ECF Volume and Osmolarity in Contexts of Low Effective Circulating Volume

  • Contexts of severely low effective circulating volume can profoundly dysregulate ECF osmolarity. As discussed previously, the effective circulating volume refers to the volume of blood functionally circulating through the vasculature and perfusing tissues. In reality, the effective circulating volume cannot be directly measured by the body. Instead, information about the intravascular blood pressure at various anatomical locations is used as a proxy for the effective circulating volume. This information is supplied by baroreceptors, particularly at the carotid sinuses and renal afferent arterioles.
When does low effective circulating volume occur
  • In the simplest cases low effective circulating volume can occur due to an insufficiency of total ECF volume as arises during contexts of profound volume depletion, such as a major hemorrhage or severe dehydration. However, low effective circulating volume also occurs in contexts such as congestive heart failure in which there is plenty of total extracellular volume but too little of it is effectively circulating through the vasculature as a result the heart’s inability to pump blood.
The response to low effective circulating volume
  • Interestingly, progressively lower effective circulating volumes trigger secretion of increasing amounts of ADH and activate the thirst instinct. Importantly, deficiencies of effective circulating volume trigger ADH release and thirst completely independently of the ECF osmolarity, regardless of how low the ECF osmolarity might be. This can lead to profound dysregulation of ECF osmolarity with large amounts of free water addition to the ECF even when the ECF osmolarity is low, clinically manifesting as progressive hyponatremia.
Functional Purpose
  • Naturally one might wonder why this physiological response to low effective circulating volume exists. As the effective circulating volume declines the body first triggers the normal mechanisms of ECF volume regulation by reducing sodium loss via inhibition of pressure natriuresis, profoundly activating the RAAS, and stimulating the sympathetic nervous system’s sodium-retaining properties. These responses will dramatically reduce urinary loss of sodium.
  • However, if the effective circulating volume continues to decline, the body will trigger the thirst instinct and secrete ADH, yielding addition of free water to the ECF. As described previously in ECF Volume Regulation, adding free water to the ECF is not very effective in increasing ECF volume (largely because the added free water volume mostly shifts intracellularly). However, even after equilibration of the added water, the ECF will expand slightly. Thus the response can be viewed as a desperate attempt to retain as much ECF volume as possible, even if that volume comes from the addition of free water.
  • In other words, when effective circulating volumes are profoundly low the body ceases to care about such fine points of body fluid dynamics. It simply attempts to add as much volume to the ECF as possible, even if it may not be terribly effective. Importantly, the body is willing to sacrifice proper osmoregulation to achieve the goal of maintaining effective circulating volume. Simply put, there is no point worrying about hyponatremia if you can’t perfuse your brain the first place.
Clinical Scenarios
  • Overview
    • Two clinical scenarios will help us understand dysregulation of ECF osmolarity in contexts of low effective circulating volume. At first glance it might be surprising that these scenarios are associated with hypoosmolarity, but the above discussion will make clear how the pathogenesis occurs.
  • Dehydrated Runner Returning Home
    • Let us imagine a runner who is volume depleted from running all day in the hot sun and has now returned to his apartment. In this volume-depleted state the runner’s body is secreting large amounts of ADH and triggering a strong thirst instinct even though his ECF osmolarity may be normal. He drinks uninhibitedly from the tap, enjoying the refreshing free water. Because of the high levels of ADH, the free water is simply added to the ECF, reducing its osmolarity and yielding hyponatremia. If the effective circulating volume had been normal, levels of ADH would have been reduced, allowing the kidneys to urinate off the added free water. However, given the volume depletion, ADH levels are high and the ingested free water is maintained in the ECF. This helps us understand why dehydrated individuals with access to even small amounts of free water are frequently hyponatremic.
  • Congestive Heart Failure
    • As discussed previously, patients with CHF display deficiencies in effective circulating volume because of the inability of their hearts to pump blood. As a result their ADH levels can be quite high in spite of low ECF osmolarity. This combined with their activated thirst instincts can yield large additions of free water to the ECF, progressively rendering the ECF hypoosmolar and in turn hyponatremic. Consequently, hyponatremia is an important clinical feature of end-stage heart failure.