Volume osmolality

Convertino, V.A., Keil, L.C., Bernauer, E.M. Greenleaf, J, E. (1981) Plasma volume, osmolality, vasopressin, and renin activity during graded exercise in man. J. Appl. Physiol. Respirat. Environ. Exercise Physiol. 50, 123-128,... 

Characteristics of the drug and the fluid such as drug volume, osmolality, pH, and density may affect i.v. drug delivery. The frequency and duration of drug administration is also important as is the need for the infusion system to handle multiple drugs. This may lead... 

Large doses of mannitol used in treating cerebral edema can alter extracellular fluid volume, osmolality, and composition and can lead under some circumstances to acute renal insufficiency, cardiac decompensation, and other complications (1). The patient s body habitus, age, total body water content relative to body weight, pretreatment plasma sodium concentration and plasma osmolality, and the presence of edema or ascites can influence the degree of extracellular fluid change and the rate of mannitol excretion to a significant degree. 

There are two general models for evaluating the nephrotoxic potential of chemicals that utilize whole animals. In one model, conscious animals are administered the test compound and renal functional parameters (Table 2) evaluated over a period of hours or days. Some of the urinary parameters routinely monitored using in vivo nephrotoxicity studies include volume, osmolality, and contents. Urine volume can increase (polyuria), decrease (oliguria), or approach a zero value (anuria). Urinary osmolality is a measure of the ability of the kidney to concentrate urine. In polyuric states, urinary osmolality usually decreases from control levels, while in oliguric states urine tends to be more concentrated and urinary osmolality values rise above the control level. 

Fluid restriction is generally unnecessary as long as sodium intake is controlled. The thirst mechanism remains intact in CKD to maintain total body water and plasma osmolality near normal levels. Fluid intake should be maintained at the rate of urine output to replace urine losses, usually fixed at approximately 2 L/day as urine concentrating ability is lost. Significant increases in free water intake orally or intravenously can precipitate volume overload and hyponatremia. Patients with stage 5 CKD require renal replacement therapy to maintain normal volume status. Fluid intake is often limited in patients receiving hemodialysis to prevent fluid overload between dialysis sessions. 

The potent antidiuretic hormone AVP orchestrates the regulation of free water absorption, body fluid osmolality, cell contraction, blood volume, and blood pressure through stimulation of three G-protein-coupled receptor subtypes Vi-vascular types a and b, V2-renal, and V3-pituitary. Increased AVP secretion is the trademark of several pathophysiological disorders, including heart failure, impaired renal function, liver cirrhosis, and SIADH. As a consequence, these patients experience excess water retention or inadequate free-water excretion, which results in the dilution of sodium concentrations, frequently manifesting as clinical hyponatremia (serum sodium concentration <135mmol/L). This electrolyte imbalance increases mortality rates by 60-fold. Selective antagonism of the AVP V2 receptor promotes water... 

The clinician also needs to monitor body weight, serum osmolality, serum electrolytes, complete blood cell count, urinalysis, and cultures (if appropriate). With an urgent or emergency situation, evaluation of the volume status of the patient is the most important outcome. 

Lithium reduces the kidney s ability to concentrate urine and may cause a nephrogenic diabetes insipidus with low urine specific gravity and low osmolality polyuria (urine volume greater than 3 L/day). This may be treated with loop diuretics, thiazide diuretics, or triamterene. If a thiazide diuretic is used, lithium doses should be decreased by 50% and lithium and potassium levels monitored. 

FIGURE 78-1. Diagnostic algorithm for the evaluation of hyponatremia. (CHF, congestive heart failure EABV, effective arterial blood volume SIADH, syndrome of inappropriate antidiuretic hormone UNa, urine sodium concentration Uosm, urine osmolality.)... 

Various organic solvents are used, such as dimethyl sulfoxide (DMSO), dimethyl-formamide, ethanol and acetone. The volume added must not be toxic to cells. Greater than 10% water v/v can be toxic because of nutrient dilution and osmolality changes. 

Influence of Osmolality on Intestinal Transit and on Chyme Volume Available for Dissolution... 

