1: Renal Functions, Basic Processes, and Anatomy

• ▸ State 8 major functions of the kidneys.

• ▸ Define the balance concept.

• ▸ Define the gross structures and their interrelationships: renal pelvis, calyces, renal pyramids, renal medulla (inner and outer zones), renal cortex, and papilla.

• ▸ Define the components of the nephron-collecting duct system and their interrelationships: renal corpuscle, glomerulus, tubule, and collecting-duct system.

• ▸ Draw the relationship between glomerulus, Bowman's capsule, and the proximal tubule.

• ▸ Define juxtaglomerular apparatus and describe its 3 cell types; state the function of the granular cells.

• ▸ List the individual tubular segments in order; state the segments that comprise the proximal tubule, Henle's loop, and the collecting-duct system; define principal cells and intercalated cells.

• ▸ Define the basic renal processes: glomerular filtration, tubular reabsorption, and tubular secretion.

• ▸ Define renal metabolism of a substance and give examples.

The kidneys are traditionally known as organs that excrete waste. Although they do indeed excrete waste, they also perform a spectrum of other functions essential for health such as assuring bone integrity and helping to maintain blood pressure. As they carry out these functions the kidneys work cooperatively and interactively with other organ systems, particularly the cardiovascular system. This chapter provides a brief account of renal functions and an overview of how the kidneys perform them, and a description of essential renal anatomy. Ensuing chapters delve into specific renal mechanisms and their interactions with other organ systems.

Function 1: Excretion of Metabolic Waste and Foreign Substances

Our bodies continuously form end products of metabolic processes. In most cases, those end products are of no use to the body and are harmful at high concentrations. Therefore, they must be excreted at the same rate as they are produced. Some of these products include urea (from protein), uric acid (from nucleic acids), creatinine (from muscle creatine), urobilin (an end product of hemoglobin breakdown that gives urine much of its color), and the metabolites of various hormones. In addition, foreign substances, including many common drugs, are excreted by the kidneys. In many cases the kidneys work in partnership with the liver. The liver metabolizes many organic molecules into water-soluble forms that are more easily handled by the kidneys.

Function 2: Regulation of Water and Electrolyte Balance

Water, salt, and other electrolytes enter our bodies at highly variable rates, all of which perturb the amount and concentration of those substances in the body. The kidneys vary their excretion of electrolytes and water to preserve appropriate levels in the body. In doing so they maintain balance, that is, match output to input so as to keep a constant amount in the body. As an example, consider water balance. Our input of water is sporadic and only rarely driven in response to body needs. We drink water when thirsty, but we also drink water because it is a component of beverages that we consume for reasons other than hydration. In addition, solid food often contains large amounts of water. The kidneys respond to increases in water content by increasing the output of water in the urine, thereby restoring body water to normal levels. The same principles apply to an array of electrolytes and other substances that have variable inputs.

Besides excreting excess amounts of various substances, the kidneys respond to deficits. Although the kidneys cannot generate lost water or electrolytes, they can reduce output to a minimum, thus preserving body stores. One of the feats of the kidneys is their ability to regulate each of these substances independently. Within limits we can be on a high-sodium, low-potassium diet or low-sodium, high-potassium diet, and the kidneys adjust excretion of each of these substances appropriately. The reader should also be aware that being in balance for a substance does not by itself imply a normal state or good health. A person may have an excess or deficit of a substance, yet still be in balance so long as output matches input. This is often the case in chronic disorders of renal function or metabolism.

Function 3: Regulation of Extracellular Fluid Volume

The kidneys work in partnership with cardiovascular system, each one performing a service for the other. By far the most important task of the kidneys in this regard is to maintain extracellular fluid volume, of which blood plasma is a significant component. This ensures that the vascular space is filled with sufficient volume so that blood can circulate normally. Maintenance of extracellular fluid volume is a result of water and salt balance described above.

