Renal Reabsorption and Secretion Notes

NOTES NOTES RENAL REABSORPTION & SECRETION TUBULAR REABSORPTION & SECRETION osms.it/tubular-reabsorption-secretion ▪ Blood chemistry balanced, urine formed through glomerular filtration, tubular reabsorption, secretion ▫ Filtered blood continues through glomerulus, substances reabsorbed/ secreted according to body’s needs ▫ Entire plasma volume filtered approx. 60 times/day Filtration with partial reabsorption ▪ Electrolytes (e.g. sodium, bicarbonate) easily reabsorbed, may be partially reabsorbed, secreted REABSORPTION SECRETION ▪ Retention of substances contained in filtrate back into peritubular capillary blood Filtration only/no reabsorption ▪ Occurs with: products of metabolism (e.g. urea, creatinine), foreign substances (e.g. drugs) Filtration with complete reabsorption ▪ Nutritional substances (e.g. glucose, amino acids) completely reabsorbed ▪ Substances not reabsorbed (e.g. organic acids), secreted into tubular fluid to become urine TUBULAR REABSORPTION OF GLUCOSE osms.it/tubular-reabsorption-glucose ▪ Filtration rate of glucose: mass of glucose filtered through kidneys per day (depends on plasma glucose concentration) ▪ Kidney filtrate passes through renal tubules in nephron before becoming urine ▫ Tubules lined by brush border cells with apical surface (lined with microvilli), basolateral surface; peritubular capillaries surround tubules GLUCOSE REABSORPTION ▪ Occurs primarily in proximal convoluted tubule OSMOSIS.ORG 543

Figure 62.1 Graph showing glucose filtration rate as a function of plasma glucose. As the plasma glucose concentration increases, the filtered load of glucose increases linearly. Two steps 1. Glucose moves across apical membrane into brush border cells ▫ Glucose concentration inside cells typically higher than outside → sodiumglucose linked transporters use energy from existing sodium concentration gradient to move glucose against concentration gradient 2. Glucose diffuses across basolateral membrane into peritubular capillaries (facilitated diffusion with GLUT1/GLUT2) ▪ Normal plasma glucose levels (< 200mg/ dL): glucose reabsorption matches filtration ▪ High plasma glucose levels (> 200mg/ dL): limited number of glucose transporter proteins prevents reabsorption from keeping up with filtration ▪ Higher glucose levels (> 350mg/dL): glucose transporter proteins fully saturated, reabsorption cannot go faster; transport maximum (Tm) GLUCOSE EXCRETION ▪ Excess glucose excreted in urine ▫ Threshold: plasma glucose level at which glucose excretion starts ▫ Splay: initial, nonlinear increase in urine excretion ▪ Glycosuria (glucose excreted in urine) may be caused by diabetes mellitus (↓ insulin → ↑ plasma glucose)/hormonal changes during pregnancy (↑ renal blood flow → ↑ glucose filtration) Figure 62.12 An illustration depicting the two steps of glucose reabsorption that occur in the proximal convoluted tubule: transport across the apical membrane of the brush border cells, followed by transport across the basolateral membrane of the brush border cells by GLUT1 or GLUT2. 544 OSMOSIS.ORG

Chapter 62 Renal Physiology: Renal Reabsorption & Secretion Figure 62.2 A graph showing glucose reabsorption and secretion rates as a function of plasma glucose. The glucose reabsorption line plateaus because the plasma [glucose] has been reached where all the GLUT1/GLUT2 transporters in virtually all the nephrons are occupied by glucose molecules. TUBULAR SECRETION OF PARAANIMOHIPPURIC ACID (PAH) osms.it/tubular-secretion-PAH ▪ Body's entire plasma volume, including some para-aminohippuric acid (PAH), filtered approx. 60 times/day ▫ PAH: organic acid; approx. 90% bound to plasma proteins, cannot be filtered ▫ Filtration rate of PAH: mass of PAH filtered through kidneys per day (depends on plasma concentration of unbound PAH) ▪ Kidney filtrate passes through renal tubules in nephron before becoming urine ▫ Tubules lined by brush border cells with apical surface (lined with microvilli), basolateral surface; peritubular capillaries surround tubules Figure 62.3 Graph showing PAH filtration rate as a function of unbound plasma PAH. OSMOSIS.ORG 545

