The kidneys are two bean-shaped organs lying retroperitoneally on each side of the vertebral column. The kidney is anatomically complex consisting of highly specialized cells. The functional unit of the kidney is called a nephron. Each nephron consists of a glomerulus and a long tubule. The nephrons are tightly packed to make the renal parenchyma.
On cut surface the pale outer cortex and a dark, inner medulla can be easily distinguished (Fig. 1.1). The medulla consists of 8 to 12 conical masses, the pyramids. The base of a pyramid is at the corticomedullary junction and the apex toward the renal pelvis forming a papilla. Each papilla contains 10 to 25 small openings that represent the distal ends of the collecting ducts. In the adult kidney the cortex is about 1 cm thick and covers the base of the renal pyramids and extends between individual pyramids to form the columns of Bertini. From the base of the pyramid, at the corticomedullary junction, longitudinal medullary rays, consisting of collecting ducts and the straight segments of the proximal and distal tubules extend into the cortex. From the renal pelvis two or three major calyces and from each of these several minor calyces extend outwards. The ureter begins at the lower portion of the pelvis, at the pelviureteric junction, and descends to open into the fundus of the bladder. Peristaltic activity of these structures propels the urine towards the bladder.
Each kidney contains about one million nephrons. A nephron consists of the glomerulus, proximal tubule, the thin limbs, the distal tubule and the connecting segment.
The structure of the glomerulus is depicted in Figure 1.2. The glomerulus is made up of a tuft of capillaries and a central region of mesangium containing cells and matrix. The capillaries arise from an afferent arteriole and eventually join to form an efferent arteriole, the entry and exit being at the vascular pole of the glomerulus.
The capillary wall consists of a fenestrated endothelium, basement membrane and the specialized epithelial cells (podocytes). The glomerulus is surrounded by the Bowman’s capsule lined by the parietal epithelium that is continuous with the visceral epithelium at the vascular pole. The Bowman’s space leads into the proximal tubule.
The capillary endothelium contains pores of 70 to 100 nm diameter. The basement membrane consists of a central dense layer, the lamina densa, lamina rara interna and lamina rara externa. The podocytes have long cytoplasmic foot processes (pedicels) that extend from the main cell body, and interdigitate and come in contact with the lamina rara externa. The gap between individual pedicel is about 25 to 60 nm and is bridged by a thin slit diaphragm. All three components of the capillary wall contain negatively charged sites because of the presence of a polyanionic surface glycoprotein, podocalyxin.
Fig 1.2: Cross-section of glomerulus. AA: afferent arteriole, C: capillary lumen, EA: efferent arteriole, MD: macula densa, EGM: extraglomerular mesangium, N: nerve terminals, GC: granular cells, SMC: smooth muscle cells, PE: parietal epithelium, PO: podocyte, M: mesangium, E: endothelium, F: foot process, GBM: glomerular basement membrane, US: urinary space.
The proximal tubule starts at the urinary pole of the glomerulus and consists of an initial convoluted portion and a straight segment (Fig. 1.3). It is contained in the cortex along with the glomerulus. The straight segment leads to the loop of Henle, which dips into the medulla. The descending limb and the initial part of ascending loop of Henle are thin walled. The latter part of ascending limb has thick walls like that of proximal tubule, and in the cortex it ends in the distal convoluted tubule. Within the cortex up to eight distal tubules join to form the cortical collecting duct that passes downwards into the medulla (where it is called outer medullary collecting duct). Several collecting ducts join to make increasingly large inner medullary collecting ducts, which eventually enter the renal pelvis through the tip of the papilla.
Fig 1.3: Diagram of the nephron. 1: renal corpuscle, 2: proximal convoluted tubule, 3: proximal straight tubule, 4: descending limb of loop of Henle, 5: ascending thin limb of Henle, 6: thick ascending limb of Henle, 7: macula densa, 8: distal convoluted tubule, 9: connecting tubule, 10: cortical collecting duct, 11: outer medullary collecting duct, 12: inner medullary collecting duct.
Papillae are conical projections of the medulla protruding into renal calyces. Each kidney has about 250 large collecting ducts, each of which drains about 4000 nephrons.
About 20 percent nephrons have their glomeruli in the deeper parts of cortex and have very long loops of Henle that descend all the way to the papillary tips. These are called juxtamedullary nephrons. The nephrons in the superficial cortex have short loops of Henle that bend at the junction between the inner and outer medulla.
