Exam 4 Review:  Chapter 25:  Water Balance & Renal Clearance

obligatory water reabsorption - The water withdrawn from the plasma filtrate as a necessary osmotic movement which is merely a passive component of the active transport of solutes (e.g., sugars, amino acids, and electrolytes) from the plasma filtrate to be returned to the blood stream; by far, the most important active transport mechanism coupled to water reabsorption is Na+ reabsorption which occurs primarily in the proximal convoluted tubule; the quantity of water reabsorbed in this fashion represents from 90% to greater than 99% of the total water reabsorbed by the renal tubules.

facultative water reabsorption - The water withdrawn from the plasma filtrate as a regulated negative feedback control of hydration status under the influence of ADH = antidiuretic hormone; this water reabsorption occurs primarily in the loops of the nephrons, particularly the juxtamedullary nephrons; the quantity of water reabsorbed in this fashion represents from ~1% to ~10% of the total water reabsorbed by the renal tubules.

osmolarity - A scientific measure of the total concentration of all particles (dissolved solutes and suspended matter) in a solution which contribute to the osmotic pressure* of the solution expressed in osmoles per liter of solution.  [Note:  Osmotic pressure = the pressure exerted by the flow of water through a semipermeable membrane separating two solutions with different concentrations of solute.]

countercurrent flow  -  Any physical arrangement of parallel pipes or vessels in which a fluid medium is transmitted in opposite directions in the parallel portions of the pipes or vessels; the opposite of cocurrent flow.

countercurrent mechanism - The complex control of facultative water reabsorption by the endocrine regulation of the kidney by ADH = antidiuretic hormone which makes use of a series of countercurrent flows in the medulla where an osmotic gradient is maintained due to active transport of sodium (primarily) and urea (secondarily); countercurrent flow is established between (a) the ascending and descending limbs of the loop of the nephron, (b) the ascending and descending portions of the vessels of the vasa recta, and (c) the loop of the nephron, and the vessels of the vasa recta; due to the complex countercurrent flow among these three overlapping systems, water can be transported by osmosis from the plasma filtrate in the loop of the nephron and from the urine in the collecting ducts to the venous drainage of the vasa recta capillaries and therefore back to the systemic circulation.  For additional details and figures, see Regulation of Water Balance.

Osmotic Gradient Within The Kidney

diuretic - Any substance (caffeine, ethyl alcohol, etc.) or drug (many such classes of drugs are known) which tends to increase the production and discharge of urine from the kidneys.

blood urea nitrogen (BUN) - A standard clinical laboratory measure of the amount of the nitrogenous waste, urea, present in the blood, expressed in terms of the proportion of elemental nitrogen present in the urea molecule.

plasma creatinine - A standard clinical laboratory measure of the amount of the nitrogenous waste, creatinine (the spontaneous breakdown product of creatine, the high energy phosphate group storage compound of skeletal muscle), present in the blood, expressed in mg/dl = milligrams per deciliter.

renal plasma clearance - The experimental measurement of the rate of elimination of a substance from the blood plasma by transfer of the substance in the urine by the process of plasma filtration at the glomerulus of the renal corpuscle with the clearance rate reported in mL of urine per unit time; for example, the amount of creatinine, a nitrogenous waste product formed from the spontaneous breakdown of creatine, can be measured in the plasma at time zero (after voiding the bladder) and then measured in a total urine specimen collected subsequently, e.g., at 2 hours or 24 hours, and a calculation can be performed to determine the rate of creatinine clearance* in mL/min; such clearance values can assist in diagnosing the adequacy of plasma filtration, and estimating the GFR = glomerular filtration rate, by the kidneys.  [*Note:  the formula for creatinine clearance (CrCl) is:  CrCl = (UrineCr x UrineVol) / (PlasmaCR x Tmin)  ]

inulin - A polysaccharide, intermediate in size between starch and simple sugars, with the general formula (C6H10O5)n which is found in the roots of various composite plants and yields fructose when hydrolyzed; it is not metabolized by the body and therefore can be used a biological marker in certain types of clinical tests and as an artificial sweetener in foods for diabetics; it is one of the compounds used in renal plasma clearance studies because it is small enough to enter the plasma filtrate freely with water and is uninvolved in processes of tubular reabsorption or secretion; therefore, when used as a marker, it estimates glomerular filtration rate = GFR.

para-aminohippuric acid (PAH) - A small organic chemical (N-(4-aminobenzoyl)glycine) which may be used as a biological marker in certain renal function studies because it is transported from the blood to the urine by toxin pumps in the renal tubule, an example of renal tubular secretion; it is generally used to assess the adequacy of renal perfusion (blood flow to the nephrons).

