Lec Renal Physiology - CCSF

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Physiology 12Kidney and Fluid regulationGuyton Ch 20, 21,22,23Roles of the KidneyRegulation of body fluid osmolarity andelectrolytesRegulation of acidacid-base balance (pH)Excretion of natural wastes and foreignchemicalsRegulation of arterial pressureSecretion of hormones (Epo(Epo))GluconeogenesisRenal PhysiologyThe Nephron and GFRKidney Gross AnatomyThe NephronGlomerular Filtration Rate (GFR)Regulation of GFRPhysio 12 -Summer ‘02 - Renal Physiology - Page 1

Renal ArteriesPhysio 12 -Summer ‘02 - Renal Physiology - Page 2

The NephronCortical andMedullaryNephronsPhysio 12 -Summer ‘02 - Renal Physiology - Page 3

Physio 12 -Summer ‘02 - Renal Physiology - Page 4

Physio 12 -Summer ‘02 - Renal Physiology - Page 5

Glomerular Filtration Rate(GFR)Glomerular capillaries have higher filterrate than other capillaries– Due to higher hydrostatic pressure andleakier capillariesGFR 125 ml/min 180 L/dayFiltered fraction GFR/Renal plasma flow 20%Figure 21-7:PNetPNet PG-PB-πGPhysio 12 -Summer ‘02 - Renal Physiology - Page 6

Influences on GFRGFR Kf x PNet– Kf leakiness of capillaries– PNet net hydrostatic pressure PG - PB - πGKf of glomerulus is 400400-fold higher thanKf of any other capillariesCapillary Pressure (out) 60 mmHgBowmans Pressure (in) 18 mmHgPlasma Colloidal (in) 32 mmHgBowman’s Colloidal (out) 0 mmHg10 mmHg outward pressure Afferent Constriction FiltrationPhysio 12 -Summer ‘02 - Renal Physiology - Page 7

Efferent Constriction FiltrationGFR Increases with:Increased glomerular blood flowDecreased afferent arteriolar resistanceIncreased efferent arteriolar resistanceSympathetic stimulation (extremesituations only) lowers GFR– NE and Epi lower GFRAutoregulation of GFRGFR is relatively constant over arterialBPs of 8080-170 mm HgPersists in isolated kidney– Independent of nervous systemNo autoregulation would create 46liters/day of urine if BP 125 mm Hg– 6 liters/day with autoregulationPhysio 12 -Summer ‘02 - Renal Physiology - Page 8

Figure 2121-9:Autoregulationof Renal BloodFlow and GFRNormalPressureDiuresisAutoregulation of GFRMediated by Tubuloglomerular FeedbackLow NaCl (flow) at Macula Densa:– Lowers afferent arteriolar resistance (?)– Raises efferent arteriolar resistance (AII)Macula Densa also regulates renal BP ructure ofJuxtaglomerularApparatusReninRenin SecretionSecretionChemicalChemicalSignalSignal fromfrom MDMDPhysio 12 -Summer ‘02 - Renal Physiology - Page 9

Renal PhysiologyFiltration and Reabsorption1o and 2o Active Transport– Passive diffusion of Cl, urea, waterSaturable reabsorption of glucose & AAsTour of reabsorption and secretion alongthe tubuleRenal ClearanceTwo Paths hysio 12 -Summer ‘02 - Renal Physiology - Page 10

SecondaryActiveTransport(Co(Co-Transport)Glucose andAA ActiveReabsorptionat ProximalTubulePhysio 12 -Summer ‘02 - Renal Physiology - Page 11

Secondary Active Transport (CounterTransport)H SecretionFiltrationFiltration PS x GFR, where PS is theplasma concentration of substance SThis represent the tubular load or filteredload that must be handledUnits: mg/ml x ml/min mg/minFigure 2121-15: Glucose Transport isSaturable: Diabetes mellitusPGlucosex GFR Glucose0.9 mg/ml x 125 ml/min 112 mg/minPGlucose x GFR Physio 12 -Summer ‘02 - Renal Physiology - Page 12

