Excretion of acid

There is a limit to the magnitude of the gradient against which pumping can occur this limit is reached when the pH of the tubular fluid falls to around 4.5. If all the hydrogen ions excreted from the body via the urine were freely ionized in the urine, the amount of acid which could be excreted would be limited to the amount present in solution with a pH of 4.5 and this is. 10 micromoles of hydrogen ions per litre of urine. If in 24 hours Ij litres of urine is excreted, this corresponds to a total daily excretion of 45 micromoles of hydrogen ions. Metabolism in a person on a typical omnivorous diet yields 

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Renal reclamation or excretion of HCOf and excretion of acids such as ammonium. 

As observed in Figure 9.4 the intrinsic clearance (as represented by oral unbound clearance CIqu) of UK-147,535 shows an allometric relationship between the rat, dog and man. This would indicate that the transporter protein involved is conserved across these species and has similar affinity. However, marked reduction in clearance in the rabbit suggests the absence, or marked alteration, of the responsible protein in the hepatic sinusoidal membrane of this species. This finding may explain the common observation of reduced biliary excretion of acidic compounds in rabbits compared to other species [24, 25]. 

Oral contraceptives decrease the plasma levels of ascorbic acid. Aspirin also decreases tissue levels of vitamin C. The renal excretion of acidic and basic drugs may be altered when they are coadministered with large doses of vitamin C. 

Ionisation determines the partitioning of drugs across membranes. Unionised molecules can easily cross and reach an equilibrium across a membrane, while the ionised form cannot cross. When the pH is different in the compartments separated by the membrane the total (ionised + unionised) concentration will be different on each side. An acidic drug will become concentrated in a compartment with a high pH and a basic drug in one with a low pH. This is known as ion-trapping, and occurs in the stomach, kidneys, and across the placenta. Urinary acidification accelerates the excretion of weak bases, such as pethidine, while alkalinisation increases the excretion of acidic drugs, such as aspirin. As an example consider pethidine (pKa 8.6) with an unbound plasma concentration of 100 (arbitrary units). At pH 7.4 only 6% of the pethidine will be unionised so that at equilibrium the concentration of unionised pethidine in the urine will be 6 units. In urine at pH 6.5 only 0.8% of the pethidine will be unionised so that the total concentration in the urine will be 744 units. 

The considerably increased (20-40-fold) excretion of acid mucopolysaccharides suggests that Marfan s syndrome also represents a defect in the metabolism of connective tissues (B4). The major mucopolysaccharides excreted were indistinguishable in their electrophoretic mobilities from hyaluronic acid and chondroitin 4- or 6-sulfate. Examination of the levels of mucoproteins and acid mucopolysaccharides in the serum of cases of Marfan s syndrome revealed an increase in the latter, while the former is decreased. Bacchus (B1) considers that this pattern might be of clinical and pathogenetic significance. 

A definite difference in the urinary excretion of acid mucopolysaccharides was also observed (S2) in Morquio s disease. Although the nature of the mucopolysaccharide excreted in Morquio s disease awaits definite characterization, it does not appear to be keratan sulfate. 

The concentration of acid mucopolysaccharides in serum, and their excretion in urine, are increased in patients with rheumatoid arthritis (D7), lupus erythematosus (D6), diabetes (C7), and leukemia (R2, SIO) and other malignant diseases (R2). The daily urinary excretion of acid mucopolysaccharides was within the normal range in cases of acute hepatitis, but was usually increased in chronic hepatitis and in florid cirrhosis (K5). A decrease in the amount of acid mucopolysaccharides excreted was found in primary hepatoma, whereas in most cases of obstructive jaundice the amount was markedly increased (K5). 

D7. Di Ferrante, N., Urinary excretion of acid mucopolysaccharides by patients with rheumatoid arthritis. J. Clin. Invest. 36, 1516-1520 (1957). 

This system is important in the excretion of acids in the urine, as is explained in the section on renal compensatory mechanisms. 

