Hypovolemia and dehydration are both examples of fluid deficiency. how do they differ?

I Introduction

The term hypovolemia refers collectively to two distinct disorders: (1) volume depletion, which describes the loss of sodium from the extracellular space (i.e., intravascular and interstitial fluid) that occurs during gastrointestinal hemorrhage, vomiting, diarrhea, and diuresis; and (2) dehydration, which refers to the loss of intracellular water (and total body water) that ultimately causes cellular desiccation and elevates the plasma sodium concentration and osmolality.1 Chapter 17 discusses the accuracy of abnormal vital signs in patients with volume depletion; this chapter discusses assorted additional findings.

CVOs in the Regulation of Salt Appetite

Hypovolemia also activates salt appetite (to restore lost solute), albeit on a slower time scale than thirst. ANG and aldosterone play roles in inducing salt appetite during hypovolemia, perhaps acting synergistically. The possible mechanism of the synergism is quite elegant: aldosterone may act via a nuclear receptor to increase expression of the AT1 subtype of receptor protein in the SFO, leading to a potentiated response of SFO neurons to ANG and thus increased salt appetite. Available data also suggest an inhibitory role of AP in salt appetite because AP lesions enhance NaCl solution intake.

Hypovolemia and Dehydration

Hypovolemia results in decreased perfusion and subsequent decreases in oxygen delivery to tissues. The most common syndromes associated with hypovolemia in neonates are diarrhea, vomiting, or decreased fluid intake. In adults, hypovolemia is compensated or partially compensated for by increasing the heart rate, concentrating the urine, and decreasing urine output. In neonates, compensatory mechanisms may be inadequate or even nonexistent. Contractile elements make up a smaller portion of the fetal myocardium (30%) compared to the adult myocardium (60%), making it difficult for the fetus to increase cardiac contractility in response to hypovolemia. Neonates also have immature sympathetic nerve fibers in the myocardium and cannot maximally increase heart rate in response to hypovolemia. Complete maturation of the autonomic nervous system does not occur until after 8 weeks of age in puppies.

MAP is lower (49 mm Hg) in normal neonates at 2 months of age and normalizes (94 mm Hg) by 9 months of age. This difference appears to be due to the immaturity of the muscular component of the arterial wall at birth. In adults, the kidneys autoregulate blood pressure over a wide range of systemic arterial pressures, but neonatal kidneys are unable to accomplish this. The neonate's glomerular filtration rate (GFR) decreases as the systemic blood pressure decreases, making restoration of fluid volume critical in neonates.

Immature kidneys are incapable of concentrating urine in response to hypovolemia. Appropriate concentration and dilution of urine is not seen until approximately 10 weeks of age. The capacity to concentrate urine increases almost linearly with age during the first year of life in humans. Inefficient countercurrent mechanisms, decreased sodium resorption in the thick ascending loop of Henle, relatively short loops of Henle, and decreased urea concentration are thought to be causative. Simultaneously, BUN and creatinine are lower in neonates than adults, making monitoring of azotemia in this group very challenging.

The skin of a neonate has an increased fat and decreased water content compared to adults; therefore skin turgor cannot be used to assess dehydration. Mucous membranes remain moist in the face of severe dehydration in neonates and cannot be used to adequately assess it.

Because neonatal fluid requirements (higher than adults) and increased losses (decreased renal concentrating ability, higher respiratory rate, and higher metabolic rate), dehydration can rapidly progress to hypovolemia and shock if not adequately treated. The most common causes of hypovolemia in neonates are gastrointestinal (GI) disturbances (e.g., vomiting, anorexia, and diarrhea) and inadequate feeding. The most common cause of diarrhea in neonatal puppies and kittens is owner overfeeding with formula.

Because it can be so difficult to adequately assess hypovolemia in neonates, some assumptions should be made. One should assume that all neonates with severe diarrhea, inadequate intake, or severe vomiting are dehydrated, and potentially hypovolemic and aggressive treatment should be started immediately. Treatment of hypovolemia includes rapid replacement fluid therapy, monitoring of electrolyte and glucose status, and nutritional support. The patient should be weighed at least every 12 hours, preferably every 8 hours. Dehydration is likely when the urine specific gravity reaches 1.020, and this should be monitored as an indicator of rehydration. An initial bolus of 45 ml/kg of warm isotonic fluids in severely dehydrated or hypovolemic animals is given as fast as possible and followed by a constant rate infusion of maintenance fluids (80 ml/kg/day), as well as estimated fluid losses. Losses can be estimated (i.e., 2 tbsp of diarrhea is equal to 30 ml of fluid). If the neonate is hypoglycemic or unable to eat, dextrose is added to the IV fluids at the lowest amount that will maintain normoglycemia (i.e., start with 1.25% dextrose).

