Potassium

Monitoring the plasma potassium (K⁺) level as an index of total body K⁺ is like evaluating the size of an iceberg by its visible tip, because less than 1% of the total body K⁺ is located in plasma (1). With this limitation in mind, this chapter describes the causes and consequences of abnormalities in the plasma K⁺ concentration (1,2,3).

I. Basics

A. Potassium Distribution

The intracellular preponderance of K⁺ is the result of a sodium-potassium (Na⁺-K⁺) exchange pump on cell membranes that moves Na⁺ out of cells and moves K⁺ into cells (1).
The total body K⁺ in healthy adults is about 50 mEq/kg, and only 2% is in the extracellular fluid (1). Since the plasma accounts for about 20% of the extracellular fluid, the K⁺ content of plasma is only 0.4% of the total body K⁺.
- EXAMPLE: A 70 kg adult is expected to have a total body K⁺ of 3,500 mEq, with only 70 mEq K⁺ in the extracellular fluid, and a miniscule 14 mEq of K⁺ in plasma.

B. Plasma Potassium

The influence of changes in total body K⁺ on plasma K⁺ is described by the curve in Figure 28.1 (4). Note the
shape of the curve, with the flat portion in the region of K⁺ deficiency.

FIGURE 28.1 Relationship between changes in total body K⁺ and the serum K⁺ concentration. Redrawn from Reference 4.
In an average-sized adult with a normal plasma K⁺, a total body K⁺ deficit of 200–400 mEq is required to produce a 1 mEq/L decrease in plasma K⁺, while a total body K⁺ excess of 100–200 mEq is required to produce a 1 mEq/L increase in plasma K⁺ (5). Therefore, for a given change in serum K⁺, the change in total body K⁺ is twofold greater with K⁺ depletion (hypokalemia) than with K⁺ excess (hyperkalemia).

C. Potassium Excretion

Small amounts of K⁺ are lost in stool (5–10 mEq/day) and sweat (0–10 mEq/day), but the majority of K⁺ loss is in urine (40–120 mEq/day, depending on K⁺ intake) (1).

2. Renal Excretion

Most of the filtered K⁺ is reabsorbed in the proximal tubules, and K⁺ is then secreted in the distal tubules and collecting ducts (1).

Potassium loss in urine is primarily a function of K⁺ secretion in the distal nephron, which is controlled by plasma K⁺ and aldosterone (which stimulates K⁺ secretion as it promotes sodium retention).
When renal function is normal, the capacity for K⁺ excretion is great enough to prevent a sustained rise in plasma K⁺ in response to an increased K⁺ load (1).

II. Hypokalemia

Hypokalemia (plasma K⁺ <3.5 mEq/L) can be the result of K⁺ movement into cells (transcellular shift), or a decrease in total body K⁺ (K⁺ depletion) (6).

A. Transcellular Shift

The following conditions can result in hypokalemia from K⁺ movement into cells.

Inhaled β₂-agonist bronchodilators (e.g., albuterol) can produce a mild decrease in plasma K⁺ (≤0.5 mEq/L) in therapeutic doses (7). The mechanism is stimulation of β₂ receptors on cell membranes of myocytes in skeletal muscle. The effect on plasma K⁺ is magnified when inhaled β₂ agonists are used in combination with insulin (7) or diuretics (8).
Alkalosis can promote the intracellular movement of K⁺ in exchange for intracellular H⁺ via a membrane H⁺-K⁺ exchange pump. However, alkalosis has a variable and unpredictable effect on plasma K⁺ (9).
Hypothermia causes a transient drop in plasma K⁺ that resolves on rewarming (10).
Insulin drives K⁺ into cells via the glucose transporter, and the effect lasts 1–2 hours (7).

B. Potassium Depletion

Potassium depletion can be the result of K⁺ loss via the kidneys or GI tract.

1. Renal Potassium Loss

Diuretics (thiazides and loop diuretics) promote K⁺ secretion in the distal nephron via two mechanisms: (a) increased sodium delivery to the distal nephron, and (b) enhanced aldosterone secretion (from volume loss) (6).
Magnesium depletion is a well-known cause of enhanced urinary K⁺ loss, but the exact mechanism is unclear (6). Hypomagnesemia is found in about 40% of patients with hypokalemia (6), and is considered an important factor in promoting K⁺ depletion in critically ill patients (11).
Loss of gastric secretions is often accompanied by hypokalemia (11). Gastric secretions have a relatively low concentration of K⁺ (10–15 mEq/L), but the resulting volume loss and alkalosis promote K⁺ loss in the urine (12).
Amphotericin B promotes K⁺ secretion in the distal nephron, and hypokalemia occurs in up to half of patients treated with this antifungal agent (6).

2. GI Potassium Loss

The major cause of extrarenal K⁺ loss is secretory diarrhea, where the concentration of K⁺ is 15–40 mEq/L (12). The daily stool volume can reach 10 liters in severe cases of secretory diarrhea, resulting in daily K⁺ losses up to 400 mEq (12).