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More than 99% of the filtered load is reabsorbed through a variety oftransport mechanisms. The gradient for sodium transport into the cells is maintained by basolateral Na+/K+ATPase pumps.■Thick ascending limb of Henle (TALH): This segment isimpermeable to water, but specialized apical Na+-K+2Cl- cotransporters facilitate reabsorption of electrolytes and dilution of the tubular fluid entering the distaltubule. These transporters are the targets for loop diuretics such as furosemide and bumetanide.
In addition,there is a backleak of K+ out of the cells into the lumen,creating a lumen-positive transepithelial potential difference (compared with interstitial fluid). This allows■paracellular movement of cations (Ca2+, Mg2+, Na+, K+)out of the tubular lumen. In addition to the Na+-K+-2Cl−cotransporter, there are also Na+/H+ antiporters, whichreabsorb Na+ and secrete H+ into the tubule.
(TALHreabsorbs ∼20% to 25% of FLNa.)Distal tubule (DT): The early DT has Na+-Cl- cotransporters that can be inhibited by thiazide diuretics. Thelate DT has Na+ (and K+) channels that are increased bythe hormone aldosterone, resulting in greater Na+ andRenal Transport Processes■water reabsorption. This aldosterone-sensitive epithelialsodium channel (ENaC) is blocked by amiloride, whichis a potassium-sparing diuretic (discussed later). Aldosterone also responds to elevated plasma K+, and increasesdistal and collecting tubule secretion of K+.
(DT reabsorbs ∼4% of FLNa.)Collecting tubule: Like the late DT, the collecting tubulehas Na+ (and K+) channels that are increased by aldosterone. (CT reabsorbs ∼3% of FLNa.)Glucose TransportBecause of the large FLNa, the reabsorption of sodium is not arate-limiting step in the reabsorption of other solutes. Formany solutes, the rate-limiting step is the number of specifictransporters available for the solute. Glucose is a good exampleof this concept. The sodium-glucose carriers have a hightransport maximum (TM), and under normal conditions, thefiltered load of glucose is low enough that the transporters cancarry all of the solute back into the blood, leaving none in thetubular fluid and urine (Fig.
17.2). Thus, the renal clearanceof glucose is normally zero.However, if the FL of glucose is high, there may be too muchglucose present in the tubular fluid and the carriers canbecome saturated. The renal threshold describes the pointwhere the first nephrons exceed their TM, resulting in glucosein the urine (glucosuria).
When the plasma glucose concentration (and hence the filtered load of glucose) is under therenal threshold for reabsorption, all of the glucose in tubularfluid will be reabsorbed (see Fig. 17.2). However, when itexceeds the threshold, the transporters are saturated (TMexceeded) and glucose appears in the urine.The plasma concentration at which the renal thresholdfor glucose reabsorption is exceeded (and glucosuria isobserved) is ∼250 mg%.
However, the calculated plasma threshold is 300 mg%. This difference between real and calculatedvalues is explained by nephron heterogeneity (also called splay),whereby different nephron populations have higher and lowerTMs for glucose. The average TM (for both kidneys) is the basisfor the calculation of the threshold for plasma glucose levels (atwhich glucosuria occurs), despite the fact that some nephronshave a lower TM that will be exceeded when plasma glucose isover ∼250 mg%.This concept is important in diabetes mellitus, in which theinability to efficiently transport glucose into tissues leads to highplasma glucose concentrations. The fasting plasma glucose ismuch higher than normal in diabetes (greater than 130 mg%compared to 80 to 90 mg%), resulting in increased FL ofglucose.
With feeding, the plasma levels can easily exceed theTM of some nephrons, causing glucosuria. In addition, becauseglucose is an osmotic agent, the glucosuria will be associatedwith diuresis (loss of water through increased urine volume).211BICARBONATE HANDLINGPlasma bicarbonate is necessary for acid–base homeostasis.At normal whole body pH balance, 100% of the filteredbicarbonate (HCO3−) is effectively reabsorbed.
However, thisoccurs indirectly through a process involving H+ secretion(through cation exchange and active H+ pumps). In thetubular lumen, filtered HCO3− and secreted H+ form CO2 andH2O (a reaction catalyzed by brush border carbonic anhydrase, CA), which diffuse into the cell (Fig.
17.3). Once in thecell, the CO2 and H2O are converted back to carbonic acid (byintracellular CA); HCO3− is transported out of the cell viabasolateral HCO3−/Cl− exchangers or Na+-HCO3− cotransporters, depending on the nephron segment. The H+ generatedfrom this process is secreted back into the tubular lumen andcan be used to reabsorb more HCO3−, or can be buffered andexcreted (see Chapter 20). This mechanism is present in threesegments of the nephron, facilitating reabsorption of filteredbicarbonate in the PT (80% of filtered load), TALH (15%),and CD (5%).Under normal conditions, the renal clearance of HCO3− is 0,meaning there is none in the urine.
