Why And How Does The Kidney Change Urine Osmolarity Notes

Why and how does the kidney change urine osmolarity? How do diuretics affect this process?

The kidney changes urine osmolarity by controlling the amount of water excreted in the urine. This is essential as it determines the osmolarity of the extracellular fluid which controls the amount of water that moves in and out of the cell through osmosis. In conditions of abnormally high water intake, the kidney adapts into a diuretic state and a large volume of dilute hypotonic urine is excreted. This is to prevent the extracellular fluid becoming hypotonic which would result in water osmosing into the cell and in extreme cases can lead to the cell bursting. But in conditions of excessive water loss through sweating or low water intake, kidney becomes anti-diuretic and water is conserved through excretion of a small volume of concentrated hypertonic urine. The switch between these two states is mediated by ADH which is a hormone released from the posterior pituitary in conditions of hydropenia.

Under average conditions, 1500ml of urine with an osmolarity of 600mOsmol is excreted. The first stage of water reabsorption occurs in the proximal tubule where 2/3^rd of the water in the ultrafiltrate is reabsorbed isotonically. This occurs as the proximal tubule has a high water permeability due the prescence of large number of aquaporins in the apical and basolateral membranes of the leaky epithelial cells. As a result of this, the reabsorption of solute, which is often coupled to Na+ is followed by water.

Counter current exchange system

The next stage of water reabsorption occurs in the loop of Henle, where a counter current exchange system reabsorbs salt in excess of water and creates a hypertonic interstitium in the renal medulla and hypotonic urine which then enters the collecting duct.

The first step of the multiplier system is known as the single effect and occurs in the thick ascending limb which is impermeable to water. It involves the transport of NaCl from the lumen into the epithelial cells by the apical, electroneutral Na/K/Cl cotransporter which couples the influx of 1Na+, 1K+ and 2Cl-. This transport is powered by the Na+ gradient created by the basolateral Na/K pump which uses the energy from the hydrolysis of ATP to couple the transport of 3Na+ out of the cell and 2K+ into the cell, both against the gradient . The Na then enters the interstitium through the Na/K pump, whereas the Cl- enters through chloride ion channels. Additional to this, there is also a small amount of Na+ that enters the interstitium through the tight junctions and is driven by the transepithelial positive voltage. As a result of these processes there is a net movement of NaCl into the interstitium which causes it to become hyperosmolar.

Following the creation of a hyperosmolar interstitium, the ultrafiltrate in the descending limb instantaneously equilibriates with the lumen of the descending limb which has a high peremabeility to water, due to the prescence of a large number of aquaporins, but has no permeability to solutes. This results in an increase in osmolarity in the tubular fluid of the descending limb as water moves from the lumen into the hypertonic interstitium down its osmotic gradient. The combination of the single effect and the instaneous equlibiration in the descending limb, creates a 200mOsm difference between the tubular fluid in the ascending limb and the combination of the interstitium and the descending limb. For example if the tubular fluid in the loop of Henle and the interstitium started off with an isotonic concentration of 300mOsm, it would result in the osmolarity of the ascending limb decreasing to 200mOsm and the osmolarity of the interstitium and descending limb rising the 400mOsm.

Following this is the axial shift, where new isomotic fluid from the proximal tubule in the cortex moves into the descending limb and pushes the fluid previously occupying the space into the ascending limb. This results in a decrease in osmolarity of the tubular fluid in the descending limb but an increase in osmolarity at the bottom of the thin ascending limb. In the thin ascending limb, the cells are relatively small with a few mitochondria, so the main transport form is paracellular transport where Na+ and Cl- diffuse through the tight junctions. This movement also contributes to the hypertonicity of the interstitium. The tubular fluid then enters the thick ascending limb and compared with the fluid previously occupying this space has a higher osmolarity due to the equilibriation between the descending limb and interstitium. The 2^nd cycle then begins, starting with the single effect, followed by equilibriation and ending with the axial shift and this again creates a 200mOsm transverse gradient along the length of the ascending limb.

Within the interstitium there is a corticopapillary osmotic gradient. This is created as the supply of Na+ and Cl- decreases as the tubular fluid ascends the ascending limb. Therefore less Na+ and Cl- is transported into the interstitium. Another reason for this gradient is the blood flow decreases from the cortical regions to the papillary regions, this means less NaCl is removed from the papillary regions and leads to accumulation. Due to this the counter...

Buy the full version of these notes or essay plans and more in our Physiology and Pharmacology Notes.