Chapter 9 Companion site for Basic Medical Endocrinology, 4th Edition Author: Dr. Goodman FIGURE 9.1 Distribution of body water and principal electrolytes. Note that water and electrolytes equilibrate freely between plasma and interstitial fluid, but only water equilibrates between the intracellular and extracellular compartments. The electrochemical gradient for sodium is maintained by the activity of the sodium/potassium ATPase. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 2 FIGURE 9.2 Schematic representation of renal tubules and their component parts. (Modified from Kriz, W. (1988) A standard nomenclature for structures of the kidney. Am. J. Physiol. 254: F1–F8.) Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 3 FIGURE 9.3 The countercurrent multiplier in the loop of Henle. Selective permeability of the tubular epithelium and active transport of sodium by the thick ascending limb create osmotic gradients. Tubular to interstitial flow of water concentrates sodium in the descending limb. Sodium movement across the water impermeable ascending limb creates the osmotic gradient in the interstitium. Yellow arrows indicate the direction of flow. Note that active sodium transport in the thick ascending limb creates the gradient in the interstitium and makes the tubular fluid hypoosmotic by the time it emerges from Henle’s loop. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 4 FIGURE 9.4 The V1 receptor mediates the pressor actions of AVP/ADH, and the V2 receptor mediates the water conservation effects. The two receptors signal by way of different G-proteins. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 5 FIGURE 9.5 Principal cells of the collecting duct before (A) and (B) after ADH. ADH binds to V2 receptors to induce formation of cAMP, which promotes insertion of aquaporin 2 (AQP2) into the luminal membrane making it permeable to water. In the presence of ADH, water can pass through the principal cell from lumen to interstitium driven by the osmotic gradient. Deep in the medulla, urea transporters also are inserted in the luminal membrane in addition to AQP2. Expression of Aquaporins 3 and 4 (Aq 3 & 4) in the basolateral membranes allows osmotic equilibration between intercellular and interstitial water. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 6 FIGURE 9.6 Relation between ADH and osmolality in plasma of unanesthetized rats. Note the appearance of thirst (increased drinking behavior) when plasma osmolality exceeds 290 mOsm/kg. (From Robertson, G.L. and Berl, T. (1996) In The Kidney, 5th ed., Brenner and Rector, eds., 881. Saunders, Philadelphia, with permission.) Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 7 FIGURE 9.7 A. Sagital view of the brain showing the circumventricular organs and their relation to ADHproducing cells. PVN = paraventricular nucleus; OVLT = organum vasculosum of the lamina terminalis; SON = supraoptic nucleus; AP = area postrema. (Adapted from Netter, F.H. (2003) In Netter’s Atlas of Human Neuroscience, David L. Felten and Ralph Jozefowicz, eds. Icon Learning Systems; Teterboro, NJ.) B. Neural and hormonal input to ADH secreting cells. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 8 FIGURE 9.8 Relation between changes in blood osmolality, pressure, or volume and ADH concentration in plasma of unanesthetized rats. (From Dunn, F.L., Brennan, T.J., Nelson, A.E., and Robertson, G.L. (1973) The role of blood osmolality and volume in regulating vasopressin secretion in the rat. J. Clin. Invest., 52: 3212, with permission.) Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 9 FIGURE 9.9 The effects of increases or decreases in blood volume or blood pressure on the relation between ADH concentrations and osmolality in the plasma of unanesthetized rats. Circled numbers indicate percent change from normal (N). (Modified from Robertson, G.L. and Berl, T. (1996) In The Kidney, 5th ed., 881. Saunders, Philadelphia, with permission.) Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 10 FIGURE 9.10 Two-step formation of angiotensin II. Amino acids are represented by the single letter amino acid code, D = aspartic acid, F = phenylalanine, H = histidine, I = isoleucine, L = l eucine, P = proline, R = arginine, S-serine, V = valine, Y = tyrosine. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 11 FIGURE 9.11 The juxtaglomerular apparatus. Red arrows indicate the direction of blood flow. (Modified from Davis, J.O. (1975) Regulation of aldosterone secretion. In Handbook of Physiology, Sect 7: Endocrinology, Vol. IV: Adrenal Gland. American Physiological Society, Washington, DC, with permission.) Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 12 FIGURE 9.12 Angiotensin II increases sodium reabsorption by stimulating sodium proton exchange in the luminal brush border and sodium bicarbonate cotransport in the basolateral membrane. Hydrogen ions and bicarbonate are regenerated in the cell cytosol from CO2 and water. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 13 FIGURE 9.13 Actions of angiotensin. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 14 FIGURE 9.14 Negative feedback control of renin and angiotensin secretion. The monitored variable is blood volume detected as decreases in sodium chloride at the macula densa, decreased pressure in the afferent arterioles, and decreased pressure in the carotid sinuses, aortic arch, and thoracic low pressure receptors. Coordinated actions of angiotensin restore plasma volume and abolish the stimuli for renin secretion. Note that angiotensin II contributes directly and indirectly to maintenance of blood volume, but its influence in this regard is inadequate in the absence of aldosterone (see Chapter 4). Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 15 FIGURE 9.15 Electron microscopic section through rat cardiac atrium showing working cardiac myocytes (x 4,500). G = Storage granules; GC = Golgi complex; My = myofribril; N = nucleus. (From de Bold, A.J. and Bruneau, B.G. (2000) Natriuretic peptides. In Fray, J.C.S., ed. Handbook of Physiology, Section VII, The Endocrine System, Volume 3, Endocrine Regulation of Water and Electrolyte Balance . American Physiological Society/Oxford University Press, 377–409.) Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 16 FIGURE 9.16 The natriuretic peptides. Amino acids are represented by the single letter amino acid code Amino acidsare represented by the single amino acid code: A = alanine, C = cysteine, D = aspartic acid, F = phenylalanine, G = glycine, H = histidine, I = isoleucine, K = lysine, L = leucine, M = methionine, N = asparagine, Q = glutamine, R = arginine, S = serine, V = valine. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 17 FIGURE 9.17 Actions of atrial natriuretic factor (ANF). Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 18 FIGURE 9.18 Direct and indirect actions of ANF on the kidney. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 19 FIGURE 9.19 Negative feedback regulation of ANF secretion. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 20 FIGURE 9.20 Hormonal responses to hemorrhage. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 21 FIGURE 9.21 Hormonal responses to dehydration. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 22 FIGURE 9.22 Responses of normal subjects to low or high intake of sodium chloride for five days. Plasma sodium concentrations were maintained within less than 2% by compensating rates of sodium excretion. The small increases or decreases in hematocrit and plasma protein concentrations indicate contraction of the plasma volume in the low sodium group and expansion in the high sodium group. The changes in hormone concentrations are in response to the small changes in osmolality and volume. Plasma renin activity is a measure of renin concentration expressed as ng of angiotensin I formed per ml of plasma in one hour. (Drawn from the data of Sagnella, G.A., Markandu, N.D., Shore, A.C., Forsling, M.L., MacGregor, G.A. (1987) Plasma atrial natriuretuc peptide: Its relationship to changes in sodium intake, plasma renin activity and aldosterone secretion in man. Clin. Sci. 72: 25–30.) Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 23