Etiology

Gastrointestinal losses occur when the normal reabsorption of fluid from the gastrointestinal tract is prevented by drainage or vomiting, or there is increased secretion resulting in diarrhea, either from an infectious or inflammatory process, or use of laxatives.

Hemorrhage from any site can result in volume depletion. Gunshot wounds, major fractures, crush injuries, or a ruptured abdominal aortic aneurysm can quickly result in massive blood and fluid loss that can be rapidly fatal. Acute or chronic bleeding into the gastrointestinal tract is also a common cause of volume depletion.[1][5][7]

Renal fluid losses are a result of excess salt and water excretion in the urine. This is seen with the overuse of diuretics, osmotic diuresis caused by substances such as glucose in the urine (due to uncontrolled diabetes), adrenal insufficiency, and, rarely, salt-wasting nephropathies. Renal water excretion can be severe in the setting of diabetes insipidus, but this primarily causes dehydration and hypernatremia and will not lead to true volume depletion unless there is significant renal loss of sodium as well.[1][5][8][9]

Skin and respiratory losses are less common etiologies of volume depletion. Massive sweating leading to excessive sodium and water losses can be seen in cases of extreme heat and physical exertion.[7][9][10] Burns can lead to large volume losses as extracellular fluid is lost through damaged tissue. Respiratory losses can be seen in individuals with draining pleural effusions or bronchorrhea (i.e., excessive discharge of mucus from the bronchi).[5][9]

Third-space sequestration is seen when abnormal collections of fluid develop in spaces where they cannot be reabsorbed into the intravascular space. This is seen when ascites develops due to cirrhosis or Budd-Chiari syndrome, venous obstruction, severe pancreatitis, or intestinal obstruction.[5][9]

Pathophysiology

Sodium is excluded from the intracellular space, but water distributes throughout all body compartments. Consequently, total body sodium content determines the size of the extracellular compartment (typically 33% of total body water). Seventy-five percent of extracellular fluid is in the interstitium, and 25% (about 8% of total body water) is in the intravascular space. Volume depletion occurs when salt loss results in a decrease in extracellular volume.

Dehydration and volume depletion are not the same, although they can be present in the same patient at the same time. Dehydration implies a total body water deficit alone or in excess of sodium loss, with a subsequent increase in plasma osmolality that usually comes to clinical attention as hypernatremia. Symptoms of pure water loss arise from the effects of consequent increased osmolality and reflect the cellular responses to hypertonicity: confusion, thirst, impaired sensorium, and, in more extreme cases, coma or seizures.

In contrast, clinical symptoms of volume depletion are a result of the hemodynamic effects of the reduction in intravascular volume. Venous return to the heart falls, leading to a drop in cardiac output and subsequently a lower mean arterial pressure. This change is noted by baroreceptors in the aortic arch and carotid sinus, leading to an increase in sympathetic activity and increased catecholamine release. The goal of this physiologic response is to maintain vital organ perfusion. It is manifested by an increase in heart rate and contractility, an increase in peripheral vascular resistance, and a restoration of blood pressure. Thus, blood is shunted from the vascular beds such as skeletal muscle, skin, kidneys, and the gastrointestinal tract toward the coronary and cerebral circulation.[2][5]

In the kidney, the decrease in blood pressure results in increased secretion of renin and activation of the renin-angiotensin-aldosterone system, leading to sodium retention. Although more sensitive to hypertonicity, the hypothalamus responds to intravascular volume depletion by stimulating the posterior pituitary to increase its release of antidiuretic hormone, thereby increasing water reabsorption in the kidney. The kidney thus attempts to preserve volume by increasing reabsorption of sodium and water in response to perceived decreased renal blood flow. This sodium and water reclamation can be impaired by renal disease or drugs that alter salt and water excretion. The normally functioning kidney reabsorbs 98% to 99% of the fluid and solutes that are filtered across the glomerular capillary bed daily. If this renal tubular reabsorption is impaired, volume depletion can occur. One cause of impaired renal solute and fluid reabsorption is the presence of osmotically active solutes in the urine, which induces an osmotic diuresis. This can occur, for example, when uncontrolled diabetes results in glucose being excreted in the urine or when mannitol is used as treatment for elevated intracranial pressure.[2][5][8][10]

With severe hypovolemia (>10% to 20% of blood volume), the compensatory cardiovascular changes are not able to maintain blood pressure, and patients manifest postural dizziness on standing. As volume loss becomes yet more severe, the patient becomes hypotensive when supine, and without appropriate resuscitation, shock with inadequate tissue perfusion will ensue.[2][5][9][11]

Hypovolemia ultimately leads to inadequate perfusion of the microcirculation, resulting in decreased oxygen delivery to cells and compromised mitochondrial activity. Thus, it is important to restore circulating volume in order to prevent prolonged tissue hypoxia and resultant organ dysfunction.[12]

Classification

Etiologic classification[5]

Gastrointestinal (GI) losses

  • Increased fluid loss from a GI tract source, including bleeding, vomiting, and diarrhea.

Skin losses

  • From profound sweating or extensive burns.

Renal losses

  • From a defect in sodium and/or water reabsorption in the kidney.

Third-space sequestration

  • Loss of extracellular fluid into the interstitial space or into a body cavity.

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