PHYSIOLOGY DEC12,2011 The blood in glomerular capillaries is separated from the fluid in bowman’s Dr. Paguirigan space by a filtration barrier that has 3 layers: 1.Single-celled capillary endothelium RENAL PHYSIOLOGY 2.single-celled layer of Epithelial lining in bowman’s capsule 3.Glans cellular layer of basement membrane -between endothelium & FUNCTIONS OF THE KIDNEY epithelium -regulate water& inorganic ion balance -removal of metabolic waste products from blood, excreted in urine TUBULES -Removal of foreign chemicals in the blood then excreted in urine -extending out from bowman’s capsule are the nephrotubules-lumen are -Secretion of hormones continuous in bowman’s space; throughtout the course of tubules, composed Erythropoietin- controls erythrocyte production of single-celled layer of epithelial cell that rest on the basement membrane. Rennin-controls formation of angiotensin As you go along the length of tubule, the epithelial cells differ in function & *angiotensin-influences blood pressure & sodium balance structure. Dihydroxy-vitamin B3 (1,25-dihydroxy-vit.B3)-influences Ca balance 4 major divisions recognized in the tubules: Proximal tubule- segment of tubule that drains directlythet bowman’s capsule STRUCTURE OF THE KIDNEYS Loop of henle- sharp hairpin-like loop consisting of descending limb from -Each kidney is composed of approx. 1million nephron (functional unit) proximal tubule & ascending limb leads to the next segment of the tubule Nephron-consist of glomerulus, tubule, collecting ducts Distal tubule - completely separates from its neighbors but several distal Glomerulus- initial component of nephron tubules from adjacent nephrons join to form the Collecting duct. -forms protein-free filtrate of blood that passes into it Distal tubules of other nephron should drain into the collecting duct that is Tubules- process is filtrate as it flows through it, processing is done before it formed from the union of the ducts towards the central cavity of the kidney. reach the kidney as urine Then Collecting ducts unite to form renal pelvis Glomerulus is formed from systemic arterial blood enters each kidney through renal artery which progressively divides into smaller branches. IMPORTANT REGIONAL DIFFERENCES IN THE KIDNEY Each smaller arteries give off a series of arterioles called afferent arterioles. Renal cortex-outer portion Each of these arterioles will conduct blood into a compact part that produce -contains all glomeruli, proximal and distal tubules, outer portion of the loop of a balloon-like hallow capsule called bowman’s capsule henle and collecting ducts The combination of glomerular capillaries &bowman’s capsule constitutes the -Loop of henle extends from cortex bound into the inner portion (renal glomerulus. medulla) to which also courses the collecting ducts on their way to the renal The capillaries in the glomerulus invaginate into the bowman’s capsule. pelvis The part of the bowman’s capsule that is in contact with the glomerullar Renal pelvis-continuous with ureter capillary are pushed inward but not actually in contact with opposite side of *ureter- a tube that passes to the kidney going to urinary bladder the capsule. There is a fluid filled space between themBowman's space where urine is temporarily stored until eliminated during urination via the which exists within the bowman s capsule. urethra To return the kidney blood vessels, Glomerular capillaries, instead of leading to the veins, recombines to form another arteriole efferent arteriole movement of protein (protein is a high molecular weight substance) *Efferent arteriole-blood leaves the glomerulus -The urine that eventually enters the renal pelvis is quite different from -divides into 2nd set of capillary peritubular capillaries which branch very glomerular filtrate ‘coz as the filtrate flows from the bowman’s capsule, profusely to form a network around the tubule and then eventually rejoins to through the tubules, to the loop of henle, the composition is altered. The form the veins in which the blood will leave the kidney alteration or exchange occurs by two general processes called tubular reabsorption and tubular secretion. *The tubule is in intimate association with the peritubular capillary JUXTAGLOMERULAR APPARATUS (JGA) network. This relationship permits the transfer of materials betweenn before the ascending limb of the lood of Henle becomes the distal tubule, it peritubular blood and the lumen of the tubules. passes between the arterioles that supply the glomerulus -When the direction of transfer is from tubular lumen to peritubular macula densa-short segment of the tubule capillary plasma, it is called tubular reabsorbtion or simply reabsobtion Wall of the afferent arteriole of the macula densa contains secretory -When the movement of substance in the opposite direction from the cellsgranular cells peritubular plasma going to the tubular lumen, it is called tubular Combination of macula densa & granular cells is the JUXTAGLOMERULAR secretion or simply secretion APPARATUS *that is a two way process; the substance is either