ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Etiology, clinical manifestations, and diagnosis of volume depletion in adults

Etiology, clinical manifestations, and diagnosis of volume depletion in adults
Literature review current through: Jan 2024.
This topic last updated: Mar 08, 2022.

INTRODUCTION — In a variety of clinical disorders, fluid losses reduce extracellular fluid volume, potentially compromising tissue perfusion. Early diagnosis and prompt treatment to restore euvolemia can be lifesaving.

True volume depletion may occur when sodium-containing fluids are lost in the urine, from the gastrointestinal tract or skin, or by acute sequestration into an internal "third-space" that results in a diminished intravascular volume.

When these fluid losses occur, two factors serve to protect against the development of hypovolemia:

Dietary sodium and water intake are generally far above basal needs. As a result, relatively large losses must occur unless intake is concomitantly reduced (as with anorexia or vomiting).

The kidney minimizes urinary losses by enhancing sodium and water reabsorption.

This topic will review the etiology, clinical manifestations, and diagnosis of volume depletion. The treatment of this disorder is presented separately:

(See "Maintenance and replacement fluid therapy in adults".)

(See "Treatment of severe hypovolemia or hypovolemic shock in adults".)

ETIOLOGY — Volume depletion results from loss of sodium and water from the following anatomic sites:

Gastrointestinal losses, including vomiting, diarrhea, bleeding, and external drainage

Renal losses, including the effects of diuretics, osmotic diuresis, salt-wasting nephropathies, and hypoaldosteronism

Skin losses, including sweat, burns, and other dermatological conditions

Third-space sequestration, including intestinal obstruction, crush injury, fracture, and acute pancreatitis

Gastrointestinal losses — Each day, approximately 3 to 6 liters of fluid are secreted by the stomach, pancreas, gallbladder, and intestines into the lumen of the gastrointestinal tract. Almost all of the secreted fluid is reabsorbed, so that only 100 to 200 mL are lost in the stool. However, volume depletion may ensue if the secreted fluid cannot be reabsorbed (as with external drainage and vomiting) or if secretion exceeds the capacity for reabsorption due either to increased secretion or reduced reabsorption. Acute bleeding from any site in the gastrointestinal tract is another common cause of volume depletion.

Renal losses — Under normal conditions, renal sodium and water excretion are adjusted to match intake. In a normal adult, approximately 130 to 180 liters is filtered across the glomerular capillaries each day. More than 98 to 99 percent of the filtrate is then reabsorbed by the tubules, resulting in a urine output averaging 1 to 2 L/day. Thus, a small (1 to 2 percent) reduction in tubular reabsorption can lead to a 2- to 4-liter increase in sodium and water excretion, which, if not replaced, can result in severe volume depletion.

Diuretic therapy and osmotic diuresis caused by glucosuria are the most common causes of excessive renal salt and water loss. Variable degrees of sodium wasting are also present in many different kidney diseases. As an example, most patients with chronic kidney disease and a glomerular filtration rate (GFR) of less than 25 mL/min are unable to maximally conserve sodium if acutely placed on a low-sodium diet. These patients may have an obligatory sodium loss of 10 to 40 mEq/day, in contrast to normal subjects who can lower sodium excretion to less than 5 mEq/day [1,2]. This degree of sodium wasting is usually not important, since normal sodium balance is maintained as long as the patient is on a regular diet. (See "Evaluation of patients with polyuria", section on 'Not causes of true polyuria: Salt wasting and typical diuretic use'.)

Rare patients may have a severe salt-wasting nephropathy with obligatory urinary losses that may exceed 100 mEq of sodium and 2 liters of water per day. Such patients develop hypovolemia unless a high sodium intake is maintained. Severe salt-wasting nephropathy is most often seen in tubular and interstitial diseases, such as autosomal dominant interstitial kidney disease. (See "Autosomal dominant tubulointerstitial kidney disease".)

Skin losses — Although sweat production is low in the basal state, it can exceed 1 to 2 L/h in a subject exercising in a hot, dry climate [3].

The skin also acts as a barrier that prevents the loss of interstitial fluid to the external environment. When this barrier is interrupted by burns or exudative skin lesions, a large volume of fluid can be lost.

Sequestration into a third-space — Volume depletion can be produced by the loss of interstitial and intravascular fluid into a third-space that is not in equilibrium with the extracellular fluid. As an example, a patient with a fractured hip may lose 1500 to 2000 mL of blood into the tissues adjacent to the fracture. Although this fluid will be resorbed back into the extracellular fluid over a period of days to weeks, the acute reduction in blood volume, if not replaced, can lead to severe volume depletion. Other examples of third-space fluid losses include intestinal obstruction, severe pancreatitis, crush injuries, bleeding (as with trauma or a ruptured abdominal aortic aneurysm), peritonitis, and obstruction of a major venous system.

