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In responseto low plasma Ca2+, vitamin D increases intestinal calcium andphosphate absorption, and PTH induces bone resorption—both actions increase Ca2+ and phosphate in ECF. At thekidneys, PTH increases calcium reabsorption but compensates for the additional ECF phosphate by decreasingphosphate transporters and increasing urinary phosphateexcretion. Thus, by this mechanism the kidneys regulateextracellular Ca2+ and phosphate concentrations.■Acute syndrome of inappropriate ADH secretion (SIADH) thatcan occur because of large fluid losses. Recall that both increasedosmolarity and fluid losses can stimulate ADH, but that thesystem is more sensitive to changes in ECF osmolarity than tochanges in fluid volume.
However, if the volume loss continuesand becomes severe, when a dehydrated athlete drinks toomuch hypotonic fluid, the increase in ADH will cause excessivefree water reabsorption by the collecting ducts, rapidly decreasing the ECF sodium concentration. In this scenario, the needto compensate for the volume will override the sodium levels,ADH secretion will continue, and plasma Na+ can fall to critically low levels (below 125 mEq/L).Early symptoms include bloating, nausea, vomiting, and headaches, which can progress to disorientation, seizures, and death ifnot immediately treated. Hyponatremia can be prevented byrestricting water intake (drinking only when thirsty).
Althoughoverhydration during the exercise is a direct cause of hyponatremia, risk factors for developing EAH include low body weight,female sex, and inexperience with marathons. ADH V2 receptorantagonists are used to treat severe hyponatremia.Postsurgical acute hyponatremia frequently occurs in elderlypatients. The stress of surgery can cause an acute SIADH, rapidlyincreasing free water reabsorption and reducing ECF Na+ concentration. As stated earlier, treatment should begin immediately,with water restriction (to limit further fluid retention) and a V2antagonist.
Correcting the hyponatremia restores normalfunction.Pseudohyponatremia occurs when there is an incorrect, low measurement of plasma sodium due to conditions that produce highlipid or proteins (e.g., hyperlipidemia, hyperproteinemia) in theblood. In this case, the substances reduce the total plasma fluid andalthough the amount of sodium is normal, the clinical measurement may be falsely low. Thus, the person is not hyponatremic andtreatment will focus on reducing the lipids and/or proteins.This page intentionally left blank219CHAPTER18Urine Concentration andDilution MechanismsTHE LOOP OF HENLE AND COLLECTINGDUCT CELLSUltimately, the regulation of plasma osmolarity and volumeare the responsibility of the loop of Henle and collecting ducts(CDs) and the vasa recta.
Changes in the permeability of theloop of Henle to solutes and water allow for the concentrationand dilution of the tubular fluid, as well as the ability of thekidneys to regulate overall water and solute reabsorption.Reabsorption is facilitated by the vasa recta that surround themedullary tubules and collecting ducts.The descending and ascending limbs of the loops of Henlehave specific permeability characteristics:■■Descending limbs of Henle’s loop are concentrating segments: permeable to water, impermeable to reabsorptionof solutes (urea can be secreted into the tubule, furtherconcentrating the tubular fluid).Thick ascending limbs of Henle’s loop are diluting segments: impermeable to water, but Na+-K+-2Cl− transporters reabsorb electrolytes, thus diluting the tubularfluid.With this mechanism in place, the tubular fluid entering thedistal tubule has an osmolarity of ∼100 mosm/L; the finetuning to concentrate urine will occur in the collecting ducts.There are antidiuretic hormone (ADH)–sensitive water channels in the collecting duct cells that allow solute-free waterreabsorption and concentration of the hypo-osmotic tubularfluid.
However, this concentration can only be achieved if anosmotic gradient exists from tubular lumen to the interstitialspace.URINE CONCENTRATING MECHANISMThe Medullary InterstitiumThe ability to reabsorb solute-free water in both the descending limb of Henle and the collecting ducts is possible becauseof the osmolar concentration gradient within the medullaryinterstitial fluid and the presence of specific water channels inthe collecting duct cells. Water can only move when there isan osmotic gradient; the factors contributing to the watermovement are illustrated by the numbers in red inFigure 18.1. In this interstitial gradient, the osmolarity is∼300 mosm/L at the corticomedullary border and rises to∼1200 mosm/L in the deepest part of the medulla. With thisgradient in place, if water channels are present, water fromthe tubules readily diffuses into the interstitium (with itshigher osmolar concentration), and then into the vasa rectanetwork.Medullary Countercurrent MultiplierThe interstitial osmolar gradient from cortex to inner medullais formed and maintained by the coordinated efforts of theascending and descending limbs of Henle and their selectivepermeability to solutes.
Important factors contributing toestablishing and maintaining the gradient are the Na+-K+-2Cl−transporters in the thick ascending limb of Henle (TALH),water absorption in the descending limb of Henle, the constant flow of tubular fluid through the loops, and urea recycling (urea reabsorption from the collecting ducts andurea diffusion from the medullary interstitium into the thinlimb of Henle). Creation of the gradient begins with thefollowing:■■■The Na+-K+-2Cl− transporters in the TALH, whichtransport solutes into the interstitium, increasinginterstitial fluid osmolarity and decreasing tubular fluidosmolarity.This increased interstitial osmolarity promotes free waterreabsorption from the descending limb of Henle, whichincreases tubular fluid osmolarity in the descendinglimb (concentrating limb).As tubular fluid flows from the descending limb, the moreconcentrated tubular fluid flows into the TALH and thesolutes are transported into the interstitium throughNa+-K+-2Cl− transporters, further increasing interstitialfluid osmolarity.
