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Renal4 - Renal Physiology Lecture4 Regulation of water...

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Unformatted text preview: Renal Physiology Lecture4 Regulation of water balance Glossary Osmolarity: total solute concentration of a solution; measure of water concentration in that the higher the solution osmolarity, the lower the water concentration Hypoosmotic: having total solute concentration less than that of normal extracellular fluid (300 mOsm) Isoosmotic: having total solute concentration equal to that of normal extracellular fluid Hyperosmotic: having total solute concentration greater than that of normal extracellular fluid physiologically regulatable Renal regulation of water balance • Water is freely filtered but ~99% is reabsorbed the 1% is very important because the filtered load of water is extremely large (180L/day) • The majority of water reabsorption (~2/3) occurs in the proximal tubule. • But the major hormonal control of reabsorption occurs in the CD. - in the case of Na the fine tuning takes place in the DCT and CCD - for water the fine tuning is shifted slightly backwards to the CD - water is filtered, reabsorbed but never secreted - sodium reabsorption is an active process - water reabsorption always follows Na reabsorption - water reabsorption is the movement from the tubular movement to the tubular epithelial cells and finally to the ISF - the initial movement of Na is from the tubular epithelial cells to the ISF on the basolateral membrane by the Na/K ATPase which pumps sodium against the concentration gradient - this causes intracellular Na concentrations to go down, allowing Na moving from the tubular lumen into the tubular epithelial cells Water reabsorption depends on Na reabsorption (proximal tubule) - as a result, the local osmolality of the tubular fluid goes down and the local osmolality in the ISF goes up -a concentration gradient exists for water to follow - water tries to move from the lumen to the ISF - this can occur 1) paracelluar through cells, passing through tight junctions 2) transcellular - moving through cells, requires water channels - due to the abundance of water in the ISF it moves via bulk flow into the capillaries Water reabsorption depends on Na reabsorption (proximal tubule) 1. Na is reabsorbed from the tubular lumen to the interstitial fluid across the epithelial cells. 2. The local osmolarity in the lumen decreases, while the local osmolarity in the interstitium increases. 3. This difference in osmolarity causes net diffusion of water from the lumen into the interstitial fluid. via tubular cells’ plasma membranes via tight junctions Water reabsorption depends on Na reabsorption (Cont’) 4. From the interstitium, water, sodium, and everything else dissolved in the interstitial fluid move together by bulk flow into peritubular capillaries. - when water intake is extremely small the urine output can be as small as 0.4L per day - urine maximum can be as large as 25L per day Maintenance of water balance The body has to maintain water balance. • When the water intake is small, the kidney reabsorbs more water (e.g. urine output 0.4 L per day). • When the water intake is large, the kidney reabsorbs less water (e.g. urine output 25 L per day). This dynamic regulation takes place in CD and there are two critical components: 1. High osmolarity of the medullary interstitium. 2. Permeability of CD to water (regulated by vasopressin) Urine concentration: countercurrent multiplier system • The kidney has the ability to concentrate urine up to 1400 mOsm/L. normal plasma osmolality is 300mOsm/L - can concentrate up to 5 times more than normal • Urinary concentration takes place as tubular fluid flows through the medullary collecting ducts. • Urinary concentration depends on the hyperosmolarity of the interstitial fluid. In the presence of vasopressin, water diffuses out of the ducts into the interstitial fluid in the medulla to be carried away. the kidney has a very high interstitial osmolality makes the CD cells permeable to water • How does the medullary interstitial fluid become hyperosmotic ? Urine concentration: countercurrent multiplier system The medullary interstitial fluid becomes hyperosmotic through the function of Henle’s loop. Distal convoluted tubule Proximal tubule Descending limb Ascending limb can be further divided in to the thin and thick portions Countercurrent flow Countercurrent multiplier system - the descending limb and the ascending limbs have opposite properties Step 1 - initially when the fluid starts to come into the loop of henle it is isosmotic - in the PT the reabsorption of Na and water occur in parallel - the osmolarity of the fluid does not change - the fluid flows into the thick ascending limb and Na is actively pumped out of the tubule into the ISF Actively reabsorb NaCl Impermeable to water Countercurrent multiplier system Step 2 - the descending limb of henle does not reabsorb sodium and it is highly permeable to water, unlike the ascending limb - in the last slide, the descending tubule was hyposmotic and the ISF was hyperosmotic - the water will move from the hyposmotic compartment, the tubule, to the hyperosmotic compartment, the ISF until the osmolarities are equal - thus, the osmolarity in the descending tubule becomes 400, the same as the ISF Does not reabsorb NaCl Permeable to water Actively reabsorb NaCl Impermeable to water Countercurrent multiplier system Move 300 Does not reabsorb NaCl Permeable to water Actively reabsorb NaCl Impermeable to water Countercurrent multiplier system After the move - after the complexion of the first cycle, and at the beginning of the second cycle 300 400 400 Countercurrent multiplier system Step 1 of the second cycle 300 Actively reabsorb NaCl 400 500 300 Impermeable to water Countercurrent multiplier system Step 2 Does not reabsorb NaCl Permeable to water 400 Actively reabsorb NaCl 500 500 300 Impermeable to water Countercurrent multiplier system Move ---> to continue….. 