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Physiology Objectives 26 1. Renal tubular secretion: amount of a substance secreted into the filtrate by the tubules 2. Two major systems for secretion in proximal tubule: a. Organic anions: PAH b. Organic cations: TEA 3. Calculate renal tubular secretion: Secretion rate = excretion rate – filtration rate Secretion rate = (urine flow)([x] in urine) – (GFR)([x] in plasma) 4. Luminal transport: a. PAH: PAH is passively exchanged for an anion b. TEA: TEA is transported throughout the proximal tubule in exchange for H+; the H+ is excreted back into the lumen in exchange for Na+, returning the H+ concentration inside the cell to normal and indirectly using the Na+ gradient to pump TEA into the lumen Basolateral transport: a. PAH: PAH is transported into the S2 proximal tubule segment via an exchanger for α-ketoglutarate, then α-ketoglutarate is exchanged for Na+, returning the α-ketoglutarate inside the cell to normal and indirectly using the Na+ gradient to pump PAH into the cell b. TEA: TEA is transported via passive diffusion down an electrochemical gradient or passive exchange for a cation 5. Clearance of a secreted substance vs. filtered only: a secreted substance will normally have a higher clearance than those which are solely filtered because the substance will be secreted into the filtrate and increase the urine concentration of the substance. Since clearance is directly proportional to the urine concentration of a substance, as urine concentration goes up, so too does the clearance. Changes in clearance of a secreted substance with changes in its concentration in plasma: as the concentration of a substance in the plasma increases, the degree to which secretion affects clearance decreases. Since the secretion remains constant, at a high concentration, the amount secreted into the tubule is nearly negligible and clearance approaches GFR. 6. Determination of: a. Renal blood flow: PAH clearance b. Renal plasma flow: RPF/(1.0 – Hct) 7. Fick equation and clearance: RPF = rate of removal of x/([x] in artery – [x] in vein) RPF = clearance of PAH 8. Calculate renal plasma flow: RPF = (urine flow)([PAH] in urine)/([PAH] in plasma) 9. Calculate renal blood flow: RBF = RPF/(1.0 – Hct)