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Sodium and water balance (Proceedings)
The volume and tonicity of body fluids are maintained within a narrow normal range by regulation of sodium and water balance. The volume of extracellular fluid (ECF) is determined by the total body sodium content, whereas the osmolality and sodium concentration of ECF are determined by water balance.
The volume and tonicity of body fluids are maintained within a narrow normal range by regulation of sodium and water balance. The volume of extracellular fluid (ECF) is determined by the total body sodium content, whereas the osmolality and sodium concentration of ECF are determined by water balance. The kidney plays a crucial role in these processes by balancing the excretion of salt and water with their intake and by avidly conserving them when intake is restricted.
The serum sodium concentration is an indication of the amount of sodium relative to the amount of water in the ECF and provides no direct information about total body sodium content. Patients with hyponatremia or hypernatremia may have a decreased, normal, or increased total body sodium content. Hypernatremia (>155 mEq/L in dogs or >162 mEq/L in cats) implies hyperosmolality, whereas a hyponatremia (<140 mEq/L in dogs or <149 mEq/L in cats) usually, but not always, implies hyposmolality. Hyponatremia develops when the patient is unable to excrete ingested water or when urinary and insensible fluid losses have a combined osmolality greater than that of ingested or parenterally administered fluids. Hypernatremia develops when water intake has been inadequate, when the lost fluid is hypotonic to extracellular fluid, or when an excessive amount of sodium has been ingested or administered parenterally.
Extracellular fluid volume is directly dependent on body sodium content. The body is able to sense and respond to very small changes in sodium content. The adequacy of body sodium content is perceived as the fullness of the circulating blood volume (so-called effective circulating volume). Lowpressure mechanoreceptors (i.e., volume receptors) in the cardiac atria and pulmonary vessels and highpressure baroreceptors (i.e., pressure receptors) in the aortic arch and carotid sinus play a primary role in the body's ability to sense the adequacy of the circulating volume. Within the kidney, the juxtaglomerular apparatus responds to changes in perfusion pressure with changes in renin production and release. The kidney constitutes the primary efferent limb of sodium control and regulates sodium balance by excreting an amount of sodium each day equal to that ingested. There are several overlapping control mechanisms for regulation of renal handling of sodium. This redundancy of controls serves to protect against sodium imbalance should one control mechanism fail.
The osmolality of ECF and serum sodium concentration are regulated by adjusting water balance. Osmoreceptors in the hypothalamus constitute the afferent limb (sensors) for regulation of water balance. Vasopressin (anti-diuretic hormone) release is stimulated when the osmoreceptors shrink in response to plasma hyperosmolality and is inhibited when they swell in response to plasma hypoosmolality. Vasopressin (water output) and thirst (water input) constitute the efferent limb (effectors) for the regulation of water balance. Changes in plasma osmolality as small as 1 to 2% above normal lead to maximal vasopressin release. The gain of the system is such that a 1 mOsm/kg increase in plasma osmolality leads to an almost 100 mOsm/kg increase in urine osmolality. The vasopressin system curtails water excretion, but further defense against hypertonicity requires a normal thirst mechanism and access to water. The next most important stimulus for vasopressin release is volume depletion sensed by baroreceptors in the left atrium, aortic sinus, and carotid sinuses. A decrease in blood volume of 5 to 10% lowers the threshold for vasopressin release and increases the sensitivity of the osmoregulatory mechanism. Nonosmotic stimulation of vasopressin by actual or perceived volume depletion plays a major role in the generation and perpetuation of hyponatremia in states of true volume depletion and in edematous states associated with hypervolemia. Other stimuli for vasopressin release include nausea, pain, and emotional anxiety. Many drugs and some electrolyte disturbances affect the release and renal action of vasopressin.
