FOCUS: THE SECRET STORIES OF SODIUM Hypernatremia TAMARA HEW-BUTLER, KEVIN WEISZ LEARNING OBJECTIVES suicide from soy sauce, death by exorcism and salting 1. Compare and contrast the pathophysiological rituals, extreme parental punishment, hunger strikes, mechanisms of hypernatremia. getting lost in the sea or desert, and mass accidental 2. Explain adaptions that occur as a result of poisonings whereas salt is mistaken for sugar. elevated extracellular fluid tonicity. + 3. Describe the pathophysiological outcome of high ABBREVIATIONS: [Na ] – sodium concentration, Downloaded from intracellular osmolyte concentration. ICP – intracranial pressure, ICU – intensive care 4. List considerations for correction of hyper- unit, TBI - traumatic brain injury natremia INDEX TERMS: Salt poisoning, dehydration, ABSTRACT dysnatremia Hypernatremia is biochemically defined by a blood http://hwmaint.clsjournal.ascls.org/ sodium concentration ([Na+]) above the normal Clin Lab Sci 2016;29(3):176-185 reference range for the laboratory performing the test (typically >145 mmol/L). The clinical relevance of an Tamara Hew-Butler, DPM, PhD, FACSM, School of above normal blood [Na+] is largely determined by Health Science, Oakland University, Rochester MI the severity of the clinical signs and symptoms associated with cellular shrinkage (crenation). High Kevin Weisz, BS, William Beaumont School of Medicine, blood sodium concentrations are largely caused by: Oakland University, Rochester MI 1) excessive water loss with inadequate fluid replacement (thirsting); 2) excessive salt ingestion; or Address for Correspondence: Tamara Hew-Butler, DPM, a likely combination of too little fluid with too much PhD, FACSM, School of Health Science, 3157 HHB, on September 25 2021 salt. Morbidity and mortality from hypernatremia Oakland University, 2200 N. Squirrel Rd, Rochester, MI has been documented in infants accidentally 49309; [email protected] poisoned with salt or having difficulties breastfeeding, children ingesting excessive amounts Definition and Diagnosis of salt as an emetic or punishment, mentally or Hypernatremia (hyper = high; natremia = sodium in the physically disabled individuals (often living in blood) is a biochemical diagnosis in which the sodium nursing homes) who cannot express thirst or have content (in millimoles) in relationship to plasma water free access to fluids, athletes who refrain from (in liters) is above the range of normal for the laboratory drinking during heavy exercise in hot conditions, performing the test. For most laboratories, hyper- and hospitalized patients with under-replaced fluid natremia represents any blood [Na+] above 145 or over-replaced sodium administration. Poor mmol/L. Both the magnitude and rapidity of increase in clinical outcomes and delayed recovery have been blood [Na+] influence the severity of clinical signs, documented in hospitalized patients with symptoms and prognostic outcomes from hypernatremia, compared with patients who are hypernatremia. Generally speaking, the higher the admitted and remain normonatremic throughout initial blood [Na+] value, the more dire the clinical their hospital stay. Clinically significant consequences, with the survival rates of infants (<1 year) hypernatremia in free living humans is extremely greater than that of adults.1 In one review of 11 adults rare, with “salt poisoning” often an indicator of (>13years) and 20 children developing salt poisoning, abuse, neglect, or mental illness. Thus, the secret only 1/11 adults (9%) with a blood [Na+] above 160 stories of hypernatremia often whisper tales of mmol/L survived while 4/9 children (44%) and 9/11 VOL 29, NO 3 SUMMER 2016 CLINICAL LABORATORY SCIENCE 176 FOCUS: THE SECRET STORIES OF SODIUM (82%) infants survived.1 The highest recorded blood well as preventative strategies. Since water intake is sodium concentration in a surviving infant appears to stimulated by behaviorally-driven thirst (in response to be 274 mmol/L.2 high osmotic and/or low circulating blood volume stimuli) hypernatremia rarely occurs in individuals The development of hypernatremia may be acute given free access to fluids and responsive to (develops in less than 24 hours) or chronic (present for physiologically-mediated thirst sensations. Our more than one day).3 Acute hypernatremia generally physiological reliance on the thirst mechanism, to occurs when sodium intake is excessive over a short actively seek fluids in order to sustain life, is best period of time, as demonstrated in both accidental2,4-6 evidenced in patients who either do not synthesize and non-accidental 7,8 cases of “salt poisoning.”9 (central diabetes insipidus), or are not responsive Chronic hypernatremia, by definition, develops more (nephrogenic diabetes insipidus) to