reabsorbed or secreted in the urine JGA FUNCTIONS: Tubular reabsorbtion and tubular secretion denotes only the direction of the Granular cell-secretes rennin which is involved in blood pressure regulation transfer mechanism but actually it’s a diffusion for some substances and it is a and sodium balance mediated transport for others Macula densa- sensor of tubular fluid flow, When in a mediated transport, the transport process are in the plasma - it also senses the fluid composition in the local hemeostatic membrane of the tubular epithelial cell responses that regulates both the secretion of rennin and the weight of fluid secretion by the glomeruli COMPOSITION OF GLOMERULAR FILTRATE - Essentially low in weight FUNDAMENTAL/BASIC RENAL PROCESSES -Contains all other substance in the plasma URINE FORMATION -Same concentration as blood plasma -begins with the glomerular filtration-> it makes a backflow of the protein free *Exceptions: plasma from glomerular capillaries to the glomerular membrane, capillary --Certain low molecular weight substances that are filterable but are bound epithelium, basement membrane, and ends in the epithelium of the to plasma protein so they cannot be filtered bowman’s capsule Example—half of plasma calcium & all fatty acids in the plasma are bound -Capsule fluid filtrated in the bowman’s capsule is called glomerular fitrate to plasma protein and not filtered *GLOMERULAR FILTRATE-contains all the substances that is present in the -The glomerular fitrate as essentially protein free is not entirely true; in reality plasma except protein there is very small amount of protein in the filtrate since the glomerular -concentration is the same as blood plasma membranes are not perfect barriers for protein. -normally does not contain protein ‘coz glomerular membrane restricts the Normally, these filtered proteins are completely removed from the tubule so there will be no protein that will appear in the final urine. -Since the glomerular capillaries are very much more permeable to fluid than -If the kidneys are diseased, the glomerular membrane may become much the capillaries in the muscle or the capillaries in the skin. The net filtration more permeable to protein even the tubules may lose their ability to remove it pressure of 10mmHg can already cause massive filtration. So a 70kg person, from the tubules. In either case, protein will appear in the urine the average volume that is filtered into the bowman’s capsule is about 180L/day compared to a net filtration of all the capillaries in the body is only FORCES THAT ARE INVOLVED IN FILTRATION 4L/day. -Glomerular filtration, like filtration across any capillary is the bulk flow process. These capillary filtration is determined by opposing forces. SEVERAL INDICATIONS THAT IS REMARKABLE IN FILTRATION RATE: -Hydrostatic pressure difference across the capillary wall favors filtration. To form a huge volume of filtrate. To do this, the kidney must receive a large While protein concentration across/between the protein concentration share of cardiac output. Each moment the kidney receives about 25% of blood differences across a wall and osmotic force opposes filtration. These opposing pumped by the left ventricle. The two kidneys’ combined weight is about 1% of forces also applies to glomerular capillaries. the body weight but it receives 25% of cardiac output. Since the total volume -The pressure of the blood in the glomerular capillary averages about of the plasma in the cardiovascular system is approximately 3Liters, it follows 25mmHg. It is higher than other capillaries in the body because the afferent then that the entire plasma volume is filtered by the kidneys about 30x/day. arteriole of the nephron has relatively large diameters so they are less resistant These opportunity of the kidneys to process such volume of plasma, enables than most arterioles so more of the arterial pressure is transmitted to the the kidneys to regulate the constitution of internal environment and excrete capillaries. These glomerular capillary hydrostatic pressure favors filtration. large quantities of water-waste products. -The fluid in the bowman’s capsule exerts a hydrostatic pressure of about 50mmHg and this is the one that also opposes filtration into the capsule. If you want to calculate the amount of tubular reabsorption, you can subtract -Another force that tends to oppose the filtration is the force that results in the filtered load less the GFR times the plasma concentration of the substance the presence of protein in the glomerular capillary plasma. Its absence would and you can get the tubular reabsorption of a certain substance. Water, for be bowman’s capsule. This unequal distribution of proteins causes the water example, the amount of water that is filtered by the kidneys per day is 180L concentration of the plasma to be less than that of the fluid in the bowman’s and amount excreted per day is 1.8L. so the percent of reabsorption is 99%. capsule so it is another opposing factor. This difference in the water Water: concentration will favor osmotic flow of the