Which hormone is most likely to cause a reduction in blood volume and pressure?

Water and the Kidney

Regulation of plasma osmolarity is accomplished by varying the amount of water excreted by the kidney. Concentrated hyperosmotic urine is produced when circulating levels of antidiuretic hormone (ADH) are high. ADH, also known as vasopressin (see Chapter 35). ADH is released from the posterior pituitary (neurohypophysis) in response to increased osmolality (sensed by magnocellular neurons in the hypothalamus), decreased circulating plasma volume and/or angiotensin II. ADH increases the number of aquaporin channels in the collecting ducts of the nephron, facilitating water reabsorption by osmosis. ADH secretion occurs in times of water deprivation or hemorrhage, or with syndrome of inappropriate ADH (SIADH). Without ADH, dilute urine is excreted owing to reduced permeability of the distal tubules and collecting ducts to water, leading to little water reabsorption and the potential for hypernatremia (see Chapter 42).

Hypernatremia.

Hypernatremia is associated with increased plasma osmolarity and is usually associated with a relative water deficit. Hypernatremia can produce symptoms of weakness, drowsiness, obtundation, and seizures. The plasma sodium concentration at which symptoms occur depends on the rapidity with which hypernatremia has developed, but symptoms are unlikely with a plasma sodium concentration of less than 155 mmol/l.

Hypernatremia may occur as the result of vigorous administration of sodium-rich solutions (0.9% sodium chloride and 8.4% sodium bicarbonate) or due to the loss of sodium-poor, hypotonic fluids. Patients are typically hypervolemic with the former and hypovolemic with the latter. Diarrhea, gastric secretions, and sweat all have sodium concentrations of less than 100 mmol/l. (In contrast, small bowel and pancreatic secretions have a sodium concentration similar to that of extracellular fluid.) During the polyuric recovery phase of acute renal failure, the ability of the renal tubules to concentrate urine is impaired, and the sodium concentration of urine is typically less than 100 mmol/l. The urinary sodium concentration in patients receiving furosemide is also less than 100 mmol/l. Untreated, the loss of water in excess of sodium leads to hypernatremia and hypovolemia.

An important cause of hypernatremia is diabetes insipidus. Diabetes insipidus involves either a failure of production of antidiuretic hormone (central diabetes insipidus) or lack of renal responsiveness to antidiuretic hormone (nephrogenic diabetes insipidus). Central diabetes insipidus may occur in patients with neurologic injury or brain death (see Chapter 38). Nephrogenic diabetes insipidus may occur due to loss of the hypertonic medullary interstitium (see Chapter 1). This is the cause of the polyuria that accompanies renal failure and diuretic administration. Nephrogenic diabetes insipidus may also occur because of reduced responsiveness of the distal nephron to antidiuretic hormone; causes of this state include drugs (e.g., amphotericin B, aminoglycosides, and lithium), hypokalemia, and hypercalcemia. Patients with diabetes insipidus produce large volumes of very dilute urine (urinary osmolality <200 mosmol/l) which, if not replaced, causes hypovolemia.

The treatment of hypernatremia depends on the cause and on the patient's intravascular volume status. With hypovolemia, initial resuscitation should include a balanced crystalloid solution such as Plasma-Lyte. Subsequent treatment should be directed at the relative water deficit. For ongoing losses of sodium-poor fluid, administration of half-normal sodium chloride (0.45% sodium chloride) or free water is appropriate. Half-normal sodium chloride is particularly useful in the management of the polyuric phase of acute renal failure. Because 0.45% sodium chloride is hypotonic, it should be given slowly or administered into a central vein to avoid hemolysis. Free water may be given enterally (as tap water added to enteral feeds) or intravenously as 5% dextrose. A dosage of between 50 and 150 ml/hr is appropriate in most circumstances. Treatment of central diabetes insipidus is described in Chapter 38.

5 Vasopressin in hypertension

Increases in 1–2% plasma osmolarity causes increases in AVP release into the bloodstream inducing vasoconstrictor and antidiuretic effects (Bankir et al., 2017). Recent studies have shown that prolonged high salt intake promotes pathological plasticity in the circuit that controls the secretion of vasopressin. This will cause chronic vasoconstrictor activity of AVP, which is mediated by the activation of V1R receptor located on vascular smooth muscle (Kawano & Ferrario, 1990; Kawano, Matsuoka, Nishikimi, Takishita, & Omae, 1997; Nishikimi, Kawano, Saito, & Matsuoka, 1996), increasing water retention in the collecting duct and also stimulating the intratubular renin angiotensin system (Gonzalez et al., 2016). Thus, the increase in AVP leads to water retention and vasoconstriction, contributing to an elevation of blood pressure, either by V1R or V2R activation.

In the collecting duct activation of AT1R and V2R induced increases in sodium and water reabsorption via epithelial sodium channel (ENaC) and AQP2, respectively suggesting that there is an amplification mechanism where exogenous Ang II and activation of V2R (Bankir et al., 2010). It is also likely that the exogenous Ang II and vasopressin stimulate the production of Ang II de novo in the kidney through the activation intratubular renin angiotensin system worsening the whole picture in hypertension.

