Thiazides act on ?
Correct Answer: Glomerulus
Description: Ans. is 'c' i.e., DCT Tubular absorption can be divided into four sites. Site 1- Proximal tubule Four mechanisms of Na' transpo have been defined in this segment ? Direct entry of M.+ along electrochemical gradient. Nat-K* sympo along with active reabsorption of glucose, aminoacids, organic anions and PO43. Exchange with W by Na* IW exchanger located in the luminal membrane of proximal tubule (PT) epithelial cells. The PT cells secrete W with the help of carbonic anhydrase. W ion exchanges with Nat- present in tubular fluid through Na+-H+ exchanger (antipoer) and forms H2CO3 by combining with HCO3-. This H2CO3 is broken into H20 + CO2 by brush border carbonic anhydrase; both CO2 and H20 diffuse inside the cell and recombine to form H2CO3 with the help of intracellular carbonic anhydrase. This H,CO3 is the source of F1*. The dissociated HCO3- in the cell is transpoed to coical E.C.F. by basolateral membrane Na-F-HCO3- sympoer resulting in net reabsorption of NaHCO3. Carbonic anydrase inhibitors (acetazolamide) act predominantly in PCT and inhibit NaHCO3 reabsorption. The disropoionately large HCO3-, acetate, PO4-3, passive driving forces for Cl- to diffuse through the paracellular pathway, paicularly in the later PT. This takes Na' and H,0 along to maintain electrical neutrality and isotonicity; reabsorption in PT is isotonic. Osmotic diuretics (mannitol) are solutes which are not absorbed in proximal tubule and therefore retain water. Site II Ascending limb of loop of Henle The thick ascending limb can be distinguished into two distinct poion. Medullary poion lined by cuboidal cells. Coical poion lined by flattened cells. Both poions are relatively impermeable to water but absorb salt actively and thus dilute tubular fluid. In the medullary poion a distinct luminal membrane carrier transpos ions in ratio of Nee-K+-2a. The sodium enters the cell is pumped to ECF by Na ATPase at the basolateral membrane. This Na+--K+--2C1: sympo is inhibited by loop diuretics (eg-Furosemide). In addition, a Na*-C1- sympoer moves CI- down its electrochemical gradient into ECF and carries Na+ along. Site III - coical diluting segment of loop of Henle and early DT This segment is also impermeable to H20 and continues to absorb salt through Nat-Ct sympoer. Thiazide diuretics act at this site. Site IV - late distal tubule and collecting duct In late DT and CD, Na is actively reabsorbed; the cation-anion balance being maintained paly by passive CI-diffusion and paly by secretion of K+ and Fr. Absorption of Na+ at this site occurs through a specific amiloride sensitive Net' channel and is controlled to a large extent by aldosterone. K paring diuretics act at this site. Collecting tubule is the most impoant site of IC secretion by the kidney and the site at which viually all diuretic induced changes in KE balance occur - as IC secretion occurs in exchange of Nat, higher the Na+ load in CD higher will be K+ excretion in urine --> Diuretics which act on PCT (maximum absoion of Na+ occurs at PCT) like acetazolamide will cause maximum kaliuresis (IC excretion in urine). The principal cells are the major sites of Nat, IC-, and water transpo, and intercalated cells are the primary sites of Ft' secretion. The collecting tubule is also the site at which the final urine concentration is determined. ADH (vasopressin) controls the permeability of this segment to water by regulating the inseion of preformed water channels (aquaporin2, AQP2) into the apical membrane a G protein - coupled cAMP - mediated process. ADH also stimulates the inseion of urea transpoer UT1 molecules into the apical membranes of medullary collecting tubule cells. Urea concentration in the medulla plays an impoant role maintaining the high osmolarity of the medulla and in the concentration of urine.
Category:
Pharmacology
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