The early part of the distal tubule in its ascent from the medulla to the cortex lies near the glomerulus of the same nephron. The cells of the tubule in the part that comes in contact with the afferent arteriole of the glomerulus are more dense than the cells in the rest of the tubule, are called macula densa (Fig. 1.2). The smooth muscle cells of the afferent arterioles that approximate macula densa contain prominent secretory cytoplasmic granules, which are the site of renin activity. The juxtaglomerular apparatus is composed of the afferent and efferent arterioles, the macula densa and lacis cells located in the triangular space in between these structures. It is involved in systemic blood pressure regulation, electrolyte homeostasis and tubuloglomerular feedback mechanisms.
The renal artery divides into five segmental arteries. The latter divide into the interlobar arteries, which branch into arcuate arteries near the junction of the cortex and the medulla. Interlobular arteries arise at right angles from the arcuate arteries and pierce into the cortex. These provide the afferent arterioles for the glomeruli. The glomerular capillaries join to from the efferent arteries that leave the glomerulus and form an extensive network of peritubular capillaries that surround the tubules, mostly in the cortex. Enormous amounts of filtrate after tubular reabsorption pass through these capillaries. From the deeper portions of these capillaries, long branching capillary loops (vasa recta) extend into the medulla adjacent to the loops of Henle. Thereafter these vasa recta loop back towards the cortex and empty into the cortical veins. Only 1-2 percent of the total renal blood flow is through the vasa recti. The vasa recti along with the loops of Henle are responsible for the urinary concentration.
The kidneys receive the greatest blood flow in proportion to weight. At rest 20 to 25 percent of cardiac output goes to the kidney. The chief elements of renal function are glomerular ultrafiltration, tubular reabsorption and tubular secretion.
The glomerular capillary hydrostatic pressure forces a virtually protein free filtrate into the Bowman’s space. The special structure of these capillaries makes them highly permeable, more than several times than ordinary capillaries. Despite that, the capillaries restrict proteins even of relatively low molecular weight (e.g., albumin, molecular weight 69,000 D). Crystalloids and low molecular weight substances such as urea, glucose and aminoacids are freely filtered. The restriction of albumin is chiefly due to the anionic charge of the glomerular basement membrane, imparted by the presence of a complex of proteoglycans. Thus the negatively charged albumin molecules are repulsed by electrostatic hindrance. Loss of glomerular capillary polyanion results in heavy albuminuria.
The glomerular filtrate has almost the same composition as that of plasma. It has no red blood cells and only 0.03 g/dl of protein. The normal glomerular filtration rate (GFR) is about 125 ml/min per 1.73 m2. Since the normal plasma flow through the kidneys is 650 ml/min, only about 20 percent is filtered. This figure is termed the filtration fraction.
Factors Affecting the GFR
The GFR is chiefly determined by the degree of constriction of afferent and efferent arterioles. Other factors including plasma colloid osmotic pressure and the pressure in Bowman’s capsule also play a role. Afferent arteriolar vasoconstriction decreases the rate of blood flow into glomerular filtration. Constriction of the efferent arteriole increases the resistance to the outflow from the glomeruli thereby increasing the glomerular pressure and glomerular filtration. Angiotensin II causes a preferential constriction of efferent arterioles.
Autoregulation of Renal Blood Flow and GFR
Despite wide change in systemic arterial pressure the renal blood flow and the GFR are kept relatively constant. This phenomenon is termed autoregulation and probably mediated through tubuloglomerular feedback. A marked fall in GFR results in excessive reabsorption of Na+ and Cl– in the ascending loop of Henle, thus reducing their concentration at macula densa. This stimulates the juxtaglomerular cells to release renin, leading to increased angiotensin II formation, which constricts efferent arterioles. The resultant rise in glomerular pressure increases the GFR restoring the normal status. Additional mechanisms may be involved in the process of autoregulation.
Tubular Reabsorption and Secretion
The glomerular filtrate undergoes a series of modifications before becoming final urine. Absorption, the movement of solute or water from the tubular lumen to blood is the predominant process in renal handling of sodium, chloride, water, bicarbonate, glucose, aminoacids, protein, phosphate, calcium, magnesium, urea and uric acid. Secretion, the movement of solute from blood into the tubular lumen is important in the renal handling of hydrogen, potassium, ammonium ions and organic acids and bases. Movement of ions and other substances occurs either by the transcellular pathway that require traversing the luminal and the basolateral cell membranes, or by the paracellular pathway between cells.
