Chapter 26: The Urinary System. An Overview of the Urinary System, p The Kidneys, p. 952

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1 Chapter 26: The Urinary System An Overview f the Urinary System, p. 952 Objective 1. Identify the cmpnents f the urinary system and describe the functins it perfrms. Figure 26-1 The urinary system has three majr functins: (1) excretin, the remval f rganic waste prducts frm bdy fluids, (2) eliminatin, the discharge f these waste prducts int the envirnment, and (3) hmestatic regulatin f the vlume and slute cncentratin f bld plasma. The excretry functins f the urinary system are perfrmed by the tw kidneys rgans that prduce urine, a fluid cntaining water, ins, and small sluble cmpunds. Urine leaving the kidneys flws alng the urinary tract, which cnsists f paired tubes called ureters, t the urinary bladder, a muscular sac fr temprary strage f urine. On leaving the urinary bladder, urine passes thrugh the urethra, which cnducts the urine t the exterir. The urinary bladder and the urethra are respnsible fr the eliminatin f urine, a prcess called urinatin r micturitin. In this prcess, cntractin f the muscular urinary bladder frces urine thrugh the urethra and ut f the bdy. In additin t remving waste prducts generated by cells thrughut the bdy, the urinary system has several ther essential hmestatic functins that are ften verlked, including the fllwing: Regulating bld vlume and bld pressure, by adjusting the vlume f water lst in urine, releasing erythrpietin, and releasing renin. Regulating plasma cncentratins f sdium, ptassium, chlride, and ther ins, by cntrlling the quantities lst in urine and cntrlling calcium in levels thrugh the synthesis f calcitril. Helping t stabilize bld ph, by cntrlling the lss f hydrgen ins and bicarbnate ins in urine. Cnserving valuable nutrients, by preventing their excretin in urine while excreting rganic waste prducts especially nitrgenus wastes such as urea and uric acid. Assisting the liver in detxifying pisns and, during starvatin, deaminating amin acids s that ther tissues can break them dwn. These activities are carefully regulated t keep the cmpsitin f bld within acceptable limits. The Kidneys, p. 952 Objectives 1. Describe the lcatin and structural features f the kidneys. 2. Identify the majr bld vessels assciated with each kidney and trace the path f bld flw thrugh a kidney. 3. Describe the structure f the nephrn and utline the prcesses invlved in the frmatin f urine. Figure 26-2 The kidneys are lcated n either side f the vertebral clumn, between vertebrae T12 and L3. The left kidney lies slightly superir t the right kidney. The superir surface f each kidney is capped by an adrenal gland. The kidneys and adrenal glands lie between the muscles f the drsal bdy wall and the parietal peritneum, in a retrperitneal psitin. The psitin f the kidneys in the abdminal cavity is maintained by (1) the verlying peritneum, (2) cntact with adjacent visceral rgans, and (3) supprting cnnective tissues. Each kidney is prtected and stabilized by three cncentric layers f cnnective tissue: The renal capsule, a layer f cllagen fibers that cvers the uter surface f the entire rgan. The adipse capsule, a thick layer f adipse tissue that surrunds the renal capsule.

2 The renal fascia, a dense, fibrus uter layer that anchrs the kidney t surrunding structures. Cllagen fibers extend utward frm the renal capsule thrugh the adipse capsule t this layer. A typical adult kidney is reddish-brwn and abut 10 cm (4 in.) lng, 5.5 cm (2.2 in.) wide, and 3 cm (1.2 in.) thick. Each kidney weighs abut 150 g (5.25 z). The hilum, a prminent medial indentatin, is the pint f entry fr the renal artery and renal nerves, and the pint f exit fr the renal vein and the ureter. Sectinal Anatmy f the Kidneys Figure 26-3 Figure 26-4 The fibrus renal capsule cvering the uter surface f the kidney als lines the renal sinus, an internal cavity within the kidney. The renal capsule is bund t the uter surfaces f the structures within the renal sinus, stabilizing the psitins f the ureter and f the renal bld vessels and nerves. The kidney itself has an uter crtex and an inner medulla. The renal crtex is the superficial prtin f the kidney, in cntact with the renal capsule. The crtex is reddish brwn and granular. The renal medulla cnsists f 6 t 18 distinct cnical r triangular structures called renal pyramids. The base f each pyramid abuts the crtex, and the tip f each pyramid a regin knwn as the renal papilla prjects int the renal sinus. Each pyramid has a series f fine grves that cnverge at the papilla. Adjacent renal pyramids are separated by bands f crtical tissue called renal clumns, which extend int the medulla. The clumns have a distinctly granular texture, similar t that f the crtex. A renal lbe cnsists f a renal pyramid, the verlying area f renal crtex, and adjacent tissues f the renal clumns. Urine prductin ccurs in the renal lbes. Ducts within each renal papilla discharge urine int a cup-shaped drain called a minr calyx. Fur r five minr calyces merge t frm a majr calyx, and tw r three majr calyces cmbine t frm the renal pelvis, a large, funnelshaped chamber. The renal pelvis, which fills mst f the renal sinus, is cnnected t the ureter, which drains the kidney. Urine prductin begins in micrscpic, tubular structures called nephrns in the crtex f each renal lbe. Each kidney has rughly 1.25 millin nephrns, with a cmbined length f abut 145 km (85 miles). Bld Supply and Innervatin f the Kidneys Figure 26-5 Yur kidneys receive percent f yur ttal cardiac utput. In nrmal, healthy individuals, abut 1200 ml f bld flws thrugh the kidneys each minute. Each kidney receives bld thrugh a renal artery, which riginates alng the lateral surface f the abdminal arta near the level f the superir mesenteric artery. As it enters the renal sinus, the renal artery prvides bld t the segmental arteries. Segmental arteries further divide int a series f interlbar arteries, which radiate utward thrugh the renal clumns between the renal pyramids. The interlbar arteries supply bld t the arcuate arteries, which arch alng the bundary between the crtex and medulla f the kidney. Each arcuate artery gives rise t a number f interlbular arteries, which supply the crtical prtins f the adjacent renal lbes. Branching frm each interlbular artery are numerus afferent arteriles, which deliver bld t the capillaries supplying individual nephrns. Frm the capillaries f the nephrns, bld enters a netwrk f venules and small veins that cnverge n the interlbular veins. The interlbular veins deliver bld t arcuate veins; these in turn empty int interlbar veins, which drain directly int the renal vein; there are n segmental veins. The kidneys and ureters are innervated by renal nerves. Mst f the nerve fibers invlved are sympathetic pstganglinic fibers frm the celiac plexus and the inferir splanchnic nerves. A

