Initial Evaluation of Hyponatremia
Today I want to quickly touch on the initial evaluation for hyponatremia. I’ll leave the full discuss to someone much smarter than me and with more time to spare. There are several approaches to evaluating and working up hyponatremia but here is one that is fairly quick and helpful to the housestaff.
Step 1: Is this real?
Remember that hyponatremia, as is any sodium abnormality, is a problem of water balance. Sodium is the major component of serum tonicity (remember calculated serum osmolality = 2[Na] + BUN (mg/dl)/2.8 + glucose (mg/dl)/18) and if it really decreases then serum osmolality should decrease. So the first thing we need to check is Serum Osms.
Check Serum Osms
If serum osmolality is elevated as is the case with hyperglycemia (but same can occur with mannitol, glycine, sorbitol, and gamma globulin) you can get a “translocational” hyponatremia, which is not considered a “true”, but “relative” hyponatremia (at least at the cellular level). There are several correction calculations including the Katz method of a decrease in sodium of 1.6 for every 100 mg/dl of glucose (which underestimates) or the Hillier method based on a small study by Hillier in 1999 from Am J Med that showed a biphasic relationship in which sodium decreases by 1.6 for every 100 when the serum glocuse is between 100-400 and decreases by 4 for every 100 mg/dL when glucose is between 400-600 mg/dL (or you can just use 2.4 if you don’t want to do math).
If serum osmolality is within normal range (something we don’t expect with a low sodium, remember that 2[Na]) then we normally assume psuedohyponatremia. This occurs when the solid phase of plasma is increased by lipids or proteins (ie. hypertriglyceridemia or paraproteinemias). There is a great case study in which an HIV patient with Hep C was found to have psuedohyponatremia that you can find here.
Now this is your true hyponatremia, once you find your patient’s serum osm to low we continue down the rabbit hole to step 2.
Step 2: Is ADH being released?
ADH (anti-diuretic hormone) or vasopressin has 2 stimuli for release: osmotic and nonosmotic (decreased effective circulating volume). The osmotic threshold is 280-290 mOsm/kg. Osmoreceptors in the anterior hypothalamus (supraoptic nuclei if you were wondering) are responsive to these changes is osmolarity and are responsible for releasing ADH. As for the non-osmotic stimuli, they take precedence over osmotic stimuli (ie low blood pressure will cause ADH release despite serum osmolality being normal). But in the causes of hyponatremia we shouldn’t be releasing any ADH in a normotensive patient that has isotonic serum.
This is where our urine osmolarity comes into play. We use this as a surrogate to determine if ADH is being released. Remember if ADH is released water is being reabsorbed at the collecting duct so we expect our urine to NOT be very dilute, meaning Urine Osm >100. Therefore the converse is also true. If the urine osm is less than 100 then there isn’t any ADH being release. We see this occur during primary polydipsia, beer potomania, malnutrition, and reset osmostat ( the reasoning of the last 3 is a little different but we will discuss that later). If the Urine Osm is > 100, then ADH is being made and we proceed to step 3 to evaluate the ECV.
Step 3: What is the patient’s volume status?
This is probably one of tougher parts of the work up, unless the patient is frankly volume contracted or volume overloaded.
In hypervolemia, if the total body Na+ is increased more than total body water, there is hyponatremia. We see this in CHF, nephrotic syndrome, and cirrhosis. In CHF there is decreased cardiac output leading to decreased stretch of arterial baroreceptors leading to increased sympathetic tone from the CNS and activation of the renin-angiotensin-aldosterone system. This leads to increased sodium and water reabsorption by way of non-osmotic ADH release (water reabsorption) and aldosterone (sodium reabsorption).
Increased sympathetic response:
- Increased angiotensin II = increased GFR (by way of vasoconstriction of efferent >> afferent arterioles)
- Increased ADH = increased water reabsorption (by way of Aquaporin 2 in the collecting duct)
- Increased aldosterone = increased sodium reabsorption (by way of increased ENac channels and Na/K ATPase in the collecting duct)
In hypovolemia, patients have deficit of both the total body sodium and water, but the sodium deficit > the water deficit. We see an appropriate non-osmotic release of ADH as these patients have volume contraction. Commonly we see renal or GI losses of water and solute. But in order to become hyponatremic they have to have an intake of hypotonic fluid such as free water (ie the patient with vomiting drink water to help stay hydrated). We can also see this in patients on diuretics. There tends to be more hyponatremia in patients on diuretics as they inhibit the Na/K/2Cl channel in the TAL and decrease the generation of the hypertonic medullary interstitium interfering with the gradient. There makes ADH less effective at reabsorbing water here. Remember that you can get hyponatremia in these patients up to 2 weeks later. In a patient with decreased ECF (extracellular fluid) we expect them to try to retain as much sodium as possible and we expect their urine sodium to be low ( < 20), if higher likely GI losses.
Check urine Na (evaluate with caution in patient on diuretics)
This tends to be the harder volume state to evaluate as the patient can appear to be euvolemic but slightly volume contracted. In any case, this is commonly seen in the hospitalized patient. Residents get here in their work-up and want to just say SIADH, as it is a fairly popular diagnosis for residents to make. But this is a diagnosis of exclusion and other causes must be ruled out. The main three are:
- Hypothyroidism Check TSH
- Adrenal insufficiency Check Cortisol
- Drugs (SSRI, DDAVP, NSAIDs, Antipsychotics, Ecstasy, Narcotics, IVIG)
If the patient isn’t on any medication that can cause hyponatremia or sodium doesn’t improve with discontinuation, and has TSH and a cortisol level within normal limits, SIADH must be considered and a cause should be investigated.
Step 4: Are the kidneys working?
The kidneys do a great job maintaining homeostasis, so should a disturbance occur they should be able to maintain a normal physiologic sodium concentration. Despite everything stated prior the kidneys should be able to handle most of the problems unless there is a problem diluting the urine. We see this occur when the GFR is diminished as there is decreased distal delivery to the distal nephron (TALH, DCT), which is where most of the diluting occurs. So not unexpected to see patients with CKD have sodium abnormalities, especially hyponatremia, therefore it’s necessary to take a throughout history and find out if they have a history of CKD. Early I mentioned about check a urine sodium if the patient has decreased ECF. If it high and the patient doesn’t have a history of CKD the differential includes diuretics (without volume contraction), osmotic diuresis, intrinsic renal disease, and post-obstructive diuresis.
- Check Serum Osms
- Check Urine Osms
- Evaluate ECF
- Check Urine Sodium
- Check TSH (if euvolemic)
- Check Cortisol (if euvolemic)