The Son of the last of a long line of thinkers. (delascabezas) wrote,
The Son of the last of a long line of thinkers.

  • Mood:
  • Music:

Loking for answers....

The cardiac output at rest is about 5 liters/min...About 1/5 of this blood (1 liter/min of blood or about 600 ml/min of plasma) enters the renal arteries and about 1/5 of that amount is filtered at the glomeruli. Thus, the GFR is about 125 ml/min or 180 liters/day. Plasma contains about 140 mM NaCl. About 67% of the filtered sodium load is reabsorbed in the proximal tubules, and with sodium move glucose, amino acids, chloride, and bicarbonate. This segment is freely permeable to water, so that solute transport from tubular fluid into blood is accompanied by water, i.e., reabsorption of solutes is isoosmotic without a change in tubular fluid osmotic pressure or in the concentration of sodium. As the tubular fluid leaves the proximal tubule to enter the descending limb of the loop of Henle, water is abstracted from the tubular fluid by the hypertonic renal interstitial fluids. The corticomedullary gradient of increasing interstitial fluid osmolality is due to NaCl and urea (about half and half). The concentration of sodium increases progressively as tubular fluid flows down the descending limb and equilibrates with the surrounding hypertonic interstitial fluid, so that luminal fluid at the turning point of the loop of Henle has a tonicity of about 1200 mOsm/L and most of this is due to NaCl. The permeability properties of the descending limb are strikingly different from those of the ascending limb. The ascending limb is virtually impermeable to water both in the presence and absence of vasopressin (ADH), but this limb is quite permeable to NaCl. In the thin ascending limb, Na probably diffuses from tubular fluid into the interstitium by a passive (carrier- mediated) transport process. (Remember that the interstitial fluid Na concentration is lower than tubular fluid Na, because of the high concentration of urea in this area.) In the thick ascending limb, however, NaCl is transported out of the tubular lumen by an active process. Here we have an active chloride pump (secondary active transport process) which moves essentially dry salt out of the tubular fluid, charging up the luminal membrane with a positive charge and leaving behind water which progressively lowers the osmolality of fluid in this segment.

There is now good evidence to suggest that chloride ions are co-transported with sodium and potassium ions on a common carrier across the luminal membrane and pumped out the other side with a standard sodium pump (recall that a similar co-transport system is used in the proximal tubule for glucose and amino acid transport). About 25% of the filtered sodium load is reabsorbed in the thick ascending limb. This reabsorptive step is the essential step in the formation of a dilute urine. Therefore, this segment is also referred to as the "diluting segment" and if the activity of the chloride pump is diminished, as it is in the presence of so-called "loop diuretics" (furosemide, ethacrynic acid), patients will not be able to appropriately dilute their urine. This happens with patients on furosemide who drink a lot of water (or beer), and they may suffer from hyponatremia and have symptoms of water intoxication. Moreover, the medullary portion of the ascending limb is crucial in establishing the corticomedullary osmotic gradient in the renal interstitium (i.e., the countercurrent multiplication function of the chloride pumps). Without a hypertonic, renal interstitium urine cannot be maximally concentrated in the medullary collecting duct, even in the presence of ADH. Thus, a patient may be secreting high levels of ADH either as a consequence of dehydration and increased plasma osmolality or as a consequence of volume depletion (bleeding, diarrhea, vomiting, etc.) and have collecting ducts, which are freely permeable to water. However, without a hypertonic interstitial fluid environment, water will not move out of the collecting duct and will be lost in the urine. Therefore, patients on furosemide cannot form a maximally concentrated urine. So the loop diuretics characteristically interfere with both dilution and concentration of the urine.

As we move from the medullary thick ascending limb into the cortical portion of the ascending limb and early distal convoluted tubule, the process of tubular fluid dilution by reabsorption of salt without water continues. In this region, the tubular lumen has a negative potential in association with primary sodium pumping. (Note: The electrical potential is a consequence of the movements in both directions of all the ions of the system and their respective permeability coefficients, which is most clearly expressed by the Goldman Constant Field Equation . However, an easy way to remember the luminal potential is that it is positive when negative ions are being preferentially removed (thick ascending limb) and negative when positive ions are being pumped out (proximal tubule, distal tubule, collecting duct). About 5% of the filtered sodium load is reabsorbed in the cortical ascending and distal convoluted tubules. Any block of sodium reabsorption here, as for instance with the use of the thiazide diuretics, will again result in a diminished ability to form a dilute urine, with a tendency for hyponatremia. Indeed, this is one of the frequent complications seen with the thiazides. However, these agents do not interfere with the formation of a concentrated urine (in the presence of ADH), because the cortical segment of the ascending limb does not participate in countercurrent multiplication. Indeed, the ability of a diuretic agent to inhibit dilution, but not concentration, of the urine has been used experimentally to determine whether a diuretic acts on the medullary or cortical limb of the loop of Henle.

The late part of the distal convoluted tubule and the cortical collecting duct is sensitive to aldosterone. It is here that about 3% of the filtered sodium load is reabsorbed. Much of the sodium reabsorbed here is reabsorbed as NaCl, but some of the sodium ions are reabsorbed in exchange for hydrogen ions and potassium ions. Diuretics which act here, such as the aldosterone antagonist "spironolactone," or the sodium channel blocker "amiloride," not only increase sodium loss into the urine, but also decrease potassium and hydrogen ion loss. Again, this phenomenon can be used for distinguishing the site of action of various diuretics. A diuretic which decreases potassium secretion must act on the cortical collecting duct, whereas a diuretic which increases potassium excretion must act prior to this site.

ADH acts on the collecting ducts. In the presence of ADH, water is abstracted from the tubular fluid as it moves through the cortical collecting duct. The major solute in the tubular fluid at this time is urea. Urea will not diffuse across the cortical collecting duct even in the presence of ADH, so that its concentration increases. Now, in the medullary collecting duct, ADH increases not only water, but also urea permeability, so that urea now diffuses into the renal interstitium and contributes about half of the corticomedullary osmotic gradient, which is functional in abstracting water not only from the collecting duct, but also from the descending limb of Henle.

You may think that a specific blocker of ADH would be a useful diuretic agent. Although such inhibitors have been synthesized and tested experimentally, it is too early to know if they will find application in clinical situations. However, keep in mind that other agents which interfere with countercurrent multiplication (i.e., furosemide) or countercurrent exchange (mannitol) indirectly inhibit the antidiuretic action of vasopressin by diminishing the trans-tubular osmotic pressure gradient in the collecting duct.

So you can see that we filter about 180 L/day of plasma containing about 140 mM NaCl. We end up reabsorbing about 99% of the filtered sodium and water to eliminate about 1.5 liters/day of urine.

  • Post a new comment


    default userpic

    Your IP address will be recorded 

    When you submit the form an invisible reCAPTCHA check will be performed.
    You must follow the Privacy Policy and Google Terms of use.