The correct answer is:

Hyperlipidemia

Educational Objective:

Discuss etiologies of pseudohyponatremia and differentiate this from true hyponatremia.

Key Point:

Both hyperlipidemia and hyperproteinemia can cause the illusion of hyponatremia despite normal total body levels of sodium

Contrast this to hyperglycemia or diabetic ketoacidosis (DKA), which shows the opposite phenomenon: DKA can cause pseudoHYPERnatremia and pseudoHYPERkalemia despite the total body levels of both electrolytes being low.

Explanation:

Hyponatremia can be broadly divided into two fundamental categories:  true hyponatremia, (in which the serum sodium concentration is truly less than normal within the total amount of serum water), and pseudohyponatremia, in which the serum sodium concentration is normal within the total amount of serum water, but the presence of either hyperlipidemia or hyperproteinemia causes the lab machinery to erroneously report a non-existent hyponatremia.

Most clinical laboratories measure sodium based on the assumption that the sample is composed of 93% water and 7% proteins and lipids. Anything that increases the protein or lipid percentage  (which does not contain sodium) at the expense of the water percentage of plasma (which contains its usual concentration of sodium will lead to an erroneously reported low sodium concentration because the machine still assumes that 93% of the total volume is water. This phenomenon can, for example, be seen in patients with familial hypercholesterolemia and highly lipemic blood.

This pseudohyponatremia should be differentiated from true hyponatremia, in which the concentration of sodium within the water compartment of serum is genuinely low.

True hyponatremia can be further differentiated into hypertonic versus hypotonic hyponatremia, depending on the relative lack/overabundance of the water compartment relative to the TOTAL osmoles. If the concentration of TOTAL osmoles is high, e.g. due to the presence of excess sugar during DKA or forced mannitol diuresis, then this will lead to a hypertonic (too little water relative to TOTAL osmoles) hyponatremia (too little sodium among the too many TOTAL osmoles).

The other conditions listed above result in true hypotonic hyponatremia with a genuinely reduced sodium concentration as well as genuinely reduced total osmoles within the plasma water.

Total measured osmolality can help differentiate these conditions. Pseudohyponatremia will present as an isotonic hyponatremia.

Pearl: Tonicity is the effective osmolality = the sum of the concentrations of the solutes that have the capacity to exert an osmotic force across the membrane.

Figure:

Hyponatremia Algorithm

Severe Euvolemic Hyptonic Hyponatremia (Serum Sodium < 125 meq/l)

References:

Pfennig CL. Electrolyte Disorders. (Chapter 117) In: Walls R, et al. Rosen’s Emergency Medicine: Concepts and Clinical Practice. 9th ed., 2018: 1516-1532.e2

Maloney GE. Diabetes Mellitus and Disorders of Glucose Homeostasis. (Chapter 118) In: Walls R, et al. Rosen’s Emergency Medicine: Concepts and Clinical Practice. 9th ed., 2018: 1533-1547.e3

Van Ness-Otunnu R, Hack JB. Hyperglycemic crisis. J Emerg Med. 2013;45(5):797-805.

Algorithm to hyponatremia courtesy Bon Secours Richmond