Renal Electrolyte Regulation Notes
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NOTES NOTES RENAL ELECTROLYTE REGULATION GLOMERULAR FILTRATION osms.it/glomerular-filtration ▪ Fluid passage through glomerular ﬁltration barrier; approx. 125mL/min ▪ Glomerular ﬁltrate: ﬂuid that passes through all glomerular ﬁltration barriers ▫ Blood minus red blood cells, plasma proteins ▪ Anything remaining in glomerulus carried away by efferent arteriole ▪ Starling forces → glomerular ﬁltration ▫ Different pressures of ﬂuids, proteins in glomerular capillaries, Bowman's space ▪ Most ﬁltration occurs at beginning of glomerulus, nearer afferent arteriole ▪ ▪ ▪ ▪ 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 Juxtaglomerular 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-like layer with tiny pores ▪ Blocks plasma protein passage ▫ Due to pore size, negative membrane charge Figure 61.1 An illustration depicting the glomerulus and its relationship to the rest of the nephron. Epithelium ▪ Comprised of podocytes (wrap around basement membrane) ▪ Also blocks plasma protein passage GLOMERULAR FILTRATION BARRIER ▪ Capillary walls of glomerulus ▫ Glomerulus: tuft of capillaries in nephron’s renal corpuscle ▫ Blood enters glomerulus through afferent arteriole → leaves through efferent arteriole → divides into Figure 61.2 The three layers of the glomerular ﬁltration barrier. OSMOSIS.ORG 533
STARLING FORCES ▪ Determine ﬂuid movement through capillary wall ▪ Includes hydrostatic/ﬂuid pressures, oncotic/protein pressures ▪ Three Starling forces at play in glomerular ﬁltration barrier ▫ Hydrostatic pressure of blood in capillary (Pgc) ▫ Hydrostatic pressure of ﬁltrate in Bowman’s space (Pbs) ▫ Oncotic pressure of proteins in capillary (ℼgc) ▪ Determines net ultraﬁltration pressure of glomerulus: Puf = Pgc - (Pbs + ℼgc) ▫ Net ultraﬁltration pressure ↓ along each glomerular capillary—as ﬂuid removed, proteins remain (↑ ℼgc) ▫ At ﬁltration equilibrium, net ultraﬁltration pressure equals 0 (no ﬂuid ﬁltered) Figure 61.3 Illustration depicting the three Starling forces at play in the glomerular ﬁltration barrier. GLOMERULAR FILTRATION RATE (GFR) ▪ Filtrate volume produced by all of body’s glomeruli in one minute ▪ GFR = Puf × Kf where Kf is ﬁltration coefﬁcient ▫ Kf: indicates capillary’s ﬂuid permeability ▫ Fenestrations, large surface area → high Kf for glomerular capillaries ▪ Depends on all three Starling forces 534 OSMOSIS.ORG Hydrostatic blood pressure in capillary ▪ Positive relationship ▪ Afferent arteriole vasoconstriction → ↓ renal blood ﬂow ▫ ↓ hydrostatic blood pressure in capillary (↓ GFR) ▪ Afferent arteriole vasodilation → ↑ renal blood ﬂow ▫ ↑ hydrostatic blood pressure in capillary (↑ GFR) ▪ Efferent arteriole vasoconstriction → ↑ ﬂuid in glomerular capillary ▫ ↑ hydrostatic blood pressure in capillary (↑ GFR) ▪ Efferent 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 (e.g. stone lodged in ureter) ▫ ↑ hydrostatic ﬁltrate pressure in Bowman’s space (↓ GFR) Oncotic protein pressure in capillary ▪ Negative relationship ▪ ↑ plasma protein concentration can ↑ oncotic protein pressure in capillary (↓ GFR) ▪ ↓ plasma protein concentration can ↓ oncotic protein pressure in capillary (↑ GFR) FILTRATION FRACTION (FF) ▪ Ratio of glomerular ﬁltration rate to renal plasma ﬂow ▫ FF = GFR / RPF ▪ Indicates how much ﬂuid reaching kidneys is ﬁltered into renal tubules
