NOTES, a OTS RENAL ELECTROLYTE REGULATION © GLOMERULAR FILTRATION Sure unc umeet MC) + Fluid passage through glomeruiar filtration, barrier, approx. 125mLimin * Glomerular frat: fluid that passes ‘through all glomerular tration barriers "Blood minus red blood cells, plasma proteins + Anything remaining in glomerulus caried away by efferent arteriole + Staring forces + glomerular fitration = Different pressures of fluids, proteins in glomerular capillaries, Bowrnan's space + Most fitration occurs at beginning of glomerulus, nearer afferent arteriole Figure 614 An ilustration depicting the glomerulus and its relationship to the rest of the nephron GLOMERULAR FILTRATION BARRIER + Capilary walls of glomerulus * Glomerulus: tuft of capilaries in nephron's renal corpuscle + Blood enters glomerulus through afferent arteriole leaves through efferent arteriole — divides into peritubular capillaries + Separates blood in capillaries from Bowman's space, Bowman's capsule + Allows only water, some solutes to pass into Bowman's space * Three layers: endothelium, basement membrane, epithelium + Juxtaglomerviar apparatus: secretes renin Endothelium + Comprised of glomerular capillary endothelial cells featuring pores (AKA fenestrations) + Allows passage of solutes, proteins + Blocks red blood cell passage Basement membrane * Gel-lke layer with tiny pores * Blocks plasina protein passage * Due to pore size, negative membrane charge Epithelium + Comprised of podocytes (wrap around basement membrane) + Also blocks plasma protein passage ro Figure 612 The three layers of the ‘glomerular fitration barrier. 5 eri tener, (Osnesessons:sSTARLING FORCES * Determine fluid movement through capilary wall + Includes nyerostatiiid pressures, oncoticprotein pressures + Three Stating forces at playin glomerular filytion barrer * Hydrostatic pressure of blood in capilary P,) Hydrostatic pressure of trate in Bowman's space (P,) * Oncetic pressure of proteins in capilary ie) + Deterrines net ulvafitration pressure of glomerulus: P, =P,,-(P,,+®,) * Net ultrafitration pressure | along each glomerular capiary—as fd removed, proteins remain (tm) + At fivation equilbium, net ultrafitration pressure equals 0 no fi Fltered) Bowman's Bowman's ‘Space CAPSULE CAPILLARY Figure 613 Illustration depicting the three ‘Starling forces at play in the glomerular filtration barrier. GLOMERULAR FILTRATION RATE (GFR) + Fitrate volume produced by all of body's glomeruli in one minute 1K, where, is filtration “Kf: indicates capillarys fuid permeability «= Fenestrations, large surface area —+ high K, for glomeruiar capilaries + Depends on all three Staring forces 534 OSMOSIS.ORG Hydrostatic blood pressure in capillary + Positive relationshio + Afferent arteriole vasoconstriction — | renal blood flow "| hydrostatic blood pressure in capillary UUGFR) + Afferent arteriole vasodllation — 1 renal blood flow * 1 hydrostatic blood pressure in capillary (GFR) + Efferent arteriole vasoconstriction —+f fluid in glomerular capillary "hydrostatic blood pressure in capillary {GFR} + Etferent arteriole vasodilation —+ | fluid in glomerular capillary * | hydrostatic blood pressure in capillary (GFR) Hydrostatic filtrate pressure in Bowman's space + Negative relationship = Doesn't normally occur * Urine flow blockage —> urine backup (es. stone lodged in ureter] = t nyarostatic filtrate pressure in Bowman's space (j GFR) Oncotic protein pressure in capillary + Negative relationship + tplasma protein concentration can t ‘oncatic protein pressure in capillary {J GFR} + [plasma protein concentration can | ‘oncotic protein pressure in capillary {| GFR) FILTRATION FRACTION (FF) + Ratio