Cuyamaca College Biology The Digestive System and The Urinary System Study Guide

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Cuyamaca College Biology The Digestive System and The Urinary System Study Guide

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Physiology Spring 2020, Professor Fontaine Lecture 23 Study Guide: Chapter 16 The Digestive System 2 and The Urinary System 1 (p597-516 and p491-498) Fill in the blanks in charts or sentences, and answer the questions as you read to prepare for class. Completion of the study guides will count towards participation points. 1. List the three sections of the small intestine: 1. 2. 3. What are the two aspects of small intestine motility? 2. 3. Define segmentation: 4. How is segmentation controlled? 5. What are the two functions of segmentation? 6. Why is it advantageous to have a slow propulsion mechanism in the small intestine? Page 1 of 11 7. What does the motility of the intestine look like during short periods of fasting? What are the three phases? 1. 2. 3. 8. What are the two structures that prevent the movement of matter from the large intestine back to the small intestine and how do they function? 9. What are the three categories of membrane spanning proteins found in the brush border that function as membrane bound digestive enzymes? 1. 2. 3. 10. Fill in the table on nutrient digestion Nutrients Enzymes for digesting nutrients Sources of enzymes Site of action of enzymes Action of enzymes Absorbable units of nutrients Carbohydrate Amylase Salivary glands Mouth and mostly body of the stomach Hydrolyzes polysaccarides and alpha limit dextrin (this space intentionally left blank) Exocrine pancreas Small intestine lumen (this space intentionally left blank) Disaccharideases Small intestine epithelial cells Small intestine brush border hydrolyze Monosaccharid disaccharides to es, especially monosaccharides glucose pepsin Stomach chief cells Stomach antrum hydrolyzes (this space protein to peptide intentionally left fragments blank) Trypsin, chymotrypsin, carboxypeptidase Exocrine pancreas Small intestine lumen Attack diferent peptide fragments aminopeptidases Small intestine epithelial cells Small intestine brush border Hydrolyze peptide fragments to amino acids Protein Amino acids and a few small peptides Page 2 of 11 Nutrients Enzymes for digesting nutrients Sources of enzymes Site of action of enzymes Action of enzymes Absorbable units of nutrients Fat lipase Exocrine pancreas Small intestine lumen Hydrolyzes triglycerides to fatty acids and monoglycerides Fatty acids and monoglycerides Bile salts liver Small intestine lumen Emulsify large fat globules for attack by pancreatic lipase (this space intentionally left blank) 11. Fill in the figure on the small intestine absorptive surface: 12. What are the four features of the villas wall, and what are their functions? 1. 2. 3. 4. 13. What are the crypts of Lieberkuhn and what do they secrete? 14. What does it mean that the crypts of Lieberkuhn are “nurseries”? Page 3 of 11 15. Fill in the figure regarding carbohydrate digestion: 16. Fill in the figure regarding protein digestion: Page 4 of 11 17. Fill in the figure regarding fat digestion: Page 5 of 11 18. Fill in the figure of the anatomy of the large intestine: 19. What is the difference between motility in the small intestine and the large intestine? 20. How are feces eliminated from the body? Page 6 of 11 21. What are the benefits of colonic microbes? 1. 2. 3. 4. 5. 6. 22. How does the large intestine absorb water and salt (active or passive or .)? 23. What are the main functions of the kidney, and how are these functions accomplished? 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Page 7 of 11 24. Fill in the following figure on the anatomy of the kidney: 25. What does it mean that the nephron is the functional unit of the kidney? Page 8 of 11 26. Fill in the figure with the details of the nephron: Vascular component Tubular component Combined vascular/tubular component Page 9 of 11 27. Fill in the figure on glomerular filtration GF Urine excretion (eliminated from the body) GF = TR = TS = Page 10 of 11 28. Fill in the figure on the glomerular membrane: 1 2 3 To be filtered, a substance must pass through: 1 2 3 Page 11 of 11 Physiology Spring 2020, Professor Fontaine Lecture 23 Study Guide: Chapter 16 The Digestive System 2 and The Urinary System 1 (p597-516 and p491-498) Fill in the blanks in charts or sentences, and answer the questions as you read to prepare for class. Completion of the study guides will count towards participation points. 1. List the three sections of the small intestine: 1. 2. 3. 2. What are the two aspects of small intestine motility? 3. Define segmentation: 4. How is segmentation controlled? 5. What are the two functions of segmentation? 6. Why is it advantageous to have a slow propulsion mechanism in the small intestine? Page 1 of 11 7. What does the motility of the intestine look like during short periods of fasting? What are the three phases? 1. 2. 3. 8. What are the two structures that prevent the movement of matter from the large intestine back to the small intestine and how do they function? 9. What are the three categories of membrane spanning proteins found in the brush border that function as membrane bound digestive enzymes? 1. 2. 3. 10. Fill in the table on nutrient digestion Nutrients Enzymes for digesting nutrients Sources of enzymes Site of action of enzymes Action of enzymes Absorbable units of nutrients Carbohydrate Amylase Salivary glands Mouth and mostly body of the stomach Hydrolyzes polysaccarides and alpha limit dextrin (this space intentionally left blank) Exocrine pancreas Small intestine lumen (this space intentionally left blank) Disaccharideases Small intestine epithelial cells Small intestine brush border hydrolyze Monosaccharid disaccharides to es, especially monosaccharides glucose pepsin Stomach chief cells Stomach antrum hydrolyzes (this space protein to peptide intentionally left fragments blank) Trypsin, chymotrypsin, carboxypeptidase Exocrine pancreas Small intestine lumen Attack different peptide fragments aminopeptidases Small intestine epithelial cells Small intestine brush border Hydrolyze peptide fragments to amino acids Protein Amino acids and a few small peptides Page 2 of 11 Nutrients Enzymes for digesting nutrients Sources of enzymes Site of action of enzymes Action of enzymes Absorbable units of nutrients Fat lipase Exocrine pancreas Small intestine lumen Hydrolyzes triglycerides to fatty acids and monoglycerides Fatty acids and monoglycerides Bile salts liver Small intestine lumen Emulsify large fat globules for attack by pancreatic lipase (this space intentionally left blank) 11. Fill in the figure on the small intestine absorptive surface: 12. What are the four features of the villas wall, and what are their functions? 1. 2. 3. 4. 13. What are the crypts of Lieberkuhn and what do they secrete? 14. What does it mean that the crypts of Lieberkuhn are “nurseries”? Page 3 of 11 15. Fill in the figure regarding carbohydrate digestion: 16. Fill in the figure regarding protein digestion: Page 4 of 11 17. Fill in the figure regarding fat digestion: Page 5 of 11 18. Fill in the figure of the anatomy of the large intestine: 19. What is the difference between motility in the small intestine and the large intestine? 20. How are feces eliminated from the body? Page 6 of 11 21. What are the benefits of colonic microbes? 1. 2. 3. 4. 5. 6. 22. How does the large intestine absorb water and salt (active or passive or ….)? 23. What are the main functions of the kidney, and how are these functions accomplished? 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Page 7 of 11 24. Fill in the following figure on the anatomy of the kidney: 25. What does it mean that the nephron is the functional unit of the kidney? Page 8 of 11 26. Fill in the figure with the details of the nephron: Vascular component Tubular component Combined vascular/tubular component Page 9 of 11 27. Fill in the figure on glomerular filtration GF Urine excretion (eliminated from the body) GF = TR = TS = Page 10 of 11 28. Fill in the figure on the glomerular membrane: 1 2 3 To be filtered, a substance must pass through: 1 2 3 Page 11 of 11 The Urinary System Steve Gschmeissner/Science Source 14 A scanning electron micrograph of glomeruli and blood vessels in the kidney. The glomeruli (yellow) are balls of highly coiled capillaries through which protein-free plasma is fltered as the frst step in urine forma tion. The kidney tubules (stripped away to reveal the glomeruli) collect the fltered fuid and convert it into urine CHAPTER AT A GLANCE 14.1 Kidneys: Functions, Anatomy, and Basic Processes 14.2 Glomerular Filtration 14.3 Tubular Reabsorption 14.4 Tubular Secretion 14.5 Urine Excretion and Plasma Clearance by making selected exchanges with peritubular capillaries that wrap around the tubules. Homeostasis Highlights The survival and proper functioning of cells depend on maintaining stable concentrations of salt, acids, and other electrolytes in the internal fuid environment. Cell survival also depends on continuous removal of toxic metabolic wastes that cells produce as they perform life-sustaining chemical reactions. The kidneys play a major role in maintaining homeostasis by regulating the concentration of many plasma constituents, especially electrolytes and water, and by eliminating all metabolic wastes (except CO2, which is removed by the lungs). As plasma repeatedly flters through the kidneys, they retain constituents of value for the body and eliminate undesirable or excess materials in the urine. Of special importance is the kidneys’ ability to regulate the volume and osmolarity (solute concentration) of the internal fuid environment by controlling salt and water balance. Also crucial is their ability to help regulate pH by controlling elimination of acid and base in the urine. 491 14.1 Kidneys: Functions, Anatomy, and Basic Processes Te composition of the fuid bathing all the cells could be nota­ bly altered by exchanges between the cells and this internal fuid environment if mechanisms did not exist to keep the extracel­ lular fuid (ECF) stable. The kidneys perform a variety of functions aimed at maintaining homeostasis. Te kidneys, in concert with hormonal and neural inputs that control their function, are primarily responsible for maintaining stable volume, electrolyte composition, and osmolarity (solute concentration) of the ECF. By adjusting the quantity of water and various plasma constituents that are either conserved for the body or eliminated in the urine, the kidneys can maintain water and electrolyte balance within the narrow range compatible with life despite a wide range of intake and losses of these constituents through other avenues. Te kidneys not only adjust for varia­ tions in ingestion of water, salt, and other electrolytes, but also adjust urinary output of these ECF constituents to compensate for abnormal losses through heavy sweating, vomiting, diarrhea, or hemorrhage. Tus, as the kidneys do what they can to main­ tain homeostasis, urine composition varies greatly. When the ECF has a surplus of water or a particular electro­ lyte such as salt, the kidneys can eliminate the excess in the urine. If a defcit exists, the kidneys cannot provide additional quantities of the depleted constituent, but they can limit urinary losses of the material in short supply and thus conserve it until the person can take in more of the depleted substance. Accord­ ingly, the kidneys can compensate more efciently for excesses than for defcits. In fact, in some instances the kidneys cannot halt the loss of a valuable substance in the urine, even though the substance may be in short supply. A prime example is a water defcit. Even if a person is not consuming any water, the kidneys must put out about half a liter of water in the urine each day to fll another major role as the body’s “cleaners.” In addition to the kidneys’ important regulatory role in maintaining fuid and electrolyte balance, they are the main route for eliminating potentially toxic metabolic wastes and foreign compounds from the body. Tese wastes cannot be eliminated as solids; they must be excreted in solution, thus obligating the kidneys to produce a minimum volume of around 500 mL of waste-flled urine per day. Because water eliminated in the urine is derived from the blood plasma, a person stranded without water eventually urinates to death: Te plasma volume falls to a fatal level as water is unavoidably removed to accompany the wastes. Overview of Kidney Functions Te kidneys perform the following specifc functions, most of which help preserve con­ stancy of the internal fuid environment and most of which will be discussed in this and the next chapter: 1. Maintaining water (H2O) balance in the body. 492 CHAPTER 14 2. Maintaining the proper osmolarity of body fuids, primarily through regulating H2O balance. Tis function prevents os­ motic fuxes into or out of the cells, which could lead to detri­ mental swelling or shrinking of the cells, respectively. Brain cells are particularly sensitive to volume changes. 