NaCl

**Basics** - Ionic compound: Na+ is the major extracellular cation, Cl- the major extracellular anion. Plasma [Na+] is ~135-145 mEq/L and [Cl-] ~95-105 mEq/L. - Na+ is the main determinant of plasma osmolality (Posm ≈ 2[Na+] + glucose/18 + BUN/2.8) and of ECF volume. Na+ is actively pumped out of cells by the Na+/K+-ATPase.

**IV fluid formulations** - 0.9% NaCl (normal saline, NS): isotonic, 154 mEq/L Na+ and Cl-, ~308 mOsm/L. It stays in the ECF, so about 1/4 remains intravascular and 3/4 goes interstitial. Uses: hypovolemia, hemorrhage (with blood products), DKA, hypercalcemia, and as the fluid given with blood transfusions. - Large-volume NS causes **hyperchloremic (non-anion gap) metabolic acidosis** through bicarbonate dilution and renal HCO3- loss. Balanced crystalloids such as lactated Ringer's are an alternative. - 0.45% NaCl (half-normal saline): hypotonic. It is used for maintenance fluids and free-water deficit (hypernatremia). It can cause hemolysis or cerebral edema if overused. - 3% NaCl: hypertonic (~1027 mOsm/L). It is used for severe symptomatic hyponatremia (seizures, coma) and for raised ICP. - Correction limit is **≤8-10 mEq/L in 24 h** (typically 4-6 mEq/L initially). - Overcorrection causes **osmotic demyelination syndrome** (central pontine myelinolysis). Features are dysarthria, dysphagia, quadriparesis, and "locked-in" syndrome, appearing 2-6 days later. - 5% dextrose in 0.45% NaCl (D5 ½NS) is a common maintenance fluid. - Isotonic saline also treats hyponatremia from hypovolemia, but it can worsen SIADH, where the urine osmolality is higher than that of the saline and water is retained while Na+ is excreted.

**Physiology/renal handling** - About 65% of filtered Na+ is reabsorbed in the proximal tubule. Thick ascending limb: NKCC2, which loop diuretics block. DCT: NCC, which thiazides block. Collecting duct: ENaC, which aldosterone upregulates and amiloride/triamterene block. - ADH controls water balance, and the RAAS controls Na+ balance and volume. - Sweat chloride: CFTR defect in cystic fibrosis causes elevated sweat Cl- (>60 mEq/L), which is diagnostic.

**Clinical associations** - Hyponatremia is classified by volume status and serum osmolality: hypovolemic, euvolemic (SIADH, psychogenic polydipsia, hypothyroidism, adrenal insufficiency), and hypervolemic (CHF, cirrhosis, nephrotic syndrome). - Hypernatremia: diabetes insipidus and free-water loss. Treat with hypotonic fluids and correct slowly to avoid cerebral edema. - Dietary salt excess contributes to hypertension. - Oral rehydration solution uses Na+-glucose cotransport (SGLT1) in the gut. - Normal saline is used to flush lines, in nebulized form (hypertonic saline for bronchiolitis/CF), and in the saline infusion test for primary aldosteronism. - Saline-responsive (chloride-responsive) metabolic alkalosis: vomiting, diuretics. Urine Cl- <20 mEq/L. It improves with NaCl and volume repletion. Saline-resistant causes include hyperaldosteronism and Bartter/Gitelman syndromes, which have urine Cl- >20 mEq/L.

**High-yield pearls** - NS = isotonic and doesn't shift water into or out of cells. Hypertonic saline pulls water out of cells (it shrinks cells). Hypotonic fluid causes water to enter cells. - Hyperchloremic acidosis is a non-anion gap acidosis (normal AG).