The regulation of potassium balance

Introduction

In the past few chapters, we made several observations about extracellular fluid (ECF) volume and osmolality:

• The stability of these parameters is critical for normal physiologic functioning

• These parameters are subject to daily changes

• The kidney counters these changes to preserve stable ECF volume and osmolality.

In this chapter and the next, we will see that the same principles apply to two other critical physiologic parameters: the plasma potassium, or [K ⁺ ], and the plasma acidity, or pH.

K ⁺ is present in human tissues at an overall concentration of about 50 mEq/kg body weight. Because plant and animal cells are filled with K ⁺ , it is also ingested daily in dietary vegetables, fruits, and meats, which adds K ⁺ to the plasma through the intestines, raising plasma [K ⁺ ] ( Fig. 21.1 ).

The kidney modulates excretion of this daily K ⁺ load to keep the plasma [K ⁺ ] stable, which in turn maintains the special distribution of K ⁺ between the intracellular fluid (ICF) and the ECF. Without this special distribution of K ⁺ , the basic functions of most tissues would not be possible.

System structure: The distribution of potassium

Just as Na ⁺ is the major cation of the ECF, K ⁺ is the major cation of the ICF.

• Roughly 98% of total body K ⁺ resides in the ICF, with 2% in the ECF.

• In absolute terms, this represents a total of 3500 mEq of potassium in the ICF and 70 mEq in the ECF in the average person ( Table 21.1 ).

  TABLE 21.1

  The Normal Distribution of Potassium

  	Intracellular Fluid	Extracellular Fluid
  Total value	–3500 mEq	–70 mEq
  Percentage of total	98%	2%
  [K + ]	140 mEq/L	4–5 mEq/L

• The Na ⁺ ,K ⁺ -adenosine triphosphatase (ATPase) pumps that drive Na ⁺ out of cells and K ⁺ into cells create this distribution.

The two basic homeostatic elements in the regulation of the potassium distribution are:

• The sensors of plasma [K ⁺ ]

  • The K ⁺ sensors are thought to be located in the adrenal gland, perhaps in the zona glomerulosa, where aldosterone is secreted.

  • Recall that aldosterone indirectly regulates K ⁺ excretion in the late distal tubule and collecting duct.

• The effectors of regulatory K ⁺

  • The proximal tubule conducts a great deal of K ⁺ reabsorption on an unregulated basis, that is, it reabsorbs K ⁺ regardless of the plasma [K ⁺ ].

System function: Potassium homeostasis

Why is a stable distribution of potassium physiologically important?

Recall that the segregation of K ⁺ inside cells is the chief determinant of the resting cell membrane potential, and that the resting membrane potential accounts for the excitability of nervous and muscle tissue. Without the potassium distribution, muscles could not contract, and neurons could not generate or transmit action potentials.

The distribution of potassium accounts for tissue excitability in the following way:

• The Na ⁺ ,K ⁺ -ATPase pump creates a large [K ⁺ ] gradient between the interior and exterior of cells.

• The high density of K ⁺ channels in most cell membranes (high K ⁺ permeability) allows K ⁺ to flow down that concentration gradient, from interior to exterior. The migration of positively charged K ⁺ ions out of the cell renders the intracellular side of the membrane electronegative (polarized).

• When a neurotransmitter stimulates an influx of Na ⁺ down its concentration gradient, the electrical potential inside of the cell increases (depolarizing the cell), and this change in transmembrane voltage triggers the opening of more epithelial sodium channels (ENaC).

• As the membrane depolarizes, more K ⁺ channels also open, leading to an efflux of K ⁺ . If the initial neurotransmitted stimulus is strong enough, the influx of Na ⁺ continues to depolarize the cell, which opens more ENaCs.

• The Na ⁺ influx continues to build until the Na ⁺ influx surpasses the K ⁺ efflux, giving the inside of the cell a positive electrical potential, or action potential.

• The threshold potential is the minimum initial depolarized potential that the neurotransmitter must achieve to send the cell into the self-amplifying ascent toward action potential.

The K ⁺ distribution thus establishes the electrophysiologic ground upon which action potentials can occur. More generally, a high intracellular [K ⁺ ] is necessary for a wide variety of enzymatic cell functions, including the regulation of protein synthesis, cell growth and division, and glycogen synthesis.

Disturbances in K ⁺ distribution, reflected in high or low plasma [K ⁺ ], therefore threaten vital tissue functions. Consequently, many mechanisms are brought to bear upon the plasma [K ⁺ ] to keep it within tight bounds.