Angiotensin II has two effects first, as a vasoconstrictor acting via receptors on vascular smooth muscle cells, and second, it stimulates the adrenal cortex gland to produce aldosterone (a mineralocorticoid steroid hormone, see Chapter 4). Aldosterone promotes the reabsorption of sodium from the renal tubule into the bloodstream and the resulting increase in osmolality (osmotic potential) of the blood causes water reabsorption in the nephrons. The outcome is an increase in blood volume and, therefore, pressure which inhibits (by negative feedback) further renin secretion from the JGA. 

The ICH S7A states that the effects of the NCE on renal parameters should be assessed for example, urinary volume, specific gravity, osmolality, pH value, fluid/electrolyte balance, proteins, cytology, and blood chemistry determinations such as blood urea... 

A second unusual action of this class of diuretics is their utility in treating nephrogenic diabetes insipidus. Patients who have an adequate supply of ADH but whose kidneys fail to respond to ADH excrete large volumes of very dilute urine, not unlike those who have an ADH deficiency. The thiazides reduce glomerular filtration modestly and decrease positive free water formation (Ch2o), that is, production of dilute urine. These actions combine to cause patients with nephrogenic diabetes insipidus to excrete a somewhat reduced urine volume with increased osmolality. 

Diabetes insipidus Urine volume and osmolality, plasma osmolality... 

Hyponatmemia is common with the thiazides and to a lesser extent with the loop diuretics. It occurs when the osmolality of the urine persistently exceeds that of the fluid intake and is associated with the inability of the kidney to produce a dilute urine. It is not usually severe. The origin is multifactorial and involves unrestricted fluid intake and increased ADH activity due to volume depletion. Co-administration of dipsogenic drugs, such as the tricyclic antidepressants, or those with ADH-like effects, such as chlorpropamide, can exacerbate the problem. There are rare occasions when hyponatraemia (Nan- concentration less than 100 mmol-L-l) can be of sufficient severity to be life threatening. 

Urea concentration in the medulla plays an important role maintaining the high osmolarity of the medulla and in the concentration of urine. ADH secretion is regulated by serum osmolality and by volume status. A new class of drugs, the vaptans (see under Agents That Alter Water Excretion), are ADH antagonists. 

Cerebral edema has been described during therapy of diabetic ketoacidosis with a large volume of fluid, resulting in rapid changes in plasma osmolality, mostly in young patients (SEDA-26, 462). However, in 10 adults with... 

Analogous to the development of the non-ionic X-ray contrast agents many years ago neutral chelates have been sythesized to reduce the osmotic pressure of the aqueous solutions. However, for MRI, injection volumes are used that are much smaller than for X-ray contrast agents. That means that the osmolality of the solutions is of minor importance for MRI contrast agents. The increase in blood osmolality after intraveneous injection of up to 0.3 mmol/kg Gd-DTPA will not cause disturbance of the organism s osmotic balance. 

The development of low osmolar non-ionic X-ray contrast agents has resulted in a distinct reduction in the toxicity and the observed side-effects in patients. However, as already mentioned the osmotic activity of MRI contrast agents is less important in view of the smaller injection volumes which are used. All the formulations of extracellular gadolinium chelates are hypertonic when compared with blood. But the overall increase in osmolality after injection of even 0.3 mmol/kg body weight is insignificant. Osmololatiy-induced adverse reactions have been observed rarely not only because of the relatively small injection volumes but also because of the rapid dilution of the injected agent in the blood. 

A key determinant of the final urine concentration is antidiuretic hormone (ADH also called vasopressin). In the absence of ADH, the collecting tubule (and duct) is impermeable to water, and dilute urine is produced. However, membrane water permeability of principal cells can be increased by ADH-induced fusion of vesicles containing preformed water channels with the apical membranes (Figure 15-6). ADH secretion is regulated by serum osmolality and by volume status. 

CM can be classified according to osmolality, which reflects the total particle concentration of the solution (the number of molecules dissolved in a specific volume) (1,2), CM with osmolality greater than that of blood may be more difficult for the kidney to excrete. Over the past 40 years, the osmolalities of available CM have been gradually decreased to physiologic levels. In the 1950s, only high-osmolar CM (e.g., diatrizoate)... 

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