3. Regulating the quantity and concentration of most ECF ions, including sodium (Na1), chloride (Cl2), potassium (K1), cal­ cium (Ca21), hydrogen ion (H1), bicarbonate (HCO32), phos­ phate (PO432), sulfate (SO422), and magnesium (Mg21). Even minor fuctuations in the ECF concentrations of some of these electrolytes can have profound infuences. For example, changes in the ECF concentration of K1 can potentially lead to fatal cardiac dysfunction. 4. Maintaining proper plasma volume, which is important in the long-term regulation of arterial blood pressure. Tis func­ tion is accomplished through the kidneys’ regulatory role in salt (NaCl) and H2O balance. 5. Helping maintain the proper acid–base balance of the body by adjusting urinary output of H1 and HCO32. 6. Excreting (eliminating) the end products (wastes) of bodily metabolism, such as urea (from proteins), uric acid (from nu­ cleic acids), creatinine (from muscle creatine), bilirubin (from hemoglobin), and hormone metabolites. If allowed to accumu­ late, many of these wastes are toxic, especially to the brain. 7. Excreting many foreign compounds, such as drugs, food ad­ ditives, pesticides, and other exogenous nonnutritive materials that have entered the body. 8. Producing renin, an enzymatic hormone that triggers a chain reaction important in salt conservation by the kidneys. 9. Producing erythropoietin, a hormone that stimulates red blood cell production (see Chapter 11). 10. Converting vitamin D into its active form (see Chapter 19). The kidneys form urine; the rest of the urinary system carries it to the outside. Te urinary system consists of the urine-forming organs—the kidneys—and the structures that carry the urine from the kid­ neys to the outside for elimination from the body (❙ Figure 14-1a). Te kidneys are a pair of bean-shaped organs about 4 to 5 inches long that lie behind the abdominal cavity (between the abdominal cavity and the back muscles), one on each side of the vertebral column, slightly above the waistline. Each kidney is supplied by a renal artery and a renal vein, which, respectively, enters and leaves the kidney at the medial indentation that gives this organ its beanlike form. Te kidney acts on the plasma fowing through it to produce urine, conserving materials to be retained in the body and eliminating unwanted materials into the urine. Afer urine is formed, it drains into a central collecting cav­ ity, the renal pelvis, located at the medial inner core of each kidney (❙ Figure 14-1b). From there urine is channeled into the ureter, a duct that exits at the medial border close to the renal artery and vein. Tere are two ureters, one carrying urine from each kidney to the single urinary bladder. Te urinary bladder, which temporarily stores urine, is a hollow, distensible, smooth muscle–walled sac. Periodically, Renal cortex Renal pyramid Renal medulla Renal artery Renal vein Renal pelvis Renal artery Renal vein Inferior vena cava Ureter Kidney Aorta (b) Longitudinal section of a kidney Ureter Urinary bladder Cortical nephron Urethra Renal cortex Juxtamedullary nephron (a) Components of the urinary system ❙ Figure 14-1 The urinary system. (a) The pair of kidneys form the urine, which the ureters carry to the urinary bladder. Urine is stored in the bladder and periodi- Renal medulla cally emptied to the exterior through the urethra. (b) The kidney consists of an outer, granular-appearing renal cortex and an inner, striated-appearing renal medulla. The renal pelvis at the medial inner core of the kidney collects urine after it is formed. (c) Each kidney has a million nephrons. The two types of these microscopic functional units are shown here, greatly exaggerated, in a medullary renal pyramid capped by a section of renal cortex. urine is emptied from the bladder to the outside through another tube, the urethra, as a result of bladder contraction. Te urethra in females is straight and short, passing directly from the neck of the bladder to the outside (❙ Figure 14-2a; see also ❙ Figure 20-2, p. 719). In males, the urethra is longer and follows a curving course from the bladder to the outside, pass­ ing through both the prostate gland and the penis (see ❙ Figures 14-1a and 14-2b; see also ❙ Figure 20-1, p. 717). Te male ure­ thra serves the dual function of providing both a route for eliminating urine from the bladder and a passageway for semen from the reproductive organs. Te prostate gland lies below the neck of the bladder and completely encircles the urethra. Prostatic enlargement, which ofen occurs during mid­ dle to older age, can partially or completely occlude the urethra, impeding the fow of urine. Unless otherwise noted, all content on this page is © Cengage Learning. (c) The two types of nephrons, the kidneys’ functional units, greatly blown up Te parts of the urinary system beyond the kidneys merely serve as “ductwork” to transport urine to the outside. Once formed by the kidneys, urine is not altered in composi­ tion or volume as it moves downstream through the rest of the tract. The nephron is the functional unit of the kidney. Each kidney consists of about 1 million microscopic functional units known as nephrons, which are bound together by con­ nective tissue (see ❙ Figure 14-1c). Recall that a functional unit is the smallest unit within an organ capable of performing all of that organ’s functions. Because the main function of the kidneys is to produce urine and, in so doing, maintain constancy in the The Urinary System 493 ECF composition, a nephron is the smallest unit capable of forming urine. Te arrangement of nephrons within the kidneys gives rise to two distinct regions—an outer region called the renal cortex, which looks granular, and an inner region, the renal medulla, which is made up of striated triangles, the renal pyramids (see ❙ Figure 14-1b Prostate gland and c). (an accessory sex gland) Knowledge of the structural arrangement of an individual nephron is essential for understand­ Bulbourethral ing the distinction between the cortical and the glands (accessory medullary regions of the kidney and, more impor­ sex glands) tant, for understanding renal function. Each nephron consists of a vascular component and a tubular component, which are intimately related Urethra structurally and functionally (❙ Figure 14-3). Ureter Smooth muscle of bladder wall Ureteral openings Internal sphincter Urethra Pelvic diaphragm External sphincter External urethral orifice (a) Female ❙ Figure 14-2 Comparison of the urethra in External urethral orifice females and males. (a) In females, the urethra is straight and short. (b) In males, the urethra, which is much longer, passes through the prostate gland (b) Male and penis. Distal tubule Collecting duct Proximal tubule Overview of Functions of Parts of a Nephron Vascular component • Afferent arteriole—carries blood to the glomerulus • Glomerulus—a tuft of capillaries that filters a protein-free plasma into the tubular component • Efferent arteriole—carries blood from the glomerulus • Peritubular capillaries—supply the renal tissue; involved in exchanges with the fluid in the tubular lumen Juxtaglomerular apparatus Efferent arteriole Afferent arteriole Bowman’s capsule Glomerulus Tubular component • Bowman’s capsule—collects the glomerular filtrate • Proximal tubule—uncontrolled reabsorption and secretion of selected substances occur here • Loop of Henle (of juxtamedullary nephrons only; not shown)—establishes an osmotic gradient in the renal medulla that is important in the kidney’s ability to produce urine of varying concentration • Distal tubule and collecting duct— variable, controlled reabsorption of Na+ and H2O and secretion of K+ and H+ occur here; fluid leaving the collecting duct is urine, which enters the renal pelvis Artery Vein Cortex Medulla Peritubular capillaries Loop of Henle Vascular Component of the Nephron Te dominant part of the nephron’s vascular compo­ nent is the glomerulus, a ball-like tuf of capillar­ ies through which part of the water and solutes is fltered from blood passing through (❙ Figure 14-4 and chapter opener photo). Tis fltered To renal pelvis Combined vascular/tubular component • Juxtaglomerular apparatus—produces substances involved in the control of kidney function ❙ Figure 14-3 A nephron. Components of a cortical nephron, the most abundant type of nephron in humans. 494 CHAPTER 14 Unless otherwise noted, all content on this page is © Cengage Learning. Glomerulus Efferent arteriole Steve Gschmeissner/Science Source Afferent arteriole ❙ Figure 14-4 Scanning electron micrograph of a glomerulus and associ­ ated arterioles. FIGURE FOCUS: Compare the diameter of the afferent arteriole and the efferent arteriole. Remember this size discrepancy; it plays a key role in kidney function, as you will learn later in this chapter. fuid, which is almost identical in composition to plasma, then passes through the nephron’s tubular component, where vari­ ous transport processes convert it into urine. On entering the kidney, the renal artery subdivides to ulti­ mately form many small vessels known as aferent arterioles, one of which supplies each nephron. Te aferent arteriole delivers blood to the glomerulus. Te glomerular capillaries rejoin to form another arteriole, the eferent arteriole, through which blood that was not fltered into the tubular component leaves the glomerulus (see ❙ Figures 14-3 and 14-4). Te eferent arterioles are the only arterioles in the body that drain from capillaries. Typically, arterioles break up into capillaries that rejoin to form venules. At the glomerular capillaries, no O2 or nutrients are extracted from the blood for use by the kidney tissues, nor are waste products picked up from the surrounding tissue. Tus, arterial blood enters the glomerular capillaries through the aferent arteriole, and arterial blood leaves the glomerulus through the eferent arteriole. Te eferent arteriole subdivides into a second set of capil­ laries, the peritubular capillaries, which supply the renal tissue with blood and are important in exchanges between the tubular system and blood during conversion of the fltered fuid into urine. Tese peritubular capillaries, as their name implies, are intertwined around the tubular system (peri means “around”). Te peritubular capillaries rejoin to form venules that ulti­ mately drain into the renal vein, by which blood leaves the kidney. Tubular Component of the Nephron Te nephron’s tubu­ lar component is a hollow, fuid-flled tube formed by a single layer of epithelial cells. Even though the tubule is continuous from its beginning near the glomerulus to its ending at the renal pelvis, it is arbitrarily divided into various segments based on dif­ ferences in structure and function along its length (see ❙ Figure 14-3). Te tubular component begins with Bowman’s capsule, an expanded, double-walled “cup” that surrounds the glomerulus to collect fuid fltered from the glomerular capillaries. From Bowman’s capsule, the fltered fuid passes into the proximal tubule, which lies within the cortex and is highly coiled or convoluted throughout much of its course. Te next segment, the loop of Henle, forms a sharp U-shaped or hairpin loop that dips into the renal medulla. Te descending limb of the loop of Henle plunges from the cortex into the medulla; the ascending limb traverses back up into the cortex. Te ascending limb returns to the glomerular region of the same nephron, where it passes through