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Structural Organization of the Mammalian Kidney

The mammalian kidney is multiform. The basic architecture is best understood in the unipapillary kidney, which is common in all small species. A coronal section of this kidney shows the main structural parts (Figure 20.1a). The renal cortex, as a whole, is cup-shaped with inverted margins, and surrounds the renal medulla. The medulla can be roughly compared to a pyramid; its top portion, the papilla, projects…

Paracrine Regulation of Renal Function by Dopamine

Classical transmitter ligands evolved about 1000 million years ago. 1 The role of dopamine as a neurotransmitter has evolved with time. In primordial and plant cells, dopamine is present, even though catecholamine signaling is not used. In invertebrate neural systems, dopamine is the pre-eminent catecholamine. In vertebrates, the catecholamine pathway terminates in norepinephrine and epinephrine. 2 Endogenous dopamine was mainly recognized as a precursor to norepinephrine…

Extracellular Nucleotides and Renal Function

Increasing evidence suggests that the ATP/P2 receptor system acts in an autocrine or paracrine fashion to affect various aspects of renal function. P2 receptors have been identified in most renal vessels and nephron segments; ATP is released from renal epithelial cells; and enzymes responsible for ATP breakdown are expressed in the vasculature and tubules. Stimulation of P2 receptors in the afferent arterioles by ATP released from…

Eicosanoids and Renal Function

Perhaps nothing underscores the special relationship between the kidney and the eicosanoids better than the profound clinical effects non-steroidal anti-inflammatory drugs (NSAIDS) have on kidney function. NSAIDs are widely used to treat pain and inflammatory diseases, and work by blocking the enzymatic synthesis of prostaglandins, a type of eicosanoid, from arachidonic acid. However, chronic NSAID use is often complicated by major side effects, including renal sodium…

Neural Control of Renal Function

One of the first observations of a potential neural control of kidney function was made by Claude Bernard in the middle of the 19th century, who reported a unilateral diuresis following section of the greater splanchnic nerve of the anesthetized dog. However, the critical role of the sympathetic nervous system in the control of renal function was long questioned due to the views of Homer Smith,…

The Renin–Angiotensin System

The renin-angiotensin system (RAS) is a master regulator of blood pressure and fluid homeostasis. This system is a multi-enzymatic cascade in which angiotensinogen, the major substrate, is processed in a two-step reaction by renin and angiotensin-converting enzyme (ACE), resulting in the sequential generation of angiotensins I and II. In recent years, several new enzymes, peptides, and receptors in this system have been identified, manifesting a complexity…

Scaffolding Proteins in Transport Regulation

In recent years, there has been an explosion of discovery about proteins that function to organize components of the signal transduction machinery with their effectors at specific subcellular locales. Many of these molecular scaffolds control the assembly, trafficking, subcellular location and activity of epithelial transport proteins and their regulators, and, thus, are critical determinants of epithelial transport modulation. Here, the review the present state of knowledge…

Principles of Cell Signaling

The successful transition from single cells to complex multicellular organisms has required the development of mechanisms for cells to communicate with each other, so as to act in concert during processes such as nutrient acquisition, motility, and defense. The most fundamental of these are cell–cell junctions that serve as structural organizers, but also provide information that individual cells can utilize to orient themselves in relation to…

Intercellular Junctions

Intercellular junctions are relatively static regions of cell–cell contact found between epithelial, endothelial and mesothelial cells that have various functions. The morphology of the junctional complex in epithelia was defined by Farquhar and Palade in 1963, Farquhar MG, Palade GE. Junctional complexes in various epithelia. J Cell Biol . May 1963;17:375–412. We now know that it consists of four major components: the tight junction or zonula…

Renal Cilia Structure, Function, and Physiology

The primary or immotile cilium is a nearly ubiquitous microtubule-based structure. It was once considered a vestigial remnant; however, recent advances have revealed that the cilium functions as a critical sensory and signaling center allowing cells to respond efficiently to external environmental cues. Seminal discoveries demonstrating that defects in cilia of mammals cause abnormal left–right body axis specification and cystic kidney disease have ignited strong research…