All clinical conditions associated with hypernatremia reflect hyperosmolality and hypertonicity of the ECF if the solute in question is impermeant. Hypertonicity of the ECF and hypernatremia can be caused by a deficit of pure water, loss of hypotonic fluids, or gain of sodium. Development of a pure water deficit is uncommon in small animal medicine. The main causes of hypertonicity related to pure water deficit are hypodipsia caused by neurologic disease and diabetes insipidus, which represents abnormal renal loss of water. Rarely, chronic hypernatremia may occur in fully conscious animals that have access to water. Hypodipsia, hypernatremia, and hypertonicity caused by an abnormal thirst mechanism have been reported in young female miniature schnauzers. Clinical signs in affected dogs are associated with hypertonicity and include anorexia, lethargy, weakness, disorientation, ataxia, and seizures. Affected dogs can be managed clinically by addition of water to their food, but hypernatremia and neurologic dysfunction recur whenever water supplementation is discontinued. Central or pituitary diabetes insipidus (CDI) is due to a partial or complete lack of vasopressin production and release from the neurohypophysis. It may be caused by trauma or neoplasia or may be idiopathic. Congenital CDI is rare. Increased plasma osmolality and hypernatremia may occur in dogs and cats with CDI. These results suggest that some affected dogs and cats do not obtain enough water to maintain water balance and are presented in a hypertonic state. In the broadest sense, the term nephrogenic diabetes insipidus (NDI) may be used to describe a diverse group of disorders in which structural or functional abnormalities interfere with the ability of the kidneys to concentrate urine. Congenital NDI is a rare disorder in small animal medicine.
Hypotonic fluid losses are the most common type encountered in small animal medicine. They may be classified as extrarenal (e.g., gastrointestinal, thirdspace loss, and cutaneous) or renal. Causes of gastrointestinal losses include vomiting, diarrhea, and small intestinal obstruction; causes of thirdspace losses include pancreatitis and peritonitis. Renal losses may result from osmotically (e.g., diabetes mellitus, mannitol) or chemically (e.g., furosemide, corticosteroids) induced diuresis or from defective urinary concentrating ability related to intrinsic renal disease (e.g., chronic renal failure, nonoliguric acute renal failure, postobstructive diuresis). Gain of impermeant solute is uncommon in small animal medicine. The addition of a sodium salt to ECF causes hypernatremia, whereas gain of an impermeant solute that does not contain sodium (e.g., glucose, mannitol) initially causes hyponatremia because water is drawn into ECF. Hypernatremia occurs, however, as osmotic diuresis develops because urine osmolality approaches plasma osmolality and the sodiumfree solute replaces sodium in urine. The sodium displaced from the urine remains in the ECF and contributes to hypernatremia. This pathophysiology may be responsible for the hyponatremia that has been reported with paint ball ingestion in dogs. Development of hypertonicity as a result of excessive salt ingestion is unlikely if the animal in question has an intact thirst mechanism and access to water.
The clinical signs of hypernatremia primarily are neurologic and related to osmotic movement of water out of brain cells. A rapid decrease in brain volume may cause rupture of cerebral vessels and focal hemorrhage. The severity of clinical signs is related more to the rapidity of onset of hypernatremia than to the magnitude of hypernatremia. In dogs and cats, clinical signs of hypernatremia are observed when the serum sodium concentration exceeds 170 mEq/L. If hypernatremia develops slowly, the brain has time to adapt to the hypertonic state by production of intracellular solutes (e.g., inositol, amino acids) called osmolytes or idiogenic osmoles. These substances prevent dehydration of the brain and allow patients with chronic hypernatremia to be relatively asymptomatic.
The main goals in treating patients with hypernatremia are to replace the water and electrolytes that have been lost and, if necessary, to facilitate renal excretion of excess sodium. The first priority in treatment should be to restore the ECF volume to normal. The next priority is to diagnose and treat the underlying disease responsible for the water and electrolyte deficits.
The presence of hyponatremia usually, but not always, implies hypoosmolality. Thus, the first step in the approach to the patient with hyponatremia is to determine whether hypoosmolality of the ECF is actually present. This can be determined by measurement of plasma osmolality. The evaluation of hyponatremia then may be approached using the patient's plasma osmolality as a guide.