the fork formed by the aferent and eferent arterioles. Both the tubular and the vascular cells at this point are specialized to form the juxtaglomerular apparatus, a structure that lies next to the glomerulus (juxta means “next to”). Tis specialized region plays an important role in regulat­ ing kidney function. Beyond the juxtaglomerular apparatus, the tubule again coils tightly to form the distal tubule, which also lies entirely within the cortex. Te distal tubule empties into a collecting duct or tubule, with each collecting duct draining fuid from up to eight separate nephrons. Each collecting duct plunges down through the medulla to empty its fuid contents (now converted into urine) into the renal pelvis. Cortical and Juxtamedullary Nephrons Two types of nephrons—cortical nephrons and juxtamedullary nephrons— are distinguished by the location and length of some of their structures (❙ Figures 14-1 and 14-5). All nephrons originate in the cortex, but the glomeruli of cortical nephrons lie in the outer layer of the cortex, whereas the glomeruli of juxtamed­ ullary nephrons lie in the inner layer of the cortex, next to the medulla. Te presence of all glomeruli and associated Bowman’s capsules in the cortex is responsible for this region’s granular appearance. Tese two nephron types difer most markedly in their loops of Henle. Te hairpin loop of cortical nephrons dips only slightly into the medulla. In contrast, the loop of juxtamedullary nephrons plunges through the entire depth of the medulla. Furthermore, the peritubular capillar­ ies of juxtamedullary nephrons form hairpin vascular loops known as vasa recta (“straight vessels”), which run in close association with the long loops of Henle. In cortical neph­ rons, the peritubular capillaries do not form vasa recta but instead entwine around these nephrons’ short loops of Henle in the same manner as the peritubular capillaries wrap around the proximal and distal tubules in both types of nephrons. As they course through the medulla, the collecting ducts of both cortical and juxtamedullary nephrons run parallel to the ascending and descending limbs of the juxtamedullary neph­ rons’ long loops of Henle and vasa recta. Te parallel arrange­ ment of tubules and vessels in the medulla creates this region’s striated appearance. More important, as you will see, this arrangement—coupled with the permeability and trans­ port characteristics of the long loops of Henle and vasa recta—plays a key role in the kidneys’ ability to produce urine of varying concentrations, depending on the needs of the body. About 80% of the nephrons in humans are of the cortical type. Species with greater urine-concentrating abili­ ties than humans, such as the desert rat, have a greater pro­ portion of juxtamedullary nephrons. The Urinary System 495 Juxtamedullary nephron: long-looped nephron important in establishing the medullary vertical osmotic gradient (20% this type) Cortical nephron: most abundant type of nephron (80% this type) Distal tubule Proximal tubule Glomerulus Bowman’s capsule Distal tubule Proximal tubule Cortex Medulla Descending limb of loop of Henle Ascending limb of loop of Henle Collecting duct Loop of Henle Other nephrons emptying into the same collecting duct Vasa recta To renal pelvis ❙ Figure 14-5 Comparison of juxtamedullary and cortical nephrons. The glomeruli of cortical nephrons lie in the outer cortex, whereas the glomeruli of juxtamedul­ lary nephrons lie in the inner part of the cortex next to the medulla. The loops of Henle of cortical nephrons dip only slightly into the medulla, but the juxtamedullary neph­ rons have long loops of Henle that plunge deep into the medulla. The juxtamedullary nephrons’ peritubular capillaries form hairpin loops known as vasa recta. (For better visualization, the kidney is rotated 90º from its normal position in an upright person, the nephrons are grossly exaggerated in size, and the peritubular capillaries have been omitted, except for the vasa recta.) The three basic renal processes are glomerular fltration, tubular reabsorption, and tubular secretion. Tree basic processes are involved in forming urine: glomerular fltration, tubular reabsorption, and tubular secretion. To aid in visualizing the relationships among these renal processes, it is useful to unwind the nephron schematically, as in ❙ Figure 14-6. Glomerular Filtration As blood fows through the glomeru­ lus, protein-free plasma flters through the glomerular capillar­ ies into Bowman’s capsule. Normally, about 20% of the plasma that enters the glomerulus is fltered. Tis process, known as glomerular fltration, is the frst step in urine formation. On average, 125 mL of glomerular fltrate (fltered fuid) are formed collectively through all the glomeruli each minute. Tis amounts to 180 liters (about 47.5 gallons) each day. Considering that the 496 CHAPTER 14 average plasma volume in an adult is 2.75 liters, this means that the kidneys flter the entire plasma volume about 65 times per day. If everything fltered passed out in the urine, the total plasma volume would be urinated in less than half an hour! Tis does not happen, however, because the kidney tubules and peritubular capillaries are intimately related throughout their lengths so that the tubular cells can transfer materials as needed between the fuid inside the tubules and the blood within the peritubular capillaries. Tubular Reabsorption As the fltrate fows through the tubules, substances of value to the body are returned to the peritubular capillary plasma. Tis selective movement of sub­ stances from inside the tubule (the tubular lumen) into the blood is called tubular reabsorption. Reabsorbed substances are not lost from the body in the urine but instead are carried by the peritubular capillaries to the venous system and then to Unless otherwise noted, all content on this page is © Cengage Learning. Afferent arteriole Efferent arteriole 80% of the plasma that enters the glomerulus is not filtered and leaves through the efferent arteriole Glomerulus Bowman’s capsule GF 20% of the plasma that enters the glomerulus is filtered TR TS Peritubular capillary Kidney tubule (entire length, uncoiled) Urine Excretion Urine excretion is the elimination of sub­ stances from the body in the urine. It is not a separate process but the result of the frst three processes. All plasma constitu­ ents fltered or secreted but not reabsorbed remain in the tubules and pass into the renal pelvis to be excreted as urine and eliminated from the body (❙ Figure 14-6). (Do not confuse excretion with secretion.) Note that anything fltered and sub­ sequently reabsorbed, or not fltered at all, enters the venous blood from the peritubular capillaries and thus is conserved for the body instead of being excreted in the urine, despite passing through the kidneys. The Big Picture of the Basic Renal Processes Glomeru­ To venous system (conserved for the body) Urine excretion (eliminated from the body) GF = Glomerular filtration—nondiscriminant filtration of a proteinfree plasma from the glomerulus into Bowman’s capsule TR = Tubular reabsorption—selective movement of filtered substances from the tubular lumen into the peritubular capillaries TS = Tubular secretion—selective movement of nonfiltered substances from the peritubular capillaries into the tubular lumen ❙ Figure 14-6 Basic renal processes. Anything fltered or secreted but not reab­ sorbed is excreted in the urine and lost from the body. Anything fltered and sub­ sequently reabsorbed, or not fltered at all, enters the venous blood and is saved for the body. FIGURE FOCUS: Name two ways that substances can enter and two ways that substances can leave the tubular fluid. the heart to be recirculated. Of the 180 liters of plasma fltered per day, 178.5 liters, on average, are reabsorbed. Te remaining 1.5 liters of fltered fuid lef in the tubules pass into the renal pelvis to be eliminated as urine. In general, substances the body needs to conserve are selectively reabsorbed, whereas unwanted substances that must be eliminated stay in the tubular fuid, which becomes urine afer tubular modifcation is complete. Tubular Secretion Te third renal process, tubular secre­ tion, is the selective transfer of substances from the peritubular capillary blood into the tubular lumen. It provides a second route for substances to enter the renal tubules from the blood, the frst being by glomerular fltration. Only about 20% of the plasma fowing through the glomerular capillaries is fltered into Bowman’s capsule; the remaining 80% fows on through the eferent arteriole into the peritubular capillaries. Tubular secretion provides a mechanism for more rapidly eliminating selected substances from the plasma by extracting an additional Unless otherwise noted, all content on this page is © Cengage Learning. quantity of a particular substance from the 80% of unfltered plasma in the peritubular capillaries and adding it to the quan­ tity of the substance already present in the tubule as a result of fltration. lar fltration is largely an indiscriminate process. With the excep­ tion of blood cells and plasma proteins, all constituents within the blood—H2O, nutrients, electrolytes, wastes, and so on— nonselectively enter the tubular lumen as a bulk unit during fltration—that is, of the 20% of the plasma fltered at the glom­ erulus, everything in that part of the plasma enters Bowman’s capsule except for the plasma proteins. Te highly discriminat­ ing tubular processes then work on the fltrate to return to the blood a fuid of the composition and volume necessary to main­ tain constancy of the internal fuid environment. Te unwanted fltered material is lef behind in the tubular fuid to be excreted as urine. Glomerular fltration can be thought of as pushing a part of the plasma, with all its essential components and those that need to be eliminated from the body, onto a tubular “con­ veyor belt” that terminates at the renal pelvis, which is the col­ lecting point for urine within the kidney. All plasma constituents that enter this conveyor belt and are not subsequently returned to the plasma by the end of the line are spilled out of the kidney as urine. It is up to the tubular system to salvage by reabsorption the fltered materials that need to be preserved for the body while leaving behind substances that must be excreted. In addi­ tion, some substances not only are fltered, but also are secreted onto the tubular conveyor belt, so the amounts of these sub­ stances excreted in the urine are greater than the amounts that were fltered. For many substances, these renal processes are subject to physiologic control. Tus, the kidneys handle each constituent in the plasma by a particular combination of fltra­ tion, reabsorption, and secretion. Te kidneys act only on the plasma, yet the ECF consists of both plasma and interstitial fuid. Te interstitial fuid is the true internal fuid environment of the body because it is the only component of the ECF that comes into direct contact with the cells. However, because of the free exchange between plasma and interstitial fuid across the capillary walls (with the exception of plasma proteins), interstitial fuid composition refects the composition of plasma. Tus, by performing their regulatory and excretory roles on plasma, the kidneys maintain the proper interstitial fuid environment for optimal cell func­ tion. Most of the rest of this chapter is devoted to considering how the basic renal processes are accomplished and the mechaThe Urinary System 497 Afferent arteriole Capillary pore Endothelial or fenestration cell Efferent arteriole Lumen of glomerular capillary 1 Glomerulus Lumen of glomerular capillary Bowman’s capsule 2 Endothelial cell Lumen of Bowman’s capsule Outer layer of Bowman’s capsule Basement membrane 3 Basement membrane Lumen of Bowman’s capsule Podocyte foot process Inner layer of Bowman’s capsule (podocytes) Filtration slit Proximal convoluted tubule Capillary pore or fenestration Filtration Podocyte slit foot process Basement membrane To be filtered, a substance must pass through nisms by which they are carefully regulated to help maintain homeostasis. Check Your Understanding 14.1 1. Name and describe the functional unit of the kidneys. 