Renal Physiology PDF

Renal Physiology The kidneys have several functions including the following: Regulate water and electrolytes balance. Excretion of metabolic waste products like urea (from the metabolism of amino acids), creatinine (from muscle creatine), uric acid (from nucleic acid), bilirubin (the end...

Renal Physiology The kidneys have several functions including the following: Regulate water and electrolytes balance. Excretion of metabolic waste products like urea (from the metabolism of amino acids), creatinine (from muscle creatine), uric acid (from nucleic acid), bilirubin (the end product of Hb breakdown), metabolites of various hormones and foreign chemicals like drugs and toxins.. A waste is any substance that is useless to the body or present in excess of the body’s needs. A metabolic waste is a waste substance produced by the body. Thus the food residue in feces, for example, is a waste but not a metabolic waste, since it was not produced by the body and, indeed, never entered the body’s tissues. Metabolism produces a great quantity of wastes that are lethal to cells if allowed to accumulate. Some of the most toxic examples are small nitrogen-containing compounds called nitrogenous wastes. About 50% of the nitrogenous waste is urea, a by-product of protein catabolism. Proteins are broken down to amino acids, and then the -NH2 group is removed from each amino acid. The -NH2 forms ammonia, which is exceedingly toxic but the liver quickly, converts it to urea. Other nitrogenous wastes in the urine include uric acid and creatinine, produced by the catabolism of nucleic acids and creatine phosphate, respectively. Although less toxic than ammonia and less abundant than urea, these wastes are far from harmless. The level of nitrogenous waste in the blood is typically expressed as blood urea nitrogen (BUN). The urea concentration is normally 7 to 18 mg/dL. An abnormally elevated BUN is called azotemia and may indicate renal insufficiency. Azotemia may progress to uremia, a syndrome of diarrhea, vomiting, dyspnea, and cardiac arrhythmia stemming from the toxic effects of nitrogenous wastes. Convulsions, coma, and death can follow within a few days. Unless a kidney transplant is available, renal failure requires hemodialysis to remove nitrogenous wastes from the blood. Regulation of arterial pressure both in long-term regulation (through excretion of variable amounts of sodium and water) and in short-term regulation (through secretion of vasoactive factors or substances such as renin). Acid-base regulation (along with the lungs and body buffers) through excreting acids and by regulating the body buffer stores. Regulation of erythrocyte production from the bone marrow by secreting erythropoietin which stimulate the bone marrow to produce erythrocytes. Regulate 1, 25- dihydroxy vit D3 production which is essential in regulation of Ca and phosphate. In kidneys, gluconeogenesis can take place. Most gluconeogenesis occurs in the liver, but a substantial fraction occurs in the kidneys, particularly during a prolonged fast. Renal function is based on four steps: Blood from renal arteries is delivered to the glomeruli. At 1/5 of cardiac output, this is the highest tissue-specific blood flow. 1. Glomeruli form ultrafiltrate, which flows into renal tubules. 2 and 3 Tubules reabsorb and secrete solute and water from the ultrafiltrate. 4. Tubular fluid leaves the kidney via the ureter to the bladder and out through the urethra. Anatomy and function of the kidney The kidney consists of: [A] Nephron. [B] Blood vessels. [C] Nerves (A) Nephron: It is a tubular system and it is the basic functional unit of the kidney that capable of forming urine by itself. There are about 1 million nephrons in each kidney in human. Kidneys cannot regenerate new nephrons and their number decrease with aging, each nephron consists of: [A] Bowman`s capsule: It is the invaginated blind end of the tubule that encased the glomerulus (which is a branching capillaries). The pressure in the glomerular capillaries is higher than that in other capillary beds. The membrane of the glomerular capillaries is called the glomerular membrane. The average total area of glomerular capillary endothelium across which filtration occurs (i.e. the glomerular membrane) is about 0.8 m2. In general, this membrane is different from other capillary membranes by having three layers instead of two. These three layers are endothelial layer of the capillary itself, a basement membrane (basal lamina), and a layer of epithelial cells (podocytes). Narrow filtration that slits between these projections are bridged by a membrane protein called nephrin, which also contributes signifi cantly to the filtration barrier. Fixed negative charges are present in the basement membrane and the filtration slits, and account for electrical repulsion of negatively charged macromolecules by the filtration barrier. Another type of cells is also present between the basal lamina and the endothelium called mesangial cells, which are contractile cells and play a