CLINICAL MANIFESTATIONS — Hypovolemic patients may present with a variety of symptoms, physical examination findings, and laboratory abnormalities. Symptoms may be related to the volume depletion itself, such as lassitude and postural dizziness, or to the underlying cause of volume depletion, such as vomiting, diarrhea, or polyuria. The physical examination may reveal decreased skin turgor, low arterial blood pressure or postural hypotension, and reduced jugular venous pressure. Patients with hypovolemia may present with a variety of laboratory abnormalities, including an elevated serum creatinine and blood urea nitrogen (BUN), hypernatremia or hyponatremia, hyperkalemia or hypokalemia, and metabolic alkalosis or metabolic acidosis.

Symptoms — Three sets of symptoms may occur in hypovolemic patients:

Those due to volume depletion

Those related to the cause of fluid loss

Those due to the electrolyte and acid-base disorders that can accompany volume depletion

Symptoms related to volume depletion — Symptoms induced by hypovolemia are primarily related to decreased tissue perfusion. The earliest complaints include lassitude, easy fatigability, thirst, muscle cramps, and postural dizziness. More severe fluid loss can lead to abdominal pain, chest pain, or lethargy and confusion due to ischemia of the mesenteric, coronary, or cerebral vascular beds, respectively. These symptoms are usually reversible, although tissue necrosis may develop if the low-flow state is allowed to persist.

Patients may also report decreased urine volume or frequency. Low urine volume (oliguria) is common in hypovolemic patients due to the combination of sodium and water avidity. If, however, concentrating ability is impaired, or if there is increased urea excretion due to catabolism, oliguria may not be present.

Symptomatic hypovolemia most often occurs in patients with isosmotic sodium and water depletion in whom most of the fluid deficit comes from the extracellular fluid. This contrasts with pure water loss due to insensible losses or diabetes insipidus, in which the elevation in the plasma osmolality (and sodium concentration) causes water to move down an osmotic gradient from the cells into the extracellular fluid. The net result of pure water loss is that approximately two-thirds of the water lost comes from the intracellular fluid, a condition which is called "dehydration" rather than "hypovolemia." Patients with pure water losses exhibit the symptoms of hypernatremia (produced by the water deficit) before those of marked extracellular fluid depletion. (See "General principles of disorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia and edema)", section on 'Definitions' and "Manifestations of hyponatremia and hypernatremia in adults".)

Symptoms related to the cause of fluid loss — Patients with hypovolemia will often have symptoms related to the cause of the fluid losses. These symptoms may include vomiting, diarrhea, polyuria, a severe skin burn, or, in the case of sequestration into a third-space, pain associated with the underlying etiology. (See 'Etiology' above.)

Symptoms related to electrolyte abnormalities — A variety of electrolyte and acid-base disorders may also occur in hypovolemic patients, depending upon the composition of the fluid that is lost. The more serious symptoms and associated abnormalities include the following:

Muscle weakness due to hypokalemia or hyperkalemia (see "Approach to the patient with muscle weakness")

Polyuria and polydipsia due to severe hypokalemia (see "Clinical manifestations and treatment of hypokalemia in adults", section on 'Kidney abnormalities')

Tachypnea due to acidosis (see "Approach to the adult with metabolic acidosis")

Neuromuscular irritability and confusion due to metabolic alkalosis (see "Clinical manifestations and evaluation of metabolic alkalosis")

Lethargy, confusion, seizures, and coma due to hyponatremia or hypernatremia (see "Manifestations of hyponatremia and hypernatremia in adults")

An additional symptom that occurs only in primary adrenal insufficiency is extreme salt craving. Patients with this disease frequently give a history of heavily salting all foods (including those not usually salted) and even of eating salt that they have sprinkled on their hands. The mechanism responsible for this appropriate increase in salt intake is not known. (See "Clinical manifestations of adrenal insufficiency in adults".)

Physical examination — Although relatively insensitive and nonspecific [4], certain findings on physical examination may suggest volume depletion. A decrease in the interstitial volume can be detected by the examination of the skin and mucous membranes, while a decrease in the plasma volume can lead to reductions in the systemic blood pressure and the venous pressure in the jugular veins.

Skin and mucous membranes — If the skin on the thigh, calf, or forearm is pinched in normal subjects, it will immediately return to its normally flat state when the pinch is released. This elastic property, called turgor, is partially dependent upon the interstitial volume of the skin and subcutaneous tissue. Interstitial fluid loss leads to diminished skin turgor, and the skin flattens more slowly after the pinch is released. In younger patients, the presence of decreased skin turgor is a reliable indicator of volume depletion. By comparison, elasticity diminishes with age, so that reduced skin turgor does not necessarily reflect hypovolemia in older patients (more than 55 to 60 years old). In these patients, skin elasticity is usually best preserved on the inner aspect of the thighs and the skin overlying the sternum. Decreased turgor at these sites is suggestive of volume depletion.

