A basic blood panel reports your sodium, potassium, chloride and bicarbonate on every line, and a fuller one adds calcium, phosphate and magnesium. Each value is held in a narrow range, and each electrolyte imbalance has its own causes and dangers. This page explains sodium, potassium, calcium, phosphate, chloride and magnesium one at a time: where each ion is in your body, how your kidneys and hormones keep it in balance, and what happens when it runs too high or too low. The theme throughout is mass balance: what you take in must match what you lose, and where an ion sits matters as much as how much of it you have.
Electrolytes and how they are measured
You met electrolytes in the chemistry primer: substances that release ions when they dissolve, so the solution carries an electric current. In body fluids the important ones are sodium (Na+), potassium (K+), calcium (Ca2+), magnesium (Mg2+), chloride (Cl−), bicarbonate (HCO3−) and phosphate. As you saw in Body fluid compartments and water balance, the ECF is rich in sodium and chloride, and the ICF in potassium, magnesium and phosphate.
Lab reports use three kinds of unit. Millimoles per liter (mmol/L) count particles. Milliequivalents per liter (mEq/L) count charge: mmol multiplied by the size of the ion's charge. For calcium, phosphate and magnesium, many labs in the United States report milligrams per deciliter (mg/dL), a mass.
Worked example 1: converting a calcium result
Problem. A patient's total calcium is 10 mg/dL. Express it in mmol/L and in mEq/L. Calcium's atomic mass is 40.
- Convert to mg/L. A deciliter is 0.1 L, so 10 mg/dL = 100 mg/L.
- Convert to mmol/L. One millimole of calcium weighs 40 mg. 100 mg/L ÷ 40 mg/mmol = 2.5 mmol/L.
- Convert to mEq/L. Calcium carries two charges, so 2.5 mmol/L × 2 = 5 mEq/L.
Answer. 2.5 mmol/L, or 5 mEq/L. For sodium, potassium and chloride, which carry one charge each, mmol/L and mEq/L are the same number.
| Usual adult plasma range | Where most of the body's store is | Main hormones | |
|---|---|---|---|
| Sodium | 135–145 mmol/L | ECF | Aldosterone, ANP (amount); ADH and thirst (concentration) |
| Potassium | 3.5–5.0 mmol/L | Inside cells (about 98%) | Aldosterone; insulin and epinephrine move it into cells |
| Calcium (total) | 8.5–10.5 mg/dL (2.1–2.6 mmol/L) | Bone (about 99%) | PTH, calcitriol; calcitonin minor |
| Phosphate | 2.5–4.5 mg/dL (0.8–1.45 mmol/L) | Bone (about 85%), then cells | PTH, calcitriol |
| Chloride | 98–106 mmol/L | ECF | Follows sodium; none of its own |
| Magnesium | 1.7–2.2 mg/dL (0.7–0.9 mmol/L) | Bone (about 60%), then cells | No single main hormone; set mostly by the kidneys |
Ranges differ a little from lab to lab. Every electrolyte obeys the same two rules. Its external balance is intake against output: the kidneys adjust the output to match the intake. Its internal balance is its distribution between cells, bone and ECF. A plasma value can change through either one.
Sodium balance
You eat roughly 100 to 200 mmol of sodium a day, most of it as salt, and on a steady diet your urine carries almost the same amount out. That match is sodium balance: intake equals output, with the kidneys doing nearly all the adjusting. Sweat and feces carry only small amounts, unless you sweat heavily or have diarrhea.
Amount sets volume; concentration reflects water
Two different things are easy to confuse:
- The amount of sodium in your body sets your ECF volume. Sodium is held outside cells by the sodium–potassium pump, and water follows it. You saw in long-term blood pressure control that 100 mmol of extra sodium holds about 0.7 L of extra ECF. The RAAS, aldosterone, ANP and pressure natriuresis all control this amount.