Structure of Tubular Segments
The structure of various segments of the tubules is different and related to their characteristic absorptive and secretary function. The epithelial cell of proximal tubular, thick ascending limb of Henle and the first part of the distal tubule have large number of mitochondria. The proximal tubular cells have a huge surface area, provided by the brush border for transfer of substances across the cell membrane. The thin segment of the loop of Henle has thin walls, few mitochondria and no brush border. The epithelial cells of the collecting ducts are cuboidal with few mitochondria and without a brush border.
General Characteristics of Tubular Reabsorption
The proximal tubule reabsorbs a large amount of the filtrate. The descending limb of loop of Henle is highly permeable to water and moderately permeable to urea, sodium and other ions. It is the site of simple diffusion of substances. The thick ascending limb is almost impermeable to both water and urea, which are retained in the lumen, as various ions are actively reabsorbed. At the end of the ascending limb the tubular fluid is very dilute but has a high urea content. The first part of the distal tubule (cortical diluting segment) like the thick ascending limb of Henle, is also impermeable to urea and water. Thus it further dilutes the tubular fluid. The latter part of distal tubule (also impermeable to urea) is involved in aldosterone controlled sodium reabsorption and potassium secretion. The secretion of potassium in this segment is responsible for maintaining the potassium concentration in the extracellular fluid. The late distal tubule and the cortical collecting duct contain specialized epithelial cells (intercalated cells) that actively secrete hydrogen ions against a concentration gradient even as high as 1000 to 1. This has a vital role in the maximum urinary acidification. The late distal tubule and cortical collecting duct are permeable to water in the presence of antidiuretic hormone (ADH). The medullary collecting duct can also secrete hydrogen ions against a very high gradient. They are permeable to water in response to ADH and slightly permeable to urea. This segment is responsible for maximum urinary concentration.
Under usual circumstances 65 percent of the glomerular filtrate (water) is reabsorbed in the proximal tubule, 15 percent in the loop of Henle, 10 percent in the distal tubule and 9 percent in the collecting duct. Thus only 1 percent of glomerular filtrate water is excreted as urine.
Tubular Maximum (Tm)
Substances such as glucose and aminoacids that are actively reabsorbed (and other that are actively secreted) require specific transport systems mediated by enzymes. Each system has a saturation point at which the particular product can be transported at a maximum (Tm for that substance).
In the adult the Tm for glucose is 320 mg/minute. A greater tubular load (plasma glucose × GFR) than that results in excretion of excess glucose in urine. Since under normal situations the tubular load is only 125 mg/min, all the filtered glucose is reabsorbed.
REABSORPTION OF SPECIFIC SUBSTANCES
On usual dietary intake, 99 percent of the filtered Na+ is reabsorbed. Sixty percent is reabsorbed in the proximal tubule and 30 percent in the loop of Henle. Sodium reabsorption in the distal tubule and the collecting duct is highly variable and controlled by the concentration of aldosterone (Fig. 1.4).
The basic mechanism for Na+ reabsorption involves its primary active transport. On the basal and lateral surface of tubular epithelial cell, Na+ is extruded out of the cell through the Na-K ATPase system. Three Na+ ions are pumped out and two K+ ions pumped inside the cell.
Fig 1.4: Pathways and mediators involved in Na reabsorption. Almost 60% of the filtered Na is reabsorbed in the proximal tubule. The distal portions of the nephron reabsorb the remainder. The chief mediators involved in Na reabsorption are shown in boxes.
Fig 1.5: Electrolyte transport in the thick ascending limb (TAL) of loop of Henle. Na+, K+ and Cl– are absorbed across the apical cell membrane by the NKCC2 co-transporter. This transporter is driven by the Na-K ATPase pump, basolateral Cl channel (ClC-Kb) and the K-Cl co-transporter.
This action reduces the Na+ concentration within the cells and also makes the cell interior electronegative because of which Na+ ions passively diffuse from the tubular lumen into the cell.