External Balance of Electrolytes and Acids and Alkali

This chapter will cover discussions on principles of external balance for electrolytes, and for acids and bases. The first section will deal with discussions on principles of electrolyte balance in general, and the second section discusses the acid–base balance. This chapter will cover discussions on principles of external balance for electrolytes, and for acids and bases. The first section will deal with discussions on principles of…

Microvascular Permeability and the Exchange of Water and Solutes Across Microvascular Walls

Exchange through microvascular walls is both the initial and the final step of transport of materials by the circulation. In most tissues, microvascular exchange is a passive process, driven by differences in hydrostatic pressure and solute concentration between the circulating plasma and the interstitial fluid that flank microvessel walls. Lipophilic molecules and small water-soluble molecules and ions can exchange rapidly in most vascular beds, but microvascular…

Renal Ion Channels, Electrophysiology of Transport, and Channelopathies

The purposes of this chapter are to explain what an ion channel is and how it works, provide an overview of the contribution ion channel proteins make to renal transport, and suggest how changes in the structure and biophysical properties of renal ion channels cause disease. Emphasis is placed on recent information gained from the latest techniques. This chapter is neither a technical manual nor a…

Electrophysiological Analysis of Transepithelial Transport

In this chapter we discuss electrophysiological approaches to the study of renal function. The purpose is to provide an overview of the available techniques, with particular emphasis on what can be learned using the latest methods. However, the chapter is neither a technical manual nor a comprehensive review of the literature. For this, we refer the reader to other sections of the book which deal with…

Solute Transport, Energy Consumption, and Production in the Kidney

The kidney uses a large amount of energy, most of which are dedicated to solute reabsorption, especially Na + , from glomerular filtrate. Reabsorption of Na + drives the cellular and paracellular transport of water and other solutes. The mechanisms for energy production and preferred substrates are different among tubular segments. Renal metabolism for energy production is regulated by transport activity, and conversely, transport is affected…

Cell Volume Control

Cells must avoid gross alterations of volume in order to survive. Obviously, excessive cell swelling will jeopardize the integrity of the cell membrane, and both cell swelling and cell shrinkage will interfere with cytoskeletal architecture. Moreover, cellular function critically depends on the hydration of cytosolic proteins. Proteins and protein-bound water occupy a large portion of the cell interior (macromolecular crowding), leaving only a small fraction of…

Mechanisms of Water Transport Across Cell Membranes and Epithelia

In this chapter we discuss the pathways and mechanisms of water transport across cell membranes and epithelia. The concepts of diffusion and osmosis are presented at the biophysical level and applied to water transport phenomena across lipid bilayers and membrane-spanning pores. Water pores (“aquaporins”) are described from biophysical and molecular points of view. The mechanism of water transport across the cell membrane is osmosis and cell…

Renal Ion-Translocating ATPases

Ion motive ATPases involved in transcellular ion transport by renal epithelial cells include two molecular families: P-ATPases (Na,K-ATPase and H,K-ATPase) and V-ATPases. Na,K-ATPase is found in the plasma membrane of every vertebrate cell and exchanges three intracellular Na + for two intracellular K + for each hydrolyzed ATP molecule. Na,K-ATPase is highly expressed in the kidney tubule where it is located in the basolateral membrane and…

Mechanisms of Ion Transport across Cell Membranes

Ion transport across the cell membrane is essential to maintain the composition of the intracellular milieu . This chapter provides an introduction to ion transport processes in the cell membrane. The cell membrane is a thin sheet containing lipids (phospholipid bilayer) and proteins, many of which span its thickness (integral membrane proteins). Certain ions can permeate the membrane via proteins, but because of their electrical charge…

Epithelial Cell Structure and Polarity

Few cell types more elegantly embody the dictum that “form follows function” than do those of polarized epithelia. It is the unique architecture of renal epithelial cells that permits them to mediate vectorial transport. This transport, in turn, essentially determines the body’s fluid and electrolyte composition. This chapter reviews the structures of renal epithelial cells and explores the mechanisms through which these structures are generated and…