Tubular Reabsorption PDF

# Tubular Reabsorption **Highly selective and quantitatively large process** For a substance to be reabsorbed, it must be transported through: * Tubular epithelial membranes into the ISF by: * **Primary active transport:** Na-K, H-K, hydrogen, and the calcium pumps on the basolateral membrane...

# Tubular Reabsorption **Highly selective and quantitatively large process** For a substance to be reabsorbed, it must be transported through: * Tubular epithelial membranes into the ISF by: * **Primary active transport:** Na-K, H-K, hydrogen, and the calcium pumps on the basolateral membrane. * **Secondary active transport** (on the luminal membrane): * **Co-transporter:** for glucose, and amino acids reabsorption * **Counter-transporter:** for hydrogen secretion * **Passive transport:** either transcellularly (through cells) or paracellularly (between the cell junctions) via luminal membrane. * **Pinocytosis:** for protein reabsorption * **Osmosis:** for water reabsorption * Peritubular capillary membrane into the blood by ultrafiltration (bulk flow) **Forces that drive the reabsorption process:** * Reabsorption = Kf × Net reabsorptive force * Reabsorption coefficient = 12.4 ml/min/mmHg * Reabsorptive forces: * **Forces that favor reabsorption:** * Hydrostatic pressure in the renal interstitium [Pif] = 6 mmHg * Colloid osmotic pressure of the peritubular capillary [πc] = 32 mmHg * **Forces that oppose reabsorption:** * Hydrostatic pressure in the peritubular capillaries [Pc] = 13 mmHg * Colloid osmotic pressure of the renal interstitium [πif] = 15 mmHg * Net reabsorptive force = (6 + 32) − (13+15) = 10 mmHg * Reabsorption = 124 ml/min (178.5 L/day) **Fate of Various Substances Filtered by the Kidneys** | Substance | AVERAGE PERCENTAGE OF FILTERED SUBSTANCE REABSORBED | AVERAGE PERCENTAGE OF FILTERED SUBSTANCE EXCRETED | |---------------------|------------------------------------------------------|----------------------------------------------------| | Water | 99 | 1 | | Sodium | 99.5 | 0.5 | | Glucose | 100 | 0 | | Urea (a waste product) | 50 | 50 | | Phenol (a waste product) | 0 | 100 | # Tubular Reabsorption in the Different Segments of Nephron ## Reabsorption in the Proximal Convoluted Tubules: * The high capacity of the proximal tubule for reabsorption results from: * PCT cells are highly metabolic and have large numbers of mitochondria * PCT cells have an extensive brush border on the luminal membrane * PCT cells are loaded with large amount of protein carriers * 65% of sodium, chloride, and water reabsorption occurs in the proximal tubule: * Reabsorption of glucose, and amino acids is linked to it * Involves a Na-K pump in the basolateral membrane: * This pump keeps sodium concentration low in the tubular cells * This pump keeps sodium concentration high outside the tubule * Absorption and secretion of other substances are linked to it: * Glucose is reabsorbed by secondary active co-transport * Amino acids are reabsorbed by secondary active co-transport * Hydrogen is secreted by secondary active counter-transport * Water follows the reabsorbed sodium molecules by osmosis * Water reabsorption: ↑ [chloride] in PCT: passive reabsorption * Oppositely charged chloride follow Na passively (paracellular) * Chloride can be reabsorbed by secondary active co-transport * Bile salt, oxalate, urate, catecholamines, penicillin, salicylates, and PAH are secreted in the proximal convoluted tubule ## Reabsorption in the Loop of Henle: ### Thin Descending Limb: * Highly permeable to water * Moderately permeable to most solutes * Responsible for 20% of water reabsorption ### Thin Ascending Limb: * Virtually impermeable to water * Very low reabsorptive capacity * Doesn't reabsorb significant amounts of solutes ### Thick Ascending Limb: * Virtually impermeable to water * 25% of sodium and chloride reabsorption * Most of the water in this segment remains in the tubule * Tubular fluid becomes very dilute as it flows toward DCT (diluting segment) ## Reabsorption in the Distal Convoluted Tubules: ### Early Distal Convoluted Tubule * Virtually impermeable to water and urea * It is referred to as the diluting segment * 5% of sodium and chloride reabsorption * Na/K+ pump transports Na out of the cell across the basolateral membrane * Na/Cl co-transporter moves NaCl from the tubular lumen into the cell * Chloride diffuses out of cell through channels in the basolateral membrane * The thiazide diuretics inhibit the sodium-chloride co-transporter ### Late Distal Convoluted Tubule and Cortical Collecting Tubule: * Composed of principal cells and intercalated cells * Virtually impermeable to urea * Water reabsorption is under the effect of ADH ### The Principal Cells * Reabsorb sodium and water from the lumen * Secrete potassium ions into the lumen * The site of action of the potassium-sparing diuretics (spironolactone) ### The Type A Intercalated Cells: * Reabsorb potassium ions and secrete hydrogen ions * Secrete hydrogen ions by: * Hydrogen-ATPase transporter * Hydrogen-potassium-ATPase transporter * For each hydrogen ion secreted, a bicarbonate ion is reabsorbed * Eliminate hydrogen ions while reabsorbing bicarbonate in acidosis ### The Type B Intercalated Cells: * Have functions opposite to those of type A cells * Secrete bicarbonate while reabsorbing hydrogen ions in alkalosis ## Reabsorption in the Medullary Collecting Ducts: * The final site for processing the urine * Reabsorb less than 5% of the filtered water and sodium * The permeability to water is controlled by the level of ADH * Unlike the cortical collecting tubule, the medullary CD is permeable to urea * Some of the urea is reabsorbed into the medullary interstitium to raise its osmolality * Capable of secreting hydrogen ions against a large concentration gradient * Play a key role in regulating acid-base balance **Concentrations of solutes in different tubular segments** * The substances represented at the top of figure such as PAH, creatinine, inulin, and urea: * Become highly concentrated in the urine. * These substances are not needed by the body. * Kidneys reabsorb them only slightly or not at all or even secrete them into the tubules. * Kidneys excreting large quantities of them * The substances represented at the bottom of the figure, such as glucose and amino acids: * Strongly reabsorbed. * Substances that the body needs to conserve. * Almost none of them are lost in the urine. **Transport Maximum for substances that are actively reabsorbed** * **Transport maximum (Tmax):** * A limit to the rate at which the solute can be transported. * This limit is due to saturation of the specific transport systems. * When the filtered load exceeds transport maximum the substance appears in urine. * Tmax: glucose = 375, AAs: 15, protein = 30, urate = 15, creatinine = 16, PAH = 80 * Sodium ions don't have transport maximum! * **Transport maximum for glucose:** * In the adult human, the transport maximum for glucose is 375 mg/min * **Normal filtered load of glucose:** * Filtered load of substance = GFR (ml/min) × plasma concentration (mg/ml) * Normal plasma concentration of glucose is 100 mg/dl = 1 mg/ml * Filtered load of glucose = 125 ml/min x 1 mg/ml = 125 mg/min * So, normally glucose doesn't appear in urine * When plasma glucose concentration reaches 200 mg/dl: * Plasma concentration of glucose is 200 mg/dl = 2 mg/ml * Filtered load of glucose = 125 ml/min x 2 mg/ml = 250 mg/min * A small amount of glucose begins to appear in the urine. * This point is termed the threshold for glucose. * Glucose appearance in the urine (at threshold) occurs before the Tmax is reached, because not all nephrons have the same Tmax for glucose. # Regulation of Tubular Reabsorption ## 1- Glomerulotubular Balance: * Intrinsic ability of the tubules to increase reabsorption in response to increased GFR. * If GFR increases from 125 to 150, the absolute rate of proximal tubular reabsorption also increases from about 81 (65% of GFR) to about 97.5 ml/min (65% of GFR) ## 2- Local Control of Tubular Reabsorption: * **Hydrostatic pressure in the peritubular capillaries [Pc]:** * ↑BP →↑ Pc → ↓ reabsorption * Arterioles constriction → ↓ Pc → ↑ reabsorption * **Colloid osmotic pressure of peritubular capillary [πc]:** * ↑ Filtration fraction → ↑ πc → ↑ reabsorption * ↑ Plasma colloid osmotic pressure → ↑ πο * **Increased Pc and reduced πc:** * ↑Fluids in the interstitium * ↑ Backleak into tubular lumen →↓ reabsorption ## 3- Hormonal Control: ### Aldosterone: * Acts on the principal cells of the cortical collecting tubule * Increases sodium reabsorption and potassium secretion * Addison's disease (aldosterone deficiency): depletion of Na, & retention of K * Conn's syndrome (aldosterone excess): retention of Na, & depletion of K ### Angiotensin II: * Stimulates aldosterone secretion. * Vasoconstriction of efferent arteriole: ↓ hydrostatic pressure in the peritubular capillaries and ↑ filtration fraction → ↑ reabsorption * Stimulates sodium reabsorption by stimulating: * Na-K pump on the basolateral membrane * Na-H exchanger in the luminal membrane * Na-bicarbonate co-transporter in the basolateral membrane ### Antidiuretic Hormone (ADH): * Acts on distal convoluted tubule and collecting duct. * Binds to specific V2 receptors: ↑ c-AMP that activates protein kinase. * Stimulates movement of aquaporin-2 (AQP-2) to the luminal membranes. * AQP-2 cluster together and fuse with membrane to form water channels. * AQP-3 & 4: present on the basolateral membrane and are ADH-independent. ### Atrial Natriuretic Peptide (ANP): * Secreted by atrial cells in response to volume expansion and increased BP. * Inhibits reabsorption of Na & water by the DCT and collecting ducts. * Inhibits renin secretion and therefore angiotensin II formation. ### Parathyroid Hormone: * Increases reabsorption of calcium, in the DCT and thick ascending LOH. * Inhibits reabsorption of phosphate by the proximal tubule. ## 4- Sympathetic Nervous System (SNS): * Vasoconstriction of renal arterioles * Stimulation of Na & water reabsorption **Table 28-3 Hormones That Regulate Tubular Reabsorption** | Hormone | Site of Action | Effects | |--------------------|------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------| | Aldosterone | Collecting tubule and duct | ↑NaCl, H₂O reabsorption; ↓K+ secretion; ↑H+ secretion | | Angiotensin II | Proximal tubule, thick ascending loop of Henle, distal tubule, collecting tubule | ↑NaCl, H₂O reabsorption; ↑H+ secretion | | Antidiuretic hormone | Distal tubule/collecting tubule and duct | ↑H₂O reabsorption | | Atrial natriuretic peptide | Distal tubule/collecting tubule and duct | ↓NaCl reabsorption | | Parathyroid hormone | Proximal tubule, thick ascending loop of Henle, distal tubule | ↓PO4 reabsorption; ↑Ca2+ reabsorption |