (Review)
Review
The respiratory system plays an integral part in maintaining acid-base homeostasis. Normal ventilation participates in the maintenance of an open buffer system, allowing for excretion of CO produced from the interaction of nonvolatile acids and bicarbonate. Quantitatively of much greater importance is the excretion of CO derived from volatile acids produced from the complete oxidation of fat and carbohydrate. A primary increase in CO tension of body fluids is the cause of respiratory acidosis and develops most commonly from one or more of the following: (1) disorders affecting gas exchange across the pulmonary capillary, (2) disorders of the chest wall and the respiratory muscles, and/or (3) inhibition of the medullary respiratory center. Respiratory alkalosis or primary hypocapnia is most commonly caused by disorders that increase alveolar ventilation and is defined by an arterial partial pressure of CO <35 mm Hg with subsequent alkalization of body fluids. Both disorders can lead to life-threatening complications, making it of paramount importance for the clinician to have a thorough understanding of the cause and treatment of these acid-base disturbances.
Topics: Humans; Acidosis, Respiratory; Alkalosis, Respiratory; Carbon Dioxide; Hypocapnia; Bicarbonates; Alkalosis; Hydrogen-Ion Concentration; Acid-Base Equilibrium
PubMed: 37341662
DOI: 10.1053/j.ajkd.2023.02.004 -
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 -
Pediatric Clinics of North America Feb 2019Bartter and Gitelman syndromes are conditions characterized by renal salt-wasting. Clinical presentations range from severe antenatal disease to asymptomatic with... (Review)
Review
Bartter and Gitelman syndromes are conditions characterized by renal salt-wasting. Clinical presentations range from severe antenatal disease to asymptomatic with incidental diagnosis. Hypokalemic hypochloremic metabolic alkalosis is the common feature. Bartter variants may be associated with polyuria and weakness. Gitelman syndrome is often subtle, and typically diagnosed later life with incidental hypokalemia and hypomagnesemia. Treatment may involve fluid and electrolyte replenishment, prostaglandin inhibition, and renin-angiotensin-aldosterone system axis disruption. Investigators have identified causative mutations but genotypic-phenotypic correlations are still being characterized. Collaborative registries will allow improved classification schema and development of effective treatments.
Topics: Bartter Syndrome; Child; Diagnosis, Differential; Gitelman Syndrome; Humans
PubMed: 30454738
DOI: 10.1016/j.pcl.2018.08.010 -
Nutrition in Clinical Practice :... Oct 2022An understanding of acid-base physiology is necessary for clinicians to recognize and correct problems that may negatively affect provision of nutrition support and drug... (Review)
Review
An understanding of acid-base physiology is necessary for clinicians to recognize and correct problems that may negatively affect provision of nutrition support and drug therapy. An overview of acid-base physiology, the different acid-base disorders encountered in practice, a stepwise approach to evaluate arterial blood gases, and other key diagnostic tools helpful in formulating a safe and effective medical and nutrition plan are covered in this acid-base primer. Case scenarios are also provided for the application of principles and the development of clinical skills.
Topics: Acid-Base Equilibrium; Acid-Base Imbalance; Acidosis; Alkalosis; Alkalosis, Respiratory; Blood Gas Analysis; Humans; Hydrogen-Ion Concentration
PubMed: 35752932
DOI: 10.1002/ncp.10881 -
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 -
Anti-cancer Agents in Medicinal... 2017It is a longstanding debate whether cancer is one disease or a set of very diverse diseases. The goal of this paper is to suggest strongly that most of (if not all) the... (Review)
Review
It is a longstanding debate whether cancer is one disease or a set of very diverse diseases. The goal of this paper is to suggest strongly that most of (if not all) the hallmarks of cancer could be the consequence of the Warburg's effect. As a result of the metabolic impairment of the oxidative phosphorylation, there is a decrease in ATP concentration. To compensate the reduced energy yield, there is massive glucose uptake, anaerobic glycolysis, with an up-regulation of the Pentose Phosphate Pathway resulting in increased biosynthesis leading to increased cell division and local pressure. This increased pressure is responsible for the fractal shape of the tumor, the secretion of collagen by the fibroblasts and plays a critical role in metastatic spread. The massive extrusion of lactic acid contributes to the extracellular acidity and the activation of the immune system. The decreased oxidative phosphorylation leads to impairment in CO2 levels inside and outside the cell, with increased intracellular alkalosis and contribution of carbonic acid to extracellular acidosis-mediated by at least two cancer-associated carbonic anhydrase isoforms. The increased intracellular alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Mitochondrial disappearance (such as seen in very aggressive tumors) is a consequence of mitochondrial swelling, itself a result of decreased ATP concentration. The transmembrane pumps, which extrude, from the mitochondria, ions, and water, are ATP-dependant. Therapy aiming at increasing both the number and the efficacy of mitochondria could be very useful.
Topics: Acidosis; Adenosine Triphosphate; Alkalosis; Animals; Carbon Dioxide; Cell Proliferation; Citrates; Glucose; Glycolysis; Humans; Mitochondria; Neoplasms; Oxidative Phosphorylation; Pentose Phosphate Pathway; Thioctic Acid
PubMed: 27804847
DOI: 10.2174/1871520616666161031143301 -
Pediatrics in Review Oct 2021Hypertrophic pyloric stenosis is a common condition seen in the first 1 to 3 months after birth. Patients typically present with nonbilious projectile emesis after feeds...
Hypertrophic pyloric stenosis is a common condition seen in the first 1 to 3 months after birth. Patients typically present with nonbilious projectile emesis after feeds that may result in hypokalemic, hypochloremic metabolic alkalosis. Although inability to tolerate feeds is frequently seen with self-limited conditions such as reflux, a low threshold to obtain an ultrasonographic image is important to prevent a delay in diagnosis. Although operative intervention is the treatment, it is imperative that patients are hydrated and serum electrolyte concentrations normalized before the induction of anesthesia. Laparoscopic pyloromyotomy is safe and effective. Postoperative emesis is normal, and reassurance to parents is appropriate. There is no significant long-term physiologic impairment from pyloric stenosis after successful surgical intervention.
Topics: Alkalosis; Humans; Infant; Pyloric Stenosis, Hypertrophic; Vomiting
PubMed: 34599053
DOI: 10.1542/pir.2020-003277