Image summary: This is a photograph. The image depicts a medical professional wearing protective gear, including a gown, mask, and cap, attending to a patient who is lying in a hospital bed and also wearing a mask. The setting is a clinical environment equipped with various medical monitors and apparatus. The scene indicates that the patient is receiving critical care or specialized medical treatment, as evidenced by the presence of advanced monitoring equipment and the sterile precautions taken by the healthcare provider.

The Urinary System

The Urinary System and Homeostasis

The urinary system contributes to homeostasis by excreting wastes; altering blood composition, pH, volume, and pressure; maintaining blood osmolarity; and producing hormones.

As body cells carry out metabolic activities, they consume oxygen and nutrients and produce waste products such as carbon dioxide, urea, and uric acid. Wastes must be eliminated from the body because they can be toxic to cells if they accumulate. While the respiratory system rids the body of carbon dioxide, the urinary system disposes of most other wastes. The urinary system performs this function by removing wastes from the blood and excreting them into urine. Disposal of wastes through the release of urine is not the only purpose of the urinary system. The urinary system also helps regulate blood composition, pH, volume, and pressure; maintains blood osmolarity; and produces hormones.

26.1 Overview of the Urinary System

Objective

• Describe the major structures of the urinary system and the functions they perform.

Components of the Urinary System

The urinary system consists of two kidneys, two ureters, one urinary bladder, and one urethra (Figure 26.1). The kidneys filter blood of wastes and excrete them into a fluid called urine. Once formed, urine passes through the ureters and is stored in the urinary bladder until it is excreted from the body through the urethra. Nephrology nefroloje; nephr-= kidney; -ology = study of) is the scientific study of the anatomy, physiology, and pathology of the kidneys. The branch of medicine that deals with the male and female urinary systems and the male

Figure 26.1 Organs of the Urinary System in a Female.

reproductive system is called urology uroloje; uro-= urine). A physician who specializes in this branch of medicine is called a urologist urolojist.

Functions of the Kidneys

The kidneys do the major work of the urinary system. The other parts of the system are mainly passageways and storage areas. Functions of the kidneys include the following:

• Excretion of wastes. By forming urine, the kidneys help excrete wastes from the body. Some wastes excreted in urine result from metabolic reactions. These include urea and ammonia from the deamination of amino acids; creatinine from the breakdown of creatine phosphate; uric acid from the catabolism of nucleic acids; and urobilin from the breakdown of hemoglobin. Urea, ammonia, creatinine, uric acid, and urobilin are collectively known as nitrogenous wastes because they are waste products that contain nitrogen. Other wastes excreted in the urine are foreign substances that have entered the body, such as drugs and environmental toxins.

Urine formed by the kidneys passes first into the ureters, then to the urinary bladder for storage, and finally through the urethra for elimination from the body.

Functions of the Urinary System

1. Kidneys regulate blood volume and composition; help regulate blood pressure, pH, and glucose levels; produce two hormones (calcitriol and erythropoietin); and excrete wastes in urine.

2. Ureters transport urine from kidneys to urinary bladder.

3. Urinary bladder stores urine and expels it into urethra.

4. Urethra discharges urine from body.

• Regulation of blood ionic composition. The kidneys help regulate the blood levels of several ions, most importantly sodium ions (Na⁺), potassium ions (K⁺), calcium ions (Ca²⁺), chloride ions (Cl⁻), and phosphate ions (hydrogenphosphate). The kidneys accomplish this task by adjusting the amounts of these ions that are excreted into the urine.

• Regulation of blood pH. The kidneys excrete a variable amount of hydrogen ions (H⁺) into the urine and conserve bicarbonate ions (bicarbonate), which are an important buffer of H⁺ in the blood. Both of these activities help regulate blood pH.

• Regulation of blood volume. The kidneys adjust blood volume by conserving or eliminating water in the urine. An increase in blood volume increases blood pressure; a decrease in blood volume decreases blood pressure.

• Regulation of blood pressure. The kidneys also help regulate blood pressure by secreting the enzyme renin, which activates the renin-angiotensin-aldosterone pathway (see Figure 18.15). Increased renin causes an increase in blood pressure.

• Maintenance of blood osmolarity. By separately regulating loss of water and loss of solutes in the urine, the kidneys maintain a relatively constant blood osmolarity close to 300 milliosmoles per liter (mOsm/liter).

• Production of hormones. The kidneys produce two hormones. Calcitriol, the active form of vitamin D, helps regulate calcium homeostasis (see Figure 18.13), and erythropoietin stimulates the production of red blood cells (see Figure 19.5).

• Regulation of blood glucose level. Like the liver, the kidneys can use the amino acid glutamine in gluconeogenesis, the synthesis of new glucose molecules. They can then release glucose into the blood to help maintain a normal blood glucose level.

As is evident from the functions listed, urine contains more than just waste products. It also contains water and other substances, such as ions, that have important roles in the body, but are in excess of the body's needs. You will learn more about the composition of urine in Section 26.8.

Checkpoint

1. Explain the role of each organ of the urinary system.

2. What are examples of wastes that may be present in urine?

26.2 Anatomy of the Kidneys

• Describe the external and internal gross anatomical features of the kidneys.

• Trace the path of blood flow through the kidneys.

The paired kidneys are reddish, kidney bean-shaped organs located just above the waist between the peritoneum and the posterior wall of the abdomen. Because their position is posterior to the peritoneum of the abdominal cavity, the organs are said to be retroperitoneal (re'-tro-per-i-to-Ne-al; retro-= behind) (Figure 26.2). The kidneys are located between the levels of the last thoracic and third lumbar vertebrae, a position where they are partially protected by ribs 11 and 12. If these lower ribs are fractured, they can puncture the kidneys and cause significant, even life-threatening damage. The right kidney is slightly lower than the left (see Figure 26.1) because the liver occupies considerable space on the right side superior to the kidney.

External Anatomy of the Kidneys

A typical adult kidney is 10 to 12 centimeters (4 to 5 in.) long, 5 to 7 centimeters (2 to 3 in.) wide, and 3 centimeters (1 in.) thick—about the size of a bar of bath soap—and has a mass of 135 to 150 g (4.5 to 5 ounces). The concave medial border of each kidney faces the vertebral column (see Figure 26.1). Near the center of the concave border is an indentation called the hilum of the kidney (Hi-lum), through which the ureter emerges from the kidney along with blood vessels, lymphatic vessels, and nerves (see Figure 26.3a).

Three layers of tissue surround each kidney (Figure 26.2). The deep layer, the fibrous capsule, is a smooth, transparent sheet of collagen-rich connective tissue that is continuous with the outer coat of the ureter. It serves as a barrier against trauma and helps maintain the shape of the kidney. The middle layer, the perirenal fat capsule (per-i-RÊ-nal), is a mass of fatty tissue surrounding the fibrous capsule.

It also protects the kidney from trauma and holds it firmly in place within the abdominal cavity. The superficial layer, the renal fascia fashea, is a collagenous and elastic dense irregular connective tissue that anchors the kidney to the surrounding structures and to the abdominal wall. On the anterior surface of the kidneys, the renal fascia is deep to the peritoneum.

Internal Anatomy of the Kidneys

A coronal section through the kidney reveals two distinct regions: a superficial, light red region called the renal cortex (cortex = rind or bark) and a deep, darker reddish-brown inner region called the renal medulla (medulla = inner portion) (Figure 26.3). The renal medulla consists of several cone-shaped The kidneys are surrounded by a fibrous capsule, perirenal fat capsule, and renal fascia.

Figure 26.3 summary: This figure consists of an anatomical diagram and a corresponding photograph of a dissected right kidney. The images illustrate the internal and external anatomy of the kidney, labeling key structures such as the fibrous capsule, renal cortex, renal medulla, renal pyramids, and the renal pelvis. It further details the vascular system via the renal artery and vein, and the drainage system including the collecting ducts, calyces, and the ureter leading toward the urinary bladder. Based on the provided labels, it can be inferred that urine follows a specific sequential path of drainage starting from the nephrons in the cortex and medulla, moving through the papillary ducts and calyces into the renal pelvis, and finally exiting the kidney through the ureter. The structural organization shows a clear division between the outer cortical layer and the inner medullary region, which facilitates the filtration and transport of waste from the blood to the bladder.

Q Why are the kidneys said to be retroperitoneal? renal pyramids. The base (wider end) of each pyramid faces the renal cortex, and its apex (narrow end), called a renal papilla, points toward the renal hilum of the kidney. The renal cortex is the smooth-textured area extending from the fibrous capsule to the bases of the renal pyramids and into the spaces between them. It is divided into an outer cortical zone and an inner juxtamedullary zone jukstamedulare. Those portions of the renal cortex that extend between renal pyramids are called renal columns.

Together, the renal cortex and renal pyramids of the renal medulla constitute the parenchyma parenkima or functional portion of the kidney. Within the parenchyma are the functional units of the kidney—about 1 million microscopic structures in each kidney called nephrons. Filtrate (filtered

Figure 26.3 Internal Anatomy of the Kidneys.

The two main regions of the kidney are the superficial, light red region called the renal cortex and the deep, dark red region called the renal medulla. fluid) formed by the nephrons drains into large papillary ducts papilare, which extend through the renal papillae of the pyramids. The papillary ducts drain into cuplike structures called minor and major calyces (KÃ-li-seз = cups; singular is calyx, pronounced KÃ-liks). Each kidney has 8 to 18 minor calyces and 2 or 3 major calyces. A minor calyx receives filtrate from the papillary ducts of one renal papilla and delivers it to a major calyx.

Once the filtrate enters the calyces it becomes urine because no further reabsorption can occur. The reason for this is that the simple epithelium of the nephron and ducts becomes urothelium in the calyces. The urothelium blocks exchanges across the walls of these tubes.

From the major calyces, urine drains into a single large cavity called the renal pelvis (pelv-= basin) and then out through the ureter to the urinary bladder.

The hilum of the kidney expands into a cavity within the kidney called the renal sinus, which contains part of the renal pelvis, the calyces, and branches of the renal blood vessels

Figure 26.4 Blood Supply of the Kidneys.

and nerves. Adipose tissue helps stabilize the position of these structures in the renal sinus.

Blood and Nerve Supply of the Kidneys

Because the kidneys remove wastes from the blood and regulate its volume and ionic composition, it is not surprising that they are abundantly supplied with blood vessels. Although the kidneys constitute less than 0.5% of total body mass, they receive 20 to 25% of the resting cardiac output via the right and left renal arteries (Figure 26.4). In adults, renal blood flow, the blood flow through both kidneys, is about 1200 mL per minute.

Figure 26.4 summary: This figure consists of an anatomical diagram of the kidney and a corresponding flow chart. The anatomical illustration shows a coronal section of the right kidney, detailing the internal structures such as the fibrous capsule, renal cortex, and renal pyramids within the medulla, while highlighting the network of renal arteries and veins. The flow chart delineates the sequential path of blood as it moves through the renal vasculature. The content demonstrates that blood enters the kidney via the renal artery and branches into progressively smaller vessels, including segmental, interlobar, arcuate, and cortical radiate arteries, before reaching the glomerular capillaries via afferent arterioles. From there, blood exits through efferent arterioles into peritubular capillaries and venules, eventually converging into cortical radiate, arcuate, and interlobar veins before exiting through the renal vein. It can be inferred that the renal circulatory system is highly organized and hierarchical, ensuring that blood is filtered through the glomeruli and then collected through a systematic venous network to maintain efficient waste removal and fluid balance.

Within the kidney, the renal artery divides into several seg-mental arteries segmental, which supply different segments (areas) of the kidney. Each segmental artery gives off several branches that enter the parenchyma and pass through the renal columns between the renal lobes as the interlobar arteries (in'ter-LÖ-bar). A kidney lobe consists of a renal pyramid, some of the renal column on either side of the renal pyramid, and the renal cortex at the base of the renal pyramid (see Figure 26.3a). At the bases of the renal pyramids, the interlobar arteries arch between the renal medulla and cortex; here they are known as the arcuate arteries arkyuat = shaped like a bow). Divisions of the arcuate arteries produce a series of cortical radiate (interlobular) arteries kortikal RÄ-dே-at). These arteries radiate outward and enter the renal cortex. Here, they give off branches called afferent glomerular arterioles aferent; af-= toward; -ferrent = to carry).

Each nephron receives one afferent glomerular arteriole, which divides into a tangled, ball-shaped capillary network called the glomerulus glomerulus = little ball; plural is glomeruli). The glomerular capillaries then reunite to form an efferent glomerular arteriole eferent; ef-= out) that carries blood out of the glomerulus. Glomerular capillaries are unique among capillaries in the body because they are positioned between two arterioles, rather than between an arteriole and a venule. Because they are capillary networks and they also play an important role in urine formation, the glomeruli are considered part of both the cardiovascular and the urinary systems.

The efferent glomerular arterioles divide to form the per- itubular capillaries peritubular; peri-= around), which surround tubular parts of the nephron in the renal cortex. Extending from some efferent glomerular arterioles are long, loop-shaped capillaries called vasa recta (VÅ-sa rekta; vasa = vessels; recta = straight) that supply tubular portions of the nephron in the renal medulla (see Figure 26.4a).

The peritubular capillaries eventually reunite to form cortical radiate (interlobular) veins, which also receive blood from the vasa recta. Then the blood drains through the arcuate veins to the interlobar veins running between the renal pyramids. Blood leaves the kidney through a single renal vein that exits at the renal hilum and carries venous blood to the inferior vena cava.

Many renal nerves originate in the renal ganglion and pass through the renal plexus into the kidneys along with the renal arteries. Renal nerves are part of the sympathetic part of the autonomic nervous system. Most are vasomotor nerves that regulate the flow of blood through the kidney by causing vasodilation or vasoconstriction of renal arterioles.

26.3 The Nephron

• Describe the parts of a nephron.

• Explain the histology of a nephron and collecting duct.

Parts of a Nephron

Nephrons nefrons are the functional units of the kidneys. Each nephron consists of two parts: a renal corpuscle korpusel = tiny body), where blood plasma is filtered, and a renal tubule into which the filtered fluid (glomerular filtrate) passes and is further regulated (Figure 26.5). Closely associated with a nephron is its blood supply, which was just described. The two components of a renal corpuscle are the glomerulus (capillary network) and the glomerular capsule or Bowman's capsule, a double-walled epithelial cup that surrounds the glomerular capillaries.

Figure 26.5 summary: This figure is a schematic diagram. It illustrates the structural components of the kidney's filtration membrane, detailing the arrangement of fenestrated glomerular endothelial cells, the slit membrane, and the pedicels of podocytes. The diagram shows how these layers create filtration slits that allow substances to pass from the blood into the urinary space. Based on the structural organization, it can be inferred that the filtration membrane acts as a multi-layered selective barrier, where the combined physical gaps of the endothelial fenestrations and the podocyte slits regulate the passage of fluids and solutes.

Blood plasma is filtered in the glomerular capsule, and then the filtered fluid passes into the renal tubule, which has three main sections. In the order that fluid passes through them, the renal tubule consists of a (1) proximal convoluted tubule (P.C.T) convoluted, (2) nephron loop (loop of Henle), and (3) distal convoluted tubule (D.C.T). Proximal denotes the part of the tubule attached to the glomerular capsule, and distal denotes the part that is further away. Convoluted means the tubule is tightly coiled rather than straight.

The renal corpuscle and both convoluted tubules lie within the renal cortex; the nephron loop extends into the renal medulla, makes a hairpin turn, and then returns to the renal cortex.

The distal convoluted tubules of several nephrons empty into a single collecting duct C.D. Collecting ducts then unite and converge into several hundred large papillary ducts, which drain into the minor calyces. The collecting ducts and papillary ducts extend from the renal cortex through the renal medulla and enter a minor calyx. So one kidney has about 1 million nephrons, but a much smaller number of collecting ducts and even fewer papillary ducts.

In a nephron, the nephron loop connects the proximal and distal convoluted tubules. The first part of the nephron loop begins at the point where the proximal convoluted tubule takes its final turn downward. It begins in the renal cortex and extends downward into the renal medulla, where it is called the descending limb of the nephron loop (Figure 26.5). It then makes that hairpin turn and returns to the renal cortex where it terminates at the distal convoluted tubule and is known as the ascending limb of the nephron loop. About 80 to 85% of the nephrons are cortical nephrons kortikul. Their renal corpuscles lie in the outer portion of the renal cortex, and they have short nephron loops that lie mainly in the renal cortex and penetrate only into the Figure 26.5 The structure of nephrons and associated blood vessels. Note that the collecting duct and papillary duct are not part of a nephron.

Nephrons are the functional units of the kidneys. outer region of the renal medulla (Figure 26.5b). The short nephron loops receive their blood supply from peritubular capillaries that arise from efferent glomerular arterioles. The other 15 to 20% of the nephrons are juxtamedullary nephrons jukstamedulare; juxta-= next to). Their renal corpuscles lie deep in the renal cortex, close to the renal medulla, and they have a long nephron loop that extends into the deepest region of the renal medulla (Figure 26.5c). Long nephron loops receive their blood supply from peritubular capillaries and from the vasa recta that arise from efferent glomerular arteriole. In addition, the ascending limb of the nephron loop of juxtamedullary nephrons consists of two portions: a thin ascending limb followed by a thick ascending limb (Figure 26.5c). The lumen of the thin ascending limb is the same as in other areas of the renal tubule; it is only the epithelium that is thinner. Nephrons with long nephron loops enable the kidneys to excrete very dilute or very concentrated urine (described in Section 26.7).

Histology of the Nephron and Collecting Duct

A single layer of epithelial cells forms the entire wall of the glomerular capsule, renal tubule, and ducts (Figure 26.6). However, each part has distinctive histological features that reflect its particular functions. We will discuss them in the order that fluid flows through them: glomerular capsule, renal tubule, and collecting duct.