Function 4: Regulation of Plasma Osmolality

Another major aspect of water and electrolyte balance is the regulation of plasma osmolality, that is, the summed concentration of dissolved solutes. Osmolality is altered whenever the inputs and outputs of water and dissolved solutes change disproportionately, as when drinking pure water or eating a salty meal. Not only must the kidneys excrete water and solutes to match inputs, they must do so at rates that keep the ratio of solutes and water at a nearly constant value.

Function 5: Regulation of Red Blood Cell Production

Red blood cell production by the bone marrow is stimulated by the peptide hormone erythropoietin. During embryological development erythropoietin is produced by the liver, but in the adult its major source is the kidneys. The renal cells that secrete it are a particular group of interstitial cells in the cortical interstitium near the border between the renal cortex and medulla (see later). The stimulus for its secretion is a reduction in the partial pressure of oxygen in the local environment of the secreting cells. Although renal blood flow is large, renal metabolism is also large and local oxygenation drops in cases of anemia, which can be caused by blood loss, arterial hypoxia, or inadequate renal blood flow. These conditions all stimulate secretion of erythropoietin. However in chronic renal failure, renal metabolism falls, resulting in lower oxygen consumption and therefore higher local tissue oxygenation. This “fools” the erythropoietin-secreting cells into diminished erythropoietin secretion. The ensuing decrease in bone marrow activity is one important causal factor of anemia associated with chronic renal disease.

Function 6: Regulation of Vascular Resistance

Besides their major role in ensuring adequate volume for the cardiovascular system, the kidneys also participate in the production of vasoactive substances (via the renin-angiotensin-aldosterone system described later) that exert major control over vascular smooth muscle. In turn, this influences peripheral vascular resistance and therefore systemic arterial blood pressure. Pathology in this aspect of renal function leads to hypertension.

Function 7: Regulation of Acid-base Balance

Acids and bases enter the body fluids via ingestion and from metabolic processes. The body has to excrete acids and bases to maintain balance and it also has to regulate the concentration of free hydrogen ions (pH) within a limited range. The kidneys accomplish both tasks by a combination of elimination and synthesis. These interrelated tasks are among the most complicated aspects of renal function and will be explored thoroughly in Chapter 9.

Function 8: Regulation of Vitamin D Production

When we think of vitamin D, we often think of sunlight or additives to milk. In vivo vitamin D synthesis involves a series of biochemical transformations, the last of which occurs in the kidneys. The active form of vitamin D (1,25-dihydroxyvitamin D), called calcitriol, is actually made in the kidneys, and its rate of synthesis is regulated by hormones that control calcium and phosphate balance and bone integrity, which will be discussed in detail in Chapter 10.

Function 9: Gluconeogenesis

Our central nervous system is an obligate user of blood glucose regardless of whether we have just eaten sugary doughnuts or gone without food for a week. Whenever the intake of carbohydrate is stopped for much more than half a day, our body begins to synthesize new glucose (the process of gluconeogenesis) from noncarbohydrate sources (amino acids from protein and glycerol from triglycerides). Most gluconeogenesis occurs in the liver, but a substantial fraction occurs in the kidneys, particularly during a prolonged fast.

Most of what the kidneys actually do is conceptually speaking fairly straightforward. Of the considerable volume of plasma entering the kidneys each minute from the renal arteries, they transfer (by filtration) about one fifth of it, minus the larger plasma proteins, into the renal tubules. They then selectively reabsorb varying fractions of the filtered substances back into the blood, leaving the unreabsorbed portions to be excreted. In some cases additional amounts are added to the excreted content by secretion or synthesis. There is a division of labor between different regions of the tubules for carrying out these tasks that depends on the type of cell expressed in a given region. In essence, the renal tubules operate like assembly lines; they accept the fluid coming into them, perform some segment-specific modification of the fluid, and send it on to the next segment. The final product (urine) contains amounts of each substance that maintain balance for each of them.

