1.3.3 Regulation of Osmolality and Water Balance Flashcards
How is urea recycled in the nephron?
Countercurrent concentration of urea.
Besides inorganic ions, urea also plays a major role in the concentration of the urine. The countercurrent system can concentrate urea in the medullary ISF and in the tubular fluid. The source of most of the urea in the medullary interstitium is the inner medullary collecting duct. Tubular fluid arriving at that point has a very high urea concentration because the fractional reabsorption of water has greatly exceeded the fractional reabsorption of urea in more proximal urea-impermeable structures. The inner medullary collecting duct is permeable to urea and there is a chemical gradient for passive diffusion of urea into the medullary ISF. Urea then diffuses from the ISF into the vasa recta.
As the vasa recta blood, high in urea concentration, flows up the ascending capillary it enters a region where the ISF concentration is not as high. Urea diffuses back into the ISF and thence into the descending capillary containing plasma which has a low urea concentration. This trapping and recycling of the urea in the medulla raise the concentration to a high level and adds to the osmotic force drawing water from the descending limb of the loop of Henle and from the collecting duct. The countercurrent trapping of urea also reduces the gradient for urea diffusion from the inner medullary collecting tubule and permits the kidney to excrete urine with a high concentration of this waste product of nitrogen metabolism.
How does the body take in and excrete water?
Drinking water
and peeing (depending on how much you drink)
What are the effects of the countercurrent mechanism in the distal and collecting tubule?
Effect of the countercurrent mechanism on the distal and collecting tubules.
The distal tubules in the cortex and the cortical collecting ducts receive the hypo-osmotic tubular fluid from the loop of Henle and, in the presence of ADH, transport the excess fluid into the cortical ISF. Thus, the solute free water is returned to the systemic circulation and a much smaller volume of isosmotic tubular fluid reenters the medulla via the collecting ducts.
The target of the final effect of the countercurrent mechanism is the medullary collecting duct. As the tubular fluid flows down the medullary collecting duct, it comes into contact through the tubular epithelium with the hyperosmotic medullary ISF. In the presence of antidiuretic hormone, water is reabsorbed in excess of solute and the tubular fluid becomes increasingly concentrated as it approaches the papilla. This is the final effect of the countercurrent process, the return of water to the circulation and the osmotic concentration of the urine.
What is the mechanism of ADH in the vasculature?
Mechanism of action of ADH in vascular smooth muscle
Basically brings calcium into the cell via channels and the SR
In addition to its antidiuretic action, ADH or vasopressin is a potent vasopressor which increases the peripheral vascular resistance. This effect results from the binding of ADH to V1 receptors coupled to Gq protein in the vascular smooth muscle. This activates phospholipase C, which releases from phosphatidyl inositol biphosphate, inositol-trisphosphate (IP3) and diacylglycerol (DAG). DAC activates protein kinase C (PKC) that stimulates calcium channels at the plasma membrane. IP3 stimulates calcium release from the sarcoplasmic reticulum. The final response is an increase in intracellular calcium, actin myosin coupling and vascular smooth muscle contraction.
ADH may also cause constriction of the initial segments of the vasa recta and thereby slow the medullary blood flow rate. This helps enhance the effectiveness of the countercurrent system (see below). ADH does not have much effect on GFR or on water reabsorption at the proximal tubules.
Explain the basic process of water diuresis. (Kidney mascot card)
What factors affect the kidney’s ability to concentrate urine?
What are the two controlling parameters that modify water amount?
Water ingest - thirst mechanism
water reabsorption by the kidney
Receptors in the hypothalamus continuously sense plasma osmolarity and through effector pathways activate systems in the kidney and brain (mechanism of thirst) to maintain ECF osmolarity.
They communicate with the thirst center and the neuronal cells responsible for synthesis and release of antidiuretic hormone (ADH), or vasopressin. Thirst and ADH centers are the effectors that will regulate water intake and excretion respectively.
Explain the process of solute diuresis. (Kidney mascot card)
What cells in the hypothalamus produce ADH?
Supraoptic and paraventricular nuclei
Finish the chart
What are the main areas of the nephron responsible for H2O reabsorption?
What are the key areas for ADH to act on?
