Electrolytes: Sodium, Potassium, and Chloride

Sodium (Na+)

Major cation of extracellular fluid (ECF), constituting 90%.
Changes in sodium levels lead to changes in plasma volume.
Largest constituent of plasma osmolality.
Excreted in urine when the renal threshold for serum Na+ exceeds 110 to 130 mmol/L.

Functions of Sodium

Regulation of Body Water:
- Osmotic activity: Sodium determines osmotic activity.
- Main contributor to plasma osmolality.
Neuromuscular Excitability:
- Extreme concentrations result in neuromuscular symptoms.
Na-K ATP-ase Pump:
- Pumps Na+ out and K+ into cells.
- Without this pump, cells would fill with Na+ and rupture due to osmotic pressure.

Regulation of Sodium Concentration

Depends on:
- Intake of water in response to thirst.
- Excretion of water due to blood volume or osmolality changes.

Renal Regulation of Sodium

Kidneys conserve or excrete Na+ depending on ECF and blood volume.
- Regulated by:
  - Aldosterone.
  - Renin-angiotensin system: Stimulates the adrenal cortex to secrete aldosterone.

Disorders of Sodium Homeostasis

Hyponatremia: Na+ < 135 mmol/L

Classification by osmolality:
- With Low Osmolality:
  - Increased sodium loss:
    - Hypoadrenalism.
    - Potassium deficiency.
    - Diuretic use.
    - Ketonuria.
    - Salt-losing nephropathy.
    - Prolonged vomiting or diarrhea.
    - Severe burns.
  - Increased water retention:
    - Renal failure.
    - Nephrotic syndrome.
    - Hepatic cirrhosis.
    - Congestive heart failure.
  - Water Imbalance
    - Excess water intake
    - SIADH
- With Normal Osmolality:
  - Increased non-sodium cations:
    - Lithium excess.
    - Increased γ-globulins (cationic) in multiple myeloma.
    - Severe hyperkalemia.
    - Severe hypermagnesemia.
    - Severe calcemia.
  - Pseudohyponatremia:
    - Hyperlipidemia.
    - Hyperproteinemia.
- With High Osmolality:
  - Hyperglycemia.
  - Mannitol infusion.
Because Na+ is a major contributor to osmolality, both levels can assist in identifying the cause of hyponatremia. Most instances of hyponatremia occur with decreased osmolality. This may be a result of Na+ loss or water retention

Hypernatremia: Na+ > 150 mmol/L

Causes:
- Excess Water Loss:
  - Diabetes insipidus.
  - Renal tubular disorder.
  - Prolonged diarrhea.
  - Profuse sweating.
  - Severe burns.
- Decreased Water Intake:
  - Older persons.
  - Infants.
  - Maternal impairment.
- Increased Intake or Retention:
  - Hyperaldosteronism.
  - Sodium bicarbonate excess.
  - Dialysis fluid excess.
- Pseudohyponatremia
  - In vitro hemolysis (most common cause for a false decrease)
  - RBCs lyse → Na+
- Hyperglycemia
  - Hyponatremia + high osmolality
  - Hyperglycemia increase serum osmolality → shift of cellular $H_2O$ to the blood (Na+ dilution)

Hypernatremia Related to Urine Osmolality

Urine Osmolality (<300 mOsm/kg):
- Diabetes insipidus (impaired secretion of AVP or kidneys cannot respond to AVP).
Urine Osmolality (300 to 700 mOsm/kg):
- Partial defect in AVP release or response to AVP.
- Osmotic diuresis.
Urine Osmolality (>700 mOsm/kg):
- Loss of thirst.
- Insensible loss of water (breathing, skin).
- GI loss of hypotonic fluid.
- Excess intake of sodium.

*AVP: Arginine Vasopressin Hormone

*Urine osmolality is necessary to evaluate the cause of hypernatremia

*With renal loss of water, the urine osmolality is low or normal

*With extrarenal fluid losses, the urine osmolality is increased

Specimen Collection: Sodium

Serum:
- Slight hemolysis is acceptable, but avoid gross hemolysis.
Plasma:
- Lithium heparin.
- Ammonium heparin.
- Lithium oxalate.
Whole Blood:
- Depending on the analyzer.
Timed (24 hour) and Random Urine.
Sweat.
Gastrointestinal Fluid.

Urine Testing and Calculation

Dilution of the urine specimen is usually required due to increased levels.
Once a number is obtained, it is multiplied by the dilution factor and reported as mEq/L or mmol/L in 24 hours.