The kidneys are bean-shaped organs about the size of a fist. They are located just under the rib cage behind the peritoneal cavity close to the posterior abdominal wall, one on each side of the vertebral column (Figure 1–1). The rounded, outer convex surface of each kidney faces the side of the body, and the indented surface, called the hilum, faces the spine. Each hilum is penetrated by blood vessels, nerves, and a ureter. The ureters bend down and travel a considerable distance to the bladder. Each ureter within a kidney is formed from several funnel-like structures called major calyces, which are themselves formed from minor calyces. The minor calyces fit over underlying cone-shaped renal tissue called pyramids. The tip of each pyramid is called a papilla and projects into a minor calyx. The calyces act as collecting cups for the urine formed by the renal tissue in the pyramids. The pyramids are arranged radially around the hilum, with the papillae pointing toward the hilum and the broad bases of the pyramids facing the convex surface of the kidney. The pyramids constitute the medulla of the kidney. Overlying the medullary tissue is a cortex, and covering the cortical tissue on the very external surface of the kidney is a thin connective tissue capsule (Figure 1–2).

The working tissue mass of both the cortex and medulla is constructed almost entirely of tubules (nephrons and collecting tubules) and blood vessels (capillaries and capillary-like vessels). Between the tubules and blood vessels is the interstitium, which comprises less than 10% of the renal volume. It contains a small amount of interstitial fluid and scattered interstitial cells (fibroblasts and others) that synthesize an extracellular matrix of collagen, proteoglycans, and glycoproteins. And as mentioned, some of these cells secrete erythropoietin. The kidneys also have a lymphatic drainage system, the function of which is to remove soluble proteins from the interstitium that are too large to penetrate the endothelium of tissue capillaries.

The cortex and medulla differ from each other both structurally and functionally. In the cortex the tubules and blood vessels are intertwined randomly, something like a plateful of spaghetti, whereas in the medulla they are organized in parallel arrays like bundles of pencils. In both cases tubules and blood vessels are very close to each other (notice the tight packing of medullary elements shown in Figure 1–3). In addition, the cortex, but not the medulla, contains scattered spherical structures called renal corpuscles. The arrangements of tubules, blood vessels, and renal corpuscles are crucial for renal function, as will be developed later.

In the medulla each pyramid is divisible into an outer zone and an inner zone. The outer zone borders the cortex, and the inner zone continues to the papilla. The outer zone is further subdivided into an outer stripe and an inner stripe. All these distinctions reflect the organized arrangement of tubules and blood vessels.

Each kidney contains approximately 1 million nephrons, which are the tubules that sequentially modify filtered fluid to form the final urine. One nephron is shown diagrammatically in Figure 1–4. Each nephron begins with a spherical filtering component, called the renal corpuscle, followed by a long tubule leading out of the renal corpuscle that continues until it merges with the tubules of other nephrons, like a series of tributaries that form a river. The merged tubules are collecting ducts, which are themselves long tubes. Collecting ducts eventually merge with other collecting ducts in the renal papilla to form a ureter that conveys urine to the bladder. Although nephrons and collecting ducts have different embryological origins, they form a continuous functional unit. For example, the commonly used term “distal nephron” implies elements of both the nephron the collecting duct.

The Renal Corpuscle

The renal corpuscle is a hollow sphere (Bowman's capsule) composed of epithelial cells. It is filled with blood vessels: a compact tuft of interconnected capillary loops called the glomerulus (Figure 1–5A to D). Two closely spaced arterioles penetrate Bowman's capsule at a region called the vascular pole. The afferent arteriole brings blood into the capillaries of the glomerulus, and the efferent arteriole drains blood from it. Another cell type—the mesangial cell—is found in close association with the capillary loops of the glomerulus. Glomerular mesangial cells act as phagocytes and remove trapped material from the basement membrane of the capillaries. They also contain large numbers of myofilaments and can contract in response to a variety of stimuli in a manner similar to vascular smooth muscle cells. The space within Bowman's capsule that is not occupied by capillaries and mesangial cells is called the urinary space or Bowman's space, and it is into this space that fluid filters from the glomerular capillaries before flowing into the first portion of the tubule, located opposite the vascular pole.