2. Schematically draw an “unwound” nephron and use arrows to show the direction of movement between its vascular and tubular components during the three basic renal processes. 1 the pores between and the fenestrations within the endothelial cells of the glomerular capillary 2 an acellular basement membrane 3 the filtration slits between the foot processes of the podocytes in the inner layer of Bowman’s capsule ❙ Figure 14-7 Layers of the glomerular membrane. 3. Distinguish between cortical and juxtamedullary nephrons. 14.2 Glomerular Filtration Fluid fltered from the glomerulus into Bowman’s capsule must pass through the three layers that make up the glomerular membrane (❙ Figure 14-7): (1) the glomerular capillary wall, (2) the basement membrane, and (3) the inner layer of Bow­ man’s capsule. Collectively, these layers function as a fne molecular sieve that retains the blood cells and plasma proteins but permits H2O and solutes of small molecular dimension to flter through. Let us consider each layer in more detail. The glomerular membrane is considerably more permeable than capillaries elsewhere. Te glomerular capillary wall consists of a single layer of fat­ tened endothelial cells. It is perforated by many large pores that make it more than 100 times more permeable to H2O and sol­ utes than capillaries elsewhere in the body. Te glomerular capillaries not only have the traditional pores found between the endothelial cells that form the capillary walls, but the endo­ thelial cells themselves also are perforated by large holes or fenestrations (see p. 353). 498 CHAPTER 14 Te basement membrane is an acellular (lacking cells) gelat­ inous layer composed of collagen and glycoproteins that is sandwiched between the glomerulus and Bowman’s capsule. Te collagen provides structural strength, and the glycoproteins discourage the fltration of small plasma proteins. Te larger plasma proteins cannot be fltered because they cannot ft through the capillary pores, but the pores are just barely large enough to permit passage of albumin, the smallest of plasma proteins. However, because the glycoproteins are negatively charged, they repel albumin and other plasma proteins, which are also negatively charged. Terefore, plasma proteins are almost completely excluded from the fltrate, with less than 1% of the albumin molecules escaping into Bowman’s capsule. Te small proteins that do slip into the fltrate are picked up by the proximal tubule by receptor-mediated endocytosis (see p. 31), then degraded into constituent amino acids that are returned to the blood. Tus, urine is normally protein free. Some renal diseases characterized by excessive albu­ min in the urine (albuminuria) are the result of dis­ ruption of the negative charges within the basement membrane, which makes the glomerular membrane more permeable to albumin even though the size of the capillary pores remains constant. (Urinary loss of proteins can also folUnless otherwise noted, all content on this page is © Cengage Learning. A Closer Look at Exercise Physiology ❚ When Protein in the Urine Does Not Mean Kidney Disease U rinAry LoSS oF ProTeinS (moSTLy albumin) usually signifes kidney disease (nephritis). However, a urinary protein loss simi­ lar to that of nephritis often occurs following exercise, but the condi­ tion is harmless, transient, and reversible. The term athletic pseudonephritis (pseudo means “false”) is used to describe this postexercise (after exercise) proteinuria (protein in the urine). Studies indicate that 70% to 80% of athletes have proteinuria after very strenuous exercise. This condition occurs in participants in both noncontact and contact sports, so it does not arise from physical trauma to the kidneys. Usually, only a very small fraction of the plasma proteins that enter the glomerulus is fltered; these fltered plasma proteins are subse­ quently reabsorbed in the tubules, so normally no plasma proteins appear in the urine. Two basic mechanisms can cause proteinuria: (1) increased glomerular permeability with no change in tubular reab­ sorption or (2) impairment of tubular reabsorption. Research has shown that the proteinuria occurring during mild to moderate exer­ cise results from changes in glomerular permeability, whereas the proteinuria occurring during short-term exhaustive exercise is caused by both increased glomerular permeability and tubular dysfunction. This reversible kidney dysfunction is believed to result from circu­ latory and hormonal changes that occur with exercise. Renal blood fow is reduced during exercise as the renal vessels are constricted and blood is diverted to the exercising muscles. This reduction is positively correlated with exercise intensity. With intense exercise, renal blood fow may be reduced to 20% of normal. As a result, glo­ merular blood fow is also reduced, but not to the same extent as renal blood fow, because of autoregulation (see p. 501). Investigators propose that decreased glomerular blood fow enhances diffusion of proteins into the tubular lumen because as the more slowly fowing blood spends more time in the glomerulus, a greater proportion of the plasma proteins have time to escape through the glomerular mem­ brane. Hormonal changes that occur with exercise may also affect glomerular permeability. For example, injection of the kidney hormone renin is a well-recognized way to experimentally induce proteinuria. Plasma renin activity increases during strenuous exercise and may contribute to postexercise proteinuria. Researchers also hypothesize that maximal tubular reabsorption is reached during severe exercise, which could impair protein reabsorption. low exercise, but it is transient and harmless. For further dis­ cussion, see the accompanying boxed feature, ❙ A Closer Look at Exercise Physiology.) Te fnal layer of the glomerular membrane is the inner layer of Bowman’s capsule. It consists of podocytes, octopuslike epi­ thelial cells that encircle the glomerular tuf. A podocyte bears multiple elongated primary foot processes (podo means “foot”; a process is a projection or appendage), each of which has many side branches, or secondary foot processes, protruding from it to the right and to the lef, similar to the fronds of a fern plant. Te secondary foot processes of one podocyte interdigitate with the secondary foot processes of adjacent podocytes as they cup around a glomerular capillary, much as you interlace your fn­ gers when you cup your hands around a ball (❙ Figure 14-8). Te narrow slits between the interdigitating secondary foot pro­ cesses of adjacent podocytes are known as fltration slits, which provide a pathway through which fuid leaving the glomerular capillaries can enter the lumen of Bowman’s capsule. Tus, the route that fltered substances take across the glo­ merular membrane is completely extracellular—frst through capillary pores, then through the acellular basement membrane, and fnally through capsular fltration slits (see ❙ Figure 14-7). Filtration slits Thomas Deerninck/NCMIR/Science Source Cell body of podocyte Primary foot processes Secondary foot processes ❙ Figure 14-8 Bowman’s capsule podocytes with foot processes and fil­ tration slits. Note the fltration slits between the fne secondary foot processes of adjacent podocytes on this scanning electron micrograph. The podocytes and their foot processes encircle the glomerular capillaries. Glomerular capillary blood pressure is the major force that causes glomerular fltration. To accomplish glomerular fltration, a force must drive a part of the plasma in the glomerulus through the openings in the glo­ merular membrane. No local energy is used to move fuid from the plasma across the glomerular membrane into Bowman’s capsule. Passive physical forces similar to those acting across capillaries elsewhere accomplish glomerular fltration. Because the glomerulus is a tuf of capillaries, the same principles of fuid dynamics apply here that cause ultrafltration across other capillaries (see p. 356), except for two important diferences: (1) Te glomerular capillaries are more permeable than capillaries elsewhere, so more fuid is fltered for a given The Urinary System 499 fltration pressure, and (2) the balance of forces across the glo­ merular membrane is such that fltration occurs the entire length of the capillaries. In contrast, the balance of forces in other capillaries shifs so that fltration occurs in the beginning part of the vessel but reabsorption occurs toward the vessel’s end (see ❙ Figure 10-20, p. 356). Forces Involved in Glomerular Filtration Tree physical forces are involved in glomerular fltration: glomerular capillary blood pressure, plasma-colloid osmotic pressure, and Bowman’s capsule hydrostatic pressure. Glomerular capillary blood pressure favors fltration, whereas the two other forces acting across the glomerular membrane oppose fltration, as follows (❙ Table 14-1): 1. Glomerular capillary blood pressure is the fuid (hydro­ static) pressure exerted by the blood within the glomerular capillaries. It ultimately depends on contraction of the heart (the source of energy that produces glomerular fltration) and the resistance to blood fow ofered by the aferent and eferent arterioles. Glomerular capillary blood pressure, at an esti­ mated average value of 55 mm Hg, is higher than capillary blood pressure elsewhere. Te reason for the higher pressure is the larger diameter of the aferent arteriole compared to that of the eferent arteriole (see ❙ Figure 14-4, p. 495). Because blood can fow more rapidly into the glomerulus through the wide aferent arteriole than it can leave through the narrower Glomerular Filtration Rate As can be seen in ❙ Table 14-1, Forces Involved in Glomerular Filtration ❙ TABLE 14-1 Force effect Glomerular capillary blood pressure Favors fltration Plasma-colloid osmotic pressure Opposes fltration eferent arteriole, glomerular capillary blood pressure is main­ tained high as a result of blood damming up in the glomerular capillaries. Also, because of the high resistance ofered by the eferent arterioles, blood pressure does not fall along the length of the glomerular capillaries as it does along other cap­ illaries. Tis elevated, nondecremental glomerular blood pres­ sure tends to push fuid out of the glomerulus into Bowman’s capsule along the glomerular capillaries’ entire length, and it is the major force producing glomerular fltration. 2. Plasma-colloid osmotic pressure (pP) is caused by the un­ equal distribution of plasma proteins across the glomerular membrane. Because plasma proteins cannot be fltered, they are in the glomerular capillaries but not in Bowman’s capsule. Ac­ cordingly, the concentration of H2O is higher in Bowman’s cap­ sule than in the glomerular capillaries. Te resulting tendency for H2O to move by osmosis down its concentration gradient from Bowman’s capsule into the glomerulus opposes glomerular fltration. Tis opposing osmotic force averages 30 mm Hg, which is slightly higher than across other capillaries. It is higher because more H2O is fltered out of the glomerular blood, so the concentration of plasma proteins is higher than elsewhere. 