Hyponatremia with normal plasma osmolality: The occurrence of a decreased serum sodium concentration as a result of laboratory methodology in the presence of normal plasma osmolality is called pseudohyponatremia or factitious hyponatremia. Pseudohyponatremia occurs in conditions associated with hyperlipidemia or severe hyperproteinemia. Plasma osmolality in patients with pseudohyponatremia is normal because lipids and proteins are very large molecules that contribute very little to plasma osmolality.
Hyponatremia with increased plasma osmolality: If an impermeant solute is added to ECF, water moves from ICF to ECF, and the osmolality of both compartments increases. If the added solute is something other than sodium, the serum sodium concentration is decreased by the translocation of water, but the plasma osmolality is higher than normal. Hyponatremia with hyperosmolality is usually due to hyperglycemia in diabetes mellitus, wherein each 100 mg/dL increase in blood glucose concentration is associated with a decrease in serum sodium concentration of 2.4 mEq/L.
Hyponatremia with decreased plasma osmolality: The total body sodium content and ECF volume of patients with hyponatremia and hypoosmolality may be normal, decreased, or increased. The second step in the evaluation of the patient with hyponatremia is therefore to estimate total body sodium content and ECF volume status. This is best done by clinical assessment of the patient on the basis of history, physical examination, and a few ancillary tests. A good history often indicates a source of fluid loss (e.g., vomiting, diarrhea, diuretic administration) and the physical examination provides important clues to the patient's volume status. The following physical findings should be assessed: skin turgor, moistness of the mucous membranes, capillary refill time, pulse rate and character, appearance of the jugular veins (distended or flat), and presence or absence of ascites or edema. Measurements of hematocrit and total plasma protein concentration, as well as systemic blood pressure and central venous pressure determinations, if available, further clarify the patient's ECF volume status.
Hyponatremia with volume depletion: For a patient with volume depletion (hypovolemia) to develop hyponatremia, the total body deficit of sodium must exceed that of water. Hyponatremic patients with volume depletion have lost fluid by renal or non-renal routes. Gastrointestinal losses (e.g., vomiting, diarrhea) and thirdspace losses such as pleural effusion or peritoneal effusion caused by peritonitis, pancreatitis, or uroabdomen are the most important non-renal losses of fluid and NaCl. Gastrointestinal losses are often hypotonic in nature. The question thus arises, "If the losses are hypotonic, how does the patient become hyponatremic?" The answer follows from three physiologic events and reflects the body's tendency to preserve volume at the expense of tonicity. First, volume depletion decreases glomerular filtration rate (GFR), enhances isosmotic reabsorption of sodium and water in the proximal tubules, and decreases delivery of tubular fluid to distal diluting sites. These events impair excretion of water. Second, volume depletion is a strong nonosmotic stimulus for vasopressin release, and the increased plasma vasopressin concentration further impairs water excretion. Third, the patient is thirsty because of volume depletion and continues to drink water if it is available. All of these factors have a dilutional effect on the remaining body fluids. Renal fluid and NaCl losses resulting in hyponatremia are usually due to hypoadrenocorticism or diuretic administration. Occasionally, dogs with gastrointestinal fluid losses develop electrolyte disturbances that mimic hypoadrenocorticism, and hyponatremia has been associated with thirdspace loss of fluid.