Figure 26.6 summary: This figure is a collection of anatomical diagrams and micrographs. The content illustrates the structure and vascular supply of a juxtamedullary nephron, including a detailed view of the renal corpuscle, the flow of fluid through the nephron, and the spatial relationship between the renal cortex and medulla. The figure highlights key components such as the glomerulus, glomerular capsule, proximal and distal convoluted tubules, the loop of Henle, and the associated blood vessels including afferent and efferent arterioles. From the provided imagery, it can be inferred that the juxtamedullary nephron is characterized by a long loop of Henle that extends deep into the renal medulla, which is essential for concentrating urine. The detailed views of the renal corpuscle demonstrate a complex filtration barrier consisting of the glomerular endothelium, podocytes, and the capsular space, facilitating the movement of fluid from the blood into the nephron.

Glomerular Capsule The glomerular capsule consists of visceral and parietal layers (Figure 26.6a). The visceral layer consists of modified simple squamous epithelial cells called podocytes (PÖD-ö-sits; podo-= foot; -cytes = cells). The many footlike projections of these cells (pedicels) wrap around the single layer of endothelial cells of the glomerular capillaries and form the inner wall of the capsule. The parietal layer of the

Figure 26.5 Continued

glomerular capsule consists of simple squamous epithelium and forms the outer wall of the capsule. Fluid filtered from the glomerular capillaries enters the capsular space, the space between the two layers of the glomerular capsule, which is continuous with the lumen of the renal tubule. Think of the relationship between the glomerulus and glomerular capsule in the following way: the glomerulus is a fist punched into a limp balloon (the glomerular capsule) until the fist is covered by two layers of balloon (the layer of the balloon touching the fist is the visceral layer and the layer not against the fist is the parietal layer) with a space in between (the inside of the balloon), the capsular space.

Renal Tubule and Collecting Duct Table 26.1 illustrates the histology of the cells that form the renal tubule and collecting duct. In the proximal convoluted tubule, the cells are simple cuboidal epithelial cells with a prominent microvillous-border on their apical surface (surface facing the lumen). These microvilli, like those of the small intestine, increase the surface area for reabsorption and secretion. The descending limb of the nephron loop and the first part of the ascending limb of the nephron loop (the thin ascending limb) are composed of simple squamous epithelium. (Recall that cortical or short-loop nephrons lack the thin ascending limb.) The thick ascending limb of the nephron loop is composed of simple cuboidal to low columnar epithelium.

Table 26.1 summary: This table outlines the histological characteristics of various segments of the renal tubule and collecting duct. It highlights the transition in epithelial cell types across different regions, ranging from simple squamous cells in the thin limbs of the nephron loop to simple cuboidal or low columnar cells in the proximal and distal convoluted tubules and the thick ascending limb. Additionally, it notes specialized features such as the microvillous border in the proximal convoluted tubule and the presence of both principal and intercalated cells within the collecting duct and the final portion of the distal convoluted tubule.

In each nephron, the final part of the ascending limb of the nephron loop makes contact with the afferent glomerular arteriole serving that renal corpuscle (Figure 26.6b). Because the columnar tubule cells in this region are crowded together, they are known as the macula densa makula densa; macula = spot; densa = dense). Alongside the macula densa, the wall of the afferent glomerular arteriole (and sometimes the efferent glomerular arteriole) contains modified smooth muscle fibers called juxtaglomerular cells J.G jukstaglomerular; juxta = next to). Together with the macula densa, they constitute the juxtaglomerular apparatus (J.G.A). As you will see later, the J.G.A helps regulate blood pressure within the kidneys. The distal convoluted tubule (D.C.T) begins a short distance past the macula densa. In the last part of the D.C.T and continuing into the collecting ducts, two different types of cells are present. Most are principal cells, which have receptors for both antidiuretic hormone (A.D.H) and aldosterone, two hormones that regulate their functions. A smaller number are intercalated cells interkalated, which play a role in the homeostasis of blood pH. The collecting ducts drain into large papillary ducts, which are lined by simple columnar epithelium.

The number of nephrons is constant from birth. Any increase in kidney size is due solely to the growth of individual

Figure 26.6 Histology of a Renal Corpuscle.

nephrons. If nephrons are injured or become diseased, new ones do not form. Signs of kidney dysfunction usually do not become apparent until function declines to less than 25% of normal because the remaining functional nephrons adapt to handle a larger-than-normal load. Surgical removal of one kidney, for example, stimulates hypertrophy (enlargement) of the remaining kidney, which eventually is able to filter blood at 80% of the rate of two normal kidneys.

Checkpoint

8. What are the two main parts of a nephron?

9. What are the components of the renal tubule?

10. Where is the juxtaglomerular apparatus located, and what is its structure?

26.4 Overview of Renal Physiology

Objective

• Identify the three basic functions performed by nephrons and collecting ducts, and indicate where each occurs.

To produce urine, nephrons and collecting ducts perform three basic processes—glomerular filtration, tubular reabsorption, and tubular secretion (Figure 26.7):

Figure 26.7 summary: This is a schematic diagram illustrating the process of urine formation within the renal system. The figure depicts the anatomy of the renal corpuscle and the renal tubule, highlighting the flow of fluids between the peritubular capillaries and the tubular lumen. It details three primary physiological processes: glomerular filtration, where plasma and small solutes enter the glomerular capsule; tubular reabsorption, where essential water and ions move from the tubule back into the blood; and tubular secretion, where wastes and drugs are moved from the blood into the tubule. The diagram demonstrates that the final urine consists of filtered substances that were not reabsorbed and substances that were actively secreted, while the bloodstream retains reabsorbed materials.

Figure 26.7 Relationship of a nephron's structure to its three basic functions: glomerular filtration, tubular reabsorption, and tubular secretion. Excreted substances remain in the urine and subsequently leave the body.

Glomerular filtration occurs in the renal corpuscle. Tubular reabsorption and tubular secretion occur all along the renal tubule and collecting duct. ① Glomerular filtration. In the first step of urine production, water and most solutes in blood plasma move across the wall of glomerular capillaries, where they are filtered and move into the glomerular capsule and then into the renal tubule. ② Tubular reabsorption. As filtered fluid flows through the renal tubules and through the collecting ducts, renal tubule cells reabsorb about 99% of the filtered water and many useful solutes. The water and solutes return to the blood as it flows through the peritubular capillaries and vasa recta. Note that the term reabsorption refers to the return of substances to the bloodstream. The term absorption, by contrast, means entry of new substances into the body, as occurs in the digestive canal.

3 Tubular secretion. As filtered fluid flows through the renal tubules and collecting ducts, the renal tubule and duct cells secrete other materials, such as wastes, drugs, and excess ions, into the fluid. Notice that tubular secretion removes a substance from the blood.

Solutes and the fluid that drain into the minor and major calyces and renal pelvis constitute urine and are excreted. The rate of urinary excretion of any solute is equal to its rate of glomerular filtration, plus its rate of secretion, minus its rate of reabsorption.

By filtering, reabsorbing, and secreting, nephrons help maintain homeostasis of the blood's volume and composition. The situation is somewhat analogous to a recycling center: Garbage trucks dump garbage into an input hopper, where the smaller garbage passes onto a conveyor belt (glomerular filtration of blood plasma). As the conveyor belt carries the garbage along, workers remove useful items, such as aluminum cans, plastics, and glass containers (reabsorption).

Other workers place additional garbage left at the center and larger items onto the conveyor belt (secretion). At the end of the belt, all remaining garbage falls into a truck for transport to the landfill (excretion of wastes in urine).

11. How do tubular reabsorption and tubular secretion differ?

26.5 Glomerular Filtration

Objectives

• Describe the filtration membrane.

• Discuss the pressures that promote and oppose glomerular filtration.

The fluid that enters the capsular space is called the glomerular filtrate. The fraction of blood plasma in the afferent glomerular arterioles of the kidneys that becomes glomerular filtrate is the filtration fraction. Although a filtration fraction of 0.16 to 0.20 (16 to 20%) is typical, the value varies considerably in both health and disease. On average, the daily volume of glomerular filtrate in adults is 150 liters in females and 180 liters in males. More than 99% of the glomerular filtrate returns to the bloodstream via tubular reabsorption, so only 1 to 2 liters (about 1–2qt) is excreted as urine.

The Filtration Membrane

Together, the glomerular capillaries and the podocytes, which completely encircle the capillaries, form a leaky barrier known as the filtration (endothelial-capsular) membrane. This sandwichlike assembly permits filtration of water and small solutes but prevents filtration of most blood plasma proteins and blood cells. Substances filtered from the blood cross three filtration barriers—a glomerular endothelial cell, the basement membrane, and a filtration slit formed by a podocyte (Figure 26.8):

Figure 26.8 summary: This figure is a detailed anatomical diagram. It illustrates the filtration barrier of the renal corpuscle, focusing on the structural layers that blood must pass through to enter the glomerular capsule. The diagram identifies three primary layers: the fenestrations of the glomerular endothelial cells, the glomerular basement membrane, and the slit membranes located between the pedicels of the podocytes. Based on the content, it can be inferred that the filtration process occurs through a series of selective barriers that act as sieves. The endothelial pores prevent the passage of blood cells, the basement membrane blocks larger proteins, and the slit membranes prevent the filtration of medium-sized proteins, ensuring that only small solutes and plasma components are filtered into the capsule.

Glomerular endothelial cells are quite leaky because they have large fenestrations fenestrations (pores) that measure 0.07 to 0.1 mu m in diameter. This size permits all solutes in blood plasma to exit glomerular capillaries but prevents filtration of blood cells. Located among the glomerular capillaries and in the cleft between afferent and efferent glomerular arterioles are mesangial cells mesanjeal; mes-= in the middle; -angi-= blood vessel) (see Figure 26.6a). These contractile cells help regulate glomerular filtration. ② The basement membrane, a porous layer of acellular material between the endothelium and the podocytes, consists of minute collagen fibers and negatively charged glycoproteins. The pores within the basement membrane allow water and most small solutes to pass through. However, the negative charges of the glycoproteins repel blood plasma proteins, most of which are anionic; the repulsion hinders filtration of these proteins.

Extending from each podocyte are thousands of footlike processes termed pedicels pedisels = little feet) that wrap around glomerular capillaries. The spaces between pedicels are the filtration slits. A thin membrane, the slit membrane, extends across each filtration slit; it permits the passage of molecules having a diameter smaller than 0.006 to 0.007 mu m, including water, glucose, vitamins, amino acids, very small blood plasma proteins, ammonia, urea, and ions. Less than 1% of albumin, the most plentiful plasma protein, passes the slit membrane because, with a diameter of 0.007 mu m, it is slightly too big to get through.

Figure 26.8 The filtration membrane. The size of the endothelial fenestrations and filtration slits has been exaggerated for emphasis.

During glomerular filtration, water and solutes pass from blood plasma into the capsular space.

Fenestration (pore) of glomerular endothelial cell: prevents filtration of blood cells but allows all components of blood plasma to pass through 2 Basement membrane of glomerulus: prevents filtration of larger proteins 3 Slit membrane between pedicels: _ _ prevents filtration of medium-sized proteins Q Which part of the filtration membrane prevents red blood cells from entering the capsular space?

The principle of filtration—the use of pressure to force fluids and solutes through a membrane—is the same in glomerular capillaries as in blood capillaries elsewhere in the body (see Starling's law of the capillaries, Section 21.2). However, the volume of fluid filtered by the renal corpuscle is much larger than in other blood capillaries of the body for three reasons:

1. Glomerular capillaries present a large surface area for filtration because they are long and extensive. Mesangial cells regulate how much surface area is available. When mesangial cells are relaxed, surface area is maximal, and glomerular filtration is very high. Contraction of mesangial cells reduces the available surface area, and glomerular filtration decreases.

2. The filtration membrane is thin and porous. Despite having several layers, the thickness of the filtration membrane is only 0.1 millimeters. Glomerular capillaries also are about 50 times leakier than blood capillaries in most other tissues, mainly because of their large fenestrations.

3. Glomerular capillary blood pressure is high. Because the efferent glomerular arteriole is smaller in diameter than the afferent glomerular arteriole, resistance to the outflow

of blood from the glomerulus is high. As a result, blood pressure in glomerular capillaries is considerably higher than in blood capillaries elsewhere in the body.

Net Filtration Pressure

Glomerular filtration depends on three main pressures. One pressure promotes filtration and two pressures oppose filtration (Figure 26.9):

Figure 26.9 summary: This figure is a scanning electron micrograph. It displays a detailed view of a podocyte as it wraps around and covers the structure of a glomerulus. The image reveals the intricate, interlocking foot processes of the podocyte that create a complex network over the glomerular surface. This structural arrangement indicates that podocytes form a specialized filtration barrier, ensuring that only specific substances pass from the blood into the capsular space during renal filtration.

- ① Glomerular blood hydrostatic pressure (G.B.H.P) is the blood pressure in glomerular capillaries. Generally, G.B.H.P is about 55 mmHg. It promotes filtration by forcing water and solutes in blood plasma through the filtration membrane.

- ② Capsular hydrostatic pressure (C.H.P) is the hydrostatic pressure exerted against the filtration membrane by fluid already in the capsular space and renal tubule. C.H.P opposes filtration and represents a “back pressure” of about 15 mmHg.

- ③ Blood colloid osmotic pressure (B.C.O.P), which is due to the presence of proteins such as albumin, globulins, and fibrinogen in blood plasma, also opposes filtration. The average B.C.O.P in glomerular capillaries is 30 mmHg.

Net filtration pressure (N.F.P), the total pressure that promotes filtration, is determined as follows:

Net filtration pressure (N.F.P) = G.B.H.P - C.H.P - B.C.O.P By substituting the values just given, normal N.F.P may be calculated:

N.F.P = 55 mmHg - 15 mmHg - 30 mmHg = 10 mmHg Thus, a pressure of only 10 mmHg causes a normal amount of blood plasma (minus plasma proteins) to filter from the glomerulus into the capsular space.

Clinical Connection

Loss of Blood Plasma Proteins in Urine Causes Edema

In some kidney diseases, glomerular capillaries are damaged and become so permeable that blood plasma proteins enter glomerular filtrate. As a result, the filtrate exerts a colloid osmotic pressure that draws water out of the blood. In this situation, the N.F.P increases, which means more fluid is filtered. At the same time, blood colloid osmotic pressure decreases because blood plasma proteins are being lost in the urine.

Because more fluid filters out of blood capillaries into tissues throughout the body than returns via reabsorption, blood volume decreases and interstitial fluid volume increases. Thus, loss of blood plasma proteins in urine causes edema, an abnormally high volume of interstitial fluid.

Figure 26.9 The pressures that drive glomerular filtration. Taken together, these pressures determine net filtration pressure (N.F.P).

Glomerular blood hydrostatic pressure promotes filtration, whereas capsular hydrostatic pressure and blood colloid osmotic pressure oppose filtration.

Glomerular Filtration Rate

The amount of filtrate formed in all renal corpuscles of both kidneys each minute is the glomerular filtration rate (G.F.R). In adults, the G.F.R averages 125 milliliters per minute in males and 105 milliliters per minute in females. Homeostasis of body fluids requires that the kidneys maintain a relatively constant G.F.R. If the G.F.R is too high, needed substances may pass so quickly through the renal tubules that some are not reabsorbed and are lost in the urine. If the G.F.R is too low, nearly all the filtrate may be reabsorbed and certain waste products may not be adequately excreted.

G.F.R is directly related to the pressures that determine net filtration pressure; any change in net filtration pressure will affect G.F.R. Severe blood loss, for example, reduces mean arterial blood pressure and decreases the glomerular blood hydrostatic pressure. Filtration ceases if glomerular blood hydrostatic pressure drops to 45 mmHg because the opposing pressures add up to 45 mmHg. Amazingly, when systemic blood pressure rises above normal, net filtration pressure and G.F.R increase very little. G.F.R is nearly constant when the mean arterial blood pressure is anywhere between 80 and 180 mmHg.

The mechanisms that regulate glomerular filtration rate operate in two main ways: (1) by adjusting blood flow into and out of the glomerulus and (2) by altering the glomerular capillary surface area available for filtration. G.F.R increases when blood flow into the glomerular capillaries increases. Coordinated control of the diameter of both afferent and efferent glomerular arterioles regulates glomerular blood flow. Constriction of the afferent arteriole decreases blood flow into the glomerulus; dilation of the afferent glomerular arteriole increases it. Three mechanisms control G.F.R: renal autoregulation, neural regulation, and hormonal regulation.

Renal Autoregulation of G.F.R The kidneys themselves help maintain a constant renal blood flow and G.F.R despite normal, everyday changes in blood pressure, like those that occur during exercise. This capability is called renal autoregulation (aw'-tô-reg'-ü-LÃ-shun) and consists of two mechanisms—the myogenic mechanism and tubulo-glomerular feedback. Working together, they can maintain nearly constant G.F.R over a wide range of systemic blood pressures.

The myogenic mechanism myojenik; myo-= muscle; -genic = producing) occurs when stretching triggers contraction of smooth muscle fibers in the walls of afferent glomerular arterioles. As blood pressure rises, G.F.R also rises because renal blood flow increases. However, the elevated blood pressure stretches the walls of the afferent glomerular arterioles. In response, smooth muscle fibers in the wall of the afferent glomerular arteriole contract, which narrows the arteriole's lumen. As a result, renal blood flow decreases, thus reducing G.F.R to its previous level. Conversely, when arterial blood pressure drops, the smooth muscle fibers are stretched less and thus relax. The afferent glomerular arterioles dilate, renal blood flow increases, and G.F.R increases. The myogenic mechanism normalizes renal blood flow and G.F.R within seconds after a change in blood pressure.

The second contributor to renal autoregulation, tubuloglomerular feedback tubuloglomerular, is so named because part of the renal tubules—the macula densa—provides feedback to the glomerulus (Figure 26.10). When G.F.R is above normal due to elevated systemic blood pressure, filtered fluid flows more rapidly along the renal tubules. As a result, the proximal convoluted tubule and nephron loop have less time to reabsorb Na⁺, Cl⁻, and water. Macula densa cells are thought to detect the increased delivery of Na⁺, Cl⁻, and water and to inhibit release of nitric oxide (no) from cells in the juxtaglomerular apparatus.

