Fluid and Electrolyte BalanceAnang Achmadi, SpAn

HomeostasisBody maintains balance of water and ionsLoss: Urine, feces, lungs, sweatIntake: Drink, eatOsmolarityDecreases: Cells swellIncreases: Cells shrinkIntegration of multiple systemsRespiratory, cardiovascularKidney

Water BalanceInput = OutputWater lossUrine, feces, sweat, lungsWater gainDrink, food, IV fluidsWater conservationKidneys

Urine ConcentrationKidneys can concentrate urineWithout allowing osmotic water responseLoop of HenleUrine becomes hyposmoticCells in ascending loop impermeable to waterCollecting ductUrine concentration determined by tubule permeability to waterImpermeable: Dilute urinePermeable: Concentrated urine

Vasopression (ADH)Causes collecting duct to insert water pores in apical membraneWater leaves by osmosisConcentrated urineNo vasopressinCollecting duct impermeable to waterDilute urine

VasopressinAquaporinWater channel regulated by vasopressinFound in Apical membrane of collecting ductCytoplasmic vesiclesVasopressinBinds to receptors on basolateral membraneActivates G-protein/cAMPCauses aquaporin vesicles to move to apical membrane and fuse with it

Vasopressin SecretionStimuli for secretionBlood pressure and volumeVolume decreases Atrial stretch receptors vasopressin release water conservedPressure decreases Carotid, aortic baroreceptors vasopressin releaseECF osmolarityAbove 280 mOsm osmoreceptors fire vasopressin releaseBelow 280 mOsm osmoreceptors dont fire no release

Loop of Henle: Countercurrent Exchange SystemHigh osmolarity of medullary intersititiumCountercurrent exchange systemDescending loop of HenlePermeable to water, not ionsAscending loop of Henle Permeable to ions, not waterTransfer of solutes into ECF by ascending limb creates osmotic gradient for water movement in descending limb

Vasa RectaPeritubular capillariesPass into renal medullaFlow opposite tubule flowDescending vasa rectaSolutes enter, water leavesAscending vasa rectaWater enters to diluteUreaIncreases osmolarity in medullary interstitium

Sodium BalanceMain ECF soluteRegulation through renin-angiotensin-aldosterone system (RAAS)AldosteroneRegulates sodium reabsorption in distal tubuleAlso causes potassium secretionSynthesized in adrenal cortexActs on principal cellsDistal tubule and collecting duct

Principal CellsNa+-K+ ATPase pumps on basolateral sideChannels and transporters on apical sideNa+, K+ leak channelsAldosteroneFast responseApical Na+ channels increase open timeNa+-K+ ATPase pump speeds upSlow responseDiffuses in, binds to cytoplasmic receptorsDirects synthesis of new protein channels and Na+-K+ ATPase pumps

Control of Aldosterone SecretionPotassium concentrationIncreased K+: Acts on adrenal cortex stimulates aldosterone secretionIncreased osmolarity: Acts on adrenal cortex inhibits aldosterone secretionIndirect stimuli:Angiotensin IIDecreased blood pressureDecreased GFR

Renin-Angiotenisn-Aldosterone PathwayAngiotensin II (ANGII)Primary control of aldosterone releasePathway:JG cells secrete reninRenin converts angiotensin to angiotensin IConverted to angiotensin II by ACELungs, blood vessel endotheliumANGII stimulates aldosterone release by adrenal cortex

Stimuli for RAAS PathwayLow renal arteriole pressureJG cells secrete reninLow blood pressureSympathetic neurons stimulate renin secretionLow distal tubule flowMacula densa secretes paracrinesSignals JG cellsHigh flow NO release Inhibits renin release

Angiotensin and Blood PressureActivation of brain ANGII receptorsVasopressin secretionIncreased water reabsorptionStimulates thirstVasoconstrictorIncreases blood pressureANGII receptors in CVCCSympathetic output to heart and blood vessels

Atrial Natriuretic PeptideReleased by atrial myocardial cellsResponse to stretchCauses sodium and water excretionIncreases GFRMore surface areaDecreases sodium and water reabsorption in collecting ductInhibits renin, aldosterone and vasopressin releaseAffects CVCC Lower BP

Potassium BalanceHyperkalemiaDecreases concentration gradient across membranes DepolarizationHypokalemiaIncrease concentration gradient HyperpolarizationIncreased potassiumAldosterone secretion K+ secretion

Behavioral MechanismsDrinking waterReplaces fluid lossHypothalamic osmoreceptors (> 280 mOsm)Oropharynx receptorsEating saltLow plasma Na+ stimulates craving for saltHypothalamic salt appetite centerAvoidance behaviors

