5.5

Regulation of Na+ and H2O by ADH and Aldosterone

• Tubular reabsorption in kidneys is large and highly selective, with 180 L of filtered water per day and high reabsorptive rates for water and ions under physiological control.
• Reabsorption occurs through diffusion, mediated transport, and bulk flow, with substances moving through transcellular and paracellular routes.
• Reabsorption from filtrate to interstitium and peritubular capillaries involves passive and active transport, with primary active transporters including Na+-K_-ATPase and H+-ATPase.
• Sodium reabsorption uses both passive and active transport, with many substances coupled to sodium reabsorption via secondary active transport.
• Passive water reabsorption by osmosis is coupled mainly to sodium reabsorption, with water permeability varying through different tubules.
• Transport maximum (Tm) limits the amount of material mediated transporters can transport, leading to conditions like glucosuria in diabetes.
• Urea reabsorption is dependent on the reabsorption of water and occurs via passive diffusion down its concentration gradient.
• Reabsorption predominates in the proximal tubule, with variations in Na+ reabsorption and urea reabsorption favoring reabsorption as water is reabsorbed.
• The proximal tubule is the site of action of osmotic diuretics, causing nonreabsorbed solutes to retain water in the lumen and be excreted.
• Osmotic diuresis affects water permeability at the proximal tubule and thin descending limb, with examples including mannitol and untreated diabetes mellitus.
• 65% of glucose and 5–7% of Na+ are reabsorbed in the proximal tubule, while 25% and 2.4% are reabsorbed in the loop of Henle and distal tubule, respectively.
• The inner medullary collecting duct has urea transporters, with approximately 50% of filtered urea reabsorbed and 50% excreted.

Regulation of Tubular Reabsorption in the Kidneys

• Tubules can increase reabsorption rates in response to increased tubular load to maintain Na+ and volume homeostasis in distal tubules
• Peritubular physical forces: increased arterial pressure raises peritubular capillary pressure; afferent and efferent arterioles reduce peritubular capillary hydrostatic pressure
• Hormones like aldosterone, angiotensin II, and antidiuretic hormone (ADH) play a crucial role in controlling extracellular fluid (ECF) volume and sodium and water reabsorption
• Sympathetic nervous system activation decreases Na+ and H2O excretion, increases tubular reabsorption by alpha-adrenergic receptors on tubular epithelium
• Antidiuretic hormone (ADH) controls ECF osmolarity and is synthesized by the hypothalamus; its secretion is influenced by plasma volume changes
• ADH binds to V2 receptors, increases cAMP, and activates protein kinases, inserting AQP2 channels into the luminal membrane
• Rate of urinary excretion of a substance can be affected by glomerular filtration, tubular reabsorption, and tubular secretion
• Fractional excretion (FE) expresses solute excretion as a percentage of filtered load and is useful in determining altered tubular transport, not just GFR
• Calculating FENA is useful in acute renal failure to determine if it is due to prerenal or renal pathology
• For a substance that is freely filtered, renal clearance is equal to GFR
• Inulin can be used to estimate GFR, while plasma creatinine is a direct index of GFR but overestimates by ~10% and is used to determine the stages of renal failure
• Clinical case questions related to hypernatremia, renal artery stenosis, potassium secretion, and maximum clearance rate are presented to test understanding of kidney function and regulation.