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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 4  |  Issue : 3  |  Page : 266-270

Hypernatremia: A systems-based approach


1 Department of Internal Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
2 Department of Nephrology, Lehigh Valley Health Network, Allentown, Pennsylvania, USA
3 Department of Internal Medicine, St. Luke's University Health Network, Bethlehem, Pennsylvania, USA

Date of Submission26-Feb-2018
Date of Acceptance10-May-2018
Date of Web Publication24-Dec-2018

Correspondence Address:
Dr. Sudip Nanda
Department of Internal Medicine, St. Luke's University Health Network, 801 Ostrum Street, Bethlehem, Pennsylvania, 18015
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJAM.IJAM_8_18

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  Abstract 


Hypernatremia is a commonly encountered disorder in hospitalized patients in which the plasma sodium concentration exceeds 145 mM. The clinical approach to hypernatremia is often challenging for clinicians, as the underlying pathophysiology is complex and serious complications can result from its improper management. As such, the purpose of this manuscript is to provide the reader with a systematic clinical approach to the diagnosis and management of patients with hypernatremia.
The following core competencies are addressed in this article: Patient care, Medical knowledge.

Keywords: Clinical approach, diagnosis, hypernatremia, sodium, systems based


How to cite this article:
Noto JG, Bollu R, Sturzoiu T, Nanda S. Hypernatremia: A systems-based approach. Int J Acad Med 2018;4:266-70

How to cite this URL:
Noto JG, Bollu R, Sturzoiu T, Nanda S. Hypernatremia: A systems-based approach. Int J Acad Med [serial online] 2018 [cited 2019 Jul 15];4:266-70. Available from: http://www.ijam-web.org/text.asp?2018/4/3/266/248335




  Introduction Top


Hypernatremia is a disorder of water balance in which the plasma sodium concentration (PNa) exceeds 145 mM.[1] It is present in approximately 1% of hospitalized patients and is associated with a mortality rate as high as 42%.[2] The clinical approach to hypernatremia is often challenging for clinicians, as symptoms are nonspecific and improper management can lead to devastating complications. The objective of this article is to present a systematic clinical approach to the diagnosis and management of patients with hypernatremia.

Vignette

An 81-year-old man presents with a 4-day history of severe nausea, vomiting, and decreased fluid intake. He has a medical history of hypertension, hyperlipidemia, congestive heart failure, and dementia. His home medications include furosemide, metoprolol, lisinopril, and atorvastatin. He is afebrile with a heart rate of 86/min, blood pressure of 110/80 mmHg, respiratory rate of 16/min, and oxygen saturation of 98% on room air. On physical examination, he is obtunded, the abdomen is soft and nontender, the skin turgor is diminished, the mucus membranes are dry, and the neck veins are flat. A chest X-ray, electrocardiogram, and complete blood count are within normal limits. The PNa is 155 mM and the potassium concentration is 4.1 mM. The body weight is 70 Kg. How would you approach this patient's hypernatremia?

Plasma sodium regulation

The PNa is regulated through changes in water balance.[3] For the PNa to remain within the normal range of 135–145 mM, water intake and output must be equal. In response to a rising PNa, osmoreceptor neurons in the hypothalamus signal the brain areas of thirst and arginine vasopressin (AVP) secretion.[4] Thirst increases water intake by stimulating water ingestion and AVP decreases water output by increasing water reabsorption in the renal collecting tubule. Together, these lead to the retention of water and lowering of the PNa[Table 1].[5] Any pathological process which limits water intake or increases water output may elevate the PNa.
Table 1: Plasma sodium regulation

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Pathogenesis

Hypernatremia is the result of hypotonic fluid loss, pure water loss, or hypertonic sodium gain that is sufficient enough to overwhelm the hypothalamic osmoregulatory system.[1] Excessive fluid loss may occur through the renal, gastrointestinal, integumentary, or respiratory system.[5] The underlying mechanism of fluid loss will determine whether it is pure water or hypotonic fluid. Hypertonic sodium gain is either iatrogenic or due to excessive NaCl ingestion. The mechanisms of fluid loss and sodium gain are outlined in [Table 2].[6],[7],[8],[9],[10],[11],[12],[13],[14],[15]
Table 2: Pathogenesis of hypernatremia