3. Bowman’s capsule hydrostatic pressure, the pressure exerted by the fuid in this initial part of the tubule, is estimated to be about 15 mm Hg. Tis pressure, which tends to push fuid out of Bowman’s capsule, opposes the fltration of fuid from the glomerulus into Bowman’s capsule. magnitude (mm Hg) 55 30 the forces acting across the glomerular membrane are not in balance. Te total force favoring fltration is the glomerular capillary blood pressure at 55 mm Hg. Te total of the two forces opposing fltration is 45 mm Hg. Te net diference favoring fltration (10 mm Hg of pressure) is called the net fl­ tration pressure. Tis modest pressure forces large volumes of fuid from the blood through the highly permeable glomerular membrane. Te actual rate of fltration, the glomerular fltra­ tion rate (GFR), depends not only on the net fltration pres­ sure, but also on how much glomerular surface area is available for penetration and how permeable the glomerular membrane is (that is, how “holey” it is). Tese properties of the glomerular membrane are collectively referred to as the fltration coef­ cient (Kf ). Accordingly, GFR 5 Kf 3 net fltration pressure Bowman’s capsule hydrostatic pressure Normally, about 20% of the plasma that enters the glomerulus is fltered at the net fltration pressure of 10 mm Hg, producing collectively through all glomeruli 180 liters of glomerular fl­ trate each day for an average GFR of 125 mL/min in males (160 L/day, 115 mL/min in females). Opposes fltration 15 net fltration pressure (difference between force favoring fltration and forces opposing fltration) 500 CHAPTER 14 Favors fltration 10 Changes in GFr result mainly from changes in glomerular capillary blood pressure. Because the net fltration pressure that accomplishes glomeru­ lar fltration is simply the result of an imbalance of opposing physical forces between the glomerular capillary plasma and Bowman’s capsule fuid, alterations in any of these physical forces can afect the GFR, as discussed next. Unless otherwise noted, all content on this page is © Cengage Learning. Unregulated Influences on the GFR Plasma-colloid Glomerulus osmotic pressure and Bowman’s capsule hydrostatic pressure normally do not vary much and cannot be Afferent arteriole Glomerular Efferent arteriole regulated. capillary Arterial blood pressure However, these forces can change blood pressure (increases blood flow pathologically and thus inadver­ into the glomerulus) Net filtration tently afect the GFR. Because pP pressure opposes fltration, a decrease in plasma protein concentration, by reducing this pressure, leads to an increased GFR. Plasma protein concentration might uncontrol­ lably drop, for example, in severely burned patients who lose a GFR large quantity of protein-rich, plasma-derived fuid through the exposed burned surface of their skin. Conversely, when pP ❙ Figure 14-9 Direct effect of arterial blood pressure on the glomerular rises, such as in cases of dehydrating diarrhea, the GFR falls. filtration rate (GFr). Bowman’s capsule hydrostatic pressure can become uncon­ trollably elevated, and fltration subsequently can decrease, given a urinary tract obstruction, such as a kidney stone or aferent arteriolar caliber, thereby adjusting resistance to fow enlarged prostate. Te damming up of fuid behind the obstruc­ through these vessels. For example, if the GFR increases as a tion elevates capsular hydrostatic pressure. direct result of a rise in arterial pressure, the net fltration pres­ sure and GFR can be reduced to normal by constriction of the Controlled Adjustments in the GFR Unlike plasmaaferent arteriole, which decreases the fow of blood into the colloid osmotic pressure and Bowman’s capsule hydrostatic glomerulus (❙ Figure 14-10a). Tis local adjustment lowers glo­ pressure—which may be uncontrollably altered in various dis­ merular blood pressure and GFR to normal. ease states and thereby may inappropriately alter the GFR— Conversely, when GFR falls in the presence of a decline in glomerular capillary blood pressure can be controlled to adjust arterial pressure, glomerular pressure can be increased to nor­ the GFR to suit the body’s needs. Assuming that all other factors mal by vasodilation of the aferent arteriole, which allows more stay constant, as glomerular capillary blood pressure rises, net fltration pressure goes up and the GFR increases correspond­ ingly. Te magnitude of the glomerular capillary blood pressure depends on the rate of blood fow within each of the glomeruli. Glomerulus Te amount of blood fowing into a glomerulus per minute is determined largely by the magnitude of the mean systemic arte­ Afferent arteriole Glomerular rial blood pressure and the resistance ofered by the aferent Efferent arteriole capillary arteriole. If aferent arteriolar resistance increases, less blood blood pressure fows into the glomerulus, decreasing the GFR. Conversely, if Net filtration aferent arteriolar resistance decreases, more blood fows into Vasoconstriction pressure the glomerulus and the GFR increases. Two major control (decreases blood flow mechanisms regulate the GFR, both directed at adjusting glo­ into the glomerulus) merular blood fow by regulating the radius and thus the resis­ tance of the aferent arteriole. Tese mechanisms are (1) autoGFR regulation, which is aimed at preventing spontaneous changes in GFR; and (2) extrinsic sympathetic control, which is aimed (a) Arteriolar vasoconstriction decreases the GFR at long-term regulation of arterial blood pressure. Mechanisms Responsible for Autoregulation of the GFR Because arterial blood pressure is the force that drives blood into the glomerulus, the glomerular capillary blood pres­ sure and, accordingly, the GFR would increase in direct propor­ tion to an increase in arterial pressure if everything else remained constant (❙ Figure 14-9). Similarly, a fall in arterial blood pressure would cause a decline in GFR. Such spontane­ ous, inadvertent changes in GFR are largely prevented by intrinsic regulatory mechanisms initiated by the kidneys them­ selves, a process known as autoregulation (auto means “self ”). Te kidneys can, within limits, maintain a constant blood fow into the glomerular capillaries (and thus a constant glomerular capillary blood pressure and a stable GFR) despite changes in the driving arterial pressure. Tey do so primarily by altering Unless otherwise noted, all content on this page is © Cengage Learning. Glomerulus Afferent arteriole Vasodilation (increases blood flow into the glomerulus) Glomerular capillary blood pressure Efferent arteriole Net filtration pressure GFR (b) Arteriolar vasodilation increases the GFR ❙ Figure 14-10 Adjustments of afferent arteriole caliber to alter the GFr. The Urinary System 501 blood to enter despite the reduction in driving pressure (❙ Fig­ ure 14-10b). Te resultant buildup of glomerular blood volume increases glomerular blood pressure, which in turn brings the GFR back up to normal. Two mechanisms contribute to autoregulation of the GFR: (1) a myogenic mechanism, which responds to changes in pressure within the nephron’s vascular component; and (2) a tubuloglomerular feedback mechanism, which senses changes in salt level in the fuid fowing through the nephron’s tubular component. Te myogenic mechanism is a common property of vascu­ lar smooth muscle (myogenic means “muscle produced”). Ar­ teriolar vascular smooth muscle contracts inherently in re­ sponse to the stretch accompanying increased pressure within the vessel (see p. 348). Accordingly, the aferent arteriole auto­ matically constricts on its own when it is stretched because of an increased arterial driving pressure. Tis response helps limit blood fow into the glomerulus to normal despite the ele­ vated arterial pressure. Conversely, inherent relaxation of an unstretched aferent arteriole when pressure within the vessel is reduced increases blood fow into the glomerulus despite the fall in arterial pressure. ■ Te tubuloglomerular feedback (TGF) mechanism in­ volves the juxtaglomerular apparatus, which is the specialized combination of tubular and vascular cells where the tubule, af­ ter having bent back on itself, passes through the angle formed by the aferent and eferent arterioles as they join the glomeru­ lus (❙ Figure 14-11; see also Figure 14-3, p. 494). Te smooth muscle cells within the wall of the aferent arteriole in this re­ gion are specialized to form granular cells, so called because they contain many secretory granules. Specialized tubular cells ■ in this region are collectively known as the macula densa. Te macula densa cells detect changes in the salt level of the fuid fowing past them through the tubule. If the GFR is increased secondary to an elevation in arterial pressure, more fuid than normal is fltered and fows through the distal tubule. In response to the resultant rise in salt deliv­ ery to the distal tubule, the macula densa cells release ATP and adenosine, both of which act locally as a paracrine on the adja­ cent aferent arteriole, causing it to constrict, thus reducing glomerular blood fow and returning GFR to normal. In the opposite situation, when less salt is delivered to the distal tu­ bule because of a spontaneous decline in GFR accompanying a fall in arterial pressure, less ATP and adenosine are released by the macula densa cells. Te resultant aferent arteriolar vasodi­ lation increases the glomerular fow rate, restoring the GFR to normal. To exert even more exquisite control over tubuloglo­ merular feedback, the macula densa cells also secrete the vaso­ dilator nitric oxide, which puts the brakes on the action of ATP and adenosine at the aferent arteriole. By means of the TGF mechanism, the tubule of a nephron is able to monitor the salt level in the fuid fowing through it and adjust the rate of fltration through the glomerulus of the same nephron ac­ cordingly to keep the early distal tubular fuid and salt delivery constant. Importance of Autoregulation of the GFR Te myo­ genic and tubuloglomerular feedback mechanisms work in unison to autoregulate the GFR within the mean arterial blood Efferent arteriole Efferent arteriole Distal tubule Bowman’s capsule Afferent arteriole Lumen of Bowman’s capsule Endothelial cell Smooth muscle cell Juxtaglomerular apparatus Podocyte Glomerular capillaries Mesangial cell Macula densa Granular cells Distal tubule Juxtaglomerular apparatus Afferent arteriole ❙ Figure 14-11 The juxtaglomerular apparatus. The juxtaglomerular apparatus consists of specialized vascular cells (the granular cells) and specialized tubular cells (the macula densa) at a point where the distal tubule passes through the fork formed by the afferent and efferent arterioles of the same nephron. 502 CHAPTER 14 Unless otherwise noted, all content on this page is © Cengage Learning. pressure range of 80 to 180 mm Hg. Within this wide range, reduced. In the long term, plasma volume must be restored to intrinsic autoregulatory adjustments of aferent arteriolar resis­ normal. One compensation for a depleted plasma volume is tance can compensate for changes in arterial pressure, thus reduced urine output so that more fuid than normal is con­ preventing inappropriate fuctuations in GFR, even though served for the body. Urine output is reduced in part by reducing glomerular pressure tends to change in the same direction as the GFR; if less fuid is fltered, less is available to excrete. arterial pressure. Normal mean arterial pressure is 93 mm Hg, so this range encompasses the transient changes in blood pres­ Role of the Baroreceptor Reflex in Extrinsic Control of the GFR No new mechanism is needed to decrease the sure that accompany daily activities unrelated to the need for the kidneys to regulate H2O and salt excretion, such as the GFR. It is reduced by the baroreceptor refex response to a fall normal elevation in blood pressure accompanying exercise. in blood pressure (❙ Figure 14-12). During this refex, sympa­ Autoregulation is important because unintentional shifs in thetically induced vasoconstriction occurs in most arterioles GFR could lead to dangerous imbalances of fuid, electrolytes, throughout the body (including the aferent arterioles) as a and wastes. Because at least a certain portion of the fltered fuid compensatory mechanism to increase total peripheral resis­ is always excreted, the amount of fuid excreted in the urine is tance. Te aferent arterioles have a1-adrenergic receptors (see automatically increased as the GFR increases. If autoregulation p. 240) and are innervated with sympathetic vasoconstrictor did not occur, the GFR would increase and H2O and solutes would be lost needlessly as a result of the rise in arterial pressure accompanying heavy exercise. If, by contrast, the GFR Short-term Long-term Arterial blood pressure adjustment for adjustment for were too low, the kidneys could not eliminate enough wastes, excess electro­ lytes, and other materials that should be excreted. Autoregulation thus greatly Detection by aortic Arterial arch and carotid sinus blunts the direct efect that changes in blood pressure baroreceptors arterial pressure would otherwise have on GFR and subsequently on H2O, sol­ ute, and waste excretion. Cardiac Sympathetic activity When changes in mean arterial pres­ output sure fall outside the autoregulatory range, these mechanisms cannot compensate. Total Terefore, dramatic changes in mean arte­ Generalized Gen Ge peripheral rial pressure (,80 mm Hg or .180 mm arteriolar arteriola lar vasoconstriction resistance Hg) directly cause the