Studies in preeclampsia characterized by hypertension and fetal growth restriction have shown high levels of AVP as early as the sixth week of gestation, which inherently is earlier than other biomarkers, supporting the conclusion that AVP secretion is increased early and throughout pregnancies that eventually develop preeclampsia (Sandgren, Deng, et al., 2018; Sandgren, Linggonegoro, et al., 2018; Sandgren et al., 2015; Santillan et al., 2014; Scroggins et al., 2018). Infusion of AVP throughout gestation is sufficient to initiate major preeclamptic phenotypes in mice, including elevated systolic blood pressure, proteinuria and intrauterine growth restriction (Sandgren, Deng, et al., 2018). Furthermore, the use of low doses of vasopressin and their analogues can be used to treat hypotension in patients prescribed renin angiotensin system inhibitors, demonstrating that vasopressin is enough to recover arterial blood pressure in the absence of renin angiotensin system activation.

Computer Controls

As discussed earlier, solute removal during hemodialysis decreases plasma osmolarity, favors fluid shift into the cells, and makes fluid removal more difficult. Increasing the dialysate sodium concentration helps to preserve plasma osmolarity and allows continued fluid removal167,168 but may lead to increased thirst, excessive weight gain, and hypertension.167,169 Computer-controlled sodium modeling allows the dialysate sodium concentration to change automatically during dialysis according to a preselected profile, usually 150 to 160 mEq/L at the beginning of dialysis to 135 to 140 mEq/L near or at the end of dialysis. Theoretically this sodium modeling offers the benefit of greater hemodynamic stability while minimizing thirst and interdialysis hypertension. To date, a few small studies support this theory,169-173 but the results are not conclusive.174,175 Most authorities advise against sodium modeling.176

Ultrafiltration modeling, like sodium modeling, provides a variable rate of fluid removal during dialysis, according to a preprogrammed profile (linear decline, stepwise changes, or exponential decline of filtration rate with time). Altering the filtration rate during dialysis theoretically allows time for the blood compartment to refill from the interstitial compartment, leading to improved hemodynamic stability and less cramping. As with sodium modeling, ultrafiltration modeling must be individualized. In fact, the effects of the two are difficult to distinguish because they are often used together.170,173,174,177

Technological advances include the development of dialysis machines with feedback control systems that allows for computer-controlled adjustments of the ultrafiltration rate and dialysate conductivity to prevent the blood volume from dropping to less than a preset value throughout the dialysis session.178,179 Studies in small groups of hemodialysis patients have reported that this device reduces symptoms in both hypotension- and non–hypotension-prone patients.178,180,181 The ability to monitor plasma conductivity throughout dialysis also ensures sodium balance during treatment despite constant modifications to the dialysate conductivity and may reduce the problem of thirst and interdialytic hypertension reported with sodium modeling.178 Automated control of dialysate temperature to maintain isothermic dialysis (constant body temperature) was superior to thermoneutral dialysis (using lower but constant dialysate temperature) in reducing intradialytic hypotension.182

Oxytocin and Sodium Balance

Oxytocin secretion is stimulated in the rat by increased plasma osmolarity and has natriuretic actions.81 Magnocellular oxytocin neurons and oxytocin secretion are also stimulated by blood volume expansion.51,82 The natriuretic action of oxytocin is exerted partly on the kidney,83 and also via the heart by stimulating ANP release by the atria.84

In late pregnancy, oxytocin receptor mRNA level in the heart and kidney, circulating ANP levels, and renal sensitivity to ANP are all reduced.85–87 Hence the oxytocin-ANP axis that would normally oppose Na+ retention and blood volume expansion is less active in pregnancy. In addition, in pregnancy, as a result of the reduced osmolarity caused by the stimulation of vasopressin secretion by relaxin, the threshold for osmotic stimulation of secretion of oxytocin is normally not reached; indeed, a hyperosmotic stimulus that does not increase osmolarity above the nonpregnant level is ineffective in pregnant rats.88 Consequently, under normal conditions in pregnancy, Na+ excretion is reduced, to an extent that enables the hyponatremia seen in pregnancy. Nonetheless, a sufficiently large hyperosmotic or hypervolemic stimulus in pregnant rats does stimulate oxytocin secretion, as the threshold is exceeded, and the stimulus-response relationship is then similar to that without pregnancy.89,90

Electrolyte losses

It is well known that equine sweat is hypertonic with respect to plasma osmolarity. Sweat contains relatively low levels of calcium, magnesium and phosphate but relatively high levels of sodium, potassium and chloride.18 Sodium concentrations in sweat and plasma are equivalent.10,22 In response to dehydration, Na+ ions are reabsorbed in the kidney in exchange for K and H+ ions. However, with substantial loss of Na+ homeostasis is disturbed and the circulatory system is affected. This can be responsible for a decrease in blood pressure and increased capillary refill time and heart rate.10 K+ losses in sweat are very high; they are worsened by the mechanisms of renal sodium reabsorption. In addition, during the race, due to the elevation of blood cortisol levels related to stress, loss of K+ in sweat and urine is increased. The loss of Cl− ions in the sweat is the sum of losses in Na+ and Cl−. Cl− is normally the primary ion reabsorbed by the kidneys. When the Cl− concentration decreases, bicarbonate ions (HCO3−) are reabsorbed to maintain the anion gap within its normal range.15 Calcium and magnesium contents in the sweat are greater than that of plasma. Sweating losses therefore can contribute to hypocalcemia and hypomagnesemia.