3 renal nerve enters each kidney at the hilum and fllws the tributaries f the renal arteries t reach individual nephrns. The sympathetic innervatin (1) adjusts rates f urine frmatin by changing bld flw and bld pressure at the nephrn and (2) stimulates the release f renin, which ultimately restricts lsses f water and salt in the urine by stimulating reabsrptin at the nephrn. The Nephrn Figure 26-6 Each nephrn cnsists f a renal tubule and a renal crpuscle. The renal tubule is a lng tubular passageway which may be 50 mm (1.97 in.) in length. It begins at the renal crpuscle, a spherical structure cnsisting f Bwman s capsule, a cupshaped chamber apprximately 200 in diameter, and a capillary netwrk knwn as the glmerulus. Bld arrives at the renal crpuscle by way f an afferent arterile. This arterile delivers bld t the glmerulus, which cnsists f abut 50 intertwining capillaries. The glmerulus prjects int Bwman s capsule much as the heart prjects int the pericardial cavity. Bld leaves the glmerulus in an efferent arterile and flws int a netwrk f capillaries, the peritubular capillaries, that surrund the renal tubule. These capillaries in turn drain int small venules that return the bld t the venus system. The renal crpuscle is the site where the prcess f filtratin ccurs. In this prcess, bld pressure frces water and disslved slutes ut f the glmerular capillaries and int a chamber the capsular space that is cntinuus with the lumen f the renal tubule. Filtratin prduces an essentially prtein-free slutin, knwn as a filtrate, that is therwise similar t bld plasma. Frm the renal crpuscle, filtrate enters the renal tubule, which is respnsible fr three crucial functins: (1) reabsrbing all the useful rganic nutrients that enter the filtrate, (2) reabsrbing mre than 90 percent f the water in the filtrate, and (3) secreting int the tubule any waste prducts that failed t enter the renal crpuscle thrugh filtratin at the glmerulus. The renal tubule has tw cnvluted (ciled r twisted) segments the prximal cnvluted tubule (PCT) and the distal cnvluted tubule (DCT) separated by a simple U-shaped tube called the lp f Henle. The cnvluted segments are in the crtex, and the lp f Henle extends at least partially int the medulla. Table 26-1 The regins f the nephrn vary by structure and functin. As it travels alng the tubule, the filtrate, nw called tubular fluid, gradually changes in cmpsitin. The changes that ccur and the characteristics f the urine that results vary with the activities under way in each segment f the nephrn. Each nephrn empties int the cllecting system, a series f tubes that carry tubular fluid away frm the nephrn. Cllecting ducts receive this fluid frm many nephrns. Each cllecting duct begins in the crtex and descends int the medulla, carrying fluid t a papillary duct that drains int a minr calyx. Figure 26-7 Nephrns frm different lcatins differ slightly in structure. Rughly 85 percent f all nephrns are crtical nephrns, lcated almst entirely within the superficial crtex f the kidney. In a crtical nephrn, the lp f Henle is relatively shrt, and the efferent arterile delivers bld t a netwrk f peritubular capillaries, which surrund the entire renal tubule. These capillaries drain int small venules that carry bld t the interlbular veins. The remaining 15 percent f nephrns, termed juxtamedullary nephrns, have lng lps f Henle that extend deep int the medulla. In these nephrns, the peritubular capillaries are cnnected t the vasa recta lng, straight capillaries that parallel the lp f Henle.

4 Because they are mre numerus than juxtamedullary nephrns, crtical nephrns perfrm mst f the reabsrptive and secretry functins f the kidneys. Hwever, it is the juxtamedullary nephrns that enable the kidneys t prduce cncentrated urine. Keys The kidneys remve waste prducts frm the bld; they als assist in the regulatin f bld vlume and bld pressure, in levels, and bld ph. Nephrns are the primary functinal units f the kidneys. The Renal Crpuscle Figure 26-8 Each renal crpuscle is in diameter. It includes bth a regin knwn as Bwman s capsule and the capillary netwrk f the glmerulus. Cnnected t the initial segment f the renal tubule, Bwman s capsule frms the uter wall f the renal crpuscle and encapsulates the glmerular capillaries. The glmerulus is surrunded by Bwman s capsule, much as the heart is surrunded by the pericardial cavity. The uter wall f the capsule is lined by a simple squamus parietal epithelium. This layer is cntinuus with the visceral epithelium, which cvers the glmerular capillaries. The capsular space separates the parietal and visceral epithelia. The tw epithelial layers are cntinuus where the glmerular capillaries are cnnected t the afferent arterile and efferent arterile. The visceral epithelium cnsists f large cells with cmplex prcesses, r feet, that wrap arund the specialized lamina densa f the glmerular capillaries. These unusual cells are called pdcytes, and their feet are knwn as pedicels. Materials passing ut f the bld at the glmerulus must be small enugh t pass between the narrw gaps, r filtratin slits, between adjacent pedicels. The glmerular capillaries are fenestrated capillaries that is, their endthelium cntains large-diameter pres. The lamina densa differs frm that fund in the basal lamina f ther capillary netwrks in that it may encircle mre than ne capillary. Special supprting cells that lie between adjacent capillaries play a rle in cntrlling their diameter and thus in the rate f capillary bld flw. Tgether, the fenestrated endthelium, the lamina densa, and the filtratin slits frm the filtratin membrane. During filtratin, bld pressure frces water and small slutes acrss this membrane and int the capsular space. The larger slutes, especially plasma prteins, are excluded. Filtratin at the renal crpuscle is bth effective and passive, but it has ne majr limitatin: In additin t metablic wastes and excess ins, cmpunds such as glucse, free fatty acids, amin acids, vitamins, and ther slutes als enter the capsular space. These ptentially useful materials are recaptured befre filtrate leaves the kidneys; much f the reabsrptin ccurs in the prximal cnvluted tubule. The Prximal Cnvluted Tubule Table 26-1 The prximal cnvluted tubule (PCT) is the first segment f the renal tubule. The entrance t the PCT lies almst directly ppsite the pint where the afferent and efferent arteriles cnnect t the glmerulus. The lining f the PCT is a simple cubidal epithelium whse apical surfaces bear micrvilli. The tubular cells absrb rganic nutrients, ins, water, and plasma prteins (if present) frm the tubular fluid and release them int the peritubular fluid, the interstitial fluid surrunding the renal tubule. Reabsrptin is the primary functin f the PCT, but the epithelial cells can als secrete substances int the lumen. The Lp f Henle The PCT makes an acute bend that turns the renal tubule tward the renal medulla. This turn leads t the lp f Henle, r nephrn lp. The lp f Henle can be divided int a descending limb and an ascending limb.