PGlucoseGFR Figure21GlucoseTransport is21x-15:Glucose3.2 mg/mlx 125 ml/min mellitusSaturable:Diabetes400 mg/minDiabetesmellitusPGlucose x GFR Diabetes:BasolateralApicalIncreasedIncreased byby AIIReabsorptionCa PAH, many drugsSecretionProcesses at Proximal Tubule HH22OO20%NaClNaCl Processes at Thin Loop of HenlePhysio 12 -Summer ‘02 - Renal Physiology - Page 13

IncreasedIncreased byby AldosteroneAldosteroneBlockedBlocked byby Lasixnono HH22OO 25%Processes at Thick Loop of HenleIncreasedIncreased byby AldosteroneAldosteroneBlockedBlocked byby AmilorideVariable %Hypoosmoticnono HH22OO ]] Reabsorption[Ca[Ca ReabsorptionIncreasedIncreased byby PTHPTHProcesses at Early Distal TubuleCalcium Homeostasis90% dietary Ca excreted in feces, 10% inurineLow [Ca] in plasma causes parathyroidcells to secrete PTH– Ca reabsorption from distal tubule– Ca reabsorption from intestine– Release of Ca stored in boneCan eventually strip bone of Ca supplyPhysio 12 -Summer ‘02 - Renal Physiology - Page 14

BlockedBlocked byby Amiloride90 % of cellsIncreasedIncreased byby AldosteroneAldosteroneDecreasedDecreased byby ANPANPVariable %10 % of cellsProcesses at Late Distal Tubule andCollecting Duct90 % of cellsIncreasedIncreased byby ADHADHH2 ODecreasedDecreased byby ANPANPVariable %10 % of cellsProcesses at Late Distal Tubule andCollecting Duct90 % of cellsVariable %LocationLocation ofof [K ][K ]ControlControl10 % of cellsProcesses at Late Distal Tubule andCollecting DuctPhysio 12 -Summer ‘02 - Renal Physiology - Page 15

Potassium HomeostasisMost K is inside cells (140 mM), not outside(4.2 mM) plasma [K ] causes K secretion fromprincipal cells:– Direct Na/K pump– Aldosterone secretion Na/K pump90 % of cellsVariable %LocationLocation ofof AcidAcidBaseBase ControlControl10 % of cellsProcesses at Late Distal Tubule andCollecting DuctAcid-Base HomeostasisDiet usually generates an excess of acidMost HCO3- is reabsorbed by PT (85%),remainder by TAL and CDControlled by tubule cells, which sense pHand [CO2]– Secrete more H if pH too low– Secrete less H if pH too highPhysio 12 -Summer ‘02 - Renal Physiology - Page 16

Acid-Base HomeostasisExcess H is secreted by Intercalated Cells inDT and CD– Urinary H is buffered by phosphate and ammoniaso that pH 4.5RelativeConcentrationsof Substancesalong TubuleGlucose & AAsRelativeConcentrationsof Substancesalong TubuleInulinH2 OPhysio 12 -Summer ‘02 - Renal Physiology - Page 17

RelativeConcentrationsof Substancesalong TubuleH HCO3-RelativeConcentrationsof Substancesalong TubuleRelativeConcentrationsof Substancesalong TubulePAHKClNaHCO3-Physio 12 -Summer ‘02 - Renal Physiology - Page 18

Renal ClearanceRenal Clearance (CS) is the volume ofplasma completely cleared of a substance(S) per minute– Units are ml/minCS (US x V)/PS– US is [S] in urine, V is urine flow rate, PS is [S]in plasmaRenal ClearanceFilteredFiltered-Only substances (no secretion orreabsorption) have CS GFR– Example: InulinSecreted substances have CS GFR– Example: PAHReabsorbed substances have CS GFR– Example: glucoseRenal ClearanceRenal clearance of inulin allows clinicaldetermination of GFR– GFR (UI x V)/PIPAH is 90% secreted. Renal clearance ofPAH allows clinical determination of RenalPlasma Flow– RPF (UPAH x V)/(PPAH x 0.9)Physio 12 -Summer ‘02 - Renal Physiology - Page 19

Renal Physiology: Renal ExchangeMechanismsExcrete excess solutesAnd/orConcentrating the UrineCreate a very high osmotic pressurein the interstitial fluid Created by active transportof ions. Increase the interstitialfluid Osmolarity.Physio 12 -Summer ‘02 - Renal Physiology - Page 20

