Bicarbonate intracellular concentration

Carbon dioxide diffuses from the site of production in metabolizing cells, through the interstitial fluid, across the wall of the systemic capillary and into the blood plasma. It readily diffuses across the membrane of the erythrocyte. When carbon dioxide enters the erythrocyte, bicarbonate and hydrogen ions are formed. The rise in intracellular concentration of bicarbonate leads to the chloride shift, described in Chapter 4. The hydration of carbon dioxide in the erythrocyte occurs very quickly, due to the presence of the enzyme carbonic anhydrase, which catalyses the reaction ... 

For each hydrogen ion excreted, one bicarbonate ion is added to the intracellular fluid of the renal tubular cell. The intracellular concentration of bicarbonate rises. In Figure 7.1 B, the reaction of CO2 is omitted and only the products Fl and HCO, are reproduced from Figure 7.1 A. Bicarbonate, being charged, is insoluble in lipid and so diffuses extremely slowly across the lipid regions of the cell membrane. On the aspect of the tubular cell membrane facing the interstitial fluid, the lipid membrane is traversed by protein macromolecules which comprise a carrier mechanism for bicarbonate ions (section A.l). The rise in intracellular concentration of bicarbonate leads to transfer of bicarbonate from the renal tubular cell cytoplasm to the renal interstitial fluid. 

Sahlin, K., Alvestrand, A., Brandt, R., Hultman, E. (1978). Intracellular pH and bicarbonate concentration in human muscle during recovery from exercise. J. Appl. Physiol. 45,474—480. 

Moreover, several buffer systems exist in the body, such as proteins, phosphates, and bicarbonates. Proteins are the most important buffers in the body. Protein molecules contain multiple acidic and basic groups that make protein solution a buffer that covers a wide pH range. Phosphate buffers (HPO T /H2P07) are mainly intracellular. The pK of this system is 6.8 so that it is moderately efficient at a physiological pH of 7.4. The concentration of phosphate is low in the extracellular fluid but the phosphate buffer system is an important urinary buffer. Bicarbonate (H2C03/HC0 3) is also involved in pH control but it is not an important buffer system because normal blood pH 7.4 is too far from its pK 6.1 [144],... 

The most convincing proposal is that camosine plays one or more roles in control of intracellular hydrogen ion concentration (Abe, 2000 Vaughan-Jones et al, 2006). Camosine is an effective physiological buffer it is presumed that this property explains its predominant association with white, glycolytic, muscles which possess relatively few mitochondria and thereby generate lactic acid. Not only may camosine, also possible in its acetylated form, help to directly suppress the rise in hydrogen ion concentration but its ability to activate the enzyme carbonic anhydrase (Temperini et al, 2005) would increase bicarbonate buffer capacity. These properties may help explain camosine s protective action in ischaemia, a condition associated with severe intracellular acidosis. 

Apical membrane Na+/H+ exchange (via NHE3) and bicarbonate reabsorption in the proximal convoluted tubule cell. Na+/K+ ATPase is present in the basolateral membrane to maintain intracellular sodium and potassium levels within the normal range. Because of rapid equilibration, concentrations of the solutes are approximately equal in the interstitial fluid and the blood. Carbonic anhydrase (CA) is found in other locations in addition to the brush border of the luminal membrane. 

All cells, including muscle and nerve cells, have inside them an intracellular fluid (ICF) which contains high levels of potassium, K+, phosphate ions, PC>43+, and protein and small amounts of Na+ ions and chlorine ions. Outside the cells in the extracellular fluid (ECF) consists mostly of sodium ions, Na+, chloride, Cl, and bicarbonate ions, HC03, but no protein, plus low concentrations of potassium ions. The inner layer of the cell membrane is negatively charged relative to the outside. When activity occurs then an ionic pumping action takes place to try to maintain the balance within the cells between the intra and extra flow of sodium and potassium... 

Intracellular fluids (also called the cytosol) are quite different compositionally from plasma and interstitial fluids (Table 4, Figures 4 and 5). The internal pH of many cells is maintained near 6.9-7.0. via various membrane transport mechanisms such as Na" /H and CP/HCO exchangers, and various phosphate and protein buffers. In contrast to the plasma, the intracellular fluids have substantially lower concentrations of sodium, calcium, chloride, and bicarbonate and higher to substantially higher concentrations of potassium, magnesium,... 

SahUn K., Alvestrand A., Bergstrom ., and HultmanE. (1977) Human intracellular pH and bicarbonate concentration as determined in biopsy samples from the quadriceps muscle of man at rest. Clinic. Set Mol. Med. 53, 459-466. 

