II-18. Sodium (Na+) and water balance disorders

ナトリウム（Na+）と水分平衡の異常

Body Fluid Compartments, Osmolality & Tonicity

ECF and ICF differ in electrolyte composition but have equal solute concentration (cell membrane is water-permeable)
Tonicity (effective osmolality) is set by impermeable solutes (Na⁺); permeable solutes (urea, ethanol) do not alter tonicity; glucose raises tonicity at high concentrations
Changes in plasma Na⁺ → hyper-/hypo-osmolar states; changes in total body water → volume depletion/expansion

Effects on cells

Hypertonicity: cell shrinkage, cytoskeletal damage, DNA breaks, apoptosis
Hypotonicity: cells can rupture
Defense by release/uptake of organic osmolytes (glutamate, taurine); the CNS is especially vulnerable (BBB permeable to water but not Na⁺); astrocytes take up taurine and swell to protect neurons

Hypernatremia (Na⁺ > 145 mmol/L) — always hypertonic

Mild 145–150, moderate 150–160, severe >160 mmol/L

Hypovolemic (hypotonic fluid loss — free water lost > Na⁺)

Renal: osmotic diuresis (diabetes), loop diuretics, diabetes insipidus (central/nephrogenic — usually euvolemic)
Extra-renal: sweating, burns, GI loss; insufficient intake (hypodipsia)

Euvolemic

Diabetes insipidus, sweating, hyperventilation

Hypervolemic

Hyperaldosteronism, Cushing (cortisol → aldosterone-like effect + inhibits ADH), iatrogenic salt infusion, salt/seawater ingestion

Consequences (mainly neurological, from cell dehydration)

Thirst; anorexia, weakness, restlessness, nausea; ↑neuromuscular excitability/hyperreflexia
Abrupt onset or >160: brain shrinkage → intracranial hemorrhage, confusion, coma, seizures; chronic → reversible encephalopathy

Treatment

Treat the cause; enteral hydration if moderate/slowly developing; quick correction if Na⁺ >150 and duration ≤1–2 days using 5% glucose; avoid rapid correction of chronic hypernatremia (cerebral edema, herniation, seizures)

Hyponatremia (Na⁺ < 135 mmol/L) — usually hypoosmotic

Mild 130–135, moderate 120–130, severe <120 mmol/L

Hypovolemic (salt loss > water loss)

Renal: osmotic diuresis, thiazides, salt-wasting nephropathy, mineralocorticoid deficiency
Extra-renal: burns, GI loss, intestinal obstruction; cerebral salt wasting (BNP from damaged brain)

Euvolemic

SIADH (ADH independent of osmotic/volume stimuli), intense exercise, water intoxication (>1 L/h; psychosis), beer-drinker’s hyponatremia, glucocorticoid deficiency

Hypervolemic (fluid retention with low effective volume → ↑ADH)

Heart failure, hepatic cirrhosis, nephrotic syndrome, acute/chronic renal failure

Consequences

Acute: hypotonicity → cerebral edema, ↑ICP, impaired cerebral flow, brainstem herniation, seizures (glutamate release)
Chronic: personality changes, lethargy; osteoporosis (Na⁺ drawn from bone → osteoclast activation)

Treatment

Hypovolemic: isotonic (0.9%) saline; hypervolemic: fluid restriction + diuretics + ADH antagonists; euvolemic: treat cause; SIADH: salt tablets + water restriction
Severe/rapid (<121 mmol/L with neuro symptoms): cautious hypertonic (3%) saline, slow/partial — too-fast correction → osmotic demyelination syndrome (“locked-in”)

Water & Sodium Balance Regulation

Water intake: regulated by thirst (hypothalamic osmoreceptors, baroreceptors, ANGII)
Water excretion: regulated by ADH (osmoreceptors, baroreceptors, nausea); unregulated insensible loss
Na⁺ excretion: regulated by RAAS/aldosterone (↑Na⁺ reabsorption, ↑K⁺ excretion in collecting duct); no proven regulation of Na⁺ intake (salt hunger only in Addison’s)
Fluid therapy by site of deficit: colloids (intravascular), isotonic saline/Ringer (ECF), 5% glucose (total body water); volume expansion → treat cause, diuretics, sometimes mechanical removal (paracentesis)

一問一答

▶What sets tonicity (effective osmolality) of body fluids?