Although reduced skin turgor is an important clinical finding, normal turgor does not exclude the presence of hypovolemia. This is particularly true with mild volume deficits, in young patients whose skin is very elastic, and in obese patients, since fat deposits under the skin prevent the changes in subcutaneous turgor from being appreciated.

The skin is also usually dry in hypovolemic patients, and a dry axilla is particularly suggestive of the diagnosis [4]. The tongue and oral mucosa may also be dry since salivary secretions are commonly decreased in this setting.

Examination of the skin may be helpful in the diagnosis of primary adrenal insufficiency. The impaired release of cortisol leads to hypersecretion of ACTH, which can result in increased pigmentation of the skin, especially in the palmar creases and buccal mucosa. (See "Clinical manifestations of adrenal insufficiency in adults".)

Arterial blood pressure — The arterial blood pressure changes from near normal with mild hypovolemia to low in the upright position and then, with progressive volume depletion, to persistently low regardless of posture. Postural hypotension leading to dizziness may be the patient's major complaint and is strongly suggestive of hypovolemia in the absence of an autonomic neuropathy or the use of sympatholytic drugs for hypertension.

An important change that can occur with marked fluid loss is that the secondary neurohumoral vasoconstriction leads to decreased intensity of both the Korotkoff sounds (when the blood pressure is being measured with a sphygmomanometer) and the radial pulse [5,6]. As a result, a very low blood pressure suggested by auscultation or palpation may actually be associated with a near-normal pressure when measured directly by an intraarterial catheter.

It should be noted that the definition of normal blood pressure in this setting is dependent upon the patient's usual value. Although <120/80 mmHg is considered "normal," it is actually low in a hypertensive patient whose blood pressure is commonly 180/100 mmHg.

Jugular venous pressure — The reduction in the vascular volume observed with hypovolemia occurs primarily in the venous circulation (which normally contains 70 percent of the blood volume), thereby leading to a decrease in venous pressure. In most patients, the venous pressure can be estimated with sufficient accuracy by physical examination. The height of the jugular venous pulse above the right atrium (5 cm above the sternal angle of Louis) approximates the atrial pressure. However, characterization of the venous pressure as either low (less than or equal to 5 cm H20) or high (greater than or equal to10 cm H20) is probably as precise an estimate as can be achieved.

Theoretically, the internal jugular vein would provide a more accurate reflection of right atrial pressure than the external jugular vein because of its larger diameter, less tortuous course, and absence of valves. However, many clinicians find that pulsations of the external jugular vein are more easily seen, and inspection of this venous pulse alone has been shown to correlate with direct measurements made by a central venous catheter positioned in the right atrium [7].

Physical examination of jugular venous pressure can be augmented with bedside ultrasound of the internal jugular vein. In a study of 100 patients with heart failure who underwent cardiac catheterization, the ultrasound estimate agreed closely with measured right atrial pressure [8]. The accuracy of the technique in the diagnosis of hypovolemia is unknown.

Laboratory abnormalities — Hypovolemic patients can have a variety of abnormal results of routinely performed laboratory tests. In addition to suggesting the presence of volume depletion, these changes may provide important clues to the etiology.

Low urine volume — As noted above, the urine volume is typically, but not always, low (oliguria) in hypovolemic patients due to the combination of sodium and water avidity. If, however, concentrating ability is impaired, or if urea excretion is high, oliguria may not be present.

Elevation of the BUN and serum creatinine concentration — In most circumstances, the BUN and serum creatinine concentration vary inversely with the glomerular filtration rate (GFR), increasing as the GFR falls. Serial measurements of these parameters can be used to assess the course of kidney disease. However, an elevation in the BUN can also be produced by an increase in the rate of urea production or tubular reabsorption. As a result, the serum creatinine concentration is a more reliable estimate of the GFR since it is produced at a relatively constant rate by skeletal muscle and is not reabsorbed by the renal tubules. (See "Assessment of kidney function".)

In normal subjects and those with uncomplicated kidney disease, the BUN/serum creatinine ratio is approximately 10:1. However, this value may be substantially elevated in hypovolemic states because of the associated increase in urea reabsorption [9]. In general, approximately 40 to 50 percent of filtered urea is reabsorbed, much of this occurring in the proximal tubule, where it is passively linked to the reabsorption of sodium and water. Thus, the increase in proximal sodium reabsorption in volume depletion produces a parallel increase in urea reabsorption. The net effect is a fall in urea excretion and elevations in the BUN and the BUN/serum creatinine ratio, frequently to greater than 20:1. This selective rise in the BUN is called prerenal azotemia. The serum creatinine concentration will increase in this setting only if the degree of hypovolemia is severe enough to lower the GFR. (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults".)

