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Physiology and Pathophysiology of Diuretic Action

The term diuretic derives from the Greek diouretikos , meaning “to promote urine.” Although infusion of saline or ingestion of water would therefore qualify as being diuretic, the term diuretic usually connotes a drug that can reduce the extracellular fluid (ECF) volume by increasing urinary solute or water excretion. The term aquaretic has sometimes been applied to drugs that increase excretion of solute free water, distinguishing…

Physiology and Pathophysiology of Hypertension

Abstract Normal blood pressure (BP) regulation involves the integrated actions of multiple cardiovascular, renal, neural, endocrine, and local tissue control systems. Chronic hypertension is a disorder of long-term BP regulation, although short-term BP control systems may also be affected. Abnormal kidney function, as reflected by resetting of renal-pressure natriuresis to higher BP, is present in all forms of chronic hypertension. However, impaired renal-pressure natriuresis and chronic…

Pathophysiology of Sodium Retention and Wastage

Extracellular fluid (ECF) volume is determined by the balance between sodium intake and renal excretion of sodium. Under normal circumstances, wide variations in salt intake lead to parallel changes in renal salt excretion, such that ECF volume is maintained within narrow limits. This relative constancy of ECF volume is achieved by a series of afferent sensing systems, central integrative pathways, and renal and extrarenal effector mechanisms…

Natriuretic Hormones

Hormones which enhance sodium excretion, i.e., natriuretic peptide hormones, are very important for the maintenance of extracellu/lar fluid volume within a narrow range, despite wide variations in dietary sodium intake. This regulation occurs through a complex interplay of the antinatriuretic renin–angiotensin–aldosterone system and the antinatriuretic renal sympathetic system, which help to conserve sodium when sodium intake is low, and the natriuretic hormones, which enhance sodium excretion…

Inherited Disorders of Renal Salt Homeostasis: Insights from Molecular Genetics Studies

Many of the mediators and regulators of renal salt reabsorption have been identified from physiologic studies. The manner in which these individual elements function in the context of integrated physiology in vivo is best understood from the consequence of mutations that alter the function of individual components. In addition, unbiased genetic screens have the ability to identify previously unrecognized elements of the regulatory network. Studies of…

Mineralocorticoid Action in the Aldosterone Sensitive Distal Nephron

The kidney of vertebrates plays a major role in the homeostasis of the extracellular fluid. Despite large changes in water and salt intake, the kidney is able to maintain the extracellular osmolarity and volume within very narrow margins. Such fine control requires specific factors or hormones. In 1952, Simpson and Tait identified aldosterone as the most potent Na + -retaining factor in mammals. When the Na…

Sodium Chloride Transport in the Loop of Henle, Distal Convoluted Tubule, and Collecting Duct

In this chapter we review the transport of ions by the loop of Henle, distal convoluted tubule, the connecting tubule, and the collecting duct. We will place special emphasis on the cellular and molecular mechanisms responsible for Na + transport in these regions, as well as the factors that regulate Na + transport. Introduction In this chapter we review the transport of ions by the loop…

Sodium and Chloride Transport: Proximal Nephron

The principal function of the proximal tubule is the reabsorption of some two-thirds to three-quarters of the glomerular filtrate. This means, primarily, reabsorption of Na + , Cl − , HCO 3 − , and in smaller quantities potassium, phosphate, and various filtered organic compounds. In view of the copious glomerular filtrate, proximal reabsorption plays a crucial role in the maintenance of fluid and electrolyte balance…

Physiology and Pathophysiology of the NaCl Co-Transporters in the Kidney

This chapter reviews the molecular physiology of the NaCl co-transporters, with emphasis on the thick ascending limb of Henle’s loop Na + -Cl − co-transporter and the distal convoluted tubule Na + -Cl − co-transporter that serve as the receptors for the loop diuretics and thiazide-type diuretics, respectively. Inactivating mutations of these co-transporters produces the hypokalemic metabolic alkalosis syndromes known as Bartter’s and Gitelman’s disease, respectively,…

