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Respiratory Acid–Base Disorders

Respiratory acid–base disorders are those abnormalities in acid-base equilibrium that are initiated by a change in blood carbon dioxide tension (PCO 2 ). An increase in PCO 2 (hypercapnia) acidifies body fluids and initiates the acid-base disturbance known as respiratory acidosis. By contrast, a decrease in PCO 2 (hypocapnia) alkalinizes body fluids and initiates the acid-base disorder known as respiratory alkalosis. For each of these disorders,…

Clinical Syndromes of Metabolic Acidosis

Abstract Metabolic acidosis is the acid–base disturbance that is initiated by a primary decrease in the plasma [HCO 3 − ]. The acidemia leads to a time-dependent and quantitatively predictable ventilatory response, i.e., a secondary decrease in CO 2 tension which is taken as the basis for the diagnostic criteria of this disorder. Under certain circumstances, this secondary hypocapnia may elicit a maladaptive renal response characterized…

Clinical Syndromes of Metabolic Alkalosis

Homeostatic control of acid–base parameters within discreet limits is vital to all living organisms. Acid–base disturbances are conditions that reflect abnormal underlying physiologic processes that can stem from a broad range of etiologies. In humans with a filtration-reabsorption nephron design, more than 4000 mEq of HCO 3 − is filtered daily at the glomerulus and virtually all of it is reabsorbed by the tubules.Two points are…

Renal Ammonium Ion Production and Excretion

The maintenance of systemic acid-base balance within relatively narrow limits is essential for life. However, the development of metabolic acidosis, which is characterized by a significant decrease in plasma pH and bicarbonate ions, is a common clinical condition. Metabolic acidosis is caused by the overproduction of acid due to a high protein diet, increased catabolism of endogenous proteins during prolonged fasting, sepsis or cachexia, and various…

Chemoreceptors, Breathing and pH

The regulation of acid–base balance depends on renal mechanisms that determine net excretion of acid or base and breathing mechanisms that alter the partial pressure of carbon dioxide (PCO 2 ) in body tissues. The level of ventilation (breathing) is regulated, in part, by pH-sensitive receptors called chemoreceptors, which are present peripherally at the carotid body and centrally within the hindbrain. Their physiology is the subject…

Cellular Mechanisms of Renal Tubular Acidification

To maintain acid–base balance, the renal tubules secrete hydrogen ions into the lumen at a rate equal to the sum of extrarenal acid generation and bicarbonate filtration. In this chapter we review the cellular mechanisms responsible for transepithelial hydrogen secretion along the nephron and describe the regulators of these processes. To maintain acid–base balance, the renal tubules secrete hydrogen ions into the lumen at a rate…

The SLC4 Anion Exchanger Gene Family

Transmembrane transport of HCO − 3 and CO 2 is central to body pH and volume homeostasis. The Na + -independent, electroneutral CI − /HCO − 3 exchangers AE1/Band 3 and the related AE2 and AE3 polypeptides of the SLC4 gene family play central roles in these processes. The SLC4/AE anion exchangers regulate intracellular pH and, through their polarized localization in renal and other epithelial cells,…

SLC4 Sodium-Driven Bicarbonate Transporters

The SLC4 ( s o l ute c arrier 4) family is a group of a membrane proteins that share sequence homology and in general mediate the transport of bicarbonate. It should be noted that bicarbonate transport is not unique to the SLC4 family. The structurally unrelated SLC26 family has at least three proteins that mediate Cl − –HCO − 3 exchange. In this chapter, the…

Control of Intracellular pH

Because virtually every biological process is sensitive to changes in pH, acid–base homeostasis is of critical importance to cells and organisms, and has attracted considerable attention. Until relatively recently, acid–base homeostasis, for both clinicians and basic scientists, has been synonymous with pH regulation in the two most easily accessed compartments, blood and cerebrospinal fluid (CSF). The pH in these extracellular compartments (pH o ) is certainly…

Clinical Disorders of Hyperkalemia

Hyperkalemia is a common electrolyte disorder that may cause life threatening cardiac arrhythmia. The trans-cellular distribution of K + limits the acute rise in P K . Regulation of K + excretion by the kidney maintains overall K + balance. To shift K + into cells requires an increase in cell interior negative voltage, this is achieved by activating the electrogenic Na-K-ATPase pump. Insulin causes the…