Hypovolemic Shock

Hypovolemia can be either absolute or relative in nature and is a common presentation of shock. Hemorrhagic shock is considered an absolute cause of hypovolemia because an actual loss of intravascular blood volume has occurred. Common clinical presentations include hemoperitoneum secondary to hemorrhage from splenic or hepatic neoplasia, coagulopathies (e.g., anticoagulant rodenticide toxicity, thrombocytopathia, thrombocytopenia), gastrointestinal hemorrhage, epistaxis, and traumatic lacerations of arteries or other major blood vessels.14,41 Nonhemorrhagic shock is associated with relative hypovolemia despite no direct loss of whole blood from the intravascular space. The primary phy-siologic event is loss of plasma volume. Examples of loss of plasma volume include severe dehydration and third-space loss (e.g., peritoneum, intestinal tract). Anaphylactic shock is a clinical form of shock that has important hypovolemic and distributive components. It occurs as a result of immunoglobulin E–mediated release of vasoactive substances that produce massive vasodilatation and pooling of as much as 60% to 80% of the circulating blood volume (i.e., distributive), as well as endothelial injury and the leak of large volumes of fluid and plasma proteins from the intravascular to interstitial spaces (i.e., hypovolemic).42

Pathologic Causes

Hypovolemia without spermatozoa in the semen, and with a pH less than 7.4 could be due to ejaculatory duct obstruction or congenital absence of the seminal vesicles (Roberts and Jarvi, 2009).

Semen chemistries should be investigated. Such symptoms are associated with either partial or complete absence of fructose (produced by the seminal vesicles). However, normal zinc and acid phosphatase content with acidic pH (produced by the prostate gland) should be present.

Hypovolemia with spermatozoa present in semen and with a pH less than 7.4 could be due to obstruction of the seminal vesicular opening by a mucus-like plug, producing a high sperm concentration (Perez-Pelaez et al, 1988).

The obstructing plug may dissolve spontaneously, causing resumption of normal ejaculate volumes; but more often than not the obstacle actually enlarges, causing azoospermia over time.

Stricture of the seminal vesicular duct, probably due to inflammation, may also result in this condition.

Hypovolemia without (or low numbers of) spermatozoa in semen and with pH more than 7.8 could be due to hypoandrogenism leading to impaired spermatogenesis, while some fructose may still be present (Jeyendran, 2000).

Hypovolemia with spermatozoa present in the semen and with a pH greater than 7.8 could be due to a partial or incomplete retrograde flow of semen.

Post ejaculate; voided urine must be examined (Kamischke and Nieschlag, 1999; Mieusset et al, 2017).

This condition may also be due to accessory sex gland impairment caused by inflammation or cancer (especially if the pH is more than 9.0; Jeyendran, 2000).

Other factors that appear to affect ejaculate volume include dietary zinc deficiency (Hunt et al, 1992), HIV -1 infection (Bujan et al., 2007), Klinefelter syndrome (Aksglaede et al, 2009), and certain drugs such as Silodosin and Tamsulosin (Nudell et al, 2002).