role in the regulation of glomerular filtration besides other functions. Yet, despite the number of layers, the permeability of the glomerular membrane is from 100-500 times as great as that of the usual capillary. The tremendous permeability of the glomerular membrane is caused by the presence of thousands of small holes which are called fenestrae in the endothelial cells, by the presence of large spaces in the basement membrane, and by incontinuity of the cells that form the epithelial layer which are finger-like projections that forms slits between themselves called slit-pores. [B] The Tubule: Throughout its course, the tubule is made up of a single layer of epithelial cells resting on a basement membrane. (Note: All epithelial cell layers rest on a basement membrane). The structural and immunocytochemical characteristics of these epithelial cells vary from segment to segment of the tubule. A common feature is the presence of tight junctions between adjacent cells that physically link them together  Proximal tubules: It includes proximal convoluted tubule and proximal straight tubule. They lie in the renal cortex along with the glomerulus. The epithelial cells of the proximal tubule are highly metabolic cells, with large number of mitochondria to support extremely rapid active transport processes and they are interdigitated with one another and are united by apical tight junction but contain lateral intercellular space. It contains a brush border due to the presence of microvilli. Reabsorption in the proximal tubule is essentially isotonic; i.e. the osmolality of fluid in all parts of the proximal tubule is approximately to that of plasma. The proximal tubule resorbs from the filtered material Na+, K+, Cl-, nearly all glucose and amino acids and a proportional amount of water. The mechanism for glucose and amino acid reabsorption involves co-transport with Na+ across the proximal tubule apical membrane. In addition, the proximal tubule also resorbs urea, phosphate, Mg, sulfate, lactate, acetoacetate ions, vitamins and lipid-soluble substances. Approximately 99% of the water filtered by the glomerulus is also resorbed by the whole renal tubule segments; and about 65% of the filtered water is resorbed by the proximal tubule. In addition, the proximal tubule epithelium also secretes H+, organic acids, bases, and certain drugs, such as penicillin into the tubule fluid. The proximal tubule is the site of glomerulotubular balance as we will see later.  Proteins are absorbed through the brush border of the proximal tubule by the process of pinocytosis. Although the amount of Na in the tubular fluid decreases markedly along the proximal tubule, the concentration of Na and the total osmolarity remains relatively constant (isotonic) because water permeability of the proximal tubules is so great that water reabsorption proportional to Na reabsorption. The proximal tubule is also the site for secretion of organic acids and bases (bile salts, oxalate, urate, Catecholamines), drugs, and toxins.  Reabsorption of HCO3- occurs primarily in the proximal tubule indirectly through the absorption of CO2 from proximal tubular fluid. Loops of Henle: The nephrons with their glomeruli located in the outer portion of the renal cortex have short loops of Henle (cortical nephrons, 70%), where as those with glomeruli in the juxtamedullary region of the cortex (juxtamedullary nephrons, 30%) have long loop extending down into medullary pyramids. The juxtamedullary nephrons are important for urine concentration. They also reabsorb a higher proportion of glomerular filtrate than cortical nephrons and are said to be “salt- conserving.” In states where effective circulating blood volume is reduced, a higher proportion of renal blood flow (RBF) is directed to the juxtamedullary nephrons, helping to conserve extracellular fluid volume. Loops of Henle include: The thin descending segment, the thin ascending segment, and the thick ascending segment. The thin descending segment of the loop of Henle: The epithelia cells of it are very thin with no brush border and very few mitochondria. They are highly permeable to water but nearly impermeable to sodium and most other ions. About 20% of the filtered water is reabsorbed in the descending thin limb loop of Henle The thin ascending segment of the loop of Henle: The epithelia cells of the ascending thin segment, on the other hand, are far less permeable to water but more permeable to urea and NaCl than is the descending portion. Because the ascending thin limb is impermeable to water, no water reabsorption is taking place in this area of the nephrone. The thick ascending segment of the loop of Henle: The epithelial cells of the ascending thick segment are similar to those of the proximal tubules except that they have a rudimentary brush border and much tighter tight junction. The cells adapted for strong active transport of Na, K, and Cl ions. On the other hand, the thick segment is almost entirely impermeable to both water and urea. Therefore, no water reabsorption is taking