Figure 26.10 summary: This figure is a flow chart illustrating a biological feedback loop. It depicts the negative feedback mechanism by which macula densa cells of the juxtaglomerular apparatus regulate the glomerular filtration rate. The process begins with a stimulus that increases the glomerular filtration rate, which is the controlled condition. This change is detected by receptors in the macula densa cells, which sense an increased delivery of sodium, chloride, and water. The juxtaglomerular apparatus acts as the control center, resulting in a decreased secretion of nitric oxide. This output affects the afferent glomerular arteriole, causing it to constrict and reduce blood flow through the glomerulus. The final response is a decrease in the glomerular filtration rate, which returns the system to homeostasis.

Because no causes vasodilation, afferent glomerular arterioles constrict when the level of no declines. As a result, less blood flows into the glomerular capillaries, and G.F.R decreases. When blood pressure falls, causing G.F.R to be lower than normal, the opposite sequence of events occurs, although to a lesser degree. Tubuloglomerular feedback operates more slowly than the myogenic mechanism.

Neural Regulation of G.F.R Like most blood vessels of the body, those of the kidneys are supplied by sympathetic A.N.S fibers that release norepinephrine. Norepinephrine causes vasoconstriction through the activation of alpha 1 receptors, which are particularly plentiful in the smooth muscle fibers of afferent glomerular arterioles. At rest, sympathetic stimulation is moderately low, the afferent and efferent glomerular arterioles are dilated, and renal autoregulation of G.F.R prevails. With moderate sympathetic stimulation, both afferent and efferent glomerular arterioles constrict to the same degree.

Blood flow into and out of the glomerulus is restricted to the same extent, which decreases G.F.R only slightly. With greater sympathetic stimulation, however, as occurs during exercise or hemorrhage, vasoconstriction of the afferent glomerular arterioles predominates. As a result, blood flow into glomerular capillaries is greatly decreased, and G.F.R drops. This lowering of renal blood flow has two consequences: (1) It reduces urine output, which helps conserve blood volume. (2) It permits greater blood flow to other body tissues.

Hormonal Regulation of G.F.R Two hormones contribute to regulation of G.F.R. Angiotensin 2 reduces G.F.R; atrial natriuretic peptide (A.N.P) increases G.F.R. Angiotensin 2 angiotensin is a very potent vasoconstrictor that narrows both afferent and efferent glomerular arterioles and reduces renal blood flow, thereby decreasing G.F.R. Cells in the atria of the heart secrete atrial natriuretic peptide (A.N.P) natriuretik. Stretching of the atria, as occurs when blood volume increases, stimulates secretion of A.N.P. By causing relaxation of the glomerular mesangial cells, A.N.P increases the capillary surface area available for filtration. Glomerular filtration rate rises as the surface area increases.

Table 26.2 summarizes the regulation of glomerular filtration rate.

Table 26.2 summary: This table outlines the various regulatory mechanisms that influence the glomerular filtration rate. Most mechanisms, including renal autoregulation via myogenic and tubuloglomerular feedback, neural stimulation, and the action of angiotensin II, result in a decrease in filtration rate through the constriction of glomerular arterioles. In contrast, atrial natriuretic peptide increases the filtration rate by expanding the available capillary surface area.

Checkpoint

12. If the urinary excretion rate of a drug such as penicillin is greater than the rate at which it is filtered at the glomerulus, how else is it getting into the urine?

13. What is the major chemical difference between blood plasma and glomerular filtrate?

14. Why is there much greater filtration through glomerular capillaries than through capillaries elsewhere in the body?

15. Write the equation for the calculation of net filtration pressure, and explain the meaning of each term.

16. How is glomerular filtration rate regulated?

26.6 Tubular Reabsorption and Tubular Secretion

Objectives

• Outline the routes and mechanisms of tubular reabsorption and secretion.

- Describe how specific segments of the renal tubule and collecting duct reabsorb water and solutes.

• Explain how specific segments of the renal tubule and collecting duct secrete solutes into the urine.

Principles of Tubular Reabsorption and Secretion

The volume of fluid entering the proximal convoluted tubules in just half an hour is greater than the total blood plasma volume because the normal rate of glomerular filtration is so high. Obviously some of this fluid must be returned somehow to the bloodstream. Reabsorption—the return of most of the filtered water and many of the filtered solutes to the bloodstream—is the second basic function of the nephron and collecting duct. Normally, about 99% of the filtered water is reabsorbed. Epithelial cells all along the renal tubule and duct carry out reabsorption, but proximal convoluted tubule cells make the largest contribution.

Solutes that are reabsorbed by both active and passive processes include glucose, amino acids, urea, and ions such as Na⁺ (sodium), K⁺ (potassium), Ca²⁺ (calcium), Cl⁻ (chloride), bicarbonate (bicarbonate), and hydrogenphosphate (phosphate). Once fluid passes through the proximal convoluted tubule, cells located more distally fine-tune the reabsorption processes to maintain homeostatic balances of water and selected ions. Most small proteins and peptides that pass through the filter also are reabsorbed, usually via pinocytosis. To appreciate the magnitude of tubular reabsorption, look at Table 26.3 and compare the amounts of substances that are filtered, reabsorbed, and secreted in urine.

Table 26.3 summary: The table illustrates the daily processing of various substances in the kidneys, showing that the vast majority of filtered water, electrolytes, and nutrients are reabsorbed back into the blood. Glucose is completely reabsorbed, while creatinine is not reabsorbed at all, remaining entirely in the urine. Most other substances, including proteins and various ions, experience high rates of reabsorption with only a small fraction being secreted as urine.

The third function of nephrons and collecting ducts is tubular secretion, the transfer of materials from the blood and tubule cells into glomerular filtrate. Secreted substances include hydrogen ions (H⁺), K⁺, ammonium ions ammonium, creatinine, and certain drugs such as penicillin. Tubular secretion has two important outcomes: (1) The secretion of H⁺ helps control blood pH. (2) The secretion of other substances helps eliminate them from the body in urine.

As a result of tubular secretion, certain substances pass from blood into urine and may be detected by a urinalysis (see Section 26.8). It is especially important to test athletes for the presence of performance-enhancing drugs such as anabolic steroids, plasma expanders, erythropoietin, hCG, G.H, and amphetamines. Urine tests can also be used to detect the presence of alcohol or illegal drugs such as marijuana, cocaine, and heroin.

Reabsorption Routes A substance being reabsorbed from the fluid in the tubule lumen can take one of two routes before entering a peritubular capillary: It can move between adjacent tubule cells or through an individual tubule cell (Figure 26.11). Along the renal tubule, tight junctions surround and join neighboring cells to one another, much like the plastic rings that hold a six-pack of soda cans together. The apical membrane (the tops of the soda cans) contacts the tubular fluid, and the basolateral membrane (the bottoms and sides of the soda cans) contacts interstitial fluid at the base and sides of the cell.

Figure 26.11 summary: This is a schematic diagram illustrating biological transport processes. The figure depicts the movement of sodium ions from the fluid within a tubule lumen, through a tubule cell and interstitial fluid, and into a peritubular capillary. It highlights two distinct pathways: paracellular reabsorption, where ions move between cells via diffusion, and transcellular reabsorption, which involves movement through the cell. The transcellular process utilizes active transport at the apical membrane and a sodium-potassium pump at the basolateral membrane powered by ATP. The diagram demonstrates that sodium is reabsorbed from the tubule back into the bloodstream through both passive diffusion and energy-dependent active transport mechanisms, with tight junctions serving as barriers that direct the flow of ions.

Fluid can leak between the cells in a passive process known as paracellular reabsorption paracellular; para-=beside). Even though the epithelial cells are connected by tight junctions, the tight junctions between cells in the proximal convoluted tubules are "leaky" and permit some reabsorbed substances to pass between cells into peritubular capillaries. In some parts of the renal tubule, the paracellular route is thought to account for up to 50% of the reabsorption of certain ions and the water that accompanies them via osmosis. In transcellular reabsorption transcellular; trans-= across), a substance passes from the fluid in the tubular lumen through the apical membrane of a tubule cell, across the cytosol, and out into interstitial fluid through the basolateral membrane.

Figure 26.11 Reabsorption Routes: Paracellular Reabsorption and Transcellular Reabsorption.

In paracellular reabsorption, water and solutes in tubular fluid return to the bloodstream by moving between tubule cells; in transcellular reabsorption, solutes and water in tubular fluid return to the bloodstream by passing through a tubule cell.

Transport Mechanisms When renal cells transport solutes out of or into tubular fluid, they move specific substances in one direction only. Not surprisingly, different types of transport proteins are present in the apical and basolateral membranes. The tight junctions form a barrier that prevents mixing of proteins in the apical and basolateral membrane compartments. Reabsorption of Na superscript plus by the renal tubules is especially important because of the large number of sodium ions that pass through the glomerular filters.

Cells lining the renal tubules, like other cells throughout the body, have a low concentration of Na⁺ in their cytosol due to the activity of sodium-potassium pumps (Na⁺-K⁺ atpases. These pumps are located in the basolateral membranes and eject Na⁺ from the renal tubule cells (Figure 26.11). The absence of sodium-potassium pumps in the apical membrane ensures that reabsorption of Na⁺ is a one-way process. Most sodium ions that cross the apical membrane will be pumped into interstitial fluid at the base and sides of the cell. The amount of A.T.P used by sodium-potassium pumps in the renal tubules is about 6% of the total A.T.P consumption of the body at rest. This may not sound like much, but it is about the same amount of energy used by the diaphragm as it contracts during quiet breathing.

As we noted in Chapter 3, transport of materials across membranes may be either active or passive. Recall that in primary active transport the energy derived from hydrolysis of A.T.P is used to "pump" a substance across a membrane; the sodium-potassium pump is one such pump. In secondary active transport the energy stored in an ion's electrochemical gradient, rather than hydrolysis of A.T.P, drives another substance across a membrane. Secondary active transport couples movement of an ion down its electrochemical gradient to the "uphill" movement of a second substance against its electrochemical gradient. Symporters are membrane proteins that move two or more substances in the same direction across a membrane. Antiporters move two or more substances in opposite directions across a membrane. Each type of transporter has an upper limit on how fast it can work, just as an escalator has a limit on how many people it can carry from one level to another in a given period. This limit, called the transport maximum ( T m ), is measured in mg/min.

Solute reabsorption drives water reabsorption because all water reabsorption occurs via osmosis. About 80% of the reabsorption of water filtered by the kidneys occurs along with the reabsorption of solutes such as Na superscript plus , Cl superscript minus , and glucose. Water reabsorbed with solutes in tubular fluid is termed obligatory water reabsorption because the water is “obliged” to follow the solutes when they are reabsorbed.

This type of water reabsorption occurs in the proximal tubule and the descending limb of the nephron loop because these segments of the nephron are always permeable to water. Reabsorption of the final 20% of the water is termed facultative water reabsorption. The word facultative means “capable of adapting to a need.” Facultative water reabsorption is regulated by antidiuretic hormone and occurs in the late distal tubule and throughout the collecting duct.

Glucosuria

When the blood concentration of glucose is above 200 milligrams/mL, the renal symporters cannot work fast enough to reabsorb all the glucose that enters the glomerular filtrate. As a result, some glucose remains in the urine, a condition called glucosuria glucosurea. The most common cause of glucosuria is diabetes mellitus, in which the blood glucose level may rise far above normal because insulin activity is deficient. Excessive glucose in the glomerular filtrate inhibits water reabsorption by kidney tubules. This leads to increased urinary output (polyuria), decreased blood volume, and dehydration.

Now that we have discussed the principles of renal transport, we will follow the filtered fluid from the proximal convoluted tubule, into the nephron loop, on to the distal convoluted tubule, and through the collecting ducts. In each segment, we will examine where and how specific substances are reabsorbed and secreted. The filtered fluid becomes tubular fluid once it enters the proximal convoluted tubule.

The composition of tubular fluid changes as it flows along the nephron tubule and through the collecting duct due to reabsorption and secretion. The fluid that drains from papillary ducts into the renal pelvis is urine.

Reabsorption and Secretion in the Proximal Convoluted Tubule

The largest amount of solute and water reabsorption from filtered fluid occurs in the proximal convoluted tubules, which reabsorb 65% of the filtered water, Na⁺, K⁺, and Ca²⁺; 100% of most filtered organic solutes such as glucose and amino acids; 50% of the filtered Cl⁻; 80% of the filtered bicarbonate; 50% of the filtered urea; and a variable amount of the filtered Mg²⁺ and hydrogenphosphate (phosphate). In addition, proximal convoluted tubules secrete a variable amount of H⁺, ammonium ions ammonium, and urea.

Most solute reabsorption in the proximal convoluted tubule (P.C.T) involves Na⁺. Na⁺ transport occurs via symport and antiport mechanisms in the proximal convoluted tubule. Normally, filtered glucose, amino acids, lactic acid, water-soluble vitamins, and other nutrients are not lost in the urine. Rather, they are completely reabsorbed in the first half of the proximal convoluted tubule by several types of Na⁺ symporters located in the apical membrane.

Figure 26.12 depicts the operation of one such symporter, the Na⁺-glucose symporter in the apical membrane of a cell in the P.C.T. Two Na⁺ and a molecule of glucose attach to the symporter protein, which carries them from the tubular fluid into the tubule cell. The glucose molecules then exit the basolateral membrane via facilitated diffusion and they diffuse into peritubular capillaries. Other Na⁺ symporters in the P.C.T reclaim filtered hydrogenphosphate (phosphate) and sulfate (sulfate) ions, all amino acids, and lactic acid in a similar way.

Figure 26.12 summary: This figure is a biological diagram illustrating the cellular mechanisms of glucose reabsorption in the kidney. The diagram depicts a proximal convoluted tubule cell situated between the tubule lumen and a peritubular capillary, highlighting the movement of sodium and glucose across the cell membranes. On the luminal side, a sodium-glucose symporter facilitates the entry of glucose and sodium into the cell. Within the cell, a sodium-potassium pump uses energy to move sodium out toward the interstitial fluid. Finally, glucose exits the cell into the capillary via a facilitated diffusion transporter. The process demonstrates that glucose is reabsorbed from the filtrate back into the bloodstream through a combination of active transport and facilitated diffusion, driven by the sodium gradient maintained by the sodium-potassium pump.

In another secondary active transport process, the sodium plus hydrogen plus antiporters carry filtered sodium plus down its concentration gradient Figure 26.12 Reabsorption of glucose by Na ^{+} -glucose symporters in cells of the proximal convoluted tubule (P.C.T).

Normally, all filtered glucose is reabsorbed in the P.C.T. into a P.C.T cell as H⁺ is moved from the cytosol into the lumen (Figure 26.13a), causing Na⁺ to be reabsorbed into blood and H⁺ to be secreted into tubular fluid. P.C.T cells produce the H⁺ needed to keep the antiporters running in the following: way: Carbon dioxide (C-O₂) diffuses from peritubular blood or tubular fluid or is produced by metabolic reactions within the cells. As also occurs in red blood cells (see Figure 23.24), the enzyme carbonic anhydrase C.A (an-H⁺-drãs) catalyzes the reaction of C-O₂ with water (H₂O) to form carbonic acid (H₂C-O₃), which then dissociates into H⁺ and bicarbonate.

Figure 26.13 summary: This figure is a set of schematic diagrams and chemical equations. The content illustrates the cellular mechanisms for sodium reabsorption and hydrogen ion secretion, as well as the process of bicarbonate reabsorption within a proximal convoluted tubule cell, showing the movement of ions and molecules between the tubule lumen, the cell, the interstitial fluid, and the peritubular capillary. The diagrams detail the roles of the sodium-hydrogen antiporter, the sodium-potassium pump, and facilitated diffusion transporters, while highlighting the catalytic role of carbonic anhydrase in the conversion between carbon dioxide, water, and bicarbonate. It can be inferred that the reabsorption of bicarbonate is an indirect process involving the secretion of hydrogen ions into the lumen and the subsequent transport of bicarbonate into the blood. Furthermore, the process is energy-dependent, as evidenced by the requirement of ATP for the sodium-potassium pump to maintain the ionic gradients necessary for these transport mechanisms.

Figure 26.13 Actions of Na ^{+} -H ^{+} Antiporters in Proximal

convoluted tubule cells. (a) Reabsorption of sodium ions (Na⁺) and secretion of hydrogen ions (H⁺) via secondary active transport through the apical membrane. (b) Reabsorption of bicarbonate ions (bicarbonate) via facilitated diffusion through the basolateral membrane. C-O₂ = carbon dioxide; H₂C-O₃ = carbonic acid; C.A = carbonic anhydrase.

Na⁺–H⁺ antiporters promote transcellular reabsorption of Na⁺ and secretion of H⁺.

Which step in Na⁺ movement in part (a) is promoted by the electrochemical gradient?

Most of the bicarbonate in filtered fluid is reabsorbed in proximal convoluted tubules, thereby safeguarding the body's supply of an important buffer (Figure 26.13b). After H⁺ is secreted into the fluid within the lumen of the proximal convoluted tubule, it reacts with filtered bicarbonate to form H₂C-O₃, which readily dissociates into C-O₂ and H₂O. Carbon dioxide then diffuses into the tubule cells and joins with H₂O to form H₂C-O₃, which dissociates into H⁺ and bicarbonate. As the level of bicarbonate rises in the cytosol, it exits via facilitated diffusion transporters in the basolateral membrane and diffuses into the blood with Na⁺. Thus, for every H⁺ secreted into the tubular fluid of the proximal convoluted tubule, one bicarbonate and one Na⁺ are reabsorbed.

Solute reabsorption in proximal convoluted tubules promotes osmosis of water. Each reabsorbed solute increases the osmolarity, first inside the tubule cell, then in interstitial fluid, and finally in the blood. Water thus moves rapidly from the tubular fluid, via both the paracellular and transcellular routes, into the peritubular capillaries and restores osmotic balance (Figure 26.14). In other words, reabsorption of the solutes creates an osmotic gradient that promotes the reabsorption of water via osmosis. Cells lining the proximal convoluted tubule and the descending limb of the nephron loop are especially permeable to water because they have many molecules of aquaporin-1 (ak-kwa-PÖR-in). This integral protein in the plasma membrane is a water channel that greatly increases the rate of water movement across the apical and basolateral membranes.

