Overview

Water and Electrolyte Homeostasis

Renal metabolism and oxygen consumption: Under physiological steady state conditions the O2 supply to the renal tissues is well in excess of the O2 demand. Renal O2 extraction in the healthy kidney is only 10–15%. The vast majority of oxygen consumption is due to reabsorption of approximately 99.5% of filtered sodium (Na+). The medullary thick ascending limbs of Henle loop (mTALs), are the major O2-consuming site owing to Na+–K+–2Cl− transporter. PO2 is normally lower in the medulla than in the cortex. Renal oxygen consumption is related directly to GFR because the latter determines the sodium load. If the GFR increases, that results in increased work by the kidneys and oxygen requirement increases. Sustained intrarenal hypoxia is the underlying cause of chronic kidney disease(CKD). Renal tubular hypertrophy, especially in the medulla can also predispose to hypoxia and CKD.

The kidney exhibits an extraordinarily efficient autoregulation relating to the myogenic and tubuloglomerular feedback, resulting in relative constancy of blood flow and glomerular ultrafiltration.

Prostaglandin E2, adenosine and nitric oxide regulate local medullary oxygen balance. Prostaglandin E2 (PGE2) is produced chiefly by collecting duct cells and interstitial cells of the papilla. It inhibits active transport by the medullary thick limb and reduces transport related oxygen consumption by mTAL cells. In addition, PGE2 enhances medullary blood flow. Inhibition of PGE2 production with indomethacin reduces medullary PO2 and presumably is responsible for the chronic interstitial nephritis of analgesic nephropathy, characterized by fibrosis that is especially marked in the renal medulla and papilla, progressing to papillary necrosis. Adenosine activates inhibitory receptors which reduces the activity of adenylate cyclase. Adenosine analogues active at the A1 receptor inhibit active transport in thick ascending limbs and reduce anoxic injury to the mTAL. Adenosine and its analogues markedly enhance tubuloglomerular feedback and increases the supply of oxygen by improving vasa recta flow. Nitric oxide (NO) is produced from arginine by nitric oxide synthase, which is heavily concentrated in the renal medulla . The effect of NO is probably a dual one, both to increase vasa recta flow and to decrease active transport by the mTAL .