LEC # 8 PAGE # 318 GUYTON PHYSIOLOGY 15th Ed:

Plasma Sodium Concentration and Fluid Status

• Plasma sodium concentration is a measurement that is easily available to clinicians.
• It is used to assess a patient’s fluid status.
• Plasma osmolarity is not routinely measured.
• Sodium and its associated anions (mainly chloride) make up more than 90% of the solutes in the extracellular fluid (ECF).
• Therefore, plasma sodium concentration is a useful indicator of plasma osmolarity in many situations.
• Normal plasma sodium concentration is 135–145 mmol/L.
• When plasma sodium concentration falls more than a few milliequivalents below normal, the condition is called hyponatremia.
• Hyponatremia = Low plasma sodium concentration.
• When plasma sodium concentration rises above the normal range, the condition is called hypernatremia.
• Hypernatremia = High plasma sodium concentration.

Causes of Hyponatremia: Excess Water or Loss of Sodium (Hyponatremia)

• A decrease in plasma sodium concentration can occur due to:
  • Loss of sodium from the extracellular fluid (ECF).
  • Addition of excess water to the extracellular fluid (ECF).
• Loss of sodium is a common cause of hyponatremia.
• Primary sodium loss usually causes:
  • Hyponatremia.
  • Dehydration.
  • Decreased extracellular fluid (ECF) volume.
• Conditions that can cause hyponatremia due to sodium loss include:
  • Diarrhea.
  • Vomiting.
• Excessive use of diuretics can cause hyponatremia.
• Diuretics reduce the kidneys’ ability to conserve sodium.
• Some sodium-wasting kidney diseases can also cause mild hyponatremia.
• Addison disease can cause a modest degree of hyponatremia.
• In Addison disease, secretion of the hormone aldosterone is decreased.
• Reduced aldosterone impairs the kidneys’ ability to reabsorb sodium.
• Hyponatremia can also occur because of excess water retention.
• Excess water dilutes sodium in the extracellular fluid.
• This condition is called hyponatremia-overhydration.
• Excess secretion of antidiuretic hormone (ADH) can cause hyponatremia-overhydration.
• ADH is also called arginine vasopressin (AVP).
• ADH increases water reabsorption by the kidney tubules.
• Increased water reabsorption leads to:
  • Water retention.
  • Hyponatremia.
  • Overhydration.

Hyponatremia Causes Cell Edema.Effects of Hyponatremia on Cells and the Brain

• Rapid changes in cell volume due to hyponatremia can seriously affect tissue and organ function.
• The brain is especially sensitive to these changes.
• A rapid decrease in plasma sodium concentration can cause brain cell edema.
• Brain cell edema means swelling of brain cells.
• Rapid hyponatremia can cause neurological symptoms, including:
  • Headache.
  • Nausea.
  • Lethargy.
  • Disorientation.
• If plasma sodium concentration rapidly falls below 115–120 mmol/L, severe brain swelling may occur.
• Severe brain swelling can lead to:
  • Seizures.
  • Coma.
  • Permanent brain damage.
  • Death.
• The skull is rigid and cannot expand.
• The brain can increase its volume by only about 10% before herniation occurs.
• Herniation means brain tissue is forced into a space where it normally does not belong.
• Brain tissue may be pushed through the foramen magnum.
• The foramen magnum is an opening at the base of the skull.
• The spinal cord connects with the brain through the foramen magnum.

Adaptation to Slowly Developing Hyponatremia

• When hyponatremia develops slowly over several days, the brain and other tissues begin to adapt.
• Cells transport solutes from inside the cell to the extracellular fluid.
• Solutes moved out of the cells include:
  • Sodium.
  • Chloride.
  • Potassium.
  • Organic solutes such as glutamate.
• This adaptation reduces the osmotic movement of water into the cells.
• Reduced water entry helps prevent excessive cell swelling.
• As a result, tissue swelling is decreased.

Correction of Chronic Hyponatremia and Risk of Brain Injury

• During slowly developing hyponatremia, cells transport solutes out of the cells.
• This loss of cellular solutes can make the brain vulnerable to injury if hyponatremia is corrected too quickly.
• Rapid administration of hypertonic solutions to correct chronic hyponatremia can be harmful.
• Rapid correction may occur faster than the brain can recapture the solutes that were lost from the cells.
• This can cause osmotic injury to neurons.
• Osmotic injury is associated with demyelination.
• Demyelination means loss of the myelin sheath from nerves.
• Osmosis-mediated demyelination can be prevented by correcting chronic hyponatremia slowly.
• Plasma sodium concentration should be increased by less than 10–12 mmol/L in 24 hours.
• Plasma sodium concentration should be increased by less than 18 mmol/L in 48 hours.
• Slow correction allows the brain to recover the osmoles lost from the cells during adaptation to chronic hyponatremia.