The structure and properties of the filtration barrier that separates plasma in the glomerular capillaries from fluid in urinary space are crucial for renal function and will be described thoroughly in the next chapter. For now, we note simply that the functional significance of the filtration barrier is that it permits the filtration of large volumes of fluid from the capillaries into Bowman's space, but restricts filtration of large plasma proteins such as albumin.

The Tubule

The tubule begins at and leads out of Bowman's capsule on the side opposite the vascular pole. The tubule has a number of segments divided into subdivisions (Figure 1–6). To avoid excessive detail we usually group together 2 or more contiguous tubular segments when discussing function. Table 1–1 lists the names and sequence of the various tubular segments. Throughout its length the tubule is made up of a single layer of epithelial cells resting on a basement membrane and connected by tight junctions that physically link the cells together (like the plastic form that holds a 6 pack of soft drinks together).

The proximal tubule is the first segment. It drains Bowman's capsule and consists of a coiled segment—the proximal convoluted tubule—followed by a shorter straight segment—the proximal straight tubule (sometimes called the S3 segment). The coiled segment is entirely within the cortex, whereas the straight segment descends a short way into the outer medulla (labeled 3 in Figure 1–6). Most of the length and functions of the proximal tubule are in the cortex.

The next segment is the descending thin limb of the loop of Henle (or simply the descending thin limb). The descending thin limbs of all nephrons begin at the same level, at the point where they connect to straight portions of proximal tubules in the outer medulla. This marks the border between the outer and inner stripes of the outer medulla. In contrast, the descending thin limbs of different nephrons penetrate down to varying depths in the medulla. At their ending they abruptly reverse at a hairpin turn and become an ascending portion of the loop of Henle parallel to the descending portion. In long loops, the ones that have penetrated deep into the inner medulla, the epithelium of the first portion of the ascending limb remains thin, although different functionally from that of the descending limb. This segment is called the ascending thin limb of Henle's loop, or simply the ascending thin limb (labeled 5 Figure 1–6). Further up the ascending portion the epithelium thickens, and this next segment is called the thick ascending limb of Henle's loop, or simply the thick ascending limb. In short loops (depicted in the right side of Figure 1–6), there is no ascending thin portion, and the thick ascending portion begins right at the hairpin loop. All thick ascending limbs begin at the same level, which marks the border between the inner and outer medulla. Therefore, the thick ascending limbs begin at a slightly deeper level in the medulla than do thin descending limbs. Each thick ascending limb rises back into the cortex right back to the very same Bowman's capsule from which the tubule originated. Here it passes directly between the afferent and efferent arterioles at the vascular pole of Bowman's capsule. The cells in the thick ascending limb closest to Bowman's capsule (between the afferent and efferent arterioles) are specialized cells known as the macula densa (labeled 7 in Figure 1–6). The macula densa marks the end of the thick ascending limb and the beginning of the distal convoluted tubule (labeled 8 in Figure 1–6). This is followed by the connecting tubule, which leads to the cortical collecting duct, the first portion of which is called the initial collecting tubule.

Connecting tubules from several nephrons merge to form a given cortical collecting duct (Figure 1–6). All the cortical collecting ducts then run downward to enter the medulla and become outer medullary collecting ducts, and continue to become inner medullary collecting ducts. These merge to form larger ducts, the last portions of which are called papillary collecting ducts, each of which empties into a calyx of the renal pelvis. Each renal calyx is continuous with the ureter. The tubular fluid, now properly called urine, is not altered after it enters a calyx.

Up to the distal convoluted tubule, the epithelial cells forming the wall of a nephron in any given segment are homogeneous and distinct for that segment. For example, the thick ascending limb contains only thick ascending limb cells. However, beginning in the second half of the distal convoluted tubule the epithelium contains 2 intermingled cell types. The first constitutes the majority of cells in a particular segment and are usually called principal cells. Thus, there are segment-specific principal cells in the distal convoluted tubule, connecting tubule, and collecting ducts. Interspersed among the segment-specific cells in these regions are cells of a second type, called intercalated cells, that is, they are intercalated between the principal cells. The last portion of the medullary collecting duct contains neither principal cells nor intercalated cells but is composed entirely of a distinct cell type called the inner medullary collecting-duct cells.

