Sodium Disorders II

Hypernatremia (>145 mEq/L)

Cause

• Excess Na intake or excess water loss

• ↑ Osmolality → water shifts ICF → ECF

Clinical Effects

• ↓ Brain volume

• Risk of cerebral vein rupture → focal intracerebral hemorrhage

• Possible irreversible neurologic damage

Correction Goal

• Target Na <145 mEq/L

• Max correction rate: 10–12 mEq/L/day

Hypernatremia – Symptoms

• Mild: lethargy, weakness, confusion, restlessness, irritability

• Moderate: twitching

• Severe: seizures, coma, death (usually acute Na >160 mEq/L)

• Other: orthostatic hypotension, tachycardia, dry mucous membranes, ↓ skin turgor, ↑ or ↓ urine output

Hypernatremia – Labs

• Serum Na >145 mEq/L

• Urine Na and/or urine osmolality may help determine cause

Hypernatremia – Risk Factors

• Hospitalized (iatrogenic), ICU

• Elderly or infants

• Tube feeding

• Diabetic non-ketotic hyperglycemia

• GI disorders

• Renal dysfunction

• Diabetes insipidus

Treatment & Limits of Correction of Severe Hypernatremia

Severe hypernatremia = plasma Na⁺ >150 mmol/L

Duration	Related Condition / Cause	Clinical Features	Initial Therapeutic Goal	Limit of Correction / Overcorrection Risk
Minutes–Hours (Acute)	• Acute salt poisoning (accidental ingestion, suicide attempt) • Hypertonic saline administration • Dialysis errors	• Seizures • Coma • Hypertonia • High fever • Intracranial hemorrhage • Dural sinus thrombosis	Rapid infusion of 5% dextrose in water (D5W) ± Emergency hemodialysis→ Immediate restoration of normonatremia	Excessive correction NOT known to be harmful
1–2 days	• Unreplaced urinary water losses • Glycosuria • Neurogenic or nephrogenic diabetes insipidus	• Persistent coma • Brain demyelination	Lower plasma Na⁺ by ~2 mmol/L/hour → Until Na⁺ reaches 145 mmol/L, then stop or replace ongoing losses	Excessive correction NOT known to be harmful
Unknown or ≥2 days	Children: diarrhea, inability to breast-feed Adults: hypodipsia, impaired mental status	• Obtundation or coma • Rehydration-associated seizures • Cerebral edema(esp. children)	Children: ↓ Na⁺ by 0.3 mmol/L/hour Adults: ↓ Na⁺ by ≤10 mmol/L/day → Replace water losses	Children: avoid ↓ Na⁺ >0.5 mmol/L/hour ⚠ Use 3% saline if seizures occur with rehydration ⚠ Adults: risk of overcorrection unclear

Treatment Algorithm

Hypovolemic Hypernatremia

• Most common cause of hypernatremia

• Primary problem: water loss >>> sodium loss

Causes

• Renal losses

  • Loop diuretics

  • Osmotic diuresis (mannitol, glucose)

  • Postoperative diuresis

  • High-output acute tubular necrosis

  • Intrinsic renal disease

• Extrarenal losses

  • GI losses

  • Cutaneous losses (burns, excessive sweating)

Physiologic Effects

• TBW ↓↓

• TBNa ↓

Laboratory Findings

• Renal losses → UOsm high, UNa high

• Non-renal losses → UOsm high, UNa low

Clinical Presentation

• Orthostasis

• Hypotension

• Tachycardia

Treatment

• 0.9% NaCl until vital signs stable, then free water replacement

Hypovolemic Hypernatremia – Treatment

• Rapid development (<48 hours)

  • Can correct more rapidly

  • Correction rate: 1–2 mEq/L/hr

• Chronic hypernatremia

  • Correct slowly to prevent cerebral edema

  • Vital signs unstable (low BP, tachycardia)

    • Give 0.9% NaCl first to restore volume and stabilize patient

    • Then switch to hypotonic fluids

  • Vital signs stable

    • Start hypotonic fluids:

      • D5W

      • 0.2% NaCl

      • 0.45% NaCl

    • More hypotonic fluid → slower infusion rate

Rate of Correction: Equations

• Hypernatremia due to water loss

• Do NOT memorize the equation

• Know TBW fraction:

  • Men: 60% (0.6)

  • Women: 50% (0.5)

  • Elderly (>60 yrs): 45% (0.45)

Free Water Deficit

• Formula:

  • Free water deficit (L) =

  • (% total body water) × (weight, kg) × [(Current Na / Ideal Na) − 1]

Expected Change in Serum Sodium

• Per liter of infusate:

  • ΔNa (mEq/L) =

  • (Infusate Na − Serum Na) ÷ (TBW + 1)

Practice: Calculate Free Water Deficit

• Patient

  • 55-yo male, 86 kg

  • Light-headed, dehydrated after working outdoors in heat

  • No access to water

  • Meds: HCTZ 25 mg, lisinopril 10 mg

• Vitals

  • BP 89/54, HR 121, Temp 97.4°F, O₂ 94% RA

• Labs

  • Na 156, K 5.3, Cl 102, CO₂ 24

  • SCr 2.2, BUN 35, glucose 119

Calculation

• TBW = 0.6

• Free water deficit:

  • 0.6 × 86 × [(156 / 140) − 1]

  • ≈ 6 L

Treatment

• Start 0.9% NaCl until vital signs stabilize

• Then switch to 0.45% NaCl

Euvolemic Hypernatremia

• Pure water loss exceeds sodium loss

  • Classically due to diabetes insipidus

• Extrarenal free water loss

  • Increased insensible losses

Characteristics (Euvolemic / Isovolemic)

