All living organisms originated in the sea. A constant salt concentration was important to maintain their vital functions. To overcome their dependency on the sea environment, a sophisticated renal system has developed in modern mammals that allows them to maintain a steady concentration of various electrolytes and water balance.
Understanding sodium and water balance is important for clinicians who treat animals with renal disorders, sodium derangements and other critical conditions. Not surprisingly, this topic may appear complex and daunting to the majority of veterinary practitioners.
Sodium and water balance is governed by 3 key players:
- Antidiuretic hormone (aka ADH, vasopressin)
- Renal tubules (predominantly, proximal convoluted tubules and collecting ducts)
When dealing with dysnatremic patients, evaluation of the integrity of these physiologic systems will provide a clinician with the most comprehensive approach to diagnosis and treatment of sodium derangements.
The kidney ‘speaks’ via the composition of urine. Thus, by determining this composition we can obtain important information about the nature of the underlying problem. However, the determination, as well as the interpretation of these values, has limitations and potential pitfalls. In this blog post, I will focus on urine sodium concentration and urine osmolality. Their assessment will help a clinician to determine if renal, ADH or aldosterone systems are functioning appropriately.
Urine osmolality vs. plasma osmolality = ADH effects
The assessment of urine osmolality (concentration of solutes) in comparison with plasma osmolality will tell you if ADH is being secreted and if it is acting on collecting ducts. It is extremely important to interpret the results of this test in the context of physical examination and history (i.e. the patient’s hydration/volume status, exposure to diuretics or high-sodium containing fluids)
Two major stimuli of ADH secretion are:
- Elevated plasma osmolality
- Reduced effective circulating volume
Every time you work out and lose free water or eat salty chips, your plasma osmolality goes up and ADH is secreted. That increases your thirst and causes reabsorption of free water from the renal collecting ducts back to your blood. This is how our plasma osmolality is maintained in a very narrow range.
Dehydrated, hypovolemic and hypernatremic patients should always have an increase in ADH secretion. ADH will cause free water reabsorption from the ultrafiltrate and will lead to an increase in urine osmolality relative to plasma. If these patients have urine osmolality that is less than plasma osmolality, this is an inadequate response. This may happen in patients with central or nephrogenic diabetes insipidus (i.e. absolute lack of ADH or impaired renal tubule response to ADH) as well as in renal failure.
In patients with hyponatremia, ADH will be secreted if a patient is hypotensive/hypovolemic, because reduced effective circulating volume will activate ADH secretion in spite of low plasma osmolality. This is the reason why many patients in shock may have an increased thirst. In contrast, a patient with hyponatremia and normal volume status should have its ADH secretion suppressed leading to urine osmolality being less or equal to plasma osmolality. ADH suppression allows the kidney to get rid of extra free water that has been accumulated in the body. If in such a hyponatremic normovolemic patient, urine osmolality remains greater than plasma, this may indicate that ADH is being secreted without appropriate stimuli (Syndrome of inappropriate ADH secretion, SIADH).
Fractional excretion of sodium (FeNa)
If urine osmolality helps us to diagnose problems with ADH and collecting ducts, FeNa will facilitate evaluation of the integrity of proximal renal tubules and aldosterone effects. As with urine osmolality, FeNa should be interpreted in the context of patient’s physical examination, history and exposure to medications.
Healthy proximal renal tubules will reabsorb 98-99.5% of filtered sodium load. Its reabsorption rate will depend on patient’s sodium intake and volume status. If you eat a ton of salty food, the body will try to eliminate this extra salt by decreasing its reabsorption. Sodium content is also important for regulation of total body water because it is the most abundant electrolyte determining the osmotic pressure in the extracellular space. If you lose sodium, you will lose water from your extracellular space because it will get shifted intracellularly due to reduced osmotic pressure.
FeNa is calculated by the following formula: (Na urine/creatinine urine)/ (Na plasma/creatinine plasma×100). As opposed to an isolated urine sodium concentration, FeNa is normalized to creatinine concentration, which increases its accuracy. The majority of chemical analyzers are able to measure sodium and creatinine in the urine.
How do we interpret FeNa?
Scenario #1: Dehydrated/hypovolemic patient with hypernatremia
In these patients hypernatremia develops due to a loss of free water in excess of sodium losses (GI or renal losses, body cavitary effusions). Patients with intact renal function are supposed to have FeNa <1% in this situation, because reduced circulating volume stimulates aldosterone secretion leading to maximum sodium reabsorption even in the face of hypernatremia. Patients with acute kidney injury (impaired renal tubular function), furosemide therapy (blocked Na reabsorption at the level of loop of Henle) and hypoadrenocorticism (unable to secrete aldosterone) will have FeNa >1% despite the presence of hypovolemic state. Therefore, FeNa will help us to differentiate the origin of hypotonic fluid losses: renal vs. extrarenal.
Scenario #2: Patients with hypernatremia due to salt poisoning or hypertonic saline administration
In this case, hypernatremia has developed not due to free water or hypotonic fluid losses but because of the solute gain. These patients are hypervolemic and are not secreting aldosterone. In the absence of circulating aldosterone, FeNa will increase to >1% to facilitate sodium excretion.
Scenario #3: Patients with hyponatremia in conjunction with hypovolemia (e.g. a patient with a foreign body obstruction leading to profuse vomiting and diarrhea, increased thirst).
Since this patient is hypovolemic, aldosterone will be secreted that will lead to maximal sodium reabsorption and FeNa<1%. That holds true only in patients with intact renal function, absence of diuretic therapy and normal adrenal function.
Urine/plasma osmolality measurements and FeNa calculations are not commonly performed in veterinary medicine as opposed to human medicine where the majority of dysnatremic people will have these tests ordered. This difference in a diagnostic approach can be explained by the fact that human physicians deal with way more complicated cases, they have institutional algorithms and nephrology services capable of interpreting the results of this testing, and the cost of additional diagnostics does not play a significant role.
It is true that in many cases of dysnatremic veterinary patients, the underlying etiology may be diagnosed via thorough history, physical examination, bloodwork and USG interpretation. That being said, complicated critical cases may require a more sophisticated diagnostic approach that may include urine electrolytes and osmolality testing. This can also significantly improve clinicians’ understanding of renal physiology and intricate interactions between various neurohormonal components governing sodium and water balance.