Physiopathology of Potassium Deficiency

Potassium (K + ) deficiency is a common and eventually life-treating condition. Hypokalemia is defined as serum K+ level less than 3.5 mM. This chapter, together with cornerstone mechanisms, reviews the newest molecular regulators of the K + homeostasis, including the feedforward signals recently hypothesized in the gut. The renal and extra-renal diseases leading to hypokalemia are reported here. Newest findings in the mechanism underlying the…

Regulation of K + Excretion

Overview of K + Distribution and Excretion–Internal and External Balance As the most abundant cation in intracellular fluid, K + plays an important role in a variety of cell functions. High K + concentration in cells and low K + concentration in extracellular fluid is essential for many cellular processes, including determining the electrical properties of cell membranes in both excitable (nerve, muscle) and nonexcitable (transporting…

Extrarenal Potassium Metabolism

Internal potassium homeostasis is defined as the regulation of potassium distribution between the intracellular and extracellular fluid compartments, as distinct from the net gain or loss of potassium from the body. While the kidney plays the predominant role in maintaining external potassium balance, nonrenal tissues, especially muscle and liver, are quantitatively the most important organs involved in the regulation of internal potassium balance. The ratio of…

The Molecular Biology of Renal K + Channels

Renal epithelial transport depends on the coordinated function of potassium channels with ion transporters (co-transporters, channels, and exchangers) and ion pumps in apical and basolateral membranes of distinct cell types along the nephron of the mammalian kidney. Potassium (K + ) channels are key members of this integrated transport system in renal epithelial cells. First, renal K + channels participate in generating cell membrane potential; since…

Polyuria and Diabetes Insipidus

Diabetes insipidus is a disorder characterized by the excretion of abnormally large volumes (<30 ml/kg body weight/day for an adult patient) of dilute urine (<250 mmol/kg). Four basic defects can be involved. The most common, a deficient secretion of the antidiuretic hormone (ADH) arginine vasopressin (AVP), is referred to as neurogenic (or central, neurohypophyseal, cranial, or hypothalamic) diabetes insipidus. Diabetes insipidus can also result from renal…

Hypernatremic States

Hypernatremia can occur with normal, increased or decreased total body sodium content. In healthy individuals and in normal conditions, the plasma concentration of sodium ranges between 136 and 143 mEq/l of plasma, despite large individual variations in the intake of salt and water. The concentration is maintained at constant levels because of the homeostatic mechanism in the body. Claude Bernard was the first to appreciate that…

Hyponatremia

Sodium and its accompanying anions are the principle osmotically active solutes in extracellular fluid. When extracellular osmolality is low, intracellular osmolality is equally low. Therefore, although there are exceptions (Table 44.1), hyponatremia is usually associated with hypoosmolality and dilution of all body fluids. The Plasma Sodium Concentration and Body Fluid Tonicity Sodium and its accompanying anions are the principle osmotically active solutes in extracellular fluid. When…

The Urine Concentrating Mechanism and Urea Transporters

Concentrated urine is produced through the generation of an osmotic gradient in the renal medulla. The gradient in the outer medulla is widely believed to be generated by means of a mechanism in which an osmotic pressure difference is amplified by countercurrent multiplication. This difference arises from active NaCl reabsorption from thick ascending limbs, which dilutes ascending limb flow relative to flow in vessels and other…

Thirst and Vasopressin

Thirst and the antidiuretic hormone, arginine vasopressin, are the principal elements of a powerful homeostatic system that regulates the “effective” osmotic pressure of body fluids. This variable, usually referred to as “tonicity,” must be important for survival since mechanisms to regulate it are found throughout the animal kingdom, and abnormalities in humans can have adverse effects, especially on central nervous function. However, it is less clear…

Aquaporin Water Channels in Mammalian Kidney

Hypernatremia can occur with normal, increased or decreased total body sodium content. In healthy individuals and in normal conditions, the plasma concentration of sodium ranges between 136 and 143 mEq/l of plasma, despite large individual variations in the intake of salt and water. The concentration is maintained at constant levels because of the homeostatic mechanism in the body. Claude Bernard was the first to appreciate that…