of glomerular tation rate to renal piasma flow SFE = GFR/RPF + Indicates how much fd reaching kidneys is fitered into renal tubules OSMOSIS.orgChapter 61 Renal Physiology: Renal Electrolyte Regulation PROXIMAL CONVOLUTED TUBULE + First renal tubule segment + Receives fitrate from renal corpuscle + Passes titrate to loop of Henle + Lined by brush border cel's * Apical surface faces lumen: lined with rmicrovil ' Basolateral surface faces interstitium + Surrounded by peritubular capillaries reabsorption, secretion of solutes to/from blood via interstitium + Reabsorbs Na’, K', Cat, Cl, Mg into bloodstream NAY MOVEMENT. ‘Natural concentration gradient from lumen into cells + Cotransporters: use this energy to move other solutes eg. Na*-glucose cotransporter} + Na’/K" ATPase: pumps 3Na’ from cel into interstitium, 2K: from interstitium inta cell «Movement against two concentration gradients + ATP required + Na‘/H' exchanger: pumps Na* from cel into cell, Hom cell into \urnen + Assists HCO,” reabsorplion by creating H,CO, -+#,0 + CO, Paracellular route + Leaky tight junctions — some Na* movement between cells, * | claudin proteins + 1 permeability + Urea, water diffuse straight across cells —+ interstturn + Glutarsine breakdown inside cell + NH," {cell—+ lumen} + HCO, {cell —»intersitidrn + Organic acids. some medications diffuse directly from capillaries inte lumen leg, penicliny te am Figure 61.4 The relationship between the proximal convoluted tubule's brush border cells and a peritubular capillary Figure 615 The Na“-glucose cotransoorter uses the concentration gradient of Na" to transport glucose against its concentration gradient, jure 61.6 Na‘iK* ATPase and the paracellular route of Na’ movernent. OSs esssone 3sLOOP OF HENLE + Receives fitrate from proximal convoluted tubule + Passes fitrate to distal convoluted tubule + Composed of descending, thin ascending, ‘thick ascending limbs + Establishes osmotic gradient; allows varying urine concentration + Lined by epithelial cells * Apical surface faces lumen * Basolateral surface faces interstitium + Surrounded by peritubular capillaries = AKA vasa recta * Reabsorption, secretion of solutes to! from blood via interstitium Descending timb + Fitrate that enters has osmolarity of ~300mOsm {intersttil osmolatity) + Squarnous epithelial co's have aquaporins on both surfaces * Water moves across cells into interstitium + Osmotarty f to ~1200m0smil at bottom of loop Thin ascending limb + No aquaporins on thin ascending limb: Na’, Cichannels instead = Move from lumen into interstitium along concentration gradient + Osmolarty | to ~600mOsmil at top of thin loop ‘Thick ascending limb + Cuboidal epithelium in thick ascending limb has Na-K-2Cl cotransporters, += Na’, K’, 2CI- maved from lumen into cells using Na‘ concentation gradient += Navk’ ATPase works as previously + K:, Cl channels —+ move from cel into Interstium along concentration gradient + Osmolarty | to ~325mOsmiL at top of thick loop. + Countercurrent multiplication: process of creating concentration gradient along loop 536 OSMOSIS.ORG Figure 617 Countercurrent multiplication Is the process of creating the concentration gradient along the loop of Henle, It uses ATP, Figure 618 Aquaporins transport H,0 ‘out of the thin descending limb; channel proteins transport Na* and Cr out of the thin ‘ascending limb; Na-K-2C! cotransporters and Channels transport Nar, K', and Cr out of the thick ascending limb.Chapter 61 Renal Physiology: Renal Electrolyte Regulation DISTAL CONVOLUTED TUBULE * GARLY DISTAL ‘ConVOLUTED TUBULE LATE DISTAL ConvatuTeD TusuLe * COLLECTING DUCT Figure 619 Fitrate passes through the early ‘and late portions of the distal convoluted tubule, then reaches the collecting duct + Receives filtrate from loop of Henle + Passes fitrate to collecting ducts + Composed of early late distal convoluted tubules * Lined by brush border cel's * Apical surface faces lumen; not lined with microvl + Basolateral surface faces interstitium + Surrounded by peritubular capillaries > reabsorption, secretion of solutes to/from blood via interstitium, Early distal convoluted tubule + Impermeable to water + Na": natural concentration gradient from lumen cells + Cotransporters use this energy to move other solutes jeg. NaCl cotransporter) += Cl moves trom cells ~» interstitium through direct channels moves across cells + interstitium ‘through direct channels, + On basolateral surface: Na'-C channel pumps Na* from interstitium —» cell, Ca? from cell — interstitium + Ca¥ reabsorption regulated by parathyroid hormone * Creates more Na'-Ca®* channels + Na'fk* ATPase works as previously Figure 6110 Illustration of transporters presentin the early distal convoluted tubule. Late distal convoluted tubule + + collecting ducts + Principal cells, a-intercalated cells dispersed among brush border cells + Aldosterone upregulates pump synthesis + Principal cells have = Ké pumps (cell lumen: uses ATP) Na pumps ‘ENaC’; lumen + cel) = Nasik ATPases + Aquaporin2 in principal cells allows for water reabsorption in respanse to antidiuretic hormone intercalated cells have *H’ ATPases, H’-K' ATPases (movement against concentration gradients -» ATP. requires} = Nati: ATPases Figure 6111 Illustration of transporters presentin the late distal convoluted tubule. Os nesssone 87538 OSMOSIS.ORG TF/P, RATIO & TE/Paniy (TE/P)x RATIO + Refers to concentration of substance (x) in tubular Mid (TF) and plasma (Pat given point nephron Helps determine substance net secretion/ absorption + (TAP) +X: not reabsorbedsecreted (e.g. freely fitereo} +X reabsorbed in proportion to water FE. (TIP) aug ~ 1 when glucose, water reabsorbed equally in Bowman's space + CFP )c<1 =X reabsorbed more than water ££. (TFIPljag < 1 when glucose reabsorbed more than water along proximal tubule + CTFPe> 1 X: reabsorbed less than water secreted into tubular fluid +Eg (TFIP],,, > Lin presence of antidiuretic Hormone (ADH at collecting ducts water reabsorbed, not urea} (TF + Inulin (inert substance—nether reabsorbed nor secrateg} concentration throughout nephvon helps determine how much is, reabsorbed + Inulin concentration wil fas water is reabsorbed + Determined using this formula Pron of tre water nabbed =e Fraction of fitered water reabsorbed = 1-112 =05 {50%) * (TFPI, = 2 when 50% of water is reabsorbed {inulin concentration doubles} + Double ratio formula determines traction of fitered load of substance in nephron at any point (rep TTP “f(T, divided by TFPhnuin = 0: ‘hen 30% sodium remains in tubule, 70% reabsorbed OSMOSIS.orgCALCIUM HOMEOSTASIS +296 Cat* found in intracelluiar fluid (ICF, Filtered load reabsorption extracellular fluid (ECF); 9996 in bones, + Coupled with Nar reabsoretion in proximal teeth tubule, loop of Henle (passively reabsorbed + Funetions: cell membrane permeability via electrachernical gradient created by Ni blood clotting, muscle contraction water) + 40% plasma Ca bound to protein = 67% reabsorbed by proximal tubule * Unbound is physiologically active + 2596 reabsorbed in thick ascending limb + Regulated by parathyroid nermone of loop of Henle (paracellular route}: loop PTH) diuretics | reabsorption/t secretion + 896 reabsorbed in distal tubule Co? HANDLING + Reabsorptive Co regulation ste: oniy nephron segment nat coupled with Na" Filtration