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School
University of Toronto St. George
Department
Physiology
Course
PSL201Y1
Professor
Yue Li
Semester
Winter

Description
19 THE URINARY SYSTEM: FLUID AND ELECTROLYTE BALANCE The Concept of Balance  To maintain homeostasis, what comes into the body and what is produced must equal the sum of what is used by the body and what is eliminated: Input + production = eliminated + output FACTORS AFFECTING THE PLASMA COMPOSITION  The volume of plasma is determined almost entirely by its water content because solutes make only a negligible direct contribution to the volume.  The amount of solute in plasma indirectly affects plasma volume because changes in plasma osmolarity can cause water to shift between the plasma and other body fluid compartments.  The transport of materials across the wall of the gastrointestinal tract normally amounts to a net gain of solutes and water by the body.  The transport of materials across the walls of the renal tubules amounts to a net loss of water and solutes by the body. SOLUTE AND WATER BALANCE  Changes in volume and/or composition occur when materials enter the plasma faster than they exit, or vice versa. Water Balance  For water balance, water intake plus any metabolically produced water must equal water output plus any water used in chemical reactions.  Only kidneys regulate the rate of water loss for the purpose of water balance.  Plasma volume is directly related to blood pressure: increase in plasma volume increases MAP.  Can also affect osmolarity: an increase in plasma water with no increase in solute decreases osmolarity; decrease in plasma water with no decrease in solute increases osmolarity. OSMOLARITY AND THE MOVEMENT OF WATER  The kidneys vary the volume of water excreted by regulating water reabsorption in the late distal tubules and collecting ducts.  Water can only move if the tubule membranes are permeable to water.  The total solute concentration of the plasma is approx. 300mOsm. It is also the normal osmolarity of the interstitial fluid and intracellular fluid, therefore osmotic pressure is equal (osmotic equilibrium).  Kidneys excrete excess solutes that were ingested while minimizing water loss by excreting a small volume of water.  Kidneys compensate for changes in plasma volume and osmolarity by adjusting the rate of water excretion. Because water is reabsorbed but not secreted, these adjustments are achieved through changes in the rate of water reabsorption.  In renal tubules, water reabsorption is passive and is coupled with active reabsorption of solutes.  Reabsorption of solute increases the osmoalrity of the peritubular fluid (drives reabsorption of water), and that in the collecting duct the medullary osmotic gradient drives reabsorption of water). WATER REABSORPTION IN THE PROXIMAL TUBULE  Primary solute is Na and most of it is reabsorbed in the proximal tubule, producing the osmotic gradient that drives water reabsorption.  Uses active transport of Na across the basolateral membrane from the epithelial cell.  Na also crosses the apical side by secondary active transport with glucose. 19 THE URINARY SYSTEM: FLUID AND ELECTROLYTE BALANCE ESTABLISHMENT OF THE MEDULLARY OSMOTIC GRADIENT  Medullary osmotic gradient: outer regions of the medulla have a lower osmolarity than the inner regions.  At the edge of the medulla = 300 mOsm; innermost portion near the renal pelvis = 1200-1400 mOsm.  This gradient exists due to the countercurrent multiplier and the facilitated diffusion of urea from the lumen of the collecting duct into the medullary interstitial fluid.  COUNTERCURRENT MULTIPLIER o The descending limb is permeable to water, so water diffuses when an osmotic gradient exists. o The thick ascending limb is impermeable to water and has Na/K/Cl active transporters. They pump the ions into the interstitial fluid, increasing osmolarity. o Countercurrent refers to the fact that fluid flowing through the descending and ascending limbs, which parallel one another, moves in opposite directions. o How the countercurrent multiplier creates osmotic gradient: 1. Starts with no osmotic gradient. Fluid entering the descending limb is iso-osmotic with the interstitial fluid, at 300mOsm. The water freely crosses the wall of the tubule and is therefore reabsorbed along with solutes. As fluid travels up the ascending limb, Na, Cl, and K are actively transported. 