The Juxtaglomerular Apparatus

Earlier we mentioned the macula densa, a portion of the end of the thick ascending limb at the point where this segment comes between the afferent and efferent arterioles at the vascular pole of the renal corpuscle from which the tubule arose. This entire area is known as the juxtaglomerular (JG) apparatus, which, as will be described in Chapter 7, plays a very important signaling function. (Do not confuse the term JG apparatus with juxtamedullary nephron, meaning a nephron with a glomerulus located close to the cortical-medullary border.) Each JG apparatus is made up of 3 cell types: (1) granular cells, which are differentiated smooth muscle cells in the walls of the afferent arterioles; (2) extraglomerular mesangial cells; and (3) macula densa cells, which are specialized thick ascending limb epithelial cells (see Figure 7–4).

The granular cells are named because they contain secretory vesicles that appear granular in light micrographs. These granules contain the hormone renin (pronounced REE'-nin). As we will describe in Chapter 7, renin is a crucial substance for control of renal function and systemic blood pressure. The extraglomerular mesangial cells are morphologically similar to and continuous with the glomerular mesangial cells, but lie outside Bowman's capsule. The macula densa cells are detectors of the flow rate and composition of the fluid within the nephron at the very end of the thick ascending limb. These detector cells contribute to the control of glomerular filtration rate (GFR—see below) and to the control of renin secretion.

The working structures of the kidney are the nephrons and collecting tubules into which the nephrons drain. Figure 1–7 illustrates the meaning of several key words that we use to describe how the kidneys function. It is essential that any student of the kidney grasp their meaning.

Filtration is the process by which water and solutes in the blood leave the vascular system through the filtration barrier and enter Bowman's space (a space that is topologically outside the body). Secretion is the process of transporting substances into the tubular lumen from the cytosol of epithelial cells that form the walls of the nephron. Secreted substances may originate by synthesis within the epithelial cells or, more often, by crossing the epithelial layer from the surrounding renal interstitium. Reabsorption is the process of moving substances from the lumen across the epithelial layer into the surrounding interstitium.¹ In most cases, reabsorbed substances then move into surrounding blood vessels, so that the term reabsorption implies a 2-step process of removal from the tubular lumen followed by movement into the blood. Excretion means exit of the substance from the body (ie, the substance is present in the final urine produced by the kidneys). Synthesis means that a substance is constructed from molecular precursors, and catabolism means the substance is broken down into smaller component molecules. The renal handling of any substance consists of some combination of these processes.

Glomerular Filtration

Urine formation begins with glomerular filtration, the bulk flow of fluid from the glomerular capillaries into Bowman's capsule. The glomerular filtrate (ie, the fluid within Bowman's capsule) is very much like blood plasma, but contains very little total protein because the large plasma proteins like albumin and the globulins are virtually excluded from moving through the filtration barrier. Smaller proteins, such as many of the peptide hormones, are present in the filtrate, but their mass in total is miniscule compared with the mass of large plasma proteins in the blood. The filtrate contains most inorganic ions and low-molecular-weight organic solutes in virtually the same concentrations as in the plasma. Substances that are present in the filtrate at the same concentration as found in the plasma are said to be freely filtered. (Note that freely filtered does not mean all filtered. It just means that the amount filtered is in exact proportion to the fraction of plasma volume that is filtered.) Many low-molecular-weight components of blood are freely filtered. Among the most common substances included in the freely filtered category are the ions sodium, potassium, chloride, and bicarbonate; the uncharged organics glucose and urea; amino acids; and peptides such as insulin and antidiuretic hormone.

The volume of filtrate formed per unit time is known as the GFR. In a healthy young adult male, the GFR is an incredible 180 L/day (125 mL/min)! Contrast this value with the net filtration of fluid across all the other capillaries in the body: approximately 4 L/day. The implications of this huge GFR are extremely important. When we recall that the average total volume of plasma in humans is approximately 3 L, it follows that the entire plasma volume is filtered by the kidneys some 60 times a day. The opportunity to filter such huge volumes of plasma enables the kidneys to excrete large quantities of waste products and to regulate the constituents of the internal environment very precisely. One of the general consequences of healthy aging as well as many kidney diseases is a reduction in the GFR (see Chapter 3).