fluid. filtered -180L -For water and all low molecular weight solutes from the bowman’s capsule excreted-1.8L goes to glomerular capillaries. and these flow is equivalent to what is produced percent of reabsorbtion-99% to a pressure difference of about 30mmHg. So the net glomerular filtation Sodium: pressure will have an algebraic sum from 3 chemical forces that we have filtered -630g mentioned is about 10mmHg. This pressure will initiate urine formation by excreted-3.2g forcing and essentially protein-free filtration of the plasma through the percent of reabsorbtion-99.5% glomerular membrane into the bowman’s capsule, then down into the tubules Glucose: and into the renal pelvis. The glomerular membrane serves only as filtration filtered -180g barrier and they have no energy-requiring function. It is just like a passive filter. excreted- normally 0 -The volume of fluid that is filtered from the glomerular capillaries into the percent of reabsorbtion-100% bowman’s capsule per unit of time is the glomerular filtration rate (GFR). Urea: filtered -54g load becomes very high. The glucose will appear in the urine because the excreted-30g tubules cannot reabsorb the entire filtered load. percent of reabsorbtion-44% Example of a passive reabsorption by means of diffusion is the reabsorption of urea. Urea reabsorption is a passive process that is dependent upon the In tubular reabsorbtion, there is little bulk flow across epithelial cells of the reabsorption of water. This process causes reabsorption of about 50% of the tubules; from the lumen to interstitial fluid. So the reabsobtion is not by mass filtered urea. Reabsorption by diffusion is of considerable importance in many movement rather reabsobtion of some substances by diffusion and others foreign chemicals. If you try to remember the plasma membranes, like that of requires, more or less, mediated transport system. Except for substances that tubular epithelium, are primarily lipid. So lipid-soluble substances can can diffuse across tight junction between cells, tubular reabsobtion requires penetrate through them readily. One of the major determinants of lipid the movement of substances across several membrane. solubility is the polarity of the molecule. Less polar, more lipid soluble. Many drugs and environmental pollutants that are nonpolar and highly lipid DEFINITION OF TERMS IN PLASMA MEMBRANE OF TUBULAR EPITHELIAL CELL soluble. So they are filtered and excreted in the urine. They are filtered in the luminar membrane-The portion of the plasma membrane facing the lumen glomerulus but reabsorption by diffusion, like in water absorption, causes of the tubules intraluminal concentration to increase. To make it more excretable, the liver basolateral membrane -Beginning at the tight junctions and constituting the transforms them into more polar metabolites. And it reduces their lipid plasma membrane of the sides/base of the cell solubility so they diffuse across the tubular wall fully and they can be excreted *To be reabsorbed through the cell, the substance must first cross the more readily. Without the liver, the metabolites cannot be excreted readily. luminal membrane then diffuses through the cytosol of the cell and finally cross the basolateral membrane into the interstitial fluid. Tubular secretion- another process by which substances move from *Membrane then the pertitubular capillary epithelium then entry to the peritubular capillaries into the tubular lumen capillaries. Hydrogen ion & potassium-most important substances that is secreted by the active process -If the movement across either the luminal membrane or the tubules. The kidney is also able to secrete a large number of organic ions. Some basolateral membrane active then the entire process is termed of which are normally occurring metabolites like choline and creatinine. While passive process-If the movement across the basement membrane into the others are foreign chemicals like for example antibiotic, penicillin. These capillary epithelium into the peritubuilar capillaries, by a combination of substances diffuse from a peritubular capillaries into the interstitial fluid that is diffusion and backflow outside the basolateral membranes of the tubular epithealial cells. They are transport maximum (TM) – the limit of many of the active-reabsorbtive then actively transported across the basolateeral membrane into the cell system in the renal tubule followed by an exit across the luminal membrane and into the tubular lumen. -the limit of amount of the material that they can transport per unit of time because the membrane protein that is responsible for the transport can The fourth function/process of the kidney,as we have mentioned,is become saturated. METABOLISM. The cells of renal tubules are able to systhesize certain substances notably ammonia which is then added into the luminal fluid then Example of the active transport process for glucose. Normal persons do not excreted. The cells are also capable in catabolizing certain organic substances. secrete glucose in their urine because all filtered glucose is