glomerular capil­ lary pressure and, accordingly, the GFR to decrease or increase in proportion to the Afferent arteriolar Af A change in arterial pressure. vvasoconstriction Importance of Extrinsic Sympathetic Control of the GFR In addition to the intrinsic autoregulatory mechanisms designed to keep the GFR constant in the face of fuctuations in arterial blood pressure, the GFR can be changed on purpose— even when the mean arterial blood pressure is within the autoregulatory range—by extrinsic control mechanisms that over­ ride the autoregulatory responses. Extrinsic control of GFR, which is mediated by sympathetic nervous system input to the aferent arterioles, is aimed at long-term regulation of arterial blood pressure. Te parasympathetic nervous system does not exert any infuence on the kidneys. If plasma volume is decreased—for example, by hemor­ rhage—the resulting fall in arterial blood pressure is detected by the arterial carotid sinus and aortic arch baroreceptors, which initiate neural refexes to raise blood pressure toward normal (see p. 367). Tese refex responses are coordinated by the car­ diovascular control center in the brain stem and are mediated primarily through increased sympathetic activity to the heart and blood vessels. Although the resulting increase in both car­ diac output and total peripheral resistance helps raise blood pressure toward normal in the short term, plasma volume is still Unless otherwise noted, all content on this page is © Cengage Learning. Glomerular capillary blood pressure GFR Urine volume Conservation of fluid and salt Arterial blood pressure ❙ Figure 14-12 Baroreceptor reflex influence on GFr in long-term regula­ tion of blood pressure. The Urinary System 503 fbers to a far greater extent than the eferent arterioles are. When the aferent arterioles carrying blood to the glomeruli constrict from increased sympathetic activity, less blood fows into the glomeruli than normal, lowering glomerular capillary blood pressure (see ❙ Figure 14-10a). Te resulting decrease in GFR, in turn, reduces urine volume. In this way, some of the H2O and salt that would otherwise have been lost in the urine are saved for the body, helping restore plasma volume to nor­ mal in the long term so that short-term cardiovascular adjust­ ments that have been made are no longer necessary. Other mechanisms, such as increased tubular reabsorption of H2O and salt, and increased thirst (described more thoroughly elsewhere), also contribute to long-term maintenance of blood pressure, despite a loss of plasma volume, by helping restore plasma volume. Conversely, if blood pressure is elevated (for example, because of an expansion of plasma volume following ingestion of excessive fuid), the opposite responses occur. When the baroreceptors detect a rise in blood pressure, sympathetic vaso­ constrictor activity to the arterioles, including the renal aferent arterioles, is refexly reduced, allowing aferent arteriolar vaso­ dilation to occur. As more blood enters the glomeruli through the dilated aferent arterioles, glomerular capillary blood pres­ sure rises, increasing the GFR (see ❙ Figure 14-10b). As more fuid is fltered, more fuid is available to be eliminated in the urine. A hormonally adjusted reduction in the tubular reab­ sorption of H2O and salt also contributes to the increase in urine volume. Tese two renal mechanisms—increased glo­ merular fltration and decreased tubular reabsorption of H2O and salt—increase urine volume and eliminate the excess fuid from the body. Reduced thirst and fuid intake also help restore an elevated blood pressure to normal in the long term. Podocytes also possess actinlike flaments, whose contrac­ tion or relaxation can, respectively, decrease or increase the number of fltration slits open in the inner membrane of Bow­ man’s capsule by changing the shapes and proximities of the secondary foot processes (❙ Figure 14-13). Te number of slits is a determinant of permeability; the more open slits, the greater the permeability. Contractile activity of the podocytes, which in turn afects permeability and the Kf, is under physiologic con­ trol by poorly understood mechanisms. The kidneys normally receive 20% to 25% of the cardiac output. At the average net fltration pressure and Kf, 20% of the plasma that enters the kidneys is converted into glomerular fltrate. Tat means at an average GFR of 125 mL/min, the total renal plasma fow must average about 625 mL/min. Because 55% of whole blood consists of plasma (that is, hematocrit 5 45; see p. 381), the total fow of blood through the kidneys averages 1140 mL/min. Tis quantity is about 22% of the total cardiac Glomerular capillary lumen Glomerular endothelial cells Glomerular basement membrane The GFr can be infuenced by changes in the fltration coeffcient. Tus far we have discussed changes in the GFR as a result of changes in net fltration pressure. Te rate of glomerular fltra­ tion, however, depends on the fltration coefcient (Kf ) as well as on the net fltration pressure. For years Kf was considered a constant, except in disease situations in which the glomerular membrane becomes leakier than usual. Research to the con­ trary indicates that Kf is subject to change under physiologic control. Both factors on which Kf depends—the surface area and the permeability of the glomerular membrane—can be modifed by contractile activity within the membrane. Te surface area available for fltration within the glomeru­ lus is represented by the inner surface of the glomerular capil­ laries that comes into contact with blood. Each tuf of glomeru­ lar capillaries is held together by mesangial cells (see ❙ Figure 14-11). Tese cells contain contractile elements (that is, actin­ like flaments). Contraction of these mesangial cells closes of a portion of the fltering capillaries, reducing the surface area available for fltration within the glomerular tuf, thus lowering the Kf and decreasing the GFR. Sympathetic stimulation causes the mesangial cells to contract, thereby providing a second mechanism (besides promoting aferent arteriolar vasocon­ striction) by which sympathetic activity can decrease the GFR. 504 CHAPTER 14 Filtration slit (a) Increased Kf on podocyte relaxation Podocyte foot processes Bowman’s capsule lumen (b) Decreased Kf on podocyte contraction ❙ Figure 14-13 Change in the number of open filtration slits caused by podocyte relaxation and contraction. (a) Podocyte relaxation narrows the bases of the fne secondary foot processes, increasing the number of fully open intervening fltration slits spanning a given area. (b) Podocyte contraction fattens the foot process branches and thus decreases the number of intervening fltration slits. (Source: Adapted from Federation Proceedings, vol. 42, pp. 3046–3052, 1983. Reprinted by permission.) Unless otherwise noted, all content on this page is © Cengage Learning. output of 5 liters (5000 mL)/min, although the kidneys com­ pose less than 1% of total body weight. Te kidneys receive such a seemingly disproportionate share of the cardiac output because they must continuously perform their regulatory and excretory functions on the huge volumes of plasma delivered to them to maintain stability in the internal fuid environment. Most of the blood goes to the kid­ neys not to supply the renal tissue but to be adjusted and puri­ fed by the kidneys. On average, 20% to 25% of the blood pumped out by the heart each minute “goes to the cleaners” instead of serving its normal purpose of exchanging materials with the tissues. Only by continuously processing such a large proportion of the blood can the kidneys precisely regulate the volume and electrolyte composition of the internal environ­ ment and adequately eliminate the large quantities of metabolic waste products that are constantly produced. We next consider how the tubules act on this large volume of fltered plasma, frst considering the process of tubular reabsorption. Check Your Understanding 14.2 1. Prepare a table showing the effect and magnitude of the physical forces involved in glomerular fltration. 2. Discuss the mechanisms and importance of autoregulation of the GFR. 3. Discuss the mechanism and importance of extrinsic control of the GFR. 14.3 Tubular reabsorption All plasma constituents except the plasma proteins are indis­ criminately fltered together through the glomerular capillaries. In addition to waste products and excess materials that the body must eliminate, the fltered fuid contains nutrients, elec­ trolytes, and other substances that the body cannot aford to lose in the urine. Indeed, through ongoing glomerular fltra­ tion, greater quantities of these materials are fltered per day than are even present in the entire body. Te essential materials that are fltered are returned to the blood by tubular reabsorp­ tion, the discrete transfer of substances from the tubular lumen into the peritubular capillaries. Tubular reabsorption is tremendous, highly selective, and variable. Tubular reabsorption is a highly selective process. All constitu­ ents except plasma proteins are at the same concentration in the glomerular fltrate as in plasma. In most cases, the quantity reabsorbed of each substance is the amount required to main­ tain the proper composition and volume of the internal fuid environment. In general, the tubules have a high reabsorptive capacity for substances needed by the body and little or no reabsorptive capacity for substances of no value. Accordingly, only a small percentage, if any, of fltered plasma constituents that are useful to the body are present in the urine, most having been reabsorbed and returned to the blood. Of the 125 mL of fuid fltered per minute, typically 124 mL/min are reabsorbed. Considering the magnitude of glomerular fltration, the extent of tubular reabsorption is tremendous: Te tubules typically reabsorb 99% of the fltered water (47 gallons per day), 100% of the fltered sugar (0.4 pound per day), and 99.5% of the fltered salt (3.5 pounds per day). Only excess amounts of essential materials such as electrolytes are excreted in the urine. For the essential plasma constituents regulated by the kidneys, absorp­ tive capacity may vary depending on the body’s needs. In con­ trast, a large percentage of fltered waste products are present in the urine. Tese wastes, which are useless or even potentially harmful to the body if allowed to accumulate, generally are not reabsorbed. Instead, they stay in the tubules to be eliminated in the urine. For example, creatinine, a waste produced during muscle metabolism, is not reabsorbed at all, so 100% of fltered creatinine is excreted in the urine. As H2O and other valuable constituents are reabsorbed, the waste products remaining in the tubular fuid become highly concentrated. Tubular reabsorption involves transepithelial transport. Troughout its length, the tubule wall is one cell thick and is close to a surrounding peritubular capillary (❙ Figure 14-14). Adjacent tubular cells do not come into contact with each other except where they are joined by tight junctions (see p. 61) at their lateral edges near their luminal membranes, which face the tubular lumen. Interstitial fuid lies in the gaps between adja­ cent cells—the lateral spaces—as well as between the tubules and the capillaries. Te basolateral membrane faces the intersti­ tial fuid at the base and lateral edges of the cell. Te tight junc­ tions largely prevent substances from moving between the cells, so materials must pass through the cells to leave the tubular lumen and gain entry to the blood. Transepithelial Transport To be reabsorbed, a substance must go across the following fve distinct barriers (the numbers correspond to the numbered barriers in ❙ Figure 14-14): 1 Leave the tubular fuid by crossing the luminal membrane of the tubular cell. 2 Pass through the cytosol from one side of the tubular cell to the other. 