SECTION VI THE KIDNEY Addison's Disease A 49-yearold womn sees her physician hecause of weakness,easy fatigability, and loss of appetite.During the past month she has lost 7 kg (15 Ib).On physical and gums.She is hypotensive,and her blood pressure (BP)falls when she assumes an upright posture (BP100/60 Hg supine,and80/0mHg erect).The following lahoratory data are obtained: 1.The serun level of which hormone(s)would be expected to be below normal in this woman? 2.What is the cause of this wona's hypotension? 3.What is the mechanis for development of hyponatremia in this woman 4.Why does this woman have hyperkalenia? 5.What is her acid-base disturbance.and what is the cause? ANSWER 1.The symptons and the electrolyte disturbances of this wowan are ost characteristic of decreased levels of adrenal cortical steroids,and especially the mineralocorticoid hormone aldosterone.This patient has Addison's disease.The presence of hyperpigentation suest that the proble is at the leve of the adrenal gland.ACIll levels are elevated in response to the decreased circulating levels of adrenal cortical steroids.These elevated levels of ACTH stimlate 2.The hypotension is a result of the negative Nat balance present in this woman which in turn reflects the decreased circulating levels of aldosterone.With hypoaldosteronism.Nat reabsorption by the collecting duct is reduced,and
SECTION VI THE KIDNEY Addison's Disease A 49-year-old woman sees her physician because of weakness, easy fatigability, and loss of appetite. During the past month she has lost 7 kg (15 lb). On physical examination she is found to have hyperpigmentation, especially of the oral mucosal and gums. She is hypotensive, and her blood pressure (BP) falls when she assumes an upright posture (BP = 100/60 mm Hg supine, and 80/50 mm Hg erect). The following laboratory data are obtained: 1. The serum level of which hormone(s) would be expected to be below normal in this woman? 2. What is the cause of this woman's hypotension? 3. What is the mechanism for development of hyponatremia in this woman? 4. Why does this woman have hyperkalemia? 5. What is her acid-base disturbance, and what is the cause? ANSWER 1. The symptoms and the electrolyte disturbances of this woman are most characteristic of decreased levels of adrenal cortical steroids, and especially the mineralocorticoid hormone aldosterone. This patient has Addison's disease. The presence of hyperpigmentation suggests that the problem is at the level of the adrenal gland. ACTH levels are elevated in response to the decreased circulating levels of adrenal cortical steroids. These elevated levels of ACTH stimulate melanocytes and cause hyperpigmentation. 2. The hypotension is a result of the negative Na+ balance present in this woman, which in turn reflects the decreased circulating levels of aldosterone. With hypoaldosteronism, Na+ reabsorption by the collecting duct is reduced, and
negative Na+balance develops (Na+excretion Na+intake).Because ECF volue reflects Natbalance,ECF volune will be decreased.Because plasma is a component 3.Hyponatremia indicates a problem in water metabolisn.Thus the ability of this woman's kidneys to excrete solute-free water is impaired,and she is in positive water balance (solute-free ater ingestionsolute-free ater Excretion of solute-free water is impaired for two primary reasons,both of which are related to decreased effective cirulating blood volue.ith the decreased reduces the filtered load of solute (NaCl)and water.Also.the proximal tubules reabsorb a greater fraction of the filtered load of NaCl.Together,these effect reducethe delivery ofsondtothe thick ascendingof o i.e..the portion of the nephron where solute-free water is generated.In addition, the decreased the seretion f.hD presentthedurbser and therebyreduceitsexretio 4.UrinaryK excretion is determined mostly by the amount of K secreted into tubular fluid by the distal tubule and collecting duct.K+secretion at these nephron sites is reduced by a decrease in the serum [aldosterone].as well as in the [Na+]and flow rate of the tubular fluid.Therefore,K+excretion hy the distal buleand reduced in this and she be inpositive K+balance (intake excretion).In addition,aldosterone causes the uptake of K+into cells (e.g,skeletal musele).In the absence of aldosterone,cellular uptake will be less.This will contribute to the development of hyperkalemia. 5.This woman's acid-base disturbance is likely to be metabolic acidosis secondaryto reduced net acid excretion by the kidneys.thou arterial blood pl is not reported,the reduced plasma [H-]is consistent with a etabolic acidosis. Net acid exeretion by the kidneys is impaired for two reasons.First,aldosterone by the the ducts.In th ahsence of aldosterone,H secretion at this site will be diminished,and less Hwill be excreted.Second,hyperkalemia inhibits amoniagenesis by cells of the
negative Na+ balance develops (Na+ excretion > Na+ intake). Because ECF volume reflects Na+balance, ECF volume will be decreased. Because plasma is a component of the ECF, vascular volume and hence blood pressure will be decreased. 3. Hyponatremia indicates a problem in water metabolism. Thus the ability of this woman's kidneys to excrete solute-free water is impaired, and she is in positive water balance (solute-free water ingestion > solute-free water excretion). Excretion of solute-free water is impaired for two primary reasons, both of which are related to decreased effective circulating blood volume. With the decreased effective circulating blood volume, the glomerular filtration rate is reduced, which reduces the filtered load of solute (NaCl) and water. Also, the proximal tubules reabsorb a greater fraction of the filtered load of NaCl. Together, these effects reduce the delivery of solute and water to the thick ascending limb of Henle's loop; i.e., the portion of the nephron where solute-free water is generated. In addition, the decreased effective circulating volume causes the secretion of ADH. With ADH present, the collecting duct will reabsorb water and thereby reduce its excretion. 4. Urinary K+ excretion is determined mostly by the amount of K+ secreted into tubular fluid by the distal tubule and collecting duct. K+ secretion at these nephron sites is reduced by a decrease in the serum [aldosterone], as well as in the [Na+] and flow rate of the tubular fluid. Therefore, K+ excretion by the distal tubule and collecting duct will be reduced in this woman, and she will be in positive K+ balance (intake > excretion). In addition, aldosterone causes the uptake of K+ into cells (e.g., skeletal muscle). In the absence of aldosterone, cellular uptake will be less. This will contribute to the development of hyperkalemia. 5. This woman's acid-base disturbance is likely to be metabolic acidosis secondary to reduced net acid excretion by the kidneys. Although arterial blood pH is not reported, the reduced plasma [HCO3-] is consistent with a metabolic acidosis. Net acid excretion by the kidneys is impaired for two reasons. First, aldosterone stimulates H+ secretion by the intercalated cells of the collecting ducts. In the absence of aldosterone, H+ secretion at this site will be diminished, and less H+ will be excreted. Second, hyperkalemia inhibits ammoniagenesis by cells of the
proximal tubule.Because ammomia is an important buffer.a reduction in its availability will contribute to the inpairment of net acid excretion
proximal tubule. Because ammonia is an important buffer, a reduction in its availability will contribute to the impairment of net acid excretion