5 Fluid in the descending limb flws tward the renal pelvis, and that in the ascending limb flws tward the renal crtex. Each limb cntains a thick segment and a thin segment. The thick descending limb has functins similar t thse f the PCT: It pumps sdium and chlride ins ut f the tubular fluid. The effect f this pumping is mst nticeable in the medulla, where the lng ascending limbs f juxtamedullary nephrns create unusually high slute cncentratins in peritubular fluid. The thin segments are freely permeable t water, but nt t slutes; water mvement ut f these segments helps cncentrate the tubular fluid. The Distal Cnvluted Tubule The thick ascending limb f the lp f Henle ends where it frms a sharp angle near the renal crpuscle. The distal cnvluted tubule (DCT), the third segment f the renal tubule, begins there. The initial prtin f the DCT passes between the afferent and efferent arteriles. In sectinal view, the DCT differs frm the PCT in that the DCT has a smaller diameter and its epithelial cells lack micrvilli. The DCT is an imprtant site fr three vital prcesses: (1) the active secretin f ins, acids, drugs, and txins, (2) the selective reabsrptin f sdium ins and calcium ins frm tubular fluid, and (3) the selective reabsrptin f water, which assists in cncentrating the tubular fluid. The Juxtaglmerular Apparatus The epithelial cells f the DCT near the renal crpuscle are taller than thse elsewhere alng the DCT, and their nuclei are clustered tgether. This regin is called the macula densa. The cells f the macula densa are clsely assciated with unusual smth muscle fibers in the wall f the afferent arterile. These fibers are knwn as juxtaglmerular cells. Tgether, the macula densa and juxtaglmerular cells frm the juxtaglmerular apparatus (JGA), an endcrine structure that secretes the hrmne erythrpietin and the enzyme renin. The Cllecting System The distal cnvluted tubule, the last segment f the nephrn, pens int the cllecting system. Individual nephrns drain int a nearby cllecting duct. Several cllecting ducts then cnverge int a larger papillary duct, which in turn empties int a minr calyx. In additin t transprting tubular fluid frm the nephrn t the renal pelvis, the cllecting system adjusts the fluid s cmpsitin and determines the final smtic cncentratin and vlume f urine. Principles f Renal Physilgy, p. 961 Objectives 1. Discuss the majr functins f each prtin f the nephrn and cllecting system. 2. Identify and describe the majr factrs respnsible fr the prductin f urine. 3. Describe the nrmal characteristics, cmpsitin, and slute cncentratins f a representative urine sample. The gal f urine prductin is t maintain hmestasis by regulating the vlume and cmpsitin f bld. This prcess invlves the excretin f slutes specifically, metablic waste prducts. Three rganic waste prducts are ntewrthy: Urea. Urea is the mst abundant rganic waste. Yu generate rughly 21 g f urea each day, mst f it thrugh the breakdwn f amin acids. Creatinine. Creatinine is generated in skeletal muscle tissue thrugh the breakdwn f creatine phsphate, a high-energy cmpund that plays an imprtant rle in muscle cntractin. Yur bdy generates rughly 1.8 g f creatinine each day, and virtually all f it is excreted in urine.

6 Uric Acid. Uric acid is a waste prduct frmed during the recycling f the nitrgenus bases frm RNA mlecules. Yu prduce apprximately 480 mg f uric acid each day. These waste prducts are disslved in the bldstream and can be eliminated nly while disslved in urine. As a result, their remval is accmpanied by an unavidable water lss. The kidneys are usually capable f prducing cncentrated urine with an smtic cncentratin f mosm L, mre than fur times that f plasma. (Methds f reprting slute cncentratins are discussed in a later sectin.) If the kidneys were unable t cncentrate the filtrate prduced by glmerular filtratin, fluid lsses wuld lead t fatal dehydratin in a matter f hurs. The kidneys als ensure that the fluid that is lst des nt cntain ptentially useful rganic substrates that are present in bld plasma, such as sugars r amin acids. These valuable materials must be reabsrbed and retained fr use by ther tissues. Basic Prcesses f Urine Frmatin Table 26-2 T perfrm their functins, the kidneys rely n three distinct prcesses: Filtratin. In filtratin, bld pressure frces water and slutes acrss the wall f the glmerular capillaries and int the capsular space. Slute mlecules small enugh t pass thrugh the filtratin membrane are carried by the surrunding water mlecules. Reabsrptin. Reabsrptin is the remval f water and slutes frm the filtrate, and their mvement acrss the tubular epithelium and int the peritubular fluid. Reabsrptin ccurs after filtrate has left the renal crpuscle. Mst f the reabsrbed materials are nutrients the bdy can use. Whereas filtratin ccurs slely based n size, reabsrptin is a selective prcess invlving either simple diffusin r the activity f carrier prteins in the tubular epithelium. Water reabsrptin ccurs passively, thrugh smsis. Secretin. Secretin is the transprt f slutes frm the peritubular fluid, acrss the tubular epithelium, and int the tubular fluid. Secretin is necessary because filtratin des nt frce all the disslved materials ut f the plasma. Tubular secretin, which prvides a backup prcess fr filtratin, can further lwer the plasma cncentratin f undesirable materials. Secretin is ften the primary methd f excretin fr sme cmpunds, including many drugs. Tgether, these prcesses prduce a fluid that is very different frm ther bdy fluids. Filtratin In filtratin, hydrstatic pressure frces water thrugh membrane pres, and slute mlecules small enugh t pass thrugh thse pres are carried alng. Filtratin ccurs as larger slutes and suspended materials are left behind. In the bdy, the heart pushes bld arund the cardivascular system and generates hydrstatic pressure. Filtratin ccurs acrss the walls f capillaries as water and disslved materials are pushed int the interstitial fluids f the bdy. In sme sites (fr example, the liver), the pres are s large that even plasma prteins can enter the interstitial fluids. At the renal crpuscle, hwever, a specialized filtratin membrane restricts the passage f even the smallest circulating prteins. Reabsrptin and Secretin The prcesses f reabsrptin and secretin at the kidneys invlve a cmbinatin f diffusin, smsis, channel-mediated diffusin, and carrier-mediated transprt. Types f Carrier-Mediated Transprt In previus chapters, we cnsidered fur majr types f carrier-mediated transprt: In facilitated diffusin, a carrier prtein transprts a mlecule acrss the cell membrane withut expending energy. Such transprt always fllws the cncentratin gradient fr the in r mlecule transprted. Active transprt is driven by the hydrlysis f ATP t ADP n the inner membrane surface. Exchange pumps and ther carrier prteins are active alng the kidney