Although an elevated BUN/serum creatinine may indicate hypovolemia, it is subject to misinterpretation for two major reasons: 1) the BUN is affected by the rate of urea production; a high ratio may be due solely to increased urea production (as with steroid therapy) rather than hypovolemia, whereas a normal ratio may occur in patients with hypovolemia if urea production is reduced (eg, due to decreased protein intake); 2) the serum creatinine is affected by muscle mass as well as GFR; a high ratio may be due to a low muscle mass (which lowers the serum creatinine concentration), increasing the BUN/serum creatinine ratio in the absence of hypovolemia.

A special case is the increased BUN/serum creatinine ratio in patients with upper gastrointestinal bleeding. In such patients, the ratio increases markedly for two reasons: the extracellular fluid volume is decreased due to the blood loss, which increases proximal tubule urea reabsorption; and the rate of urea production is increased due to the catabolism and absorption of blood proteins from the gastrointestinal tract.

Hypernatremia and hyponatremia — A variety of factors can influence the serum sodium concentration in hypovolemic states, and it is the interplay between them that determines the level observed in a given patient. Primary water loss, as in insensible losses or diabetes insipidus, results in hypernatremia. On the other hand, salt and water loss may be associated with hyponatremia. Volume depletion stimulates the release of antidiuretic hormone (ADH), which will tend to cause retention of ingested water.

(See "General principles of disorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia and edema)".)

(See "Etiology and evaluation of hypernatremia in adults".)

(See "Causes of hypotonic hyponatremia in adults".)

Hypokalemia and hyperkalemia — Either hypokalemia or hyperkalemia can occur in hypovolemic patients. The former is much more common because of potassium loss from the gastrointestinal tract or in the urine. However, there may be an inability to excrete the dietary potassium load in the urine because of kidney failure, hypoaldosteronism, or volume depletion itself since the delivery of sodium and water to the potassium secretory site in the cortical collecting tubule will be reduced. (See "Causes and evaluation of hyperkalemia in adults".)

Metabolic alkalosis and acidosis — The effect of fluid loss on acid-base balance also is variable. Although many patients maintain a normal extracellular pH, either metabolic alkalosis or metabolic acidosis can occur. Patients with vomiting or nasogastric suction or those given diuretics tend to develop metabolic alkalosis because of hydrogen ion loss and volume contraction. On the other hand, bicarbonate loss (due to diarrhea or intestinal fistulas) can lead to metabolic acidosis. In addition, lactic acidosis can occur in shock and ketoacidosis in uncontrolled diabetes mellitus. (See "Causes of metabolic alkalosis" and "Approach to the adult with metabolic acidosis".)

Hematocrit and serum albumin concentration — Since red blood cells and albumin are essentially limited to the vascular space, a reduction in the plasma volume due to volume depletion tends to elevate both the hematocrit (ie, relative polycythemia) and serum albumin concentration. However, these changes are frequently absent because of underlying hypoalbuminemia and/or anemia, due, for example, to bleeding.

Manifestations of shock — The symptoms and physical findings that have been described apply to patients with mild to moderate volume depletion who are still able to maintain an adequate level of tissue perfusion. However, as the degree of hypovolemia becomes more severe, due, for example, to the loss of 30 percent of the blood volume from a ruptured aortic aneurysm, there is a marked reduction in tissue perfusion, resulting in a clinical syndrome referred to as hypovolemic shock [5,10]. This syndrome is associated with a marked increase in sympathetic activity and is characterized by tachycardia, cold, clammy extremities, cyanosis, a low urine output (usually less than 15 mL/h), and agitation and confusion due to reduced cerebral blood flow. (See "Definition, classification, etiology, and pathophysiology of shock in adults".)

Manifestations in older adults — Unlike in younger individuals, excessive fluid loss in older individuals often presents with nonspecific signs and symptoms. The most specific for hypovolemia is acute weight loss; however, obtaining an accurate weight over time may be difficult in older adults. Weight loss is particularly important to identify because older adults, compared with the young, have a greater proportion of fat (relative to lean) muscle mass. Since there is less water in fat than in muscle, older individuals have a lower total body water (relative to weight) and therefore, for a given degree of fluid loss, will have a greater reduction in extracellular fluid volume.

Many clinical signs and symptoms that would suggest volume depletion in a younger individual may be unreliable in older adults. Postural hypotension, for example, is not uncommon in euvolemic older adult patients as a result of sympathetic dysfunction and poor physical conditioning. In addition, a dry tongue and mouth, muscle weakness, confusion, speech difficulty, and sunken eyes can occur in older adults for many reasons other than volume depletion [6].