3 Cross the basolateral membrane of the tubular cell to enter the interstitial fuid. 4 Difuse through the interstitial fuid. 5 Penetrate the capillary wall to enter the plasma. Tis entire sequence of steps is known as transepithelial trans­ port (transepithelial means “across the epithelium”). Passive Versus Active Reabsorption Te two types of tubular reabsorption—passive and active—depend on whether local energy expenditure is needed for reabsorbing a particular substance. In passive reabsorption, all steps in the transepithe­ lial transport of a substance from the tubular lumen to the plasma are passive—that is, no energy is spent for the sub­ stance’s net movement, which occurs down electrochemical or The Urinary System 505 Tubular lumen Tubular epithelial cell Interstitial fluid Peritubular capillary Filtrate Plasma Tight junction Luminal membrane Lateral space 1 2 3 4 5 3 Basolateral membrane Capillary wall To be reabsorbed (to move from the filtrate to the plasma), a substance must cross five distinct barriers: 1 the luminal cell membrane 3 the basolateral cell membrane 2 the cytosol 4 the interstitial fluid 5 the capillary wall ❙ Figure 14-14 Steps of transepithelial transport. osmotic gradients. In contrast, active reabsorption takes place if any step in the transepithelial transport of a substance requires energy, even if the four other steps are passive. With active reabsorption, net movement of the substance from the tubular lumen to the plasma occurs against an electrochemical gradient. Substances that are actively reabsorbed are of particu­ lar importance to the body, such as glucose, amino acids, and other organic nutrients, as well as Na1 and other electrolytes, such as PO432. Rather than specifcally describing the reabsorp­ tive process for each of the many fltered substances returned to the plasma, we provide illustrative examples of the general mechanisms involved, afer frst highlighting the unique and important case of Na1 reabsorption. na1 reabsorption depends on the na1–K1 ATPase pump in the basolateral membrane. Sodium reabsorption is unique and complex. Of the total energy spent by the kidneys, 80% is used for Na1 transport, indicating the importance of this process. Unlike most fltered solutes, Na1 is reabsorbed throughout most of the tubule, but this occurs to varying extents in diferent regions. Of the Na1 fltered, 99.5% is normally reabsorbed. Of the Na1 reabsorbed, on average 67% is reabsorbed in the proximal tubule, 25% in the loop of Henle, and 8% in the distal and collecting tubules. Sodium reabsorption plays diferent important roles in each of these segments, as will become apparent as our discussion con­ tinues. Here is a preview of these roles: Sodium reabsorption in the proximal tubule plays a pivotal role in reabsorbing glucose, amino acids, H2O, Cl2, and urea. ■ Sodium reabsorption in the ascending limb of the loop of Henle, along with Cl2 reabsorption, plays a critical role in the ■ 506 CHAPTER 14 kidneys’ ability to produce urine of varying concentrations and volumes, depending on the body’s need to conserve or eliminate H2O. ■ Sodium reabsorption in the distal and collecting tubules is variable and subject to hormonal control. It plays a key role in regulating ECF volume, which is important in long-term con­ trol of arterial blood pressure, and is linked in part to K1 secretion. Sodium is reabsorbed throughout the tubule with the exception of the descending limb of Henle’s loop. You will learn about the signifcance of this exception later. Troughout all Na1reabsorbing tubular segments, the active step in Na1 reabsorp­ tion involves the energy-dependent Na1–K1 ATPase carrier located in the tubular cell’s basolateral membrane (❙ Figure 14-15). Tis carrier is the same Na1–K1 pump present in all cells that actively extrudes Na1 from the cell (see p. 73). As this basolateral pump transports Na1 out of the tubular cell into the lateral space, it keeps the intracellular Na1 concentration low while simultaneously building up the Na1 concentration in the lateral space—that is, it moves Na1 against a concentration gradient. Because the intracellular Na1 concentration is kept low by basolateral pump activity, a concentration gradient is established that favors passive movement of Na1 from its higher concentration in the tubular lumen across the luminal border into the tubular cell. Te nature of the luminal Na1 channels and transport carriers that permit Na1 movement from the lumen into the cell varies for diferent parts of the tubule, but in each case, Na1 movement across the luminal membrane is always a passive step. For example, in the proxi­ mal tubule, Na1 crosses the luminal border by a symport carrier that simultaneously moves Na1 and an organic nutrient such as glucose from the lumen into the cell. You will learn more about Unless otherwise noted, all content on this page is © Cengage Learning. Lumen Na+ Tubular cell Interstitial fluid Peritubular capillary Na+ + Na channel or cotransport carrier K+ ATP K+ Basolateral Na+– K+ pump Na+ Na+ Na+ Lateral space KEY = Active transport of ion against concentration gradient = Passive movement of ion down concentration gradient ❙ Figure 14-15 Sodium reabsorption. The basolateral Na1–K1 pump actively transports Na1 from the tubular cell into the interstitial fuid within the lateral space. This process establishes a concentra­ 90% of the ECF’s osmotic activity. Whenever we speak of Na1 load, we tacitly mean salt load, too, because Cl2 goes along with Na1. (NaCl is common table salt.) Te Na1 load is subject to regulation; Cl2 passively follows along. Recall that osmotic pressure can be thought of loosely as a “pulling” force that attracts and holds H2O (see p. 67). When the Na1 load is above normal and the ECF’s osmotic activity is therefore increased, the extra Na1 “holds” extra H2O, expanding ECF volume. Conversely, when the Na1 load is below normal, thereby decreasing ECF osmotic activity, less H2O than normal can be held in the ECF, so ECF volume is reduced. Because plasma is part of the ECF, the most important result of a change in ECF volume is the matching change in blood pressure with expansion (increased blood pressure) or reduc­ tion (decreased blood pressure) of the plasma volume. Tus, long-term control of arterial blood pressure ultimately depends on Na1­ regulating mechanisms. We now turn attention to these mechanisms. tion gradient for passive movement of Na1 from the lumen into the tubular cell and from the lateral space into the peritubular capillary, accomplishing net transport of Na1 from the tubular lumen into the blood at the expense of energy. this cotransport process shortly. By contrast, in the collecting duct, Na1 crosses the luminal border through a Na1 leak chan­ nel (see p. 58). Once Na1 enters the cell across the luminal border by whatever means, it is actively extruded to the lateral space by the basolateral Na1–K1 pump. Tis step is the same throughout the tubule. Na1 continues to difuse down a con­ centration gradient from its high concentration in the lateral space into the surrounding interstitial fuid and fnally into the peritubular capillary blood. Tus, net transport of Na1 from the tubular lumen into the blood occurs at the expense of energy. First, we consider the importance and mechanism of regu­ lating Na1 reabsorption in the distal portion of the nephron. Aldosterone stimulates na1 reabsorption in the distal and collecting tubules. In the proximal tubule and loop of Henle, a constant percentage of the fltered Na1 is reabsorbed regardless of the Na1 load (the total amount of Na1 in the body fuids, not the concentration of Na1 in the body fuids). In the distal and collecting tubules, the reabsorption of a small percentage of the fltered Na1 is subject to hormonal control. Te extent of this controlled, discretion­ ary reabsorption is inversely related to the magnitude of the Na1 load in the body. If there is too much Na1, little of this controlled Na1 is reabsorbed; instead, it is lost in the urine, thereby removing excess Na1 from the body. If Na1 is depleted, most or all of this controlled Na1 is reabsorbed, conserving for the body Na1 that otherwise would be lost in the urine. Te Na1 load in the body is refected by ECF volume. Sodium and its accompanying anion Cl2 account for more than Unless otherwise noted, all content on this page is © Cengage Learning. Activation of the Renin–Angiotensin– Aldosterone System Te most important and best-known hormonal system involved in regulating Na1 is the renin–angiotensin– aldosterone system (RAAS). Te granular cells of the juxtaglo­ merular apparatus (see ❙ Figure 14-11) secrete an enzymatic hor­ mone, renin, into the blood in response to a fall in NaCl, ECF volume, and arterial blood pressure. Tis function is in addition to the role the macula densa cells of the juxtaglomerular appara­ tus play in autoregulation. Specifcally, the following three inputs to the granular cells increase renin secretion: 1. Te granular cells themselves function as intrarenal barore­ ceptors. Tey are sensitive to pressure changes within the afer­ ent arteriole. When the granular cells detect a fall in blood pressure, they secrete more renin. 2. Te macula densa cells in the tubular portion of the juxta­ glomerular apparatus are sensitive to the NaCl moving past them through the tubular lumen. In response to a fall in NaCl, the macula densa cells trigger increased renin secretion. 3. Te granular cells are innervated by the sympathetic ner­ vous system. When blood pressure falls below normal, the baroreceptor refex increases sympathetic activity. As part of this refex response, increased sympathetic activity stimulates the granular cells to secrete more renin. Tese interrelated signals for increased renin secretion all indi­ cate the need to expand plasma volume to increase arterial pressure to normal in the long term. Trough a complex series of events involving RAAS, increased renin secretion brings about increased Na1 reabsorption by the distal and collecting tubules (with Cl2 passively following Na1’s active movement). Te ultimate beneft of this salt retention is osmotically induced H2O retention, which helps restore plasma volume. The Urinary System 507 Let us examine in further detail the RAAS mechanism that ultimately leads to increased Na1 reabsorption (❙ Figure 14-16). Once secreted into the blood, renin acts as an enzyme to acti­ vate angiotensinogen into angiotensin I. Angiotensinogen is a plasma protein synthesized by the liver and always present in the plasma in high concentration. On passing through the lungs via the pulmonary circulation, angiotensin I is converted into angiotensin II by angiotensin-converting enzyme (ACE), which is abundant in the pulmonary capillaries. ACE is located in small pits in the luminal surface of the pulmonary capillary endothelial cells. Angiotensin II is the main stimulus for secre­ tion of the hormone aldosterone from the adrenal cortex. Te adrenal cortex is an endocrine gland that produces several hor­ mones, each secreted in response to diferent stimuli. Functions of the Renin–Angiotensin–Aldosterone System Two distinct types of tubular cells are located in the distal and collecting tubules: principal cells and intercalated cells. Te more abundant principal cells are the site of action of aldosterone and vasopressin, a H2O-conserving hormone, and thus are involved in Na1 reabsorption and K1 secretion (both regulated by aldosterone) and in H2O reabsorption (regulated by vasopressin). Intercalated cells, by contrast, are concerned with acid–base balance. Among its actions, aldosterone increases Na1 reabsorption by the principal cells of the distal and collecting tubules. It does so by promoting insertion of additional Na1 leak channels into the luminal membranes and additional Na1–K1 pumps into the basolateral membranes of these cells. Te net result is greater Helps correct NaCl / ECF volume / Arterial blood pressure Liver Kidney Lungs H2O conserved Kidney Adrenal cortex Na+ (and CI– ) osmotically hold more H2O in ECF Na+ (and CI– ) conserved Angiotensin­ converting enzyme Renin Circulation Angiotensinogen * Angiotensin I Vasopressin H2O reabsorption by kidney tubules Angiotensin II * Thirst Na+ reabsorption by kidney tubules ( CI– reabsorption follows passively) Aldosterone * Arteriolar vasoconstriction Fluid intake *Other factors related to fluid balance also bring about these responses. ❙ Figure 14-16 renin–angiotensin–aldosterone system (rAAS). The kidneys secrete the enzymatic hormone renin in response to reduced NaCl, ECF volume, and arte­ rial blood pressure. Renin activates angiotensinogen, a plasma protein produced by the liver, into angiotensin I. Angiotensin I is converted into angiotensin II by angiotensin­ converting enzyme (ACE) produced in the lungs. Angiotensin II stimulates the adrenal cortex to secrete the hormone aldosterone, which stimulates Na1 reabsorption by the kidneys. The resulting retention of Na1 exerts an osmotic effect that holds more H2O in the ECF. Together, the conserved Na1 and H2O help correct the original stimuli that activated this hormonal system. Angiotensin II also exerts other effects that help rectify the original stimuli, such as by promoting arteriolar vasoconstriction. FIGURE FOCUS: If a person’s blood pressure falls because of loss of fluid and salt through heavy sweating, summarize the short-term and long-term compensatory measures shown in this figure and Figure 14-12 to help restore blood pressure to normal. 