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Aldosterone increases the Na+/K+ ATPase, Na+/H+ antiporters,and Na+-Cl− cotransporters in the late distal tubules andCDs, independent of plasma potassium levels. Thisincreases K+ secretion into the renal tubules, as statedearlier.■■Acid–base status: To compensate for acidosis, H+ can besecreted into the collecting ducts from the principal cellswhile K+ is reabsorbed.
Conversely, during alkalosis, H+will be retained, and K+ will be secreted from CD αintercalated cells (see Chapter 20).Tubular fluid flow rate: When tubular fluid flow is high,the concentration gradient for K+ (from collecting ductcell to the lumen) is high, and K+ secretion will increase.CALCIUM AND PHOSPHATE TRANSPORTCalcium and phosphate are important during fetal and childhood development for bone and tissue growth, and continueto be important in the adult for bone health. The kidneyscontrol plasma levels of calcium and phosphate by altering214Renal PhysiologyLow K+ DietNormal and High K+ Diet67%67%3%10%–50%5%–30%20%20%9%1%15%–80%Principal CellIntercalated CellLumenBloodBloodLumenHCO3–H+Na+ATPNa+Cl–ATPK+K+ATPH+K+Physiologic Factors ThatStimulate K+ SecretionPhysiologic Factors ThatStimulate K+ ReabsorptionFactors That AlterK+ Secretion (Stimulate)Factors That AlterK+ Secretion (Inhibit)AldosteroneHyperkalemiaLow K+ dietIncreased urine flow rateAcute and chronic alkalosisChronic acidosisAcute acidosisFigure 17.4 Renal Potassium Handling To maintain normal plasma K+ concentration (3.5 to 5 mEq/L),the kidney must control K+ excretion, and the amount of K+ excreted changes with dietary intake.
Diets lowin K+ stimulate avid K+ reabsorption throughout the nephron, whereas diets high in K+ stimulate distal K+secretion (in green).their rate of reabsorption. Most of the calcium and phosphatein the body (99% and 85%, respectively) is found in bonematrix. Renal phosphate and calcium reabsorption are bothregulated by PTH (see Chapter 30).Calcium HandlingAbout 40% of plasma Ca2+ is bound to proteins, leaving60% free for filtration at the glomeruli.
The kidneys reabsorb∼99% of the filtered Ca2+ at sites throughout the nephron(Fig. 17.5A):■■Proximal tubule: Ca2+ reabsorption is paracellular, viasolvent drag initiated by bulk reabsorption of Na+ andwater. This accounts for ∼70% of Ca2+ reabsorption.Thick ascending limb of Henle (TALH): Reabsorption isparacellular, again in parallel with Na+ reabsorption. Inaddition, the lumen-positive transepithelial potentialRenal Transport ProcessesA. Calcium excretion215B.
Phosphate excretion25%–75%70%~9%10%–15%~5%20%1%1%Distal Tubule5%–25%Proximal TubuleLumenBloodBloodLumenCa2+Na+ATPCa2+PiK+IICa2+Pi2Na+3Na+Ca2+A–PiModulation of Ca2+ Transport(Decreased Excretion)FactorNephron SiteModulation of Pi Transport(Increased Excretion)MechanismFactorNephron SiteCa2+PTHProximal tubuleApical symporterECFProximal tubuleSolvent drag/symporterPi intakeProximal tubuleApical symporterPTHDCTActivateECFProximal tubuleSolvent dragPi intakeDCTchannelsPTH secretionMechanismFigure 17.5 Renal Calcium and Phosphate Handling Calcium is reabsorbed along much of thenephron, and very little is excreted. Regulation of distal calcium reabsorption is by parathyroid hormone(PTH), which opens apical calcium channels.
Under normal conditions, ∼75% of the filtered load of phosphate is reabsorbed, with all of the reabsorption occurring in the proximal tubule via Na+-Pi cotransporters.This is highly dependent on the dietary intake of phosphate as well as PTH levels. In response to PTH,proximal tubular reabsorption of phosphate is inhibited, and phosphate excretion increases.
This also occurswith diets high in phosphate. Low-phosphate diets significantly increase Pi reabsorption, recruiting transporters in sites distal to the proximal convoluted tubule (in green), which can reduce phosphate excretionto 5% to 10%.■favors paracellular reabsorption of divalent cations inthis segment (∼20% of reabsorption). Because Ca2+follows sodium reabsorption, changes in sodium reabsorption (such as with loop diuretics) will also reduceCa2+ reabsorption.Distal tubule: Although this segment accounts foronly ∼8% to 9% of Ca2+ reabsorption, this is the siteof hormonal control.
