Extracellular fluid space

The volume of colloid administered is primarily confined to the intravascular space, in contrast to isotonic crystalloid solutions that distribute throughout the extracellular fluid space. 

Plasma volume and the extracellular fluid space have been observed to constrict 30% during reducing diets (300-600 calories per day) (B22). These changes can be accompanied by functional impairment of glomerular filtration and hepatic perfusion with transient increases up to 2 mg/100 ml in serum creatinine and BSP retention up to 40% (B22). In rare instances a significant fall in serum calcium, magnesium, or potassium was observed. Hyperuricemia was also observed, with concentrations as high as 9 mg/100 ml (B22). 

Pharmacokinetics Approximately 1 % to 2% of total body magnesium is located in the extracellular fluid space. Magnesium is 30% bound to albumin. With IV use, the onset of anticonvulsant action is immediate and lasts approximately 30 minutes. With IM use, onset occurs in 1 hour and persists for 3 to 4 hours. Magnesium is excreted by the kidney. 

Except for respiratory and dermal insensible water-vapor losses, all remaining water lost by the body contains electrolytes, mainly sodium and chloride. The normal cation and anion constituent composition of the fluid spaces is given in Table IV. In the extracellular fluid space, sodium is the major cation and chloride the major anion. Those two ions constitute 95 of the extracellular fluid osmolality. Changes in plasma sodium concentration reflect changes in extracellular fluid volume. Potassium is the major cellular cation and phosphates and proteins comprise the major anions. The total cellular osmolality (175 + 135 = 310 mosraol/kg H2O) is equal to the total extracellular osmolality (155 + 155 = 310 mosmol/kg HaO) therefore, equal total osmotic concentrations are maintained between two fluid compartments of widely different ionic contents (Table IV). 

As discussed in Chapter 3, proteins and mABs distribute initially into the plasma volume and then more slowly into the interstitial fluid space. It can be seen from Table 32.11 that the initial distribution volume of interleukin-2 (IL-2) IL-12/ granulocyte colony-stimulating factor (G-CSF)/ and recombinant tissue plasminogen activator (rt-PA) approximates that of plasma volume. In contrast/ the initial distribution volume of FIX is approximately twice that of plasma volume. On the other hand/ the volumes of distribution at steady state (Vd(ss)) for IL-12/ G-CSF/ and rt-PA are considerably smaller than is the Vd(ss) of inuliii/ a marker for extracellular fluid space (ECF). When distribution volume estimates are much less than expected values for ECF/ they could reflect the slow transport of large molecules across membranes and the fact that either assay sensitivity or sampling time has been inadequate to characterize the true elimination phase of the compound. 

In man, the volume of distribution of the cyclic nucleotides exceeds the extracellular fluid space [125], and only about 15% of injected labelled cyclic AMP is excreted by the kidney. Extrarenal cyclic nucleotide clearance probably involves hepatic metabolism and/or biliary excretion, but cyclic AMP is also destroyed by renal phosphodiesterase. The isolated perfused rat kidney rapidly removes cyclic AMP from the perfusion medium [126]. 

Gadolinium chelates for MRI (SEDA 18, 446) (SEDA-20, 419) (SEDA-21, 475) (SEDA-22, 503) are inert, non-metabolized, small molecules, with essentially the same pharmacokinetic properties as the iodinated contrast agents. They are rapidly distributed in the extracellular fluid spaces, both intravascular and extravascular, although they do not cross the normal blood-brain barrier, and are almost entirely excreted by glomerular filtration, with no significant active tubular excretion or re-absorption. Hepatic excretion occurs in patients with... 

Mannitol, the most commonly employed osmotic diuretic, is a large polysaccharide molecule. It is often selected for use in the prophylaxis or treatment of oliguric ARF. It is not absorbed from the gastrointestinal tract and, therefore, is only administered i.v. with its elimination dependent on the GFR (within 30 to 60 min with normal renal function). Mannitol is distributed within the plasma and extracellular fluid spaces and produces an increase in the serum osmolality and expansion of the circulating volume. It is not generally used for the treatment of edema because any mannitol retained in the extracellular fluid can promote further edema formation. Furthermore, acute plasma volume expansion may challenge individuals with poor cardiac contractility and can precipitate pulmonary edema. Mannitol is commonly administered for the treatment of cerebral edema consequent to head trauma or to hypoxic-ischemic encephalopathy in neonatal foals. Because mannitol promotes water excretion, hypernatremia is a potential complication in patients that do not have free access to water (Martinez-Maldonado Cordova 1990, Wilcox 1991). 

Hyperkalemia poses an immediate threat to the life of the uremic patient. Although potassium excretion decreases with increasing nephron loss, hyperkalemia occurs infrequently in stable chronic renal failure when the glomerular filtration rate exceeds 10 ml/minute. Serum potassium, however, may rise sharply if renal function deteriorates suddenly or if an excessive potassium load enters the extracellular fluid space. The latter event may result from dietary indiscretion extracellular shift of potassium by acidemia potassium release by hemolysis, rhabdomyolysis, or tumor lysis, or administration of potassium-containing drugs. 

Acidosis. Hyperkalaemia results from a redistribution of potassium from the intracellular to the extracellular fluid space (Fig. 2). 

Thyroxine (T4) enters the extracellular fluid space through blood brain barrier (11) and the choroid plexus (12) delivery systems. The potentially important role of the latter system has become a matter of considerable interest, following the demonstration of Dickson et al that T4 binding pre-albumin (transthyretin) is strongly localized and independently controlled within choroid plexus cells (]2). T4 (and any T3 entering the brain) is transported from the extracellular fluid space into groups of selected nerve somata and their axonal and dendritic terminals (synaptosomes), Moreover, with time after i.v. administration of a T4 or a T3 pulse, there is progressive accumulation of iodothyronines in synaptosomal particles (Fig.l). 

Due to morphine s hydrophilic nature, the spinal cord s exposure over time to intrathecal morphine greatly exceeds that of other spinal opioids, leading to a prolonged analgesic effect but also greater rostral spread and the potential for delayed respiratory depression and sedation. Compared to less hydrophilic opioids, morphine has a lower spinal cord distribution volume, slower clearance from the spinal cord into the plasma, and higher bioavailability in the extracellular fluid space of the spinal cord [1]. 

Current MRI process involves use of contrast agent, usually Gadolinium-based, to improve tissue discrimination [9]. This paramagnetic compound mainly resides at intravascular and extracellular fluid space and increases the brightness of these Gadolinium-enhanced tissues greatly. It helps in better detection of vascular tissues such as lesions. 

Rice, M. E., Gerhardt, G. A., Hierl, P. M., Nagy, G., Adams, R. N., Diffusion-coefficients of neurotrans-mitters and their metabolites in brain extracellular fluid space. Neuroscience 1985, 15(3), 891-902. 

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