2. Increasing the osmolarity of the interstitial fluid from 300 to 400 mOsm and lowering the osmolarity of fluid in the ascending limb to 200 mOsm. When osmolarity in the peritubular fluid increases, water moves out of the descending limbd and into the peritubular fluid. 3. The descending limb and the peritubular fluid are iso-osmotic again at 400 mOsm. The fluid in the ascending limb now has a lower osmolarity. 4. As more 300 mOsm fluid enters the loop of Henle from the proximal tubule, the fluid pushes the 400 mOsm deeper into the medulla. 5. Active transport of Na, Cl, K in the ascending limb raises the osmolarity of deeper medullary interstitial fluid from 400 mOsm to 50 mOsm, which causes water movement into the interstitial fluid from the descending limb. 6. The descending limb is now iso-osmotic with the interstitial fluid. More 300 mOsm enters the loop of Henle from the proximal tubule, pushing the higher osmolarity fluid toward the tip of the loop of Henle. 7. The process continues until the osmotic gradient is created and the system is in a steady state. o At the steady state: entering fluid is iso-osmotic with the interstitial fluid at 300 mOsm. But the osmolarity in the tubular fluid in the limbs is greater in deeper portions of the renal medulla. The tip of the loop of Henle is 1400 mOsm. o Any given level in the medulla, the osmolarity of the fluid in the ascending ilmb is always lower than the fluid in the descending limb, because the ascending limb has active transports but prevents water from following them. o As the fluid leaves it is hypoosmotic to the interstitial fluid at approx. 100-200 mOsm.  ROLE OF UREA IN THE MEDULLARY OSMOTIC GRADIENT o Additional solute is needed to maintain the gradient. That is urea, a waste product generated during catabolism of proteins.  ROLE OF THE VASA RECTA IN PREVENTING DISSIPATION OF THE MEDULLARY OSMOTIC GRADIENT o The vasa recta capillaries prevents the diffusion of water and solutes from dissipating the medullary osmotic gradient. o As vasa recta enter the medulla with higher osmolarity, water leaves the capillaries by osmosis, and solutes enter the plasma by diffusion. o It continues to the tip of the vasa recta because of increasing osmolarity. o However, as the blood flow goes back to the cortex, the direction of the osmotic gradient acros the capillary walls reverses: water moves in, and solutes move out. 19 THE URINARY SYSTEM: FLUID AND ELECTROLYTE BALANCE o This tends to rise the osmolarity of the interstitial fluid. o Result: the osmolarity of the interstitial fluid stays constant, and the osmolarity in the plasma leaving the medulla in the vasa recta is slightly hyperosmotic. ROLE OF THE MEDULLARY OSMOTIC GRADIENT IN WATER REABSORPTION IN THE DISTAL TUBULE AND COLLECTING DUCT  70% of the water filtered from plasma at the renal corpuscle is reabsorbed in the proximal tubule.  Approximately 20% of the filtered water is reabsorbed in the distal tubule.  10% is reabsorbed in the collecting ducts.  AQUAPORINS AND WATER PERMEABILITY o The epithelial cells lining the late distal tubule and collecting duct are connected by tight junctions such that water can’t pass between cells from peritubular fluid to tubular fluid. o The lipid bilayers of these cells are impermeable to water. Water depends on aquaporins (water channels or pores). o Aquaporins are always present in the basolateral membrane and in the apical membrane (only in the presence of ADH). o The more permeable these tubules, the greater the water reabsorption. o The walls of the late distal tubule and collecting duct are impermeable to water. Osmotic gradient exists, but can’t move the water. Therefore the osmotic gradient gets larger as it travels down the collecting duct. Final result: excretion of large volume of urine with low osmolarity. o Kidneys can conserve water when the late distal tubule and the collecting duct are permeable to water. Fluid is initially hypo-osmotic to the cortical interstitial fluid, and water is reabsorbed. As the collecting duct leaves, the fluid is iso-osmotic. Water continues to be reabsorbed from the collecting duct into the interstitial space such that the fluid is always nearly iso-osmotic with the interstitial fluid. Tubular fluid osmolarity can never exce
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