Osmolarity, extracellular

Osmotic pressure from high concentrations of dissolved solutes is a serious problem for cells. Bacterial and plant cells have strong, rigid cell walls to contain these pressures. In contrast, animal cells are bathed in extracellular fluids of comparable osmolarity, so no net osmotic gradient exists. Also, to minimize the osmotic pressure created by the contents of their cytosol, cells tend... 

The kidneys also regulate the osmolarity of extracellular fluid, in particular plasma osmolarity. The maintenance of plasma osmolarity close to 290 mOsm prevents any unwanted movement of fluid into or out of the body s cells. An increase in plasma osmolarity causes water to leave the cells, leading to cellular dehydration a decrease in plasma osmolarity causes water to enter the cells, leading to cellular swelling and possibly lysis. Plasma osmolarity is regulated primarily by altering the excretion of water in the urine. 

The process of tubular reabsorption is essential for the conservation of plasma constituents important to the body, in particular electrolytes and nutrient molecules. This process is highly selective in that waste products and substances with no physiological value are not reabsorbed, but instead excreted in the urine. Furthermore, reabsorption of many substances, such as Na+, H+, and Ca++ ions, and water is physiologically controlled. Consequently, volume, osmolarity, composition, and pH of the extracellular fluid are precisely regulated. 

Osmotic diuretics such as mannitol act on the proximal tubule and, in particular, the descending limb of the Loop of Henle — portions of the tubule permeable to water. These drugs are freely filtered at the glomerulus, but not reabsorbed therefore, the drug remains in the tubular filtrate, increasing the osmolarity of this fluid. This increase in osmolarity keeps the water within the tubule, causing water diuresis. Because they primarily affect water and not sodium, the net effect is a reduction in total body water content more than cation content. Osmotic diuretics are poorly absorbed and must be administered intravenously. These drugs may be used to treat patients in acute renal failure and with dialysis disequilibrium syndrome. The latter disorder is caused by the excessively rapid removal of solutes from the extracellular fluid by hemodialysis. 

Regulation of the osmolarity of extracellular fluid, including that of the plasma, is necessary in order to avoid osmotically induced changes in intracellular fluid volume. If the extracellular fluid were to become hypertonic (too concentrated), water would be pulled out of the cells if it were to become hypotonic (too dilute), water would enter the cells. The osmolarity of extracellular fluid is maintained at 290 mOsm/1 by way of the physiological regulation of water excretion. As with sodium, water balance in the body is achieved when water intake is equal to water output. Sources of water input include ... 

The osmoreceptors of the hypothalamus monitor the osmolarity of extracellular fluid. These receptors are stimulated primarily by an increase in plasma osmolarity they then provide excitatory inputs to the thirst center and the ADH-secreting cells in the hypothalamus. The stimulation of the thirst center leads to increased fluid intake. The stimulation of the ADH-secreting cells leads to release of ADH from the neurohypophysis and, ultimately, an increase in reabsorption of water from the kidneys and a decrease in urine output. These effects increase the water content of the body and dilute the plasma back toward normal. Plasma osmolarity is the major stimulus for thirst and ADH secretion two additional stimuli include ... 

Four approved Gd(III) complexes are now widely used clinically. Complexes containing DTPA 71 (Magnevist) and DOTA 72 (Dotarem) are ionic, whereas those of DTPA-BMA 73 (Omniscan) and HP-DOTA 74 (Prohance) are neutral their low osmolarity decreases the pain of the injections. All these agents are extracellular and they rapidly diffuse into the interstitial space. Doses are usually in the region of 0.1 mmol kg-1, which means that total injected doses are close to 4 g. 

Pharmacology Normal osmolarity of the extracellular fluid ranges between 280 to 300 mOsm/L it is primarily a function of sodium and its accompanying ions, chloride, and bicarbonate. Sodium chloride is the principal salt involved in maintenance of plasma tonicity. One gram of sodium chloride provides 17.1 mEg sodium and 17.1 mEq chloride. 

Fig. 12.4. Example of a two-component pathway in S. cerevisiae. Model of signal transdnction via the SLNl protein. The SLNl protein is a transmembrane protein with two transmembrane elements, which is assumed to exist as a dimer. The sensor domain and the regulator domain are localized on the same protein chain in the SLNl protein. The SLNl protein is activated by an extracellular signal (e.g., decrease in osmolarity). Autophosphorylation takes place on His (H) in the sensor domain and on Asp (D) in the regulator domain. A phosphate transfer takes place from the phosphohisti-dine to the effector protein SSKl. In the unphosphory-lated form, SSKl activates a MAPK pathway, which contains the protein kinase HOGl as a MAPK element. Various cellular reactions are triggered by HOGL If SSKl is phosphorylated in the course of activation of the two-component pathway, stimulation of the MAPK pathway is stopped. According to Swanson et al., (1994).