Anion Channels

Recent years have marked an exciting time in the field of anion channel research. More and more of the molecular identities of the functional anion channel groups have been discovered and this new knowledge has given us an expanded view of the importance of anion channels in both kidney physiology and human physiology. So too have we been forced to acknowledge the shifting landscape that has…

Epithelial Na + Channels

Epithelial Na + channels (ENaCs) have a key role in the regulation of extracellular fluid volume and blood pressure. Over the two decades since the initial characterization of ENaCs at a molecular level, investigators have identified key structural features within channel subunits and have defined mechanisms by which hormones and other factors regulate ENaC activity. Mutations within ENaC subunits have been identified that result in a…

Renal Hyperplasia and Hypertrophy

The tight regulation of cell growth and division within an organ is essential for the development and maintenance of correct structure and function. Perturbations of renal growth occurring either developmentally or following injury to mature renal cells contribute to the abnormalities observed in a wide range of diseases. The changes in growth are increasingly recognized as an influence on the progression of the initial disease process,…

Postnatal Renal Development

The adult kidney functions to keep the organism in a steady state and protect against changes in the volume and composition of the extracellular fluid. Unlike the adult, the neonate must be in positive balance for several solutes to promote growth.There are several developmental changes that occur during the postnatal maturation of the kidney that affect glomerular filtration as well as the mechanisms and regulation of…

Molecular and Cellular Mechanisms of Glomerular Capillary Development

Among all of the capillaries in the body, the glomerulus is arguably the most unusual and important, if not the most aesthetically interesting. In this chapter, we review the morphogenesis of this unique capillary, discuss the origins of its cells and extracellular matrices, and describe some of the primary regulatory events that occur during glomerular development. Among all of the capillaries in the body, the glomerulus…

Molecular and Cellular Mechanisms of Kidney Development

Kidney development begins with interactions between the ureteric bud, an epithelial outgrowth of the Wolffian duct, and the surrounding metanephric mesenchyme. These mutually inductive interactions results in formation of the branched collecting system from the ureteric bud and most of the tubular nephron as well as the epithelial portion of the glomerulus from the metanephric mesenchyme.As a result of a great deal of in vivo knockout…

Renal Cortical and Medullary Microcirculations: Structure and Function

Approximately 170 liters per day of glomerular filtrate is formed in the human renal cortex. Nephrons and collecting ducts perform the enormous task of reabsorbing ~99% of the filtrate while regulating the small quantity finally excreted. Highly specific tubular-vascular relationships in the cortex and medulla accommodate the task of reabsorption. Postglomerular capillaries in the cortex form a dense plexus that surrounds proximal and distal tubules. In…

Function of the Juxtaglomerular Apparatus: Control of Glomerular Hemodynamics and Renin Secretion

More than a century ago, Golgi observed that “the ascending limb of the loop of Henle returns with invariable constancy to its capsule of origin”. At this point of contact at the glomerular hilum, the afferent and efferent arterioles together with the adherent distal tubule form a wedge-shaped compartment which contains the three defining cell types of the juxtaglomerular apparatus (JGA) ( Figure 23.1 ). The…

Glomerular Cell Biology

The glomerulus or renal corpuscle is comprised of the glomerular tuft surrounded by Bowman’s capsule and space. The tuft is a specialized microvascular bed which contains three cell types including the fenestrated or sinusoidal glomerular endothelial cells, the visceral epithelial cells known as podocytes, and mesangial cells. The glomerular filtration barrier is made up of the endothelial cells and podocytes together with an intervening glomerular basement…

Biophysical Basis of Glomerular Filtration

Marcello Malpighi (1628–1694) discovered the renal corpuscle and proposed that each glomerular body embraces the ampullar extremity of a tubule to form a “glandular follicle”. Thereafter, progress toward understanding the structure and function of the nephron stalled for two centuries, until William Bowman finally established the proper anatomic relationship between the glomerular arterioles, capillary tuft, and uriniferous tubule in 1842. In that same year, Carl Ludwig,…