Renal PhysiologyD. C. MikuleckyFaculty Mentoring ProgramVirginia Commonwealth Univ.

FUNCTIONS OF THE KIDNEYWater balanceElectrolyte balancePlasma volumeAcid-base balanceOsmolarity balanceExcretionHormone secretion

THE URINARY SYSTEMKidneysBlood supply: Renal arteries and veinsUreterUrinary bladderUrethra

THE NEPHRON IS THE FUNCTIONAL UNIT OF THE KIDNEYBowmansCapsuleGlomerulusProximal ConvolutedTubuleDistal ConvolutedTubule

Loop of Henle CortexMedullaArteryVeinPeritubular CapillariesCollectingDuct

THREE BASIC RENAL PROCESSESGlomerular Filtration: Filtering of blood into tubule forming the primitive urineTubular Reabsorption: Absorption of substances needed by body from tubule to bloodTubular Secretion: Secretion of substances to be eliminated from the body into the tubule from the blood

BASIC RENAL PROCESSES

GFTRTAUrine ExcretedEfferent ArterioleAfferentArterioleGlomerulusKidneyTubulePeritubular Capillary

Glomerular FiltrationFirst step in urine formation180 liters/day filteredEntire plasma volume filtered 65 times/dayProteins not filtered

Forces Involved inGlomerular Filtration

Glomerular CapillaryBlood Pressure+55Plasma Colloid Osmotic Pressure-301510Bowmans CapsuleHydrostatic Pressure -Net Filtration Pressure+

Tubular ReabsorptionWater: 99% reabsorbed

Sodium: 99.5% reabsorbed

Urea: 50% reabsobed

Phenol: 0% reabsorbed

Tubular ReabsorptionBy passive diffusion

By primary active transport: Sodium

By secondary active transport: Sugars and Amino Acids

Tubular Reabsorption is a Function of the Epithelial Cells Making up the TubuleLumenPlasmaCells

Sodium ReabsorptionLumenPlasmaCellsPUMP: Na/K ATPaseSodiumPotassiumChlorideWater

Rennin-Angiotensin-Aldosterone SystemStimulates Sodium Reabsorption in distal and collecting tubulesNaturetic peptide inhibitsIn absence of Aldosterone, 20mg of sodium/day may be excretedAldosterone can cause 99.5% retention

Rennin-Angiotensin-Aldosterone SystemFall in NaCl, extracellular fluid volume, arterial blood pressureJuxtaglomerularApparatusReninLiverAngiotensin+AngiotensinAngiotensinAldosteroneLungsConvertingEnzymeAdrenalCortexIncreasedSodiumReabsorptionHelpsCorrect

DIURETICSACE Inhibitors (Angiotensin Converting Enzyme): Cause loss of salt---> water followsAtrial Naturetic Peptide (ANP) also inhibits sodium reabsorptionOsmotic diuretics: Are not reabsorbed

Glucose and Amino Acids are reabsorbed by secondary active transportThey are actively transported across the apical cell membranes of the epithelial cellsTheir active transport depends on the sodium gradient across this membraneAll other steps are passive

GLUCOSE REABSORPTION HAS A TUBULAR MAXIMUMRenal threshold (300mg/100 ml)Plasma Concentration of GlucoseGlucoseReabsorbedmg/minFiltered ExcretedReabsorbed

Tubular SecretionProtons (acid/base balance)

Potassium

Organic ions

Potassium SecretionLumenPlasmaCellsPUMP: Na/K ATPaseSodiumPotassiumChlorideWater

DUAL CONTROL OF ALDOSTERONE SECRETIONFall in sodiumECF VolumeBlood PressureIncreased PlasmaPotassiumIncreased Aldosterone secretionIncreased TubularPotassium SecretionIncreased UrinaryPotassium SecretionIncreased TubularSodium ReabsorptionFall in UrinarySodium Excretion

Reabsorption in Proximal Tubule (Summary) Glucose and Amino Acids67% of Filtered SodiumOther Electrolytes65% of Filtered Water50% of Filtered UreaAll Filtered Potassium

Secretion in Proximal Tubule (Summary)Variable Proton secretion for acid/base regulation

Organic Ion secretion

Reabsorption in Distal Tubule (Summary)Variable Sodium controlled by Aldosterone

Chloride follows passively

Variable water controlled by vasopressin

Secretion in Distal Tubule (Summary)Variable Proton for acid/base regulation

Variable Potassium controlled by aldosterone

Collecting Duct (Summary)Variable water reabsorption controlled by vasopressin

Variable Proton secretion for acid/base balance

REGULATION OF URINE CONCENTRATIONMedullary countercurrent system

Vasopressin

Medullary countercurrent systemOsmotic gradient established by long loops of Henle

Descending limb

Ascending limb

Descending limbHighly permeable to water

No active sodium transport

Ascending limbActively pumps sodium out of tubule to surrounding interstitial fluid

Impermeable to water

COUNTERCURRENT MAKESTHE OSMOTIC GRADIENT30045060075090010501200 1200From ProximalTubuleTo DistalTubuleCortexMedulla

300450600750900105012001200

10025040055070085010001000ActiveSodiumTransportPassiveWaterTransportLong Loopof Henle

THE OSMOTIC GRADIENT CONCENTRATES THE URINE WHEN VASOPRESSIN (ANTI DIURETIC HORMONE [ADH]) IS PRESENTFrom DistalTubuleCortexMedulla

300450600750900105012001200

300400550700850100011001200Interstitial FluidCollectingDuctPoresOpenPassive Water Flow

WHEN VASOPRESSIN (ANTI DIURETIC HORMONE [ADH]) IS ABSENT A DILUTE URINE IS PRODUCEFrom DistalTubuleCortexMedulla

300450600750900105012001200

100100100100100100100100Interstitial FluidCollectingDuctPoresClosedNo Water FlowOut of Duct

Renal FailureAcute: Sudden onset, rapid reduction in urine output - usually reversible

Chronic: Progressive, not reversible

Up to 75% function can be lost before it is noticeable

THE URINARY BLADDER STORES THE URINEGravity and peristaltic contractions propel the urine along the ureterParasympathetic stimulation contracts the bladder and micturition results if the sphincters (internal and external urethral sphincters) relaxThe external sphincter is under voluntary control

Reflex and Voluntary Control of MicturitionBladder filling reflexively contracts the bladderInternal Sphincter mechanically opensStretch receptors in bladder send inhibitory impulses to external sphincterVoluntary signals from cortex can override the reflex or allow it to take place