12.2 Electrolyte Disorders
Key Takeaways
- Hyponatremia is categorized by volume status (hypo-/eu-/hypervolemic) and reflects excess free water relative to sodium; hypernatremia reflects free-water deficit (or sodium gain) with impaired thirst or access to water.
- Acute K+ shifts into cells are driven by insulin, β2-agonists, and alkalosis; shifts out occur with acidosis, hyperosmolarity, and cell lysis—distinct from total-body K+ depletion or overload.
- Magnesium depletion causes refractory hypokalemia and hypocalcemia (impaired PTH release/action); always correct Mg2+ when K+ will not rise.
- Calcium–phosphate balance is governed by PTH (↑ bone resorption, ↑ renal Ca reabsorb, ↑ 1α-hydroxylase) and 1,25-(OH)2-vitamin D (↑ gut Ca/PO4 absorption).
- Bartter mimics loop diuretics (NKCC2), Gitelman mimics thiazides (NCC), and Liddle is ENaC gain-of-function (hypertension, low aldosterone, hypokalemia).
12.2 Electrolyte Disorders
Quick Answer: Classify sodium disorders by plasma osmolality and volume (hypo/eu/hypervolemic hyponatremia; hypernatremia = free-water deficit). Separate potassium shifts (insulin, β2-agonists, pH) from total-body K+ changes. Use the PTH–vitamin D axis for Ca/PO4, correct Mg2+ in refractory hypokalemia, and match Bartter/Gitelman/Liddle to NKCC2/NCC/ENaC.
Electrolyte questions almost always hide a volume, acid–base, or hormone clue. Translate the vignette into: (1) water vs sodium balance, (2) shift vs total body store, (3) which transporter or hormone is mis-set.
Plasma Sodium and Body Water
Plasma [Na+] is the main determinant of plasma osmolality (Posm ≈ 2[Na+] + glucose/18 + BUN/2.8 in common clinical units). Hyponatremia usually means relative excess free water; hypernatremia means relative free-water deficit (or, less often, pure Na+ gain).
Normal plasma Na+ is about 135–145 mEq/L. Symptoms (confusion, seizures) correlate more with acuity and degree than with a single cutoff; chronic adaptive lowering of brain osmolytes means overly rapid correction of chronic hyponatremia risks osmotic demyelination, while delayed correction of severe acute hyponatremia risks cerebral edema—clinical management details vary, but the physiology of brain water is the tested concept.
Hyponatremia by Volume Status
| Category | Effective volume | ADH? | Examples | Urinary Na+ (typical teaching) |
|---|---|---|---|---|
| Hypovolemic | Low (true volume depletion) | Yes (baroreceptor) | GI losses + hypotonic replacement; skin losses; diuretics | Low if extrarenal losses; high if renal Na+ loss (diuretics, salt wasting) |
| Euvolemic | Clinically normal / mild ↑ TBW | Yes (inappropriate or non-osmotic) | SIADH, severe hypothyroidism, glucocorticoid deficiency, psychogenic polydipsia (ADH off if pure primary polydipsia) | High in SIADH (often >40 mEq/L) with high Uosm |
| Hypervolemic | High total body Na+ and water; low effective arterial blood volume in HF/cirrhosis | Yes (low EABV) | Heart failure, cirrhosis, nephrosis; also advanced CKD with water intake | Low in HF/cirrhosis (secondary hyperaldosteronism); variable in renal failure |
SIADH pattern (classic): euvolemic hyponatremia, Posm low, Uosm inappropriately high (e.g., >100 mOsm/kg), urine Na+ not low, normal thyroid/adrenal, and no diuretic. Pathophysiology is ADH-driven free-water reabsorption plus mild volume expansion that increases natriuresis.
Pseudohyponatremia (normal Posm with extreme hyperlipidemia/hyperproteinemia in older assays) and translocational hyponatremia (high glucose or mannitol drawing water into plasma) must be separated from true hypo-osmolar hyponatremia. Corrected Na+ rises ~1.6 mEq/L for each 100 mg/dL glucose above normal in common teaching formulas (some use 2.4)—the exact coefficient is less important than recognizing hyperglycemia lowers measured Na+ by dilution.