reabsorption; PTH, thiazide diuretics + Only unbound Ca" (60%) is fitered +1 Ca reabsorption (hypocaleiuric * Calcuistion of Cat Fitered load if total action} plasma Ca” = BmEaj. and GFR = 180L/ Excretion day teise + 1BOX5X 06 = 540mEqiday MAGNESIUM HOMEOSTASIS + <1% Ma® found in ECF; 60%6in bones, Filtered load reabsorption 20%6in skeleta muscie, 19% insohts5ves, _« 3096 reabuarbed by proximal tubule remainder found inICF + 60% reabsorbed by thick ascending lm of + Functions: neuromuscular act loop of Henle enzymatic reactons within cls ATP + Loop curtis | Ma? reabsorption production; Nav, Ca transport across cell eee ne Ms pron membranes + 5% reabsorbed by distal tubule +2036 plasma Mg"+ bound to protein See reabsorved by distal + Unbound is physiologically active Exeration = 5% Mg** HANDLING Filtration * Only unbound Mg* (80% is filtered MaSMORSORE540 OSMOSIS.ORG PHOSPHATE HOMEOSTASIS 'ICF phosphate (15%) used for DNA, ATP synthesis, other metabolic processes "ECF phosohate (<0.5%) serves as buffer for He + 85% in bones PHOSPHATE HANDLING Fitration + Froely filtered across glomerular capillaries Filtered load reabsorption + 7036 reabsorbed by proxirnal tubule: 15% by proxirnal straight tubule via Nav-phosphate cotransporter in lrminal membrane + Excess phosphate excreted when T,, [transgort maximum) is reached + PTH inhibits No*-phosphate cotransporter, “+ | phosphate T, + phosphaturia Excretion = 159% POTASSIUM HOMEOSTASIS + Potassium (k') primary intracellular cation + Regulates intracellular osmolarity * Concentration gradient across cell membrane establishes resting membrane potential, essential for excitable cell function (e.g. myocardium) INTERNAL kK’ BALANCE * Difference between intracellular I concentration {98% of total K' extracellular K" concentration (296 of total i) maintained by Na’-K* ATPase 1 K> shifts infout of cells «Potentially causes hypo-/nyperkalemia Outward K* shifts + insulin "| Na-K" ATPase activity — | cellular K’ Uptake + Cell lysis «= K° released from ICF V-K" exchange in acidosis =? blood HH" enters cell + K* moves {rom ICF to ECF = TECF osmolarity * Osmotic gradient causes Hj movement out of cals» f Intracellular Ks diffusion of Krom ICF to £C (H,0 brings K° with it) + Beercise * Cellular ATP stores depleted — k channels open in muscle cell membrane =k’ moves down concentration gradient to ECF + e-adrenergic eceator activation Hepatic Ca-dependent-*-channel activation +k! moves from ICF to CF Inward K* shifts + Insulin *TNa'-K° ATPase activity — f cellular K? uptake + Hi-K* exchange in alkalosis, + | blood H! +H" leaves cell + K’ enters cell + J ECF osmolality * Osmotic gradient causes H,0 movement into cells + CF K* concentration + diffusion of K’ fromECF to ICF +B, adrenergic receptor activation “Nav! ATPase activity — K'enters cell EXTERNAL kK’ BALANCE + Dietary K' intake = renal excretion of K* via renal mechanisms Ke HANDLING Filtration + Freely filtered across glomerular capillaries Filtered load reabsorption + 67% reabsorbed by proxinal tubule {isosmotic fuid reabsorption along with water, Na‘) + 20% reabsorbed by thick ascending limo *K" reabsorbed without water [impermeable to water] via Na-k*-2C" cotransporter + K: lffuses through K* channels across basolateral membrane {reabsorption\/K* diffuses into lumen {no reabsorption} + Fine-tuning of K* balance at distal tubule, collecting duct depending on current physiological requirements Chapter 61 Renal Physiology: Renal Electrolyte Regulation + Reabsorbed by a-intercalated cells! secreted by principal cells, «Dietary K's high K° diet—K° enters ces ‘via insulin} +t intracellular K* 1 K in principal cells ~+ | K" secretion