reabsorbed Peptides,for example, is taken up from the tubular lumen or peritubular however if the plasma glucose concentration is high and therefore the filtered capillaries & eliminated from the body,as if excreted in the urine. PROCESS OF MICTURATION/URINATION and the parasympathetic will not fire nerve impulses but as the bladder is filled -The composition of urine is not significantly altered after it already reached with urine, become distended and the stretch receptors is stimulated, reflexly the collecting ducts, the tubules and the loop of henle where the alteration stimulated, stimulation of the parasympathetic neurons so there's contractions takes place. of the bladder. So anytime anywhere the infant will just urinate by spinal reflex. -The composition of the urine once it has reached the collecting ducts and the The contraction will just pull the bladder outlet the pressure required the urine renal pelvis, is not altered anymore. to flow through the urethra. Urine from collecting ducts & renal pelvis The voluntary control of micturition is learned during childhood and involves ↓ the skeletal muscles of the pelvic diaphragm, forms the floor of pelvis and goes to the ureters helps support the lower part of the UrinaryBladder. Voluntary relaxation of the pelvic diaphragm will allow the neck of the by pumping process; continuously bladder to move downwards, opens the bladder outlet while simultaneously propelled by contractions of the stretching the wall of the bladder and eliciting a reflex bladder contraction via smooth muscles of the urethral wall parasympathetic nerves. If the increase pressure resulting from the contractions of the bladder wall is to the urinary bladder insufficient to force the urine into the urethra, the pressure can further ↓ increase by voluntary contraction of the abdominal muscles and the respiratory intermittently ejected during urination or micturition diaphragm can even increase the intra-abdominal pressure so these can increase the pressure acting on the bladder so you can expel the urine. The urinary bladder is a balloon-like chamber that its walls are made up of The voluntary control is now in the pelvic diaphragm, which we learn from smooth muscles. childhood to control it, not like the infants that they cannot control urination The smooth muscle at the neck of the urinary bladder is the one that act as ‘coz they it’s just the basic spinal reflex. the sphincter and we call it the internal urethral sphincter. This is not a distinct muscle from the muscle of the UrinaryBladder which is Micturition can also be stopped voluntarily, just simply by contracting the only a last portion of the bladder and first portion of the urethra. pelvic diaphragm. Halimbawa Umiihi ka bigla kang nakakita ng ahas, edi When the bladder is relaxed, the outlet of the bladder is closed. When the gagawin mo, tumayo kaagad. urinary bladder is either actively contracts or passively distended, the outlet is The last drop of urine is expelled by different muscles… full open by changes in the bladder's shape. It open so you can urinate, but this In the female, the urinary bladder wall that expels the last drop of urine can be controlled by several factors. In male, I think it's the flexor digitorum (lol) . So if I ask that in the examination, In an infant, the micturition is basically a local spinal reflex and the time, it would be a subjective answer. It depends if you’re a male or female (lol). even the place, when they urinate is dependent entirely on the volume of urine in the bladder active to this spinal reflex only. The bladder wall stretch receptors afferent fibers enter the spinal cord and this stimulates the Parasympathetic nerves smooth muscle to the bladder. If they are stimulated, there's bladder contraction and the bladder they contain only small amount of urine but the internal pressure is low so little stimulus PROCESSES THAT INVOLVE VOLUNTARY CONTROL OF MICTURITION voluntary control, mawawala na un, so just purely spinal reflex. Brain: conscious desire to urinate Another situation associated in bladder control and bladder emptying is fear. ↓ The sudden fear, mapapaihi ka, hindi mo na makontrol yung pag-ihi mo. goes to descending pathways, Or others, strong emotions, which acts via descending pathway into bladder ↓ innervation. inhibition of efferent nerves to the pelvic diaphragm ↓ Maganda pala maglecture kapag may microphone, hindi ka na mapapagod. then pelvic diaphragm relaxes Wahahahahaha ↓ bladder neck moves down REGULATION OF SODIUM(Na) & WATER(H20) BALANCE ↓ -The other function of the kidney bladder outlet opens -The total body balance and the internal distribution of sodium and water. ↓ If we try to look at the amounts that we take in and is excreted, parang the wall stretches ganito.. ↓ WATER INTAKE from: wall stretch receptors are stimulated > we normally drink - usually 1200ml or 1.2L ↓ > contents in the food we take in - 1000ml or about 1L stimulation of the parasympathetic to the bladder smooth muscle is activated > those that are metabolically produced - 350ml ↓ TOTAL WATER