place in this area of the nephrone. Therefore, this segmant is called the diluting segment. It is the only segment in which active Cl pumping normally occur. This active transport of ions can be inhibited by drugs called loop diuretics such as frusemide, ethacrynic acid, and bumetanide, which consequently abolish the intraluminal positivity. Eventually the passive absorption of Na ions ceases. This thick ascending segment ascends all the way back to the same glomerulus from which the tubule originated and passes tightly through the angle between the afferent and efferent arterioles. The cells of this portion of the thick ascending segment which are in complete attachment with the epithelial cells of the afferent and efferent arterioles are called Macula densa. The specialized smooth muscle cells of the afferent arterioles that come in contact with the macula densa are called juxtaglomerular cells (JG cells) which contain renin granules. Macula densa and JG cells plus few granulated cells between them are collectively known as juxtaglomerular complex or apparatus which has a dense adrenergic neural innervation.  About 25% of filtered loads of Na, Cl, and K (and other ions such as Ca, HCO3-, Mg) are reabsorbed in the loop of Henle mainly in the thick ascending limb. Because the thick segment of the ascending loop of Henle is impermeable to water, most of the water delivered to this segment remains in the tubule, despite the reabsorption of large amounts of solute. Thus, the tubular fluid in the ascending limb becomes very dilute as it flows toward the distal tubule (hypotonic). Distal convoluted tubule: They lie in the renal cortex. The distal tubule (also called the diluting segment) has almost the same characteristics as the thick segment of ascending limb of the loop of Henle. It reabsorbs Na ions and other ions but is almost entirely impermeable to both water and urea. This segment is the site of action of special type of diuretics called thiazide and loop diuretics.  Reabsorption of water can occurs in the distal tubule but only in the presence of antidiuretic hormone (ADH, or vasopressin). With high level of ADH, these tubular segments are permeable to water, but in the absence of ADH, they are virtually impermeable to water.  Reabsorb Na ions while secrete K ions through increase the activity of Na-K ATPase countertransporter at the basolateral side of the cells under the effect of the hormone aldosterone.  Reabsorb K ions while secrete H ions via H-K ATPase countertransporter at the luminal border of the cell.  Secretion of H ions (by H-ATPase pump) at the luminal border of the cells after being generated inside the cell by the action of carbonic anhydrase on water and CO2 to form  carbonic acid which then dissociates into H ions and HCO3- ions. Then the available HCO3- ions are reabsorbed across the basolateral membrane. Aldosterone also increases H ion secretion by stimulating the H-ATPase pump. Collecting tubules and ducts: About eight distal tubules coalesce to form the collecting tubule which turns once again away from the cortex and passes downward into medulla where it becomes the collecting ducts. The epitheliums of the medullary collecting ducts are involved in:  Na ions reabsorption while secrete K ions under the effect of aldosterone through increase the activity of Na-K ATPase countertransporter.  Vasopressin-stimulated water reabsorption.  H ions secretion and bicarbonate ions transport (by H- ATPase pump) under the effect of aldosterone. It is the final site for urine processing, and reabsorb less than 10% of the filtered water and Na. It plays an extremely important role in determining the final urine output of water and solutes.  Its permeability to water is under the control of ADH similar to the cortical collecting duct.  It is permeable to urea (unlike the cortical collecting duct) which is increased in the presence of ADH.  It is capable of secreting H ions against concentration gradient.  At each horizontal level, the medullary interstitium is concentrated by the transport of solute from the ascending loop of Henle as the descending loop of Henle is freely water permeable, ie water passively leaves the tubule concentrating the luminal contents these two processes proceed at each horizontal level so that the final concentration of solute deep in the medullary interstitium is ~ 1200-1400 mosmol/l the gradient at each horizontal level across the ascending loop of Henle remains at only 200 mosmol/l, while that across the descending loop of Henle is near zero therefore, the osmolality in the ascending loop of Henle is always less than that of the descending loop of Henle the fluid leaving the thick ascending loop of Henle for the distal tubule is ~ 200 mosmol/l below plasma, ie. ~ 100 mosmol/l. (B) Blood vessels: The renal fraction of the total cardiac output is about 21% (vary from 12-30%). In resting adult, the blood flow in renal cortex is about 98% of the total renal blood flow while in medulla is only 2% of the total renal blood flow. This is why the O2 