Transport is transcellular andis facilitated by the high electrochemical gradientfrom the tubule into the cell. Once in the cell, transportinto the interstitium is through active Ca2+ ATPase andNa+/Ca2+ exchangers on the basolateral membrane (seeFig. 17.5A).
The transporters in the distal tubule areunder hormonal control by parathyroid hormone(PTH).Renal handling of Ca2+ is regulated by the effects of PTH oncalcium transporters. Low plasma Ca2+ directly stimulatesPTH release from the parathyroid glands (see Chapter 30).PTH activates apical calcium channels and stimulates basolateral Ca2+ transporters in the distal tubule.Phosphate HandlingPhosphates are required for bone matrix formation as wellas for intracellular high-energy mechanisms (e.g., ATP216Renal PhysiologyCLINICAL CORRELATEKidney Stones (Renal Calculi)Kidney stones are solid aggregates of minerals that form in thekidney (nephrolithiasis) or ureters (urolithiasis). The size of stonesis variable, and many small stones will pass through the uretersand urethra without problem.
However, if stones grow largeenough (2 to 3 mm), they can block the ureter and cause intensepain and vomiting. The most common stones are calcium oxalate,and it is the presence of oxalate (not the calcium) that drivesmineral precipitation. Treatment depends on size of the stone andduration of the blockage. Typically, unless there are severe symptoms, small stones will be left to pass; however, long-term (morethan 30 days) blockage can result in renal failure, and interventionwith stent placement and laser or ultrasound may be performed.Plain film: multiple renal calculiMultiple small calculiBilateral staghorn calculiStaghorn calculus plus smaller stoneRenal Calculiformation and utilization).
The majority of plasma phosphate(Pi) (more than 90%) is available for filtration, and Pi reabsorption and excretion are highly dependent on diet and age.As with glucose, Pi has a TM that can be saturated. Undernormal dietary conditions, transporters are present only inthe proximal tubules, and ∼75% of the filtered phosphateis reabsorbed by apical Na+-Pi cotransporters (see Fig.
17.5B).The remaining 25% of the Pi load is excreted; part of thePi can be used to buffer H+, forming titratable acids (seeChapter 20).Renal Transport ProcessesIn growing children and with diets low in Pi, Na+-Pi cotransporters are also present in the proximal straight tubules anddistal tubules, facilitating reabsorption of up to 90% of thefiltered Pi load.Renal Pi reabsorption is primarily controlled by diet and parathyroid hormone (PTH), both of which affect the number ofNa+-Pi cotransporters in the apical membranes:■Diet: High dietary Pi causes reduction in the number ofNa+-Pi cotransporters in the apical membrane, increasing Pi excretion.
Conversely, low dietary Pi will increasetransporters on the proximal tubule brush border,as well as in sites distal to the proximal tubule. Thiswill allow avid Pi uptake and reduced urinaryPi excretion.CLINICAL CORRELATEHyponatremiaHyponatremia is defined as the state of low plasma sodium (lessthan 135 mEq/L). This can be caused by several mechanisms thatresult in low sodium concentrations and reduced plasma osmolarity. During hyponatremia, fluid shifts into cells, reestablishingnormal ECF osmolarity but causing cellular swelling. This canhave important effects, especially on brain tissues which are confined to a bony space and are unable to tolerate swelling:■■Rapid fluid shifts into cells can be a critical problem, becauseacute cerebral swelling can lead to disoriented mental status,seizures, coma, and death.
In these cases, reducing the ECF isnecessary to draw the fluid out of cells. Water restriction and/orADH (V1) antagonists are used to increase urinary free waterexcretion.If the hyponatremia is established over time (for example, inAddison’s disease), brain tissues compensate for fluid shifts bydecreasing intracellular content of osmolytes (organic solutessuch as inositol and glutamine). This reduces the osmotic forcethat would draw fluid into the cells and allows the cells tomaintain normal volume. Because of this, treatment of hyponatremia should involve slow restoration of salt and fluidbalance to normal levels. Otherwise, the brain cells will shrink,inducing an acute, potentially critical, intracellular imbalance.Gradual correction of this type of hyponatremia will allow theosmolytes to increase in brain cells.Exercise-associated hyponatremia (EAH) can occur as a result offluid and electrolyte losses through sweat during long-term exercise (marathons, triathlons).
Although most people do not experience a serious drop in ECF Na+ concentration, the critical cases ofEAH are most likely to occur from a combination of thefollowing:■An initial imbalance of fluid and electrolyte losses, due to overhydration during the exercise.■217PTH: PTH is secreted from the parathyroid glands inresponse to high plasma Pi concentrations or lowplasma calcium concentrations. It decreases apical Na+Pi cotransporters, reducing reabsorption and increasingurinary excretion of Pi.Plasma Ca2+ and phosphate regulation are intertwined becauseof the constant bone resorption and deposition.
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