Figure 26.14 summary: This is a schematic diagram. The figure illustrates the movement of solutes and water from the fluid in the tubule lumen, through the proximal convoluted tubule cell, and into the peritubular capillary. It depicts the paracellular and transcellular pathways for various substances, including chloride, potassium, calcium, magnesium, urea, and water. The diagram shows that solutes move via diffusion while water moves via osmosis. It can be inferred that the proximal convoluted tubule allows for the passive reabsorption of various ions and waste products, as well as water, moving from the tubule lumen back into the bloodstream.

As water leaves the tubular fluid, the concentrations of the remaining filtered solutes increase. In the second half of the P.C.T, electrochemical gradients for Cl⁻, K⁺, Ca²⁺, Mg²⁺, and urea promote their passive diffusion into peritubular capillaries via both paracellular and transcellular routes. Among these ions, Figure 26.14 Passive reabsorption of Cl⁻, K⁺, Ca²⁺, Mg²⁺, urea, and water in the second half of the proximal convoluted tubule.

chloride is present in the highest concentration. Diffusion of negatively charged Cl⁻ into interstitial fluid via the paracellular route makes the interstitial fluid electrically more negative than the tubular fluid. This negativity promotes passive paracellular reabsorption of cations, such as K⁺, Ca²⁺, and Mg²⁺.

Ammonia nitrogen hydrogen 3) is a poisonous waste product derived from the deamination (removal of an amino group) of various amino acids, a reaction that occurs mainly in hepatocytes (liver cells). Hepatocytes convert most of this ammonia to urea, a less toxic compound. Although tiny amounts of urea and ammonia are present in sweat, most excretion of these nitrogen-containing waste products occurs via the urine. Urea and ammonia in blood are both filtered at the glomerulus and secreted by proximal convoluted tubule cells into the tubular fluid.

Proximal convoluted tubule cells can produce additional ammonia by deaminating the amino acid glutamine in a reaction that also generates bicarbonate. The ammonia quickly binds hydrogen ion to become an ammonium ion, which can substitute for hydrogen ion aboard sodium hydrogen antiporters in the apical membrane and be secreted into the tubular fluid. The bicarbonate generated in this reaction moves through the basolateral membrane and then diffuses into the bloodstream, providing additional buffers in blood plasma.

Reabsorption in the Nephron Loop

Because all of the proximal convoluted tubules reabsorb about 65% of the filtered water (about 80 milliliters per minute), fluid enters the next part of the nephron, the nephron loop, at a rate of 40 to 45 milliliters per minute. The chemical composition of the tubular fluid now is quite different from that of glomerular filtrate because glucose, amino acids, and other nutrients are no longer present. The osmolarity of the tubular fluid is still close to the osmolarity of blood, however, because reabsorption of water by osmosis keeps pace with reabsorption of solutes all along the proximal convoluted tubule.

The nephron loop reabsorbs about 15% of the filtered water, 25% of the filtered Na⁺, K⁺, and Ca²⁺, 35% of the filtered Cl⁻, 10% of the filtered bicarbonate, and a variable amount of the filtered Mg²⁺. Here, for the first time, reabsorption of water via osmosis is not automatically coupled to reabsorption of filtered solutes because part of the nephron loop is relatively impermeable to water. The nephron loop thus sets the stage for independent regulation of both the volume and osmolarity of body fluids.

The apical membranes of cells in the thick ascending limb of the nephron loop have sodium plus potassium plus two chloride symporters that simultaneously reclaim one sodium, one potassium, and two chloride from the fluid in the tubular lumen (Figure 26.15). Sodium that is actively transported into interstitial fluid at the base and sides of the cell diffuses into the vasa recta. Chloride moves through leakage channels in the basolateral membrane into interstitial fluid and then into the vasa recta. Because many potassium leakage channels are present in the apical membrane, most potassium brought in by the symporters moves down its concentration gradient back into the tubular fluid. Thus, the main effect of the sodium plus potassium plus two chloride symporters is reabsorption of sodium and chloride.

Figure 26.15 summary: This figure is a biological diagram illustrating cellular transport mechanisms within the kidney. The diagram depicts the movement of ions between the fluid in the tubule lumen, the cells of the thick ascending limb, and the vasa recta. It highlights the role of the sodium-potassium-two chloride symporter on the apical membrane, the sodium-potassium pump on the basolateral membrane, and various leakage channels. The process shows sodium, potassium, and chloride ions moving from the lumen into the cell and subsequently into the interstitial fluid and vasa recta, while other cations like calcium and magnesium also move toward the interstitial space. It can be inferred that the thick ascending limb utilizes secondary active transport to reabsorb salts, driven by the primary active transport of the sodium-potassium pump. Because the apical membrane is impermeable to water, the reabsorption of these ions creates an interstitial fluid that is more negatively charged and hypertonic compared to the fluid remaining in the tubule lumen, effectively separating solute reabsorption from water reabsorption in this segment of the nephron.

sodium ion with a charge of plus one The movement of positively charged K⁺ into the tubular fluid through the apical membrane channels leaves the interstitial fluid and blood with more negative charges relative to fluid in the ascending limb of the nephron loop. This relative negativity promotes reabsorption of cations—Na⁺, K⁺, Ca²⁺, and Mg²⁺—via the paracellular route.

Although about 15% of the filtered water is reabsorbed in the descending limb of the nephron loop, little or no water is reabsorbed in the ascending limb. In this segment of the tubule, the apical membranes are virtually impermeable to water. Because ions but not water molecules are reabsorbed, the osmolarity of the tubular fluid decreases progressively as fluid flows toward the end of the ascending limb.

Reabsorption in the Early Distal Convoluted Tubule

Fluid enters the distal convoluted tubules at a rate of about 25 milliliters per minute because 80% of the filtered water has now been reabsorbed. The early or initial part of the distal convoluted tubule (D.C.T) reabsorbs 5% of the filtered Na⁺ and 5% of the filtered Cl⁻. Reabsorption of Na⁺ and Cl⁻ occurs by means of Na⁺-Cl⁻ symporters in the apical membranes. Sodium-potassium pumps and Cl⁻ leakage channels in the basolateral membranes then permit reabsorption of Na⁺ and Cl⁻ into the peritubular capillaries. The early D.C.T also is a major site where parathyroid hormone P.T.H stimulates reabsorption of Ca²⁺. The amount of Ca²⁺ reabsorption in the early D.C.T varies depending on the body's needs.

Reabsorption and Secretion in the Late Distal Convoluted Tubule and Collecting Duct

By the time fluid reaches the end of the distal convoluted tubule, 90 to 95% of the filtered solutes and water have returned to the bloodstream. Recall that two different types of cells—principal cells and intercalated cells—are present at the late or terminal part of the distal convoluted tubule and throughout the collecting duct. The principal cells reabsorb Na⁺ and secrete K⁺. These cells also have receptors for aldosterone and antidiuretic hormone (A.D.H). The intercalated cells reabsorb bicarbonate and secrete H⁺, thereby playing a role in blood pH regulation. In addition, the intercalated cells reabsorb K⁺. In the late distal convoluted tubules and collecting ducts, the amount of water and solute reabsorption and the amount of solute secretion vary depending on the body's needs.

In contrast to earlier segments of the nephron, sodium ion passes through the apical membrane of principal cells via sodium ion leakage channels rather than by means of symporters or antiporters (Figure 26.16). The concentration of sodium ion in the cytosol remains low, as usual, because the sodium-potassium pumps actively transport sodium ion across the basolateral membranes. Then sodium ion passively diffuses into the peritubular capillaries from the interstitial spaces around the tubule cells.

Normally, transcellular and paracellular reabsorption in the proximal convoluted tubule and nephron loop return most filtered potassium ion to the bloodstream. To adjust for varying dietary intake of potassium and to maintain a stable level of potassium ion in body fluids, principal cells secrete a variable amount of potassium ion (Figure 26.16). Because the basolateral sodium-potassium pumps continually bring potassium ion into principal cells, the intracellular concentration of potassium ion remains high. Potassium ion leakage channels are present in both the apical and basolateral membranes. Thus, some potassium ion diffuses down its concentration gradient into the tubular fluid, where the potassium ion concentration is very low. This secretion mechanism is the main source of potassium ion excreted in the urine.

Figure 26.16 Reabsorption of Na⁺ and Secretion of K⁺ by Principal Cells in the Last Part of the Distal Convoluted Tubule and in the Collecting Duct.

In the apical membrane of principal cells, sodium plus leakage channels allow entry of sodium plus while potassium plus leakage channels allow exit of potassium plus into the tubular fluid.

Key:

- ☐ Diffusion

- Leakage channels

- Sodium-potassium pump

Which hormone stimulates reabsorption and secretion by principal cells, and how does this hormone exert its effect?

Homeostatic Regulation of Tubular Reabsorption and Tubular Secretion

Five hormones affect the extent of Na⁺, Ca²⁺, and water reabsorption as well as K⁺ secretion by the renal tubules. These hormones include angiotensin two, aldosterone, antidiuretic hormone, atrial natriuretic peptide, and parathyroid hormone.

Renin-Angiotensin-Aldosterone System

Cross-insin-Aldosterone System When blood volume and blood pressure decrease, the walls of the afferent arterioles are stretched less, and the juxtaglomerular cells secrete the enzyme renin (RÊ-nin) into the blood. Sympathetic stimulation also directly stimulates release of renin from juxtaglomerular cells. Renin clips off a 10-amino acid peptide called angiotensin I angiotensin from angiotensinogen, which is synthesized by hepatocytes (see Figure 18.16). By clipping off two more amino acids, angiotensin-converting enzyme ace converts angiotensin I to angiotensin two, which is the active form of the hormone.

Angiotensin 2 affects renal physiology in three main ways:

1. It decreases the glomerular filtration rate by causing vasoconstriction of the afferent glomerular arterioles.

2. It enhances reabsorption of Na⁺ and water in the proximal convoluted tubule by stimulating the activity of Na⁺–H⁺ antiporters.

3. It stimulates the adrenal cortex to release aldosterone aldosterone, a hormone that in turn stimulates the principal cells in the collecting ducts to reabsorb more Na⁺ and secrete more K⁺. The osmotic consequence of reabsorbing more Na⁺ is that more water is reabsorbed, which causes an increase in blood volume and blood pressure.

Antidiuretic Hormone Antidiuretic Hormone (A.D.H)

or vasopressin is released by the posterior pituitary. It regulates facultative water reabsorption by increasing the water permeability of principal cells in the last part of the distal convoluted tubule and throughout the collecting duct. In the absence of A.D.H, the apical membranes of principal cells have a very low permeability to water. Within principal cells are tiny vesicles containing many copies of a water channel protein known as aquaporin-2.* A.D.H stimulates insertion of the aquaporin-2-containing vesicles into the apical membranes via exocytosis.

As a result, the water permeability of the principal cell's apical membrane increases, and water molecules move more rapidly from the tubular fluid into the cells. Because the basolateral membranes are always relatively permeable to water, water molecules then move rapidly into the blood. This results in an increase in blood volume and blood pressure.

When the A.D.H level declines, the aquaporin-2 channels are removed from the apical membrane via endocytosis, and water permeability of the principal cells decreases.

A negative feedback system involving A.D.H regulates facultative water reabsorption (Figure 26.17). When the osmolarity or osmotic pressure of plasma and interstitial fluid increases—that is, when water concentration decreases—by as little as 1%, osmoreceptors in the hypothalamus detect the change. Their nerve impulses stimulate secretion of more A.D.H into the blood, and the principal cells become more permeable to water. As facultative water reabsorption increases, plasma osmolarity decreases to normal. A second powerful stimulus for A.D.H secretion is a decrease in blood volume, as occurs in hemorrhaging or severe dehydration. In the pathological absence of A.D.H activity, a condition known as diabetes insipidus, a person may excrete up to 20 liters of very dilute urine daily.

Figure 26.17 summary: This figure is a flowchart illustrating a biological feedback loop. It depicts the negative feedback mechanism that regulates facultative water reabsorption through the action of antidiuretic hormone. The process begins with a stimulus that increases the osmolarity of blood plasma and interstitial fluid, which is detected by osmoreceptors in the hypothalamus. These receptors send nerve impulses to the control center, consisting of the hypothalamus and posterior pituitary, triggering the release of antidiuretic hormone. This hormone acts on the principal cells of the kidneys, which serve as effectors, making them more permeable to water and increasing facultative water absorption. The resulting response is a decrease in blood plasma osmolarity, which completes the negative feedback loop by returning the system to homeostasis.

The degree of facultative water reabsorption caused by A.D.H in the late distal tubule and collecting duct depends on whether the body is normally hydrated, dehydrated, or overhydrated.

A.D.H does not govern the previously mentioned water channel (aquaporin-1).

• Normal hydration. Under conditions of normal body hydration (adequate water intake), enough A.D.H is present in the blood to cause reabsorption of 19% of the filtered water in the late distal tubule and the collecting duct. This means that the total amount of filtered water reabsorbed in the renal tubule and collecting duct is 99%: 65% in the proximal tubule + 15% in the nephron loop + 19% in the late distal tubule and collecting duct. The remaining 1% of the filtered water (about 1.5 to 2 L/day) is excreted in urine. Therefore, when the body is normally hydrated, the kidneys produce about 1.5 to 2 L of urine on a daily basis and the urine is slightly hyperosmotic (slightly concentrated) compared to blood.

• Dehydration. When the body is dehydrated, the concentration of A.D.H in the blood increases. This in turn causes an increase in the amount of filtered water that is reabsorbed in the late distal tubule and collecting duct. Depending on how much the blood A.D.H level increases, the amount of filtered water that is reabsorbed in the late distal tubule and collecting duct can increase from just above 19% to as high as 19.8%. As a result, less than 1% of filtered water remains unreabsorbed in the late distal tubule and collecting duct, which corresponds to a urine output below the normal 1.5 to 2 L/day. The urine produced under these circumstances is very hyperosmotic (highly concentrated) compared to blood because it contains less water than normal.

In the case of severe dehydration, the amount of filtered water that is reabsorbed in the late distal tubule and collecting duct reaches a maximum limit of 19.8%. This means that the total amount of filtered water reabsorbed in the renal tubule and collecting duct is 99.8%: 65% in the proximal tubule + 15% in the nephron loop + 19.8% in the late distal tubule and collecting duct. The remaining 0.2% of the filtered water (about 400 mL/day) is excreted in urine. Thus, the kidneys produce a small volume of highly concentrated urine when the body is dehydrated.

• Overhydration. When the body is overhydrated (too much water intake), the concentration of A.D.H in the blood decreases. This in turn causes a decrease in the amount of filtered water that is reabsorbed in the late distal tubule and collecting duct. Depending on how much the blood A.D.H level decreases, the amount of filtered water that is reabsorbed in the late distal tubule and collecting duct can decrease from just below 19% to as low as 0%. As a result, more than 1% of filtered water remains unreabsorbed in the late distal tubule and collecting duct, which corresponds to a urine output above the normal 1.5 to 2 L/day. The urine produced under these conditions is hypoosmotic (dilute) compared to blood because it contains more water than normal.

In the case of severe overhydration, no A.D.H is present in the blood, and the amount of water reabsorbed in the late distal tubule and collecting duct is 0%. This means that the total amount of filtered water that is reabsorbed in the renal tubule and collecting duct is 80%: 65% in the proximal tubule + 15% in the nephron loop + 0% in the late distal tubule and collecting duct. The remaining 20% of filtered water (about 36 L/day) is excreted in urine. Hence, the kidneys produce a large volume of dilute urine when the body is overhydrated.

Atrial Natriuretic Peptide A large increase in blood volume promotes release of atrial natriuretic peptide (A.N.P) from the heart. Although the importance of A.N.P in normal regulation of tubular function is unclear, it can inhibit reabsorption of Na superscript plus and water in the proximal convoluted tubule and collecting duct. A.N.P also suppresses the secretion of aldosterone and A.D.H. These effects increase the excretion of Na superscript plus in urine (natriuresis) and increase urine output (diuresis), which decreases blood volume and blood pressure.

Parathyroid Hormone Although the hormones mentioned thus far involve regulation of water loss as urine, the kidney tubules also respond to a hormone that regulates ionic composition. For example, a lower than normal level of Ca superscript 2 plus in the blood stimulates the parathyroid glands to release parathyroid hormone P.T.H. P.T.H in turn stimulates cells in the early distal convoluted tubules to reabsorb more Ca superscript 2 plus into the blood. P.T.H also inhibits H.P.O 4 superscript 2 minus (phosphate) reabsorption in proximal convoluted tubules, thereby promoting phosphate excretion.

Table 26.4 summarizes hormonal regulation of tubular reabsorption and tubular secretion.

Table 26.4 summary: This table outlines how various hormones regulate renal tubular reabsorption and secretion. Angiotensin II, aldosterone, and antidiuretic hormone generally act to increase the reabsorption of water and sodium to raise blood volume and pressure or lower fluid osmolarity. In contrast, atrial natriuretic peptide opposes these effects by promoting the excretion of sodium and water to reduce blood volume and pressure. Additionally, parathyroid hormone specifically increases the reabsorption of calcium in response to low plasma levels.

Checkpoint

17. Diagram the reabsorption of substances via the transcellular and paracellular routes. Label the apical membrane and the basolateral membrane. Where are the sodium-potassium pumps located?

18. Describe two mechanisms in the P.C.T, one in the nephron loop, one in the D.C.T, and one in the collecting duct for reabsorption of Na⁺. What other solutes are reabsorbed or secreted with Na⁺ in each mechanism?

19. How do intercalated cells secrete hydrogen ions?

20. Graph the percentages of filtered water and filtered Na⁺ that are reabsorbed in the P.C.T, nephron loop, D.C.T, and collecting duct. Indicate which hormones, if any, regulate reabsorption in each segment.

26.7 Production of Dilute and Concentrated Urine

Objective

- Describe how the renal tubule and collecting ducts produce dilute and concentrated urine.

Even though your fluid intake can be highly variable, the total volume of fluid in your body normally remains stable. Homeostasis of body fluid volume depends in large part on the ability of the kidneys to regulate the rate of water loss in urine. Normally functioning kidneys produce a large volume of dilute urine when fluid intake is high, and a small volume of concentrated urine when fluid intake is low or fluid loss is large. A.D.H controls whether dilute urine or concentrated urine is formed. In the absence of A.D.H, urine is very dilute. However, a high level of A.D.H stimulates reabsorption of more water into blood, producing a concentrated urine.

