Bicarbonate extracellular concentration

Diuretic therapy is a common iatrogenic origin of metabolic disturbances of acid-base physiology. Diuretics are administered for their naturetic properties particularly in patients with cardiac, hepatic, pulmonary and renal disease, to rid the body of excess extracellular fluid. When the loss of sodium is matched by losses of other extracellular electrolytes in proportion to their extracellular concentrations, no disturbance of acid-base balance occurs. In cases where there is a disproportionate loss of bicarbonate, the result is metabolic acidosis. Conversely when there is an exaggeration of loss of ammonium or chloride ions by comparison with sodium, this leads to metabolic alkalosis. 

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],... 

Pharmacokinetics Sodium bicarbonate in water dissociates to provide sodium and bicarbonate ions. Sodium is the principal cation of extracellular fluid. Bicarbonate is a normal constituent of body fluids and normal plasma level ranges from 24 to 31 mEq/L. Plasma concentration is regulated by the kidney. Bicarbonate anion is considered labile because, at a proper concentration of hydrogen ion, it may be converted to carbonic acid, then to its volatile form, carbon dioxide, excreted by lungs. Normally, a ratio of 1 20 (carbonic acid bicarbonate) is present in extracellular fluid. In a healthy adult with normal kidney function, almost all the glomerular filtered bicarbonate ion is reabsorbed less than 1% is excreted in urine. 

The onset of local anesthesia can be accelerated by the addition of sodium bicarbonate (1-2 mL) to the local anesthetic solution. This maximizes the amount of drug in the more lipid-soluble (unionized) form. Repeated injections of local anesthetics can result in loss of effectiveness (ie, tachyphylaxis) due to extracellular acidosis. Local anesthetics are commonly marketed as hydrochloride salts (pH 4.0-6.0) to maximize aqueous solubility. After injection, the salts are buffered in the tissue to physiologic pH, thereby providing sufficient free base concentration for diffusion through the axonal membrane. However, repeated injections of the local anesthetic can deplete the buffering capacity of the local tissues. The ensuing acidosis increases the extracellular cationic form, which diffuses poorly and results in tachyphylaxis. Tachyphylaxis to local anesthetics is common in areas with a limited buffer capacity (eg, the cerebrospinal fluid). 

The pH-buffering of extracellular fluid depends in part on the carbon dioxide/ bicarbonate equilibrium so that the intake of sodium bicarbonate is followed by a brief alkalosis and an increased excretion of sodium carbonate in the urine. Depending on its carbonate concentration, the pH of the urine may rise to 8.07. Large doses (80—100 g/day) of sodium bicarbonate were needed if the pH of stomach contents was to be maintained at 4 or over in patients with duodenal ulcers8. Oxidation of organic anions in the body to carbon dioxide and water permits the use of sodium citrate, lactate or tartrate instead of sodium bicarbonate. In an analogous manner the ingestion of ammonium chloride induces a brief acidosis as a result of the metabolic conversion of ammonia to urea and lowers the pH of the urine. 

Effect of Holding One s Breath on Blood pH The pH of the extracellular fluid is buffered by the bicarbonate/carbonic acid system. Holding your breath can increase the concentration of C02(g) in the blood. What effect might this have on the pH of the extracellular fluid Explain by showing the relevant equilibrium equation(s) for this buffer system. 

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... 

AHAs may also limit or prevent the cross-linking of proteins in the extracellular matrix. Unlike TCA or phenol, AHAs do not bind with proteins and so are not neutralized by them. The type of action they produce depends on their concentration, the pH of the solution, the pK of the acids and the contact time with the skin before neutralization with a base solution. For example, a 70% glycolic acid solution (pH 0.5 for pK 3.83) in contact with the skin for 5 minutes will be more aggressive than a partially buffered (pH 3.5) 50% solution left in contact with the skin for 2 minutes before neutralization with a base solution (a saturated solution of sodium bicarbonate, for example). 

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 body s buffering system can be divided into three components bicarbonate/carbonic acid, proteins, and phosphates. The bicarbonate buffer is the most important of the body s buffers, because (1) there is more bicarbonate present in the extracellular fluid (ECF) than any other buffer component (2) the supply of carbon dioxide is unlimited and (3) the acidity of ECF can be regulated by controlling either the bicarbonate concentration or the PCO2. 

The dose of hydrochloric acid is usually infused intravenously over 12 to 24 hours." A severe transient respiratory acidosis may occur if the hydrochloric acid is infused too quickly because of the slower reduction of the elevated bicarbonate concentration in the cerebrospinal fluid than in the extracellular fluid. Improvement is usually seen within 24 hours of initiating therapy. Arterial blood gases and serum electrolytes should be drawn every 4 to 8 hours to evaluate and adjust therapy. 

Metabolic acid-base disorders are those which directly cause a change in the bicarbonate concentration. Examples incluile diabetes mcliitus. where altered intemiediary metabolism in the absence of insulin cau.ses a build up of hydrogen ion from the ioni/ation of aceloacetic and P-hydroxybutyric acids, or loss of bicarbonate from the extracellular Iluid. e.g. from a duodenal fistula. 

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]. 

In patients with QRS interval prolongation or hypotension, administer sodium bicarbonate (see p 419), 1-2 mEq/kg IV, and repeat as needed to maintain the arterial pH between 7.45 and 7.55. Sodium bicarbonate may reverse membrane-depressant effects by increasing extracellular sodium concentrations and by a direct effect of pH on the fast sodium channel. 

The most important ions for extracellular conductance by far are Na" " and Cl (Table 2.6). Note that free protein in plasma are charge carriers with a negative charge (anions) and in this context protein can be regarded as macro-ions and a conductance contributor. This charge is also the basis of DC electrophoresis as an important analytical tool in clinical chemistry (Section 2.5.1). To maintain electroneutrality, an increased protein concentration must increase the concentration of cations or reduce the concentration of other anions. The anion HCO3 is the bicarbonate related to the transport of CO2 in the blood therefore, a ehange in bicarbonate concentration (anion) will have consequences for the cation concentration. 

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. 

Figure 2.2. As for Figure 2.1, but more information displayed. The scale around the top shows hydrogen ion concentration both in units of nanomoles per litre and in units of pH. The relationships are shown for distilled water, 24 mM bicarbonate solution, plasma and blood. The perfect buffer does not exist in a closed system, but physiologically the extracellular fluid is an open system and physiological mechanisms are able in some situations to ensure perfect buffering, as shown by the line so labelled on this graph. 

Figure 3.1. Bicarbonate concentration as a function of PCO2. The normal blood line is shown and the oblique line representing a normal extracellular hydrogen ion concentration. Point N is a typical point representing normal acid-base status. Arrow NA indicates the change accompanying uncompensated respiratory acidosis and arrow AB indicates renal compensation.

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