7 tubules. Active transprt mechanisms can perate despite an ppsing cncentratin gradient. In ctransprt, carrier prtein activity is nt directly linked t the hydrlysis f ATP. Instead, tw substrates (ins, mlecules, r bth) crss the membrane while bund t the carrier prtein. The mvement f the substrates always fllws the cncentratin gradient f at least ne f the transprted substances. Ctransprt mechanisms are respnsible fr the reabsrptin f rganic and inrganic cmpunds frm the tubular fluid. Cuntertransprt resembles ctransprt in all respects, except that the tw transprted ins mve in ppsite directins Cuntertransprt mechanisms perate in the PCT, DCT, and cllecting system. Characteristics f Carrier-Mediated Transprt All carrier-mediated prcesses share five features that are imprtant fr an understanding f kidney functin: A Specific Substrate Binds t a Carrier Prtein That Facilitates Mvement acrss the Membrane. A Given Carrier Prtein Typically Wrks in One Directin Only. In facilitated diffusin, that directin is determined by the cncentratin gradient f the substance being transprted. In active transprt, ctransprt, and cuntertransprt, the lcatin and rientatin f the carrier prteins determine whether a particular substance is reabsrbed r secreted. The carrier prtein that transprts amin acids frm the tubular fluid t the cytplasm, fr example, will nt carry amin acids back int the tubular fluid. The Distributin f Carrier Prteins Can Vary amng Prtins f the Cell Surface. Transprt between tubular fluid and interstitial fluid invlves tw steps the material must enter the cell at its apical surface and then leave the cell and enter the peritubular fluid at the cell s baslateral surface. Each step invlves a different carrier prtein. The Membrane f a Single Tubular Cell Cntains Many Types f Carrier Prtein. Each cell can have multiple functins, and a cell that reabsrbs ne cmpund can secrete anther. Carrier Prteins, Like Enzymes, Can Be Saturated. When an enzyme is saturated, further increases in substrate cncentratin have n effect n the rate f reactin. When a carrier prtein is saturated, further increases in substrate cncentratin have n effect n the rate f transprt acrss the cell membrane. Fr any substance, the cncentratin at saturatin is called the transprt maximum r tubular maximum. The saturatin f carrier prteins invlved in tubular secretin seldm ccurs in healthy individuals, but carriers invlved in tubular reabsrptin are ften at risk f saturatin, especially during the absrptive state fllwing a meal. Tm and the Renal Threshld Nrmally, any plasma prteins and nutrients, such as amin acids and glucse, are remved frm the tubular fluid by ctransprt r facilitated diffusin. If the cncentratins f these nutrients rise in the tubular fluid, the rates f reabsrptin increase until the carrier prteins are saturated. A cncentratin higher than the transprt maximum will exceed the reabsrptive abilities f the nephrn, s sme f the material will remain in the tubular fluid and appear in the urine. The transprt maximum thus determines the renal threshld the plasma cncentratin at which a specific cmpund r in begins t appear in the urine. The renal threshld varies with the substance invlved. The renal threshld fr glucse is apprximately 180 mg dl. When plasma glucse cncentratins exceed 180 mg dl, glucse cncentratins in tubular fluid exceed the f the tubular cells, s glucse appears in urine. The presence f glucse in urine is a cnditin called glycsuria.

8 The renal threshld fr amin acids is lwer than that fr glucse; amin acids appear in urine when plasma cn- Tm Tm > > (Tm) centratins exceed 65 mg dl. Plasma amin acid levels cmmnly exceed the renal threshld after yu have eaten a prtein-rich meal, causing sme amin acids t appear in yur urine. This cnditin is termed aminaciduria. Cells f the renal tubule ignre a number f ther cmpunds in the tubular fluid. As water and ther cmpunds are remved, the cncentratins f the ignred materials in the tubular fluid gradually rise. An Overview f Renal Functin Figure 26-9 Table 26-4 Mst regins perfrm a cmbinatin f reabsrptin and secretin, but the balance between the tw prcesses shifts frm ne regin t anther: Filtratin ccurs exclusively in the renal crpuscle, acrss the filtratin membrane. Water and slute reabsrptin ccurs primarily alng the prximal cnvluted tubules, but als elsewhere alng the renal tubule and within the cllecting system. Active secretin ccurs primarily at the prximal and distal cnvluted tubules. The lps f Henle especially the lng lps f the juxtamedullary nephrns and the cllecting system interact t regulate the final vlume and slute cncentratin f the urine. Nrmal kidney functin can cntinue nly as lng as filtratin, reabsrptin, and secretin functin within relatively narrw limits. A disruptin in kidney functin has immediate effects n the cmpsitin f the circulating bld. If bth kidneys are affected, death will ccur within a few days unless medical assistance is prvided. The majr differences between the tw types f nephrn are that the lp f Henle f a crtical nephrn is shrter and des nt extend as far int the medulla as des the lp f Henle f a juxtamedullary nephrn. The lng lp f Henle in a juxtamedullary nephrn extends deep int the renal pyramids, where it plays a vital rle in water cnservatin and the frmatin f cncentrated urine. The smtic cncentratin, r smlarity, f a slutin is the ttal number f slute particles in each liter. Osmlarity is usually expressed in smles per liter (Osm L) r millismles per liter (mosm L). If each liter f a fluid cntains 1 mle f disslved particles, the slute cncentratin is 1 Osm L, r 1000 mosm L. Bdy fluids have an smtic cncentratin f abut 300 mosm L. In cncentratins are ften reprted in milliequivalents per liter (meq L), whereas the cncentratins f large rganic mlecules are usually reprted in grams r milligrams per unit vlume f slutin (typically, mg r g per dl). Renal Physilgy: Filtratin at the Glmerulus, p. 965 Objective 1. List and describe the factrs that influence filtratin pressure and the rate f filtrate frmatin. Filtratin ccurs in the renal crpuscle as fluids mve acrss the wall f the glmerulus and int the capsular space. The prcess f glmerular filtratin invlves passage acrss a filtratin membrane, which has three cmpnents: (1) the capillary endthelium, (2) the lamina densa, and (3) the filtratin slits. Glmerular capillaries are fenestrated capillaries with pres ranging frm 60 t 100 nm (0.06 t ) in diameter. These penings are small enugh t prevent the passage f bld cells, but they are t large t restrict the diffusin f slutes, even thse the size f plasma prteins. The lamina densa is mre selective: Only small plasma prteins, nutrients, and ins can crss it. The filtratin slits are the finest filters f all. Their gaps are nly 6 9 nm wide, which is small enugh t prevent the passage f mst small plasma prteins. Filtratin Pressures