Hyponatremia with volume excess: Hyponatremia may occur despite the presence of increased total body sodium and expansion of the ECF compartment in patients with ascites or edema. Some of the pathophysiologic events in these patients impair the excretion of ingested water and exert a dilutional effect on the serum sodium concentration. Hyponatremia with volume excess (hypervolemia) is observed in three clinical conditions: congestive heart failure, severe liver disease, and nephrotic syndrome. In these disorders, there is a perception of circulating volume depletion by the body, and the regulatory mechanisms invoked result in volume expansion. Three major pathophysiologic mechanisms are operative in the pathogenesis of sodium retention and impaired water excretion in these clinical conditions. The reninangiotensin system is activated by reduced renal perfusion and causes increased sodium retention by the kidneys. Decreased renal perfusion, decreased GFR, and increased proximal tubular reabsorption of sodium and water result in decreased delivery of tubular fluid to distal diluting sites and impairment of free water excretion. A decrease in effective arterial blood volume results in nonosmotic stimulation of vasopressin release and further impairment of water excretion. Impaired free water excretion causes dilution of retained sodium and results in hyponatremia despite the presence of increased total body sodium content and expansion of the ECF compartment.
In cirrhosis and the nephrotic syndrome, intravascular volume may be reduced as a result of decreased oncotic pressure caused by hypoalbuminemia. This volume depletion causes nonosmotic stimulation of vasopressin release and impaired water excretion. Decreased cardiac output also has been observed to increase plasma concentrations of vasopressin. In congestive heart failure, decreased cardiac output is sensed by baroreceptors in the carotid and aortic sinuses, resulting in nonosmotic release of vasopressin. The pathophysiology of sodium retention in the nephrotic syndrome appears to be complex. In some nephrotic patients with hypervolemia, the reninangiotensin system appears to be suppressed. This conclusion is based on decreased plasma concentrations of renin and aldosterone and suggests a primary intrarenal mechanism for sodium retention. In severe liver disease, arteriovenous shunting, splanchnic venous pooling, ascites caused by portal hypertension, and decreased oncotic pressure caused by hypoalbuminemia all may lead to decreased effective circulating volume resulting in nonosmotic stimulation of vasopressin release and activation of the reninangiotensin system. Sodium retention and impairment of water excretion result.
Hyponatremia with hypervolemia may also be seen in advanced renal failure. Positive water balance may occur in the presence of continued polydipsia if there is an insufficient number of functional nephrons to excrete the required amount of free water.
Hyponatremia with normal volume: Hyponatremia with normal volume (normovolemia) may occur as a result of psychogenic polydipsia, syndrome of inappropriate secretion of vasopressin, administration of hypotonic fluids or drugs with antidiuretic effects, and myxedema coma of severe hypothyroidism.
The clinical signs of hyponatremia are related more to the rapidity of onset than to the severity of the associated plasma hypoosmolality. Cerebral edema and water intoxication occur if hyponatremia develops faster than the brain's defense mechanisms can be called into play. Decreased plasma osmolality and influx of water into the central nervous system cause the clinical signs observed in acute hyponatremia. Clinical signs are often absent in chronic disorders characterized by slower decreases in serum sodium concentration and plasma osmolality. Acute water intoxication is likely only if the patient has some underlying cause of impaired water excretion at the time a water load occurs.
The two main goals of treatment in hyponatremia are to diagnose and manage the underlying disease and, if necessary, increase serum sodium concentration and plasma osmolality. Severe, symptomatic hyponatremia of rapid onset, however, is rare in small animal practice. Because of limited experience with the management of acute hyponatremia in dogs and cats and the known risks of overly rapid correction of hyponatremia, only use of conventional crystalloid solutions (e.g., lactated Ringer's solution, 0.9% saline) is recommended. Symptomatic dogs with chronic hyponatremia should be treated conservatively at correction rates < 10 to 12 mEq/L/day (0.5 mEq/L/h) to avoid osmotic demyelination syndrome (myelinolysis). Correction should be carried out with conventional crystalloid solutions (e.g., lactated Ringer's solution, 0.9% NaCl) in a volume calculated specifically to replace the patient's volume deficit. Water intake should be carefully restricted to a volume less than urine output in normovolemic patients with hyponatremia (e.g., psychogenic polydipsia), or drugs causing an antidiuretic effect should be discontinued if possible. In edematous patients, dietary sodium restriction and diuretic therapy should be considered.
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