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The effect of each basic cause of hypernatremia on fluid compartment volumes is illustrated in [Figure 1].[16],[17],[18] Pure water loss increases the extracellular osmolality causing water to flow out of cells until the intracellular and extracellular osmolality are equal. As a result, pure water loss derives its volume proportionately from the total body water (1/3 extracellular and 2/3 intracellular). Since the majority of total body water is intracellular, the effect on extracellular fluid volume (ECFV) is minimal. Therefore, pure water loss results in euvolemic hypernatremia. Hypotonic fluid loss depletes sodium and water from the extracellular fluid. The compensatory osmotic shift is less because sodium is lost in addition to water. The ECFV is depleted to a greater extent in these cases resulting in hypovolemic hypernatremia. Hypertonic sodium gain adds sodium and water to the extracellular fluid, which expands the ECFV resulting in hypervolemic hypernatremia.[18]
Figure 1: Effect of Hypernatremia on Body Fluid Compartment VolumesICF=intracellular fluid, ECF=extracellular fluid, TBW=total body water, AQP=aquaporin

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Clinical presentation

Hypernatremia always causes hypertonicity of the extracellular fluid and plasma. This leads to an osmotic efflux of water from cells and a decrease in cell volume [Figure 1].[18] As the brain is particularly sensitive to changes in cell volume, the symptoms of hypernatremia are primarily neurologic. Symptoms include restlessness, irritability, muscle twitching, and in severe cases coma or death.[19] In acute hypernatremia, brain shrinkage is mitigated by the uptake of electrolytes such as Na+, K+, and Cl through cell membrane transporters. This increases the intracellular osmolality leading to an osmotic influx of water and partial normalization of brain cell volume. In the chronic setting, brain volume is further normalized by the uptake and synthesis of organic osmolytes such as amino acids, polyols, and methylamines.[19],[20] Due to these differences, the symptoms of hypernatremia tend to be more severe when the rise in PNa occurs rapidly.[19]

History and physical examination

A complete history is essential in patients with hypernatremia. In every case, the presence or absence of thirst as well as access to water should be noted. In hypernatremia due to excessive-free water loss, the history should focus on identifying the source. Water loss may occur through the renal, gastrointestinal, integumentary, or respiratory system.[5] Depending on the source, symptoms such as polyuria, vomiting, diarrhea, excessive sweating, or hyperventilation may be present. Sodium gain is usually iatrogenic, but may also be due to excessive NaCl intake.[1] A complete differential diagnosis is shown in [Table 3].
Table 3: Differential diagnosis of hypernatremia

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A complete physical examination is crucial in patients with hypernatremia. In every case, a complete neurological examination should be performed as acute changes in PNa may lead to serious brain injury. The focus of the physical examination is the determination the ECFV. Assess the mucus membranes, skin turgor, neck veins, blood pressure (orthostatic), and lung sounds. [Table 4] describes the pertinent physical examination findings in each form of hypernatremia.[1],[3] Pure water loss derives most of its volume from the intracellular fluid and does not typically present with the clinical signs of ECFV depletion until the PNa is >160 mM.[3]
Table 4: Physical examination in hypernatremia

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Laboratory data

Laboratory data will confirm the findings of the history and physical examination [Table 5].[3],[21] Assess the plasma osmolality, urine osmolality (UOsm), and urine sodium concentration (UNa). As the kidneys seek to minimize water loss, hypernatremia normally leads to the secretion of AVP and concentration of the urine.[3],[4] If the UOsm is <300 mOsm/kg in the setting of hypernatremia, central or nephrogenic diabetes insipidus (DI) is the most likely cause.[22] An increase in UOsm following the administration of synthetic AVP (1-deamino-8-D-arginine vasopressin) will occur only in central DI but not in nephrogenic DI.[3],[22]
Table 5: Laboratory testing in hypernatremia

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To delineate between the remaining possible causes of hypernatremia, evaluate the UNa.[21] The UNa is a reflection of the ECFV.[23] Hypotonic fluid loss decreases the ECFV, leading to the retention of sodium and a UNa<20 mM. An exception to this rule is if the kidneys are the source of hypotonic fluid loss. In these cases, the UNa will be >20 mM. Pure water losses do not always have a significant effect on the ECFV, and the UNa is variable in these cases. Hypertonic sodium gain expands the ECFV, and the kidneys respond by excreting excess sodium.[21] In these cases, the UNa is >20 mM and will usually be >100 mM.[14],[15]

Treatment

In all cases of hypernatremia, treatment is to remove the underlying cause and administer-free water until the PNa returns to normal. Oral rehydration is recommended, but if this is not feasible, the use of hypotonic intravenous fluids is appropriate. Normal saline is only indicated in hypernatremia to restore a depleted ECFV in cases of frank circulatory compromise.[1],[12] A step-wise approach to the use of intravenous hypotonic fluids is outlined in [Table 6] and is discussed in detail below.[1],[24]
Table 6: Treatment of hypernatremia