consumption of cortex is much higher than that of medulla. Arterial system of the kidney is technically a portal system, because branches twice in the following arrangement: Renal artery  Segmantal artery  Interlobar artery  arcuate artery  Interlobular artery  Afferent arteriole  branching capillaries in Bowman`s capsule (glomerulus) Efferent arterioles  branching around the tubules so called (Peritubular capillaries)  Venules  Interlobular veins  arcuate vein  interlobar vein  Renal veins. Most of the peritubular capillary network lies in the renal cortex alongside the proximal, distal, and collecting tubules. In the juxtamedullary glomeruli, long efferent arterioles extend from the glomeruli down into the outer medulla and then divide into specialized long and straight capillary loops called vasa recta extended downward into the medulla to lay side by side with the lower parts of thin segments of juxtaglomerular loops of Henle all the way to the renal papillae. Then, like the loop of Henle, they also loop back toward the cortex and empty into the cortical veins. This specialized network of capillaries in the medulla plays an essential role in the formation of concentrated urine. [C] Nerve supply: The kidney has a rich adrenergic sympathetic nerve supply distributed to the: [A] Vascular smooth muscle to cause vasoconstriction. [B] Juxtaglomerular cells to cause renin secretion. [C] Tubular cells to stimulate Na and water reabsorption. There is no significant parasympathetic innervation Glomerular function: Glomerular filtration rate (GFR): It is the fluid that filtrate through the glomerulus into Bowman`s capsule each minute in all nephrons of both kidneys which is about 125 ml/min or 180 L/day in males (10% lower in female). The high GFR of the glomerular membrane is due to very high permeability of the capillaries of the glomerulus, which is about 100-500 times as great as that of the usual capillary. Yet, despite the tremendous permeability of the glomerular membrane, it has an extremely high degree of selectivity. The selectivity of the glomerular membrane depends on: Size of the molecules: Neutral substance with effective molecular diameter of less than 4 nm are freely filtrated, and those with diameter more than 8 nm (80 A), filtration is zero. Between these two values, filtration is inversely proportional with diameter.  The electrical charges of the molecules: This is because the inner side of the pores of the glomerular membrane is negatively charged repelling other negatively charged molecules that tend to pass through pores. For these two reasons, the glomerular membrane is almost completely impermeable to all plasma proteins but is highly permeable to all other dissolved substances in normal plasma. The composition of the glomerular filtrate is the same as plasma except that it has no significant amount of proteins. The filtration fraction is the fraction of the renal plasma flow that becomes glomerular filtrate. Since the normal plasma flow through both kidneys is 650 ml/min and the normal GFR is 125 ml/min, the average filtration fraction is about 1/5 or 19%. Renal Function Tests: There are several tests for diagnosing kidney diseases, evaluating their severity, and monitoring their progress. Here we examine two methods used to determine renal clearance and glomerular filtration rate. Renal clearance: is the volume of blood plasma from which a particular waste is completely removed in 1 minute. It represents the net effect of three processes: Glomerular filtration of the waste + Amount added by tubular secretion - Amount reclaimed by tubular reabsorption = Renal clearance The substance used to measure the clearance should fulfill the following criteria: [A] freely filtered. [B] Neither reabsorbed nor secreted by the tubules. [C] Not metabolised or stored in the kidney. [D] Not toxic and not affecting the GFR. Such of these substances are inulin, creatinine, and Para-aminohippuric acid.  In principle, we could determine renal clearance by sampling blood entering and leaving the kidney and comparing their waste concentrations. In practice, it is not practical to draw blood samples from the renal vessels, but clearance can be assessed indirectly by collecting samples of blood and urine, measuring the waste concentration in each, and measuring the rate of urine output. Suppose the following values were obtained for urea: U (urea concentration in urine) = 6.0 mg/mL, V (rate of urine output) = 2 mL/min, P (urea concentration in plasma) = 0.2 mg/mL. Renal clearance (C) is C = UV/P = (6.0 mg/mL) (2 mL/min)/ 0.2 mg/mL = 60 mL/min This means the equivalent of 60 mL of blood plasma is completely cleared of urea per minute. If this person has a normal GFR of 125 mL/min, then the kidneys have cleared urea from only 60/125 = 48% of the glomerular filtrate. This is a normal rate of urea clearance, however, and is sufficient to maintain safe levels of urea in the blood. Using clearance to estimate GFR: GFR can be measured indirectly by calculating the clearance of a substance. The