Formation of Dilute Urine

Glomerular filtrate has the same ratio of water and solute particles as blood; its osmolarity is about 300 mOsm/liter. As previously noted, fluid leaving the proximal convoluted tubule is still isotonic to plasma. When dilute urine is being formed (Figure 26.18), the osmolarity of the fluid in the tubular lumen increases as it flows down the descending limb of the nephron loop, decreases as it flows up the ascending limb, and decreases still more as it flows through the rest of the nephron loop.

Figure 26.18 summary: This figure is a biological diagram illustrating the structure of a nephron and the associated collecting duct. The diagram labels the various components of the renal system, including the glomerulus, glomerular capsule, proximal convoluted tubule, nephron loop, distal convoluted tubule, and the collecting duct, while indicating the relative solute concentrations of the fluid within these structures and the surrounding interstitial fluid in the renal cortex and medulla. Based on the concentration gradients shown, it can be inferred that the ascending limb of the nephron loop and the distal convoluted tubule are the primary regions where solutes are reabsorbed more extensively than water, leading to the production of dilute urine as the fluid moves toward the papillary duct.

Figure 26.18 Formation of dilute urine. Numbers indicate osmolarity in milliosmoles per liter (mOsm/liter). Heavy brown lines in the ascending limb of the nephron loop and in the distal convoluted tubule indicate impermeability to water; heavy blue lines indicate the last part of the distal convoluted tubule and the collecting duct, which are impermeable to water in the absence of A.D.H; light blue areas around the nephron represent interstitial fluid. and collecting duct. These changes in osmolarity result from the following conditions along the path of tubular fluid:

1. Because the osmolarity of the interstitial fluid of the renal medulla becomes progressively greater, more and more water is reabsorbed by osmosis as tubular fluid flows along the descending limb toward the tip of the nephron loop. (The source of this medullary osmotic gradient is explained shortly.) As a result, the fluid remaining in the lumen becomes progressively more concentrated.

2. Cells lining the thick ascending limb of the loop have symporters that actively reabsorb Na⁺, K⁺, and Cl⁻ from the tubular fluid (see Figure 26.15). The ions pass from the tubular fluid into thick ascending limb cells, then into interstitial fluid, and finally some diffuse into the blood inside the vasa recta.

3. Although solutes are being reabsorbed in the thick ascending limb, the water permeability of this portion of the nephron is always quite low, so water cannot follow by osmosis. As solutes—but not water molecules—are leaving the tubular fluid, its osmolarity drops to about 150 mOsm/liter. The fluid entering the distal convoluted tubule is thus more dilute than plasma.

4. While the fluid continues flowing along the distal convoluted tubule, additional solutes but only a few water molecules are reabsorbed. The early distal convoluted tubule cells are not very permeable to water and are not regulated by A.D.H.

5. Finally, the principal cells of the late distal convoluted tubules and collecting ducts are impermeable to water when the A.D.H level is very low. Thus, tubular fluid becomes progressively more dilute as it flows onward. By the time the tubular fluid drains into the renal pelvis, its concentration can be as low as 65 to 70 mOsm/liter. This is four times more dilute than blood plasma or glomerular filtrate.

Formation of Concentrated Urine

When water intake is low or water loss is high (such as during heavy sweating), the kidneys must conserve water while still eliminating wastes and excess ions. Under the influence of A.D.H, the kidneys produce a small volume of highly concentrated urine. Urine can be four times more concentrated (up to 1200 mOsm/liter) than blood plasma or glomerular filtrate (300 mOsm/liter).

The ability of A.D.H to cause excretion of concentrated urine depends on the presence of an osmotic gradient of solutes in the interstitial fluid of the renal medulla. Notice in Figure 26.19 that the solute concentration of the interstitial fluid in the kidney increases from about 300 mOsm/liter in the renal cortex to about 1200 mOsm/liter deep in the renal medulla. The three major solutes that contribute to this high osmolarity are Na⁺, Cl⁻, and urea.

Two main factors contribute to building and maintaining this osmotic gradient: (1) differences in solute and water permeability and reabsorption in different sections of the long nephron loops and the collecting ducts, and (2) the countercurrent flow of fluid through tube-shaped structures in the renal medulla. Countercurrent flow refers to the flow of fluid in opposite directions. This occurs when fluid flowing in one tube runs counter (opposite) to fluid flowing in a nearby parallel tube.

Examples of countercurrent flow include the flow of tubular fluid through the descending and ascending limbs of the nephron loop and the flow of blood through the ascending and descending parts of the vasa recta. Two types of countercurrent mechanisms exist in the kidneys: countercurrent multiplication and countercurrent exchange.

Countercurrent Multiplication Countercurrent multiplication is the process by which a progressively increasing osmotic gradient is formed in the interstitial fluid of the renal medulla as a result of countercurrent flow. Countercurrent multiplication involves the long nephron loops of juxtamedullary nephrons. Note in Figure 26.19a that the descending limb of the nephron loop carries tubular fluid from the renal cortex deep

Figure 26.19 Mechanism of Urine Concentration in Long-Loop Juxtamedullary Nephrons. The

green line indicates the presence of sodium potassium chloride symporters that simultaneously reabsorb these ions into the interstitial fluid of the renal medulla; this portion of the nephron is also relatively impermeable to water and urea. All concentrations are in miliosmoles per liter (mOsm/liter).

The formation of concentrated urine depends on high concentrations of solutes in interstitial fluid in the renal medulla. into the medulla, and the ascending limb carries it in the opposite direction. Since countercurrent flow through the descending and ascending limbs of the long nephron loop establishes the osmotic gradient in the renal medulla, the long nephron loop is said to function as a countercurrent multiplier. The kidneys use this osmotic gradient to excrete concentrated urine.

Production of concentrated urine by the kidneys occurs in the following way (Figure 26.19):

1 Symporters in thick ascending limb cells of the nephron loop cause a buildup of sodium ion and chloride ion in the renal medulla.

In the thick ascending limb of the nephron loop, the sodium potassium chloride symporters reabsorb Na⁺ and Cl⁻ from the tubular fluid (Figure 26.19a). Water is not reabsorbed in this segment, however, because the cells are impermeable to water. As a result, there is a buildup of Na⁺ and Cl⁻ ions in the interstitial fluid of the renal medulla.

- ② Countercurrent flow through the descending and ascending limbs of the nephron loop establishes an osmotic gradient in the renal medulla. Since tubular fluid constantly moves from the descending limb to the thick ascending limb

of the nephron loop, the thick ascending limb is constantly reabsorbing Na⁺ and Cl⁻. Consequently, the reabsorbed Na⁺ and Cl⁻ become increasingly concentrated in the interstitial fluid of the renal medulla, which results in the formation of an osmotic gradient that ranges from 300 mOsm/liter in the outer medulla to 1200 mOsm/liter deep in the inner medulla. The descending limb of the nephron loop is very permeable to water but impermeable to solutes except urea. Because the osmolarity of the interstitial fluid outside the descending limb is higher than the tubular fluid within it, water moves out of the descending limb via osmosis.

This causes the osmolarity of the tubular fluid to increase. As the fluid continues along the descending limb, its osmolarity increases even more: At the hairpin turn of the loop, the osmolarity can be as high as 1200 mOsm/liter in juxtamedullary nephrons. As you have already learned, the ascending limb of the loop is impermeable to water, but its symporters reabsorb Na⁺ and Cl⁻ from the tubular fluid into the interstitial fluid of the renal medulla, so the osmolarity of the tubular fluid progressively decreases as it flows through the ascending limb. At the junction of the medulla and cortex, the osmolarity of the tubular fluid has fallen to about 100 mOsm/liter. Overall, tubular fluid becomes progressively more concentrated as it flows along the descending limb and progressively more dilute as it moves along the ascending limb.

3 Cells in the collecting ducts reabsorb more water and urea. When A.D.H increases the water permeability of the principal cells, water quickly moves via osmosis out of the collecting duct tubular fluid, into the interstitial fluid of the inner medulla, and then into the vasa recta. With loss of water, the urea left behind in the tubular fluid of the collecting duct becomes increasingly concentrated. Because duct cells deep in the renal medulla are permeable to it, urea diffuses from the fluid in the duct into the interstitial fluid of the renal medulla.

Urea recycling causes a buildup of urea in the renal medulla. As urea accumulates in the interstitial fluid, some of it diffuses into the tubular fluid in the descending and thin ascending limbs of the long nephron loops, which also are permeable to urea (Figure 26.19a). However, while the fluid flows through the thick ascending limb, distal convoluted tubule, and cortical portion of the collecting duct, urea remains in the lumen because cells in these segments are impermeable to it. As fluid flows along the collecting ducts, water reabsorption continues via osmosis because A.D.H is present. This water reabsorption further increases the concentration of urea in the tubular fluid, more urea diffuses into the interstitial fluid of the inner renal medulla, and the cycle repeats. The constant transfer of urea between segments of the renal tubule and the interstitial fluid of the renal medulla is termed urea recycling.

In this way, reabsorption of water from the tubular fluid of the ducts promotes the buildup of urea in the interstitial fluid of the renal medulla, which in turn promotes water reabsorption. The solutes left behind in the lumen thus become very concentrated, and a small volume of concentrated urine is excreted.

Countercurrent Exchange Countercurrent exchange is the process by which solutes and water are passively exchanged between the blood of the vasa recta and interstitial fluid of the renal medulla as a result of countercurrent flow. Note in Figure 26.19b that the vasa recta also consists of descending and ascending limbs that are parallel to each other and to the nephron loop. Just as tubular fluid flows in opposite directions in the nephron loop, blood flows in opposite directions in the ascending and descending parts of the vasa recta. Since countercurrent flow between the descending and ascending limbs of the vasa recta allows for exchange of solutes and water between the blood and interstitial fluid of the renal medulla, the vasa recta is said to function as a countercurrent exchanger.

Blood entering the vasa recta has an osmolarity of about 300 mOsm/liter. As it flows along the descending part into the renal medulla, where the interstitial fluid becomes increasingly concentrated, Na superscript plus , Cl superscript minus , and urea diffuse from interstitial fluid into the blood and water diffuses from the blood into the interstitial fluid. But after its osmolarity increases, the blood flows into the ascending part of the vasa recta. Here blood flows through a region where the interstitial fluid becomes increasingly less concentrated.

As a result Na superscript plus , Cl superscript minus , and urea diffuse from the blood back into interstitial fluid, and water diffuses from interstitial fluid back into the vasa recta. The osmolarity of blood leaving the vasa recta is only slightly higher than the osmolarity of blood entering the vasa recta. Thus, the vasa recta provides oxygen and nutrients to the renal medulla without washing out or diminishing the osmotic gradient.

The long nephron loop establishes the osmotic gradient in the renal medulla by countercurrent multiplication, but the vasa recta maintains the osmotic gradient in the renal medulla by countercurrent exchange.

Figure 26.20 summarizes the processes of filtration, reabsorption, and secretion in each segment of the nephron and collecting duct.

Clinical Connection

Diuretics

Diuretics diuretics are substances that slow renal reabsorption of water and thereby cause diuresis, an elevated urine flow rate, which in turn reduces blood volume. Diuretic drugs often are prescribed to treat hypertension (high blood pressure) because lowering blood volume usually reduces blood pressure. Naturally occurring diuretics include caffeine in coffee, tea, and sodas, which inhibits Na⁺ reabsorption, and alcohol in beer, wine, and mixed drinks, which inhibits secretion of A.D.H. Most diuretic drugs act by interfering with a mechanism for reabsorption of filtered Na⁺. For example, loop diuretics, such as furosemide (Lasix®), selectively inhibit the sodium potassium chloride symporters in the thick ascending limb of the nephron loop (see Figure 26.15). The thiazide diuretics, such as chlorothiazide (Diuril®), act in the distal convoluted tubule, where they promote loss of Na⁺ and Cl⁻ in the urine by inhibiting Na⁺-Cl⁻ symporters.

Figure 26.20 Summary of Filtration, Reabsorption, and Secretion in the Nephron and Collecting Duct.

Filtration occurs in the renal corpuscle; reabsorption occurs all along the renal tubule and collecting ducts.

Renal Corpuscle

Glomerular filtration rate: 105 to 125 milliliters per minute of fluid that is isotonic to blood Filtered substances: water and all solutes present in blood (except proteins), including ions, glucose, amino acids, creatinine, uric acid

Proximal Convoluted Tubule

Reabsorption (into blood) of filtered:

Table summary: The table describes the secretion of various substances into the urine within the nephron loop, noting that hydrogen ions and urea vary, ammonium levels increase during acidosis, and creatinine is secreted in limited quantities, while the tubular fluid remains isotonic to blood by the end of the proximal convoluted tubule.

Figure 26.28 summary: The tables illustrate the differential reabsorption and secretion of water and solutes across different segments of the nephron. The majority of water, sodium, potassium, and calcium, as well as all glucose and amino acids, are reabsorbed in the first segment. The second segment handles a smaller portion of water and electrolytes, while also managing urea secretion. The final segments provide fine-tuning of water and sodium levels under hormonal control, alongside variable secretion of potassium and hydrogen ions to maintain homeostasis.

Early Distal Convoluted Tubule

Table summary: The table outlines the reabsorption of various ions into the blood, showing a small, equal percentage of sodium and chloride reabsorbed via symporters, while calcium reabsorption remains variable and is influenced by parathyroid hormone.

Late Distal Convoluted Tubule and Collecting Duct

H C O 3 minus variable amount, depends on H plus secretion (antiporters)

Urea variable (recycling to nephron loop)

Secretion (into urine) of:

Tubular fluid leaving the collecting duct is dilute when A.D.H level is low and concentrated when A.D.H level is high.

Checkpoint

21. How do symporters in the ascending limb of the nephron loop and principal cells in the collecting duct contribute to the formation of concentrated urine?

22. How does A.D.H regulate facultative water reabsorption?

23. What is the countercurrent mechanism? Why is it important?

26.8 Evaluation of Kidney Function

Objectives

• Define urinalysis and describe its importance.

• Define renal plasma clearance and describe its importance.

Routine assessment of kidney function involves evaluating both the quantity and quality of urine and the levels of wastes in the blood.

Urinalysis

An analysis of the volume and physical, chemical, and microscopic properties of urine, called a urinalysis urinalysis, reveals much about the state of the body. Table 26.5 summarizes the major characteristics of normal urine. The volume of urine eliminated per day in a normal adult is 1 to 2 liters (about 1 to 2 qt). Fluid intake, blood pressure, blood osmolarity, diet, body temperature, diuretics, mental state, and general health influence urine volume.

Table 26.5 summary: This table outlines the physical and chemical properties of healthy human urine, noting that volume, color, odor, and pH levels are subject to significant variation based on factors such as diet, hydration, and health status. It describes the typical appearance and scent of fresh versus standing urine and explains that density is directly related to the concentration of solutes.

For example, low blood pressure triggers the renin-angiotensin-aldosterone pathway. Aldosterone increases reabsorption of water and salts in the renal tubules and decreases urine volume. By contrast, when blood osmolarity decreases—for example, after drinking a large volume of water—secretion of A.D.H is inhibited and a larger volume of urine is excreted.

Water accounts for about 95% of the total volume of urine. The remaining 5% consists of electrolytes, solutes derived from cellular metabolism, and exogenous substances such as drugs. Normal urine is virtually protein-free. Typical solutes normally present in urine include filtered and secreted electrolytes that are not reabsorbed, urea (from breakdown of proteins), creatinine (from breakdown of creatine phosphate in muscle fibers), uric acid (from breakdown of nucleic acids), urobilinogen (from breakdown of hemoglobin), and small quantities of other substances, such as fatty acids, pigments, enzymes, and hormones.

If disease alters body metabolism or kidney function, traces of substances not normally present may appear in the urine, or normal constituents may appear in abnormal amounts. Table 26.6 lists several abnormal constituents in urine that may be detected as part of a urinalysis. Normal values of urine components and the clinical implications of deviations from normal are listed in Appendix D.

Table 26.6 summary: This table outlines various abnormal constituents found in urine and their associated clinical implications. It details how the presence of proteins, sugars, blood cells, and ketone bodies typically signals specific metabolic disorders, organ injury, or systemic diseases. Additionally, it describes the significance of bilirubin and urobilinogen levels in relation to liver and blood conditions, while noting that the presence of casts and various microbes generally indicates infection or structural damage within the urinary tract.

Blood Tests

Two blood-screening tests can provide information about kidney function. One is the blood urea nitrogen B.U.N test, which measures the blood nitrogen that is part of the urea resulting from catabolism and deamination of amino acids. When glomerular filtration rate decreases severely, as may occur with renal disease or obstruction of the urinary tract, bun rises steeply. One strategy in treating such patients is to minimize their protein intake, thereby reducing the rate of urea production.

Another test often used to evaluate kidney function is measurement of plasma creatinine creatinine, which results from catabolism of creatine phosphate in skeletal muscle. Normally, the blood creatinine level remains steady because the rate of creatinine excretion in the urine equals its discharge from muscle. A creatinine level above 1.5 milligrams/dL (135 millimoles/liter) usually is an indication of poor renal function. Normal values for selected blood tests are listed in Appendix C along with situations that may cause the values to increase or decrease.

Renal Plasma Clearance

Even more useful than bun and blood creatinine values in the diagnosis of kidney problems is an evaluation of how effectively the kidneys are removing a given substance from blood plasma. Renal plasma clearance is the volume of blood that is “cleaned” or cleared of a substance per unit of time, usually expressed in units of milliliters per minute. High renal plasma clearance indicates efficient excretion of a substance in the urine; low clearance indicates inefficient excretion.

For example, the clearance of glucose normally is zero because it is completely reabsorbed (see Table 26.3); therefore, glucose is not excreted at all. Knowing a drug's clearance is essential for determining the correct dosage. If clearance is high (one example is penicillin), then the dosage must also be high, and the drug must be given several times a day to maintain an adequate therapeutic level in the blood.

