Renal Physiology II – Tubular Reabsorption PDF

Renal Physiology II – Tubular Reabsorption Som Mukhopadhyay M.D.; Ph.D. Assoc. Prof., Pharmacology & Toxicology Office: BME 3.510E E-mail: [email protected] Outline Basic mechanisms of tubular reabsorption Reabsorption in different segments of the nephron Mechanisms of urine concentration (count...

Renal Physiology II – Tubular Reabsorption Som Mukhopadhyay M.D.; Ph.D. Assoc. Prof., Pharmacology & Toxicology Office: BME 3.510E E-mail: [email protected] Outline Basic mechanisms of tubular reabsorption Reabsorption in different segments of the nephron Mechanisms of urine concentration (countercurrent multiplier/vasa recta/ADH/Urea) Materials from Guyton and Hall, 13th Edition Tubular Reabsorption: Basic principles Tubular Reabsorption: Basic principles Tubular Reabsorption: Primary Active Transport Tubular Reabsorption: Secondary Active Transport Entry of glucose into the tubular cell from the lumen is coupled with entry of Na+ down the concentration gradient. Glucose then exits the cell from the basolateral aspect down its own concentration gradient. Tubular Reabsorption: Secondary Active Transport of protons In this case, downhill movement of Na ions is coupled with uphill movement of protons in the opposite direction. Outline Basic mechanisms of tubular reabsorption Reabsorption in different segments of the nephron Mechanisms of urine concentration (countercurrent multiplier/vasa recta/ADH/Urea) Materials from Guyton and Hall, 13th Edition Reabsorption in different parts of the nephron: proximal tubule ~65% of the filtered load of sodium and water and a slightly lower percentage of filtered chloride are reabsorbed by the proximal tubule. The proximal tubule is also an important site for secretion of organic acids and bases such as bile salts, oxalate, urate, and catecholamines. Reabsorption in different parts of the nephron: Loop of Henle Loop of Henle has three segments: thin descending, thin ascending, and thick ascending. The descending segment is highly permeable to water but not so permeable to sodium chloride and urea. About 20% of the filtered load of water is reabsorbed in the loop of Henle; most in the descending segment. Reabsorption in different parts of the nephron: Loop of Henle The thin ascending segment is impermeable to water, but reabsorbs some sodium chloride. This makes the tubular fluid dilute; more on this in a bit… Reabsorption in different parts of the nephron: Loop of Henle Thick ascending segment is also impermeable to water, but reabsorbs large amounts of sodium, chloride, potassium, and other ions due to active transport. This makes the urine very dilute by the time it reaches the distal tubule. This feature is important in allowing the kidneys to dilute or concentrate the urine under different conditions. Loop diuretics In the thick ascending loop, movement of sodium across the luminal membrane is mediated primarily by a 1-sodium, 2chloride, 1-potassium cotransporter. This cotransporter is inhibited by powerful “loop” diuretics like furosemide, ethacrynic acid, and bumetanide. Reabsorption in different parts of the nephron: Early distal tubule The early part of the distal tubule has re-absorptive properties similar to the thick ascending segment of the loop of Henle; so, urine gets further diluted. Thiazide diuretics ~5% of the filtered load of sodium chloride is reabsorbed in the early distal tubule. The sodium chloride cotransporter moves both ions from the lumen into cells. This transporter is inhibited by thiazide diuretics. Reabsorption in different parts of the nephron: Late distal tubule & cortical collecting duct Two cell types: Principal cells and Intercalated cells. Principal cells: Reabsorb sodium and water; secrete potassium. Permeability to water depends on levels of anti diuretic hormone (more on this later…) Intercalated cells: Maintain acid/ base balance. Principal cells: Reabsorb sodium; secrete potassium Na+-K+ ATPase located on basolateral membrane pumps Na+ out to interstitial space Luminal Na+ enters into cells by special channels. ATPase activity increases intracellular K+, which is secreted to lumen by specialized channels. Principal cells are the primary site of action of potassium sparing diuretics Aldosterone increases Na+ reabsorption. Spironolactone and eplerenone are mineralocorticoid receptor antagonists that compete with aldosterone for receptor sites in the principal cells. This inhibits the stimulatory effects of aldosterone on sodium reabsorption and potassium secretion. Principal cells are the primary site of action of potassium sparing diuretics Amiloride and triamterene are sodium channel blockers that directly inhibit the entry of sodium into the sodium channels of the luminal membranes. Reabsorption in different parts of the nephron: Medullary Collecting Duct Reabsorb