Based upon the type of fluid lost and clinical setting, the older adult patient may have a normal, low, or high serum sodium concentration. Older individuals are particularly prone to hypernatremia because of impaired thirst mechanisms and an inability to increase water intake due to compromised mobility and/or swallowing ability.

DIAGNOSIS — In almost all cases, hypovolemia is a clinical diagnosis based upon the characteristic manifestations mentioned above and confirmed by a low urine sodium concentration. (See 'Clinical manifestations' above.)

An accurate history and physical examination not only provides evidence for the presence of volume depletion but may also help determine the etiology. In most individuals, the history should identify the source of fluid loss.

In older adults, however, the history may not identify the cause of hypovolemia. Such elements of the history may be absent in these patients because of confusion or cognitive issues.

An additional problem is the frequent inability to detect relative hypovolemia in patients with underlying edematous disorders or kidney failure. Although clinical and/or laboratory abnormalities may suggest relative volume depletion in some cases, others may require empiric fluid replacement therapy and/or intravascular monitoring to reverse the consequences of hypovolemia.

Urine sodium concentration — A low urine sodium concentration (or low urine chloride concentration in patients who have metabolic alkalosis) is strongly suggestive of reduced tissue perfusion, and it is usually present in hypovolemic patients unless there is a salt-wasting state (eg, diuretics, underlying kidney disease), selective kidney ischemia (eg, acute glomerulonephritis or bilateral renal artery stenosis), or a very low-sodium diet.

However, the presence of a low urine sodium does not necessarily mean that the patient has true volume depletion, since edematous patients with heart failure, cirrhosis with ascites, and the nephrotic syndrome also avidly conserve sodium. These disorders are characterized by reduced effective arterial blood volume due to a primary reduction in cardiac output (heart failure), to splanchnic vasodilatation and sequestration of fluid in the peritoneal cavity and arterial shunts (cirrhosis), and to a low plasma oncotic pressure (in some patients with severe or acute nephrotic syndrome).

The response of the kidney to true volume depletion and reduced effective arterial blood volume is to conserve sodium and water in an attempt to expand the extracellular volume. With the exception of those disorders in which sodium reabsorption is impaired, the urine sodium concentration in hypovolemic states should be less than 20 mEq/L and may be as low as 1 mEq/L. There are two additional exceptions in which the urine sodium concentration may be higher than 20 mEq/L despite the presence of hypovolemia:

When there is also a high rate of water reabsorption; in this setting, the rate of sodium excretion and urine volume are low, but the urine sodium concentration is higher than expected due to concentration of the urine.

When sodium is excreted with another anion [11]. This most often occurs in metabolic alkalosis due to vomiting or nasogastric suction. In such disorders, the metabolic alkalosis is associated with a high filtered bicarbonate load. The stimuli that increase renal sodium and bicarbonate reabsorption (volume depletion and hypokalemia) may sometimes be inadequate to remove all of the filtered sodium and bicarbonate from the urine. Under these conditions, urinary bicarbonate excretion occurs (with sodium as the accompanying cation). This occurs early in the disorder and also intermittently during established alkalosis, usually when transient further increases in serum bicarbonate occur (disequilibration phases of metabolic alkalosis). In such settings, the urine chloride concentration remains low (ie, below 20 mEq/L) and is a better index of extracellular fluid volume. (See "Clinical manifestations and evaluation of metabolic alkalosis".)

Less specific laboratory tests — Other laboratory tests can provide evidence for the presence of hypovolemia or reduced effective arterial blood volume, but are less specific than a low urine sodium or chloride concentration. These include the fractional excretion of sodium, the urine osmolality and specific gravity, and the urinalysis.

Fractional excretion of sodium — An alternative to measurement of the urine sodium concentration is calculation of the fractional excretion of sodium (FENa) using either standard units (calculator 1) or SI units (calculator 2). The FENa directly evaluates sodium handling and, in contrast to the urine sodium concentration, is not affected by changes in urine volume. (See "Fractional excretion of sodium, urea, and other molecules in acute kidney injury".)

The FENa is most useful in the differential diagnosis of oliguric acute kidney injury with a reduced glomerular filtration rate (GFR). In this setting, the FENa is usually under 1 percent in hypovolemic patients and above 1 percent when the oliguria is due to acute tubule necrosis [12,13]. By comparison, this measurement is more difficult to evaluate in patients with a normal GFR since the filtered sodium load is so high in this setting that a different value (FENa <0.1 to 0.2 percent) must be used to diagnose volume depletion. (See "Fractional excretion of sodium, urea, and other molecules in acute kidney injury", section on 'Fractional excretion of sodium varies with glomerular filtration rate'.)