INTAKE: usually 255Oml bladder contracts WATER OUTPUT: ↓ > insensible water loss (what we lose in the skin and the lungs)-900ml urine is micturated > sweat - 50ml (in not very warm, in the normal temperature) > feces - about 100ml unless You have diarhhrea When you were young, esp in the males, meron tayong palayuan ng ihi which > urine - 1500ml we call the parabolic curve. Malayo ang mararating ng ihi mo ‘pag bata ka. TOTAL OUTPUT: 2550ml Palayuan nga! Contest yun! But as you grow old, this parabolic curve decreases In normal condition, normally functioning kidney, and normal system of the esp. when you are above 50y/o which will drasctically decrease bec. of the body, the water intake is equal to the water output. enlargement of the prostate gland. So there's diminution or even absence of Being a low molecular weight and not bound to plasma protein, Na and H20 parabolic curve. So there are individuals that when they urinate, wala na yung are both freely filtered by the glomerulus, they both undergo considerable parabolic curve, they just dribble. It’s just dribbling of the urine. Sabi nga nila, reabsorption normally as we saw it is 99% and there is no secretion of these kapag matanda ka na, naiihian na yung paa mo. That is also because of the two. Na reabsorbtion is primarily an active process and water reabsorbtion is decrease in the force of contraction in the UrinaryBladder. by osmosis. And water reabsorbtion is also dependent upon Na In adults, if they have damage in the CNS that interrupts the descending reabsorbtion…That is very important! pathways mediating the voluntary control of pelvic diaphragm, micturition will The primary active transport of Na is via the Na-K ATPase pump that is again go back, will come again as purely spinal reflex, like in infancy. So if located in the epithelial cell basolateral membrane. Na is taken up to this there's a damage in descending pathway coming from the brain controlling the system, it goes out of the cell into the interstitial fluid. This active transport keeps the intracellular concentration of Na very low and the cell inferior fluid leaving the proximal tubule like the fluid entering it from the bowman’s becomes electrically negative with respect to the outside. Therefore, there capsule is therefore isotonic to plasma which is about 300milliosmol/L. exist a chemical difference and also an electrical difference to move the Na out But water permeability of the segments of the nephron beyond the proximal of the lumen into the luminal epithelial cells. tubules vary considerably. The water permeability of the distal tubule and This movement across the luminal membrane is either by diffusion through collecting ducts can be high or low because it is subject to physiological Na channels or by carrier-mediated transport. The specific mechanism varying control. from segment to segment of the tubule, depends upon which protein channel The major determinant of water permeabiIity in this segment is a peptide or transporters present on their luminal membranes. When Na moves through hormone that is secreted by the posterior pituitary hormone that is known as the channels, it moves along. But if it is the carrier mediated pathway , it ADH or vasopressin. The ADH stimulates production of cyclicAMP in the cotransports or countertransports a large number of substances together with epithelial cells of the distal tubules and collecting ducts leading to the Na. These substances undergo secondary active reabsorbtion or secretion. So appearance in the luminal membrane in these segments, a protein that for this people Na reabsorbtion is critical not only for retention of Na itself but functions as a water channel. for the renal processes of many other solutes. In the presence of high plasma concentration of ADH, the water permeability For example: in the distal tubule and the collecting duct is much very high, water -the countertransport of glucose and Na into the proximal tubular epithelial reabsorbtion is maximal, final urine volume becomes small that can reach less cells, than 1% of filtered water. -the cotransport of amino acid and lactate with Na in the proximal tubule, In the absence of the ADH, H20 permeability of this segments is very low, -the cotransport of Na and Cl in the ascending limb of loop of henle, this little water is reabsorbed and therefore there is large volume of urine is system even cotransports potassium. We call this, Na-K-Cl cotransporter. secreted. The urine secreted is hyperosmotic that is it has an osmolality much -hydrogen ion, these are countertransported with Na in the proximal tubules. lower than that of the plasma. This increase urine secretion resulting from a they are transported from the cells to lumen as Na moves in the lumen to cells. very low ADH is termed as water diuresis. It’s not Na alone that moves but it cotransports or countertransports other In the disease which we know as diabetes insipidus, illustrates what happens substances as well. when the ADH system is destructed. Persons with this dse have lost the ability The movement of Na from the