On the apical membrane, a number of transporters ensure Na+, K+ and Cl– transport. Much of Na+ reabsorption in the proximal tubule results from active co-transport with organic solutes such as glucose and aminoacids, or through the Na+-hydrogen exchanger. The primary mediator of Na+ uptake in the thick ascending limb of Henle is the frusemide sensitive Na-K-2 Cl (NKCC2) co-transporter (Fig. 1.5). The levels of K+ in the lumen of the loop of Henle are much lower than Na+ and Cl–. Therefore K+ entering the tubular cell from the lumen must be recycled to permit sustained NKCC2 activity. The renal outer medullary K+ channel (ROMK) is an ATP-sensitive channel that ‘recycles’ reabsorbed K+ back into the tubular lumen ensuring efficient Na+ and Cl– uptake by NKCC2. The Cl– channel, ClC-Kb, allows Cl– reabsorption from the tubular cell into the bloodstream.
Fig 1.6: Electrolyte transport in the distal convoluted tubule. Na+ and Cl– are reabsorbed across the apical membrane by the thiazide-sensitive NCCT co-transporter and leave the cell through the Cl– channels and the Na-K ATPase pump. A K-Cl co-transporter is also present at the apical membrane. Calcium enters the cell through the calcium channels and exits via the Na-Ca exchanger.
In the proximal tubule, Na+ reabsorption is controlled by glomerulotubular balance (the amount reabsorbed being directly proportional to the amount filtered) and the state of intravascular volume. Expansion of intravascular volume decreases Na+ reabsorption and its contraction increases it, irrespective of the serum Na+ level.
In the distal convoluted tubule, the thiazide-sensitive apical Na/Cl co-transporter (NCCT) is the principal mediator of Na+ and Cl– reabsorption (Fig. 1.6). The amiloride-sensitive, epithelial Na+ channels (ENaC) mediate Na+ reabsorption in collecting tubules and collecting ducts (Fig. 1.7). The mineralocorticoid hormone, aldosterone, regulates Na+/K+ balance in the distal nephron chiefly through its effect on the synthesis of ENaC. In the distal tubule, Na+ is completely reabsorbed in the presence of aldosterone whereas in its absence, almost all of Na+ is excreted.
Fig 1.7: Solute reabsorption in the principal cell of the collecting tubule. Na+ is reabsorbed across the amiloride-sensitive epithelial Na+ channel (ENaC). Na+ uptake is coupled to K+ and H+ secretion. Aldosterone binds to the nuclear mineralocorticoid receptor (MR), and upregulates ENaC and Na-K ATPase. This increases Na+ reabsorption and K+ and H+ secretion, resulting in hypokalemic alkalosis.
Aldosterone secretion is stimulated by angiotensin II, ECF volume contraction and decreased ECF sodium concentration. A decrease in ECF volume reduces arterial pressure and increases sympathetic activity. The renal perfusion is reduced stimulating the renin-angiotensin II-aldosterone mechanism and increasing Na+ reabsorption.
Potassium is freely filtered at the glomerulus with 65 to 70 percent passively reabsorbed in the proximal tubule. Another 25 percent is reabsorbed in the thick ascending loop of Henle through the action of Na-K-2Cl co-transporter so that less than 10 percent reaches the distal part of the nephron (Fig. 1.8). The greater part of K+ regulation occurs in the distal tubule and collecting duct. The fractional excretion of K+, under normal conditions, is 10-20 percent. In the cortical collecting duct, the most important cell that secretes K+ into the tubular lumen is the principal cell. K+ accumulates within the principal cell under the influence of Na-K ATPase, located at the basolateral membrane, and escapes into the tubular lumen by passive diffusion along the electrochemical gradient. Potassium movement occurs through selective apical K+ channels. The major determinants for K+ secretion by the principal cell are aldosterone, urinary flow and distal Na+ delivery, the serum K+ level and functioning apical K+ channels.
Aldosterone is the chief regulatory factor, acting on late distal and cortical collecting duct. It stimulates Na+ reabsorption and thus increases the electrochemical gradient for K+ diffusion into the tubular lumen. Aldosterone also increases the activity of Na-K ATPase that helps K+ accumulation within the tubular cells. Metabolic as well as respiratory acid-base alterations affect K+ secretion by collecting duct cells; the secretion is decreased by acute acidosis and increased by alkalosis. Tubular K+ excretion is greatly affected by the rate of flow of the tubular fluid and the delivery of Na+. An increase in the tubular fluid flow causes a fall in the intraluminal concentration of potassium and facilitates its movement out of the tubular cells. Increased sodium delivery causes a rise in its absorption, which increases the electrochemical gradient, thus promoting K+ diffusion into the tubular Iumen. With severe hypokalemia, the urinary concentration of K+ is very low. This is achieved through the reabsorption of K+ by intercalated A and B cells present in the collecting tubules.