Strotmann, R., Harteneck, C., Nunnenmacher, K., Schultz, G., Plant, T.D. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity, Nature Cell Biol. 2000, 2, 695-702. 

Several mechanisms have evolved to prevent this catastrophe. In bacteria and plants, the plasma membrane is surrounded by a nonexpandable cell wall of sufficient rigidity and strength to resist osmotic pressure and prevent osmotic lysis. Certain freshwater protists that live in a highly hypotonic medium have an organelle (contractile vacuole) that pumps water out of the cell. In multicellular animals, blood plasma and interstitial fluid (the extracellular fluid of tissues) are maintained at an osmolarity close to that of the cytosol. The high concentration of albumin and other proteins in blood plasma contributes to its osmolarity. Cells also actively pump out ions such as Na+ into the interstitial fluid to stay in osmotic balance with their surroundings. 

FIGURE 2-13 Effect of extracellular osmolarity on water movement across a plasma membrane. When a cell in osmotic balance with its surrounding medium (that is, in an isotonic medium) (a) is transferred into a hypertonic solution (b) or hypotonic solution (c), water moves across the plasma membrane in the direction that tends to equalize osmolarity outside and inside the cell. 

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. 

Figure 6.1. Compositions and concentrations of intracellular and extracellular fluids of selected marine animals having widely different total osmolarities. M = intracellular fluids of muscle tissue PI = plasma or hemolymph TMAO = trimethylamine-A-oxide Bet = glycine betaine FAA = free amino acids. (Data compiled from various sources for a comprehensive list of osmolyte compositions and concentrations in diverse species, see Kirschner, 1991 Somero and Yancey, 1997 Yancey et al., 1982.)...

Q7 An excess of vasopressin produces a hypo-osmolar condition with excessive water retention. This greatly dilutes the sodium content of plasma and causes an overall dilution of the extracellular fluid (ECF), which can lead to tissue swelling, for example in the brain. Mental symptoms such as confusion, irritability, seizures and coma can occur when ECF sodium falls below 120 mEq l-1. 

Hypotonic The concentration is less than the concentration of intracellular fluid (hypo-osmolar range less than 240 mOsm/L). Moves fluid from extracellular space into inside cells. 

Vasopressin (antidinretic hormone) is a nonapeptide that controls resorption of water by distal tubules of the kidney to regulate the osmotic pressure of blood. It functions to conserve body water by reducing the output of urine, and thus it is known as an antidiuretic. Vasopressin is synthesized in the supraoptic nucleus of the hypothalamus where it is bound to a neurophysin protein carrier, packaged in granules, and delivered by intracellular transport to nerve terminals in the posterior pituitary. Vasopressin bound to neurophysin is released from the granules in response to increased extracellular osmolarity sensed by hypothalamic osmoreceptors, signaling by atrial stretch receptors or after a rise in angiotensin n levels. Its secretion is increased by dehydration or stress and decreased after alcohol consumption. 

The efficacy of Dy(PPP)2 and Dy(TTHA)3- as shift reagents for a variety of ions, including 23Na+, 39K+ and 87Rb+, has been examined,7 and the effect of temperature, osmolarity and shift reagent concentration on the chemical shift has been studied by Burnstein and Fossel.63 The chemical shift of 87Rb+ as a function of Dy(TTHA)3- concentration in the presence of 6.7 g% bovine serum albumin (BSA) is shown in Fig. 8. The BSA was included to mimic the extracellular plasma environment. 

Fig. 12.4 Principle of the two-component pathway. The figure shows the principal steps of the two-component pathway in bacterial systems. An extracellular signal (change in osmolarity, N availability, etc.) is registered by a receptor. An interaction takes place with the first component, the "sensor kinase , which undergoes autophosphorylation at a His residue (H). The phosphate residue is transferred to the carboxyl side chain of an Asp residue (D) of the reaction regulator. Phosphorylation of the second component activates this for further signal conduction. The "sensor kinase may also be localized in the cytoplasmic domain of the receptor.

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