9 The primary factr invlved in glmerular filtratin is basically the same as that gverning fluid and slute mvement acrss capillaries thrughut the bdy: the balance between hydrstatic pressure (fluid pressure) and cllid smtic pressure (pressure due t materials in slutin) n either side f the capillary walls. Hydrstatic Pressure The glmerular hydrstatic pressure (GHP) is the bld pressure in the glmerular capillaries. This pressure tends t push water and slute mlecules ut f the plasma and int the filtrate. The GHP is significantly higher than capillary pressures elsewhere in the systemic circuit, due t the arrangement f vessels at the glmerulus. Bld pressure is lw in typical systemic capillaries because capillary bld flws int the venus system, where resistance is relatively lw.at the glmerulus, bld leaving the glmerular capillaries flws int an efferent arterile, whse diameter is smaller than that f the afferent arterile. The efferent arterile thus ffers cnsiderable resistance, s relatively high pressures are needed t frce bld int it. Glmerular pressures are similar t thse f small arteries, averaging abut 50 mm Hg instead f the 35 mm Hg typical f peripheral capillaries. Glmerular hydrstatic pressure is ppsed by the capsular hydrstatic pressure (CsHP), which tends t push water and slutes ut f the filtrate and int the plasma. This pressure results frm the resistance t flw alng the nephrn and the cnducting system The CsHP averages abut 15 mm Hg. The net hydrstatic pressure (NHP) is the difference between the glmerular hydrstatic pressure, which tends t push water and slutes ut f the bldstream, and the capsular hydrstatic pressure, which tends t push water and slutes int the bldstream. Net hydrstatic pressure can be calculated as fllws: Cllid Osmtic Pressure The cllid smtic pressure f a slutin is the smtic pressure resulting frm the presence f suspended prteins. The bld cllid smtic pressure (BCOP) tends t draw water ut f the filtrate and int the plasma; it thus ppses filtratin. Over the entire length f the glmerular capillary bed, the BCOP averages abut 25 mm Hg. Figure Filtratin Pressure The filtratin pressure (FP) at the glmerulus is the difference between the hydrstatic pressure and the cllid smtic pressure acting acrss the glmerular capillaries This is the average pressure frcing water and disslved materials ut f the glmerular capillaries and int the capsular spaces. Prblems that affect filtratin pressure can seriusly disrupt kidney functin and cause a variety f clinical signs and symptms. The Glmerular Filtratin Rate The glmerular filtratin rate (GFR) is the amunt f filtrate the kidneys prduce each minute. Each kidney cntains abut sme 64 square feet f filtratin surface, and the GFR averages an astunding 125 ml per minute. This means that rughly 10 percent f the fluid delivered t the kidneys by the renal arteries leaves the bldstream and enters the capsular spaces. A creatinine clearance test is ften used t estimate the GFR. When necessary, a mre accurate GFR determinatin can be perfrmed by using the cmplex carbhydrate inulin, which is nt metablized in the bdy and is neither reabsrbed nr secreted by the kidney tubules. In the curse f a single day, the glmeruli generate abut 180 liters (50 gal) f filtrate, rughly 70 times the ttal plasma vlume. But as filtrate passes thrugh the renal tubules, abut 99 percent f it is reabsrbed. The glmerular filtratin rate depends n the filtratin pressure acrss glmerular capillaries. Any factr that alters the filtratin pressure therefre alters the GFR, thereby affecting kidney functin.