Calcium exists in three forms in the plasma. The biologically active form termed the ‘ionized calcium’ constitutes 50 percent; 45 percent is bound to plasma proteins (chiefly albumin) and 5 percent is complexed to anions such as phosphate and citrate. Metabolic acidosis reduces protein binding and thus increases ionized calcium level. The extracellular concentration of calcium is very closely regulated by parathormone (PTH), 1,25(OH)2D3 and calcitonin. PTH increases renal calcium reabsorption and its resorption form bone. It also enhances renal conversion of 25(OH)D3 to 1,25(OH2)D3; the latter stimulates gastrointestinal calcium absorption.
The non-protein bound calcium is freely filtered and about 99 percent is reabsorbed. Proximal tubule reabsorbs 50-55 percent and the loop of Henle 20-30 percent, being linked to sodium reabsorption. Distal tubular and collecting duct reabsorption (about 10-15% and 2-8% respectively) is independent of sodium transport.
Calcium Sensing Receptor
Parathyroid cells and renal tubules express a cell-surface calcium-sensing receptor (CaSR) that enables these cells to detect small changes in the extracellular calcium concentration. CaSR is also expressed in other tissues related to calcium homeostasis such as thyroid C-cells, intestines and bones. An increase in extracellular calcium concen-tration activates CaSR, which decreases PTH secretion and inhibits renal calcium reabsorption, whereas a decrease in extracellular calcium has the opposite effect. The CaSR gene is located on chromosome 3q13.3-q21. Several inherited disorders of calcium metabolism result from mutations in CaSR gene. Inactivating mutations cause familial hypocalciuric hypercalcemia and severe hyperparathyroidism, while activating mutations result in hypocalcemia with hypercalciuria.
Calcium Sensing Receptor and Renal Water Handling
The CaSR is located in the same endosomes in the collecting duct that contain aquaporin 2 (water channels). ADH stimulates water reabsorption by inserting aquaporin 2 into the cell membranes of the collecting ducts. The reduction in renal concentrating ability and the resulting polyuria in hypercalcemia may be explained by a decrease in the availability and activity (or both) of these water channels.
The plasma concentration of inorganic phosphate is chiefly regulated by renal tubular reabsorption of filtered phosphate, which is decreased by PTH and enhanced by 1,25(OH2)D3. The latter increases renal reabsorption of phosphate as well as its absorption from the intestine. Plasma phosphate levels are influenced by dietary intake of phosphate, age and sex. Normally more than 85 percent of filtered phosphate is reabsorbed, 60-70 percent proximally and the remainder in distal segments, but may approach 100 percent during phosphate deprivation.
Only one percent of the total body magnesium is extracellular. Of the serum magnesium 20 percent is protein bound and the remainder is freely filtered. Normally more than 95 percent is reabsorbed, 20-30 percent proximally and the rest in the loop of Henle, particularly in the thick ascending limb.
The plasma concentration of aminoacids is maintained within 2.5 to 3.5 mM/l through several mechanisms. Digestion of dietary proteins and absorption of the fragments adds to the aminoacid pool, whereas their deamination and formation of urea and ammonia subtract from the pool. Proximal tubular reabsorption of aminoacids is almost total with negligible amounts excreted in the urine. Groups of aminoacids share common transport mechanism. One mechanism reabsorbs lysine, arginine, cystine and ornithine and another glutamic and aspartic acids. The reabsorptive mechanisms have transport maximum characteristics.
Despite electrostatic hindrance imparted by the glomerular capillaries significant amounts of proteins are filtered. These are almost totally reabsorbed in the proximal tubule through the brush border by pinocytosis. Within the cell the protein molecule is digested into its aminoacid components, which diffuse across the basolateral membranes into the interstitial fluid and the peritubular capillaries.
Usually 40 to 60 percent of filtered urea appears in the urine. As a general rule reabsorption of urea is by passive diffusion and parallels the movement of water. A recirculation mechanism of urea through the loop of Henle, the distal tubule and the collecting duct is responsible for the high urea concentration in the urine.
Creatinine is not reabsorbed except in the premature infant. There is an actual secretion of small amounts of creatinine by the proximal tubule.
The role of the kidney is to maintain plasma bicarbonate at a level of 24 to 26 mEq/l. The respiratory system maintains the plasma carbonic acid at 1.3 to 1.4 mEq/l. The concentrations of these two determine the pH of the plasma and interstitial fluid and indirectly the intracellular pH.