508 CHAPTER 14 Unless otherwise noted, all content on this page is © Cengage Learning. passive movement of Na1 into these distal and collecting tubu­ lar cells from the lumen and increased active pumping of Na1 out of the cells into the plasma—that is, an increase in Na1 reabsorption, with Cl2 following passively. RAAS thus pro­ motes salt retention and a resulting H2O retention and rise in arterial blood pressure. Acting in a negative-feedback fashion, this system alleviates the factors that triggered the initial release of renin—namely, salt depletion, plasma volume reduction, and decreased arterial blood pressure (❙ Figure 14-16). In addition to stimulating aldosterone secretion, angioten­ sin II is a potent constrictor of the systemic arterioles, directly increasing blood pressure by increasing total peripheral resis­ tance (see p. 349). Furthermore, it stimulates thirst (increasing fuid intake) and stimulates vasopressin (increasing H2O reten­ tion by the kidneys), both of which contribute to plasma vol­ ume expansion and elevation of arterial pressure. (As you will learn later, other mechanisms related to long-term regulation of blood pressure and ECF osmolarity are also important in con­ trolling thirst and vasopressin secretion.) Te opposite situation exists when the Na1 load, ECF and plasma volume, and arterial blood pressure are above normal. Under these circumstances, renin secretion is inhibited. Tere­ fore, because angiotensinogen is not activated to angiotensin I and II, aldosterone secretion is not stimulated. Without aldoste­ rone, the small aldosterone-dependent part of Na1 reabsorp­ tion in the distal segments of the tubule does not occur. Instead, this nonreabsorbed Na1 is lost in the urine. In the absence of aldosterone, the ongoing loss of this small percentage of fltered Na1 can rapidly remove excess Na1 from the body. Even though only about 8% of the fltered Na1 depends on aldoste­ rone for reabsorption, this small loss, multiplied many times as the entire plasma volume is fltered through the kidneys many times per day, can lead to a sizable loss of Na1. Te amount of aldosterone secreted, and consequently the relative amount of salt conserved versus salt excreted, varies depending on the body’s needs. For example, an average salt consumer typically excretes nearly 10 g of salt per day in the urine, a heavy salt consumer excretes more, and someone who has lost considerable salt during heavy sweating excretes less urinary salt. With maximum aldosterone secretion, all the fl­ tered Na1 (and, accordingly, all the fltered Cl2) is reabsorbed, so salt excretion in the urine is zero. By varying the amount of renin and aldosterone secreted in accordance with the saltdetermined fuid load in the body, the kidneys can fnely adjust the amount of salt conserved or eliminated. In doing so, they maintain the salt load, ECF volume, and arterial blood pressure at a relatively constant level despite wide variations in salt con­ sumption and abnormal losses of salt-laden fuid. Role of the Renin–Angiotensin–Aldosterone System in Various Diseases Some cases of hyper­ tension (high blood pressure) are the result of abnor­ mal increases in RAAS activity. Tis system is also responsible in part for the fuid retention and edema accompanying con­ gestive heart failure. Because of the failing heart, cardiac out­ put is reduced and blood pressure is low despite a normal or even expanded plasma volume. When a fall in blood pressure is the result of a failing heart rather than a reduced salt and fuid load in the body, the salt- and fuid-retaining refexes triggered by the low blood pressure are inappropriate. Sodium excretion may fall to zero despite continued salt ingestion and accumulation in the body. Te resulting ECF expansion pro­ duces edema and intensifes the congestive heart failure because the weakened heart cannot pump the additional plasma volume. Drugs that Affect Na1 Reabsorption Because their salt-retaining mechanisms are being inappropri­ ately triggered, patients with congestive heart failure are placed on low-salt diets. Ofen they are treated with diuretics, therapeutic agents that cause diuresis (increased urinary output) and thus promote fuid loss from the body. Many of these drugs function by inhibiting tubular reabsorp­ tion of Na1. For example, thiazide diuretics such as hydrochlo­ rothiazide inhibit Na1 reabsorption in the distal tubule. As more Na1 is excreted, more H2O is also lost from the body, helping remove excess ECF. ACE inhibitor drugs, which block the action of ACE, and aldosterone receptor blockers (ARBs), which block the binding of aldosterone with its renal receptors, are both also benefcial in treating hypertension and congestive heart failure. Tese two classes of drugs halt the ultimate salt- and fuid-conserving actions and arteriolar constrictor efects of RAAS. The natriuretic peptides inhibit na1 reabsorption. Whereas RAAS exerts the most powerful infuence on renal handling of Na1, this Na1-retaining, blood pressure–raising system is opposed by a Na1-losing, blood pressure–lowering system that involves the hormones atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Tese peptides produce natriuresis, or excretion of large amounts of sodium in the urine. Te heart, in addition to its pump action, pro­ duces ANP and BNP. As its name implies, ANP is produced in the atrial cardiac muscle cells. BNP was frst discovered in the brain (hence its name) but is produced primarily in the ven­ tricular cardiac muscle cells. ANP and BNP are stored in granules and released when the heart muscle cells are mechan­ ically stretched by an expansion of the circulating plasma volume when ECF volume is increased. Tis expansion, which occurs as a result of Na1 and H2O retention, increases blood pressure. In turn, the NPs promote natriuresis and accompa­ nying diuresis, decreasing the plasma volume, and also directly infuence the cardiovascular system to lower blood pressure (❙ Figure 14-17). Te main action of ANP and BNP is to directly inhibit Na1 reabsorption in the distal parts of the nephron, thus increasing Na1 excretion and accompanying osmotic H2O excretion in the urine. Tey further increase Na1 excretion in the urine by inhibiting two steps of the Na1-conserving RAAS. Te NPs inhibit renin secretion by the kidneys and act on the adrenal cortex to inhibit aldosterone secretion. In addi­ tion, they inhibit the secretion and actions of vasopressin, the H2O-conserving hormone. ANP and BNP also promote natri­ uresis and accompanying diuresis by increasing the GFR. The Urinary System 509 Helps correct NaCl / ECF volume / Arterial blood pressure Atria Ventricles ANP BNP Natriuretic peptides Helps correct We now shif attention to the reabsorption of other fltered sol­ utes. Nevertheless, we continue to discuss Na1 reabsorption because the reabsorption of many other sol­ utes is linked in some way to Na1 reabsorption. Glucose and amino acids are reabsorbed by na1­ dependent secondary active transport. Large quantities of nutritionally impor­ tant organic molecules such as glucose Na+ reabsorption Salt-conserving Smooth muscle Sympathetic and amino acids are fltered each day. by kidney tubules renin–angiotensin– of afferent arterioles nervous system Because these molecules normally are aldosterone system completely reabsorbed into the blood by energy- and Na1-dependent mech­ anisms located in the proximal tubule, Afferent Cardiac Total none of these nutrients are usually arteriolar output peripheral vasodilation resistance excreted in the urine, thus protecting against their loss. Glucose and amino acids are reab­ sorbed by secondary active trans­ GFR Arterial blood port. With this process, specialized pressure symport carriers, such as the sodium + Na excretion and glucose cotransporter (SGLT), in urine + and H O simultaneously transfer both Na1 and Na 2 (osmotic effect) filtered the specifc organic molecule from the H2O excretion lumen into the cell (see ❙ Figure 3-18, in urine p. 76). Within the kidney, SGLT is located only in the proximal tubule. ❙ Figure 14-17 Atrial and brain natriuretic peptide. The cardiac atria secrete the hormone atrial natriuretic pep­ Tis luminal cotransport carrier is the 1 tide (ANP) and the cardiac ventricles secrete brain natriuretic peptide (BNP) in response to being stretched by Na re­ means by which Na1 passively crosses tention, expansion of the ECF volume, and increase in arterial blood pressure. ANP and BNP, in turn, promote natri­ the luminal membrane in the proxi­ uretic, diuretic, and hypotensive effects to help correct the original stimuli that resulted in their release. mal tubule. Once transported into the tubular cell, glucose and amino acids passively difuse down their concen­ Tey dilate the aferent arterioles and constrict the eferent tration gradients across the basolateral membrane into the arterioles, thus raising glomerular capillary blood pressure plasma, facilitated by a carrier, such as the glucose transporter and increasing the GFR. Tey further increase the GFR by (GLUT), which does not depend on energy (see p. 72). relaxing the glomerular mesangial cells, leading to an increase in Kf. As more salt and water are fltered, more salt and water in general, actively reabsorbed substances are excreted in the urine. Besides indirectly lowering blood 1 exhibit a tubular maximum. pressure by reducing the Na load and hence the fuid load in the body, ANP and BNP directly lower blood pressure by All actively reabsorbed substances bind with plasma membrane decreasing cardiac output and reducing total peripheral resis­ carriers that transfer them across the membrane against a con­ tance by inhibiting sympathetic nervous activity to the heart centration gradient. Each carrier is specifc for the types of and blood vessels, respectively. substances it can transport; for example, SGLT can transport Te relative contributions of ANP and BNP in maintain­ glucose but not amino acids. Because a limited number of each ing salt and H2O balance and blood pressure regulation are carrier type is present in the tubular cells, an upper limit exists presently being intensively investigated. A defciency of the on how much of a particular substance can be actively trans­ counterbalancing natriuretic system may underlie some cases ported from the tubular fuid in a given period. Te maximum of long-term hypertension by leaving the powerful Na1reabsorption rate is reached when all of the carriers specifc for conserving system unopposed. Te resulting salt retention, a particular substance are fully occupied or saturated so that especially in association with high salt intake, could expand they cannot handle additional passengers at that time (see ECF volume and elevate blood pressure. p. 71). Tis maximum reabsorption rate is designated as the 510 CHAPTER 14 Unless otherwise noted, all content on this page is © Cengage Learning. Glucose is an actively reabsorbed substance not regulated by the kidneys. Te normal plasma concentration of glucose is 100 mg of glu­ cose for every 100 mL of plasma. Because glucose is freely flter­ able at the glomerulus, it passes into Bowman’s capsule at the same concentration it has in the plasma. Accordingly, 100 mg of glucose are present in every 100 mL of plasma fltered. With 125 mL of plasma normally being fltered each minute (average GFR 5 125 mL/min), 125 mg of glucose pass into Bowman’s capsule with this fltrate every minute. Te quantity of any sub­ stance fltered per minu…