Urine osmolality — In hypovolemic states, the urine is relatively concentrated with an osmolality often exceeding 450 mosmol/kg [12-14]. This response may not be seen, however, if concentrating ability is impaired by kidney disease, an osmotic diuresis, the administration of diuretics, or central or nephrogenic diabetes insipidus. As an example, both severe volume depletion (which impairs urea accumulation in the renal medulla) [15] and hypokalemia (which induces antidiuretic hormone [ADH] resistance) can limit the increase in the urine osmolality in some patients. Thus, a high urine osmolality is consistent with hypovolemia, but a relatively isosmotic value does not exclude the disorder [14].

Urinary concentration can also be assessed by measuring the specific gravity. The results are less reliable than the urine osmolality because specific gravity is determined by the mass rather than number of solute particles in the urine. A value above 1.015 is suggestive, but not diagnostic, of a concentrated urine, as is usually seen with hypovolemia. The urine specific gravity is misleadingly high with proteinuria or after administration of radiocontrast agents. (See "Urinalysis in the diagnosis of kidney disease", section on 'Specific gravity'.)

Urinalysis — Examination of the urine is an important diagnostic tool in patients with elevations in the BUN and plasma creatinine concentration. The urinalysis is generally normal in hypovolemic states since the kidney is not diseased. This is in contrast to most, but not all, of the other causes of kidney function impairment in which the urinalysis reveals protein, cells, and/or casts. (See "Urinalysis in the diagnosis of kidney disease".)

Central venous pressure — It is the left ventricular end-diastolic pressures (LVEDP), and not the right atrial pressure, that is the important determinant of left ventricular output which, together with vascular resistance, determines tissue perfusion. Although an estimate of central venous pressure can help determine a patient's volume status, the central venous pressure does not adequately predict whether or not an intravenous fluid challenge will increase stroke volume and cardiac index [16].

There are two major clinical settings in which the central venous or right atrial pressure provides an unreliable estimate of the LVEDP:

In patients with pure left-sided heart failure, the wedge pressure is increased, but the central venous pressure may remain unchanged if right ventricular function is normal. In this setting, treating a low central venous pressure with volume expanders can precipitate pulmonary edema.

The central venous pressure tends to exceed the LVEDP in patients with pure right-sided heart failure (as with cor pulmonale or following an acute right-sided myocardial infarction). These patients may have high central venous pressures even in the presence of volume depletion; as a result, the central venous pressure cannot be used as a guide to therapy. (See "Pulmonary hypertension due to lung disease and/or hypoxemia (group 3 pulmonary hypertension): Epidemiology, pathogenesis, and diagnostic evaluation in adults".)

Bedside ultrasound — Bedside ultrasound examination of the respiratory variation of the inferior vena cava diameter has been used to augment physical examination. However, this tool has not been shown to reliably predict fluid responsiveness [17].

Diagnosis in certain clinical settings

Heart failure — Congestive heart failure and hypovolemia share several biochemical features (a high BUN/creatinine ratio and a low urine sodium concentration). Physical examination allows easy differentiation between the two conditions. (See "Heart failure: Clinical manifestations and diagnosis in adults".)

However, persistently edematous patients with congestive heart failure who are aggressively treated with diuretics may develop a fall in cardiac output due to relative volume depletion, and the decrease in tissue perfusion will result in a rise in the BUN. It can be difficult to distinguish clinically between progression of intrinsic heart disease and relative hypovolemia. Such patients may require a cautious therapeutic trial of saline infusion or placement of a pulmonary artery catheter for optimal fluid management. (See "Pulmonary artery catheterization: Indications, contraindications, and complications in adults".)

Cirrhosis — As in congestive heart failure, the low urine sodium concentration found in cirrhotic patients with ascites and, in many cases, peripheral edema should not be confused with true volume depletion. The progressive vasodilation seen in cirrhosis leads to the activation of endogenous vasoconstrictors, sodium and water retention, and increasing renal vasoconstriction, thereby leading to a very low urine sodium concentration, hyponatremia, decreased tissue perfusion, and occasionally the hepatorenal syndrome. (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis".)

The hepatorenal syndrome is a prerenal disease, as the kidneys are normal histologically and have been used successfully for kidney transplantation. However, decreased kidney perfusion in this setting can also be induced by concurrent volume losses, including gastrointestinal losses, bleeding, or overly aggressive diuretic therapy. As a result, diagnosis of the hepatorenal syndrome requires the lack of improvement in kidney function following discontinuation of potential nephrotoxins and a trial of fluid repletion. (See "Ascites in adults with cirrhosis: Initial therapy" and "Hepatorenal syndrome".)

Kidney disease — The laboratory diagnosis of hypovolemia may be difficult to establish in patients with underlying kidney disease. In this setting, the urine sodium concentration may exceed 20 mEq/L, and the urine osmolality may be less than 350 mosmol/kg, since kidney function impairment impairs the ability to maximally conserve sodium and to concentrate the urine [2,14,18]. In addition, the urinalysis may be abnormal due to the primary disease.

