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5 Pearls on Hyponatremia Diagnostics

Core IM

This podcast from CORE IM offers five pearls of knowledge covering Hyponatremia Diagnostics.

First, listen to the podcast. After listening, ACP members can take the CME/MOC quiz for free.

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Up to 1 AMA PRA Category 1 Credits ™ and MOC Points
Expires February 10, 2024   active

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Free to Members

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Podcasts and Audio Content

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Core IM

Welcome to Core IM, a virtual medical community! Core IM strives to empower its colleagues of all levels and backgrounds with clinically applicable information as well as inspire curiosity and critical thinking. Core IM promotes its mission through podcasts and other multimodal dialogues. ACP has teamed up with Core IM to offer continuing medical education, available exclusively to ACP members by completing the CME/MOC quiz.

Pearl 1 - General Approach

  • Hyponatremia is a significant clinical problem:
    • MC electrolyte disorder, occurring in up to 30% of hospitalized patients
    • May result from:
      • Underlying medical conditions such as heart failure, liver failure, renal insufficiency, GI losses and SIADH 
      • Medications such as loop, thiazide, K-sparing diuretics, RAS-acting agents, ADH-stimulating drugs
    • Mild chronic hyponatremia associated with more frequent falls, which may be related to gait and attention impairments which have also been observed.
  • Understand what each diagnostic test adds vs. rote dependence on algorithm
  •  H&P – may be helpful, but don’t ignore other objective data that contradicts!
    • History:
      • Quickly assess for red flags (confusion, seizures) → immediate intervention, ICU admission
      • Ask about dietary history, fluid/EtOH intake, new meds, endocrine ROS, relevant comorbidities
    • Physical Examination:
      •  Volume status is theoretically helpful as diagnostic algorithms hinge on it, but error prone
  • Our approach focuses on understanding what each diagnostic test adds vs. rote dependence on algorithm
    • More helpful given that most hyponatremia in the hospital is multifactorial
    • Ask yourself where your patient with hyponatremia is on “Cartesian space” with:
      • ADH secretion, as indirectly measured by UOsm relative to
      • Effective arterial blood volume (EABV), as estimated based on clinical examination and measurement of urine sodium
  • What if we encounter a patient after intervention, and without complete labs?
    • Still obtain appropriate serum and urine studies as you can assess response to interventions (urine output, change in urine concentration and serum sodium) and the patient’s current ADH/EABV state

Pearl 2 – Serum Osmolality (Nl value 280-285 mOsm/kg)

  • We expect patients with true hyponatremia to have a low osmolality (<275 mOsm/kg)
    • This makes sense because sodium is the most significant contributor to osmolality SOsm= 2 [Na+] + [Glu]/18 + [BUN]/2.8
  • Serum osmolality can be thought of as a “quality check” to verify the hypothesis that low sodium is accompanied by low osmolality, as it should be.
    • If osmolality is normal assess if the patient has high triglycerides or a paraproteinemia (ex. Multiple myeloma, recent IVIG administration)
      • Such cases referred to as “pseudohyponatremia” – laboratory artifact that results on assumption that aqueous component of blood is 93%, with 7% serum particles (high lipids or extra protein changes this ratio)
      • Serum osmolality isn’t subject to this error (whole blood sample)
      • This type of “hyponatremia” is not of clinical significance
  • If osmolality is elevated (usually >280-285), or if normal osmolality without elevated proteins/lipids, go looking for extra osmoles, either measured or unmeasured!
  • Serum osmolality assessment prompts us to consider effective and ineffective osmoles at play:
    • Effective osmoles (sodium, glucose, potassium) do not cross the plasma membrane, and therefore cause shifts in water movement (have tonicity)
      • Ineffective osmoles (ethanol, urea, lactate) cross the plasma membrane more readily, and therefore do not cause shifts in water movement (do not have tonicity)
  • Sodium and other effective osmoles, such as glucose do not cross the plasma membrane readily, and therefore cause shifts in water movement.
    • Most of the clinical complications that arise as a result of hyponatremia (and its correction) are driven by the fact that sodium is an effective osmole – it impacts tonicity, and therefore cell size.
  • Serum osmolarity is not a serially measured lab!
    • Measure it once unless you are following clearance of an unmeasured osmole (such as a toxic alcohol) or if there is a significant sodium change that is difficult to contextualize.