Chapter 61 Renal Physiology: Renal Electrolyte Regulation PROXIMAL CONVOLUTED TUBULE osms.it/proximal-convoluted-tubule First renal tubule segment Receives ﬁltrate from renal corpuscle Passes ﬁltrate to loop of Henle Lined by brush border cells ▫ Apical surface faces lumen; lined with microvilli ▫ Basolateral surface faces interstitium ▪ Surrounded by peritubular capillaries → reabsorption, secretion of solutes to/from blood via interstitium ▪ Reabsorbs Na+, K+, Ca2+, Cl-, Mg2+ into bloodstream ▪ ▪ ▪ ▪ Figure 61.4 The relationship between the proximal convoluted tubule's brush border cells and a peritubular capillary. NA+ MOVEMENT Natural concentration gradient from lumen into cells ▪ Cotransporters: use this energy to move other solutes (e.g. Na+-glucose cotransporter) ▪ Na+/K+ ATPase: pumps 3Na+ from cell into interstitium, 2K+ from interstitium into cell ▫ Movement against two concentration gradients → ATP required ▪ Na+/H+ exchanger: pumps Na+ from cell into cell, H+ from cell into lumen ▫ Assists HCO3- reabsorption by creating H2CO3 → H2O + CO2 Paracellular route ▪ Leaky tight junctions → some Na+ movement between cells ▫ ↓ claudin proteins → ↑ permeability ▪ Urea, water diffuse straight across cells → interstitium ▪ Glutamine breakdown inside cell → NH4+ (cell → lumen) + HCO3- (cell → interstitium) ▪ Organic acids, some medications diffuse directly from capillaries into lumen (e.g. penicillin) Figure 61.5 The Na+-glucose cotransporter uses the concentration gradient of Na+ to transport glucose against its concentration gradient. Figure 61.6 Na+/K+ ATPase and the paracellular route of Na+ movement. OSMOSIS.ORG 535
LOOP OF HENLE osms.it/loop-of-henle ▪ Receives ﬁltrate from proximal convoluted tubule ▪ Passes ﬁltrate 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 limb ▪ Filtrate that enters has osmolarity of ~300mOsm/L (interstitial osmolarity) ▪ Squamous epithelial cells have aquaporins on both surfaces ▫ Water moves across cells into interstitium ▪ Osmolarity ↑ to ~1200mOsm/L at bottom of loop Figure 61.7 Countercurrent multiplication is the process of creating the concentration gradient along the loop of Henle. It uses ATP. Thin ascending limb ▪ No aquaporins on thin ascending limb; Na+, Cl- channels instead ▫ Move from lumen into interstitium along concentration gradient ▪ Osmolarity ↓ to ~600mOsm/L at top of thin loop Thick ascending limb ▪ Cuboidal epithelium in thick ascending limb has Na-K-2Cl cotransporters ▫ Na+, K+, 2Cl- moved from lumen into cells using Na+ concentration gradient + ▪ Na /K+ ATPase works as previously ▪ K+, Cl- channels → move from cell into interstitium along concentration gradient ▪ Osmolarity ↓ to ~325mOsm/L at top of thick loop ▪ Countercurrent multiplication: process of creating concentration gradient along loop 536 OSMOSIS.ORG Figure 61.8 Aquaporins transport H2O out of the thin descending limb; channel proteins transport Na+ and Cl- out of the thin ascending limb; Na-K-2Cl cotransporters and channels transport Na+, K+, and Cl- out of the thick ascending limb.