10 One f the mst significant factrs is a drp in renal bld pressure. If bld pressure at the glmeruli drps by 20 percent (frm 50 mm Hg t 40 mm Hg), kidney filtratin will cease, because the filtratin pressure will be 0 mm Hg. Cntrl f the GFR Glmerular filtratin is the vital first step essential t all ther kidney functins. If filtratin des nt ccur, waste prducts are nt excreted, ph cntrl is jepardized, and an imprtant mechanism fr regulating bld vlume is lst. Filtratin depends n adequate bld flw t the glmerulus and n the maintenance f nrmal filtratin pressures. Three interacting levels f cntrl stabilize GFR: (1) autregulatin, at the lcal level, (2) hrmnal regulatin, initiated by the kidneys, and (3) autnmic regulatin, primarily by the sympathetic divisin f the autnmic nervus system. Autregulatin f the GFR Autregulatin maintains an adequate GFR despite changes in lcal bld pressure and bld flw. Maintenance f the GFR is accmplished by changing the diameters f afferent arteriles, efferent arteriles, and glmerular capillaries. The mst imprtant regulatry mechanisms stabilize the GFR when systemic bld pressure declines. A reductin in bld flw and a decline in glmerular bld pressure trigger (1) dilatin f the afferent arterile, (2) relaxatin f supprting cells and dilatin f the glmerular capillaries, and (3) cnstrictin f the efferent arterile. This cmbinatin increases bld flw and elevates glmerular bld pressure t nrmal levels. As a result, filtratin rates remain relatively cnstant. The GFR als remains relatively cnstant when systemic bld pressure rises. A rise in renal bld pressure stretches the walls f afferent arteriles, and the smth muscle cells respnd by cntracting. The reductin in the diameter f afferent arteriles decreases glmerular bld flw and keeps the GFR within nrmal limits. Hrmnal Regulatin f the GFR The GFR is regulated by the hrmnes f the renin angitensin system and the natriuretic peptides (ANP and BNP). There are three triggers fr the release f renin by the juxtaglmerular apparatus (JGA): (1) a decline in bld pressure at the glmerulus as the result f a decrease in bld vlume, a fall in systemic pressures, r a blckage in the renal artery r its tributaries; (2) stimulatin f juxtaglmerular cells by sympathetic innervatin; r (3) a decline in the smtic cncentratin f the tubular fluid at the macula densa. These stimuli are ften interrelated. Because the tubular fluid is then in the ascending limb f the lp f Henle lnger, the cncentratin f sdium and chlride ins in the tubular fluid reaching the macula densa and DCT becmes abnrmally lw. At the nephrn, angitensin II causes the cnstrictin f the efferent arterile, further elevating glmerular pressures and filtratin rates. Angitensin II als directly stimulates the reabsrptin f sdium ins and water at the PCT. At the adrenal glands, angitensin II stimulates the secretin f aldsterne by the adrenal crtex. The aldsterne then accelerates sdium reabsrptin in the DCT and crtical prtin f the cllecting system. In the CNS, angitensin II (1) causes the sensatin f thirst; (2) triggers the release f antidiuretic hrmne (ADH), stimulating the reabsrptin f water in the distal prtin f the DCT and the cllecting system; and (3) increases sympathetic mtr tne, mbilizing the venus reserve, increasing cardiac utput, and stimulating peripheral vascnstrictin. In peripheral capillary beds, angitensin II causes a brief but pwerful vascnstrictin f arteriles and precapillary sphincters, elevating arterial pressures thrughut the bdy. The cmbined effect is an increase in systemic bld vlume and bld pressure and the restratin f nrmal GFR. If bld vlume rises, the GFR increases autmatically, and this prmtes fluid lsses that help return bld

11 vlume t nrmal levels. If the elevatin in bld vlume is severe, hrmnal factrs further increase the GFR and accelerate fluid lsses in the urine. Natriuretic peptides are released in respnse t the stretching f the walls f the heart by increased bld vlume r bld pressure. These hrmnes are released by the heart; atrial natriuretic peptide (ANP) is released by the atria, and brain natriuretic peptide (BNP) is released by the ventricles. Amng their ther effects, the natriuretic peptides trigger the dilatin f afferent arteriles and cnstrictin f efferent arteriles. This mechanism elevates glmerular pressures and increases the GFR. The natriuretic peptides als increase tubular reabsrptin f sdium ins, and the net result is increased urine prductin and decreased bld vlume and pressure. Autnmic Regulatin f the GFR Mst f the autnmic innervatin f the kidneys cnsists f sympathetic pstganglinic fibers. (The rle f the few parasympathetic fibers in regulating kidney functin is nt knwn.) Sympathetic activatin has ne direct effect n the GFR: It prduces a pwerful vascnstrictin f afferent arteriles, decreasing the GFR and slwing the prductin f filtrate. When the sympathetic divisin alters reginal patterns f bld circulatin, bld flw t the kidneys is ften affected. These changes may be ppsed, with variable success, by autregulatin at the lcal level. At maximal levels f exertin, renal bld flw may be less than 25 percent f nrmal resting levels. Keys Rughly 180 L f filtrate is prduced at the glmeruli each day, and that represents 70 times the ttal plasma vlume. Almst all f that fluid vlume must be reabsrbed t avid fatal dehydratin. Renal Physilgy: Reabsrptin and Secretin, p. 969 Objectives 1. Identify the types f transprt mechanisms fund alng the nephrn and discuss the reabsrptive r secretry functins f each segment f the nephrn and cllecting system. 2. Explain the rle f cuntercurrent multiplicatin in the frmatin f a cncentratin gradient in the renal medulla. 3. Describe hw antidiuretic hrmne and aldsterne influence the vlume and cncentratin f urine. Reabsrptin recvers useful materials that have entered the filtrate, and secretin ejects waste prducts, txins, r ther undesirable slutes that did nt leave the bldstream at the glmerulus. Bth prcesses ccur in every segment f the nephrn except the renal crpuscle, but their relative imprtance changes frm segment t segment. Reabsrptin and Secretin at the PCT Figure The cells f the prximal cnvluted tubule nrmally reabsrb percent f the vlume f the filtrate prduced in the renal crpuscle. The reabsrbed materials enter the peritubular fluid and diffuse int peritubular capillaries. The PCT has five majr functins: Reabsrptin f Organic Nutrients. Under nrmal circumstances, befre the tubular fluid enters the lp f Henle, the PCT reabsrbs mre than 99 percent f the glucse, amin acids, and ther rganic nutrients in the fluid. This reabsrptin invlves a cmbinatin f facilitated transprt and ctransprt. Active Reabsrptin f Ins. The PCT actively transprts several ins, including sdium, ptassium, and bicarbnate ins, plus magnesium, phsphate, and sulfate ins. The in pumps invlved are individually regulated and may be influenced by