Abnormalities of Body Fluid Volume Regulation

Hyponatremia—Dehydration

• Causes:
  • Adrenal insufficiency.
  • Overuse of diuretics.
  • Diarrhea.
  • Vomiting.
  • Sodium-wasting kidney diseases.
• Plasma sodium concentration: ↓
• Extracellular fluid volume: ↓
• Intracellular fluid volume: ↑

Hyponatremia—Overhydration

• Causes:
  • Excess ADH (SIADH).
  • Bronchogenic tumors.
  • Heart failure.
  • Cirrhosis.
  • Polydipsia.
• Plasma sodium concentration: ↓
• Extracellular fluid volume: ↑
• Intracellular fluid volume: ↑

Hypernatremia—Dehydration

• Causes:
  • Central diabetes insipidus.
  • Nephrogenic diabetes insipidus.
  • Excessive sweating.
• Plasma sodium concentration: ↑
• Extracellular fluid volume: ↓
• Intracellular fluid volume: ↓

Hypernatremia—Overhydration

• Causes:
  • Cushing disease.
  • Primary aldosteronism.
• Plasma sodium concentration: ↑
• Extracellular fluid volume: ↑
• Intracellular fluid volume: ↓

Frequency of Hyponatremia

• Hyponatremia is the most common electrolyte disorder seen in clinical practice.
• It may occur in about 15% to 25% of hospitalized patients.

Key Concepts

• Slow adaptation to hyponatremia causes cells to lose solutes.
• Rapid correction of chronic hyponatremia can cause osmotic neuronal injury.
• Demyelination occurs when the myelin sheath is lost from nerves.
• Correct chronic hyponatremia slowly:
  • < 10–12 mmol/L in 24 hours.
  • < 18 mmol/L in 48 hours.
• Hyponatremia may occur with dehydration or overhydration.
• Hypernatremia may occur with dehydration or overhydration.
• Hyponatremia is the most common electrolyte disorder in hospitalized patients.

Causes of Hypernatremia: Water Loss or Excess Sodium

• An increase in plasma sodium concentration causes an increase in plasma osmolarity.
• Increased plasma sodium concentration can occur due to:
  • Loss of water from the extracellular fluid (ECF).
  • Excess sodium in the extracellular fluid (ECF).
• Loss of water from the extracellular fluid concentrates the sodium ions.
• Primary loss of water from the extracellular fluid causes:
  • Hypernatremia.
  • Dehydration.
• Hypernatremia can occur when the body is unable to secrete ADH.
• ADH is required for the kidneys to conserve water.
• In the absence of ADH, the kidneys excrete large amounts of dilute urine.
• This disorder is called central diabetes insipidus.
• Central diabetes insipidus is also called AVP-deficiency.
• Excessive loss of dilute urine causes:
  • Dehydration.
  • Increased concentration of sodium chloride in the extracellular fluid.
• In some kidney diseases, the kidneys cannot respond to ADH.
• This condition causes a type of nephrogenic diabetes insipidus.
• Nephrogenic diabetes insipidus is also called AVP-resistance.
• A common cause of hypernatremia with decreased extracellular fluid volume is simple dehydration.
• Simple dehydration occurs when water intake is less than water loss.
• This can happen during prolonged heavy exercise with excessive sweating.

Key Concepts

Simple dehydration occurs when water loss exceeds water intake.

Hypernatremia = Increased plasma sodium concentration.

Hypernatremia increases plasma osmolarity.

Hypernatremia can result from:

Water loss.

Excess sodium.

Water loss from the ECF causes hypernatremia and dehydration.

Lack of ADH causes central diabetes insipidus (AVP-deficiency).

Failure of the kidneys to respond to ADH causes nephrogenic diabetes insipidus (AVP-resistance).

Excessive loss of dilute urine leads to dehydration and hypernatremia.