- The concentration of sodium in your plasma, the number on a lab report, reflects the balance of water. The plasma osmolarity feedback loop, through ADH and thirst, holds it steady by adding or removing water.
So a patient can have too much total sodium and a low plasma sodium concentration at once, as in heart failure: the kidneys keep salt and water, and ADH makes them keep even more water.
Sodium and the anions that travel with it make up almost all the solute in the ECF. That gives a quick way to estimate plasma osmolality from a lab report.
Worked example 2: estimating plasma osmolality
Problem. A patient's sodium is 140 mmol/L, glucose 90 mg/dL and urea nitrogen 14 mg/dL. Estimate the plasma osmolality with: 2 × Na + glucose ÷ 18 + urea nitrogen ÷ 2.8. Then repeat with a glucose of 900 mg/dL.
- Sodium and its anions. Each sodium ion is matched by an anion, mainly chloride or bicarbonate, so count sodium twice: 2 × 140 = 280.
- Glucose. Dividing by 18 converts mg/dL to mmol/L: 90 ÷ 18 = 5.
- Urea. 14 ÷ 2.8 = 5.
- Add. 280 + 5 + 5 = 290 mOsm/kg, in the normal range.
- With glucose at 900. 900 ÷ 18 = 50, so 280 + 50 + 5 = 335 mOsm/kg.
Answer. About 290 mOsm/kg normally, and 335 with very high glucose. Glucose stays outside most cells when insulin is lacking, so it draws water out of them. That extra water dilutes the plasma sodium, which is why very high glucose lowers the measured sodium.
Urea is different. It crosses cell membranes, so a high urea raises the measured osmolality without drawing water out of cells. Only solutes that stay outside cells, like sodium and (without insulin) glucose, set tonicity.
Hyponatremia
Hyponatremia (hypo- = under, natr- = sodium, from natrium, its Latin name, -emia = blood condition) is a plasma sodium below 135 mmol/L. Below about 125 it is severe. It is the most common electrolyte disorder in hospital patients.
Take a runner who finishes a marathon after drinking at every station. She has sweated 2 L and drunk 4 L of water and sports drink, and her ADH has stayed high from the effort and nausea. She has gained water. Her sodium is 126 mmol/L. That is the key idea: hyponatremia is almost always a problem of too much water relative to sodium, not too little sodium. The causes sort by what has happened to the ECF volume:
- Low ECF volume: losing salt and water (vomiting, diarrhea, diuretics, especially thiazides) and replacing it with plain water. The fall in volume keeps ADH high, so the water is kept.
- Normal ECF volume: SIADH; drinking very large volumes; a diet so low in solute that the kidneys cannot excrete much water, as you saw in the last topic.
- High ECF volume: heart failure, liver cirrhosis and kidney failure. Salt and water are kept, and more water than salt.
Low plasma sodium usually means low ECF osmolality, so water moves into cells. Brain cells swell inside the rigid skull, causing headache, nausea, confusion, falls and, when severe or sudden, seizures, coma and death.
Over about two days, brain cells adapt. They release potassium and small organic solutes, so less water is drawn in and they return toward their normal size. That adaptation makes treatment tricky. If the plasma sodium of someone with long-standing hyponatremia is raised too fast, water rushes out of the adapted brain cells, and they are damaged; the myelin of the pons is especially at risk. This osmotic demyelination can cause paralysis and difficulty speaking and swallowing, days after the correction. So chronic hyponatremia is corrected slowly, by no more than about 8 to 10 mmol/L in the first 24 hours. Sudden, severe hyponatremia with seizures is different: the brain has not adapted, and small doses of 3% saline are given quickly.
Hypernatremia
Hypernatremia (hyper- = over) is a plasma sodium above 145 mmol/L. It almost always means a water deficit. Anyone who can feel thirst and reach water drinks long before the sodium climbs far, so it happens mainly to people who cannot: infants, frail older adults, and people who are unconscious or sedated. Diabetes insipidus, fever, sweating and very high glucose, which pulls water into the urine, add to the loss.