Physio 12 -Summer ‘02 - Renal Physiology - Page 21

Physio 12 -Summer ‘02 - Renal Physiology - Page 22

Create a very high osmotic pressurein the interstitial fluid Created by active transport ofions. Increase the interstitial fluidOsmolarity. Arteriole and Capillary systemtransports ions tomedullary areas of thekidney.Physio 12 -Summer ‘02 - Renal Physiology - Page 23

KidneyDialysisRegulation of Renal OutputandCardio-vascular VolumeControlGermann Ch 18Physio 12 -Summer ‘02 - Renal Physiology - Page 24

Hormonal Control of Renal Outputand Cardiovascular PressureThree main systems: Renin-Angiotension System Aldosterone Antidiuretic HormoneStructure ate, excess inNa and Clreabsorption,decreased ionconcentrationin thefiltrate.ReninRenin SecretionSecretionChemicalChemicalSignalSignal fromfrom MDMDPhysio 12 -Summer ‘02 - Renal Physiology - Page 25

Renin-Angiotension System: Act on vascular system (directly) to increase totalperipheral resistance Act on the Kidney tubule system to increaseretention of salts and water. (vasoconstriction ofafferent arteriole and peritubular capillaries) Stimulation of Aldosterone System.Physio 12 -Summer ‘02 - Renal Physiology - Page 26

Antidiuretic HormoneRegulation of Urine Secretionand Body FluidsAnteroventral Border of the Third Ventricle(AV3V Nucleus of the Hypothalamus) extracellular fluid osmolarity - ADH SecretionInduce thirstPhysio 12 -Summer ‘02 - Renal Physiology - Page 27

ADH effects on the body Vasoconstriction Stimulate reabsorption of Water from the DistalConvoluted Tubule and Collecting Ducts Binds to receptors on the basolateral membrane ofthe epithelial cells. Initiates a second (intracellular) messenger(cAMP) Cause the fusion of vesicles (containing pores) tothe luminal membrane. Water rushes from the lumen into the cell and intothe interstitium.Physio 12 -Summer ‘02 - Renal Physiology - Page 28

Physio 12 -Summer ‘02 - Renal Physiology - Page 29

Metabolic Acidosis and AlkalosisAbnormalities of Acid-Base balance besides thosecaused by excess or insufficient carbon dioxide inthe body fluidsEffects of: Metabolic AcidosisSigns or Symptoms Depression of the Central Nervous System ( pH 7.0) Increased respiratory rate and depth. (H )Causes Diarrhea - excess loss of sodium bicarbonate Uremia - failure of kidney filtration of H Diabetes Mellitus - excess production of glucose basedacids (acetoacetic acid)Effects of: Metabolic AlkalosisSigns or Symptoms Overexcitability of the Central Nervous System(muscle tetany)Causes Excessive Ingestion of Alkaline Drugs Excessive Vomiting (loss of Cl-) Excess Aldosterone (reabsorption of Na , release ofH )Physio 12 -Summer ‘02 - Renal Physiology - Page 30

Hydrogen Ion RegulationHydrogen Ion buffer systemCarbonic AnhydraseCO2 H2O H2CO3 HCO3- H Physio 12 -Summer ‘02 - Renal Physiology - Page 31

Take home messageKidneys are homeostatic regulators of thebody’s Hydrogen Ion concentration (pH)Kidneys maintain balance by regulatingplasma bicarbonate concentrationKidneys and the Renal System are important for bothshort and long-term control of body fluid levels. Byregulating these fluid levels the Renal system will workin conjunction with the Cardiovascular system tomaintain blood pressure.Physio 12 -Summer ‘02 - Renal Physiology - Page 32

Urea Secretion 30 grams dailyFactors determining excretion: Concentration in Plasma Glomerular Filtration RateMicturitionPhysio 12 -Summer ‘02 - Renal Physiology - Page 33

Physio 12 -Summer ‘02 - Renal Physiology - Page 34

Physio 12 -Summer ‘02 - Renal Physiology - Page 6 Glomerular Filtration Rate (GFR) Glomerular capillaries have higher filter rate than other capillaries – Due to higher hydrostatic pressure and leakier capillaries GFR 125 ml/min 180 L/day Filtered fraction GFR/Renal

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