The following equation is used to calculate clearance:

Math summary: This computation determines the renal plasma clearance of a substance. It multiplies the urine concentration by the urine flow rate and divides the result by the plasma concentration.

where U and P are the concentrations of the substance in urine and plasma, respectively (both expressed in the same units, such as milligrams per milliliter), and V is the urine flow rate in milliliters per minute.

The clearance of a solute depends on the three basic processes of a nephron: glomerular filtration, tubular reabsorption, and tubular secretion. Consider a substance that is filtered but neither reabsorbed nor secreted. Its clearance equals the glomerular filtration rate because all molecules that pass the filtration membrane appear in the urine.

This is the situation for the plant polysaccharide inulin insulin; it easily passes the filter, it is not reabsorbed, and it is not secreted. (Do not confuse inulin with the hormone insulin, which is produced by the pancreas.) Typically, the clearance of inulin is about 125 milliliters per minute, which equals the G.F.R. Clinically, the clearance of inulin can be used to determine the G.F.R. The clearance of inulin is obtained in the following way: Inulin is administered intravenously and then the concentrations of inulin in plasma and urine are measured along with the urine flow rate. Although using the clearance of inulin is an accurate method for determining the G.F.R, it has its drawbacks: Inulin is not produced by the body and it must be infused continuously while clearance measurements

Hemodialysis

As you learned previously, the kidneys have many essential functions, such as regulating electrolyte levels in the blood; influencing blood pressure, volume, and pH; and excreting wastes. When one or both kidneys operate at only 10 to 15% of their capacity, a person is a candidate for hemodialysis hemodialysis, a process that removes wastes and excess fluid from the blood and restores electrolyte balance in order to maintain homeostasis. The leading cause of renal failure is diabetes.

In the procedure, blood is removed from an artery, such as the radial artery, and passed into a kidney dialysis machine. This device is basically a computer that monitors blood flow, blood pressure, fluid volume and other vital information. Only one pint of blood of the 10 to 12 pints in the body is outside of the body at a time. The arterial blood is pressure monitored and an anticoagulant (heparin) is added to prevent blood clot formation.

The blood then passes into a dialyzer, which is an artificial kidney, equivalent to nephrons. The dialyzer consists of a selectively permeable membrane that separates blood moving in one direction on one side of it from a solution called the dialysate moving in the opposite direction on the other side of the membrane. The dialysate has the same solute concentration as blood plasma. As blood moves through the dialyzer, the blood cells do not pass through the membrane. However, any wastes, such as area, and excess fluid and electrolytes move from the blood into the dialysate. At the same time, substances lacking in the blood move from the dialysate into the blood. Basically, the dialyzer removes wastes and excess fluid and restores the proper balance of electrolytes in the blood.

The dialysate is continuously replaced and the used dialysate is then flushed into a drainage receptacle. Once blood has been processed, it leaves the dialyzer and then passes through a venous pressure monitor and then through an air embolus detector to remove any gas bubbles from the blood. The blood is then returned to the patient through a vein, such as the radial vein.

Hemodialysis usually lasts for about 3 to 5 hours and is performed three times a week.

In addition to using a kidney dialysis machine, in which the selectively permeable membrane is outside the body, there is an alternative procedure which uses one of the body's own selectively permeable membranes. This procedure uses the lining of the abdominal cavity called the peritoneum as the selectively permeable membrane and is referred to as peritoneal dialysis P.D. The dialysate is introduced through a catheter into the abdomen. Wastes and excess fluid and electrolytes pass from the blood into the dialysate.

After a few hours, the used dialysate is drained into a bag and replaced with a fresh dialysate. This is usually repeated four to six times a day. are being determined. Measuring the creatinine clearance is an easier way to assess the G.F.R because creatinine is a substance that is naturally produced by the body as an end product of muscle metabolism. Once creatinine is filtered, it is not reabsorbed, and is secreted only to a very small extent.

Image summary: This figure is a schematic diagram. It illustrates the process of hemodialysis, showing the path of blood from a patient's arm through an external filtration system and back into the body. The system includes an arterial pressure monitor, a blood pump, a heparin injection point, a dialyzer for filtering waste using fresh dialysate, an air embolus detector, and a venous pressure monitor. The diagram demonstrates that blood is extracted from an artery, pumped through a dialyzer where it is cleaned by exchanging waste with dialysate, and then safely returned to a vein after passing through safety monitors.

Because there is a small amount of creatinine secretion, the creatinine clearance is only a close estimate of the G.F.R and is not as accurate as using the inulin clearance. The creatinine clearance is normally about 120 to 140 milliliters per minute.

The clearance of the organic anion para-aminohippuric acid P.A.H paraaminohypuric is also of clinical importance. After P.A.H is administered intravenously, it is filtered and secreted in a single pass through the kidneys. Thus, the clearance of P.A.H is used to measure renal plasma flow, the amount of plasma that passes through the kidneys. in one minute. Typically, the renal plasma flow is 650 mL per minute, which is about 55% of the renal blood flow (1200 mL per minute).

26.9 Urine Transportation, Storage, and Elimination

Objective

• Describe the anatomy, histology, and physiology of the ureters, urinary bladder, and urethra.

From collecting ducts, urine drains into the minor calyces, which join to become major calyces that unite to form the renal pelvis (see Figure 26.3). From the renal pelvis, urine first drains into the ureters and then into the urinary bladder for storage. Urine is then discharged from the body through the single urethra (see Figure 26.1).

Ureters

Each of the two ureters (Ü-re-ters) transports urine from the renal pelvis of one kidney to the urinary bladder. Peristaltic contractions of the muscular walls of the ureters push urine toward the urinary bladder, but hydrostatic pressure and gravity also contribute. Peristaltic waves that pass from the renal pelvis to the urinary bladder vary in frequency from one to five per minute, depending on how fast urine is being formed.

Figure 26.21 Ureters, urinary bladder, and urethra in a female.

Figure 26.21 summary: This figure is an anatomical diagram showing a coronal section of the human urinary system. The illustration depicts the urinary bladder and its associated structures, including the ureters that bring urine from the kidneys, the detrusor muscle, the trigone area, and the urethral sphincters leading to the external urethral orifice. The diagram highlights the pathway urine takes from the ureteral openings through the bladder and out via the urethra. It can be inferred that the bladder is designed for expansion through mucosal folds to store urine and that the expulsion of urine is controlled by both involuntary and voluntary sphincter muscles.

The ureters are 25 to 30 centimeters (10 to 12 in.) long and are thick-walled, narrow tubes that vary in diameter from 1 millimeters to 10 millimeters along their course between the renal pelvis and the urinary bladder. Like the kidneys, the ureters are retroperitoneal. They descend anterior to the common iliac vessels and at the base of the urinary bladder, the ureters curve medially and pass obliquely through the wall of the posterior aspect of the urinary bladder (Figure 26.21).

Even though there is no anatomical valve at the opening of each ureter into the urinary bladder, a physiological one is quite effective. As the urinary bladder fills with urine, pressure within it compresses the oblique openings into the ureters and prevents the backflow of urine. When this physiological valve is not operating properly, it is possible for microbes to travel up the ureters from the urinary bladder to infect one or both kidneys.

Three layers of tissue form the wall of the ureters. The deepest coat, the mucosa, is a mucous membrane with urothelium (transitional epithelium) (see Table 4.1) and an underlying lamina propria of areolar connective tissue with considerable collagen, elastic fibers, and lymphatic tissue. Urothelium is able to stretch—a marked advantage for any organ that must accommodate a variable volume of fluid. Mucus secreted by the goblet cells of the mucosa prevents the cells from coming in contact with urine, the solute concentration and pH of which may differ drastically from the cytosol of cells that form the wall of the ureters.

Throughout most of the length of the ureters, the intermediate coat, the muscular layer, is composed of inner longitudinal and outer circular layers of smooth muscle fibers. This arrangement is opposite to that of the digestive canal, which contains inner circular and outer longitudinal layers. The muscularis of the distal third of the ureters also contains an outer layer of longitudinal muscle fibers. Thus, the muscular layer in the distal third of the ureter is inner longitudinal, middle circular, and outer longitudinal. Peristalsis is the major function of the muscularis.

The superficial coat of the ureters is the adventitia, a layer of areolar connective tissue containing blood vessels, lymphatic vessels, and nerves that serve the muscular layer and mucosa. The adventitia blends in with surrounding connective tissue and anchors the ureters in place.

Urinary Bladder

The urinary bladder is a hollow, distensible muscular organ situated in the pelvic cavity posterior to the pubic symphysis. In males, it is directly anterior to the rectum; in females, it is anterior to the vagina and inferior to the uterus (see Figure 26.22). Folds of the peritoneum hold the urinary bladder in position. When slightly distended due to the accumulation of urine, the urinary bladder is spherical. When it is empty, it collapses. As urine volume increases, it becomes pear-shaped and rises into

Figure 26.22 summary: This figure consists of anatomical diagrams showing sagittal sections of the human pelvic region. The diagrams illustrate the reproductive and urinary systems of both males and females, labeling key structures such as the urinary bladder, rectum, and urethra. In the male section, it details the divisions of the urethra including the prostatic, membranous, and spongy segments, as well as the prostate, penis, and testes. The female section highlights the uterus, vagina, and a significantly shorter urethra. Comparison between the two figures reveals that the male urethra is considerably longer and more complex, serving as a shared pathway for both urine and semen. In contrast, the female urethra is a shorter, dedicated tube for urinary excretion, keeping the urinary and genital systems entirely separate.

Figure 26.22 Comparison Between Male and Female Urethras.

the lower abdominal cavity. Urinary bladder capacity averages 700 to 800 mL. It is smaller in females because the uterus occupies the space just superior to the urinary bladder.

Anatomy and Histology of the Urinary Blad-

der In the floor of the urinary bladder is a small triangular area called the trigone trigon = triangle). The two posterior corners of the trigone contain the two ureteral openings; the opening into the urethra, the internal urethral orifice orifis, lies in the anterior corner (see Figure 26.21). Because its mucosa is firmly bound to the muscular layer, the trigone has a smooth appearance.

Three coats make up the wall of the urinary bladder. The deepest is the mucosa, a mucous membrane composed of urothelium and an underlying lamina propria similar to that of the ureters. The urothelium permits stretching.

Mucosal folds (rugae) are also present to permit expansion of the urinary bladder. Surrounding the mucosa is the intermediate muscular layer, also called the detrusor muscle detrooser = to push down), which consists of three layers of smooth muscle fibers: the inner longitudinal, middle circular, and outer longitudinal layers. Around the opening to the urethra the circular fibers form an internal urethral sphincter; inferior to it is the external urethral sphincter, which is composed of

The male urethra is about 20 centimeters (8 in.) in length, while the female urethra is about 4 centimeters (1.5 in.) in length.

• The urethra is a common duct for the urinary and genital systems in males. These two systems are entirely separate in females.

skeletal muscle and is a modification of the deep muscles of the perineum (see Figure 11.12). The most superficial coat of the urinary bladder on the posterior and inferior surfaces is the adventitia, a layer of areolar connective tissue that is continuous with that of the ureters. Over the superior surface of the urinary bladder is the serosa, a layer of visceral peritoneum.

The Micturition Reflex Discharge of urine from the urinary bladder, called micturition micturition; mictur-= urinate), is also known as urination or voiding. Micturition occurs via a combination of involuntary and voluntary muscle contractions. When the volume of urine in the urinary bladder exceeds 200 to 400 mL, pressure within the bladder increases considerably, and stretch receptors in its wall transmit nerve impulses into the spinal cord. These impulses propagate to the micturition center in sacral spinal cord segments S.2 and S.3 and trigger a spinal reflex called the micturition reflex.

In this reflex arc, parasympathetic impulses from the micturition center propagate to the urinary bladder wall and internal urethral sphincter. The nerve impulses cause contraction of the detrusor muscle and relaxation of the internal urethral sphincter muscle. Simultaneously, the micturition center inhibits somatic motor neurons that innervate skeletal muscle in the external urethral sphincter.

On contraction of the urinary bladder wall and relaxation of the sphincters, urination takes place. Urinary bladder filling causes a sensation of fullness that initiates a conscious desire to urinate before the micturition reflex actually occurs. Although emptying of the urinary bladder is a reflex, in early childhood we learn to initiate it and stop it voluntarily. Through learned control of the external urethral sphincter muscle and certain muscles of the pelvic floor, the cerebral cortex can initiate micturition or delay its occurrence for a limited period.

Clinical Connection

Cystitis

Cystitis (sis-Tl-tis; cysto-= bladder; -itis = inflammation of) is an inflammation of the urinary bladder, frequently caused by the bacterium E. coli. It can also be caused by chemotherapy drugs, radiation, long-term use of catheters, and complications of other conditions such as enlarged prostate, diabetes, and kidney stones. Cystitis is characterized by pelvic pain, frequent urination, a burning sensation when urinating, strong-smelling urine, blood in the urine, and a low-grade fever. Cystitis caused by a bacterial infection is treated with antibiotics.

Urethra

The urethra (ü-Re-thra) is a small tube leading from the internal urethral orifice in the floor of the urinary bladder to the exterior of the body (Figure 26.22). In both males and females, the urethra is the terminal portion of the urinary system and the passageway for discharging urine from the body. In males, it discharges semen (fluid that contains sperm) as well.

In males, the urethra also extends from the internal urethral orifice to the exterior, but its length and passage through the body are considerably different than in females (Figure 26.22a). The male urethra first passes through the prostate, then through the deep perineal muscles, and finally through the penis, a distance of about 20 centimeters (8 in.).

The male urethra, which also consists of a deep mucosa and a superficial muscular layer, is subdivided into three anatomical regions: (1) The prostatic urethra passes through the prostate. (2) The membranous urethra, the shortest portion, passes through the deep perineal muscles of the perineum. (3) The spongy urethra, the longest portion, passes through the penis. The epithelium of the prostatic urethra is continuous with that of the urinary bladder and consists of urothelium that becomes stratified columnar or pseudostratified columnar epithelium more distally. The mucosa of the membranous urethra contains stratified columnar or pseudostratified columnar epithelium.

The epithelium of the spongy urethra is stratified columnar or pseudostratified columnar epithelium, except near the external urethral orifice. There it is nonkeratinized stratified squamous epithelium. The lamina propria of the male urethra is areolar connective tissue with elastic fibers and a plexus of veins.

The muscular layer of the prostatic urethra is composed of mostly circular smooth muscle fibers superficial to the lamina propria; these circular fibers help form the internal urethral sphincter of the urinary bladder. The muscular layer of the membranous urethra consists of circularly arranged skeletal muscle fibers of the deep muscles of the perineum that help form the external urethral sphincter of the urinary bladder.

Several glands and other structures associated with reproduction deliver their contents into the male urethra (see Figure 28.9). The prostatic urethra contains the openings of (1) ducts that transport secretions from the prostate and (2) the seminal glands and ductus (vas) deferens, which deliver sperm into the urethra and provide secretions that both neutralize the acidity of the female genital tract and contribute to sperm motility and viability. The openings of the ducts of the bulbourethral glands (bul'-bo-u-Re-thral) or Cowper's glands empty into the spongy urethra. They deliver an alkaline substance prior to ejaculation that neutralizes the acidity of the urethra.

The glands also secrete mucus, which lubricates the end of the penis during sexual arousal. Throughout the urethra, but especially in the spongy urethra, the openings of the ducts of urethral glands or Littré glands (Ll-tre) discharge mucus during sexual arousal and ejaculation.

In females, the urethra lies directly posterior to the pubic symphysis; is directed obliquely, inferiorly, and anteriorly; and has a length of 4 centimeters (1.5 in.) (Figure 26.22b). The opening of the urethra to the exterior, the external urethral orifice, is located between the clitoris and the vaginal opening (see Figure 28.11a). The wall of the female urethra consists of a deep mucosa and a superficial muscularis. The mucosa is a mucous membrane composed of epithelium and lamina propria (areolar connective tissue with elastic fibers and a plexus of veins). Near the urinary bladder, the mucosa contains urothelium that is continuous with that of the urinary bladder; near the external urethral orifice, the epithelium is nonkeratinized stratified

Urinary Incontinence

A lack of voluntary control over micturition is called urinary incontinence incontinence. In infants and children under 2 to 3 years old, incontinence is normal because neurons to the external urethral sphincter muscle are not completely developed; voiding occurs whenever the urinary bladder is sufficiently distended to stimulate the micturition reflex. Urinary incontinence also occurs in adults. There are four types of urinary incontinence—stress, urge, overflow, and functional. Stress incontinence is the most common type of incontinence in young and middle-aged females, and results from weakness of the deep muscles of the pelvic floor.

As a result, any physical stress that increases abdominal pressure, such as coughing, sneezing, laughing, exercising, straining, lifting heavy objects, and pregnancy, causes leakage of urine from the urinary bladder. Urge incontinence is most common in older people and is characterized by an abrupt and intense urge to urinate. squamous epithelium. Between these areas, the mucosa contains stratified columnar or pseudostratified columnar epithelium. The muscular layer consists an outer sheath of skeletal muscle and an inner layer of smooth muscle fibers.

A summary of the organs of the urinary system is presented in Table 26.7. followed by an involuntary loss of urine. It may be caused by irritation of the urinary bladder wall by infection or kidney stones, stroke, multiple sclerosis, spinal cord injury, or anxiety. Overflow incontinence refers to the involuntary leakage of small amounts of urine caused by some type of blockage or weak contractions of the musculature of the urinary bladder. When urine flow is blocked (for example, from an enlarged prostate or kidney stones) or when the urinary bladder muscles can no longer contract, the urinary bladder becomes overfilled and the pressure inside increases until small amounts of urine dribble out. Functional incontinence is urine loss resulting from the inability to get to a toilet facility in time as a result of conditions such as stroke, severe arthritis, or Alzheimer's disease. Choosing the right treatment option depends on correct diagnosis of the type of incontinence. Treatments include Kegel exercises (see Clinical Connection: Injury of Levator Ani and Urinary Stress Incontinence in Chapter 11), urinary bladder training, medication, and possibly even surgery.

Table 26.7 summary: This table provides a comprehensive overview of the organs within the urinary system, detailing the anatomical location, physical description, and primary physiological function of the kidneys, ureters, urinary bladder, and urethra. It highlights the progression of urine from production and regulation in the kidneys, through transport via the ureters, temporary storage in the bladder, and final excretion through the urethra.

