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The amount excreted in urine depends in large measure on the magnitude of tubular transport. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 1 Reabsorption involves transport › Across the tubular epithelial membranes into the interstitial fluid,then › Through peritubular capillary membrane back into blood. Reabsorption across the tubular epithelial membranes into the interstitial fluid includes active and passive transport. › Transcellular › Para cellular Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 2 Tubular Reabsorption Figure 27-1; Guyton and Hall Copyright © 2006 by Elsevier, Inc. Through the peritubular capillary walls into the blood by ultrafiltration Active transport can move a solute against electrochemical gradient and requires energy. › Primary active transport. › Second active transport. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 4 Primary active transporters include: › Na+ - K+ ATPase, H+ ATPase, H+ - K+ATPase,Ca2+ - ATPase. Active transport mechanism for reabsorption of large molecules such as protein ( Pinocytosis) Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 5 Primary Active Transport of Na+ Figure 27-2; Guyton and Hall Copyright © 2006 by Elsevier, Inc. Mechanisms of Secondary Active Transport Copyright © 2006 by Elsevier, Inc. Figure 27-3; Guyton and Hall For most substances that are actively reabsorbed or secreted, there is a limit to the rate at which the solute can be transported. › Transport maximum. Occur when tubular load exceeds the capacity of carrier proteins and specific enzymes involved in the transport process. . Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 8 Figure 27-4; Guyton and Hall Copyright © 2006 by Elsevier, Inc. Proximal tubular fluid is essentially isosmotic to plasma. Overall 65% filtered solutes and water are reabsorbed along the proximal tubule. Na+ are major osmotically active solutes in the plasma and glomerular filtrate. Though the osmolality ( total solute concentration) does not change detectably along the proximal convoluted tubule, the concentration of individual solutes vary widely . Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 10 65% of filtered Na+ is reabsorbed along with filtered water,also 65% of K+ Creatinine and urea are very poorly reabsorbed. PAH is secreted into tubule. Inulin is neither reabsorbed nor secreted. Glucose, amino acids are almost completely reabsorbed. › Cl and HCO3 accompany Na+ in plasma and glomerular filtrate. › › › › Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 11 Cellular Ultrastructure and Primary Transport Characteristics of Proximal Tubule Figure 27-6; Guyton and Hall Copyright © 2006 by Elsevier, Inc. Na+ reabsorption › is the major driving force › for reabsorption of solutes and water in the proximal convoluted tubules Na+ enters the cell from the lumen across the luminal membrane and is pumped out across the basolateral cell membrane by Na+/ K+ ATPase pump. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 13 The Na+ and accompanying anions and water are taken up by the blood surrounding the tubule across the interstitial fluid. At luminal cell membrane ( brush border), › Na+ enter the cell down a combined electrical and chemical potential gradient. Na+ is reabsorbed together with › glucose, AA; Phosphate and other solutes by way of separate,specific contransportes. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 14 The down hill movement of Na+ drives the up hill transport of these solutes (secondary active transport). › Na+ is also reabsorbed across the luminal cell membrane in exchange for H+, › Na± H+ exchangers is also secondary active transport mechanism. › Cl-are reabsorbed by way of an electrical potential and [ Cl- ] gradient, also by secondary active transport.(contransport of Cl- with Na+ across luminal membrane. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 15 Accumulated K+ in tubular cells diffuse out of the basolateral cell membrane, mostly through K+ channels. Glucose and AA accumulated in the cell because of secondary active transport exit across the basolateral cell membrane by diffusion. Bicarbonates exist together with Na+ by an electrogenic mechanism, Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 16 Cl- may leave the cell by way of an electrically neutral K – Cl cotransporter. Reabsorption of Na+ and accompanying solutes establishes an osmotic gradient across the proximal tubule epithelium › that is the driving force for water reabsorption. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 17 Reasorption of Water and Solutes is Coupled to Na+ Reabsorption Tubular Cells Interstitial Fluid - 70 mV Na + K+ ATP Na + ATP 0 mv Copyright © 2006 by Elsevier, Inc. K+ Tubular Lumen H+ Na + glucose, amino acids Na + Urea H20 Na + Cl- - 3 mV Mechanisms by which Water, Chloride, and Urea Reabsorption are Coupled with Sodium Reabsorption Figure 27-5; Guyton and Hall Copyright © 2006 by Elsevier, Inc. Uptake of reabsorbed solutes and water by peritubular capillaries involve the usual starling forces that operate across the capillary wall. › Low peritubular capillaries hydrostatic pressure. › High peritubular capillaries oncotic pressure Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 20 The proximal tubules secrete organic acids and bases. › Endogenous compounds,drugs, toxins e.g.. Oxalate, urate, bile salts, catecholamine. › By secondary active transport (counter transport). Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 21 5 4 Cretinin e 3 Cl- 2 5 Na+ 1 HCO3- 0.5 0.2 0.1 0.005 50 Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 100 5/9/2017 22 Filtrate entering the loop is isosmotic to plasma. › Proximal straight tubule has transport properties similar to those proximal convoluted tubule. Thin descending and thin ascending segments have thin epithelia membrane, no brush borders, few mitochondria. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 23 The descending segment is highly permeable to water and moderate permeable to most solutes includes urea and Na+. › This segment allows simple diffusion substances. › Ascending limb is virtually impermeable to water. › 25% of filtered Na+, Cl-, K+ are reabsorbed by loop of Henle, mostly in the thick ascending limb. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 24 Cellular Ultrastructure and Transport Characteristics of Thin and Thick Loop of Henle very permeable to H2O) not permeable to H2O) Figure 27-8; Guyton and Hall Copyright © 2006 by Elsevier, Inc. Thick ascending limb is rich of Na+K+ATPase which is the driving force for reabsorption of other solutes. › Movement of Na+ across the luminal membrane is mediated primarily by 1-Na+, 2Cl-, 1K+ contransporter. › There is also Na+ - H+ countertransport mechanism in the luminal cell membrane which mediates H+ secretion. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 26 Most of the water delivered to the ascending limb remains in the tubule. › Tubular fluid becomes more dilute as it flows toward the distal tubule. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 27 Sodium Chloride and Potassium Transport in Thick Ascending Loop of Henle Figure 27-9; Guyton and Hall Copyright © 2006 by Elsevier, Inc. 1. More solute than water is added to the renal medulla (i.e., solutes are “trapped” in the renal medulla). 2. Fluid in the ascending loop is diluted. 3. Horizontal gradient of solute concentration established by the active pumping of NaCl is “multiplied” by countercurrent flow of fluid. Copyright © 2006 by Elsevier, Inc. First portion of Distal tubule forms part of Juxtaglomerular complex. The rest of early distal tubule is convoluted and has reabsorptive characteristics almost the same as those of thick ascending limb of loop of Henle. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 30 Sodium Chloride Transport in Early Distal Tubule Figure 27-10; Guyton and Hall Copyright © 2006 by Elsevier, Inc. Sodium Chloride Reabsorption and Potassium Secretion in Collecting Tubule Principal Cells Figure 27-12; Guyton and Hall Copyright © 2006 by Elsevier, Inc. Tubular membranes are almost impermeable to urea › Also the early distal tubule. Two distinct cell types. › Principal cells › Intercalated cells Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 33 The principal cells reabsorb Na+ and water from the lumen and secrete K+ › Na+ reabsorbed because of Na+/K+pump › K+ secreted because of Na+/K+ pump in basolateral membrane, and concentration gradient across the luminal membrane. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 34 Intercalated cell › Reabsorb K+ and HCO3- and secrete H+. › H+ secretion is mediated by H+ - ATPase transport mechanism.( primary active transport) › H+ generated by action of carbonic anhydrate H2O + CO2 H2CO3- ⇌ H+ +HCO3-. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 35 • not permeable to H2O • not very permeable to urea • permeability to H2O depends on ADH • not very permeable to urea Figure 27-11; Guyton and Hall Copyright © 2006 by Elsevier, Inc. Na+ reabsorption and K+ secretion is controlled by hormones,especially aldosterone. Permeability of late distal tubules and cortical collecting tubule to water is controlled by ADH. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 37 Cortical Collecting Tubules Intercalated Cells Tubular Cells Tubular Lumen H20 (depends on ADH) H+ K+ K+ ATP ATP Na + K+ H+ ATP ATP ATP Cl Copyright © 2006 by Elsevier, Inc. › Reabsorb less than 10% of filtered water and Na+ › Permeability of membrane to water id controlled by level of ADH. › Medullary collecting duct is permeable to urea. › Capable of secreting H+ against large concentration gradient. Copyright © 2006 by Elsevier, Inc. Functional anatomy of the kidney 5/9/2017 39 Cellular Ultrastructure and Transport Characteristics of Medullary Collecting Tubules Figure 27-13; Guyton and Hall Copyright © 2006 by Elsevier, Inc. Normal Renal Tubular Na+ Reabsorption 7% (16,614 mEq/day) 25,560 mEq/d (1789 mEq/d) 65 % 25 % 2.4% (6390 mEq/d) (617 mEq/day) 0.6 % (150 mEq/day) Copyright © 2006 by Elsevier, Inc. Summary of Water Reabsorption and Osmolarity in Different Parts of the Tubule • Proximal Tubule: 65% reabsorption, isosmotic • Desc. loop: 15-20% reabsorption, osmolarity increases • Asc. loop: 0% reabsorption, osmolarity decreases • Early distal: 0% reabsorption, osmolarity decreases • Late distal and coll. tubules: ADH dependent water reabsorption and tubular osmolarity • Medullary coll. ducts: ADH dependent water reabsorption and tubular osmolarity Copyright © 2006 by Elsevier, Inc.