Volume dysregulation

Hypovolemia has been reported in a significant portion of patients with POTS (Rosen and Cryer, 1982; Fouad et al., 1986; Khurana, 1995; Raj et al., 2005a). Twenty-four–hour urinary sodium excretion correlates with plasma volume as measured by Evans blue dye, with 170 mEq/24 h corresponding to normovolemia (El-Sayed and Hainsworth, 1996). In one large series of patients with POTS, 29% were hypovolemic using conservative criteria of urinary sodium excretion less than 100 mEq/24 h (Thieben et al., 2007). As a result of low plasma and total blood volumes, not enough blood returns to the heart upon standing (reduced preload). In many cases, these patients have low levels of plasma renin activity and aldosterone compared with controls (Jacob et al., 1997a; Raj et al., 2005a); these patients may have a primary renal defect. Other patients have reduced angiotensin-converting enzyme 2 activity, leading to inappropriately high plasma angiotensin II levels (Stewart et al., 2009). Hypovolemia alone is unlikely to cause POTS, however, since overnight hydration did not reverse OI (Masuki et al., 2007a). Secondary OI/POTS is common in patients with functional gastrointestinal disorders associated with poor oral intake due to nausea or excess fluid loss due to diarrhea (Benarroch, 2012). The gastrointestinal diagnosis is the preferred diagnosis, since treating it will usually improve volume status and OI.

With or without hypovolemia, excessive venous pooling also occurs in many patients with POTS (Stewart and Weldon, 2001). As a result of poor venomotor tone (see neuropathic POTS covered previously), blood pools in the veins of the lower limbs and abdomen (splanchnic–mesenteric bed) (Tani et al., 2000). Red blood cell labeling with sodium pertechnetate Tc 99m has demonstrated excessive sequestration of isotope to the calves while standing that corrected after venous compression (Streeten, 1987; Streeten et al., 1988). Venous pooling is also suggested by an excessive fall in end-diastolic volume and stroke volume during head-up tilt (Low et al., 1994). OI symptoms can be treated with compression garments at a pressure that reduces venous capacitance (Streeten, 1987).

Capillary leakage on standing, which is compounded by venous pooling, leads to a net loss of plasma volume (Stewart, 2003) and mechanistically links venous pooling to hypovolemia. Pooling also reduces cardiac preload, unloads the baroreceptors in the upright position, and results in increased sympathetic outflow, providing a mechanistic link between venous pooling and hyperadrenergic POTS.

Blood Volume Status Parameters

Hypovolemia should be addressed in patients before therapy for dehydration. Volume status is classically divided into preload and forward flow parameters. The Frank–Starling law of the heart dictates that cardiac output is related to end-diastolic volume, a component of cardiac preload; for this reason adequate venous return is vital to ensuring appropriate perfusion. Preload parameters are indicators of the adequacy of venous return to the heart and include venous volume and cardiac chamber diameters. Venous volume cannot be directly measured in vivo and must be estimated by assessing the ease of venous distention, central venous pressure, and radiographic diameter of the caudal vena cava.

In a patient with normal blood volume, both jugular and peripheral veins should distend easily when occluded. Lack of venous distention in vessels above the level of the heart may indicate hypovolemia. Obviously, this is a subjective assessment, but it can give some idea of relative volume status.

Venous volume can also be indirectly assessed by measuring CVP. CVP is the hydrostatic pressure of the blood entering the heart, as measured by a catheter with its tip in the right atrium or vena cava. CVP is proportional to the volume of blood in the anterior vena cava and venous tone. This pressure is decreased by hypovolemia or venodilation and is increased by fluid therapy or venoconstriction. Several other factors can contribute to the accuracy of CVP measurement, such as cardiac or respiratory pathology, making it a somewhat unreliable (but useful) physiologic variable.

CVP can be measured with a column manometer (the most common method) or a direct pressure transducer. The normal range is 0 to 10 cm H2O. However, because of variations in venous tone and other technical factors, single CVP values are often difficult to interpret without the aid of other monitoring. Normal and abnormal values can overlap; for example, CVP can range from −5 to +5 cm of H2O in hypovolemic animals and from 5 to 15 cm H2O in animals with volume overload. Therefore measurements should be considered meaningful to the fluid therapy prescription only if they are below 0 or above 10 cm of water and, more important, if the overall trend in CVP is considered. Taking into account all available parameters, if a patient's CVP is consistently below 0 cm H2O, consideration should be given to either a bolus of fluids or an increased rate of fluid administration. If a patient's CVP value is consistently above 10 cm H2O, fluid administration should be slowed or discontinued, and diuretic administration should be considered.

CVP measurements are primarily indicated during volume restoration for shock and in patients for whom volume overload is a concern, such as patients in acute renal failure or those with concurrent cardiac disease.

Observation of correct technique for CVP measurement is very important, insofar as there is considerable interoperator variability. For the most accurate and clinically useful results, the patient's position should be recorded in the medical record and the same staff should perform the readings whenever possible.

