Potassium Disturbances: Hypokalemia and Hyperkalemia

Hypokalemia

Hypokalemia is defined as low potassium in the plasma, typically below the reference range of the local laboratory, often less than 3.5 millimoles per liter.

Effects of Hypokalemia

1. Transmembrane Potential: Hypokalemia affects the transmembrane potential in muscle and nerve cells, rendering it more electronegative, leading to hyperpolarization initially and enhanced membrane excitability due to increased sodium channel activation.

2. Skeletal Muscle Weakness

3. Cardiac Muscle Effects:

   • ECG changes include flattened T waves, U waves, ectopics, and ventricular arrhythmias (ventricular tachycardia or fibrillation).

   • Possible atrial and ventricular ectopic beats, sinus bradycardia, paroxysmal atrial junction tachycardia, and AV block.

4. Gastrointestinal Effects: Ileus leading to pseudo-obstruction.

5. Renal Effects: Long-term hypokalemia can cause polyuria associated with nephrogenic diabetes insipidus due to increased fibrosis within the tubular interstitial compartment, often seen in chronic conditions like Gittelman syndrome or Bartus syndrome.

Myocardial Action Potential

Resting Membrane Potential

Normally around $-90$ mV in cardiac cells.

Depolarization (Phase Zero)

Mediated by sodium entry into the cells due to increased open sodium channels.

Repolarization

Associated with closure of sodium channels and potassium and calcium transit.

Impact of Hypokalemia

1. More negative membrane potential initially, making initial depolarization more difficult.

2. Increased number of open sodium channels, leading to a net increase in membrane excitability.

3. Delayed ventricular repolarization prolongs the refractory period, predisposing to reentrant arrhythmias.

ECG Example

Plasma potassium around 2 mmol/L showing flat or inverted T waves and U waves.

Causes of Hypokalemia

1. Redistribution: Alkalosis.

2. Reduced Intake: Extreme dietary deficiency (rare).

3. Excess Loss (Most Common)

   • Renal Loss:

     • Diuretics acting at sites one, two, or three.

     • Excess aldosterone (Conn's syndrome).

     • Renal tubular acidosis.

   • Gut Loss:

     • Vomiting associated with GI loss and volume contraction, leading to increased aldosterone.

     • Diarrhea and purgative use.

Urinary Potassium

Useful to differentiate between gut and kidney causes but can be misleading in hypovolemic patients due to increased aldosterone.

Conn's Syndrome

Described as a cause of hypertension, usually associated with an adrenal adenoma or bilateral adrenal hyperplasia. Hyperkalemia is present in only about 30% of cases.

Mechanism

Excess aldosterone targets the principal cell (site four of the nephron), increasing sodium reabsorption through the epithelial sodium channel and potassium leak in the apical membrane, and increasing activity of the sodium-potassium ATPase.

Treatment of Hypokalemia

1. Reverse the underlying cause (e.g., stop diarrhea).

2. Replace potassium with an appropriate salt (usually potassium chloride) either orally (e.g., Slow-K or Span-K) or intravenously.

   • Avoid potassium bicarbonate, as it may cause metabolic alkalosis and exacerbate hypokalemia.

3. Amiloride to block potassium secretion in site four by antagonizing the epithelial sodium channel.

Hyperkalemia

Hyperkalemia is defined as a high potassium concentration in the plasma, usually above 5 millimoles per liter.

Effects of Hyperkalemia

1. Skeletal Muscle: Paralysis.

2. Cardiac Muscle: ECG changes include peaked T waves, prolonged QRS complex, and, in severe cases, cardiac arrest.

3. Cell Membrane Potential: Becomes less electronegative, leading to excess depolarization initially but reduced membrane excitability due to reduced sodium channel activity.

ECG Examples

1. Early hyperkalemia (potassium around 6-6.5 mmol/L): Peaked T waves, slightly widened QRS.

2. Severe hyperkalemia (potassium 9.8 mmol/L): Very widened QRS complex with extremely peaked T waves, forming a sine wave pattern.

Myocardial Action Potential

Early Phase

Less negative resting potential increases membrane excitability.

Later Phase

Reduced sodium channels in the cell membrane decrease membrane excitability, leading to impaired cardiac conduction, neuromuscular weakness, or paralysis.

Causes of Hyperkalemia

1. Spurious Causes:

   • Hemolysis of blood sample, releasing intracellular potassium.

2. Redistribution:

   • Acidosis (high hydrogen ion concentrations) redistributes potassium to maintain electron neutrality.

   • Lack of insulin (e.g., diabetic ketoacidosis).

   • Beta-blockade.

3. Increased Intake:

   • Excessive dietary potassium intake in individuals with kidney disease.

4. Renal Retention:

   • Reduced glomerular filtration rate (acute or chronic).

   • Tubular secretory failure (normal GFR):

     • Lack of aldosterone (Addison's disease).

     • Blockage of the epithelial sodium channel in site four (e.g., amiloride).

     • Renal tubular acidosis.

Addison's Disease

Autoimmune disease associated with adrenal insufficiency, leading to a lack of aldosterone, resulting in hyperkalemia, hyponatremia, and hypotension.

Mechanism

Aldosterone acts on the principal cell at site four. Insufficiency of aldosterone leads to the characteristic features of Addison's disease.

Treatment of Hyperkalemia

1. Emergency Measures (e.g., potassium of 9.8 mmol/L):

   • Stabilize the cell membrane using calcium salts (calcium gluconate or calcium chloride).

   • Shift potassium into the cells using:

     • Insulin (with glucose to prevent hypoglycemia).

     • Beta-2 adrenergic agonists (e.g., salbutamol).

     • Bicarbonate to change the plasma pH.

2. Remove Potassium:

   • Diuretics to enhance potassium excretion via the kidneys.

   • Potassium binders in the gut to prevent absorption.

   • Dialysis, if required.

Summary

Abnormalities in potassium homeostasis (hypokalemia and hyperkalemia) are common, clinically significant, and treatable conditions, provided the underlying pathophysiology is understood.