Despite this difficulty, making the correct diagnosis is important since volume depletion is a reversible cause of worsening kidney function, in contrast to progression of the underlying kidney disease. The history and physical examination may be helpful in some patients, but these findings are not always present. As a result, a cautious trial of fluid repletion may be warranted in the patient whose kidney function has deteriorated without obvious cause. (See "Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting" and "Overview of the management of chronic kidney disease in adults".)

The diagnosis of intravascular volume depletion in the patient with nephrotic syndrome is particularly difficult. Despite a great deal of study, the relative roles of underfilling due to hypoalbuminemia and overflow due to renal sodium retention remain unclear and probably vary among patients [19,20]. Patients with "underfill" edema are more commonly those with a GFR greater than 75 percent of normal and with either minimal change disease of acute onset or severe hypoalbuminemia (often below 1 g/dL) [21,22]. The ability to distinguish between these two possibilities is extremely important, as diuretic therapy may be useful in those with elevated intravascular volumes but deleterious in patients with underfilling. (See "Pathophysiology and treatment of edema in adults with the nephrotic syndrome".)

Older adults — Although associated with nonspecific manifestations among older adults, the findings of hypernatremia and/or weight loss are suggestive for fluid loss. Additional helpful objective clinical signs, although less specific than in younger individuals, include an elevated BUN-to-creatinine ratio and a low urinary sodium concentration.

Shock — Although hypotension is generally present in patients with shock, it is not required for the diagnosis, since vasoconstriction sometimes maintains a relatively normal blood pressure [5,10]. Shock, independent of etiology, is characterized by tachycardia, cold, clammy extremities, cyanosis, a low urine output (usually less than 15 mL/h), and agitation and confusion due to reduced cerebral blood flow. Shock due to hypovolemia may be suggested by the history (whether obtained from the patient, observer, or family), physical examination, laboratory studies, and/or invasive monitoring (including pulmonary artery catheterization). (See "Definition, classification, etiology, and pathophysiology of shock in adults".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Fluid and electrolyte disorders in adults".)

SUMMARY

In a variety of clinical disorders, fluid losses reduce extracellular fluid volume, potentially compromising tissue perfusion. Early diagnosis and prompt treatment to restore euvolemia can be lifesaving. (See 'Introduction' above.)

Volume depletion results from loss of sodium and water from the following anatomic sites (see 'Etiology' above):

Gastrointestinal losses, including vomiting, diarrhea, bleeding, and external drainage

Renal losses, including the effects of diuretics, osmotic diuresis, salt-wasting nephropathies, and hypoaldosteronism

Skin losses, including sweat, burns, and other dermatological conditions

Third-space sequestration, including intestinal obstruction, crush injury, fracture, and acute pancreatitis

Hypovolemic patients may present with a variety of symptoms, physical examination findings, and laboratory abnormalities. Symptoms may be related to the volume depletion itself, such as lassitude and postural dizziness, or to the underlying cause of volume depletion, such as vomiting, diarrhea, or polyuria. The physical examination may reveal decreased skin turgor, low arterial blood pressure or postural hypotension, and reduced jugular venous pressure. Patients with hypovolemia may present with a variety of laboratory abnormalities, including an elevated serum creatinine and blood urea nitrogen (BUN), hypernatremia or hyponatremia, hyperkalemia or hypokalemia, and metabolic alkalosis or metabolic acidosis. (See 'Clinical manifestations' above.)

As the degree of hypovolemia becomes more severe, there is a marked reduction in tissue perfusion, resulting in a clinical syndrome referred to as hypovolemic shock. This syndrome is associated with a marked increase in sympathetic activity and is characterized by tachycardia, cold, clammy extremities, cyanosis, a low urine output, and agitation and confusion due to reduced cerebral blood flow. (See 'Manifestations of shock' above.)

Unlike in younger individuals, excessive fluid loss in older individuals often presents with nonspecific signs and symptoms. The most specific for hypovolemia is acute weight loss; however, obtaining an accurate weight over time may be difficult in older adults. Many clinical signs and symptoms that would suggest volume depletion in a younger individual may be unreliable in older adults. Postural hypotension, for example, is not uncommon in euvolemic older adult patients as a result of sympathetic dysfunction and poor physical conditioning. (See 'Manifestations in older adults' above.)

In almost all cases, hypovolemia is a clinical diagnosis based upon the characteristic manifestations mentioned above and confirmed by a low urine sodium concentration. An accurate history and physical examination not only provides evidence for the presence of volume depletion but may also help determine the etiology. In most individuals, the history should identify the source of fluid loss. (See 'Diagnosis' above.)