12 circulating in r hrmne levels. By absrbing carbn dixide, the PCT indirectly recaptures rughly 90 percent f the bicarbnate ins frm tubular fluid. Bicarbnate is imprtant in stabilizing bld ph. Reabsrptin f Water. The reabsrptive prcesses have a direct effect n the slute cncentratins inside and utside the tubules. The filtrate entering the PCT has the same smtic cncentratin as that f the surrunding peritubular fluid. As transprt activities prceed, the slute cncentratin f tubular fluid decreases, and that f peritubular fluid and adjacent capillaries increases. Osmsis then pulls water ut f the tubular fluid and int the peritubular fluid. Alng the PCT, this mechanism results in the reabsrptin f rughly 108 liters f water each day. Passive Reabsrptin f Ins. As active reabsrptin f ins ccurs and water leaves tubular fluid by smsis, the cncentratin f ther slutes in tubular fluid increases abve that in peritubular fluid. If the tubular cells are permeable t them, thse slutes will mve acrss the tubular cells and int the peritubular fluid by passive diffusin. Urea, chlride ins, and lipid-sluble materials may diffuse ut f the PCT in this way. Such diffusin further reduces the slute cncentratin f the tubular fluid and prmtes additinal water reabsrptin by smsis. Secretin. Active secretin als ccurs alng the PCT. Because the DCT perfrms cmparatively little reabsrptin, we will cnsider secretry mechanisms when we discuss the DCT. Sdium in reabsrptin plays an imprtant rle in all f the freging prcesses. Sdium ins may enter tubular cells by diffusin thrugh leak channels; by the sdium-linked ctransprt f glucse, amin acids, r ther rganic slutes; Na+ Na+ r by cuntertransprt fr hydrgen ins. The reabsrptin f ins and cmpunds alng the PCT invlves many different carrier prteins. Sme peple have an inherited inability t manufacture ne r mre f these carrier prteins and are therefre unable t recver specific slutes frm tubular fluid. The Lp f Henle and Cuntercurrent Multiplicatin Rughly percent f the vlume f filtrate prduced at the glmerulus has been reabsrbed befre the tubular fluid reaches the lp f Henle. In the prcess, useful rganic substrates and many mineral ins have been reclaimed. The lp f Henle reabsrbs rughly half f the water, and twthirds f the sdium and chlride ins, remaining in the tubular fluid. This reabsrptin is perfrmed efficiently accrding t the principle f cuntercurrent exchange. The thin descending limb and the thick ascending limb f the lp f Henle are very clse tgether, separated nly by peritubular fluid. The exchange that ccurs between these segments is called cuntercurrent multiplicatin. Cuntercurrent refers t the fact that the exchange ccurs between fluids mving in ppsite directins: Tubular fluid in the descending limb flws tward the renal pelvis, whereas tubular fluid in the ascending limb flws tward the crtex. Multiplicatin refers t the fact that the effect f the exchange increases as mvement f the fluid cntinues. The tw parallel segments f the lp f Henle have very different permeability characteristics. The thin descending limb is permeable t water but relatively impermeable t slutes. The thick ascending limb, which is relatively impermeable t bth water and slutes, cntains active transprt mechanisms that pump sdium and chlride ins frm the tubular fluid int the peritubular fluid f the medulla. Sdium and chlride are pumped ut f the thick ascending limb and int the peritubular fluid. This pumping actin elevates the smtic cncentratin in the peritubular fluid arund the thin descending limb. The result is an smtic flw f water ut f the thin descending limb and int the peritubular fluid, increasing the slute cncentratin in the thin descending limb.

13 The arrival f the highly cncentrated slutin in the thick ascending limb accelerates the transprt f sdium and chlride ins int the peritubular fluid f the medulla. Slute pumping at the ascending limb leads t higher slute cncentratins in the descending limb, which then result in accelerated slute pumping in the ascending limb. Figure Active transprt at the apical surface mves sdium, ptassium, and chlride ins ut f the tubular fluid. The carrier is called a Na + -K + /2 Cl - transprter, because each cycle f the pump carries a sdium in, a ptassium in, and tw chlride ins int the tubular cell. Ptassium and chlride ins are pumped int the peritubular fluid by ctransprt carriers. Ptassium ins are remved frm the peritubular fluid as the sdium ptassium exchange pump pumps sdium ins ut f the tubular cell. The ptassium ins then diffuse back int the lumen f the tubule thrugh ptassium leak channels. The remval f sdium and chlride ins frm the tubular fluid in the ascending limb elevates the smtic cncentratin f the peritubular fluid arund the thin descending limb. Because the thin descending limb is permeable t water but impermeable t slutes, as tubular fluid travels deeper int the medulla alng the thin descending limb, smsis mves water int the peritubular fluid. Slutes remain behind, s the tubular fluid reaching the turn f the lp f Henle has a higher smtic cncentratin than it did at the start. The pumping mechanism f the thick ascending limb is highly effective: Almst tw-thirds f the sdium and chlride ins that enter it are pumped ut f the tubular fluid befre that fluid reaches the DCT. In ther tissues, differences in slute cncentratin are quickly reslved by smsis. As Na+ and Cl- are remved, the slute cncentratin in the tubular fluid declines. Tubular fluid arrives at the DCT with an smtic cncentratin f nly abut 100 mosm L, ne-third the cncentratin f the peritubular fluid f the renal crtex. The rate f in transprt acrss the thick ascending limb is prprtinal t an in s cncentratin in tubular fluid. Mre sdium and chlride ins are pumped int the medulla at the start f the thick ascending limb, where NaCl cncentratins are highest, than near the crtex. This reginal difference in the rate f in transprt is the basis f the cncentratin gradient within the medulla. The Cncentratin Gradient f the Medulla Nrmally, the maximum slute cncentratin f the peritubular fluid near the turn f the lp f Henle is abut 1200 mosm L. Sdium and chlride ins pumped ut f the lp s ascending limb accunt fr rughly tw-thirds f that gradient (750 mosm L). The rest f the cncentratin gradient results frm the presence f urea. The thick ascending limb f the lp f Henle, the DCT, and the cllecting ducts are impermeable t urea. As water is reabsrbed, the cncentratin f urea gradually rises. The tubular fluid reaching the papillary duct typically cntains urea at a cncentratin f abut 450 mosm L. Because the papillary ducts are permeable t urea, the urea cncentratin in the deepest parts f the medulla als averages 450 mosm L. Benefits f Cuntercurrent Multiplicatin The cuntercurrent mechanism perfrms tw functins: It efficiently reabsrbs slutes and water befre the tubular fluid reaches the DCT and cllecting system. It establishes a cncentratin gradient that permits the passive reabsrptin f water frm the tubular fluid in the cllecting system. This reabsrptin is regulated by circulating levels f antidiuretic hrmne (ADH). Reabsrptin and Secretin at the DCT Figure The cmpsitin and vlume f tubular fluid change dramatically as it flws frm the capsular space t the distal cnvluted tubule.