Chapter 61 Renal Physiology: Renal Electrolyte Regulation DISTAL CONVOLUTED TUBULE osms.it/distal-convoluted-tubule Figure 61.9 Filtrate passes through the early and late portions of the distal convoluted tubule, then reaches the collecting duct. ▪ Receives ﬁltrate from loop of Henle ▪ Passes ﬁltrate to collecting ducts ▪ Composed of early, late distal convoluted tubules ▪ Lined by brush border cells ▫ Apical surface faces lumen; not lined with microvilli ▫ 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 (e.g. Na+-Cl- cotransporter) ▪ Cl- moves from cells → interstitium through direct channels ▪ Ca2+ moves across cells → interstitium through direct channels ▫ On basolateral surface: Na+-Ca2+ channel pumps Na+ from interstitium → cell, Ca2+ from cell → interstitium ▪ Ca2+ reabsorption regulated by parathyroid hormone ▫ Creates more Na+-Ca2+ channels ▪ Na+/K+ ATPase works as previously Figure 61.10 Illustration of transporters present in the early distal convoluted tubule. Late distal convoluted tubule ▪ → collecting ducts ▪ Principal cells, α-intercalated cells dispersed among brush border cells ▪ Aldosterone upregulates pump synthesis ▪ Principal cells have ▫ K+ pumps (cell → lumen; uses ATP) ▫ Na+ pumps (“ENaC”; lumen → cell) ▫ Na+/K+ ATPases ▪ Aquaporin 2 in principal cells allows for water reabsorption in response to antidiuretic hormone ▪ α-intercalated cells have ▫ H+ ATPases, H+-K+ ATPases (movement against concentration gradients → ATP required) ▫ Na+/K+ ATPases Figure 61.11 Illustration of transporters present in the late distal convoluted tubule. OSMOSIS.ORG 537
TF/PX RATIO & TF/PINULIN osms.it/TF_Px-ratio-TF_Pinulin [TF/P]x RATIO ▪ Refers to concentration of substance (X) in tubular ﬂuid (TF) and plasma (P) at given point in nephron Helps determine substance net secretion/ absorption ▪ [TF/P]x = 1 ▫ X: not reabsorbed/secreted (e.g. freely ﬁltered) ▫ X: reabsorbed in proportion to water ▫ E.g. [TF/P]glucose = 1 when glucose, water reabsorbed equally in Bowman’s space ▪ [TF/P]x < 1 ▫ X: reabsorbed more than water ▫ E.g. [TF/P]glucose < 1 when glucose reabsorbed more than water along proximal tubule ▪ [TF/P]x > 1 ▫ X: reabsorbed less than water/X secreted into tubular ﬂuid ▫ E.g. [TF/P]urea > 1 in presence of antidiuretic hormone (ADH) at collecting ducts (water reabsorbed, not urea) 538 OSMOSIS.ORG [TF/P]INULIN ▪ Inulin (inert substance—neither reabsorbed nor secreted) concentration throughout nephron helps determine how much is reabsorbed ▪ Inulin concentration will ↑ as water is reabsorbed ▪ Determined using this formula: Fraction of filtered water reabsorbed = 1− 1 [TF / P]inulin ▫ Fraction of ﬁltered water reabsorbed = 1 - 1/2 = 0.5 (50%) ▫ [TF/P]inulin = 2 when 50% of water is reabsorbed (inulin concentration doubles) ▪ Double ratio formula determines fraction of ﬁltered load of substance in nephron at any point [TF / P]x [TF / P]inulin ▪ If [TF/P]Na+ divided by [TF/P]inulin = 0.3, then 30% sodium remains in tubule, 70% reabsorbed
Chapter 61 Renal Physiology: Renal Electrolyte Regulation CALCIUM HOMEOSTASIS osms.it/calcium-homeostasis ▪ 1% Ca2+ found in intracellular ﬂuid (ICF), extracellular ﬂuid (ECF); 99% in bones, teeth ▪ Functions: cell membrane permeability, blood clotting, muscle contraction ▪ 40% plasma Ca2+ bound to protein ▫ Unbound is physiologically active ▫ Regulated by parathyroid hormone (PTH) Ca2+ HANDLING Filtration ▪ Only unbound Ca2+ (60%) is ﬁltered ▪ Calculation of Ca2+ ﬁltered load if total plasma Ca2+ = 5mEq/L and GFR = 180L/ day ▫ 180 X 5 X 0.6 = 540mEq/day Filtered load reabsorption ▪ Coupled with Na+ reabsorption