• Water & Sodium: Water loss only

• Causes:

  • Congenital or acquired diabetes insipidus (DI)

  • Nephrogenic DI

• Effect on TBW: ↓

• Effect on TB Na: ↔

• Laboratory:

  • Renal: UOsm low, UNa variable

  • Non-renal: UOsm high, UNa variable

• Clinical Presentation:

  • Depends on severity: lethargy, seizures

• Treatment:

  • Free water replacement

  • Vasopressin

Treatment Principles

• Treat underlying cause of free water loss

• Replace:

  • Free water deficit

  • Ongoing losses

  • Daily maintenance needs

• Diabetes insipidus

  • Discontinue offending agents

  • Initiate pharmacotherapy

Diabetes Insipidus

• Inadequate ADH secretion (central) OR

• Renal tubules unresponsive to ADH (nephrogenic)

Clinical Manifestations

• Polyuria

• Polydipsia

• Nocturia

• Urine output: 3–18 L/day

• Urine specific gravity: < 1.005

• Urine osmolality: < 200 mOsm/kg

Euvolemic Hypernatremia – Treatment

• Free access to water or D5W

• Correct serum Na slowly

  • Rate: 0.5 mEq/L/hr

  • Max correction: 10–12 mEq/L/day

  • Goal: prevent cerebral edema

Treatment of Diabetes Insipidus

• Remove underlying cause if possible

• Central DI

  • Replace ADH

  • Desmopressin 5–20 mcg intranasal q12–24h

• Chronic cases

  • Pharmacologic therapy as needed

  • Lithium-induced DI → treat with amiloride

Drug-Induced Diabetes Insipidus

Lithium = most common offender

• DI incidence with lithium: 15–87%

• Long-term lithium patients: ~12%

• Usually reversible

• Rarely fatal (only 3 reported deaths)

Mechanism

• Antagonizes adenylyl cyclase & cAMP

• Inhibits aquaporin channel opening in renal tubules

• Prevents water reabsorption in collecting duct

Euvolemic Hypernatremia – Diabetes Insipidus Treatment

Drug	Indication	Dose
Desmopressin acetate	Central and nephrogenic DI	5–20 mcg intranasal q12–24 h
Chlorpropamide	Central DI	125–250 mg PO daily
Carbamazepine	Central DI	100–300 mg PO BID
Clofibrate	Central DI	500 mg PO QID
Hydrochlorothiazide	Central and nephrogenic DI	25 mg PO q12–24 h
Amiloride	Lithium-induced nephrogenic DI	5–10 mg PO daily
Indomethacin	Central and nephrogenic DI	50 mg PO q8–12 h

Hypervolemic Hypernatremia

• Uncommon

• Caused by addition of sodium to the ECF

• Sodium gain > water gain

Causes

• Iatrogenic (most common)

• NaHCO₃ infusion

• Hypertonic saline infusion

• Salt tablets

• Hypertonic tube feedings

• Hypertonic dialysate

• Sodium-containing medications

• Hyperalimentation (TPN)

• Cushing’s syndrome

• Ingestion of sea water

• Hypertonic dialysis

Physiology

• ↑ Total body water (TBW)

• ↑↑ Total body sodium (TBNa)

Laboratory Findings

• Urine osmolality: high

• Urine sodium: high

Clinical Presentation

• Peripheral edema

• Pulmonary edema

• Variable blood pressure

Treatment

• Free water AND loop diuretics

• Loop diuretics alone are not sufficient

• May require hemodialysis to remove excess volume

Classifications of Hypernatremia

Feature	Hypovolemic	Euvolemic (Isovolemic)	Hypervolemic
Water & Sodium	Water loss >>> sodium loss	Water loss only	Sodium gain > water gain
Causes	DiureticsOsmotic diuresisPost-op diuresis	Diabetes insipidus (central or nephrogenic)Primary polydipsia	Na overload (3% NaCl, NaHCO₃, salt tablets, tube feedings)
Effect on TBW	↓↓	↓	↑
Effect on TBNa	↓	↔	↑↑
Laboratory	UOsm highUNa high (renal)UNa low (non-renal)	DI: UOsm lowUNa variable	UOsm highUNa high
Clinical Presentation	OrthostasisHypotensionDry mucous membranes	Neurologic symptoms (seizures, lethargy)	Peripheral/pulmonary edemaVariable BP
Treatment	0.9% NaCl first until stableThen free water replacement	Free water replacementVasopressin for DI	Free water + loop diureticMay require dialysis

Patient

• 31-year-old male

• Bipolar disorder

• Lithium increased from 200 mg BID → 400 mg BID

• Now has polyuria and polydipsia

Labs

• Na 154

• K 4.1

• Cl 115

• CO₂ 22

• BUN 16

• SCr 1.1

• Glucose 110

Question
What is the best treatment option?

Answer Choices

• A. Stop lithium, give one-time amiloride

• B. Decrease lithium back to 200 mg BID, start amiloride daily

• C. Stop lithium, give D5W

• D. Continue lithium, give furosemide

Decrease lithium back to 200 mg BID, start amiloride daily

Patient

• 83-year-old female

• Recently discharged for SIADH

• On NaCl 1 g TID for 1 week

• Now thirsty, retaining water, gained 5 lb

Labs

• Na 149

Question
What is the best treatment option?

Answer Choices

• A. Decrease NaCl to 1 g once daily

• B. Stop NaCl, give amiloride

• C. Stop NaCl, encourage free water, give furosemide

• D. Stop NaCl, give desmopressin

Stop NaCl, encourage free water, give furosemide