Managing Electrolyte Disorders: Is it Just Salt and Water? Mark L. Zeidel, M.D Herrman L. Blumgart Professor of Medicine Harvard Medical School Chair, Department of Medicine Physician-in-Chief, BIDMC Boston, Massachusetts
Each of these creatures survives by highly effective management of salt and water 2
Case 2 Case 1
Case 1 A 56 year old man discovers that he has hypertension when he uses a blood pressure machine in a pharmacy. He is seen by his PCP, who notes a blood pressure of 155/95 on multiple readings. After salt restriction fails to alter the blood pressure, the patient is started on hydrochlorothiazide, 25 mg/day. His blood pressure is 140/85 on follow- up. Routine electrolytes reveal: Na + 135; K + 3.0; Cl - 96; HCO 3 - 29, BUN 32 and Cr 0.9. How does thiazide lower BP? Since he continues the thiazide, why does he not go into shock? Why is he now alkalotic, hypokalemic, with a high BUN/Cr ratio? Why do some patients receiving thiazides become hyponatremic? 1 4
Defense Against Volume Depletion Sensors of Volume Depletion Extrarenal Renal Effector Mechanisms Sympathetic Outflow Renin-Angiotensin Aldosterone Anti-Diuretic Hormone Effectors act on the kidney.
Extrare rarenal nal volu lume e senso sors rs
Rena nal l sensor nsors s of volume lume depletion pletion renin nin release lease • Barorec ecep eptors tors in the affere rent nt arterio riole • Sympa pathe theti tic input t to the JG apparatus atus • Macul ula densa feedbac ack (fall in tubular r flow in dista tal nephron on eithe her r becaus use of GFR or proxima mal reabsor orpti ption on)
Defense Against Volume Depletion Sensors of Volume Depletion Extrarenal Renal Effector Mechanisms Sympathetic Outflow Renin-Angiotensin Aldosterone Anti-Diuretic Hormone Salt Hunger and Thirst
Sympa pathet thetic ic Effec ector tor Mech chanism anisms Cardiac Output Preload Increased Venous Return Renal Salt Retention Direct, R-A-A system Increased Cardiac Performance Increased Contractility Increased Heart Rate Peripheral Arterial Resistance Circulating Catecholeamines, Angiotensin II
What at does es Renin nin do?
Angiot iotens ensin in II • Potent nt syste temi mic vasoc ocons nstric tricto tor • Retenti tion n of sodium m and water through ghou out t the nephron (espec ecially in proximal mal tubule) e) • Regulati tion on of glomeru erular ar filtration tration rate • Stimul mulates ates releas ase of aldoste teron rone
Aldos osteron terone Primary mary effect t is to increase rease sodium m reabsorp rpti tion n in the distal tal nephron
Na+ transport along the nephron Filter 180l/d P Na = 140 FL = 25,200 mEq/d NaCl 60-80% NaCl 5% NaCl 3% NaCl 25% NaCl 5% Hoenig and Zeidel CJASN 2014;9:1272-1281
Angiotensin II and increased sympathetic tone increase sodium reabsorption in proximal tubule Angiot iotensin sin Cate techo cholami lamines NB. sodium and bicarbonate reabsorption are intimately linked! L. Lee Hamm et al. CJASN 2015;10:2232-2242
Aldosterone paradox: Volume Depletion: Kidney augments NaCl retention with minimal K+ secretion Hyperkalemia: Kidney wastes K+ without Na+ retention Biff F. Palmer CJASN 2015;10:1050-1060
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Case e 1 A 5 56 year old man discover ers that he has hypert erten ension on when he uses a blood pressure ure machine e in a p pharma macy. . He is seen by his PCP, who notes a b blood pressure ure of 155/95 5 on multiple e readi ding ngs. After salt restr tricti tion on fails to a alter the blood pressure, ure, the patient t is starte ted d on hydrochl ochlorot orothi hiazi azide de, 25 mg/day. . His blood pressure ure is 140/85 5 on follow-up up. Routine ne electr trolytes tes reveal al: : Na + 135; K + 3.0; Cl - 96; HCO 3 - 29, BUN 32 and Na Cr 0.9. How does thiazide lower BP? Since he continues the thiazide, why does he not go into shock? Why is he now alkalotic, hypokalemic, with a high BUN/Cr ratio? 1 20
So, we’ve explained why he does not go into shock. ock. Why hy does this is therapy rapy treat eat hypertens pertension ion? BP is down, CO is the same so SVR must st be decr crease sed. How does s this s happen? • Titze, J and Luft, F. Kidney Int 2017 91:1324-35.
Salt load alters skin Na + storage in rats and people.
Peripheral Na + storage might influence peripheral vascular tone
Case 2 • A 67 year old man suffers a major MI, from which he recovers. One month later he notes increased edema, dyspnea on exertion, and 2 pillow orthopnea. • PE reveals P = 120, BP = 100/65, RR = 22, afebrile. Exam notable for Volume and distended neck veins, rales 1/3 up, a Osmoregulation palpable S3, and 2+ pitting edema to the mid calf. Serum Na + 125, K + 3.0, HCO 3 - 32, • Cl - 81, BUN 36, Cr 1.1 Urine Na + is 2. Urine osmolality is • 685; Serum Osmolality is 262.
Extrare rarenal nal volu lume e senso sors rs
Na+ transport along the nephron Filter 180l/d P Na = 140 FL = 25,200 mEq/d NaCl 60-80% NaCl 5% NaCl 3% NaCl 25% NaCl 5% Hoenig and Zeidel CJASN 2014;9:1272-1281
Lowell, BB NEJM 380:459-71, 2019
Control of Salt Appetite Resch, JM et al Neuron 96:190-206, 2017
Case 2 • A 67 year old man suffers a major MI, from which he recovers. One month later he notes increased edema, dyspnea on exertion, and 2 pillow orthopnea. • PE reveals P = 120, BP = 100/65, RR = 22, afebrile. Exam notable for Volume and distended neck veins, rales 1/3 up, a Osmoregulation palpable S3, and 2+ pitting edema to the mid calf. Serum Na + 125, K + 3.0, HCO 3 - 32, • Cl - 81, BUN 36, Cr 1.1 Urine Na + is 2. Urine osmolality is • 685; Serum Osmolality is 262.
Osmoreceptor functions of the OVLT nuclei and SON control thirst and vasopressin release, respectively. Danziger J , and Zeidel M L CJASN
Neurobi biol ology gy of Thirst t and ADH release Nat. Rev Neurosci 18:459 2017
Thirs rst adapt pts to antic icipat ipated d rather er than n real l changes nges in body fluid uid osmolalit olality.
Hyperosmolality: a major stimulus for Hyperosmolality: a major stimulus for ADH release ADH release thirst thirst adapted from Robertson et al, Am J Med 1982 adapted from Robertson et al, Am J Med 1982
Volume Status Modulates ADH Release Robertson, G. J Clin Endocrinol Metab. 1976;42:613 – 20
ADH IS NOT PRESENT NT ADH IS PRESENT NT Large volume of Small volume of dilute urine concentrated urine* * provided the interstitium is concentrated (H 2 O moves along gradient with the help of aquaporins)
Cellular action of vasopressin Danziger J , and Zeidel M L CJASN
Managing Electrolyte Disorders: Is it Just Salt and Water? Mark L. Zeidel, M.D Herrman L. Blumgart Professor of Medicine Harvard Medical School Chair, Department of Medicine Physician-in-Chief, BIDMC Boston, Massachusetts
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