Hypernatremia
Hypernatremia ([Na+] >145 mEq/L) means the patient has a free-water deficit relative to sodium, or rarely iatrogenic Na+ gain (hypertonic saline/NaHCO3). Intact thirst and access to water usually prevent sustained hypernatremia; thus hospital patients, infants, and elders with impaired thirst or access dominate vignettes.
| Mechanism | Water balance | Examples |
|---|---|---|
| Hypotonic fluid loss | TBW ↓ > Na+ ↓ | Osmotic diuresis (glucose, mannitol), loop diuretics, GI losses, burns |
| Pure water loss | TBW ↓ | Central or nephrogenic diabetes insipidus, insensible losses |
| Sodium gain | Na+ ↑ | Hypertonic NaHCO3, salt poisoning, seawater |
In DI, large volumes of dilute urine persist; desmopressin distinguishes central (responds) from nephrogenic (does not). Lithium is a classic cause of nephrogenic DI via AQP2/pathway impairment.
Potassium: Shifts vs Total-Body Balance
Normal plasma K+ is about 3.5–5.0 mEq/L, but only ~2% of total body K+ is extracellular. Small shifts produce large concentration changes.
Transcellular Shifts (Rapid)
| Shift K+ into cells (↓ serum K+) | Shift K+ out of cells (↑ serum K+) |
|---|---|
| Insulin (stimulates Na/K-ATPase) | Insulin deficiency |
| β2-agonists (Na/K-ATPase) | β-blockers (lesser effect) |
| Alkalosis | Acidosis (especially mineral acidosis; organic acidosis less shift) |
| Periodic paralysis (hypokalemic, channelopathies) | Hyperosmolarity (solvent drag), succinylcholine, digoxin toxicity, cell lysis (rhabdo, tumor lysis) |
Exam trap: catecholamine surge or albuterol can drop measured K+ without large total-body depletion. Conversely, succinylcholine or acute mineral acidosis can raise K+ acutely.
Total-Body Potassium Disorders
Hypokalemia causes (total body ↓): GI loss (diarrhea—metabolic acidosis + low K+), skin loss, poor intake (rare alone), and renal loss driven by mineralocorticoid excess, diuretics (loop/thiazide), Bartter/Gitelman, hypomagnesemia, and ampphotericin-like tubular injury. Renal K+ wasting often shows high transtubular K+ gradient / high urine K+ while depleted.
Hyperkalemia causes (total body ↑ or redistribution + impaired excretion): AKI/CKD, hypoaldosteronism (type 4 RTA pattern), K+-sparing drugs (spironolactone, eplerenone, amiloride, triamterene), ACEI/ARB, trimethoprim (ENaC block), NSAIDs, and massive load/lysis.
Aldosterone and distal Na+ delivery are the twin requirements for K+ secretion: principal cells reabsorb Na+ via ENaC (lumen-negative potential) and secrete K+ via ROMK. Low distal delivery (volume depletion, HF) or ENaC blockade reduces K+ secretion.
Magnesium
Normal serum Mg2+ is roughly 1.7–2.2 mg/dL. Most filtered Mg2+ is reabsorbed in the TAL (paracellular, driven by NKCC2-dependent lumen-positive potential); DCT handles finer regulation.
Hypomagnesemia causes: GI loss, alcohol use, PPIs, loop/thiazide diuretics, calcineurin inhibitors, EGF pathway defects, and Gitelman (DCT Mg wasting). Clinical importance:
- Refractory hypokalemia — K+ will not correct until Mg2+ is repleted (ROMK disinhibition when Mg is low promotes K+ secretion).
- Hypocalcemia — impaired PTH secretion and end-organ resistance.
- Neuromuscular irritability, torsades risk with severe depletion.
Hypermagnesemia is usually iatrogenic (Mg infusions, antacids) in the setting of reduced GFR; it causes diminished reflexes, bradycardia, and hypotension at high levels.
