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1
Question:

A 37-year-old man is admitted to the hospital due to a 10-day-history of fever, nonproductive cough, and dyspnea on exertion.  The patient has a history of HIV infection for 10 years and has been noncompliant with medications.  Temperature is 38.5 C (101.3 F), blood pressure is 120/80 mm Hg, pulse is 102/min, and respirations are 20/min.  Pulse oximetry shows 90% on room air and 96% on 2 L/min oxygen.  BMI is 20 kg/m2.  Physical examination reveals bilateral lung crackles and chest x-ray reveals bilateral interstitial infiltrates.  The patient is started on appropriate antibiotics and intravenous normal saline at 150 mL/hr.  Two days later, his dyspnea is improved but he develops confusion.  Repeat vital signs are as follows:  Temperature is 37.5 C (99.5 F), blood pressure is 118/80 mm Hg, pulse is 84/min, and respirations are 16/min.  Mucous membranes are moist.  There is no jugular venous distension.  Lung examination reveals better air entry with reduction of crackles.  Heart sounds are normal.  There is no peripheral edema.  Laboratory studies from the day of admission and today are as follows:

Serum chemistryAdmissionToday
    Sodium132 mEq/L124 mEq/L
    Potassium4.2 mEq/L3.8 mEq/L
    Chloride94 mEq/L98 mEq/L
    Bicarbonate24 mEq/L22 mEq/L
    Blood urea nitrogen12 mg/dL10 mg/dL
    Creatinine1.0 mg/dL0.8 mg/dL
    Calcium9.0 mg/dL8.6 mg/dL
    Glucose96 mg/dL94 mg/dL

Total intravenous intake of normal saline since admission is ~5 L.  Which of the following is the most likely cause of this patient's hyponatremia?

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Explanation:

Hyponatremia

Serum osmolality

ECV

Urine findings

Cause

Low
(<275 mOsm/kg)

Hypovolemic

UNa <40 mEq/L

  • Nonrenal salt loss (eg, vomiting, diarrhea, dehydration)

UNa >40 mEq/L

  • Renal salt loss (eg, diuretics, primary adrenal insufficiency)

Euvolemic

UOsm <100 mOsm/kg

  • Psychogenic polydipsia
  • Beer potomania

UOsm >100 mOsm/kg & UNa >40 mEq/L

  • SIADH (rule out hypothyroidism, secondary adrenal insufficiency)

Hypervolemic

Variable

  • CHF, hepatic failure, nephrotic syndrome

Normal

Variable

  • Pseudohyponatremia (eg, paraproteinemia, hyperlipidemia)

High
(>295 mOsm/kg)

  • Hyperglycemia
  • Exogenous solutes (eg, mannitol)

CHF = congestive heart failure; ECV = extracellular volume; SIADH = syndrome of inappropriate antidiuretic hormone; UNa = urine sodium; UOsm = urine osmolality.

This patient with HIV, who has fever, nonproductive cough, and dyspnea following a period of medication noncompliance, likely has Pneumocystis pneumonia (PCP).  His initial laboratory studies show hyponatremia (<135 mEq/L), which worsens after receiving a large amount of normal saline (NS) over 2 days.  The serum osmolality (SOsm) and extracellular fluid volume status are important considerations in determining the etiology of hyponatremia.

In this patient, low SOsm - calculated using the formula: (2 × serum sodium [mEq/L]) + (serum glucose [mg/dL]/18) + (serum blood urea nitrogen [mg/dL]/2.8) = 257 mOsm/kg H2O - in the setting of clinical euvolemia (eg, moist mucous membranes, absence of jugular venous distension) is consistent with the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Two processes likely contributed to this patient's worsening hyponatremia:

  • Pulmonary pathology (eg, PCP) is a common precipitant of SIADH, and patients with HIV are particularly prone to SIADH.
  • In patients with SIADH, ongoing receipt of NS can result in net free water retention (if urine osmolality exceeds the osmolality of NS [~310 mOsm/kg H2O]); because sodium handling by the kidney is intact and the patient is euvolemic, all of the solute from each 1 L of NS is excreted in <1 L of urine (water in > water out), which worsens hyponatremia.

(Choice A)  Dilutional hyponatremia with appropriately suppressed antidiuretic hormone secretion can occur due to excess free water intake (eg, psychogenic polydipsia).  The kidneys respond appropriately with excretion of very dilute urine (<100 mOsm/kg H2O); however, the capacity to excrete water becomes overwhelmed and euvolemic hyponatremia develops.  This patient has no evidence of excessive free water intake; the free water content in ~5 L of normal saline is not high enough to cause significant dilutional hyponatremia in the absence of SIADH; and pulmonary pathology is commonly associated with SIADH (not suppressed antidiuretic hormone secretion).

(Choice B)  Effective arterial blood volume (EABV) depletion with secondary hyperaldosteronism can lead to hypovolemic hyponatremia in patients with volume depletion or hypervolemic hyponatremia in patients with cirrhosis or heart failure.  However, EABV depletion is very unlikely in this normotensive patient with evidence of clinical euvolemia.

(Choices C and E)  Inappropriate diuretic use leading to excessive renal losses of salt and water is a potential cause of factitious hyponatremia.  Hyponatremia may also occur due to other causes of total body volume depletion (eg, diarrhea, poor oral intake).  In these cases, evidence of hypovolemia (eg, dry mucous membranes, decreased skin turgor, serum blood urea nitrogen/creatinine ratio >20) should be present.

Educational objective:
Pulmonary pathology may lead to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which is characterized by hypotonic hyponatremia in a euvolemic patient.  Infusion of normal saline may worsen hyponatremia in patients with SIADH.