High ECF osmolality draws water out of cells. Brain cells shrink, causing intense thirst (if the person is awake), irritability, confusion, muscle twitching and seizures. As the brain shrinks, it pulls on its bridging veins, which can tear and bleed. Brain cells adapt to this too, by gaining solute, so chronic hypernatremia is also corrected slowly, with water given by mouth or as a dilute IV fluid. Correcting it too fast can let water rush into the adapted cells and swell the brain. This is well documented in infants and children, and less clearly in adults, but the usual advice is still to lower sodium by no more than about 10 mmol/L a day.
| Hyponatremia | Hypernatremia | |
|---|---|---|
| Plasma sodium | Below 135 mmol/L | Above 145 mmol/L |
| Usual underlying problem | Too much water for the sodium | Too little water for the sodium |
| Plasma osmolality | Usually low | High |
| Water movement | Into cells: brain cells swell | Out of cells: brain cells shrink |
| Typical causes | SIADH, thiazides, replacing losses with plain water, heart failure | No access to water, diabetes insipidus, fever and sweating |
| Main symptoms | Headache, nausea, confusion, seizures | Thirst, irritability, confusion, seizures |
| Danger of correcting a chronic case too fast | Osmotic demyelination | Brain swelling (shown mainly in children) |
Potassium balance
Your cells hold about 3,500 mmol of potassium; your whole ECF holds only about 60. So about 98% of your potassium is inside cells, and the plasma value reports only a sliver of it. Potassium balance has two parts, and both matter:
- Internal balance: the split between cells and ECF, which can change within minutes.
- External balance: intake of roughly 70 to 100 mmol a day against output, about 90% of it in urine and the rest in feces.
Worked example 3: why small shifts matter
Problem. A man's cells hold 3,500 mmol of potassium and his ECF is 14 L at 4.0 mmol/L. After a crush injury, damaged muscle releases 1% of his cell potassium into the ECF. What is his new plasma potassium, assuming none is excreted yet?
- Potassium released. 1% of 3,500 mmol = 35 mmol.
- Rise in concentration. 35 mmol ÷ 14 L = 2.5 mmol/L.
- New plasma potassium. 4.0 + 2.5 = 6.5 mmol/L.
Answer. About 6.5 mmol/L, a dangerous level, from moving just one hundredth of his cell potassium. The same arithmetic run backwards explains why an injection of insulin can lower plasma potassium within minutes.
Internal balance: moving potassium into and out of cells
After a meal, the potassium you absorb would raise your plasma potassium sharply if it stayed in the ECF. It doesn't, because the insulin released for the meal's glucose also stimulates sodium–potassium pumps, which move potassium into cells within minutes. The kidneys then excrete it over the next hours. Epinephrine does the same through beta-2 receptor proteins. Other shifts:
- Acid–base changes. When the ECF becomes more acidic, potassium tends to leave cells, raising plasma potassium; when it becomes more alkaline, potassium moves into cells. The shift is largest when the acid is a mineral acid, such as hydrochloric acid. Lactic acid and ketone bodies shift much less, as you will see with acid–base disorders.
- Cell damage. Crushed muscle, destroyed tumor cells and burst red blood cells release their potassium.
- Lack of insulin. In untreated type 1 diabetes, potassium leaves cells. Without insulin, the pumps move less of it in, and the very high glucose draws water out of cells, which carries potassium with it. So plasma potassium can be normal or high even while the body's total store is being lost in urine.
External balance: the kidneys
You saw in tubular transport that filtered potassium is mostly reabsorbed before the distal tubule, and that the potassium in your urine is secreted by principal cells in the last part of the distal tubule and the collecting duct. Three things raise that secretion:
- A high plasma potassium, directly and by stimulating aldosterone release from the zona glomerulosa. Aldosterone makes principal cells build more sodium channels, potassium channels and sodium–potassium pumps.