14 Only percent f the initial filtrate vlume reaches the DCT, and the cncentratins f electrlytes and rganic wastes in the arriving tubular fluid n lnger resemble the cncentratins in bld plasma. Selective reabsrptin r secretin, primarily alng the DCT, makes the final adjustments in the slute cmpsitin and vlume f the tubular fluid. Reabsrptin at the DCT Thrughut mst f the DCT, the tubular cells actively transprt and ut f the tubular fluid. Tubular cells alng the distal prtins f the DCT als cntain in pumps that reabsrb tubular Na + in exchange fr anther catin (usually K + ). The in pump and the channels invlved are cntrlled by the hrmne aldsterne, prduced by the adrenal crtex. Aldsterne stimulates the synthesis and incrpratin f sdium in pumps and sdium channels in cell membranes alng the DCT and cllecting duct. The net result is a reductin in the number f sdium ins lst in urine. Sdium in cnservatin is assciated with ptassium in lss. Prlnged aldsterne stimulatin can therefre prduce hypkalemia, a dangerus reductin in the plasma cncentratin. The secretin f aldsterne and its actins n the DCT and cllecting system are ppsed by the natriuretic peptides (ANP and BNP). The DCT is als the primary site f reabsrptin, a prcess regulated by circulating levels f parathyrid hrmne and calcitril. Secretin at the DCT The bld entering peritubular capillaries still cntains a number f ptentially undesirable substances that did nt crss the filtratin membrane at the glmerulus. The rate f and secretin rises r falls in respnse t changes in their cncentratins in peritubular fluid. The higher their cncentratin in the peritubular fluid, the higher the rate f secretin. Ptassium In Secretin Ptassium ins diffuse int the lumen thrugh ptassium channels at the apical surfaces f the tubular cells. In effect, tubular cells trade sdium ins in the tubular fluid fr excess ptassium ins in bdy fluids. Hydrgen In Secretin Hydrgen in secretin is als assciated with the reabsrptin f sdium. Bth invlve the generatin f carbnic acid by the enzyme carbnic anhydrase. Hydrgen ins generated by the dissciatin f the carbnic acid are secreted by sdium-linked cuntertransprt in exchange fr in the tubular fluid. The bicarbnate ins diffuse int the peritubular fluid and then int the bldstream, where they help prevent changes in plasma ph. Hydrgen in secretin acidifies the tubular fluid while elevating the ph f the bld. Hydrgen in secretin accelerates when the ph f the bld falls as in lactic acidsis, which can develp after exhaustive muscle activity, r ketacidsis, which can develp in starvatin r diabetes mellitus. The cmbinatin f remval and prductin at the kidneys plays an imprtant rle in the cntrl f bld ph. Because ne f the secretry pathways is aldsterne sensitive, aldsterne stimulates secretin. Prlnged aldsterne stimulatin can cause alkalsis, r abnrmally high bld ph. Under these cnditins, the PCT and DCT deaminate amin acids in reactins that strip ff the amin grups The reactin sequence ties up and yields bth ammnium ins. The ammnium ins are then pumped int the tubular fluid by sdium-linked cuntertransprt, and the bicarbnate ins enter the bldstream by way f the peritubular fluid. Tubular deaminatin thus has tw majr benefits: It prvides carbn chains suitable fr catablism, and it generates bicarbnate ins that add t the buffering capabilities f plasma. Reabsrptin and Secretin alng the Cllecting System The cllecting ducts receive tubular fluid frm many nephrns and carry it tward the renal sinus, thrugh the cncentratin gradient in the medulla. The nrmal amunt f water and slute lss in the cllecting system is regulated in tw ways:

15 By aldsterne, which cntrls sdium in pumps alng mst f the DCT and the prximal prtin f the cllecting system. These actins are ppsed by the natriuretic peptides. By ADH, which cntrls the permeability f the DCT and cllecting system t water. The secretin f ADH is suppressed by the natriuretic peptides, and this cmbined with its effects n aldsterne secretin and actin can dramatically increase urinary water lsses. The cllecting system als has ther reabsrptive and secretry functins, many f which are imprtant t the cntrl f bdy fluid ph. Reabsrptin in the Cllecting System Imprtant examples f slute reabsrptin in the cllecting system include the fllwing: Sdium In Reabsrptin. The cllecting system cntains aldsterne-sensitive in pumps that exchange in tubular fluid fr in peritubular fluid. Bicarbnate Reabsrptin. Bicarbnate ins are reabsrbed in exchange fr chlride ins in the peritubular fluid. Urea Reabsrptin. The cncentratin f urea in the tubular fluid entering the cllecting duct is relatively high. The fluid entering the papillary duct generally has the same smtic cncentratin as that f interstitial fluid f the medulla abut 1200 mosm L but cntains a much higher cncentratin f urea. As a result, urea tends t diffuse ut f the tubular fluid and int the peritubular fluid in the deepest prtin f the medulla. Secretin in the Cllecting System The cllecting system is an imprtant site fr the cntrl f bdy fluid ph by means f the secretin f hydrgen r bicarbnate ins. If the ph f the peritubular fluid declines, carrier prteins pump hydrgen ins int the tubular fluid and reabsrb bicarbnate ins that help restre nrmal ph. If the ph f the peritubular fluid rises (a much less cmmn event), the cllecting system secretes bicarbnate ins and pumps hydrgen ins int the peritubular fluid. The net result is that the bdy eliminates a buffer and gains hydrgen ins that lwer the ph. Keys Reabsrptin invlves a cmbinatin f diffusin, smsis, channel-mediated diffusin, and active transprt. Many f these prcesses are independently regulated by lcal r hrmnal mechanisms. The primary mechanism gverning water reabsrptin can be described as water fllws salt. Secretin is a selective, carrier-mediated prcess. The Cntrl f Urine Vlume and Osmtic Cncentratin Figure Urine vlume and smtic cncentratin are regulated thrugh the cntrl f water reabsrptin. Water is reabsrbed by smsis in the prximal cnvluted tubule and the descending limb f the lp f Henle. The water permeabilities f these regins cannt be adjusted, and water reabsrptin ccurs whenever the smtic cncentratin f the peritubular fluid exceeds that f the tubular fluid. The ascending limb f the lp f Henle is impermeable t water, but 1 2 percent f the vlume f water in the riginal filtrate is recvered during sdium in reabsrptin in the distal cnvluted tubule and cllecting system. Because these water mvements cannt be prevented, they represent bligatry water reabsrptin, which usually recvers 85 percent f the vlume f filtrate prduced. The vlume f water lst in urine depends n hw much f the water in the remaining tubular fluid (15 percent f the filtrate vlume, r rughly 27 liters per day) is reabsrbed alng the DCT and cllecting system. The amunt can be precisely cntrlled by a prcess called facultative water reabsrptin. Precise cntrl is pssible because these segments are relatively impermeable t water except in the presence f ADH. This hrmne causes the appearance f special water channels in the apical cell membranes, dramatically enhancing the rate f smtic water mvement. The higher the circulating levels