Checkpoint

28. What forces help propel urine from the renal pelvis to the urinary bladder?

29. What is micturition? How does the micturition reflex occur?

30. How do the location, length, and histology of the urethra compare in males and females?

26.10 Waste Management in Other Body Systems

Objective

• Describe the ways that body wastes are handled.

As we have seen, just one of the many functions of the urinary system is to help rid the body of some kinds of waste materials. Besides the kidneys, several other tissues, organs, and processes contribute to the temporary confinement of wastes, the transport of waste materials for disposal, the recycling of materials, and the excretion of excess or toxic substances in the body. These waste management systems include the following:

• Body buffers. Buffers in body fluids bind excess hydrogen ions ( H superscript plus ), thereby preventing an increase in the acidity of body fluids. Buffers, like wastebaskets, have a limited capacity; eventually the H superscript plus , like the paper in a wastebasket, must be eliminated from the body by excretion.

• Blood. The bloodstream provides pickup and delivery services for the transport of wastes, in much the same way that garbage trucks and sewer lines serve a community.

• Liver. The liver is the primary site for metabolic recycling, as occurs, for example, in the conversion of amino acids into glucose or of glucose into fatty acids. The liver also converts toxic substances into less toxic ones, such as ammonia into urea. These functions of the liver are described in Chapters 24 and 25.

• Lungs. With each exhalation, the lungs excrete C-O 2 , and expel heat and a little water vapor.

• Sweat glands. Especially during exercise, sweat glands in the skin help eliminate excess heat, water, and C-O 2 , plus small quantities of salts and urea as well.

• Digestive canal. Through defecation, the digestive canal excretes solid, undigested foods; wastes; some C-O 2 ; water; salts; and heat.

Checkpoint

31. What roles do the liver and lungs play in the elimination of wastes?

Image summary: This figure is a medical illustration. It depicts a fetus in a curled position within a womb, connected to the uterine wall by an umbilical cord. The illustration demonstrates the fetal position and the anatomical relationship between the developing embryo and the surrounding gestational environment.

26.11 Development of the Urinary System

• Describe the development of the urinary system.

Starting in the third week of fetal development, a portion of the mesoderm along the posterior aspect of the embryo, the intermediate mesoderm, differentiates into the kidneys. The intermediate mesoderm is located in paired elevations called urogenital ridges urogenital. Three pairs of kidneys form within the intermediate mesoderm in succession: the pronephros, the mesonephros, and the metanephros (Figure 26.23). Only the last pair remains as the functional kidneys of the newborn.

Figure 26.23 summary: This figure is a series of anatomical diagrams. It illustrates the developmental progression of the urogenital system in an embryo across several stages, from the fifth week through the eighth week, including an anterior view of the final stage. The diagrams track the transformation and positioning of structures such as the pronephros, mesonephros, and metanephros, as well as the formation of the urinary bladder, ureters, and gonads. The sequence shows that the early renal structures degenerate or are replaced as the permanent kidneys develop from the metanephros. It can be inferred that the urogenital system undergoes significant remodeling, where primitive structures are phased out to make way for specialized organs like the kidneys and bladder, while the urogenital sinus differentiates into distinct urinary and reproductive components.

The first kidney to form, the pronephros pronephros; pro-= before; -nephros = kidney), is the most superior of the three and has an associated pronephric duct. This duct empties into the cloaca (klö-Ä-ka), the expanded terminal part of the hindgut, which functions as a common outlet for the urinary, digestive, and reproductive ducts. The pronephros begins to degenerate during the fourth week and is completely gone by the sixth week.

The second kidney, the mesonephros mesonephros; meso-= middle), replaces the pronephros. The retained portion of the pronephric duct, which connects to the mesonephros, develops into the mesonephric duct. The mesonephros begins to degenerate by the sixth week and is almost gone by the eighth week.

At about the fifth week, a mesodermal outgrowth, called a ureteric bud ureteric, develops from the distal portion of the mesonephric duct near the cloaca. The metanephros metanephros; meta-= after), or ultimate kidney, develops from the ureteric bud and metanephric mesoderm. The ureteric bud forms the collecting ducts, calyces, renal pelvis, and ureter.

The metanephric mesoderm metanephric forms the nephrons of the kidneys. By the third month, the fetal kidneys begin excreting urine into the surrounding amniotic fluid; indeed, fetal urine makes up most of the amniotic fluid.

During development, the cloaca divides into a urogenital sinus, into which urinary and genital ducts empty, and a rectum that discharges into the anal canal. The urinary bladder develops from the urogenital sinus. In females, the urethra develops as a result of lengthening of the short duct that extends from the urinary bladder to the urogenital sinus. In males, the urethra is considerably longer and more complicated, but it is also derived from the urogenital sinus.

Although the metanephric kidneys form in the pelvis, they ascend to their ultimate destination in the abdomen. As they do so, they receive renal blood vessels. Although the inferior blood vessels usually degenerate as superior ones appear, sometimes the inferior vessels do not degenerate. Consequently, some individuals (about 30%) develop multiple renal vessels.

In a condition called unilateral renal agenesis agenesis; a-= without; -genesis = production; unilateral = one side) only one kidney develops (usually the right) due to the absence of a ureteric bud. The condition occurs once in every 1000 newborn infants and usually affects males more than females. Other kidney abnormalities that occur during development are malrotated kidneys (the hilum faces anteriorly, posteriorly, or laterally instead of medially); ectopic kidney (one or both kidneys may be in an abnormal position, usually inferior); and horseshoe kidney (the fusion of the two kidneys, usually inferiorly, into a single U-shaped kidney).

Figure 26.23 Development of the Urinary System.

Three pairs of kidneys form within intermediate mesoderm in succession: pronephros, mesonephros, and metanephros.

Checkpoint

32. Which type of embryonic tissue develops into nephrons?

33. Which tissue gives rise to collecting ducts, calyces, renal pelves, and ureters?

26.12 Aging and the Urinary System

Objective

• Describe the effects of aging on the urinary system.

With aging, the kidneys shrink in size, have a decreased blood flow, and filter less blood. These age-related changes in kidney size and function seem to be linked to a progressive reduction in blood supply to the kidneys as an individual gets older; for example, blood vessels such as the glomeruli become damaged or decrease in number. The mass of the two kidneys decreases from an average of nearly 300 g in 20-year-olds to less than about 200 g by age 80, a decrease of about one-third. Likewise, renal blood flow and filtration rate decline by 50% between ages 40 and 70. By age 80, about 40% of glomeruli are not functioning and thus filtration, reabsorption, and secretion decrease. Kidney diseases that become more common with age include acute and chronic kidney inflammations and renal calculi (kidney stones).

Because the sensation of thirst diminishes with age, older individuals also are susceptible to dehydration. Urinary bladder changes that occur with aging include a reduction in size and capacity and weakening of the muscles. Urinary tract infections are more common among the elderly, as are polyuria (excessive urine production), nocturia (excessive urination at night), increased frequency of urination, dysuria (painful urination), urinary retention or incontinence, and hematuria (blood in the urine).

34. To what extent do kidney mass and filtration rate decrease with age?

To appreciate the many ways that the urinary system contributes to homeostasis of other body systems, examine Focus on Homeostasis: Contributions of the Urinary System. Next, in Chapter 27, we will see how the kidneys and lungs contribute to maintenance of homeostasis of body fluid volume, electrolyte levels in body fluids, and acid-base balance.

Disorders: Homeostatic Imbalances

Renal Calculi

The crystals of salts present in urine occasionally precipitate and solidify into insoluble stones called renal calculi calculi = pebbles) or kidney stones. They commonly contain crystals of calcium oxalate, uric acid, or calcium phosphate. Conditions leading to calculus formation include the ingestion of excessive calcium, low water intake, abnormally alkaline or acidic urine, and overactivity of the parathyroid glands.

When a stone lodges in a narrow passage, such as a ureter, the pain can be intense. Shock-wave lithotripsy lithotripsy; litho-= stone) is a procedure that uses high-energy shock waves to disintegrate kidney stones and offers an alternative to surgical removal. Once the kidney stone is located using x-rays, a device called a lithotripter delivers brief, high-intensity sound waves through a water-or gel-filled cushion placed under the back. Over a period of 30 to 60 minutes, 1000 or more shock waves pulverize the stone, creating fragments that are small enough to wash out in the urine.

Urinary Tract Infections

The term urinary tract infection U.T.I is used to describe either an infection of a part of the urinary system or the presence of large numbers of microbes in urine. U.T.I's are more common in females due to the shorter length of the urethra. Symptoms include painful or burning urination, urgent and frequent urination, low back pain, and bed-wetting. U.T.I's include urethritis urethritis, inflammation of the urethra; cystitis cystitis, inflammation of the urinary bladder; and pyelonephritis pyelonephritis, inflammation of the kidneys.

If pyelonephritis becomes chronic, scar tissue can form in the kidneys and severely impair their function. Drinking cranberry juice can prevent the attachment of E. coli bacteria to the lining of the urinary bladder so that they are more readily flushed away during urination.

Glomerular Diseases

A variety of conditions may damage the kidney glomeruli, either directly or indirectly because of disease elsewhere in the body. Typically, the filtration membrane sustains damage, and its permeability increases.

Glomerulonephritis glomerulonephritis is an inflammation of the kidney that involves the glomeruli. One of the most common causes is an allergic reaction to the toxins produced by streptococcal bacteria that have recently infected another part of the body, especially the throat. The glomeruli become so inflamed, swollen, and engorged with blood that the filtration membranes allow blood cells and plasma proteins to enter the filtrate. As a result, the urine contains many erythrocytes (hematuria) and a lot of protein. The glomeruli may be permanently damaged, leading to chronic renal failure.

Nephrotic syndrome nephrotic is a condition characterized by proteinuria proteinuria, protein in the urine, and hyperlipidemia (hi'-per-lip-i-De-me-a), high blood levels of cholesterol, phospholipids, and triglycerides. The proteinuria is due to an increased permeability of the filtration membrane, which permits proteins, especially albumin, to escape from blood into urine. Loss of albumin results in hypoalbuminemia (hi'-po-al-bu-mi-Ne-me-a), low blood albumin level, once liver production of albumin fails to meet increased urinary losses.

Edema, usually seen around the eyes, ankles, feet, and abdomen, occurs in nephrotic syndrome because loss of albumin from the blood decreases blood colloid osmotic pressure. Nephrotic syndrome is associated with several glomerular diseases of unknown cause, as well as with systemic disorders such as diabetes mellitus, systemic lupus erythematosus S.L.E, a variety of cancers, and AIDS.

Renal Failure

Renal failure is a decrease or cessation of glomerular filtration. In acute renal failure A.R.F, the kidneys abruptly stop working entirely (or almost entirely). The main feature of A.R.F is the suppression of urine flow, usually characterized either by oliguria (ol'-i-Gü-rê-a), daily urine output between 50 mL and 250 mL, or by anuria (an-Ü-rê-a), daily urine output less than 50 mL. Causes include low blood volume (for example, due to hemorrhage), decreased cardiac output, damaged renal tubules, kidney stones, the dyes used to visualize blood vessels in angiograms, nonsteroidal anti-inflammatory drugs, and some antibiotic drugs. It is also common in people who suffer a devastating illness or overwhelming traumatic injury; in such cases it may be related to a more general organ failure known as multiple organ dysfunction syndrome mods.

Renal failure causes a multitude of problems. There is edema due to salt and water retention and metabolic acidosis due to an inability of the kidneys to excrete acidic substances. In the blood, urea builds up due to impaired renal excretion of metabolic waste products and potassium level rises, which can lead to cardiac arrest. Often, there is anemia because the kidneys no longer produce enough erythropoietin for adequate red blood cell production. Because the kidneys are no longer able to convert vitamin D to calcitriol, which is needed for adequate calcium absorption from the small intestine, osteomalacia also may occur.

Chronic renal failure C.R.F refers to a progressive and usually irreversible decline in glomerular filtration rate (G.F.R). C.R.F may result from chronic glomerulonephritis, pyelonephritis, polycystic kidney disease, or traumatic loss of kidney tissue. C.R.F develops in three stages. In the first stage, diminished renal reserve, nephrons are destroyed until about 75% of the functioning nephrons are lost. At this stage, a person may have no signs or symptoms because the

Focus on Homeostasis

Contributions of the Urinary System for All Body Systems

• Kidneys regulate volume, composition, and pH of body fluids by removing wastes and excess substances from blood and excreting them in urine

• Ureters transport urine from kidneys to urinary bladder, which stores urine until it is eliminated through urethra

Image summary: This figure is an anatomical illustration. It depicts a full-body human figure with a series of horizontal lines overlaying the entire body from head to toe. The illustration suggests a mapping or measurement system applied across the human anatomy to indicate specific levels or segments.

Image summary: This is an anatomical illustration. The figure depicts the human urinary system within a male body, highlighting the kidneys, ureters, and bladder. The illustration shows that the kidneys are positioned in the upper abdominal region, connected by tubes that lead down to a central bladder located in the pelvic area, indicating the pathway of fluid filtration and excretion from the upper torso to the lower pelvic region.

Integumentary System

• Kidneys and skin both contribute to synthesis of calcitriol, the active form of vitamin D

remaining nephrons enlarge and take over the function of those that have been lost. Once 75% of the nephrons are lost, the person enters the second stage, called renal insufficiency, characterized by a decrease in G.F.R and increased blood levels of nitrogen-containing wastes and creatinine. Also, the kidneys cannot effectively concentrate or dilute the urine.

The final stage, called end-stage renal failure, occurs when about 90% of the nephrons have been lost. At this stage, G.F.R diminishes to 10 to 15% of normal, oliguria is present, and blood levels of nitrogen-containing wastes and

Image summary: This figure is an anatomical diagram. It depicts a full-body human figure represented through a series of horizontal cross-sectional slices. The visualization shows the internal structure of the body from head to toe, illustrating how different anatomical layers align vertically. The image suggests a method of volumetric imaging or medical scanning, indicating that a complete three-dimensional representation of the human body can be reconstructed from multiple two-dimensional transverse sections.

Image summary: This figure is an anatomical illustration. It depicts the muscular system of a human body from a frontal perspective, showing the distribution of muscles across the torso, arms, and legs. The illustration demonstrates the symmetrical arrangement of muscle groups and their relationship to the underlying skeletal structure, indicating the complex organization of the human musculoskeletal system.

Image summary: This figure is an anatomical illustration. It depicts a human figure with a focus on the internal organs located in the abdominal region. The illustration indicates that the primary area of interest is the digestive system, specifically the liver and intestinal tract, which are highlighted relative to the rest of the body.

Image summary: This figure is an anatomical diagram. It depicts the human circulatory system, illustrating the network of arteries and veins distributed throughout the entire body from the head to the lower extremities. The diagram demonstrates that the circulatory system is an extensive and interconnected network that reaches all major organs and limbs, ensuring the distribution of blood across the entire human anatomy.

Image summary: This figure is an anatomical illustration. It depicts a full-body human female figure with various internal organs and biological systems visible through the skin. The illustration highlights the placement of the heart, lungs, digestive tract, and other internal structures within the torso. From this representation, it can be inferred that the figure is intended to show the spatial relationship and relative positioning of major internal organs within the human body.

Image summary: This figure is an anatomical illustration. It depicts a human body in a standing position, highlighting internal organs within the chest cavity. The illustration shows a concentration of activity or presence in the lungs and upper respiratory area, suggesting a focus on the pulmonary system.

Image summary: This figure is an anatomical illustration. It depicts a human figure with internal organs visible, specifically highlighting the thoracic and abdominal regions. The illustration indicates the placement and relative size of major organs within the body cavity, suggesting a focus on internal anatomy and the spatial relationship between different organ systems.

Skeletal System

• Kidneys help adjust levels of blood calcium and phosphates, needed for building extracellular bone matrix

Muscular System

• Kidneys help adjust level of blood calcium, needed for contraction of muscle

Nervous System

• Kidneys perform gluconeogenesis, which provides glucose for A.T.P production in neurons, especially during fasting or starvation

Endocrine System

• Kidneys participate in synthesis of calcitriol, the active form of vitamin D

• Kidneys release erythropoietin, the hormone that stimulates production of red blood cells

Cardiovascular System

• By increasing or decreasing their reabsorption of water filtered from blood, kidneys help adjust blood volume and blood pressure

• Renin released by juxtaglomerular cells in kidneys raises blood pressure

• Some bilirubin from hemoglobin breakdown is converted to a yellow pigment (urobilin), which is excreted in urine

Lymphoid (Lymphatic) System and Immunity

• By increasing or decreasing their reabsorption of water filtered from blood, kidneys help adjust volume of interstitial fluid and lymph plasma; urine flushes microbes out of urethra

Respiratory System

• Kidneys and lungs cooperate in adjusting pH of body fluids

Digestive System

• Kidneys help synthesize calcitriol, the active form of vitamin D, which is needed for absorption of dietary calcium

Genital (Reproductive) Systems

• In males, portion of urethra that extends through prostate, deep perineal muscles, and penis is passageway for semen as well as urine

Image summary: This figure is an anatomical illustration. It depicts a full-body human figure with horizontal lines across the torso and limbs, featuring a highlighted area in the pelvic region. The illustration suggests a mapping of specific bodily regions, indicating that the pelvic area is the primary point of interest or focus within the overall anatomical context.

creatinine increase further. People with end-stage renal failure need dialysis therapy and are possible candidates for a kidney transplant operation.

Polycystic Kidney Disease

Polycystic kidney disease P.K.D polycystic is one of the most common inherited disorders. In P.K.D, the kidney tubules become riddled with hundreds or thousands of cysts (fluid-filled cavities). In addition, inappropriate apoptosis (programmed cell death) of cells in noncystic tubules leads to progressive impairment of renal function and eventually to end-stage renal failure.

People with P.K.D also may have cysts and apoptosis in the liver, pancreas, spleen, and gonads; increased risk of cerebral aneurysms; heart valve defects; and diverticula in the colon. Typically, symptoms are not noticed until adulthood, when patients may have back pain, urinary tract infections, blood in the urine, hypertension, and large abdominal masses. Using drugs to restore normal blood pressure, restricting protein and salt in the diet, and controlling urinary tract infections may slow progression to renal failure.

