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?

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 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

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 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 ammonia is
an important buffer, a reduction in its availability will contribute to the impairment of net acid
excretion.