Reduced excretion of acids (H ) as occurs in renal failure and some RTAs, resulting in an accumulation of acid that consumes bicarbonate. 

If possible, the kidneys respond to restore the normal pH by increased excretion of acid and preservation of base (increased rate of Na -H exchange, increased ammonia formation, and increased reabsorption of bicarbonate). When the renal compensating mechanisms are ftinction-ing, urinary acidity and urinary ammonia are increased. The total amount of excreted may be as much as... 

In patients with adequate renal function, urinary pH values are usually increased because of the decreased excretion of acid and increased excretion of bicarbonate. Urinary ammonia values are decreased because of decreased formation of ammonia in the tubules. In K depletion, is preferentially exchanged for Na and the pH of the urine may be low. This is called paradoxical aciduria. 

B20. Brunish, R., and Sorensen, B., Urinary excretion of acid mucopolysaccharides and hydroxyproline in psoriasis. Dermatologica 130, 165-172 (1965). 

Henderson, L. J. (1910). On the excretion of acid from the animal organism. VIH. 

The primary action of BARs is to bind bile acids in the intestinal lumen, with a concurrent interruption of enterohepatic circulation of bUe acids and a markedly increased excretion of acidic steroids in the feces. This decreases the bile acid pool size and stimulates hepatic synthesis of bile acids from cholesterol. Depletion of the hepatic pool of cholesterol results in an increase in cholesterol biosynthesis and an increase in the number of LDL receptors on the hepatocyte membrane. 

Major functions of the distal nephron include the regeneration of bicarbonate, the excretion of acid (hydrogen ion), the secretion of potassium, and the reabsorption of water. Damage to this portion of the nephron may present as significant acidemia and either hypo-or hyperkalemia, depending on the mechanism of injury. For example, amphotericin B produces small pores in the luminal membrane of distal tubular cells. These pores allow small molecules such as potassium to leak out the molecules are then wasted in the urine. Consequently, amphotericin B nephrotoxicity is characterized by hypokalemia secondary to renal potassium wasting. ATN is associated with urinary sediment characterized by the presence of tubular cells, coarse granular casts, and rarely, RBC casts. 

The effects of selected compounds on the cellular metabolic activity (rate of excretion of acidic metabolites) of CHO cells transfected with human muscarinic receptor subtypes were determined utilizing a Cytosensor micro-physiometer (McConnell, 1992). 

The effects of 6m enantiomers on receptor-mediated excretion of acidic metabolites by Hmi-Hm -CHO cells is measured. 

L15. Lubec, G., Legenstein, E., Poliak, A., and Meznik, E., Glomerular basement membrane changes, Hb Aj. and urinary excretion of acid glycosaminoglycans in children with diabetes mellitus. Clin. Chim. Acta 103, 45-49 (1980). 

Influence of age. The influence of age on the blood citrate level has already been discussed. Excretion of acids of the citric acid cycle, as well as of other organic acids, has been studied by Zweimiiller and McCance (Z6, Z7) in urine passed before and shortly after birth the acids of the tricarboxylic acid cycle are already present in such urine samples. 

Fig. 3. Hypothetical mechanism of phytoplankton repulsion of bacterial attachment by excretion of acidic cell constituents forming an external pH transition zone into the alkaline seawater (from Sieburth, 1968).

FIGURE 1A4-1 The cell biology of extracellular acidification. When a receptor is stimulated, signal transduction pathways are Induced. Adenosine triphosphate (ATP) consumption is then compensated by the increased uptake and metabolism of glucose, which results m an increase in the excretion of acid waste products. The extracellular acidification is measured by the LAPS. (From F. Hafner. Biosens. 8/betecfron., 2000. 15. 149. With permission.)... 

W14. Winand, R. J., Increased urinary excretion of acidic mucopolysaccharides in exophthalmos. /. Clin. Invest. 47, 2503-2568 (1967). 

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