anti-diuretic slowly and more often results from either water loss hormone.24,25 Individuals with diabetes insipidus cannot and/or water lack commonly seen in: newborns with retain water (all fluid intake is promptly excreted by the Downloaded from breastfeeding difficulties,10,11 children with diarrheal kidneys as urine) but able to maintain normal sodium disease,12 nursing home patients with mental or physical concentrations (normonatremia) by drinking to thirst, disabilities9,13-17or individuals participating in hunger upwards of 15-20 L of fluid per day, to match maximal strikes.18 The brain adapts to chronic hypernatremia via urinary losses.26,27 Additionally, the thirst drive is so active intracellular reuptake of sodium, potassium, and robust that dehydrated patients will actively seek out http://hwmaint.clsjournal.ascls.org/ organic osmolytes (glutamine, glutamate, taurine, and water, drinking out of flower vases28 and sinks,19 to myo-inositol), which serve to maintain cellular size (i.e. satisfy an innate biological requirement to maintain limit brain shrinkage), thereby reducing the severity of whole body fluid homeostasis at all times. Figures 1, 2, neurological symptoms.3 and 3 summarize the three different volemic classifications and treatment detailed below. Hypernatremia triggers intense thirst in healthy humans,19 infants,1,2,20 and in individuals with Down 1) Dehydration and negative water balance Syndrome1 to protect against cellular dehydration. (hypovolemia): The hypovolemic variant of Nausea, vomiting, and falls and weakness are common hypernatremia (or more commonly referred to as symptoms of severe hypernatremia in patients “hypernatremic dehydration”) is associated with a presenting to an emergency department.21 Other negative water balance and results from either on September 25 2021 neurological symptoms associated with hypernatremia significant fluid losses (i.e. urine, sweat, or include lethargy, weakness, irritability, drowsiness, gastrointestinal losses), inadequate water intake or a hyperreflexia, involuntary muscle twitching, spasticity, likely combination of both. In one study, 82% of seizures, and coma.6,11,22 Hyperthermia1,5 fever, hypernatremic patients admitted to the hospital were tachycardia, tachypnea, and mild leukocytosis may also volume depleted.22 This suggests that hypovolemic be associated with acute hypernatremia.6 Body weight hypernatremic is the dominant variant seen in sick loss exceeding 10% of birth weight has been useful in individuals who lose disproportionately more water the diagnosis of breastfeeding-associated neonatal than they can replace.22 Hypernatremic dehydration hypernatremia,10,23 except during the first week of life from excessive fluid losses is typically associated with where weight loss is expected and false positives occur.23 high gastrointestinal fluid losses12 or sweat losses29,30 coupled with nausea and vomiting, which would Pathophysiology preclude voluntary fluid intake in response to osmotic In a simplistic description of a highly complex and and/or volemic-driven thirst. overlapping spectrum of fluid and sodium imbalance, the development of hypernatremia can be broadly The most common cause of hypernatremic categorized into: hypovolemic (negative fluid balance), dehydration, however, is inadequate fluid intake. euvolemic (stable body water), and hypervolemic Unsuccessful breastfeeding10,11,31 coupled with parental (positive fluid balance) variants. Proper identification of inability to suspect poor hydration status31,32 has led to the associated variant of hypernatremia is important morbidity and mortality in infants during the first two when considering the most appropriate treatment as weeks of life. Severe hypovolemic hypernatremia with 177 VOL 29, NO 3 SUMMER 2016 CLINICAL LABORATORY SCIENCE FOCUS: THE SECRET STORIES OF SODIUM osmotic demyelination has also been documented in a ingested for six days.18 Hypernatremic dehydration is 19-year old asylum seeker whereas no food or fluid was also seen in mentally and physically handicapped Downloaded from http://hwmaint.clsjournal.ascls.org/ Figure 1. Schematic diagram of the pathophysiology of hypernatremia. See text for more information regarding the pathophysiology corresponding to the circled numbers. on September 25 2021 Figure 2. Examples of the underlying etiologies of hypernatremia. See text for more information regarding the pathophysiology corresponding to the circled numbers. VOL 29, NO 3 SUMMER 2016 CLINICAL LABORATORY SCIENCE 178 FOCUS: THE SECRET STORIES OF SODIUM Downloaded from http://hwmaint.clsjournal.ascls.org/ Figure 3. Treatment of hypernatremia categorized by underlying pathophysiology. See text for more information regarding the pathophysiology corresponding to the circled