To measure CVP (see Figure 5-4), the patient is positioned in right lateral recumbency and the level of the right atrium (near the manubrium—the cranial tip of the sternum) is identified. The clinician should ensure that the stopcock is level with the right atrium (this line is known as the phlebostatic axis) using a bubble level. This serves as the reference point and is the “zero” mark on the manometer.

With the stopcock closed towards the patient, the clinician opens the fluid bag line and fills the manometer to about 25 to 30 cm H2O. The clinician then opens the stopcock toward the patient (turning it off toward the fluid bag) and allows the fluid in the manometer to run into the patient. At some point the fluid will begin to oscillate with the patient's heartbeat and will stop falling as it equilibrates with the pressure in the vena cava (usually about 25 to 30 seconds); this is the CVP measurement and should be noted in the patient's record.

Venous volume can also be very roughly estimated by evaluating the diameter of the caudal vena cava on a lateral thoracic radiograph. Normal diameter is roughly equivalent to one rib width. A small caudal vena cava diameter suggests hypovolemia, and further fluid administration may be indicated depending on the patient's status. A large caudal vena cava diameter may suggest hypervolemia or heart failure, and the fluid therapy prescription should be re-evaluated.

Papillary Necrosis

Hypovolemia and dehydration during prolonged or excessive NSAID administration can predispose to papillary necrosis. It is often seen on post-mortem examination in horses with a clinical history of NSAID administration, but rarely does it produce clinical signs.

Necrosis of renal papillae, or in the horse the medullary crest, is a response of the inner medulla to ischemia. Papillary necrosis can be a primary or secondary lesion; however, papillary necrosis occurs as a primary disease in horses treated with NSAIDs. The primary disease occurs quite frequently in horses treated for prolonged periods with phenylbutazone or flunixin meglumine. The medullary interstitial cells are the primary targets for NSAIDs, and interstitial cell damage results in inhibition of cyclooxygenase and decreased prostaglandin synthesis. The resulting reduction in inner medullary blood flow causes ischemia/hypoxia, and it also causes degenerative changes in tubular epithelial cells and ischemic necrosis (infarction) of the medullary crest.

Affected horses also often have ulcers within various areas of the alimentary tract. Usually, clinical cases of NSAID toxicosis present with signs of alimentary tract disease ranging from excessive salivation and inappetence to diarrhea and colic. At autopsy (syn: necropsy), medullary crest necrosis may be present. Acute renal lesions are irregular, discolored areas of necrotic inner medulla sharply delineated from the surviving medullary tissue (see Fig. 11-48). The affected inner medulla is yellow-gray, green, or pink. The cortices may be slightly swollen. With time, the necrotic tissue sloughs, resulting in a detached, friable, and discolored tissue fragment in the pelvis. The remaining inner medulla is usually attenuated and on cross section is narrowed. Overlying cortex can be somewhat shrunken because of atrophy of some of the nephrons caused by blockage of their tubules in the affected medulla.

Clinicopathologic Evaluation

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PCV

Total plasma protein (TPP)

Complete blood count (CBC)

Blood gases

Electrolyte determination

Lactate

RAAS, Blood Volume, and Blood Pressure Regulation

Hypovolemia and hypotension are common in critically ill people and animals, and regulation of blood pressure and blood volume is quite complex. The RAAS, HPA axis, and arginine vasopressin (AVP, also known as antidiuretic hormone or ADH) work independently and in concert to control these responses during both health and illness. The RAAS is activated when macula densa cells in the renal juxtaglomerular apparatus sense decreases in blood volume or blood sodium concentration or increases in plasma potassium concentration, resulting in renin release. Renin cleaves plasma angiotensinogen to angiotensin I, which is then further processed to the potent vasoconstrictor angiotensin II by pulmonary angiotensin-converting enzyme (ACE). In addition to vasoconstriction, angiotensin II induces aldosterone release from the adrenal cortices. Aldosterone increases blood volume and pressure by activating the renal tubular sodium potassium ATPase and epithelial sodium channels to enhance renal sodium and water reabsorption, as well as potassium excretion. Increases in plasma osmolality and decreases in arterial pressure are also detected by hypothalamic osmoreceptors and arterial stretch receptors, respectively, stimulating hypothalamic AVP synthesis and release from the posterior pituitary. The primary effect of AVP is the insertion of aquaporin channels in the renal medullary collecting ducts to increase water reabsorption, thus increasing blood volume and blood pressure. AVP also can directly induce arteriolar vasoconstriction and activates the HPA axis by inducing pituitary ACTH release. HPA axis activation and resultant increases in plasma cortisol further aid blood pressure regulation via direct cardiac inotropic effects and downregulation of the vasodilator nitric oxide.