Calcium–Phosphate–PTH–Vitamin D Axis
| Hormone | Source / activation | Main effects |
|---|---|---|
| PTH | Parathyroid (chief cells); stimulated by low Ca2+, high PO4, low 1,25-D | ↑ bone resorption; ↑ renal Ca2+ reabsorption (DCT); ↓ renal PO4 reabsorption (PCT NPT2a internalization); ↑ 1α-hydroxylase → 1,25-(OH)2D |
| 1,25-(OH)2-vitamin D | Kidney 1α-hydroxylase | ↑ intestinal Ca2+ and PO4 absorption; feedback suppresses PTH |
| FGF23 | Osteocytes | ↓ renal PO4 reabsorption; ↓ 1,25-D (phosphate economy) |
| Calcitonin | C cells | Minor acute ↓ bone resorption in humans (less CBSE-central) |
Hypocalcemia patterns: hypoparathyroidism (low PTH, high PO4), vitamin D deficiency (low/normal Ca, low/normal PO4, high PTH—secondary hyperparathyroidism), CKD (low 1,25-D, high PO4, high PTH), pancreatitis, citrate binding, and hungry bone syndrome.
Hypercalcemia patterns: primary hyperparathyroidism (high/inappropriately normal PTH, high/normal Ca, low/normal PO4), PTHrP malignancy (PTH low), osteolytic mets, excess 1,25-D (granulomatous disease, lymphoma), milk-alkali, thyrotoxicosis, and thiazides (reduce urinary Ca).
Phosphate: Hyperphosphatemia from renal failure, massive lysis, or hypoparathyroidism; hypophosphatemia from refeeding, hungry bone, hyperparathyroidism, FGF23 excess (tumor-induced osteomalacia, XLH), and phosphate binders.
Thiazides decrease urinary calcium (useful in stone formers with hypercalciuria); loops increase urinary calcium (can cause hypocalcemia with prolonged use).
Genetic Transporter Lesions vs Diuretic Sites
These syndromes are pure mechanism questions—treat them as “endogenous diuretic” or “ENaC stuck on.”
| Disorder | Defect | Mimics | BP | K+ | Acid–base | Other |
|---|---|---|---|---|---|---|
| Bartter | TAL: NKCC2, ROMK, ClC-Kb, etc. | Loop diuretic | Low/normal | ↓ | Metabolic alkalosis | Hypercalciuria; may see nephrocalcinosis; high renin/aldosterone |
| Gitelman | DCT: NCC | Thiazide | Low/normal | ↓ | Metabolic alkalosis | Hypomagnesemia; hypocalciuria |
| Liddle | ENaC gain-of-function | Opposite of amiloride | Hypertension | ↓ | Metabolic alkalosis | Low renin and aldosterone; responds to amiloride, not spironolactone |
| Apparent mineralocorticoid excess / 11β-HSD2 deficiency | Cortisol activates MR | Mineralocorticoid excess | HTN | ↓ | Alkalosis | Low renin/aldosterone |
| Primary hyperaldosteronism | Adrenal aldosterone excess | — | HTN | ↓ | Alkalosis | Low renin, high aldosterone |
Distinguishing Bartter vs Gitelman (exam favorite): both have normotensive hypokalemic metabolic alkalosis with high renin/aldosterone, but Gitelman has prominent hypomagnesemia and hypocalciuria (thiazide-like), whereas classic antenatal/severe Bartter more often shows hypercalciuria (loop-like).
Liddle vs hyperaldosteronism: both hypertensive hypokalemic alkalosis, but Liddle has suppressed aldosterone and responds to ENaC blockade (amiloride/triamterene), not mineralocorticoid receptor blockade alone as the primary fix.
Integrated Approach on Exam Day
- Na+: Is Posm low? What is volume status? Is ADH expected or inappropriate?
- K+: Is this a shift (insulin, pH, β-agonist, lysis) or total-body change (kidney vs gut, aldosterone state)?
- Mg2+: Is refractory hypokalemia/hypocalcemia present?
- Ca/PO4: Draw PTH direction and whether vitamin D or FGF23 logic fits.
- Genetic/diuretic: Name the transporter before naming the syndrome.
Connect each answer back to the nephron map from section 12.1—electrolyte disorders are applied renal physiology, not free-standing lists.
A euvolemic patient has plasma Na+ 122 mEq/L, low plasma osmolality, urine osmolality 520 mOsm/kg, and urine Na+ 55 mEq/L. Thyroid and adrenal tests are normal. Which mechanism best explains the hyponatremia?
Which intervention is most likely to lower serum potassium within minutes primarily by shifting K+ into cells rather than by increasing total-body potassium excretion?
A normotensive adolescent has hypokalemia, metabolic alkalosis, high plasma renin and aldosterone, hypomagnesemia, and low urinary calcium. Which nephron lesion best fits?