tubular lumen into the interstitium across the to produce ADH. Usually as a result of the damage of the hypothalamus. DI is epithelial cells will lower the osmolality. So the lower osmolality because it characterized by constant H20 diuresis as much as 25L/day. raises the concentration of the luminal fluid. When it does this, it also The urinary concentration or the concentration of the urine takes place as simultaneously raises the osmolality that is it lowers the water concentration tubular fluid flows through the collecting ducts forcing to the medulla to the of the interstitial fluid that is adjacent to the epithelial cells. renal pelvis. InterstitialFluid surrounding these ducts are hyperosmolar. The difference in water concentration between the lumen and the interstitia causes a net osmosis of water from the lumen across the tubular cells, plasma In the presence of ADH membrane, and the tight junction of the interstitial. From there, water, Na, and ↓ everything else in the interstitial fluid moves together by bulk flow into the water diffuses out of the ducts into the InterstitialFluid peritubular capillaries as the final step in reabsorbtion. ↓ Normally, the water permeability of the proximal tubule is always very high. goes back to the BloodVessels in the medulla Water molecules are reabsorbed almost as rapidly as Na ions. As a result, the proximale tubule always reabsorb Na and water in the same proportion. The HOW DOES MEDULLARY INTERSTITIAL FLUID BECOME HYPEROSMOTIC? countercurrent multiplier system → concentrated descending limb fluid Process is… this a complex process that sets up this interstitial ↓ hyperosmolarity, collectively called the countercurrent multiplier system immediately rediluted which takes place in the loop of henle. This loop, like the collecting duct, ↓ extends to medulla of the kidney. The fluid first flow in one direction down to Enters distal tubule (which is more dilute than the plasma) the descending limb, and then to the opposite direction up to the ascending ↓ ←presence of ADH limb. The fluid entering the descending limb from the proximal tubule is about water movement across the tubular epithelium 300milliosmol (osmotic like the plasma). ↓ The ascending limb actively cotransports Na and Cl and is relatively fluid in the distal tubule will reequilibrate with the peritubular plasma by impermeable to water. So little water follows the salt. The pumps in the using water until it becomes isotonic to plasma that is present in the ascending limb do not transport Na and Cl into the descending limb but rather peritubular capillaries, until it becomes 300millioslol/L in the InterstialFluids that surrounds the limbs. ↓ In contrast, the descending limb does not pump Na -Cl and highly permeable enters and flows along the collecting ducts. to water. Therefore, the net diffusion of water out of the descending limb out ↓ into the more concentrated InterstitialFluid until the osmolality inside limb and Under the influence of ADH, the collecting ducts become more permeable to interstitial fluid becomes equal. The interstitial osmolality is maintained at water 400milliosmol/L during this equilibrium because the ascending limb continues ↓ to pump Na-Cl to maintain the 200milliosmol/L difference between it and the water diffuses from the collecting duct into the interstitial fluid as a result of interstitium. the high osmolality by the loop counter current multiplier system. The osmolality of the descending limb and the InterstialFluid becomes equal ↓ and both are 200milliosmol higher than that of the ascending limb. This is the Water enters the medullary capillaries essence of the countercurrent system. ↓ The loop countercurrent multiplier causes the interstitial fluid of the medulla carried out of the kidneys by venous blood to become concentrated. It is its hyperosmolality that will draw water out of the collecting ducts and concentrate the urine. If this system is not functioning, then you will have water dieresis. The urine that your patient will be excreting This water reabsorption occurs all along the length of the collecting duct. will be not concentrated. Fluid along the collecting ducts is essentially the same osmolality with the However, it must be emphasized at this point that the active Na-Cl transport interstitial fluid surrounding the loop of henle that is in the bottom of the mechanism in the ascending limb is the essential component of this entire medulla. So final urine becomes hyperosmotic. system. If there is a defect in the Na-Cl transport, then the ascending limb and Now if the plasma ADH concentration is low, the opposite will happen, distal the whole system will be disrupted. tubules and collecting ducts become relatively permeable to water. As a result, a large volume of hypoosmotic urine will be excreted. If we try to analyze the processes that we mentioned, you we will see that countercurrent multiplier system concentrated the descending limb fluid but it then immediately rediluted it so that it can entering the distal tubule that is actually more dilute than the plasma.