The higher interstitial osmolarityfacilitates more free water reabsorption from thedescending limb, concentrating the tubular fluid. Thiscycle (movement of concentrated tubular fluid into theTALH, transport of solutes by the Na+-K+-2Cl− transporters into the interstitium, and water movement outof the descending limb of Henle) is repeated until thefull interstitial gradient is established (“countercurrentmultiplier” concept). The osmolar concentration in theRenal PhysiologyWATER, ION, AND UREA EXCHANGE IN PRODUCTION OF HYPERTONIC URINE (ADH PRESENT)285528285285100% offiltrate lNa C200H2OUrea100285NaClUrea 100H2 OH2ONaCl1UreaH2O750UreaH2O97539755NaClH2OUrea325NaClUrea 550H2O7504H2OUreaNaClNaClUreaH2O775H2OUreaNaClH2OUreaNote: Figures given areexemplary rather than specific120015%of filtrateADHNaCl750ADHUreaNaClUreaNaCl525525750NaClH2OUreaH2OUreaNaClUreaH2O1200ADH300ADH525750285H2OUreaH2OUreaNaClNaCl5252285525300NaClUreaH2OUreaH2ONaCl15%offiltr.28530%offiltr.525ADHH2O285285300H2O3128515fil %tra ofte100750CortexNa Cl UreaH 2ONa Cl H2OUrea975285Medulla2209759754ADH10000012H2OUreaNaCl120012001% offiltr.Figure 18.1 Medullary Interstitial and Tubular Concentration Gradients The concentrationgradient is established by (1) transport of solutes, but not water, out of the thick ascending limb of Henle(TALH) via the Na+-K+-2Cl− transporters (diluting limb); (2) free water reabsorption from the descending limbof Henle, which increases the tubular fluid osmolarity in the descending limb (concentrating limb); (3) asmore tubular fluid flows from the descending limb to the TALH, the more concentrated tubular fluid allowsfurther transport of solutes into the interstitium; and (4) urea recycling contributes to the gradient, becauseit remains in the tubular fluid in the loop of Henle contributing to the tubular fluid osmolarity while water isreabsorbed from the descending limb, and when ADH is present, both water and urea reabsorption increasesin the medullary collecting ducts (CDs), and the urea is recycled to the inner medulla.Urine Concentration and Dilution Mechanisms■interstitium deep in the medulla is dependent on thelength of the loops of Henle (the longer the loops, thehigher the concentrating ability).
In humans, the highestinterstitial concentration (deep in the inner medulla) is∼1200 mosm/L. This allows the concentration of tubularfluid to reach ∼1200 mosm/L at the bottom of the loopsof Henle (see Fig. 18.1).Finally, urea recycling contributes to developing andmaintaining the interstitial osmolar gradient, because■ it remains in the tubular fluid while water is reabsorbed from the descending limb, contributing to thetubular fluid osmolarity, and■ ADH increases both water and urea reabsorption inthe medullary (but not cortical) collecting ducts(CD); the urea is recycled into the inner medulla, contributing to the interstitial concentrationgradient.The ability to concentrate urine differs between species.Animals that live in desert environments (desert rodents,camels) have exceptionally long loops of Henle and have theability to concentrate their urine to more than 2000 mosm/L,allowing tremendous fluid retention.
The medullary interstitium of these animals appears to have additional osmotic agents(∼20% extra “osmolytes” such as sorbitol and myo-inositol) tohelp accomplish this action.221interstitium when ADH is elevated helps maintain the interstitial gradient for water reabsorption. Therefore, dehydration→ higher plasma osmolarity → higher ADH levels → increasedAQP and water reabsorption → more concentrated urine.Under extreme conditions, the urine can be concentratedmaximally to 1200 mosm/L, with minimal urinary waterloss.DILUTION OF URINEWhen there is excess extracellular fluid, plasma osmolarity isreduced and pituitary ADH release is inhibited.
This affectswater reabsorption in both the descending limb of Henle andthe CDs. If less water is absorbed out of the tubular fluid inthe descending limb, the tubular fluid cannot be concentratedto as high a level, and there is increased tubular fluid flow tothe TALH, which reduces the amount of solutes that can betransported into the interstitium. This effectively disrupts theinterstitial gradient, as illustrated in Figure 18.3. This decreasein ADH results in fewer water channels in the CDs, and lessmedullary water and urea reabsorption, producing diuresis(increased production of hypotonic urine). When the excessfluid is excreted, the plasma osmolarity will increase, stimulating ADH, and the interstitial concentration gradient will bereestablished over several hours.FREE WATER CLEARANCEConcentration of the UrineAs discussed in Chapter 1, to maintain plasma (and thus cellular) osmolarity, fluid volume must be controlled.
Either asmall increase in plasma osmolarity (∼1%) or a significantdecrease (a greater than 10% loss) in plasma volume (from,for example, hemorrhage or severe dehydration) will elicitrelease of antidiuretic hormone (ADH, also called vasopressin) from the posterior pituitary gland. This hormone bindsto V2 receptors on principal cells of the renal collecting ducts(Fig.
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