Impermeable solutes, mainly Na⁺; permeable solutes (urea, ethanol) do not alter tonicity, while glucose raises it at high concentrations.

▶What are the cellular effects of hypertonicity vs hypotonicity?

Hypertonicity causes cell shrinkage, cytoskeletal damage, DNA breaks, and apoptosis; hypotonicity can cause cells to rupture.

▶Why do ECF and ICF have equal solute concentration despite different composition?

The cell membrane is freely water-permeable, so water shifts until osmotic concentrations equalize.

▶How do cells defend against tonicity changes, and why is the CNS vulnerable?

By releasing/taking up organic osmolytes (glutamate, taurine); the CNS is especially vulnerable because the BBB is permeable to water but not Na⁺ (astrocytes take up taurine and swell to protect neurons).

▶How is hypernatremia defined and graded?

Na⁺ >145 mmol/L (always hypertonic): mild 145–150, moderate 150–160, severe >160 mmol/L.

▶What are the renal vs extra-renal causes of hypovolemic hypernatremia?

Renal: osmotic diuresis (diabetes), loop diuretics, diabetes insipidus; extra-renal: sweating, burns, GI loss, and insufficient intake (hypodipsia).

▶What are the hypervolemic causes of hypernatremia?

Hyperaldosteronism, Cushing (cortisol → aldosterone-like effect + inhibits ADH), iatrogenic salt infusion, and salt/seawater ingestion.

▶What are the neurological consequences of hypernatremia?

Thirst, anorexia, weakness, restlessness, nausea, ↑neuromuscular excitability/hyperreflexia; abrupt onset or >160 causes brain shrinkage → intracranial hemorrhage, confusion, coma, seizures.

▶How is hypernatremia treated and what must be avoided?

Treat the cause; enteral hydration if moderate/slow; quick correction with 5% glucose if Na⁺ >150 and duration ≤1–2 days; avoid rapid correction of chronic hypernatremia (risk of cerebral edema, herniation, seizures).

▶How is hyponatremia defined and graded?

Na⁺ <135 mmol/L (usually hypoosmotic): mild 130–135, moderate 120–130, severe <120 mmol/L.

▶What are the causes of hypovolemic hyponatremia?

Renal: osmotic diuresis, thiazides, salt-wasting nephropathy, mineralocorticoid deficiency; extra-renal: burns, GI loss, intestinal obstruction, and cerebral salt wasting (BNP from damaged brain).

▶What are the euvolemic causes of hyponatremia?

SIADH (ADH independent of osmotic/volume stimuli), intense exercise, water intoxication (>1 L/h; psychosis), beer-drinker's hyponatremia, and glucocorticoid deficiency.

▶What are the hypervolemic causes of hyponatremia?

Heart failure, hepatic cirrhosis, nephrotic syndrome, and acute/chronic renal failure (fluid retention with low effective volume → ↑ADH).

▶What are the acute consequences of hyponatremia?

Hypotonicity → cerebral edema, ↑ICP, impaired cerebral flow, brainstem herniation, and seizures (glutamate release).

▶What are the chronic consequences of hyponatremia?

Personality changes, lethargy, and osteoporosis (Na⁺ drawn from bone → osteoclast activation).

▶How is hyponatremia treated by volume status?

Hypovolemic: isotonic (0.9%) saline; hypervolemic: fluid restriction + diuretics + ADH antagonists; euvolemic: treat cause; SIADH: salt tablets + water restriction.

▶Why must severe hyponatremia be corrected slowly?

Too-fast correction (e.g., of <121 mmol/L with neuro symptoms) causes osmotic demyelination syndrome ("locked-in"); use cautious, slow/partial hypertonic (3%) saline.

▶How are water intake and water excretion regulated?

Water intake by thirst (hypothalamic osmoreceptors, baroreceptors, ANGII); water excretion by ADH (osmoreceptors, baroreceptors, nausea), plus unregulated insensible loss.

▶How is Na⁺ excretion regulated, and is Na⁺ intake regulated?

Na⁺ excretion is regulated by RAAS/aldosterone (↑Na⁺ reabsorption, ↑K⁺ excretion in collecting duct); there is no proven regulation of Na⁺ intake (salt hunger only in Addison's).

▶How is fluid therapy chosen by the site of deficit?

Colloids for intravascular space, isotonic saline/Ringer for ECF, and 5% glucose for total body water.