Iso-osmolar hyponatremia from polyethylene glycol

Abstract

Understanding and applying pathophysiological concepts to patient care is an important skill for physicians in the clinical setting. Here, we present a case that demonstrates how the application of common physiological concepts relating to the widely accepted hyponatremia algorithm led to an accurate diagnosis of hyponatremia. This case documents iso-osmolar hyponatremia caused by orally administered polyethylene glycol absorption in the gastrointestinal tract. Herein, we discuss the workup and differential diagnosis for iso-osmolar hyponatremia in juxtaposition with the pathophysiological mechanisms unique to this case. We discuss these pathophysiological mechanisms based on the patients' laboratory data and responses to therapeutic interventions.

Keywords: hyperkalemia; hyponatremia; ileus; iso-osmolar; osmolality; polyethylene glycol; sarcoidosis.

FIGURE 1

Patient’s labs, urine sediment and timeline. (A) Patient’s laboratory results during inpatient admission. (B) Photomicrograph of patient’s urinary sediment examination, unpolarized. (C) Patients hospitalization during the first 13 days (x-axis) demonstrating the relationship between patient’s sodium, potassium and creatinine as they relate to PEG dose (thin red arrows = 17 g PEG dose; thick red arrows = 34 g PEG dose). Both a temporal and dose-dependent relationship is reliably seen; sodium decreases and potassium increases after each PEG dose. When PEG is discontinued, the electrolyte abnormalities and creatinine fluctuations also resolved. WBC, white blood cells; Hgb, hemoglobin; Plt, platelets; Na, sodium; K, potassium; Cl, chloride; TCO₂, total carbon dioxide; Cr, creatinine; Ca, calcium; RBC, red blood cells.

FIGURE 2

Mechanism of iso-osmolar hyponatremia from oral intake of PEG 3350. (A) PEG administered in the setting of an ileus and many other risk factors for tight junction dysfunction resulted in a higher risk of PEG permeability. With >24 h exposure, enterocyte death can occur, further increasing PEG absorption. (B) Once in the blood, PEG has similar actions as it would have in the intestinal lumen. (b1) The most prominent biochemical change is from the large volume of water movement due to the higher serum osmolality. Water will move from a low osmolality environment to a higher osmolality environment, diluting the sodium and resulting in hyperosmolar/iso-osmolar hyponatremia. (b2) This large amount of water movement can also influence the movement of other ions, most notably here, potassium. This effect, referred to as solvent drag, is when the movement of fluid (or solvent) ‘drags’ potassium from a high intracellular concentration, down its concentration gradient to a lower potassium concentration extracellularly. (C) This large osmotic load in the systemic circulation will be filtered by the kidney. The proximal tubule has a limited capacity to reabsorb macromolecules in the proximal tubule. This usually includes proteins that once reabsorbed are degraded into amino acids through lysozyme vesicles. Synthetic substances are typically not amenable to degradation, but proximal tubular reabsorption will occur, and this process can be more active if a prerenal state is present as in our patient, due to effective intravascular volume depletion. The inability to break down these macromolecules will cause proximal tubular renal cells to increase in size eventually resulting in their dysfunction (osmotic injury), sluffing and excretion in the urine. If enough of these cells are injured, then an increased serum creatinine is seen, resulting in osmotic nephropathy, which is presumed to be present here based on many factors discussed in the manuscript.