This whole scenario - where solute extraction from the ascending limb leads to increased interstitial osmolality and water extraction from the descending limb - is generally referred to as the single effect. The term is not used consistently in the literature, but appears in papers often enough for it to seem like it is A Thing in renal physiology.
It seems to date back to the very earliest representation of this countercurrent process by Werner Kuhn and Kaspar Ryffel in The countercurrent multiplication of this one ion-pumping effect is the origin of the medullary concentration gradient, they posed; and it appears later authors have reproduced the terminology in English without any modification.
So, let us now add some new fresh glomerular filtrate, to produce a countercurrent flow and multiply this "single efect":. The countercurrent flow here refers to the fact that flow in the ascending and descending tubules is happening in opposite directions. In contrast, concurrent flow would be flow going in the same direction down both vessels. As it comes out of the proximal tubule, the fluid has an osmolality close to that of normal blood, as absorption of water and solutes in the proximal tubule is isoosmolar.
As it enters the thin descending limb, it displaces some of the concentrated tubular fluid from the bend of the loop and up into the ascending limb. The ascending tubule transfers some solutes out of the tubule and into the interstitium, making the interstitium more hyperosmolar; except this time, there is something of a concentration gradient in play, which means the ions have to be pumped "uphill".
Again the hyperosmolar interstitium dehydrates the contents of the water-permeable descending limb. And, as before, the distal ascending limb ends up removing even more electrolytes from the tubular contents, leaving behind some rather dilute tubular fluid.
In short, by this point, the cyclicality of this process becomes apparent to most people. In spite of that, usually tube diagrams of the countercurrent mechanism continue for another cycle, as if expecting that those who have not yet grasped the concept will surely grasp it if only somebody were to patiently repeat it to them again without adding any new explanatory material.
Without insulting the reader with any further diagrams, the gist of this is that a small difference in osmotic pressure generated by a single effect the effect of ion pumps in the thick ascending limb ends up being multiplied by the countercurrent flow which brings fluid of increasingly higher and higher osmolality to the aforementioned pumps, allowing their One Weird Trick to produce increasingly higher and higher interstitial osmolalities.
Moreover, even as the osmolality climbs higher and higher, the gradient between the tubular fluid and the intersititum remains relatively stable, which means the ion pumps never have to pump against a very high gradient, making this whole thing a lot more efficient. On the basis of these italicised underlined elements, this process is generally referred to as the countercurrent multiplier effect.
How much does this multiplier mechanism multiply the medullary interstitial solute concentration? What are the values in the tubules of the living human kidney? One might be tempted to retort tartly that surely this must depend on the individual kidney, and in any case the understanding of the mechanism is more important than memorising numbers. Unfortunately, this is both true, and a terrible attitude to adopt for the CICM First Part Exam, which is built on the foundation of memorising pointless values.
What's a reputable resource for these sort of data? The college's need for quotable numbers does not diminish the fact that most of the values are measured in experimental animals, and not even from whole animals but often from tortured chunks of kidney. Moreover, they all give different values, and have different starting conditions.
If aquaporin water channels are present, water will be osmotically pulled from the collecting duct into the surrounding interstitial space and into the peritubular capillaries. This process allows for the recovery of large amounts of water from the filtrate back into the blood, which produces a more concentrated urine. If less ADH is secreted, fewer aquaporin channels are inserted and less water is recovered, resulting in dilute urine.
By altering the number of aquaporin channels, the volume of water recovered or lost is altered. This, in turn, regulates the blood osmolarity, blood pressure, and osmolarity of the urine.
These figures are from McKinley 2nd ed. Aldosterone is secreted by the adrenal cortex in response to angiotensin II stimulation. As an extremely potent vasoconstrictor, angiotensin II functions immediately to increase blood pressure. By also stimulating aldosterone production, it provides a longer-lasting mechanism to support blood pressure by maintaining vascular volume water recovery. In addition to receptors for ADH, principal cells have receptors for the steroid hormone aldosterone.
Peritubular capillaries or vasa recta receive the solutes and water, returning them to the circulation. The kidney regulates water recovery and blood pressure by producing the enzyme renin. It is renin that starts a series of reactions, leading to the production of the vasoconstrictor angiotensin II and the salt-retaining steroid aldosterone. Water recovery is also powerfully and directly influenced by the hormone ADH. Even so, it only influences the last 10 percent of water available for recovery after filtration at the glomerulus, because 90 percent of water is recovered before reaching the collecting ducts.
The descending and ascending limbs of the loop of Henle consist of thick and thin segments. In the presence of ADH, which increases water permeability, the hyposmotic fluid that enters the distal tubule DT from the thick ascending limb TAL looses most of its water by osmotic equilibration with the surrounding cortical interstitium along the CNT and cortical collecting duct CCD.
The relatively small amount of isoosmotic fluid that flows into the medullary collecting ducts losses progressively more and more water to the hyperosmotic medullary and papillary interstitia and is finally excreted as hyperosmotic, highly concentrated urine.
A lumen positive electrical potential difference is generated by the luminal Na-K-2Cl cotransporter operating in parallel with channels that allow K to recycle into the lumen. If the collecting ducts are water permeable then the huge concentration gradient between the medulla and the collecting ducts will drag water out of the urine into the medulla. Finally we have a concentrated urine. Next stop after the collecting ducts is the bladder. The extent to which the urine is concentrated depends mainly on how water permeable the collecting ducts are.
The water permeability of the collecting ducts is controlled by anti-diuretic hormone ADH. In the absence of ADH, the collecting ducts are water impermeable, no water is reabsorbed and a large volume of dilute urine is produced. In the presence of a high concentration of ADH the collecting ducts are highly water permeable, a lot of water is reabsorbed and a small volume of very concentrated urine is produced.
ADH, working via cAMP as a second messenger stimulates insertion of water channels aquaporins into the plasma membrane. Way back in the first plenary, I mentioned that aquaporins are not gated, i. The way to get variable water permeability is therefore to change the number of aquaporins in the membrane. When the water permeability must be low, collecting duct cells move the aquaporins from the membrane by exocytosis and keep them in little membrane vesicles inside the cell; when water permeability must be high, they reverse the process.
Activation of V2 receptors by ADH also stimulates synthesis of additional receptors. The V2 receptors for ADH is yet another example of a 7-membrane-spanning-domain-G-protein-coupled receptor, but more about that later. All intermediate stages of water permeability are possible so that the volume and the concentration of urine can respond to the changing needs of the body in regulating fluid and electrolyte homeostasis.
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