The regulation of bicarbonate handling is an integral part of acid–base homeostasisand will be discussed in Chapter 20.POTASSIUM HANDLINGAs with all of the major electrolytes, potassium balance isimportant to overall homeostasis, and dietary intake must bematched by urinary and fecal excretion. Plasma K+ concentration must be maintained at relatively low levels (3 to 5 mEq/L)and is regulated by the kidneys. Potassium is pumped intocells (via Na+/K+ ATPase, which is stimulated by insulin andepinephrine), and the excess in the extracellular fluid (ECF)is excreted in urine.
Figure 17.4 illustrates potassium handlingthrough the nephron and the effects of dietary K+ intake.Potassium handling varies along the nephron:■■■■Proximal tubule: Potassium reabsorption occurs by paracellular movement, not by entry into the cells. Reabsorption initially occurs via solvent drag, initiated bywater reabsorption. In the S2 and S3 segments, the positive potential of the tubular lumen allows (paracellular)potassium reabsorption by diffusion down the electrochemical gradient (this accounts for ∼70% reabsorptionof filtered potassium).Thick ascending limb of Henle: The Na+-K+-2Cl− cotransporters in the TALH use the sodium and chloride gradients to facilitate transport of K+ (∼20% of filteredpotassium).Late distal tubules: Potassium can be secreted into theDTs via aldosterone-sensitive K+ channels.Collecting ducts: Potassium is secreted into the collectingducts through aldosterone-sensitive apical K+ channels212Renal PhysiologyBelow TMConcentration of glucose in plasma,and consequently in filtrate, is lessthan reabsorptive capacity of tubule; itis fully reabsorbed and none appearsin urineAt TMConcentration of glucose inplasma, and consequently infiltrate, is just sufficient to saturatereabsorptive capacity of tubuleAbove TMConcentration of glucose in plasma,and consequently in filtrate, exceedsreabsorptive capacity of tubule;glucose appears in urineedterFil400AmountfilteredReabsorbed200TMGlucose (mg/min)6000200edretcExAmountAmountAmount⫽⫺filteredexcretedreabsorbed600400Plasma glucose (mg/dL)8001,000Figure 17.2 Renal Handling of Glucose Glucose is freely filtered at the glomerulus and is 100%reabsorbed in the proximal tubules by sodium-glucose cotransporters.
However, if blood glucose levelsbecome elevated, as in diabetes, the maximal tubular reabsorption rate (TM) is exceeded, and glucoseappears in the urine (far right panel).in principal cells. K+ is also secreted into the collectingducts by α-intercalated cells, in exchange for H+. Undernormal conditions there is a net secretion of K+. Netreabsorption can occur during dietary K+ depletion.Renal potassium handling is influenced by the following:■Dietary potassium intake: Increased intestinal K+absorption elevates plasma K+ concentration.
TheLoop diuretics, such as furosemide (Lasix) andbumetanide, inhibit the Na+-K+-2Cl− cotransporters,causing natriuresis/diuresis, which is beneficial in controllinghypertension. Extended use can cause urinary K+ loss, andplasma K+ must be monitored. Potassium-sparing diuretics,such as thiazides, target the distal tubule Na+-Cl− cotransportersand control potassium losses.Renal Transport ProcessesLumenLumenBloodBloodNa+Na+213K+K+ATPK+H+H+H+H++HCO3–H++HCO3–ATP3HCO3–H2CO3CACO2 + H2ONa+CACO2 + H2OReabsorbs 80% of filtered loadNa+H+HCO3–ATPCl–H2CO3CACO2 + H2OCO2 + H2OReabsorbs 5% of filtered loadNa+ATPK+H+H++HCO3–H+ATP3HCO3–H2CO3CACO2 + H2ONa+CO2 + H2OReabsorbs 15% of filtered loadFigure 17.3 Renal HCO3- Reabsorption Bicarbonate is freely filtered at the glomerulus and is reabsorbed along the nephron through a process involving secretion of H+.
Under normal conditions, 100% ofthe filtered bicarbonate is reabsorbed.■mineralocorticoid aldosterone increases basolateral Na+/K+ ATPase activity, pumping more K+ into the cells (seeChapter 19). K+ is then secreted into the collecting ductsthrough apical channels in the principal cells. Whendietary K+ intake is low, K+ secretion from the principalcells is inhibited, and K+ reabsorption from the collecting duct α-intercalated cells predominates.Plasma volume: In addition to responding to increasedplasma K+ concentrations, aldosterone is also released inresponse to decreased plasma volume, as part of therenin-angiotensin-aldosterone system (RAAS).
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