 Excretion refers to the removal of solutes and water from the body in urine  Reabsorption (movement from tubular fluid to peritubular blood) and,  S ecretion (movement from peritubular blood to tubular fluid) refer to direction of movement of solutes and water across the renal tubular epithelium

 The luminal cell membranes are those that face the tubular lumen (“urine” side)  The basolateral cell membranes are those are in contact with the lateral intercellular spaces and peritubular interstitium (“blood” side)

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 Solute reaborption in the proximal tubule is isosmotic (water follows solute osmotically and tubular fluid osmolality remains similar to that of plasma).  65%-70% of water and sodium reabsorption occurs in the proximal tubule  90% of bicarbonate, calcium, K+  100% of glucose & amino acids  Proximal tubules: coarse adjustment  Distal tubules: fine adjustment (hormonal control).

 Responsible for producing a concentrated urine by forming a concentration gradient within the medulla of kidney.  When ADH is present, water is reabsorbed and urine is concentrated.  Counter-current multiplier 8

Loop of Henle: Acts in manner of counter current exchanger. Note that each limb of loop has fluid moving in opposite directions (even though connected at one end). Further concentrates urine. Also means that salt concentration will be highest near bend in the loop.

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Absorption through loop of Henle: Descending limb: is water permeable and allow absorption of 25% of filtered H2O. It is impermeable to Na-CL. Thin ascending limb: is impermeable to H2O, but permeable to Na-Cl, where they are absorbed passively in this part. Thick ascending limb: is impermeable to H2O. Na-K-2Cl co-transport occur in this part.

 What happens here depends on hormonal control:  Aldosterone affects Na+ and K+  ADH – facultative water reabsorption  Parathyroid hormone – increases Ca++ reabsorption 12

 Tubular secretion to rid body of substances: K+, H+, urea, ammonia, creatinine and certain drugs  Secretion of H+ helps maintain blood pH (can also reabsorb bicarb and generate new bicarb) 13

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 Na + absorbed by active transport mechanisms, NOT by T M mechanism. Basolateral ATPases establish a gradient across the tubule wall.  Proximal tubule is very permeable to Na +, so ions flow down gradient, across membranes.  Microvilli create large surface area for absorption.  Electrical gradient created also draws Cl - across.  H 2 O follows Na + due to osmotic force.  Means fluid left in tubule is concentrated.

 Glucose absorption also relies upon the Na + gradient.  Most reabsorbed in proximal tubule.  At apical membrane, needs Na + /glucose cotransporter (SGLT)  Crosses basolateral membrane via glucose transporters (GLUT’s), which do not rely upon Na +.

 K + is major cation in cells and balance is essential for life.  Small change from 4 to 5.5 mmoles/l = hyperkalaemia = ventric. fibrillation = death.  Reabsorb K + at proximal tubule.  Changes in K + excretion due to changes in K + secretion in distal tubule

 K + reabsorption along the proximal tubule is largely passive and follows the movement of Na + and fluid (in collecting tubules, may also rely active transport).  K + secretion occurs in cortical collecting tubule (principal cells), and relies upon active transport of K + across basolateral membrane and passive exit across apical membrane into tubular fluid.

 Countercurrent is that, fluid flows down the descending limb and up the ascending limb.  The critical characteristics of the loops which make them countercurrent multipliers are:  1. The ascending limb of the loop of Henle actively co-transports Na + and Cl - ions out of the tubule lumen into the interstitium. The ascending limb is impermeable to H 2 O.  2. The descending limb is freely permeable to H 2 O but relatively impermeable to NaCl. H 2 O that moves out of tubule into intersitium is removed the blood vessels called vasa recta – thus gradients maintained and H 2 O returned to circulation.

Mechanisms of tubular transport: Active transport: i.Primary active transport: e.g. Na-K-pump, H+-pump ii.Secondary active transport : e.g. Na-K-2Cl co- transport, glucose-sodium co-transport, amino acid-sodium co-transport. Passive transport: i.Simple diffusion. ii.Facilitated diffusion. Osmosis. Pinocytosis. Solvent drag.

 Movement of a substance across a membrane as a result of random molecular motion down concentration and electrochemical gradient. No energy needed.  E.g. bicarbonate, chloride,

 Movement of a substance across a membrane down its electrochemical gradient after binding with a specific carrier protein in the membrane.  Needs a carrier.

 Glucose, amino acids: At Basolateral membranes of proximal tubules  Sodium: luminal membranes of proximal tubules

 Movement of a substance across a membrane in combination with a carrier protein but against an electrochemical gradient

 Directly requires metabolic energy (i.e. hydrolysis of ATP)  Saturable (has a V max )  Structural specificity and affinity of the carrier for the substance transported

 Na + -K + ATPase  H + ATPase  H + -K + ATPase  Ca +2 ATPase

 In renal tubular cells found only in basolateral membrane  When ATP is hydrolyzed, 2 K + ions are pumped into the cell and 3 Na + ions are pumped out  Maintains favorable electrochemical gradient for Na + entry at luminal membrane  Maintains cell membrane potential difference and intracellular osmolality

Proximal: the Na-K pump on the apical (interstitial side) membrane is the driving force for the electrochemical gradient which drives passive transport into the cell and keeps intracellular Na low, pumping against the gradient into the basal-lateral space. Passive entry into the cell is by diffusion, facillitated diffusion through a transporter or co-transporter, and by electroneutral “exchange” with hydrogen ions (H+). Na + pump Tubular lumen Interstitial space

 Two substances interact with one specific carrier in the cell membrane and both substances are translocated across the membrane  Co-transport Transported substances move in the same direction across the membrane  Counter-transport Transported substances move in opposite directions across the membrane

Paracellular = 50% Transcellular K+ 50%

LUMINAL BASOLATERAL Glucose, P i amino acids Na + H+H+H+H+ 3 Na + 2 K + K+K+K+K+ HCO H 2 CO 3

 “Uphill” transport of one substance is linked to “downhill” transport of another substance  Carrier must be occupied by both substances (or be unoccupied) to be mobile in the membrane  Saturable (has a V max )

 Glucose, amino acids, or phosphate with sodium in luminal membranes of proximal tubules  Sodium and hydrogen ions in luminal membranes of proximal tubules.  Na-K-2CL transport in the thick ascending limb of Henle

 Urea is passively reabsorbed in the proximal tubule

Water Reabsorption: In the proximal tubule, water follows sodium passibvely and isosmotically because the proximal tubule is very permeable to water. Water moves both transcellularly and paracellularly. The transcellular movement is facillitated by “aquaporin” water channels in both the apical and basalateral membranes.

What do the kidneys do? The glomeruli “non-discriminantly” filter the blood, and the tubules take back what the body needs leaving the rest as waste to be excreted. Some wastes also can be actively added to the tubular fluid. Thick ascending : Na-K- 2Cl co-transport Descending limb: 25% H2O2 absorption