in proximal tubule, loop of Henle (passively reabsorbed via electrochemical gradient created by Na+, water) ▫ 67% reabsorbed by proximal tubule ▫ 25% reabsorbed in thick ascending limb of loop of Henle (paracellular route); loop diuretics ↓ reabsorption/↑ secretion ▪ 8% reabsorbed in distal tubule ▫ Reabsorptive Ca2+ regulation site: only nephron segment not coupled with Na+ reabsorption; PTH, thiazide diuretics → ↑ Ca2+ reabsorption (hypocalciuric action) Excretion ▪ < 1% MAGNESIUM HOMEOSTASIS osms.it/magnesium-homeostasis ▪ < 1% Mg2+ found in ECF; 60% in bones, 20% in skeletal muscle, 19% in soft tissues, remainder found in ICF ▪ Functions: neuromuscular activity; enzymatic reactions within cells; ATP production; Na+, Ca2+ transport across cell membranes ▪ 20% plasma Mg2+ bound to protein ▫ Unbound is physiologically active Filtered load reabsorption ▪ 30% reabsorbed by proximal tubule ▪ 60% reabsorbed by thick ascending limb of loop of Henle ▫ Loop diuretics ↓ Mg2+ reabsorption (↑ excretion) ▪ 5% reabsorbed by distal tubule Excretion ▪ 5% Mg2+ HANDLING Filtration ▪ Only unbound Mg2+ (80%) is ﬁltered OSMOSIS.ORG 539
PHOSPHATE HOMEOSTASIS osms.it/phosphate-homeostasis ▪ ICF phosphate (15%) used for DNA, ATP synthesis, other metabolic processes ▫ ECF phosphate (<0.5%) serves as buffer for H+ ▫ 85% in bones PHOSPHATE HANDLING Filtration ▪ Freely ﬁltered across glomerular capillaries Filtered load reabsorption ▪ 70% reabsorbed by proximal tubule; 15% by proximal straight tubule via Na+-phosphate cotransporter in luminal membrane ▪ Excess phosphate excreted when Tm (transport maximum) is reached ▪ PTH inhibits Na+-phosphate cotransporter → ↓ phosphate Tm → phosphaturia Excretion ▪ 15% POTASSIUM HOMEOSTASIS osms.it/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 K+ BALANCE ▪ Difference between intracellular K+ concentration (98% of total K+), extracellular K+ concentration (2% of total K+) maintained by Na+-K+ ATPase ▪ K+ shifts in/out of cells ▫ Potentially causes hypo-/hyperkalemia Outward K+ shifts ▪ ↓ insulin ▫ ↓ Na+-K+ ATPase activity → ↓ cellular K+ uptake ▪ Cell lysis ▫ K+ released from ICF + ▪ H -K+ exchange in acidosis ▫ ↑ blood H+ → H+ enters cell → K+ moves from ICF to ECF 540 OSMOSIS.ORG ▪ ↑ ECF osmolarity ▫ Osmotic gradient causes H2O movement out of cells → ↑ intracellular K+ → diffusion of K+ from ICF to ECF (H2O brings K+ with it) ▪ Exercise ▫ Cellular ATP stores depleted → K+ channels open in muscle cell membrane → K+ moves down concentration gradient to ECF ▪ 𝝰-adrenergic receptor activation ▫ Hepatic Ca2+-dependent-K+-channel activation → K+ moves from ICF to ECF Inward K+ shifts ▪ Insulin ▫ ↑ Na+-K+ ATPase activity → ↑ cellular K+ uptake ▪ H+-K+ exchange in alkalosis ▫ ↓ blood H+ → H+ leaves cell → K+ enters cell ▪ ↓ ECF osmolality ▫ Osmotic gradient causes H2O movement into cells → ↓ ICF K+ concentration → diffusion of K+ from
Chapter 61 Renal Physiology: Renal Electrolyte Regulation ECF to ICF ▪ β2-adrenergic receptor activation ▫ ↑ Na+-K+ ATPase activity → K+ enters cell EXTERNAL K+ BALANCE ▪ Dietary K+ intake = renal excretion of K+ via renal mechanisms K+ HANDLING Filtration ▪ Freely ﬁltered across glomerular capillaries Filtered load reabsorption ▪ 67% reabsorbed by proximal tubule (isosmotic ﬂuid reabsorption along with water, Na+) ▪ 20% reabsorbed by thick ascending limb ▫ K+ reabsorbed without water (impermeable to water) via Na+-K+-2Clcotransporter ▫ K+ diffuses 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 ▪ Reabsorbed by 𝝰-intercalated cells/ secreted by principal cells ▫ Dietary K+: high K+ diet—K+ enters cells (via