PHOSPHATE AND ORGANIC ACIDS AS BUFFERS in Visual C#.NET

Scan Denso QR Bar Code in Visual C#.NET PHOSPHATE AND ORGANIC ACIDS AS BUFFERS

PHOSPHATE AND ORGANIC ACIDS AS BUFFERS
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Filtered phosphate is normally the most important non-bicarbonate urinary buffer Most free plasma phosphate exists in a mixture of monovalent and divalent forms In Equation 9 5, monovalent dihydrogen phosphate (on the left) is a weak acid, and divalent monohydrogen phosphate (on the right) is its conjugate base
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2 H2PO4 H1 1 HPO422
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We can write this in the form of the Henderson-Hasselbalch equation:
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2 pH 5 68 1 log [HPO422]/[H2PO4 ]
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At the normal pH of plasma (74) and, therefore, of the glomerular filtrate, we find that about 80% of the phosphate is in the base (divalent) form and 20% is in the acid (monovalent) form As the tubular fluid is acidified in the collecting ducts, most of the base form combines with secreted hydrogen ions By the time the minimum intratubular pH of 44 is reached, virtually all the base (HPO422) has been converted to acid (H2PO42) Therefore, secreted hydrogen ions that combined with the base form are excreted, and the bicarbonate that was generated intracellularly in the process enters the blood How much phosphate is available for this process The amount is somewhat variable, depending on a number of factors (see 10), but a typical plasma concentration is about 1 mmol/L, of which about 90% is free (the rest being loosely bound to plasma proteins) At a GFR of 180 L/day, the total filtered load of phosphate is about160 mmol/day The fraction reabsorbed is also variable: from 75% to 90% Thus, unreabsorbed divalent phosphate available for buffering is roughly 40 mmol/day In other words, the kidneys can excrete hydrogen ions, using the phosphate buffer system, at a rate of about 40 mmol/day However, the availability of phosphate cannot be easily upregulated to increase acid excretion There are other organic buffers in the urine, and under certain conditions these may appear in the tubular fluid in sufficient quantities to allow them also to act as important buffers A particularly important example is a patient with uncontrolled diabetes mellitus Because of metabolic processes that result from insulin deficiency, such a patient may become extremely acidotic due to the excess production of acetoacetic acid and -hydroxybutyric acid At normal plasma pH,
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these species completely dissociate to yield the anions -hydroxybutyrate and acetoacetate (and hydrogen ions) These anions are filtered at the renal corpuscle but are only partly reabsorbed because they are present in great enough quantities to exceed the renal reabsorptive Tms Accordingly, they are available in the tubular fluid to buffer a portion of the hydrogen ions being secreted by the tubules However, their usefulness in this role is limited by the fact that their pKs are low: approximately 45, meaning that only at very low pH will the secreted hydrogen ions combine with them At the limiting urine pH of 44 only half of them have actually combined with a hydrogen ion The rest remain in the base form
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HYDROGEN ION EXCRETION ON AMMONIUM
Ordinarily, hydrogen ion excretion associated with phosphate and other filtered buffers is no greater than about 40 mmol/day This amount is not sufficient to balance the normal hydrogen ion production of 50 100 mmol/day or take care of any unusually high (usually pathological) production of acid loads To excrete the rest of the hydrogen ion and achieve balance, there is a second means of excreting hydrogen ions that involves ammoniagenesis and excretion of hydrogen ions as ammonium Quantitatively, far more hydrogen ions can be excreted by means of ammonium than via organic buffers There are many nuances to hydrogen ion excretion via ammonium, but the basic concepts are straightforward As described in 5, the catabolism of protein and oxidation of the constituent amino acids by the liver generates CO2, water, urea, and some glutamine Protein catabolism, which occurs constantly, even in starvation, requires the continuous excretion of urea by the kidneys to prevent uremia Although, as described earlier, metabolism of the side chains of amino acids can lead to the addition of acid or base, the processing of the core of an amino acid the carboxyl group and amino group is acid-base neutral After many intermediate steps, processing of the carboxyl group of the amino acid produces a bicarbonate, and processing of the amino group produces an ammonium ion Processing does not stop there, however, because ammonium in more than miniscule levels is quite toxic Ammonium is further processed by the liver to either urea or glutamine In both cases, each ammonium consumed also consumes a bicarbonate Thus, the bicarbonate produced from the carboxyl group is just an intermediate, consumed as fast as it is made, and the process as a whole is acid-base neutral We can write this process as follows: 2 amino acids (1oxygen) 2NH4+ 1 2HCO32 urea or glutamine (1CO2 and water)
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When the urea (or glutamine) is excreted, the body has completed the catabolism of protein in a manner that promotes total body protein nitrogen balance, but is acid-base neutral
regulation of hydrogen ion balanCe / 171
Renal handling of urea is somewhat complicated from the osmotic point of view, as described in earlier chapters, but the handling is acid-base neutral Glutamine, however, is different Although the production of glutamine by the liver is acidbase neutral, it is important to recognize that glutamine can be thought to contain 2 components: a base component (bicarbonate) and an acid component (ammonium) Ammonium is the protonated form of ammonia and is an acid because it contains a dissociable proton, as shown in Equation 9 8, though an extremely weak acid The pK of ammonium is near 92 At physiological pH over 98% of the total exists as ammonium, and less than 2% exists as ammonia For renal acidbase purposes, this is a good thing because virtually all excreted ammonia is in the protonated form and takes a hydrogen ion with it
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