across luminal membrane -» 1 K* excretion, low K* diet—1 K: secretion by principal cel, K* reabsorption by a-intercalated cells, * Aldosterone effects on principal cals: presence of aldosterone! hyperaldosteronism {t K* secretion): hypoaldosteronism (1 K" secretion) + Acid-base imbalance effects on principal Celis: alkalosis (tK* secretion}; acidosis (1 K* secretion} + Diuretic effects on principal cells: oop, thiazide ([K" secretion): K" sparing (inhibit aldosterone effects ~+ | K* secretion) + Lumina anions (eg. sulfate, HCO, } in distal tubule. collecting duct (flumen electronegativity by non-reabsorbable anions + 1 K° secretion} Excretion + Varies from 1-110% of fiteres load SODIUM HOMEOSTASIS CousieAry + Sodium (Na‘}: primary cation in ECF ' Determines ECF osmolarity No’ BALANCE REGULATION * Na’ balance (Na’ excretion = Na' intake) determines ECF volume, biood volume, blood pressure (BP) + Positive Na* balance: | Nat retained Ss} Nat in ECF» ECF expansion» blood volume, 7 blood pressure + Negative Na* balance: f excreted. lost in Urine -+ | Na* in ECF —+ ECF contraction “+ [blood volume, j blood pressure Oued Effective arterial blood volume (EABV) * ECF volume with arteral system perfuses tissue + Normal ECF changes — parallel ABV changes (eg.7 ECF = 1 EASF) + Edema: fluid fitered into interstitial space => TECF —» | EABY {1 BP} —+ Na” excretion altered by kidneys {attempts to restore normal EABF, BP) Na+ excretion regulation (1/1) mechanisms + Sympathetic nervous system activity * Baroreceptors detect | BP + sympathetic nervous system activation — afferent arteriole vasoconstriction, ¢ ) S MOSMOSISORG-541Nat reabsorption by proximal tubule + Natriuretic hormones: respond to 7 ECF volume — | GFR, natures (renal Ne", ‘water excretion) —» | ECF “Atrial natriuretic peptide (ANP): volume receptors detect atl wall stretching — ANP secteted by cells in atria + Brain natriuretic peptide (BNP): volume receptors in ventricles detect stretching + BNP secreted by cells in ventricles + Urodilatin: synthesized in distal tubular cells paracrine actions on kidney * Peritubular Starling forces © TEC volume —+ ECF dilution, |, {capilary encote pressure): | proximal tubule Na* reabsorption += J ECF volume» 1 ECF concentration, 1 151 proximal tubule Na* reabsorption + Renin-angiotensin-aldosterone system (RAAS):| arterial Blood pressure (BP) + | renal perfusion + juxtaglomerular apparatus secretes renin + angiotensinogen (plasma protein) converted to angiotensin |» Angiotensin | converted to angiotensin i “+ adrenal cortex secretes aldosterone, vasoconstriction —+ T Nat, Cl, water reabsorption + t ECF volume, | BP Excess Na’ intake response + Na" ECF distribution + 7 ECF, t EABV, it, | sympathetic activity, t ANP [and ‘ther natriuretic hormones), | RAAS + t Nar excretion Decreased Na’ intake response +L ECF, | EABV, 11m, — f sympathetic activity, | ANP {and other natriuretic hormones), RAAS —+ | Nat excretion 542 OSMOSIS.ORG Na’ HANDLING Filtration, + Freely filtered across glomerular capillaries Filtered load reabsorption + 67% reabsorbed by proximal tubule *Isosmotic reabsorption of water, Nat » Water reabsorption coupled with Na* reabsorption (TPP), = 1) + 25% reabsorbed by tick ascending limb * Na reabsorbed without water {impermeable to water} via Na*-K™-2Cl cotransporter + Influenced by ADH, loop diuretics + 5% reabsorbed by ea istal convoluted tubule * Na’ reabsorbed without water {impermeable to water] via Na’-2C! cotransporter + Influenced by thazide diuretics + 3% reabsorbed by late distal convoluted tubule “Influenced by aldosterone Excretion 1 /< 196 excreted (99% net Na* reabsorption} OSMOSIS.org