In conclusion, the administration of sodium bicarbonate increases plasma pH but has the opposite effect in the CSF and intracellular fluid, which may be extremely detrimental to the acidotic patient. It may further increase the plasma lactate and sodium concentrations and may decrease the ionized calcium concentration. It corrects one laboratory value (pH) without addressing the underlying pathophysiology (poor tissue perfusion), by imposing a hypematremic alkalosis on an already deranged metabolic balance. 

The intracellular negative electrical potential opposes chloride entry into cells. In the early proximal tubule the main cation, sodium, is predominantly reabsorbed concomitantly with bicarbonate so that the luminal chloride concentration actually increases. There are two main reabsorption mechanisms for chloride. The first is via an antipoiter in exchange for secretion of other anions (e.g., bicarbonate) or formate. The second occurs in the final two thirds of the proximal tubule. In the thick ascending limb of the loop of Henle, chloride is reabsorbed in association with sodium via NKCC2. The concentration gradient is maintained by a basolateral chloride pump, CLC-Kb (see Figure 45-7). A further chloride channel, CLC-5, is expressed at multiple sites in the nephron. ... 

Intracellular fluid makes up 30-40% of body weight, or about two-thirds of total body water. Potassium and magnesium are the predominant cations. The anions are mainly proteins and organic phosphates, with chloride and bicarbonate at low concentrations. 

Two-thirds of total body water is distributed intracellularly while one-third is contained in the extracellular space. Sodium and its accompanying anions, chloride and bicarbonate, comprise more than 90% of the total osmolality of the extracellular fluid (ECF), while intracellular osmolality is primarily dependent on the concentration of potassium and its accompanying anions (mostly organic and inorganic phosphates). The differential concentrations of sodium and potassium in the intra- and extracellular fluid is maintained by the Na+-K+-ATPase pump. Most cell membranes are freely permeable to water, and thus the osmolality of intra- and extracellular body fluids is the same. Symptoms in patients with hypo- and hypernatremia are primarily related to alterations in cell volume. It is therefore essential to understand the factors that cause changes in cell volume. 

The initial response of the body to acute respiratory alkalosis is chemical buffering. Hydrogen ions are released from the body s buffers— intracellular proteins, phosphates, and hemoglobin—and titrates down the serum bicarbonate concentration. This process occurs within minutes. Acutely, the bicarbonate concentration can be decreased by a maximum of 3 mEq/L for each 10-mm Hg decrease in PaC02 (see Table 5IM). When only the physicochemical buffering has occurred, the disturbance is referred to as acute respiratory alkalosis. 

In vivo, the concentrations of C02 are relatively high due to the high levels of bicarbonate in intracellular (12 mM) and interstitial (30mM) fluids [25]. Thus, the reaction of ONOO" with C02 is expected to be the major pathway of decay of peroxynitrite in biological systems [4, 5]. 

Dennis Veere has become dehydrated because he has lost so much water through vomiting and diarrhea (see Chapter 4). Cholera toxin increases the efflux of sodium and chloride ions from his intestinal mucosal cells into the intestinal lumen. The increase of water in his stools results from the passive transfer of water from inside the cell and body fluids, where it is in high concentration (i.e., intracellular Na+ and Cl concentrations are low), to the intestinal lumen and bowel, where water is in lower concentration (relative to high Na+ and Cl ). The watery diarrhea is also high in K+ ions and bicarbonate. All of the signs and symptoms of cholera generally derive from this fluid loss. 

Finally, we address the physiological consequences of this conforitational transition. The major intracellular buffer is phosphate buffer (92). Furthermore, although the bicarbonate buffer system is present in higher concentration in the eye, the phosphate buffer exists even in intraocular fluid (93). We may thus have one answer to the question "What molecular mechanisms in cells are so extraordinarily sensitive that a change in H" " concentration of as little as 3 x 10 M (approximately the difference between blood at pH 7.4 and blood at pH 7.0) can be lethal " [Ref. 92, p. 51], in the particular buffering action of phosphates on hyaluronates. 

The most functional pH for this buffer system is 6.8, and this system works best in the renal tubules and intracellular fluid (ICF), where phosphates are more concentrated and the pH is optimal owing to constant production of metabolic acids, as opposed to the ECF, where bicarbonate is more readily available, and the pH is higher. 

Most of the chloride in the body fluid is in the extracellular fluid, and only a small amount of the chloride ions are in the intracellular fluid. (There are 95-llOmEq of chloride per liter of extracellular fluid, and only one mEq of chloride per liter of intracellular fluid.) In contrast, in the intracellular fluid, mainly protein and phosphate anions are present. In the extracellular fluid, the concentration of bicarbonate is second to that of chloride. 

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