Urinary Bladder Cancer

Each year, nearly 12,000 Americans die from urinary bladder cancer. It generally strikes people over 50 years of age and is three times more likely to develop in males than females. The disease is typically painless as it develops, but in most cases blood in the urine is a primary sign of the disease. Less often, people experience painful and/or frequent urination.

As long as the disease is identified early and treated promptly, the prognosis is favorable. Fortunately, about 75% of urinary bladder cancers are confined to the epithelium of the urinary bladder and are easily removed by surgery. The lesions tend to be low-grade, meaning that they have only a small potential for metastasis.

Urinary bladder cancer is frequently the result of a carcinogen. About half of all cases occur in people who smoke or have at some time smoked cigarettes. The cancer also tends to develop in people who are exposed to chemicals called aromatic amines. Workers in the leather, dye, rubber, and aluminum industries, as well as painters, are often exposed to these chemicals.

Kidney Transplant

A kidney transplant is the transfer of a kidney from a donor to a recipient whose kidneys no longer function. In the procedure, the donor kidney is placed in the pelvis of the recipient through an abdominal incision. The renal artery and vein of the

Medical Terminology

Azotemia azotemia; azot-= nitrogen; -emia = condition of blood) Presence of urea or other nitrogen-containing substances in the blood.

Cystocele cystocel; cysto-= bladder; -cele = hernia or rupture) Hernia of the urinary bladder.

Diabetic kidney disease A disorder caused by diabetes mellitus in which glomeruli are damaged. The result is the leakage of proteins into the urine and a reduction in the ability of the kidney to remove water and waste.

Dysuria (dis-Ü-re-a; dys-= difficult or painful; -uria = urine) Painful urination. transplanted kidney are attached to a nearby artery or vein in the pelvis of the recipient and the ureter of the transplanted kidney is then attached to the urinary bladder. During a kidney transplant, the patient receives only one donor kidney, since only one kidney is needed to maintain sufficient renal function. The nonfunctioning diseased kidneys are usually left in place. As with all organ transplants, kidney transplant recipients must be ever-vigilant for signs of infection or organ rejection. The transplant recipient will take immunosuppressive drugs for the rest of his or her life to avoid rejection of the “foreign” organ.

Cystoscopy

Cystoscopy cystoscopy; cysto-= bladder; -scopy = to examine) is a very important procedure for direct examination of the mucosa of the urethra and urinary bladder and prostate in males. In the procedure, a cystoscope (a flexible narrow tube with a light) is inserted into the urethra to examine the structures through which it passes. With special attachments, tissue samples can be removed for examination (biopsy) and small stones can be removed. Cystoscopy is useful for evaluating urinary bladder problems such as cancer and infections. It can also evaluate the degree of obstruction resulting from an enlarged prostate.

Image summary: This is an anatomical diagram. It illustrates the procedure of male cystoscopy, showing a cystoscope being inserted through the penis and urethra, passing the prostate, and entering the urinary bladder. The diagram labels key anatomical structures including the urinary bladder, prostate, scrotum, and penis, as well as components of the medical device such as the light cord, tube for fluid, and eye piece. The figure demonstrates that a cystoscope provides a direct pathway for medical professionals to visually examine the interior of the bladder and the urinary tract by navigating through the male reproductive and urinary anatomy.

Enuresis (en'-ü-RÊ-sis = to void urine) Involuntary voiding of urine after the age at which voluntary control has typically been attained.

Hydronephrosis hydronephrosis; hydro-= water; nephro-= kidney; -osis = condition) Swelling of the kidney due to dilation of the renal pelvis and calyces as a result of an obstruction to the flow of urine. It may be due to a congenital abnormality, a narrowing of the ureter, a kidney stone, or an enlarged prostate.

Intravenous pyelogram I.V.P intravenous Pi-e-lo-gram'; intra-= within; -veno-= vein; pyelo-= renal pelvis; -gram = record) Radiograph (x-ray) of the kidneys, ureters, and urinary bladder after venous injection of a radiopaque contrast medium.

Nephropathy nephropathy; nephro-= kidney; -pathos = suffering) Any disease of the kidneys. Types include diabetic (from complications of diabetes), analgesic (from long-term and excessive use of drugs such as ibuprofen), lead (from ingestion of lead-based paint), and organic solvents such as toluene/xylene.

Nocturnal enuresis (nokt-Ü-rê-a en'-ü-RÊ-sis) Discharge of urine during sleep, resulting in bed-wetting; occurs in about 15% of 5-year-old children and generally resolves spontaneously, afflicting only about 1% of adults. It may have a genetic basis, as bed-wetting occurs more often in identical twins than in fraternal twins and more often in children whose parents or siblings were bed-wetters. Possible causes include smaller than normal bladder capacity, failure to awaken in response to a full bladder, and above-normal production of urine at night. Also referred to as nocturia (nok-too-rê-a).

Pyelonephritis pyelonephritis; -pyelo = renal pelvis; nephr-= kidney) A type of urinary tract infection in which the renal pelvis and parenchyma of one or both kidneys become infected, usually by the bacterium E.coli. Typically, the bacteria find their way into the urethra, urinary bladder, ureter(s), and kidney(s). Signs and symptoms include chills; high fever; pain in the back, side, and

Chapter Review

Review

26.1 Overview of the Urinary System

1. The organs of the urinary system are the kidneys, ureters, urinary bladder, and urethra.

2. The kidneys excrete wastes; alter blood ionic composition, blood volume, blood pressure, and blood pH; maintain blood osmolarity; produce the hormones calcitriol and erythropoietin; and perform gluconeogenesis.

3. The ureters convey urine from the kidneys to the urinary bladder; the urinary bladder stores urine; and the urethra allows urine to pass from the urinary bladder to the outside environment.

26.2 Anatomy of the Kidneys

1. The kidneys are retroperitoneal organs attached to the posterior abdominal wall.

2. Three layers of tissue surround the kidneys; fibrous capsule, perirenal fat capsule, and renal fascia.

3. Internally, the kidneys consist of a renal cortex, a renal medulla, renal pyramids, renal papillae, renal columns, major and minor caly-ees, and a renal pelvis.

4. Blood flows into the kidney through the renal artery and successively into segmental, interlobar, arcuate, and cortical radiate arteries; afferent glomerular arterioles; glomerular capillaries; efferent glomerular arterioles; peritubular capillaries and vasa recta; and cortical radiate, arcuate, and interlobar veins before flowing out of the kidney through the renal vein.

5. Vasomotor nerves from the sympathetic part of the autonomic nervous system supply kidney blood vessels; they help regulate the flow of blood through the kidney.

groin; nausea and vomiting. Among the risk factors are pregnancy, enlarged prostate, diabetes, renal calculi, compromised immune system, backflow (reflux) of urine from the ureter(s) to the kidney(s), and catheters.

Polyuria (pol'-e-Ü-re-a; poly-= too much) Excessive urine formation. It may occur in conditions such as diabetes mellitus and glomerulonephritis.

Stricture stricture Narrowing of the lumen of a canal or hollow organ, as may occur in the ureter, urethra, or any other tubular structure in the body.

Uremia (ü-Re-me-a; -emia = condition of blood) Toxic levels of urea in the blood resulting from severe malfunction of the kidneys.

Urinary retention A failure to completely or normally void urine; may be due to an obstruction in the urethra or neck of the urinary bladder, to nervous contraction of the urethra, or to lack of urge to urinate. In men, an enlarged prostate may constrict the urethra and cause urinary retention. If urinary retention is prolonged, a catheter (slender rubber drainage tube) must be placed into the urethra to drain the urine.

26.3 The Nephron

1. The nephron is the functional unit of the kidneys. A nephron consists of a renal corpuscle (glomerulus and glomerular capsule) and a renal tubule.

2. A renal tubule consists of a proximal convoluted tubule, a nephron loop, and a distal convoluted tubule, which drains into a collecting duct (shared by several nephrons). The nephron loop consists of a descending limb and an ascending limb.

3. A cortical nephron has a short loop that dips only into the superficial region of the renal medulla; a juxtamedullary nephron has a long nephron loop that stretches through the renal medulla almost to the renal papilla.

4. The wall of the entire glomerular capsule, renal tubule, and ducts consists of a single layer of epithelial cells. The epithelium has distinctive histological features in different parts of the tubule. Table 26.1 summarizes the histological features of the renal tubule and collecting duct.

5. The juxtaglomerular apparatus consists of the juxtaglomerular cells of an afferent glomerular arteriole and the macula densa of the final portion of the ascending limb of the nephron loop.

26.4 Overview of Renal Physiology

1. Nephrons perform three basic tasks: glomerular filtration, tubular secretion, and tubular reabsorption.

26.5 Glomerular Filtration

1. Fluid that is filtered by glomeruli enters the capsular space and is called glomerular filtrate.

2. The filtration membrane consists of the glomerular endothelial cells, basement membrane, and filtration slits between pedicels of podocytes.

3. Most substances in blood plasma easily pass through the glomerular filter. However, blood cells and most proteins normally are not filtered.

4. Glomerular filtrate amounts to up to 180 liters of fluid per day. This large amount of fluid is filtered because the filter is porous and thin, the glomerular capillaries are long, and the capillary blood pressure is high.

5. Glomerular blood hydrostatic pressure (G.B.H.P) promotes filtration; capsular hydrostatic pressure (C.H.P) and blood colloid osmotic pressure (B.C.O.P) oppose filtration. Net filtration pressure (N.F.P) = G.B.H.P - C.H.P - B.C.O.P. N.F.P is about 10 mmHg.

6. Glomerular filtration rate (G.F.R) is the amount of filtrate formed in both kidneys per minute; it is normally 105 to 125 milliliters per minute.

7. Glomerular filtration rate depends on renal autoregulation, neural regulation, and hormonal regulation. Table 26.2 summarizes regulation of G.F.R.

26.6 Tubular Reabsorption and Tubular Secretion

1. Tubular reabsorption is a selective process that reclaims materials from tubular fluid and returns them to the bloodstream. Reabsorbed substances include water, glucose, amino acids, urea, and ions, such as sodium, chloride, potassium, bicarbonate, and phosphate (Table 26.3).

2. Some substances not needed by the body are removed from the blood and discharged into the urine via tubular secretion. Included are ions (K⁺, H⁺, and ammonium, urea, creatinine, and certain drugs.

3. Reabsorption routes include both paracellular (between tubule cells) and transcellular (across tubule cells) routes. The maximum amount of a substance that can be reabsorbed per unit time is called the transport maximum ( T m ).

4. About 80% of water reabsorption is obligatory; it occurs via osmosis, together with reabsorption of solutes, and is not hormonally regulated. The remaining 20% is facultative water reabsorption, which varies according to body needs and is regulated by antidiuretic hormone.

5. Sodium ions are reabsorbed throughout the basolateral membrane via primary active transport.

6. In the proximal convoluted tubule, Na⁺ ions are reabsorbed through the apical membranes via Na⁺-glucose symporters and Na⁺-H⁺ anti-porters; water is reabsorbed via osmosis; Cl⁻, K⁺, Ca²⁺, Mg²⁺, and urea are reabsorbed via passive diffusion; and ammonia and ammonium are secreted.

7. The nephron loop reabsorbs 25% of the filtered Na⁺, K⁺, Ca²⁺, and bicarbonate; 35% of the filtered Cl⁻; and 15% of the filtered water.

8. The distal convoluted tubule reabsorbs sodium and chloride ions via Na⁺-Cl⁻ symporters.

9. In the collecting duct, principal cells reabsorb Na⁺ and secrete K⁺; intercalated cells reabsorb K⁺ and bicarbonate and secrete H⁺.

10. Angiotensin 2, aldosterone, antidiuretic hormone, atrial natriuretic peptide, and parathyroid hormone regulate solute and water reabsorption, as summarized in Table 26.4.

26.7 Production of Dilute and Concentrated Urine

1. In the absence of antidiuretic hormone (A.D.H), the kidneys produce dilute urine; renal tubules absorb more solutes than water.

2. In the presence of A.D.H, the kidneys produce concentrated urine; large amounts of water are reabsorbed from the tubular fluid into interstitial fluid, increasing solute concentration of the urine.

3. The countercurrent multiplier establishes an osmotic gradient in the interstitial fluid of the renal medulla that enables production of concentrated urine when A.D.H is present.

26.8 Evaluation of Kidney Function

1. A urinalysis is an analysis of the volume and physical, chemical, and microscopic properties of a urine sample. Table 26.5 summarizes the principal physical characteristics of normal urine.

2. Chemically; normal urine contains about 95% water and 5% solutes. The solutes normally include urea, creatinine, uric acid, urobilinogen, and various ions.

3. Table 26.6 lists several abnormal components that can be detected in a urinalysis, including albumin, glucose, red and white blood cells, ketone bodies, bilirubin, excessive urobilinogen, casts, and microbes.

4. Renal clearance refers to the ability of the kidneys to clear (remove) a specific substance from blood.

26.9 Urine Transportation, Storage, and Elimination

1. The ureters are retroperitoneal and consist of a mucosa, muscular layer, and adventitia. They transport urine from the renal pelvis to the urinary bladder, primarily via peristalsis.

2. The urinary bladder is located in the pelvic cavity posterior to the pubic symphysis; its function is to store urine before micturition.

3. The urinary bladder consists of a mucosa with mucosal folds, a muscular layer (detrusor muscle), and an adventitia (serosa over the superior surface).

4. The micturition reflex discharges urine from the urinary bladder via parasympathetic impulses that cause contraction of the detrusor muscle and relaxation of the internal urethral sphincter muscle and via inhibition of impulses in somatic motor neurons to the external urethral sphincter.

5. The urethra is a tube leading from the floor of the urinary bladder to the exterior. Its anatomy and histology differ in females and males. In both sexes, the urethra functions to discharge urine from the body; in males, it discharges semen as well.

26.10 Waste Management in Other Body Systems

1. Besides the kidneys, several other tissues, organs, and processes temporarily confine wastes, transport waste materials for disposal, recycle materials, and excrete excess or toxic substances.

2. Buffers bind excess H⁺, the blood transports wastes, the liver converts toxic substances into less toxic ones, the lungs exhale C-O₂, sweat glands help eliminate excess heat, and the digestive canal eliminates solid wastes.

1. The kidneys develop from intermediate mesoderm.

2. The kidneys develop in the following sequence: pronephros, mesonephros, and metanephros. Only the metanephros remains and develops into a functional kidney.

26.12 Aging and the Urinary System

1. With aging, the kidneys shrink in size, have a decreased blood flow, and filter less blood.

2. Common problems related to aging include urinary tract infections, increased frequency of urination, urinary retention or incontinence, and renal calculi.

Critical Thinking Questions

1. Imagine the discovery of a new toxin that blocks renal tubule reabsorption but does not affect filtration. Predict the short-term effects of this toxin.

2. For each of the following urinalysis results, indicate whether you should be concerned or not and why: (a) dark yellow urine that is turbid; (b) ammonia-like odor of the urine; (c) presence of

Answers to Figure Questions

26.1 The kidneys, ureters, urinary bladder, and urethra are the components of the urinary system.

26.2 The kidneys are retroperitoneal because they are posterior to the peritoneum.

26.3 Blood vessels, lymphatic vessels, nerves, and a ureter pass through the hilum of the kidney.

26.4 About 1200 mL of blood enters the renal arteries each minute.

26.5 Cortical nephrons have glomeruli in the superficial renal cortex, and their short nephron loops penetrate only into the superficial renal medulla. Juxtamedullary nephrons have glomeruli deep in the renal cortex, and their long nephron loops extend through the renal medulla nearly to the renal papilla.

26.6 This section must pass through the renal cortex because there are no renal corpuscles in the renal medulla.

26.7 Secreted penicillin is being removed from the bloodstream.

26.8 Fenestrations (pores) in of glomerular epithelial cells prevent red blood cells from entering the capsular space because they are too small for red blood cells to pass through.

26.9 Obstruction of the right ureter would increase C.H.P and thus decrease N.F.P in the right kidney; the obstruction would have no effect on the left kidney.

26.10 Auto-means self; tubuloglomerular feedback is an example of autoregulation because it takes place entirely within the kidneys.

26.11 The tight junctions between tubule cells form a barrier that prevents diffusion of transporter, channel, and pump proteins between the apical and basolateral membranes.

26.12 Glucose enters a P.C.T cell via a Na ^{+} -glucose symporter in the apical membrane and leaves via facilitated diffusion through the basolateral membrane. excessive albumin; (d) presence of epithelial cell casts; (e) pH of 5.5; (f) hematuria.

3. Bruce is experiencing sudden, rhythmic waves of pain in his groin area. He has noticed that, although he is consuming fluids, his urine output has decreased. From what condition is Bruce suffering? How is it treated? How can he prevent future episodes?

26.13 The electrochemical gradient promotes movement of Na⁺ into the tubule cell through the apical membrane antiporters.

26.14 Reabsorption of the solutes creates an osmotic gradient that promotes the reabsorption of water via osmosis.

26.15 This is considered secondary active transport because the symporter uses the energy stored in the concentration gradient of Na⁺ between extracellular fluid and the cytosol. No water is reabsorbed here because the thick ascending limb of the nephron loop is virtually impermeable to water.

26.16 In principal cells, aldosterone stimulates secretion of potassium ion and reabsorption of sodium ion by increasing the activity of sodium-potassium pumps and number of leakage channels for sodium ion and potassium ion.

26.17 Aldosterone and atrial natriuretic peptide influence renal water reabsorption along with A.D.H.

26.18 Dilute urine is produced when the thick ascending limb of the nephron loop, the distal convoluted tubule, and the collecting duct reabsorb more solutes than water.

26.19 The high osmolarity of interstitial fluid in the renal medulla is due mainly to Na⁺, Cl⁻, and urea.

26.20 Secretion occurs in the proximal convoluted tubule, the nephron loop, and the collecting duct.

26.21 Lack of voluntary control over micturition is termed urinary incontinence.

26.22 The three subdivisions of the male urethra are the prostatic urethra, membranous urethra, and spongy urethra.

26.23 The kidneys start to form during the third week of development.

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