substance is called glomerular marke such as Inulin. For inulin, GFR is equal to the renal clearance. Inulin is a low-molecular-weight polysaccharide that is small enough to pass freely through the glomerular filtration barrier. Inulin is neither reabsorbed nor secreted by the nephron and cannot be metabolized. Therefore, the rate of inulin filtration equals the rate of inulin excretion in urine so the volume of plasma cleared per minute equals GFR. Inulin usually is not used clinically because it must be intravenously infused. Suppose, for example, that a patient’s plasma concentration of inulin is P = 0.5 mg/mL, the urine concentration is U =30 mg/mL, and urine output is V = 2 mL/min. This person has a inulin clearance = UV/P = (30 mg/mL)(2 mL/min)/ 0.5 mg/mL = 120 mL/min. Therefore, for inulin, its clearance is equal to GFR. In clinical practice, GFR is more often estimated from creatinine excretion. This has a small but acceptable error of measurement, and is an easier procedure than injecting inulin and drawing blood to measure its concentration. However, measurement of endogenous creatinine clearance is more suitable because it does not need intravenous infusion as in inulin. Using clearance to estimate RBF: Para-aminohippuric acid (PAH) clearance is used as a measure of renal blood (plasma) flow (RPF): PAH, like inulin in its criteria. However, it is different from inulin in that it is cleared from the plasma by a single passage through the kidney and the remaining PAH in the plasma after the glomerular filtrate is formed, is secreted into the tubules by the proximal tubule, i.e zero PAH in renal vein. Where a substance is completely cleared from the plasma by a single passage through the kidney and all the cleared material is excreted in the urine, the clearance is equal to the renal plasma flow. Therefore: Factors that affect GFR: GFR is determined by: The filtration pressure is the net pressure forcing fluid through glomerular membrane (the Starling forces) which is determined by: [A] Glomerular capillary hydrostatic pressure: This can be affected by several factors: Renal blood flow: Increase blood flow through the nephrons greatly increases the GFR for two reasons: (A) The increasing flow increases the glomerular pressure which enhances filtration. (B) The increased flow through the nephrons allows less time for plasma proteins to be more concentrated at the venous end of the glomerular capillaries bed. Therefore, oncotic pressure has far less inhibitory influence on glomerular filtration. Afferent arteriolar constriction: Leads to decrease the rate of blood flow into the glomeruli and also decrease the glomerular pressure and decrease the GFR, and vice versa. Efferent arteriolar constriction: A slight efferent arteriolar constriction increases the glomerular pressure causing slight increase in GFR. However, moderate and severe efferent arteriolar constriction causes a paradoxical decrease in the GFR despite the elevated glomerular pressure. This is due to the fact that plasma in this case will remain for long period of time in the glomerulus, and extra large portion of plasma will filter out. This will increase the plasma colloid osmotic pressure to excessive level causing a decrease in the GFR. [B] A change in Bowman’s capsule hydrostatic pressure: Increasing the hydrostatic pressure in Bowman’s capsule (as in urinary tract obstruction) reduces GFR and vice versa.  [C] A change in glomerular capillary colloid osmotic pressure: A decrease in the glomerular capillary colloid osmotic pressure increases GFR and vice versa. [D] An increase in the Bowman’s colloid osmotic pressure: This may occur in diseases that causes filtration of proteins across glomerular membrane and consequently increases GFR. The capillary filtration coefficient, which is the product of the permeability and filtering surface area of the capillaries. It can be affected by: [A] The changes in the permeability of the glomerular capillaries, which may be changed in disease state with consequent changes in the GFR. [B] The thickness and the surface area of the capillary bed across which filtration is taking place which can be changed with a consequent change in the GFR. An example of such change is contraction or relaxation of mesangial cells in response to various substances can induce a decrease or an increase in the effective filtration surface area and eventual changes in the GFR. In summary: GFR can be affected by : The filtration pressure, which is influenced by: A. Glomerular capillary hydrostatic pressure which is affected by: I. Renal blood flow. II. Afferent arteriolar constriction. III. Efferent arteriolar constriction. B. Bowman’s capsule hydrostatic pressure. C. Glomerular capillary colloid osmotic pressure.  