Pearl 3 – Urine Osmolality is a window into ADH activity

  • Urine osmolality (UOsm) is the nearest to a direct measure of ADH activity as we have in clinical practice (although copeptin has promise as a surrogate for ADH)

o   Range of possible urine osmolality in healthy kidneys is broad (50-1200 mOsm/kg)

o   ADH secretion results in resorption of free water in collecting duct, resulting in high urine Osm; ADH suppression results in low urine Osm

  •  If ADH is not active, dilute urine results (UOsm <100-200). Low urine osmolality on presentation is indicative of:
    • Too little solute to keep up with reasonable fluid intake (tea-toast syndrome) 
    • Too much fluid to keep up with reasonable solute intake (primary polydipsia)
    • Some combination of low solute and high intake of hypo-osmolar fluid (beer potomania)
    • Can also occur in the setting of acute illness, where many patients will push large volumes of hypotonic fluids (i.e. sports drinks) in the setting of GI losses
  • The story of hyponatremia is often the story of ADH activity; one study found that non-osmotic ADH release is present in 97% of patients with hyponatremia
    • ADH activity is reflected by UOsm >200-300 in patients with hyponatremia
    • ADH on? Next step is to figure out whether because of decreased EABV, increased osmolality, or independent of physiologic stimulus (see pearl 4 below)
  • Remember that renal insufficiency impacts our ability to maximally dilute urine
    • Hyponatremia may develop as a result of acute or chronic renal failure for this reason
    • Renal insufficiency limits our ability to interpret UOsm as a direct window into ADH activity
  • Change in UOsm (and urine output) can be assessed serially to determine response to treatment
    • If urine osmolality gently declines with volume resuscitation, this indicates that your intervention has resulted in suppression of ADH (proving hypothesis)
    • Heads up! If UOP and UOsm change dramatically in response to an intervention, this may be an early indicator a patient is correcting too quickly

Pearl 4 – Urine sodium, FeNa, FeUrea reveal RAAS activity

  • UOsm gives us a window into ADH activity at a given time – it does not tell us why ADH is activated.
    •  Physiologic or “appropriate” ADH activity can occur in the following circumstances:
      •  Hyperosmolarity (readily apparent when serum Osm >285 mOsm/kg)
      • Low sensed effective arterial blood volume (may be hypovolemic or hypervolemic)
    • ADH activity that is not stimulated by one of the above mechanisms is by definition inappropriate (may occur in SIADH, adrenal insufficiency, hypothyroidism)
  • Urine sodium is a window into activity of renin-angiotensin-aldosterone activity, which is more sensitive than ADH to low EABV states
    • Low EABV (hypovolemic or hypervolemic) → RAAS activation → UNa <20 mEq/L
    • SIADH → no RAAS activation → UNa >40
  •  In patients with intermediate UNa (20-40 mEq/L), FeNa (and especially FeNa + FeUrea) is more sensitive for reflecting low EABV
    • FeNa <1% indicates RAAS is active, low EABV
    • Validated in oliguric patients, less reliable in patients putting out large quantity of dilute urine
  • Caveats to UNa & FeNa use
    • Use of diuretics (thiazide or loop) increases UNa, in which case FeUrea <55% is a reasonable surrogate (and FeNa <0.5% + FeUrea < 55% better than either alone)
    • CKD impairs Na reabsorption, making UNa less helpful in this population
    • UNa will be low in patients with low Na diets (rare in US)

Pearl 5 – Urine uric acid is a tiebreaker for distinguishing between SIADH and other causes of hyponatremia

  • Expected characteristics of uric acid in SIADH:
    • Serum uric acid → low <4 mg/dL
    • Urine uric acid → high
    • FeUricAcid → high >12%
  • FeUricAcid may be a more helpful diagnostic test when trying to distinguish between causes of hyponatremia with low EABV and normal/elevated EABV (UCr X SUricAcid / SCr x UUricAcid x 100)
    • Patients with saline-responsive hyponatremia (increase Na by 5 mmol/L with 2L NS) have significantly lower FeUricAcid compared with saline non-responders (P<0.01)

 

Contributors

Shreya Trivedi, MD - Editor, Host

Martin Fried, MD - Editor, Host

Timothy Rowe, MD - Editor, Host

Jeffery William, MD - Guest Expert

John Hwang, MD - Guest Expert

Sean Burke, MD - Editor

Clem Lee, MD - Editor

Reviewers

Helbert Rondon, MD, MS, FACP, FASN, FNKF

Larissa Kruger Gomes, MD

None of the individuals in control of content for this educational activity have relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

Release Date: February 10, 2021

Expiration Date: February 10, 2024

CME Credit

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the American College of Physicians and the Core IM.  The American College of Physicians is accredited by the ACCME to provide continuing medical education for physicians.

The American College of Physicians designates each enduring material (podcast) for 1 AMA PRA Category 1 Credit™.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1 medical knowledge MOC Point in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program.  Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

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After listening to the podcast, complete a brief multiple-choice question quiz. To claim CME credit and MOC points you must achieve a minimum passing score of 66%. You may take the quiz multiple times to achieve a passing score.