Tubular Reabsorption and Tubular Secretion

The volume and composition of the final urine are quite different from those of the glomerular filtrate. Clearly, almost all the filtered volume must be reabsorbed; otherwise, with a filtration rate of 180 L/day, we would urinate ourselves into dehydration very quickly. As the filtrate flows from Bowman's capsule through the various portions of the tubule, its composition is altered, mostly by removing material (tubular reabsorption) but also by adding material (tubular secretion). As described earlier, the tubule is, at all points, intimately associated with the vasculature, a relationship that permits rapid transfer of materials between the capillary plasma and the lumen of the tubule via the interstitial space.

Most of the tubular transport consists of reabsorption rather than tubular secretion. An idea of the magnitude and importance of tubular reabsorption can be gained from Table 1–2, which summarizes data for a few plasma components that undergo reabsorption. The values in Table 1–2 are typical for a healthy young adult on an average diet. There are at least 3 important generalizations to be drawn from this table:

1. Because of the huge GFR, the quantities filtered per day are enormous, generally larger than the amounts of the substances in the body. For example, the body of a 70-kg person contains about 42 L of water, but the volume of water filtered each day may be as large as 180 L.

2. Reabsorption of waste products, such as urea, is partial, so that large fractions of their filtered amounts are excreted in the urine.

3. Reabsorption of most “useful” plasma components (eg, water, electrolytes, and glucose) is either complete (eg, glucose), or nearly so (eg, water and most electrolytes), so that very little of the filtered amounts are excreted in the urine.

For each plasma substance, a particular combination of filtration, reabsorption, and secretion applies. The relative proportions of these processes then determine the amount excreted. A critical point is that the rates of these processes are subject to physiological control. By triggering changes in the rates of filtration, reabsorption, or secretion when the body content of a substance goes above or below normal, these mechanisms regulate excretion to keep the body in balance. For example, consider what happens when a person drinks a large quantity of water: Within 1 to 2 hours, all the excess water has been excreted in the urine, partly as the result of an increase in GFR but mainly as the result of decreased tubular reabsorption of water. The body is kept in balance for water by increasing excretion.

Metabolism by the Tubules

Although most sources list glomerular filtration, tubular reabsorption, and tubular secretion as the 3 basic renal processes, we cannot overlook metabolism by the tubular cells. The tubular cells extract organic nutrients from the glomerular filtrate or peritubular capillaries and metabolize them as dictated by the cells' own nutrient requirements. In so doing, the renal cells are behaving no differently than any other cells in the body. In addition, there are other metabolic transformations performed by the kidney that are directed toward altering the composition of the urine and plasma. The most important of these are gluconeogenesis, and the synthesis of ammonium from glutamine and the production of bicarbonate, both described in Chapter 9.

Regulation of Renal Function

The most complex and least understood feature of the kidneys is regulation of renal processes. Details, to the extent known, will be presented in later chapters. Neural signals, hormonal signals, and intrarenal chemical messengers combine to regulate the processes described above in a manner to help the kidneys meet the needs of the body. Neural signals originate in the sympathetic celiac plexus. These sympathetic neural signals exert major control over renal blood flow, glomerular filtration and the release of vasoactive substances that affect both the kidneys and the peripheral vasculature. Known hormonal signals originate in the adrenal gland, pituitary gland, parathyroid glands, and heart. The adrenal cortex secretes the steroid hormones aldosterone and cortisol, and the adrenal medulla secretes the catecholamines epinephrine and norepinephrine. All of these hormones, but mainly aldosterone, are regulators of sodium and potassium excretion by the kidneys. The posterior pituitary gland secretes the hormone arginine vasopressin (AVP, also called ADH). ADH is a major regulator of water and urea excretion, as well as a partial regulator of sodium excretion. The heart secretes hormones—natriuretic peptides—that increase sodium excretion by the kidneys. Another complicated aspect of regulation lies in the realm of intrarenal chemical messengers (ie, messengers that originate in one part of the kidney and act in another part). It is clear that an array of substances (eg, nitric oxide, purinergic agonists, superoxide, and eicosanoids) influence basic renal processes. The precise roles of these substances are just now being elucidated.