A low urine sodium concentration is strongly suggestive of reduced tissue perfusion, and it is usually present in hypovolemic patients unless there is a salt-wasting state (eg, diuretics, underlying kidney disease), selective kidney ischemia (eg, acute glomerulonephritis or bilateral renal artery stenosis), or a very low-sodium diet. There are two additional exceptions in which the urine sodium concentration may be higher than 20 mEq/L despite the presence of hypovolemia (see 'Urine sodium concentration' above):

When there is also a high rate of water reabsorption; in this setting, the rate of sodium excretion and urine volume are low, but the urine sodium concentration is higher than expected due to concentration.

When sodium is excreted with another anion; this is most often seen in metabolic alkalosis (due, for example, to vomiting), where the need to excrete the excess bicarbonate (as sodium bicarbonate) may raise the urine sodium concentration despite the presence of volume depletion. In this setting, the urine chloride concentration remains low (ie, below 20 mEq/L) and is frequently a better index of volume status.

  1. Coleman AJ, Arias M, Carter NW, et al. The mechanism of salt wastage in chronic renal disease. J Clin Invest 1966; 45:1116.
  2. Danovitch GM, Bourgoignie J, Bricker NS. Reversibility of the "salt-losing" tendency of chronic renal failure. N Engl J Med 1977; 296:14.
  3. Better OS. Impaired fluid and electrolyte balance in hot climates. Kidney Int Suppl 1987; 21:S97.
  4. McGee S, Abernethy WB 3rd, Simel DL. The rational clinical examination. Is this patient hypovolemic? JAMA 1999; 281:1022.
  5. Weil MH, von Planta M, Rackow EC. Acute circulatory failure (shock). In: Heart Disease. A Textbook of Cardiovascular Medicine, Braunwald E (Ed), Saunders, Philadelphia 1988.
  6. Cohn JN. Blood pressure measurement in shock. Mechanism of inaccuracy in ausculatory and palpatory methods. JAMA 1967; 199:118.
  7. Vinayak AG, Levitt J, Gehlbach B, et al. Usefulness of the external jugular vein examination in detecting abnormal central venous pressure in critically ill patients. Arch Intern Med 2006; 166:2132.
  8. Wang L, Harrison J, Dranow E, et al. Accuracy of Ultrasound Jugular Venous Pressure Height in Predicting Central Venous Congestion. Ann Intern Med 2022; 175:344.
  9. Dossetor JB. Creatininemia versus uremia. The relative significance of blood urea nitrogen and serum creatinine concentrations in azotemia. Ann Intern Med 1966; 65:1287.
  10. Baskett PJ. ABC of major trauma. Management of hypovolaemic shock. BMJ 1990; 300:1453.
  11. Sherman RA, Eisinger RP. The use (and misuse) of urinary sodium and chloride measurements. JAMA 1982; 247:3121.
  12. Miller TR, Anderson RJ, Linas SL, et al. Urinary diagnostic indices in acute renal failure: a prospective study. Ann Intern Med 1978; 89:47.
  13. Espinel CH, Gregory AW. Differential diagnosis of acute renal failure. Clin Nephrol 1980; 13:73.
  14. Rose BD. Pathophysiology of Renal Disease, 2d ed, McGraw-Hill, New York City 1987. p.82.
  15. LEVINSKY NG, DAVIDSON DG, BERLINER RW. Effects of reduced glomerular filtration on urine concentration in the presence of antidiuretic hormone. J Clin Invest 1959; 38:730.
  16. Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest 2008; 134:172.
  17. Millington SJ. Ultrasound assessment of the inferior vena cava for fluid responsiveness: easy, fun, but unlikely to be helpful. Can J Anaesth 2019; 66:633.
  18. DORHOUT MEES EJ. Relation between maximal urine concentration, maximal water reabsorption capacity, and mannitol clearance in patients with renal disease. Br Med J 1959; 1:1159.
  19. Meltzer JI, Keim HJ, Laragh JH, et al. Nephrotic syndrome: vasoconstriction and hypervolemic types indicated by renin-sodium profiling. Ann Intern Med 1979; 91:688.
  20. Schrier RW, Fassett RG. A critique of the overfill hypothesis of sodium and water retention in the nephrotic syndrome. Kidney Int 1998; 53:1111.
  21. Vande Walle JG, Donckerwolcke RA, van Isselt JW, et al. Volume regulation in children with early relapse of minimal-change nephrosis with or without hypovolaemic symptoms. Lancet 1995; 346:148.
  22. Vande Walle JG, Donckerwolcke RA, Koomans HA. Pathophysiology of edema formation in children with nephrotic syndrome not due to minimal change disease. J Am Soc Nephrol 1999; 10:323.
Topic 2298 Version 23.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