300 Does not reabsorb NaCl Permeable to water 400 Actively reabsorb NaCl 500 500 300 Impermeable to water Figure 14.15 300 - when the fluid enters the descending limb it is isosmotic - as the fluid goes down the descending limb, the osmolality increases (water is freely permeable to be reabsorbed but Na remains in the tubule) - as the fluid turns the corner, the osmolality begins to decrease again (Na is reabsorbed actively but water is impermeable) - by the time it leaves the loop of henle the osmolality is usually hyposmotic - the gradient of the osmolality in the ISF - close to the cortex, it is isosmotic - deeper into the medulla, the osmolality increase, usually equilibrating with the tubule - this is how the interstitial hyperosmolarity is achieved 900 1200 Vasa recta: blood vessels in the medulla Its hairpin-loop structure, minimizes excessive loss of solute from the interstitium. - there is a limited size to the interstitium, how can it accommodate the large amounts of Na and water? - there is a vascular supply to the kidney medulla - it was a loop structure as well - vasa recta = straight vessels - because of the loop structure, the vessels carry away solutes and fluid, but it does not completely waste the hyperosmolarity of the interstitium Water permeability of the tubules • Water reabsorption depends on the water permeability of the tubules. • Permeability of the epithelium depends on the tubular segment. always permeable to water e.g. proximal tubule: high permeability to water • Permeability largely depends on the presence of water channels (termed aquaporins) in the plasma membrane. • Water permeability (regulated by the amount of aquaporins in the plasma membrane) in the CCD and MCD is subject to physiological control and vasopressin is the key hormone in this control. Role of vasopressin in water reabsorption will be discussed in the review lecture Water reabsorption most water is absorbed in the proximal tubule, but reabsorption is unregulated - where vasopressin is acting - always in the cortex, impermeable to water - does not contribute to the interstitial hyperosmolality Hormonal control (vasopressin) - this portion can be permeable to water, or completely impermeable to water depending of the presence of ADH Descending thin limb of Henle 15% unregulated reabsorption Impermeable to water Vasopressin Peptide hormone, also called anti-diuretic hormone (ADH) increase water reabsorption, decrease the amount of water excreted Produced by a group of hypothalamic neurons Released from the posterior lobe of the pituitary gland two isoforms of the vasopressin receptor: Couples to GPCR V1 (smooth muscle) and V2 (kidney) G-protein coupled receptor water channels Vasopressin stimulates the insertion of aquaporins in the luminal membrane of the collecting duct cells and CCD cells already increases the water permeability. -basolateral side have water channels in the - there is no paracellular water reabsorption in the CCD so 100% of water reabsorption is dependent on transcellular reabsorption Vasopressin (Cont’) When vasopressin is present, collecting ducts become permeable to water ----> water reabsorption When vasopressin is not present, collecting ducts become impermeable to water ----> water diuresis Diabetes insipidus (DI) is caused by malfunction of the vasopressin system (vasopressin does NOT work). - does not matter where the malfunction is e.g. vasopressin is not produced, vasopressin receptors are unresponsive - causes massively diluted urine - can be caused by genetics or medication e.g. a drug that is used to treat bipolar disease is known to cause diabetes insipidus - these patients drink a lot of water and urinate a lot as well - tubular fluid becomes more hyposmotic in the DCT because it is impermeable to water and active sodium reabsorption continues - the moment that the fluid enters the CCD, with vasopressin this portion is highly permeable to water - it is in the cortex, so the ISF surrounding it is 300mOsm - water will diffuse out into the ISF to equilibrate the osmolality of the tubule to the ISF in the cortex - as the fluid continues to move down the MCD, in the presence of vasopressin, the fluid osmolality continues to go up to the maximum osmolality, 1400mOsm with vasopressin with vasopressin without with vasopressin with vasopressin vasopressin 50 50 50 50 - in diabetes insipidus, the fluid will enter the CCD but it will be impermeable to water (there are no aquaporins and vasopressin present) - Na reabsorption will continue in the CCD - the tubular fluid will reach the minimum osmolality, about 50mOsm - the walls of the MCD are impermeable to water despite the large osmolarity gradient - the result is a maximum amount of very low, diluted urine 50 50 Regulation of vasopressin Water excretion is mainly regulated by the rate of water reabsorption from the tubules. Vasopressin regulates this rate. Hence, vasopressin is a major regulator of water excretion. There are two mechanisms to regulate vasopressin secretion: 1. 2. Osmoreceptor control (most important) Baroreceptor control (less sensitive) Osmoreceptor control of vasopressin secretion can respond to changes in plasma osmolarity of 2-3% Baroreceptor control of vasopressin secretion must have a change in plasma volume of 5-10% to trigger the baroreceptor reflex - kicks in later than the osmoreceptors Why do we feel thirsty ? most important mechanism - works well for young people - older people have a less sensitive thirst response --> elderly people are more sensitive to heat waves Figure 14.23 lose a lot of water and a small amount of salt preservation of salt preservation of water - sodium plasma concentration is not a good marker of total body sodium - plasma sodium concentrations are higher than normal because the loss of water is far greater than the loss of sodium - just by looking at the number it will appear as if the person has a high plasma Na concentration loss of water>loss of Na PNa ⇑ (e.g. 150 mEq/L) Normal PNa 140 mEq/L ...
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