Integrated ControlOsmolarity and ECF volume can change independentlyEach has 3 possible statesNormal Increased Decreased

CompensationIncreased volume, increased osmolarityExcrete hypertonic urineIncreased volume, unchanged osmolarityExcrete isotonic urine equal in volumeIncreased volume, decreased osmolarityExcrete dilute urineNormal volume, decreased osmolarityConserve solutes, ingest more solutes

CompensationDecreased volume, increased osmolarityThirst, fluid ingestionDecreased volume, no osmolarity changesBlood transfusion, isotonic fluid replacementDecreased volume, decreased osmolarityUncommonTable 19-2

DehydrationDecreased volume, increased osmolarityAdrenal cortexSecrete and not secrete aldosteroneFix osmolarity first!BaroreceptorsDecrease firing PSNS, SNS output blood pressure HR, CO, vasoconstriction, GFR reninRenin secretionSNS stimulation BP, GFRThirst, vasoconstriction, vasopressin

Compensatory MechanismsCardiovascular responseAngiotensin IIVasopressinThirstNet resultRestoration of blood volumeMaintenance of blood pressureRestoration of normal osmolarity

Acid-Base BalancepH homeostasisClosely regulatedProteins sensitiveEnzymes, membrane channels, nervous systemAcidosis: Decreased neuron excitabilityAlkalosis: Neuron hyperexcitabilityRegulation linked to K+ balanceK+-H+-ATPase antiporter

Acid-Base SourcesAcid inputOrganic acidsMetabolic intermediates, foodsLactic acidosisCO2 and aerobic respirationHCO3 and H+Base inputFew significant sources

PH HomeostasisControlled by:BuffersVentilationRenal regulationBuffer systemsIntracellular buffersProteins, phosphate ions, hemoglobinExtracellular buffersBicarbonate ion

VentilationPCO2 reflects CO2 content of bloodChanges in PCO2 alter H+ and HCO3 Hypoventilation: CO2 H+ and HCO3Hyperventilation: CO2 H+ and HCO3Control of ventilationCarotid, aortic chemoreceptors: H+Central chemoreceptors: PCO2

Renal RegulationDirectRetaining or excreting H+IndirectReabsorption or excreting HCO3AcidosisKidney secretes H+ into proximal and distal tubulesAmmonia and phosphate buffers in urineHCO3 reabsorbedAlkalosisKidney secretes HCO3, reabsorbs H+

Renal RegulationCellular mechanismsApical Na+-H+ antiporterIndirect active transporterBasolateral Na+-HCO3 symporterIndirect active transporterH+-ATPaseSecretes H+ against concentration gradientH+-K+-ATPaseH+ into urine, K+ reabsorbedNa+-NH4+-ATPaseNa+-K+-ATPaseHCO3-Cl- Antiporter

Proximal TubuleMost HCO3 reabsorbed here2 pathwaysSecretion of H+ into tubule (Na+-H+ antiport)Combines with filtered HCO3 CO2CO2 diffuses into proximal cell and dissociates to H+ and HCO3H+ secreted and HCO3 transporter out by HCO3-Na+ symporter

Proximal TubuleGlutamine pathwayGlutamine loses 2 amino groupsBecome ammoniaBuffers H+ NH4NH4 transported into lumen in exchange for Na+a-ketoglutarate metabolized to HCO3Transported into blood with Na+

Distal NephronFine regulation of acid-base balanceIntercalated cellsBetween principal cellsType A: Acidosis; secrete H+, reabsorb HCO3H+-ATPase, H+-K+-ATPaseHCO3-Cl- antiporterType B: Alkalosis; secrete HCO3, reabsorb H+Same transporters, opposite polarityCarbonic anhydrasePotassium balance

Acid-Base DisturbancesRespiratory AcidosisVentilation inadequate to remove CO2 plasma pH, HCO3Compensation: Renal ONLYSecrete H+, Reabsorb HCO3Metabolic AcidosisDietary and metabolic acid input exceeds acid excretion HCO3CompenstionRenal: Excrete H+, Reabsorb HCO3Respiratory: Increase ventilation

Acid-Base DisturbancesRespiratory AlkalosisIncreased alveolar ventilation without increase in CO2 HCO3 and pHCompensationRenal ONLY: HCO3 excreted and secreted, H+ reabsorbedMetabolic AlkalosisAcid excretion exceeds acid input HCO3CompensationRespiratory: Decreased ventilationRenal: HCO3 excreted, H+ reabsorbed