“Excitable” tissues

• Rely on the potassium concentration gradient across cell membranes to establish resting membrane potentials.
• Excitable tissues include: nerve, skeletal muscle, and cardiac muscle.

Two key forms of potassium balance:

Internal

• Describes potassium distribution between the intra- and extracellular fluid compartments.

External

• Describes the relationship between dietary intake of potassium and its renal excretion.

INTERNAL BALANCE

Homeostasis

• ICF contains 98% of body’s total K+
• ECF contains 2%
• Sodium-potassium ATPase (aka, pump) maintains this homeostatic internal potassium balance.
• Shifts in internal potassium balance can cause cardiac arrhythmia and muscle weakness.

Hypokalemia

Reduced extracellular potassium concentration

• Potassium movement into the cell – intracellular potassium concentration increases and extracellular concentration increases.
• External imbalance can cause hypokalemia from an increased potassium excretion-to-intake ratio.
• Causes of increased intracellular concentration, include hormones, medications, and disease states.
• Specific causes include:
  – Metabolic alkalosis.
  – Diarrhea-induced loss of potassium.
  – Medications
  – Hormones, such as:
  Aldosterone, which acts on the kidney’s reabsorption of potassium (an external balance mechanism).
  Beta-2 adrenergic stimulators and insulin, which drive potassium into the cell (an internal balance mechanism).

Clinical correlation

A rapid correction of hyperkalemia (elevated extracellular potassium) can be achieved with:
– An albuterol inhaler (a beta-2 adrenergic stimulator)
– insulin, which drives potassium from the plasma into the cell (an internal mechanism)
– Kayexylate, which produces a diarrhea-wasting of potassium (an external mechanism)

Hyperkalemia

Increased extracellular potassium concentration

• Potassium movement out of the cell – intracellular potassium concentration decreases and extracellular concentration increases.
• External imbalance can cause hyperkalemia from a reduced potassium excretion-to-intake ratio.
• Specific causes include:
  – Metabolic acidosis.
  – Cell lysis (when the cell bursts, its contents are released) (an internal balance mechanism)
  – Increased ECF osmolarity (water will exit the cell, “dragging” potassium with it) (another internal balance mechanism)
  – Medications, such as:
  ACE Inhibitors, which acts on the kidney’s reabsorption of potassium in the opposite manner as aldosterone (an external balance mechanism).
  Beta-blockers prevent potassium entry into the cell (the opposite of beta-adrenergic stimulators).

Clinical correlation

Chronic kidney failure patients (who can’t excrete potassium) can develop hyperkalemia if they become constipated: they rely on the GI tract for external balance of potassium.

EXTERNAL BALANCE

• Potassium reabsorption and secretion in the distal nephron are hormonally regulated to ensure that renal excretion matches dietary intake, which varies widely both intra- and inter-individually from day to day.
• Potassium is freely filtered within the glomerulus.
• Approximately 67% of the filtered load of potassium is reabsorbed from the proximal tubule.
• 20% is reabsorbed from the thick ascending limb.
  – Recall that potassium reabsorption in these segments is linked with sodium reabsorption, and is, therefore, relatively constant.
• Variable amount of potassium is reabsorbed from the distal tubule to conserve it when dietary intake is low; when dietary intake is high, potassium is secreted into the nephron.

Alpha-intercalated cells

• In the distal nephron, conserve potassium when dietary intake is low.
• Reabsorb potassium down the electrochemical gradient created by hydrogen-potassium ATPase (aka, pumps).
• The hydrogen-potassium ATPase on the luminal membrane moves hydrogen to the tubule lumen while sending potassium into the tubule cell.
• Potassium then diffuses through the basolateral membrane into the interstitium and capillaries.

Principal cells

• Return excess potassium to the tubular lumen when dietary intake is high.
• Secrete potassium down the electrochemical gradient created by sodium-potassium ATPase.
• Sodium-potassium ATPase moves potassium from the blood into the cell, while projecting sodium from it.
• Potassium then diffuses out of the cell, into the lumen to be excreted in the urine.