Explain:

1. how renal clearance of different substances, inulin versus para-aminohippuric acid (PAH) can be used to evaluate different aspects of renal function.

Substance Used in a Renal Clearance Study Aspect of Renal Function Evaluated
inulin Inulin is a polysaccharide, intermediate in size between starch and simple sugars, with the general formula (C6H10O5)n which is not metabolized by the body and therefore can be used a biological marker in clearance studies because it is small enough to enter the plasma filtrate freely with water and is uninvolved in processes of tubular reabsorption or secretion; therefore, when used as a marker, it estimates glomerular filtration rate = GFR.
para-aminohippuric acid (PAH) Para-aminohippuric acid (PAH) is a small organic chemical (N-(4-aminobenzoyl)glycine) which may be used as a biological marker in certain renal function studies because it is transported from the blood to the urine by toxin pumps in the renal tubule, an example of renal tubular secretion; it is generally used to assess the adequacy of renal perfusion (blood flow to the nephrons).

2. the role of the countercurrent multiplier mechanism of Henle's loop versus the vasa recta of Henle's loop in forming a hyperosmotic medullary interstitial fluid and why this hyperosmotic medullary fluid is important in the formation of a concentrated urine? Why must the kidney always form some urine (assuming filtration is occurring normally)?

Explain the role of the countercurrent multiplier mechanism of Henle's loop versus the vasa recta of Henle's loop in forming a hyperosmotic medullary interstitial fluid.
(1)  Active transport of sodium ions and urea molecules from the filtrate into the medullary interstitial space occurs in the loop of the nephron and in the collecting ducts.  Chloride ions tend to follow passively.
(2)  An osmotic gradient exists, due to countercurrent flow between the loop of the nephron and the vasa recta.  [You can see this countercurrent flow in the diagram to the right.  Notice that filtrate is flowing downward on the left and upward on the right in the loop while blood is flowing downward on the right (red = arterial side of capillary flow) and upward on the left (blue = venous side of capillary flow) in the vasa recta.]
(3)  Water follows the salt (sodium chloride) and urea.  The salt and urea tend to be carried toward the medulla by moving into the arterial side of the vasa recta flow, thus increasing their concentration gradients, and, therefore, the osmotic gradient as one progresses into the medulla.  At the same time, water which has followed the salt and urea from the filtrate is drawn into the highly osmotic blood plasma of the vasa recta and carried upward on the left, on the venous side of vasa recta flow, so that it does not dilute the salt and urea in the medulla, but, rather, is returned to the cortex and to the systemic circulation and, thus, to the rest of the body.  [The green arrows in the figure represent the movement of the salt and urea.]
hyperosmotic medullary interstitial fluid gradient

Why is this hyperosmotic medullary fluid important in the formation of a concentrated urine?
Without the osmotic gradient which is maintained within the medullary interstitial fluid, there would be no effective force (the osmotic force) to force water to leave the lumen of the nephron and return to the medullary interstitial space.  Once in the medullary interstitial space, the water can be further drawn into the hyperosmotic plasma of the vasa recta and ultimately returned to the systemic circulation and the body as a whole.

Why must the kidney always form some urine (assuming filtration is occurring normally)?
Because there are always wastes, including electrolytes (K+, HPO4-, H+, etc.) and nitrogenous wastes (urea, creatinine, and uric acid), to name a few dependable and important wastes, to be eliminated and because the ability of the kidney to reabsorb water is not infinite, i.e., the kidney cannot excrete wastes unless they are dissolved in some quantity of water.

3. the regulatory mechanisms that determine if the nephron produces a dilute or a concentrated urine.

(1)  Chemoreceptors in the JuxtaGlomerular Apparatus (JGA) and in the hypothalamus monitor water and electrolyte composition of the blood and the urine in the vicinity of the JGA.  (2) Indicators of dehydration or reduced blood pressure will trigger the renin-angiotensin system.  (3)  In response, autonomic impulses will adjust blood pressure and initiate thirst while the combined effects of three hormones, ADH = antidiuretic hormone = vasopressin, angiotensin (I&II), and aldosterone will act on the kidney at various points within the nephrons to encourage water and salt reabsorption.  (4)  When the body is well hydrated, this system will reduce its activity as a form of negative feedback control.