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The clinical scenario will determine the type, amount, and rate of intravenous fluid infusion. Pure water losses should be replaced with 5% dextrose in water (D5W) because dextrose is rapidly metabolized and pure water remains. Hypotonic fluid losses should be replaced with hypotonic saline solutions because there is both a water and sodium deficit in these cases. Hypertonic sodium gain should be treated with a combination of furosemide and D5W. Furosemide induces renal hypotonic fluid loss and D5W replaces it with pure water, lowering the ECFV, and the PNa simultaneously.[1]

The administration of 3 mL/kg bodyweight of electrolyte-free water will lower the PNa by approximately 1 mM in the absence of ongoing fluid losses.[24] If a solution is not completely electrolyte free, a greater volume is needed. For example, 6 mL of ½ normal saline are needed to provide 3 mL of electrolyte-free water because the solution is only one-half electrolyte free.

During the correction of chronic hypernatremia (duration >2 days), accumulated intracellular organic osmolytes are slowly extruded from the brain. Inappropriately rapid correction will cause an osmotic influx of water into brain cells leading to cerebral edema. If the duration of hypernatremia is >2 days or unknown, the correction rate should not exceed 10 mM/day.[24],[25] In acute cases, of 1–2 days duration, it is safe to correct at a rate of 2 mM/h because accumulated intracellular electrolytes are rapidly extruded from the brain.[24] In cases of hypernatremia due to acute salt poisoning over the course of minutes to hours, rapidly lowering the PNa with D5W infusion may be necessary.[14],[24]


  Conclusions Top


We opened with the case of an 81-year-old man with hypovolemic hypernatremia secondary to upper gastrointestinal hypotonic fluid loss and decreased water intake. Since this patient has a hypotonic fluid deficit, the use of intravenous hypotonic saline is recommended. To restore normonatremia, this patient's PNa needs to be lowered by 10 mM. To accomplish this, 3 mL × 70 kg × 10 mM = 2.1 L of free water are needed. To avoid causing cerebral edema, this deficit should be replenished over the course of 24 h.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Ethical conduct of research

This research did not require ethical approval because it did not involve human or animal participants.



 
  References Top

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Hall JE. The Body Fluid Compartments: Extracellular and Intracellular Fluids. Edema. Guyton and Hall Textbook of Medical Physiology. 13th ed. Philadelphia, PA: Elsevier; 2016. p. 305-21.  Back to cited text no. 10
    
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Shapiro M, Weiss JP. Diabetes Insipidus: A review. J Diabetes Metab 2012;S6:9.  Back to cited text no. 11
    
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Bhave G, Neilson EG. Body fluid dynamics: Back to the future. J Am Soc Nephrol 2011;22:2166-81.  Back to cited text no. 16
    
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Day RE, Kitchen P, Owen DS, Bland C, Marshall L, Conner AC, et al. Human aquaporins: Regulators of transcellular water flow. Biochim Biophys Acta 2014;1840:1492-506.  Back to cited text no. 17
    
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Feig PU, McCurdy DK. The hypertonic state. N Engl J Med 1977;297:1444-54.  Back to cited text no. 18
    
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Verbalis JG. Brain volume regulation in response to changes in osmolality. Neuroscience 2010;168:862-70.  Back to cited text no. 19
    
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Strange K. Cellular volume homeostasis. Adv Physiol Educ 2004;28:155-9.  Back to cited text no. 20
    
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Kumar S, Berl T. Sodium. Lancet 1998;352:220-8.  Back to cited text no. 21
    
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Miller M, Dalakos T, Moses AM, Fellerman H, Streeten DH. Recognition of partial defects in antidiuretic hormone secretion. Ann Intern Med 1970;73:721-9.  Back to cited text no. 22
    
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Rose BD, Post TW. Meaning and application of urine chemistries clinical physiology of acid-base and electrolyte disorders. 5th ed. New York: McGraw-Hill, Medical Pub. Division; 2001. p. 405-14.  Back to cited text no. 23
    
24.
Sterns RH. Disorders of plasma sodium – Causes, consequences, and correction. N Engl J Med 2015;372:55-65.  Back to cited text no. 24
    
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Blum D, Brasseur D, Kahn A, Brachet E. Safe oral rehydration of hypertonic dehydration. J Pediatr Gastroenterol Nutr 1986;5:232-5.  Back to cited text no. 25
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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