In critical illness, RAAS activation is important for blood pressure and electrolyte regulation, but excessive activation can have detrimental effects. Angiotensin II has recently been demonstrated to have proinflammatory effects, and associations between angiotensin II and increased organ failure and mortality have been described.53 Transient hyperreninemic hypoaldosteronism is observed frequently in people with septic shock and is associated with the development of acute renal failure in these patients.54 This hypoaldosteronism could be a reflection of adrenocortical suppression in CIRCI and could play a role in persistent hypotension in affected patients, but as described earlier, specific signs of mineralocorticoid deficiency like electrolyte derangements are uncommon in CIRCI. Information regarding specific RAAS responses in critically ill horses is limited. Hypotensive adult horses demonstrated increased aldosterone concentrations before fluid resuscitation, but aldosterone responses to hypotension appear to be exaggerated in neonatal foals.55 RAAS activation in critically ill foals is mainly characterized by an increase in angiotensin II and aldosterone concentrations.56 Renin activity and aldosterone concentrations were also increased in horses with experimentally induced laminitis but might represent appropriate responses to concurrent hyponatremia rather than pathologic RAAS activation.57 Effects of RAAS on activation on inflammatory status and mortality are not described in horses or foals.

AVP concentrations are initially increased in most acutely critically ill patients, stimulated by the development of hypotension and systemic inflammation (proinflammatory cytokines are potent AVP secretagogues).3,58 In many patients with septic shock, AVP concentrations tend to fall dramatically despite persistent hypotension, consistent with relative AVP deficiency due to both depletion of stored AVP and inhibition of AVP synthesis.58 Tissue AVP activity may also be impaired by inflammatory responses in critical illness.3 However, there are conflicting reports regarding associations between increases or decreases in AVP concentration and mortality in critically ill patients.58 Increased AVP concentrations were observed in adult horses with naturally occurring hypovolemia, but not in a small group of hypotensive foals, suggesting AVP responses in foals might be immature.55 Larger studies documented higher AVP concentrations in septic foals and an association among high AVP concentrations, hypoperfusion, and decreased survival.59 Vasopressin infusions are sometimes used as vasopressors in hypotensive people, but variable efficacy and concerns regarding potential side effects associated with decreased skin and splanchnic blood flow limit its clinical application.21,58 Studies investigating the safety and efficacy of vasopressin infusions in horses and foals are lacking, though vasopressin is used anecdotally as a vasopressor in some critically ill neonatal foals with reported success.

Adrenomedullin also plays a role in hemodynamics. Adrenomedullin is a vasodilator peptide of the calcitonin gene family produced by chromaffin cells of the adrenal medulla, cardiac myocytes, and cells in other tissues. It has antiapoptotic and antiinflammatory properties, attenuates ischemia and reperfusion injury, modulates vascular tone, enhances microcirculatory function, promotes angiogenesis, reduces intestinal mucosa permeability, counteracts the RAAS, inhibits aldosterone secretion, increases natriuresis, and supports cardiovascular function during SIRS and sepsis.60,61 Adrenomedullin concentrations are increased in people with sepsis and endotoxemia, hypertension, heart failure, and myocardial infarction.61-63 Its production by cardiac myocytes is stimulated by TNF-α, IL-1β, angiotensin II, endothelin-1, and hypoxia. Adrenomedullin concentrations were valuable to individualize human patients who require hemodynamic support.64 Adrenomedullin analogs have been proposed as therapeutic agents and there are ongoing clinical studies using monoclonal antibodies to the N-terminus of adrenomedullin to prolong its half-life in septic human patients.60 A recent study found high plasma adrenomedullin concentrations in critically ill compared with healthy foals; however, concentrations were not different between septic and nonseptic foals and were not associated with survival.65