The bicarbonate filtered is largely (80-85%) reabsorbed in the proximal tubule and the remainder in the initial part of distal tubule. The maximum urinary acidification is achieved distally, through the processes of titratable acid and ammonia excretion. The basic mechanism is an exchange of filtered sodium for hydrogen ion along the entire length of the nephron and is dependent upon the enzyme carbonic anhydrase. Titratable acid is formed by the buffering of hydrogen ions by phosphate in the tubular fluid. Ammonia is formed within the tubular cells and diffuses into the lumen where it combines with hydrogen ions to form ammonium that is trapped in the lumen. In the collecting duct bicarbonate is almost completely removed from the tubular lumen. During maximal stimulation the urine pH can be lowered to 5.2-5.5.
Fig 1.9: Antidiuretic hormone (vasopressin) mediated water reabsorption in the distal tubule. Binding of vasopressin to the vasopressin receptor leads to activation of adenylyl cyclase with increased intracellular levels of cyclic AMP. Activation of cAMP-dependent protein kinase A (PKA) mediates protein phosphorylation that triggers exocytic insertion of AQP2 channels into the apical membrane. These channels increase the water permeability of the apical membrane, facilitating water transport.
The tonicity of the body fluid is maintained constant, between 280 to 290 mOsm/kg, through renal handling of water. The integrity of hypothalamus-posterior pituitary-antidiuretic hormone system and the adequacy of nephron structure and function are necessary for maintaining normal tonicity.
Water is passively reabsorbed in the proximal tubule and thin descending limb of the loop of Henle. The ascending limb of the loop of Henle and the distal convoluted tubule are impermeable to water. Epithelial cells of the collecting tubules and ducts are permeable to water in the presence of the antidiuretic hormone, arginine vasopressin (ADH). The aquaporins (AQP) are a family of membrane channel proteins that serve as selective pores through which water crosses cell membranes (Fig. 1.9). AQP2, exclusively present in the principal cells of the collecting tubules and ducts, is the chief ADH regulated water channel.
Regulation of ADH Secretion
ADH (arginine vasopressin) is synthesized in the neurons of supraoptic and paraventricular nuclei of the anterior hypothalamus and then transported down to the nerve endings in the posterior pituitary gland. ADH accumulates in large secretory granules and is released when appropriate stimuli are received.
The chief function of ADH is to increase the permeability of the collecting ducts to water. This results from the insertion of water channels in apical membranes of principal cells in the collecting ducts. ADH also causes arteriolar constriction and a rise in arterial blood pressure, but the physiological significance of this effect is not important.
Changes in the osmolality of ECF are sensed by osmoreceptors, which are a group of cells situated close to the cells that synthesize ADH. An increase in the ECF osmolality leads to a rise in the blood levels of ADH resulting in increased reabsorption of water. During maximum urinary concentration the urinary osmolality is about 1000–1400 mOsm/kg. Osmoreceptors are extremely sensitive to small variations in ECF osmolality, and just a 2 percent increase in the latter can cause maximum secretion of ADH. At plasma osmolality below 280 mOsm/kg, ADH level in plasma is almost undetectable.
Non-osmotic factors also affect ADH release; of these, hypovolemia and hypotension are most important. These act through baroreceptors in the carotid sinuses, aortic arch and cardiac atria. Dehydration is the most common cause of hypovolemia and ADH release. Relatively larger changes in plasma volume are necessary to affect baroreceptor-mediated ADH release, and at small variations in plasma volume, the osmotic stimulus mediates ADH release. With severe contraction of the plasma volume, the baroreceptor mechanism stimulates ADH release, irrespective of the plasma osmolality.
Thirst and Body Water
Thirst and oral fluid intake play a crucial role in the regulation of body fluid volume. The thirst center is located in the hypothalamus in close proximity to osmoreceptors. Intracellular dehydration is the chief factor for stimulating the thirst center and inducing a desire to drink. The commonest cause of intracellular dehydration is depletion of extracellular fluid and a rise in ECF tonicity. Thirst center is also stimulated by hemorrhage and a low cardiac output.
Atrial Natriuretic Peptides
Expansion of intravascular volume causes activation of stretch sensors in the atria, leading to increase in atrial natriuretic peptides. These act on the collecting ducts to cause sodium and water diuresis.
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