Tumor extracellular fluid

Hyperaldosteronism is a syndrome caused by excessive secretion of aldosterone. It is characterized by renal loss of potassium. Sodium reabsorption in the kidney is increased and accompanied by an increase in extracellular fluid. Clinically, an increased blood pressure (hypertension) is observed. Primary hyperaldosteronism is caused by aldosterone-producing, benign adrenal tumors (Conn s syndrome). Secondary hyperaldosteronism is caused by activation of the renin-angiotensin-aldosterone system. Various dtugs, in particular diuretics, cause or exaggerate secondary peadosteronism. 

Figure 4. A schematic of tumor cells (or small colonies of tumor cells) with extracellular fluid from the interstitium trapped between them. The electrochemical double layer is indicated for each negatively charged tumor cell with positive ions (in extra-cellular fluid) poised against the negative charge.25...

Figure 5. A small portion of the electrochemical double layer at the tumor cell-extracellular fluid (electrolyte) interface is shown to depict the microscopic structure and the potential drops involved, by analogy with the metal-electrolyte interface taken from Conway.47...

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. 

Geer, C.P. and S.A. Grossman, Extracellular fluid flow along white matter tracts in brain a potentially important mechanism for dissemination of primary brain tumors. Proceedings of ASCO, 1993, 12, 177. 

Another feature of tumors that can have a major impact on the distribution of targeted radiotherapeutics is tumor interstitial fluid pressure. Interstitial fluid pressure results in a pressure gradient that can inhibit the delivery of molecules from the plasma to the extracellular fluid in central regions of a tumor. Tliis pressure gradient is not present in normal tissues because they have a lymphatic system however, tumors do not, creating an additional barrier that must be overcome. Experimental evidence of an elevated interstitial pressure in murine tumor models has been reported by Boucher et al. (1990). As expected, the effect was most apparent at the tumor periphery. Using a mathematical model, the magnitude of this outward convection fluid flow was predicted to be 0.1-0.2 pm/s (Jain and Baxter 1988). 

After seeping copiously out of the highly permeable tumor microvessels—an equilibrium is reached when the hydrostatic and oncotic pressures within the microvessels and the respective interstitial pressures become equal—fluid accumulates in the tumor extracellular matrix and a high interstitial fluid pressure (IFP) builds up in sohd tumors (Young et al. 1950 Gutmann et al. 1992 Less et al. 1992 Milosevic et al. 2001,2004). 

Sodium Excess. Most of the sodium ingested is excessive, and for the most part it is excreted by the kidneys in combination with bicarbonate or phosphate. However, under some circumstances sodium accumulates in the extracellular fluid and causes edema since the retention of sodium is accompanied by water retention. Such conditions include (1) cardiac or renal failure, (2) adrenal tumors which secrete excessive cortical hormones, and (3) adrenocorticotropic hormone (ACTH) or steroid hormone therapy. In these conditions, individuals benefit from sodium-restricted diets. 

The occurrence of oxidation-reduction (redox) reactions in the body has also been reported as a means to control spatial drug release in the body [44, 45]. Oxidative conditions exist in extracellular fluids and inflamed or tumor tissues, while intracellular compartments are known to be reductive [46, 47]. Hubbell and co-workeis developed oxidation responsive Ps based on PEG-PPS-PEG [48]. The hydrophobic PPS was oxidized and transformed within 2 h into hydrophilic... 

Linker hydrolysis there is presence of acid-labile linkages between the pol5mier and drug in the pol5mier backbone or side-chain. Presence of these acid-sensitive spacers between drug and polymer enables release of drug either in relatively acidic extracellular fluids in a tumor, or after endocytosis in the... 

---