Collecting duct
Distal tubule
How are plasma pressure/volume related to ADH release?
Regulation of ADH release
Pressure and volume changes in plasma are sensed by the baroreceptors and stimuli travel through the vagal nerve to the supraoptic and paraventricular nuclei. This causes release of AVP. The plot shows the chaqnges of the pressure and volume in relation to AVP release. Notice that AVP release is more sensitive to osmotic changes than to pressure/volume changes.
Where does most of the water get lost throughout the day?
What is the mechanism of action of ADH on the renal tubule?
How does ADH levels relate to urine osmolality and flow rate?
ADH Effects on urine flow rate, osmolality and solute content
When ADH is low a large volume of urine is excreted (diuresis) and the urine is dilute. When ADH is high a small urine volume is produced (antidiuresis) and the urine is concentrated.
How does the Vasa recta act as countercurrent exchanger?
Vasa recta as countercurrent exchangers.
The vasa recta serve as countercurrent exchangers and they are essential to conserve the composition of the medullary interstitium while providing nutrients to the cells. The hairpin construction of the vasa recta, coupled with a blood flow rate that is much slower than the flow rate in the cortex, allows blood to flow through the medulla without causing more than a minimal disturbance in the osmotic gradient. Plasma entering the descending limb of the vasa recta with the usual systemic osmotic concentration of 290 mosmole/kg H2O, comes into contact through the capillary wall with the high [Na+], [Cl-] and osmotic concentration of the medullary ISF. Water flows out of the descending limb in response to the osmotic gradient and Na+ and Cl- diffuse in. Thus, the plasma becomes increasingly more concentrated as it approaches the tip of the papilla. As this concentrated fluid flows into the ascending limb of the vasa recta and back toward the cortex, it encounters interstitial fluid that is more diluted. Water then flows down the osmotic gradient into the ascending vasa recta and Na+ and Cl- diffuse out.
The rate of leakage of solute out of the medulla via the vasa recta increases as the osmotic concentration of the ISF increases until a steady state is achieved when, at some high osmotic concentration of the ISF, the rate of solute transport out of the thick ascending limb is balanced by the rate of solute leakage into the exiting plasma.
Describe the sensitivity of ADH release to changes in Osm.
The sensitivity of ADH release is extremely sensitive. There will be changes in ADH levels with even 1 mosmole difference in plasma osmolality
Explain the relative osmolarity of the tubular fluid along the nephron in the presence and absence of ADH.
Changes induced by the different nephron segments in tubular fluid osmolarity.
The plot shows the changes the tubular fluid experiences in its osmolarity compared to that of plasma as it flows along the nephron. The red line represent the case in which the kidney is maximally concentrating the urine (antidiuresis). The blue one shows a case of ingestion of water in excess, where the kidney forms a high volume of diluted urine (Diuresis). The first part of the Loop of Henle is the concentrating segment. The second part of the Loop of Henle is the diluting segment. Then, depending on the antidiuretic hormone, the osmolarity increases in its presence (antidiuresis), or it decreases in its absence (diuresis).
What is the countercurrent principle in the Loop of Henle?
While in the loop of Henle the descending loop is permeable to both water and ions. This causes the levels of sort equilibrate. The ascending loop of henle, in relatively impermeable to H2O which prevents it from following the solute. Thus as it leaves the loop, the osmolality is much lower than the beginning.
The impermeability of the ascending limb epithelium to water prevents it from following the solute, so the osmotic concentration of the tubular fluid is reduced as it moves up in the loop of Henle, and the concentration of the ISF is raised. It is this initial, small, horizontal gradient (approximately 200 mosmole/kg H2O) across the tubular wall that is “multiplied” vertically along the length of the loop by countercurrent flow.
The hyperosmotic concentration of the ISF then causes water to move out of the descending limb, thereby progressively raising the concentration of the remaining tubular fluid as it flows towards the tip of the loop.
Sodium and chloride diffuse from the medullary ISF down their chemical gradients back into the tubular fluid in the descending limb. This also serves to increase the osmotic concentration of the tubular fluid.
After the fluid flows around the bend and starts back up in the ascending limb, Na+ and Cl-, but little water, are removed and fluid is diluted as it approaches the distal tubule.