▪ No renal reabsorption of PAH ▪ PAH secretion occurs primarily in proximal convoluted tubule ▫ Special carrier proteins on basolateral membrane transport PAH, other organic anions directly into tubules ▪ Low plasma PAH levels: PAH secretion increases linearly with PAH concentration ▪ Higher plasma PAH levels: limited number of carrier proteins prevents secretion from increasing, even with increasing PAH concentration (Tm) → some PAH left behind in peritubular capillaries ▪ Both filtered, secreted PAH excreted in urine Using PAH to estimate renal plasma flow (RPF) ▪ Fick’s principle: PAHentering = PAHleaving ▪ PAH enters kidney via renal artery; leaves via renal vein/urine ▪ Low PAH concentrations (< Tm): all PAH leaves via urine ▪ PAHentering = PAHexcreted ▪ [PAH]R.A. x RPF = [PAH]urine x urine flow rate (UFR) ▫ Renal, urine concentrations of PAH both measured in milligrams per millilitre ▫ RPF, urine flow rate (UFR) both measured in liters per minute ▪ RPF = ([PAH]urine x UFR)/[PAH]R.A. (milliliters of plasma per minute) ▪ Some PAH may remain in renal vein → estimate usually accurate to 10% of true RPF ▪ Renal plasma flow can be used to calculate renal blood flow (RBF) ▫ RBF = RPF/(1-Hct) ▫ Hematocrit (Hct): volume of blood occupied by red blood cells (RBCs) Figure 62.4 Graph showing PAH secretion and excretion rates as a function of plasma PAH. 546 OSMOSIS.ORG

Chapter 62 Renal Physiology: Renal Reabsorption & Secretion UREA RECYCLING osms.it/urea-recycling ▪ Urea: one of body’s waste products (byproduct of amino acid breakdown) ▪ Freely filtered across kidneys’ glomerular capillaries, travels through renal tubule ▪ Part of reabsorbed urea secreted back into loop of Henle → “urea recycling” ▫ Helps establish corticopapillary gradient (reabsorbs water from kidneys back into blood) Four steps to urea recycling ▪ 50% of urea reabsorbed by simple diffusion in proximal convoluted tubule (leaving behind 50% of initial urea), together with water ▪ Urea from medullary interstitium secreted back into tubule in descending limb of loop of Henle (resulting in 110% of initial urea in bottom of loop of Henle) ▫ Occurs due to higher urea concentration in medullary interstitium ▪ Ascending limb of loop of Henle, early distal convoluted tubule impenetrable to urea, water (urea levels stay same) ▪ 70% of initial urea reabsorbed into interstitium in late distal convoluted tubule, cortical, outer medullary collecting ducts (leaving behind 40% of initial urea to be excreted in urine) ▫ Occurs due to antidiuretic hormone (ADH)-induced water reabsorption through aquaporins → concentration gradient of urea towards interstitium WEAK ACIDS & BASES NON-IONIC DIFFUSION osms.it/non-ionic_diffusion ▪ Many substances secreted by proximal tubule weak acids/bases ▪ Exist in uncharged (nonionic)/charged (ionized) forms; amount depends on pH of tubular fluid ▫ Urine with low pH: nonionic forms dominate ▫ Urine with higher pH: ionized forms dominate ▪ Nonionic weak acids, bases lipid soluble, able to passively diffuse back into blood from urine ▪ Ionized weak acids, bases not lipid soluble, remain in tubular fluid to be excreted ▪ Excretion of unwanted substances, toxins accomplished by manipulating urine pH, promoting ionization OSMOSIS.ORG 547