Plasma sodium is a ratio: the sodium in the plasma divided by the water that holds it. A number that is off can come from the laboratory or from a real move of water, and the two look the same on the report. A real change moves the osmolality of plasma, and a laboratory error does not. Once the change is real, the patient’s volume shows which way water and salt have gone, and the urine shows what the kidney is doing about it.
Is the number real?
A plasma sodium below 135 or above 145 mmol/L starts the search. But not every abnormal sodium means that the tonicity of the body fluids has changed. So the first check is whether the number is true.
Can the laboratory report a low sodium that is not there?
In hyponatremia, the first step is to separate true hypotonic hyponatremia, where the low sodium reflects low tonicity, from situations where the reported sodium is misleading. Why does that matter? A false low reading looks just like a real one on the report, so something other than the sodium has to tell them apart.
In pseudohyponatremia the plasma osmolality is normal, but the reported sodium is low. Protein takes up part of the plasma, so less of the sample is water. The analyser assumes a normal water fraction and therefore reads the sodium as low. Pseudohyponatremia occurs with:
- hyperproteinemia, as in multiple myeloma
- hyperlipidemia
- laboratory error
- hyperglycemia, which works by a different route (see below)
These patients are usually euvolemic. No water has moved, so the body is neither short of water nor full of it, and nothing in the patient needs correcting.
The test is the plasma osmolality. True hyponatremia lowers it. A false low reading leaves it normal. Osmolality is counted per kilogram of solvent, not per litre. Measuring it separates the true disorder from these artifacts.
What if the glucose is high?
Glucose is a different case. Here the laboratory is not wrong, and water really has moved. Water crosses cell membranes and moves toward the side with more solute, and glucose is one of the solutes counted in plasma tonicity. Glucose stays outside the cells and draws water out of them. The same sodium now sits in more plasma water, so the measured sodium is low. That is why, in hyperglycemia, the sodium value must be corrected for the raised glucose: the correction adds back the dilution.
Which way has the water gone?
Once hyponatremia is confirmed as true, volume status sorts it into three groups. Each group shows a different response of the body, and each points to different causes.
- Hypovolemic. Sodium and water have both been lost, with proportionally greater loss of sodium. The body is left with relatively more water, and the fall in blood pressure switches on ADH, which keeps that water. Examples are vomiting, diarrhea and diuretic use.
- Euvolemic. The most common cause is SIADH, where ADH keeps water although plasma osmolality is low. Hypothyroidism and adrenal (glucocorticoid) deficiency are the other causes to think of.
- Hypervolemic. Water is retained in heart failure, cirrhosis or kidney injury. In cirrhosis and heart failure the fluid volume rises while the blood reaching the tissues falls, so the kidney holds water.
Why can volume not decide it alone?
Volume is judged at the bedside, and that is where it fails. Clinical assessment of volume status is unreliable, even in experienced hands. So volume status is combined with laboratory markers and not trusted on its own, and urine is a more reliable guide than the examination. Two urine measurements supply these markers and localise the problem.
What does the urine say about the water?
Urine osmolality shows whether ADH is acting. ADH high means the kidney keeps water; ADH low lets dilute urine go out. In hyponatremia the plasma is dilute, so under normal physiology ADH is switched off and the urine becomes maximally dilute. A urine osmolality above 100 mOsm/kg therefore means that ADH is present. That is inappropriate, because ADH should not be acting when the plasma is dilute.
Dilute urine tells the opposite story. The kidney is already excreting water, so the excess points to too much water intake, or to a very low solute intake, which limits how much free water the kidney can excrete.
What does the urine say about the salt?
Urine osmolality reads the water. Urine sodium reads the salt, and it is a surrogate for how the kidney handles sodium and for the effective intravascular volume. Why does it follow the volume? The renin-angiotensin-aldosterone system promotes sodium retention, and natriuretic peptides promote sodium excretion. When effective volume falls, arterial underfilling activates ADH and the renin-angiotensin-aldosterone system, and the kidney conserves sodium.
- A urine sodium below 20 mmol/L suggests that the kidney is conserving sodium, as in gastrointestinal losses. The loss is outside the kidney, and the normal renal response is to hold on to sodium.
- A urine sodium above 20 mmol/L suggests renal sodium loss or diuretic use. Thiazide diuretics block the sodium-chloride cotransporter that reabsorbs sodium in the distal convoluted tubule, so sodium passes into the urine.
- In a euvolemic patient, a urine sodium above 20 mmol/L fits SIADH. Nothing stimulates the kidney to keep sodium, so sodium goes out in the urine.
When the number is high, what is the cause?
The same search runs the other way when sodium is high. Hypernatremia always reflects a deficit of total body water relative to sodium. Plasma sodium is a ratio of sodium to the water that holds it, so the same sodium in less water gives a higher number. The cause is usually clear from the history, which therefore comes first.
The usual causes are a water intake that is too low, or water lost through the gut, skin or kidney. Water lost with less sodium leaves the body fluid more concentrated. Less often, sodium is gained from hypertonic fluids.
When the history does not give the cause, what does the urine show?
Sometimes the history does not identify the cause, or hypernatremia recurs despite free access to water, which is what normally prevents it, together with thirst. Then the urine volume and osmolality are measured. A kidney that is wasting water keeps making dilute urine even when water is withheld.
A large volume of dilute urine, with an osmolality below 300 mOsm/kg, points to diabetes insipidus, central or nephrogenic. Water deprivation raises plasma osmolality, which raises ADH, and desmopressin supplies ADH directly. Urine that stays dilute after water deprivation or desmopressin means the kidney is not responding to ADH.
What does the urine show when the water is lost outside the kidney?
When the losses are extrarenal, the kidney is trying to save water and salt, and the urine shows it. Rising plasma osmolality triggers thirst and ADH, so the urine is usually concentrated. The response to low effective volume is to hold sodium, so urinary sodium is usually low.
Knowing the cause is half the task: how fast can the sodium be brought back without harming the brain?