D. Bowman’s colloid osmotic pressure. : The capillary filtration coefficient (K f), which can be affected by: A. The permeability of the glomerular capillaries. B. The thickness and surface area of capillary bed. Factors affect urine volume: These factors play a significant role in determining the rate of fluid volume excretion (i.e. the urine). Presence of excessive quantities of osmotic particles (Osmotic diuresis): An important example on the osmotic diuresis is the diabetes mellitus in which the proximal tubules fail to reabsorb all the glucose, as normally occurs. Instead, the nonabsorbed glucose passes the entire distance through the tubules and carries with it a large portion of the tubular water. Osmotic diuresis also occurs when substances that are poorly or cannot be reabsorbed by the tubules are filtered in excessive quantities from the plasma into glomerular filtrate. Examples of such substances are sucrose, mannitol, and urea. Plasma colloid osmotic pressure: A sudden increase in plasma colloid osmotic pressure instantaneously decreases the rate of fluid volume excretion. The cause of this is due to (A) a decrease in GFR and (2) an increase tubular reabsorption. Sympathetic stimulation: Sympathetic stimulation causes constriction of the afferent arterioles via 1 receptors stimulation. It greatly decreases the glomerular pressure and simultaneously decreases GFR. At the same time, the blood flow into the peritubular capillaries is decreased and consequently, the capillary pressure is decreased, thus increasing tubular reabsorption. Also sympathetic stimulation stimulate juxtaglomerular complex (via β1 receptors) to release renin.  Arterial pressure: Under normal condition (when the renal autoregulatory mechanism is intact), a change in blood pressure causes a slight change diuresis and natriuresis. Unlike in renal diseases (when the renal autoregulatory mechanism is impaired), small increase in arterial pressure often causes marked increase in urinary excretion of Na and water. This results from two separate effects: (A) the increase in arterial pressure increases glomerular pressure, which in turn increases GFR, thus leading to increased urine output. (B) The increase in arterial pressure also increases the peritubular capillary pressure, thereby decreasing tubular reabsorption. Hormonal control: Such as: ADH: When excess antidiuretic hormone is secreted by the posterior pituitary gland, the effect is to increase the water permeability of the distal tubule, collecting tubule and collecting duct with a consequent decrease the urinary volume output acutely. However, when excess ADH is secreted for long periods of time, the acute effect of decreasing urinary output is not sustained. The reason is that other factors, such as the arterial pressure, colloid osmotic pressure, and concentrations of the osmolar substances in the glomerular filtrate all change in the direction that leads eventually to a urinary volume output equal to the daily need. Aldosterone: This is secreted by the zona glomerulosa cells of the adrenal cortex by its action on the principal cells of the cortical collecting tubule to increase Na reabsorption and to increase K secretion. Angiotensin II: It stimulates aldosterone secretion, which in turn increases Na and water reabsorption.  It constricts the efferent arterioles and consequently increases Na and water reabsorption through the following mechanisms: [A] When the angiotensin constricts the efferent arterioles, this reduces the peritubular capillary pressure causing an increase in the rate of reabsorption of water and electrolytes from the tubular system especially from the proximal tubule, because the balance forces at the capillary membrane is now in favor of absorption. [B] Because of the constriction of the efferent arterioles, the blood flow through glomeruli is decreased while the GFR is still near normal. This will lead that a very high proportion of plasma fluid to filter through the glomerular membrane into tubules. Therefore, the concentration of the plasma proteins in the blood leaving the glomeruli becomes very high and this concentrated plasma flows on into the peritubular capillaries. As the result, the colloid osmotic pressure in these capillaries is greatly increased, which is an additional factor that enhances reabsorption of water and salt. [C] There is evidence that angiotensin also has a direct effect on the distal tubules in causing increased active reabsorption of Na. It act directly especially on the proximal tubule to increase Na and water reabsorption (by stimulating Na-K ATPase pump at the basolateral membrane of the tubular cell) and Na-H exchange (at the luminal side of the tubular cell). Mesangial cells constrict in response to angiotensin II and reduce the capillary filtration coefficient resulting in an overall decrease in GFR. Atrial natriuretic peptide: It is released from specific cells of the cardiac atria upon distension as a result of plasma volume expansion. It inhibits the reabsorption of Na and water by the renal tubules especially in the collecting ducts with consequent increase in the urinary output. Parathyroid hormone: It increases the reabsorption of Ca and Mg ions from the ascending limb of loop of Henle and distal tubule. It inhibits the reabsorption of phosphate from the proximal tubule.