insulin) → ↑ intracellular K+ → ↑ K+ in principal cells → ↑ K+ secretion across luminal membrane → ↑ K+ excretion; low K+ diet—↓ K+ secretion by principal cell, ↑ K+ reabsorption by 𝝰-intercalated cells ▫ Aldosterone effects on principal cells: presence of aldosterone/ hyperaldosteronism (↑ K+ secretion); hypoaldosteronism (↓ K+ secretion) ▪ Acid-base imbalance effects on principal cells: alkalosis (↑ K+ secretion); acidosis (↓ K+ secretion) ▪ Diuretic effects on principal cells: loop, thiazide (↑ K+ secretion); K+ sparing (inhibit aldosterone effects → ↓ K+ secretion) ▪ Luminal anions (e.g. sulfate, HCO3-) in distal tubule, collecting duct (↑ lumen electronegativity by non-reabsorbable anions → ↑ K+ secretion) Excretion ▪ Varies from 1–110% of ﬁltered load SODIUM HOMEOSTASIS osms.it/sodium-homeostasis ▪ Sodium (Na+): primary cation in ECF ▫ Determines ECF osmolarity Na+ BALANCE REGULATION ▪ Na+ balance (Na+ excretion = Na+ intake) determines ECF volume, blood volume, blood pressure (BP) ▫ Positive Na+ balance: ↑ Na+ retained → ↑ Na+ in ECF → ECF expansion → ↑ blood volume, ↑ blood pressure ▫ Negative Na+ balance: ↑ excreted, lost in urine → ↓ Na+ in ECF → ECF contraction → ↓ blood volume, ↓ blood pressure Effective arterial blood volume (EABV) ▪ ECF volume with arterial system perfuses tissue ▪ Normal ECF changes → parallel EABV changes (e.g. ↑ ECF = ↑ EABF) ▪ Edema: ﬂuid ﬁltered into interstitial space → ↑ ECF → ↓ EABV (↓ BP) → Na+ excretion altered by kidneys (attempts to restore normal EABF, BP) Na+ excretion regulation (↑/↓) mechanisms ▪ Sympathetic nervous system activity ▫ Baroreceptors detect ↓ BP → sympathetic nervous system activation → afferent arteriole vasoconstriction, ↑ OSMOSIS.ORG 541
Na+ reabsorption by proximal tubule ▪ Natriuretic hormones: respond to ↑ ECF volume → ↑ GFR, natriuresis (renal Na+, water excretion) → ↓ ECF ▫ Atrial natriuretic peptide (ANP): volume receptors detect atrial wall stretching → ANP secreted 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 ▫ ↑ ECF volume → ECF dilution, ↓ ℼc (capillary oncotic pressure); ↓ proximal tubule Na+ reabsorption ▫ ↓ ECF volume → ↑ ECF concentration, ↑ ℼc; ↑ 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 I → angiotensin I converted to angiotensin II → adrenal cortex secretes aldosterone, vasoconstriction → ↑ Na+, Cl-, water reabsorption → ↑ ECF volume, ↑ BP Excess Na+ intake response ▪ → Na+ ECF distribution → ↑ ECF, ↑ EABV, ↓ ℼc → ↓ sympathetic activity, ↑ ANP (and other natriuretic hormones), ↓ RAAS → ↑ Na+ excretion Decreased Na+ intake response ▪ → ↓ ECF, ↓ EABV, ↑ ℼc → ↑ sympathetic activity, ↓ ANP (and other natriuretic hormones), ↑ RAAS → ↓ Na+ excretion 542 OSMOSIS.ORG Na+ HANDLING Filtration ▪ Freely ﬁltered across glomerular capillaries Filtered load reabsorption ▪ 67% reabsorbed by proximal tubule ▫ Isosmotic reabsorption of water, Na+ ▫ Water reabsorption coupled with Na+ reabsorption ([TF/P]Na+ = 1) ▪ 25% reabsorbed by thick ascending limb ▫ Na+ reabsorbed without water (impermeable to water) via Na+-K+-2Clcotransporter ▫ Inﬂuenced by ADH, loop diuretics ▪ 5% reabsorbed by early distal convoluted tubule ▫ Na+ reabsorbed without water (impermeable to water) via Na+-2Clcotransporter ▫ Inﬂuenced by thiazide diuretics ▪ 3% reabsorbed by late distal convoluted tubule ▫ Inﬂuenced by aldosterone Excretion ▪ < 1% excreted (99% net Na+ reabsorption)
Osmosis High-Yield Notes
This Osmosis High-Yield Note provides an overview of Renal Electrolyte Regulation essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Renal Electrolyte Regulation by visiting the associated Learn Page.