- More sodium and more fluid reaching the principal cells. More sodium entering them makes the lumen more negative, which pushes potassium out, and faster flow carries secreted potassium away. This is why loop and thiazide diuretics cause potassium loss.
- Alkalosis, which increases secretion.
Anything that lowers aldosterone or blocks its action reduces secretion: adrenal insufficiency, ACE inhibitors and potassium-sparing diuretics.
Hypokalemia and hyperkalemia
You met hypokalemia and hyperkalemia with the resting membrane potential. Potassium's gradient sets the resting potential, so both disorders act first on excitable cells, and the heart is where they kill.
- Hypokalemia (below 3.5 mmol/L): with less potassium outside, more leaks out of cells, so the resting potential becomes more negative. Skeletal muscle fibers are further from threshold and harder to excite, so they weaken. Heart cells behave differently: low potassium outside also lets less current through some of their potassium channels, so they repolarize more slowly (the flattened T wave and the U wave) and can fire extra beats. That is how hypokalemia causes arrhythmias.
- Hyperkalemia (above 5.0 mmol/L): the resting potential moves toward threshold. A small rise makes cells easier to excite. A larger, lasting rise keeps them partly depolarized, which inactivates voltage-gated sodium channels, so action potentials become smaller and slower, and cells become harder to excite.
| Hypokalemia | Hyperkalemia | |
|---|---|---|
| Plasma potassium | Below 3.5 mmol/L | Above 5.0 mmol/L |
| Effect on resting potential | More negative (hyperpolarized) | Less negative (depolarized) |
| Common causes | Vomiting, diarrhea, loop and thiazide diuretics, too much aldosterone, insulin treatment | Kidney failure, ACE inhibitors, potassium-sparing diuretics, adrenal insufficiency, cell damage, acidosis |
| Skeletal muscle | Weakness, cramps; severe: paralysis | Weakness; severe: paralysis |
| Smooth muscle | Slow gut, constipation | Little effect |
| ECG | Flattened T waves, an extra U wave after the T wave | Tall, peaked T waves; later a wide QRS complex |
| Deadly risk | Arrhythmias, worse in people taking digoxin | Ventricular fibrillation or cardiac arrest |
| Main treatment | Replace potassium, by mouth or slowly by vein | Calcium by vein to protect the heart, insulin with glucose to shift potassium into cells, then remove it (diuretics, binders, dialysis) |
Look at the hyperkalemia treatment row. IV calcium does not lower potassium at all. It raises the threshold of heart muscle cells, restoring the gap between rest and threshold and protecting the heart for 30 to 60 minutes, while insulin and glucose shift potassium into cells and the kidneys, binders or dialysis remove it.
Calcium and phosphate balance
About 99% of your calcium and about 85% of your phosphate are in bone, as hydroxyapatite. Most of the rest of the phosphate is inside cells, in ATP, nucleic acids and membrane phospholipids. Calcium and phosphate balance is the matching of intake, absorption by the intestine, exchange with bone and excretion by the kidneys, so that plasma calcium and phosphate stay in range. You met its controllers with the thyroid and parathyroid glands:
- PTH, released when calcium falls: releases calcium and phosphate from bone, makes the kidneys keep calcium and excrete phosphate, and switches on calcitriol. Net effect: calcium up, phosphate down.
- Calcitriol: raises absorption of both calcium and phosphate from food. Net effect: both up.
- Calcitonin: inhibits osteoclasts and lowers calcium, but its effect in adults is small.
Only the free calcium counts
Calcium in plasma exists in three forms (Figure 3). About half is ionized (free) calcium, the only form that crosses membranes, acts on nerves and muscle, and is sensed by the parathyroid glands. About 40% is bound to plasma proteins, mainly albumin, and about 10% is bound to small anions such as phosphate and citrate.
Two consequences follow:
- Albumin changes the total. A patient with low albumin, from liver disease or malnutrition, has less bound calcium, so the total calcium reads low while the ionized calcium may be normal.
