Pathophysiology of metabolic alkalosis: a new classification based on the centrality of stimulated collecting duct ion transport.

Metabolic alkalosis is a unique acid-base disorder because it can be induced and sustained by functional alterations in renal ion transport. This review summarizes more than 50 years of research into the pathophysiologic processes causing this disorder. The evidence reviewed supports the hypothesis that virtually all forms of metabolic alkalosis are sustained by enhanced collecting duct hydrogen ion secretion, induced by stimulation of sodium uptake through the epithelial sodium channel (ENaC). Enhanced collecting duct hydrogen ion secretion in metabolic alkalosis occurs most commonly secondary to changes in ion transport earlier along the nephron, but also can occur as the result of primary stimulation of ENaC. In both these settings, potassium secretion is stimulated, and abnormal potassium losses cause depletion of body potassium stores. Potassium depletion has a key role in sustaining metabolic alkalosis by stimulating renal hydrogen ion secretion, enhancing renal ammonium production and excretion, and downregulating sodium reabsorption in the loop of Henle and early distal tubule. A new classification of the causes of metabolic alkalosis is proposed based on these pathophysiologic events rather than response to treatment.

Inherited primary renal tubular hypokalemic alkalosis: a review of Gitelman and Bartter syndromes.

Inherited hypokalemic metabolic alkalosis, or Bartter syndrome, comprises several closely related disorders of renal tubular electrolyte transport. Recent advances in the field of molecular genetics have demonstrated that there are four genetically distinct abnormalities, which result from mutations in renal electrolyte transporters and channels. Neonatal Bartter syndrome affects neonates and is characterized by polyhydramnios, premature delivery, severe electrolyte derangements, growth retardation, and hypercalciuria leading to nephrocalcinosis. It may be caused by a mutation in the gene encoding the Na-K-2Cl cotransporter (NKCC2) or the outwardly rectifying potassium channel (ROMK), a regulator of NKCC2. Classic Bartter syndrome is due to a mutation in the gene encoding the chloride channel (CLCNKB), also a regulator of NKCC2, and typically presents in infancy or early childhood with failure to thrive. Nephrocalcinosis is typically absent despite hypercalciuria. The hypocalciuric, hypomagnesemic variant of Bartter syndrome (Gitelman syndrome), presents in early adulthood with predominantly musculoskeletal symptoms and is due to mutations in the gene encoding the Na-Cl cotransporter (NCCT). Even though our understanding of these disorders has been greatly advanced by these discoveries, the pathophysiology remains to be completely defined. Genotype-phenotype correlations among the four disorders are quite variable and continue to be studied. A comprehensive review of Bartter and Gitelman syndromes will be provided here.

Using an algorithm to interpret arterial blood gases.

The arterial blood gas (ABG) analysis, one of the most common tests ordered, provides clinicians with valuable information on a patient's oxygenation and acid-base balance. Interpreting ABG analysis results can be challenging, even for the most experienced practitioners, because it requires knowledge of the physiology and cause-and-effect relationship of the disturbances. Applying the principles and the ABG algorithm described in this article will provide nurses with a systematic way to interpret uncomplicated arterial blood gas results, including primary, mixed, and compensated acidbase disturbances.

[Diagnosis, therapy and classification of alkalosis].

The pathogenesis, classification, diagnosis and treatment of alkalosis are described. Alkalemia is defined as an elevation in the blood pH and alkalosis refers to processes that tend to raise the pH, and divided into two types; metabolic alkalosis (a primary increase in plasma HCO3- concentration) and respiratory alkalosis (a primary decrease in PCO2). These disorders are most frequently observed in the hospitalized patients. As the critically ill-patients with severe alkalemia are often associated with high mortality, treatment should be directed to the underlying diseases and severe alkalemia should be corrected promptly.

Clinical approach to the diagnosis of acid-base disorders.

An ability to rapidly and effectively diagnose and treat acid-base disorders is essential to the management of seriously ill patients. In this paper an approach to the diagnosis of pure and mixed acid-base disorders is presented that is based upon an understanding of the bicarbonate buffer system and a knowledge of the well defined and predictable compensatory responses that occur in association with each of the primary acid-base disorders. With this approach a number of acid-base problems are presented and solved.