Urinary Control of Blood pH

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],... 

When a dmg is in its unionised form it will more readily diffuse from the urine to the blood. In an acidic urine, acidic drugs will diffuse back into the blood from the urine. Acidic compounds such as nitrofurantoin are excreted faster when the urinary pH is alkaline. Amfetamine, imipramine and amitriptyline are excreted more rapidly in acidic urine. The control of urinary pH in studies of pharmacokinetics is thus vital. It is difficult, however, to find compounds to use by the oral route for deliberate adjustment of urinary pH. Sodium bicarbonate and ammonium chloride may be used but are unpalatable. Intravenous administration of acidifying salt solutions presents one approach, especially for the forced diuresis of basic dmgs in cases of poisoning. 

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]. 

Beckett AH, Salmon JA, Mitchard M. The relation between blood levels and urinary excretion of amphetamine under controlled acidic and under fluctuating urinary pH values using [ ejamphetamine. JPharm Pharmacol (1969) 21, 251—8. 

Disposition in the Body. Readily absorbed after oral administration and accumulates in the tissues. The major metabolite in the blood is the A-desethyl derivative, norfenfluramine, which is active. It is also metabolised by oxidation to m-trifluoromethyl-benzoic acid which is conjugated with glycine to form m-trifluoromethylhippuric acid. The rate of elimination is influenced by urinary pH and urinary flow. In acidic urine about 23% of a dose is excreted unchanged, and about 17% as norfenfluramine in 48 hours the remainder consists of m-trifluoromethylhippuric acid in alkaline urine about 2% is excreted as unchanged drug and norfenfluramine when the urinary pH is not controlled, 3 to 10% may be excreted as unchanged drug and 3 to 14% as norfenfluramine. Up to 5% of a dose is eliminated in the faeces as fenfluramine and norfenfluramine. 

The reverse of alkalosis is a condition known as acidosis. This condition is often caused by a depletion of HCO ions from the blood, which can occur as a result of kidney dysfunction. The kidney controls the excretion of HCO j" ions. If there are too few HCO j" ions in solution, the forward reaction is favored and H3O+ ions accumulate, which lowers the blood s pH. Acidosis can also result from the body s inability to expel CO2, which can occur during pneumonia, emphysema, and other respiratory disorders. Perhaps the single most common cause of acidosis is uncontrolled diabetes, in which acids normally excreted in the urinary system are instead retained by the body. 

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