In this post…

• Why drinking seawater causes dehydration
  
• Why giving 0.9% NaCl can exacerbate hyponatraemia in some circumstances
  
• How much water do you have to drink to cause hyponatraemia
  
• Why most patients on furosemide should also have restricted water intake
  
• Why a “tea and toast” diet causes hyponatraemia
  
• Why limiting dietary solute intake can help in nephrogenic diabetes insipidus

Physicists may still be searching for the grand unified theory of everything, but nephrologists have come pretty close to a unified theory of urine. One very simple relationship can be used to explore an impressive array of renal / electrolyte phenomena. It is such a simple relationship that it’s simplicy belies its utility - and for that reason it could reasonably be called the “E = mc² of nephrology.”

It is the relationship between osmolar load (OL), urine volume (V) and urine osmolality (U_Osm):

\[V = \frac{OL}{U_{Osm}}\]

This equation has at least six corollaries.

Corollary 1: drinking seawater causes dehydration

The osmolality of seawater is ~1000 mOsm/kg. Imagine 1L of seawater is ingested by somebody whose kidneys are only able to concentrate urine to a maximum of 900 mOsm/kg. The osmolar load (1000 mOsm) must then be excreted in a minimum of 1.11L of urine (=1000/900), leading to a net loss of 0.11L of free water from the body.

Corollary 2: giving 0.9% NaCl can exacerbate hyponatraemia in some circumstances

Hyponatraemia may occur in the context of unregulated ADH release (e.g. SiADH or profound volume depletion). In this context, urine osmolality is fixed so as to generate a concentrated urine. Suppose hyponatraemia develops in a person in whom ADH activation sets U_Osm at 600 mOsm/kg. If we were to administer 1L of intravenous 0.9% NaCl (=150 mM), this would deliver an osmolar load of 300 mOsm. This load would be excreted in 0.5L of urine, leaving 0.5L of free water in the body to exacerbate the hyponatraemia. For this reason, hypertonic saline is usually required in the treatment of severe or symptomatic hyponatraemia.

Corollaries 3 & 4: calculating the water intake required to cause hyponatraemia (and ditto on furosemide)

Hyponatraemia is a problem of excess body water. In normal circumstances - i.e. with completely normal renal function and an intact ADH axis - the kidney is able to respond to water challange by producing a dilute urine. The minimum possible urine osmolality will be ~50 mOsm/kg. A typical daily osmolar load is around 10 mOsm per kg body weight (for somebody taking a Western diet); therefore ~700 mOsm in a 70 kg person.

This load can be accompanied by a free water intake of anything up to 14L per day (700/50), and that water can still be excreted in a urine that might be as dilute as 50 mOsm/kg. However, any water intake exceeding this threshold cannot be excreted and would be retained as free water, resulting in hyponatraemia.

Therefore it should be apparent that in normal circumstances, the volume of water required to generated hyponatraemia through polydipsia is remarkably high (~14L per day). However, in many patients who are unwell and may have low dietary solute intake and / or some limit to renal water excretion (e.g. mild CKD) then drinking a relatively low volume of water might result in hyponatraemia. If daily solute intake = 350 mOsm and U_Osm cannot be lowered beyond 100 mOsm/kg then water intake in excess of 3.5L per day (350/100) would cause hyponatraemia.

One patient group worthy of consideration are those patients taking loop diuretics. In these individuals, U_Osm will be fixed at ~300 mOsm/L. Therefore, assuming an osmolar load of 700 mOsmoles, any water intake exceeding ~2.3L per day risks inciting hyponatraemia. It is usually sensible to institute a water restriction alongside any furosemide prescription.

Corollary 5: poor diet (low dietary solute intake) can cause hyponatraemia

When dietary solute intake is low, the volume of urine used to excrete that osmolar load will also be low (for any given U_Osm). This may limit water excretion, resulting in hyponatraemia.

A diet that is relatively rich in carbohydrate will be low in solutes: carbohydrate is metabolised to CO₂ and H₂O, whereas protein is metabolised to urea. Thus hyponatraemia arising from this mechanism is commonly encountered in beer potomania and in patients on a “tea and toast diet”.

Corollary 6: limiting dietary solute intake can help in diabetes insipidus

In health, U_Osm is dynamic: our kidneys set a urine concentration that is appropriate to maintain water homeostasis. When U_Osm is fixed, then V is determined by osmolar load.

Above, we considered two potential implications of a fixed U_Osm. U_Osm may be fixed a some high level when ADH is present or at a middling-level when furosemide is acting. But what about when U_Osm is fixed low (i.e. dilute urine)? This is most commonly encountered in diabetes insipidus. In this context, limiting dietary solute (i.e. salt and protein) intake should help to reduce urine volumes. This can be a helpful part of management in patients with nephrogenic DI.