Chapter 046. Sodium and Water (Part 13) pot

Chapter 046. Sodium and Water
(Part 13)

Redistribution into Cells
Movement of K
+
into cells may transiently decrease the plasma K
+

concentration without altering total body K
+
content. For any given cause, the
magnitude of the change is relatively small, often <1 mmol/L. However, a
combination of factors may lead to a significant fall in the plasma K
+

concentration and may amplify the hypokalemia due to K
+
wasting. Metabolic
alkalosis is often associated with hypokalemia. This occurs as a result of K
+

redistribution as well as excessive renal K
+
loss. Treatment of diabetic
ketoacidosis with insulin may lead to hypokalemia due to stimulation of the Na
+
-
H
+
antiporter and (secondarily) the Na

+
, K
+
-ATPase pump. Furthermore,
uncontrolled hyperglycemia often leads to K
+
depletion from an osmotic diuresis
(see below). Stress-induced catecholamine release and administration of β
2
-
adrenergic agonists directly induce cellular uptake of K
+
and promote insulin
secretion by pancreatic islet βcells. Hypokalemic periodic paralysis is a rare
condition characterized by recurrent episodic weakness or paralysis (Chap. 382).
Since K
+
is the major ICF cation, anabolic states can potentially result in
hypokalemia due to a K
+
shift into cells. This may occur following rapid cell
growth seen in patients with pernicious anemia treated with vitamin B
12
or with
neutropenia after treatment with granulocyte-macrophage colony stimulating
factor. Massive transfusion with thawed washed red blood cells (RBCs) could
cause hypokalemia since frozen RBCs lose up to half of their K
+
during storage.

Nonrenal Loss of Potassium

Excessive sweating may result in K
+
depletion from increased
integumentary and renal K
+
loss. Hyperaldosteronism, secondary to ECF volume
contraction, enhances K
+
excretion in the urine (Chap. 336). Normally, K
+
lost in
the stool amounts to 5–10 mmol/d in a volume of 100–200 mL. Hypokalemia
subsequent to increased gastrointestinal loss can occur in patients with profuse
diarrhea (usually secretory), villous adenomas, VIPomas, or laxative abuse.
However, the loss of gastric secretions does not account for the moderate to severe
K
+
depletion often associated with vomiting or nasogastric suction. Since the K
+

concentration of gastric fluid is 5–10 mmol/L, it would take 30–80 L of vomitus to
achieve a K
+
deficit of 300–400 mmol typically seen in these patients. In fact, the
hypokalemia is primarily due to increased renal K
+
excretion. Loss of gastric
contents results in volume depletion and metabolic alkalosis, both of which

promote kaliuresis. Hypovolemia stimulates aldosterone release, which augments
K
+
secretion by the principal cells. In addition, the filtered load of HCO
3
–
exceeds
the reabsorptive capacity of the proximal convoluted tubule, thereby increasing
distal delivery of NaHCO
3
, which enhances the electrochemical gradient favoring
K
+
loss in the urine.

Renal Loss of Potassium

(See also Chap. 336) In general, most cases of chronic hypokalemia are due
to renal K
+
wasting. This may be due to factors that increase the K
+
concentration
in the lumen of the CCD or augment distal flow rate. Mineralocorticoid excess
commonly results in hypokalemia. Primary hyperaldosteronism is due to
dysregulated aldosterone secretion by an adrenal adenoma (Conn's syndrome) or
carcinoma or to adrenocortical hyperplasia. In a rare subset of patients, the
disorder is familial (autosomal dominant) and aldosterone levels can be suppressed
by administering low doses of exogenous glucocorticoid. The molecular defect
responsible for glucocorticoid-remediable hyperaldosteronism is a rearranged

gene (due to a chromosomal crossover), containing the 5'-regulatory region of the
11β-hydroxylase gene and the coding sequence of the aldosterone synthase gene.
Consequently, mineralocorticoid is synthesized in the zona fasciculata and
regulated by corticotropin. A number of conditions associated with
hyperreninemia result in secondary hyperaldosteronism and renal K
+
wasting.
High renin levels are commonly seen in both renovascular and malignant
hypertension. Renin-secreting tumors of the juxtaglomerular apparatus are a rare
cause of hypokalemia. Other tumors that have been reported to produce renin
include renal cell carcinoma, ovarian carcinoma, and Wilms' tumor.
Hyperreninemia may also occur secondary to decreased effective circulating
arterial volume.
In the absence of elevated renin or aldosterone levels, enhanced distal
nephron secretion of K
+
may result from increased production of non-aldosterone
mineralocorticoids in congenital adrenal hyperplasia. Glucocorticoid-stimulated
kaliuresis does not normally occur due to the conversion of cortisol to cortisone by
11β-hydroxysteroid dehydrogenase (11β-HSDH). Therefore, 11β-HSDH
deficiency or suppression allows cortisol to bind to the aldosterone receptor and
leads to the syndrome of apparent mineralocorticoid excess. Drugs that inhibit the
activity of 11β-HSDH include glycyrrhetinic acid, present in licorice, chewing
tobacco, and carbenoxolone. The presentation of Cushing's syndrome may include
hypokalemia if the capacity of 11β-HSDH to inactivate cortisol is overwhelmed
by persistently elevated glucocorticoid levels.