Reference Range: Sodium

Serum: 135 - 145 mEq/L or mmol/L
Urine (24-hour collection): 40 - 220 mEq/L
CSF: 135 - 150 mmol/L

Methods: Sodium

Colorimetry: Albanese Lein
Flame Emission Spectrophotometry
Atomic Absorption Spectrophotometry (AAS)
ISEs: Most routinely used method

ISE Method

Uses a semipermeable membrane to develop a potential.
Two electrodes used:
- Reference electrode: Has a constant potential.
- Measuring electrodes.
Calculation of the ion concentration in solution:
- Based on the difference in potential between the reference and measuring electrodes.
- Most analyzers use a glass ion-exchange membrane in its ISE system for Na+ measurement.

ISE Source of Error

Protein buildup on the membrane causes poor selectivity, resulting in poor reproducibility of results.
Routine maintenance involves the removal of this protein buildup.

Potassium (K+)

The major cation of intracellular fluid
Only 2% of potassium is in the plasma
Potassium concentration inside cells is 20× greater than it is outside
This is maintained by the Na-K pump
Exchanges 3 Na+ for 1 K+
Diet
Easily consumed by food products such as bananas

Function of Potassium

Important to the functions of neuromuscular cells
Acid-base balance
Intracellular fluid volume
Control heart muscle contraction
Promotes muscular excitability
Decrease potassium decreases excitability (Paralysis and Arrhythmias)

Regulation of Potassium

Kidneys
Responsible for regulation; potassium is readily excreted but gets reabsorbed in the proximal tubule - under the control of aldosterone
Diet
Cell uptake/exchange
Urine

Reference Ranges: Potassium

SERUM (ADULTS)
- 3.5 - 5.1 mmol/L
PLASMA
- MALES: 3.5 - 4.5 mmol/L
- FEMALES: 3.4 - 4.4 mmol/L
NEWBORNS:
- 3.7- 5.9 mEq/L
URINE (24 HOUR COLLECTION):
- 25 - 125 mmol/D

Disorders of Potassium Homeostasis

Hypokalemia: K+ < 3.5 mmol/L
Hyperkalemia: K+ > 5.1 mmol/L

Specimen Collection: Potassium

Non-hemolyzed
Heparinized Plasma
24-hour Urine Sample

Specimen Considerations

Lithium heparin plasma = preferred

Methods: Potassium

FEP: Flame Emission Photometry
AAS: Atomic Absorption Spectrometry
ISE: Ion-selective Electrolytes
Colorimetry

Chloride (Cl-)

The major anion of extracellular fluid
Chloride moves passively with Na+ or against HCO_3-
Chloride usually follows Na+ (if one is abnormal, so is the other)

Functions of Chloride

Body hydration/water balance
Osmotic pressure
Electrical neutrality

Regulation of Chloride

Regulation via diet and kidneys

Kidneys
- Cl- reabsorbed in the renal proximal tubules, with Na+
- Deficiencies of either one limits the reabsorption of the other

Reference Ranges: Chloride

SERUM
- 98 to 107 mEq/L or mmol/L
24-HOUR URINE
- 110 to 250 mEq/L varies with intake
CSF
- 12O to 132 mEq/L

*NOTE: Bacterial meningitis

*CSF Cl = low

*CSF CHON = high

Causes of Changes in Chloride Levels

Decreased Chloride (Hypochloremia)

Gastrointestinal Loss
- Vomiting
- Diarrhea
- Gastric suction
- Intestinal tumor
- Malabsorption
- Cancer therapy
  - chemotherapy
  - radiation therapy
- Large dose of laxatives
Cellular Shift
- Alkalosis
- Insulin overdose
Renal Loss
- Diuretics
  - thiazides
  - mineralocorticoids
- Nephritis
- Renal tubular acidosis
- Hyperaldosteronism
- Cushing’s syndrome
- Hypomagnesemia
- Acute leukemia
Decreased Intake
Decreased Renal Excretion
- Acute or chronic renal failure
  - GFR <20 mL/min
- Hypoaldosteronism
- Addison’s disease
- Diuretics
Cellular Shift
- Acidosis
- Muscle/Cellular injury
- Chemotherapy
- Leukemia
- Hemolysis

Increased Chloride (Hyperchloremia)

Increased Intake
- Oral / Intravenous potassium replacement therapy
Artifactual
- Sample hemolysis
- Thrombocytosis
- Prolonged tourniquet use
- Excessive fist clenching
- 0. 5% hemolysis = increased 0.5 mmol/L
- Gross hemolysis = increased 30%
- Serum K > Plasma K by 0.1cto 0.7 mmol/L because of platelets (clot)
- 10 to 20% in muscle activity
- 2. 3 to 1.2 mmol/L = mild to moderate exercise
- 2 to 3 mmol/L = vigorous exercise; fist clenching