Extracellular volume

Diuretics are needed to return to normal the expanded extracellular volume that other antihypertensive agents produce, such as fluid retention and blood volume expansion, via compensatory mechanisms of the body. The loss of efficacy of antihypertensive agents can be restored if a diuretic is used concomitandy. In the treatment of hypertension, high ceiling or loop diuretics, such as furosemide, ethacrynic acid, and bumetanide, are no more efficacious than the thiazide-type of diuretics. In fact, these agents cause more side effects, such as dehydration, metaboHc alkalosis, etc, and therefore, should not be used except in situations where rapid elimination of duid volume is cleady indicated. 

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

The analytic validity of an abstract parallel elastic component rests on an assumption. On the basis of its presumed separate physical basis, it is ordinarily taken that the resistance to stretch present at rest is still there during activation. In short, it is in parallel with the filaments which generate active force. This assumption is especially attractive since the actin-myosin system has no demonstrable resistance to stretch in skeletal muscle. However, one should keep in mind, for example, that in smooth muscle cells there is an intracellular filament system which runs in parallel with the actin-myosin system, the intermediate filament system composed of an entirely different set of proteins, (vimentin, desmin, etc.), whose mechanical properties are essentially unknown. Moreover, as already mentioned, different smooth muscles have different extracellular volumes and different kinds of filaments between the cells. 

FIGURE 10-2. Distribution of body fluids showing the extracellular fluid volume, intracellular body fluid volume, and total body fluids in a 70 kg adult. Extracellular volume (ECV) comprises 14 liters of total body fluid (42 liters). Plasma volume makes up approximately 3 liters of the 14 liters of ECV. Intracellular volume accounts for the remaining 28 liters of total body fluids with roughly 2 liters being located within the red blood cells. Blood volume (approximately 5 liters) is also depicted and is made up of primarily red blood cells and plasma. (Reprinted from Guyton AC, Hall JE. Textbook of Medical Physiology. 8th ed. Philadelphia Saunders, 1991 275, with permission.)... 

Therapeutic measures that have been used to decrease the incidence of contrast-induced nephropathy include extracellular volume expansion, minimization of the amount of contrast administered, and treatment with oral acetylcysteine. Theophylline, fenoldopam, loop diuretics, mannitol, dopamine, and calcium antagonists have no effect or may worsen ARF. 

The most common therapeutic maneuver to decrease the incidence of contrast-induced nephropathy is extracellular volume expansion.36 Several recent studies have compared the efficacy of isotonic sodium chloride (0.9%) to half normal... 

It is extremely important to select the correct type of nutrition when feeding severely malnourished individuals or patients. The provision of food can be dangerous unless carefully controlled as it can lead to what is known as the refeeding syndrome . This is characterised by a rapid increase in extracellular volume, due to increased sodium intake, and decreased blood levels of phosphate and potassium due to increased levels of insulin which stimulate the entry of these into muscle. (The latter changes are also seen when type 1 diabetic patients in a severe hyper-glycaemic state are treated with insulin.) A recommended refeeding schedule is as follows ... 

A possible way to improve differentiation between normal and diseased tissues is the use of non-specific contrast agents which achieve contrast enhancement based on morphological and physiological properties of tumour tissue. Contrast agents for X-ray, CT and MRI are preferentially taken up by tumour tissue shortly after intravenous injection due to increased tumour vasculature, leaky endothelial structures and enlarged extracellular volumes [34], a phenomenon that is in principle exploitable for optical contrast agents. 

In humans, for all these compounds, Vp is about 0.15-0.27 L kg (consistent with the extracellular volume which, in humans, is about 0.25 L kg ), Tj/ja is 4- 10min,Ti/2 is between 100 and 130 min and total clearance is 1-2 mLmin kg [5]. These compounds are characterized by a rapid distribution about 70% of the injected dose is cleared from plasma (diffusion and excretion) within 2-5 minutes after injection [5]. Because of their high hydrophilicity, they do not enter the intracellular space to a significant extent. 

Orai Prevention or treatment of extracellular volume depletion, dehydration, or sodium depletion aid in the prevention of heat prostration. 

A) The fall of blood pressure that occurs in the first 2 weeks of therapy results from a decrease of extracellular volume. 

Increased plasma and extracellular volumes may lead to an increased VD and decreased drug levels. 

Mannitol is rapidly distributed in the extracellular compartment and extracts water from cells. Prior to the diuresis, this leads to expansion of the extracellular volume and hyponatremia. This effect can complicate heart failure and may produce florid pulmonary edema. Headache, nausea, and vomiting are commonly observed in patients treated with osmotic diuretics. 

This volume was assumed to represent tissue extracellular volume. 

Sykova E, Svoboda J, Polak J, Chvatal A (1994) Extracellular volume fraction and diffusion characteristics during progressive ischemia and terminal anoxia in the spinal cord of the rat. J Cereb Blood Flow Metab 14 301-311 Van der Toorn A, Dijkhuizen RM, Tulleken CA, Nicolay K (1996a) Diffusion of metabolites in normal and ischemic rat brain measured by localized 1H MRS. Magn Reson Med 36 914-922... 

Actions Thiazide diuretics, such as hydrochlorothiazide [hye droe klor oh THYE a zide], lower blood pressure, initially by increasing sodium and water excretion. This causes a decrease in extracellular volume, resulting in a decrease in cardiac output and renal blood flow (Figure 19.6). With long-term treatment, plasma volume approaches a normal value, but peripheral resistance decreases. Spironolactone [spye row no LAK tone], a potassiumsparing diuretic, is often used with thiazides. (A complete discussion of diuretics is found on p. 223.)... 

The patient discussed in the illustrative case presented with orthostatic hypotension, poor skin turgor, dry mucous membrane, a ketotic odor to the breath, elevations in BUN and creatinine, and ketoacidosis. She had severe extracellular volume depletion, which can be estimated using the following clinical criteria ... 

The intravenous administration of isotonic saline (0.9% NaCl) should be used to restore ECF and intracellular fluid volumes. Infusion of isotonic saline restores the extracellular volume deficit. Isotonic saline also restore intracellular volume deficits in patients with DKA and hypotonicity. Aggressive hydration itself... 

Thirst is sensed in the hypothalamus and occurs when extracellular volume decreases or osmotic pressure increases. ADH is then released from the posterior pituitary, increases water reabsorption in the nephron and reduces the volume of urine produced. 

The interstitial volume is the extracellular volume outside of the blood vessels. Note that it is three times larger than the intravascular volume While its ionic composition closely resembles that of blood plasma (with which it is in equilibrium for all small solutesthat are not protein-bound), it has a considerably lower protein content. 

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