The practice of electrolyte administration by owners has significantly changed over the last 10-20 years; these practices may affect biochemical derangements currently identified on rides. Decreases in plasma [Na+], [K+], [Cl−] and [Ca++] are usually described at the end of the ride as compared with pre-ride values.17,20,21,23 The magnitude of the fluid and electrolyte losses appears to be more marked in exhausted than in successful endurance horses.24,25 Increasing speed, the presence of muddy terrain and increasing temperature contribute significantly to ion losses during endurance rides.22,25

Osmolar Gap

Ingestion of low molecular weight toxins will increase the difference between the measured and the calculated plasma osmolarity or osmolar gap. The calculated osmolarity

=2×Na++blood urea nitrogen/2.8+glucose/18+ethanol/4.6

Osmolar gap=measured Osm−calculated Osm

An osmolar gap greater than 10 mOsm indicates the presence of osmotically active substances such as ethanol, methanol, isopropyl alcohol, and ethylene glycol.36 Hospitalized patients may develop an osmolar gap from glycerol, intravenous (IV) immunoglobulin, propylene glycol, radiocontrast media, and sorbitol.37 Propylene glycol is a common vehicle for intravenous medications and can cause an osmolar gap. Its metabolite, lactic acid, can contribute to a high anion gap acidosis.38 Accumulation of propylene glycol in patients receiving high doses of IV medications such as diazepam, which have propylene glycol as their carrier, may lead to severe acidosis with hemodynamic instability.39 Rarely this may require treatment with hemodialysis.39 Table 51-3 lists the contribution to the osmolar gap of various drugs and toxins. The table displays the expected concentration of a substance in mg/dl that would cause an osmolar gap of 10 mOsm/L.

A number of toxins such as ethylene glycol and methanol will no longer produce an osmolar gap as they are metabolized, and in these cases, a normal gap does not exclude intoxication, only a late presentation.5 Another factor that lowers the sensitivity of the osmolar gap is the considerable variation in the normal osmolar gap in the general population. Indeed, patients may have an increased gap that is still below 10 mOsm/kg.40 Thus a high osmolar gap is supportive of intoxication, but a normal gap does not rule it out. On the other hand, the osmolar gap can also be falsely elevated. Patients who are critically ill may have an elevated gap because of the presence of endogenous substances such as amino acids.41 Patients with hyperlipidemia or hyperproteinemia will have spurious hyponatremia leading to an elevated gap.42 There is also an accumulation of osmotically active substances in chronic renal failure.43 For all these reasons, the osmolar gap should be used with caution as additional evidence of an alcohol intoxication but should not be used as the primary determinant of intoxication or as a screening test.44

Volume Expansion

Dietary ingestion and intravenous infusion represent the most common routes for fluid gain. The consequences of hypotonic, isotonic, and hypertonic fluid expansion are contrasted below. Again, the letters correspond to those in Table 3-1 and Figure 3-4.

D Intravenous infusion of isotonic saline (0.9% NaCl) dilutes plasma albumin, does not change plasma osmolarity, but slightly increases plasma Na+ and to a greater extent plasma [Cl−]. The lack of an osmotic change means that the added fluid will expand only extracellular (plasma and interstitial fluid) spaces. Plasma albumin is diluted, resulting in a tendency for fluid to accumulate in the interstitial space.

E Hypertonic saline infusion increases plasma osmolarity. The increased osmolarity causes an osmotic movement of water from the cellular space to the extracellular space. Consequently, the extracellular volume expansion is larger than the volume of saline that was infused. Again, the volume expansion causes a dilution of plasma albumin, and consequently some of the expanded plasma volume is lost to the interstitial fluid space.

F Intravenous H2O infusion dilutes both plasma ions and plasma albumin. The decrease in osmolarity causes the osmotic movement of water into cells, including red blood cells. The dilution of albumin causes movement of water from the plasma into the interstitial fluid at the capillaries. Consequently, water infusion expands the plasma space, interstitial fluid space, and cell water space. Red blood cells exposed to an osmolarity of less than 200 mOsm will swell and rupture. Consequently, an effect equivalent to water infusion is achieved by infusing a 5% dextrose solution. The dextrose is gradually transported into the cells, and the water distributes as described above. Alternatively, a half-normal NaCl solution (0.045%, 77 mmol/L) can also be used to expand both the cellular and the extracellular volumes.

Which hormone causes reduction in blood volume and pressure?

What hormone can decrease blood pressure?

What hormone decreases the blood volume?

Which hormone reduces blood volume and pressure and increases urine volume?