- pH changes the free fraction. In alkalosis, albumin gives up hydrogen ions and binds more calcium, so ionized calcium falls. A person who hyperventilates during a panic attack blows off CO2, the blood becomes more alkaline, and they feel tingling around the mouth and in the fingers, the same signs as hypocalcemia, although their total calcium is normal.
Worked example 4: adjusting calcium for a low albumin
Problem. A malnourished patient has a total calcium of 7.6 mg/dL and an albumin of 2.0 g/dL (normal about 4.0). A common bedside estimate is: adjusted calcium = measured calcium + 0.8 × (4.0 − albumin). Is his calcium really low?
- Albumin shortfall. 4.0 − 2.0 = 2.0 g/dL.
- Calcium that shortfall would have bound. 0.8 × 2.0 = 1.6 mg/dL.
- Adjusted calcium. 7.6 + 1.6 = 9.2 mg/dL.
- Compare. 9.2 is within 8.5 to 10.5.
Answer. The adjusted value is about 9.2 mg/dL, which suggests the low total may just reflect low albumin. But the formula is only an estimate, and it misclassifies patients most often in exactly this setting, a very low albumin, sometimes hiding a real hypocalcemia. When the answer matters, the lab measures ionized calcium directly.
Hypocalcemia and hypercalcemia
You met both with the thyroid and parathyroid glands. Low extracellular calcium lets voltage-gated sodium channels open more easily, so nerves and muscles become overexcitable; high calcium does the reverse.
| Hypocalcemia | Hypercalcemia | |
|---|---|---|
| Total calcium | Below 8.5 mg/dL | Above 10.5 mg/dL |
| Nerve and muscle | Overexcitable | Less excitable |
| Signs | Tingling, cramps, tetany, seizures; twitching of the face when the facial nerve is tapped (Chvostek sign); spasm of the hand under an inflated blood pressure cuff (Trousseau sign) | Tiredness, weakness, constipation, confusion, kidney stones, passing a lot of urine |
| Common causes | Hypoparathyroidism, vitamin D deficiency, kidney failure, low magnesium | Hyperparathyroidism, cancer that spreads to bone or releases a PTH-like protein |
| ECG | Longer QT interval | Shorter QT interval |
Phosphate
Phosphate is handled mainly by the kidneys. The proximal tubule reabsorbs about 80% of filtered phosphate on sodium–phosphate symporters, and PTH removes those carriers, so more phosphate is lost in urine. Calcium and phosphate are linked in the blood: together they can reach a level at which calcium phosphate crystals form, so when phosphate rises, free calcium falls.
Hyperphosphatemia (phosphate above about 4.5 mg/dL) is most often caused by kidney failure, because the kidneys are the main exit. Mass release from cells, as when chemotherapy destroys a large tumor or muscle is crushed, and hypoparathyroidism also cause it. The high phosphate binds calcium, so ionized calcium falls, with tingling and tetany. Over months, calcium phosphate is deposited in blood vessels and other soft tissues. People with kidney failure take phosphate binders with meals, which hold dietary phosphate in the gut.
Hypophosphatemia (phosphate below about 2.5 mg/dL) usually comes from phosphate moving into cells or being lost. The classic case is refeeding: when a starved person is fed, insulin drives glucose and phosphate into cells to make ATP and glycogen, and plasma phosphate can crash. Long-term heavy alcohol use, insulin treatment of very high blood glucose, hyperparathyroidism and heavy use of antacids that bind phosphate are other causes. Without phosphate, cells cannot make enough ATP. Muscles, including the diaphragm, weaken; red blood cells stiffen and burst; and they make less 2,3-BPG, so hemoglobin holds on to oxygen more tightly.
Chloride and magnesium balance
Chloride and magnesium balance covers two ions with no dedicated hormone of their own: chloride, the main anion of the ECF, and magnesium, the second most plentiful cation inside cells.
