Learning Objectives: Disorders of Sodium Homeostasis

Pseudohyponatremia

occurs with markedly elevated lipids or proteins when indirect potentiometry is used

direct ion-selective electrodes (blood gas analyzers)

are not affected by lipid/protein interference

serum osmolality

What is normal in pseudohyponatremia?

measured vs calculated osmolality

What shows a gap in pseudohyponatremia?

-hyperlipidemia

-hyperproteinemia

-multiple myeloma

What are the causes of pseudohyponatremia?

serum sodium

What is low in pseudohyponatremia?

plasma water sodium

What is normal in pseudohyponatremia?

serum osmolality is normal

How is pseudohyponatremia different from hypotonic hyponatremia?

management of pseudohyponatremia

-address underlying lipid/protein disorder

-avoid unnecessary sodium correction

hyperglycemia

is the most frequent cause of hypertonic hyponatremia

corrected sodium

distinguishes dilutional hyponatremia from true hyponatremia

limiting correcting to prevent osmotic demyelination

What do both the European and US guidelines for managing hyponatremia emphasize?

≤ 8-12 mEq/L

The US guidelines recommend correcting sodium no more than ___________ in the first 24 hrs.

≤ 10 mEq/L

European guidelines recommend correcting sodium ________ in 24 hrs.

≤ 18 mEq/L

European guidelines recommend correcting sodium __________ in 48 hrs.

hypertonic saline

European guidelines recommend earlier use of ____________ for severe symptomatic hyponatremia.

Diabetes insipidus

inadequate AVP secretion (central) or renal resistance (nephrogenic)

Desmopressin (DDAVP)

acts as AVP analog, increasing water reabsorption in collecting ducts

-serum sodium

-urine osmolality

-urine output

What do you monitor when managing tx of diabetes insipidus with DDAVP?

hyponatremia due to water retention

What is the risk with overtreatment in diabetes insipidus with DDAVP?

-SSRIs

-Cabamazepine

-Cyclophosphamide

-Vincristine

-MDMA

-Antipsychotics

-NSAIDs

What are the common culprits that are most likely to cause drug-induced SIADH?

Mechanisms of drug-induced SIADH

-increase AVP release

-increase renal sensitivity to AVP

-direct vasopressin agonist activity

Demeclocycline

induces nephrogenic diabetes insipidus, reducing renal response to AVP

Tolvaptan

is a V2 vasopressin receptor antagonist that increases aquaresis

-serum sodium

-liver function tests (Tolvaptan)

-urine output

-neurologic status

What is monitored with Demeclocycline and Tolvaptan when managing tx of SIADH?

overly rapid sodium correction -> osmotic demyelination

What are the risks of using Demeclocycline or Tolvaptan in the tx of SIADH?

hepatotoxicity

What are the risks of using Tolvaptan in the tx of SIADH?

Thiazides

impair urinary dilution by blocking sodium reabsorption in the distal convoluted tubule while preserving concentrating ability

within 1-2 weeks thiazide therapy but may occur later

When does thiazide-induced hyponatremia usually develop?

thiazide-induced hyponatremia

increased AVP activity and water intake worsen hyponatremia

dx of thiazide-induced hyponatremia

-hx of thiazide use

-hypotonic hyponatremia with euvolemic or hypovolemic findings

discontinue thiazide, restrict free water intake, give isotonic saline if hypovolemic

How do you manage thiazide-induced hyponatremia?

hypertonic saline or vasopressin antagonists with careful monitoring

How do you manage severe cases of thiazide-induced hyponatremia?

heart failure, cirrhosis, nephrotic syndrome

What are the causes of hypervolemic hyponatremia?

patho of hypervolemic hyponatremia

sodium/water retention plus AVP-driven water reabsorption → dilutional hyponatremia

fluid and sodium restriction, loop diuretics, vasopressin antagonists

How do you treat hypervolemic hyponatremia?

-daily weights

-serum sodium

-neurologic symptoms

What do you monitor with hypervolemic hyponatremia?

275-290 mOsm/kg

What is the normal serum osmolality?

effective osmoles

-sodium

-glucose

bc it crosses cell membranes freely

Why is BUN not an effective osmole?

2.3 g/day

What is the normal daily sodium requirement and typical in take in adults and children ≥ 13 in the US?

1.8 g/day

What is the normal daily sodium requirement and typical in take in ages 9-13 yrs in the US?

1.2 g/day

What is the normal daily sodium requirement and typical in takes in ages 4-8 yrs in the US?

exceeds

The typical US intake often _________ the recommended sodium intake.

RAAS

increases sodium reabsorption via aldosterone

Sympathetic activation

increases tubular sodium reabsorption

natriuretic peptides

oppose sodium retention

kidney

is the primary regulator of sodium balance

hypertension

Excess sodium intake contributes to:

high sodium intake

is associated with increased risk of cardiovascular events and progression of CKD

causes of hypernatremia

-diabetes insipidus

-osmotic diuresis

-GI water loss

-burns

-excess sodium admin (hypertonic saline, sodium bicarb)

hypernatremia

causes intracellular dehydration and brain shrinkage

clinical manifestations of hypernatremia

-confusion

-neuromuscular irritability

-seizures

-risk of intracranial hemorrhage

10-12 mEq/L per day

When correcting hypernatremia correction should not exceed _________

cerebral edema and neurologic injury

What dose overly rapid correction of hypernatremia cause?

Tolvaptan and Conivaptan

block V2 receptors, causing aquaresis without sodium loss

SIADH, Cirrhosis, HF

What are the indications for vasopressin receptor antagonists in hyponatremia management?

-overly rapid correction

-hepatotoxicity (Tolvaptan)

What are the risks with vasopressin receptor antagonists (vaptans) in hyponatremia management?

hypertonic saline in symptomatic hyponatremia

-Reserved for severe, symptomatic hyponatremia (e.g., seizures, coma).

-Dose and infusion rate must be carefully calculated

2-4 hrs

How often should serum sodium be monitored in hypertonic saline tx in symptomatic hyponatremia?

most chronic, asymptomatic euvolemic or hypervolemic hyponatremia cases

When is fluid restriction the first line therapy in hyponatremia?

< 1-1.5 L/day

What is the fluid restricted to in hyponatremia when fluid restriction is used as first line tx?

patient adherence and ongoing AVP activity

What does the effectiveness depend on when using fluid restriction in first line therapy for hyponatremia?