Two points about regulation should be kept in mind. First, excretion of major substances is regulated by overlapping, redundant controls. Failure of one may be compensated by the operation of another. Second, control systems adapt to chronic conditions and may change in effectiveness over time.

In ensuing chapters of this book we discuss specific mechanisms of reabsorption and secretion. When describing regulation of these mechanisms we are also implying regulation of excretion because any substance present in the tubule and not reabsorbed is destined to be excreted.

Overview of Regional Function

We conclude this chapter with a broad overview of the tasks performed by the individual nephron segments. Later, we examine renal function substance by substance and see how tasks performed in the various regions combine to produce an overall result that is useful for the body.

The glomerulus is the site of filtration—about 180 L/day of volume and proportional amounts of solutes that are freely filtered, which is the case for most solutes (large plasma proteins are an exception). The glomerulus is where the greatest mass of excreted substances enters the nephron. The proximal tubule (convoluted and straight portions together) reabsorbs about two thirds of the filtered water, sodium, and chloride. It reabsorbs all of the useful organic molecules that the body conserves (eg, glucose, amino acids). It reabsorbs significant fractions, but by no means all, of many important ions, such as potassium, phosphate, calcium, and bicarbonate. It is the site of secretion of a number of organic substances that are either metabolic waste products (eg, uric acid, creatinine) or drugs (eg, penicillin) that clinicians must administer appropriately to make up for renal excretion.

The loop of Henle contains different segments that perform different functions, but the key functions occur in the thick ascending limb. As a whole, the loop of Henle reabsorbs about 20% of the filtered sodium and chloride and 10% of the filtered water. A crucial consequence of these different proportions is that, by reabsorbing relatively more salt than water, the luminal fluid becomes diluted relative to normal plasma and the surrounding interstitium. During periods when the kidneys excrete dilute final urine, the role of the loop of Henle in diluting the luminal fluid is crucial.

The end of the loop of Henle contains cells of the macula densa, which sense the sodium and chloride content of the lumen and generate signals that influence other aspects of renal function, specifically the renin-angiotensin system (discussed in Chapter 7). The distal tubule and connecting tubule together reabsorb some additional salt and water, perhaps 5% of each. The cortical collecting duct is where several connecting tubules join to form a single tubule. Cells of the connecting tubule and cortical collecting duct are strongly responsive to and are regulated by the hormones angiotensin II and aldosterone, which enhance sodium reabsorption. ADH enhances water reabsorption in the collecting ducts. The degree to which these processes are stimulated or not stimulated plays a major role in regulating the amount of solutes and water present in the final urine.

The medullary collecting duct continues the functions of the cortical collecting duct in salt and water reabsorption. In addition, it plays a major role in the excretion of acids and bases, and the inner medullary collecting is important in regulating urea excretion. The final result of these various transport processes to keep the various plasma solutes close to the typical values is shown in Table 1–3.

• In addition to excreting waste, the kidneys perform many necessary functions in partnership with other body organ systems.

• The kidneys regulate the excretion of many substances at a rate that balances their input, thereby maintaining appropriate body content of those substances.

• A major function of the kidneys is to regulate the volume and osmolality of extracellular fluid volume.

• The kidneys are composed mainly of tubules and closely associated blood vessels.

• Each functional renal unit is composed of a filtering component (glomerulus) and a transporting tubular component (the nephron and collecting duct).

• The tubules are made up of multiple segments with distinct functions.

• Basic renal mechanisms consist of filtering a large volume, reabsorbing most of it, and adding substances by secretion, and, in some cases, synthesis.