Chloride
Plasma chloride is about 98 to 106 mmol/L. Chloride mostly follows sodium: where the tubules reabsorb sodium, chloride goes with it, through the paracellular route, on NKCC2 and on the sodium–chloride symporter. Plasma must hold equal positive and negative charge, and chloride and bicarbonate are the two main anions, so when one goes up, the other tends to go down.
- Hypochloremia (chloride below about 98 mmol/L) most often follows prolonged vomiting. Stomach acid is hydrochloric acid, so vomiting removes chloride and hydrogen ions. For every hydrogen ion the stomach secretes, one bicarbonate enters the blood (the alkaline tide). With the acid vomited instead of reaching the intestine, that bicarbonate is never used up. The low volume and low chloride then make the kidneys keep bicarbonate instead of excreting the excess. Bicarbonate rises as chloride falls, and the blood becomes alkaline (alkalosis). Loop and thiazide diuretics also lower chloride.
- Hyperchloremia (chloride above about 106 mmol/L) is common after large volumes of 0.9% saline, which contains 154 mmol/L of chloride, half again as much as plasma. Plasma chloride rises, bicarbonate falls, and the blood becomes mildly acidic. Diarrhea, which removes bicarbonate from the gut, does the same.
Magnesium
About 60% of your magnesium is in bone, most of the rest is inside cells, and less than 1% is in plasma. Inside cells, magnesium binds ATP: most enzymes that use ATP, including the sodium–potassium pump, work on the magnesium–ATP complex. Outside cells, magnesium steadies nerve and muscle membranes and competes with calcium at calcium channels.
The kidneys set magnesium balance. As you saw in tubular transport, most filtered magnesium is reabsorbed in the thick ascending limb, pushed between cells by the positive lumen that NKCC2 creates. That is why loop diuretics, which block NKCC2, cause magnesium loss.
Hypomagnesemia (magnesium below about 1.7 mg/dL) is common in hospital patients. Causes include heavy alcohol use, diarrhea, loop and thiazide diuretics, and long-term use of proton pump inhibitors, the acid-blocking drugs, which reduce magnesium absorption. Its effects:
- Overexcitable nerve and muscle: tremor, tetany and seizures.
- Arrhythmias, including torsades de pointes, a twisting ventricular tachycardia that is treated with IV magnesium.
- Low potassium that won't correct. Magnesium inside principal cells normally limits potassium flow through their potassium channels. Without it, potassium keeps leaking into the urine, so potassium given by mouth is lost until the magnesium is replaced.
- Low calcium. The parathyroid glands need magnesium to release PTH, and target tissues need it to respond. Low magnesium therefore causes hypocalcemia that responds only once magnesium is restored.
High magnesium is uncommon, because healthy kidneys excrete excess quickly. It happens when kidney failure is combined with magnesium-containing laxatives or antacids, or during IV magnesium treatment, which is given to pregnant women with a dangerous rise in blood pressure to prevent seizures. It depresses nerves and muscles: the tendon reflexes disappear first, which is why nurses check them during magnesium infusions, then come weakness, low blood pressure, slow breathing and, at very high levels, cardiac arrest. IV calcium counters it.
Putting it together: kidney failure
Mr. Reyes, 66, has kidney failure and has missed two dialysis sessions. His kidneys are the exit for most of these ions, so his blood panel shows almost every imbalance on this page:
- Potassium high (6.8 mmol/L). His principal cells cannot secrete it, and any acidosis shifts more out of cells. His ECG shows peaked T waves: the most urgent problem.
- Phosphate high. It cannot be excreted, and it binds calcium.
- Calcium low. High phosphate binds it, and his failing kidneys make little calcitriol, so he absorbs little from food. His PTH is high.
- Magnesium high, especially if he takes magnesium-containing antacids.
- Sodium low (130 mmol/L), with edema. He has kept salt and water, and more water than salt.
Treatment follows the order of danger: calcium by vein to protect his heart, insulin and glucose to shift potassium into cells, then dialysis to remove potassium, phosphate, magnesium and water together.