Hypernatremia Due to Excess Sodium Retention

• Hypernatremia can occur when excessive sodium chloride is added to the extracellular fluid (ECF).
• Excess sodium chloride in the ECF often causes hypernatremia-overhydration.
• Excess sodium chloride retention is usually associated with some degree of water retention by the kidneys.
• Excessive secretion of aldosterone can cause a mild degree of hypernatremia.
• Excessive aldosterone can also cause overhydration.
• Aldosterone is a sodium-retaining hormone.
• Hypernatremia is usually not severe in this condition.
• Sodium retention stimulates the secretion of ADH.
• ADH causes the kidneys to reabsorb greater amounts of water.
• Increased water reabsorption helps limit the rise in plasma sodium concentration.
• The sodium-retaining effects of excess aldosterone are often opposed by compensatory mechanisms.
• One compensatory mechanism is a decrease in other antinatriuretic hormones, such as angiotensin II.
• Another compensatory mechanism is an increase in blood pressure.
• Increased blood pressure causes pressure natriuresis.

Evaluation of Plasma Sodium Abnormalities

• When analyzing abnormalities of plasma sodium concentration, the cause should be identified first.
• Determine whether the abnormality is due to:
  • A primary loss of sodium.
  • A primary gain of sodium.
  • A primary loss of water.
  • A primary gain of water.
• Proper therapy depends on identifying the primary cause of the abnormality.

Key Concepts

• Excess sodium chloride in the ECF can cause hypernatremia.
• Excess sodium retention is usually accompanied by water retention.
• Hypernatremia with sodium retention often causes hypernatremia-overhydration.
• Excess aldosterone causes sodium retention, mild hypernatremia, and overhydration.
• Sodium retention stimulates ADH secretion.
• ADH increases water reabsorption by the kidneys.
• Water retention helps prevent severe hypernatremia.
• Compensatory mechanisms include:
  • Decreased angiotensin II.
  • Increased blood pressure.
  • Pressure natriuresis.
• Correct evaluation requires determining whether the primary problem is sodium loss/gain or water loss/gain.

Hypernatremia Causes Cell Shrinkage

Hypernatremia: Clinical Features

• Hypernatremia is much less common than hyponatremia.
• Severe symptoms usually occur only when plasma sodium concentration increases rapidly and markedly.
• Severe symptoms are usually seen when plasma sodium concentration rises above 158–160 mmol/L.
• Hypernatremia usually stimulates intense thirst.
• Hypernatremia also stimulates secretion of ADH.
• Thirst and ADH secretion help protect against large increases in plasma sodium concentration.
• Thirst and ADH secretion also help protect against large increases in extracellular fluid sodium concentration.
• Severe hypernatremia can occur in patients with hypothalamic lesions.
• Hypothalamic lesions may impair the sensation of thirst.
• Severe hypernatremia can occur in infants who may not have easy access to water.
• Severe hypernatremia can occur in older patients with altered mental status.
• Severe hypernatremia can also occur in persons with diabetes insipidus.

Key Concepts

• Hypernatremia is less common than hyponatremia.
• Severe symptoms usually occur with rapid and large increases in plasma sodium concentration.
• Severe symptoms are typically seen when plasma sodium exceeds 158–160 mmol/L.
• Hypernatremia stimulates:
  • Intense thirst.
  • ADH secretion.
• Thirst and ADH help prevent excessive increases in plasma sodium concentration.
• Severe hypernatremia may occur in:
  • Patients with hypothalamic lesions.
  • Infants with limited access to water.
  • Older patients with altered mental status.
  • Persons with diabetes insipidus.

Correction of Hypernatremia

• Hypernatremia can be corrected by administering a hypo-osmotic sodium chloride solution.
• Hypernatremia can also be corrected by administering a dextrose solution.
• Hypernatremia should be corrected slowly in patients with chronic increases in plasma sodium concentration.
• Chronic hypernatremia activates defense mechanisms that protect cells from changes in volume.
• These defense mechanisms help cells adapt to hypernatremia.
• The defense mechanisms in hypernatremia are opposite to those seen in hyponatremia.
• These mechanisms increase the intracellular concentration of sodium.
• These mechanisms also increase the intracellular concentration of other solutes.

Key Concepts

• Hypernatremia can be treated with:
  • Hypo-osmotic sodium chloride solution.
  • Dextrose solution.
• Chronic hypernatremia should be corrected slowly.
• Hypernatremia activates cellular defense mechanisms.
• These defenses protect cells from volume changes.
• The adaptive response is opposite to that seen in hyponatremia.
• Adaptation increases intracellular sodium and other solutes.