Page 205 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

CHAPTER • 7

Disorders of Phosphorus:

Hypophosphatemia and

Hyperphosphatemia

Stephen P. DiBartola and Michael D. Willard

1 þ 2 þ 3 þ H þ
Phosphorus plays an essential role in cellular structure and H 3 PO 4 ⇄ H 2 PO 4 þ H ⇄ HPO 4 þH ⇄ PO 4
function. 91 A constituent of structural phospholipids in pK 2:0 pK 6:8 pK 12:4
a a a
cell membranes and hydroxyapatite in bone, phosphorus
also is an integral component of nucleic acids and The pK a for the reaction between H 2 PO 4 1 and HPO 4 2
phosphoproteins involved in mitochondrial oxidative is 6.8 at the ionic strength and temperature of extracellu-
phosphorylation. Energy for essential metabolic processes lar fluid (ECF), and these are the two prevailing ionic spe-
(e.g., muscle contraction, neuronal impulse conduction, cies at the normal ECF pH of 7.4. At this pH, H 3 PO 4 and
epithelial transport) is stored in high-energy phosphate PO 4 3 are present in negligible amounts, and plasma
bonds of adenosine triphosphate (ATP). The compound inorganic phosphorus principally consists of H 2 PO 4 1
2,3-diphosphoglycerate (2,3-DPG) decreases the affinity and HPO 4 2 . At a pH of 7.4, the HPO 4 2 :H 2 PO 4 1
of hemoglobin for oxygen and facilitates the delivery of ratio is 4.0, and the average valence of phosphate in serum
oxygen to tissues. Cyclic adenosine monophosphate reflects this ratio. There are four times as many HPO 4 2
(cAMP) is an intracellular second messenger for many 1 ions at a pH of 7.4, and therefore the average
as H 2 PO 4
polypeptide hormones. Phosphate is also an important valence of phosphate at this pH is (4/5)( 2) þ (1/5)
urinary buffer, and urinary phosphate constitutes the ( 1) ¼ 1.8. Because the valence and number
majority of titratable acidity (see Chapter 9). of milliequivalents (mEq) of phosphate in ECF are
Phosphorus is important in the intermediary metabo- influenced by pH, it is easier to measure phosphate
lism of protein, fat, and carbohydrate and as a component in millimoles (mmol) or milligrams (mg) of elemental
of glycogen. It stimulates glycolytic enzymes (e.g., hexo- phosphorus. Serum phosphorus concentrations typically
kinase, phosphofructokinase) and participates in the are reported as elemental phosphorus and expressed
phosphorylation of many glycolytic intermediates. Nico- as milligrams of elemental phosphorus per deciliter
tinamide adenine dinucleotide phosphate (NADP )is a of serum. One millimole of phosphate contains 31 mg
þ
coenzyme for important biochemical reactions. Phos- of elemental phosphorus. To convert milligrams per
phate regulates the activity of enzymes such as the gluta- deciliter to millimoles per liter, divide milligrams per
minase essential for ammoniagenesis (stimulated by deciliter by 3.1. At a pH of 7.4, 1 mmol of phosphate
increased phosphate concentrations) and the 1a-hydrox- equals 1.8 mEq, and conversion from millimoles per
ylase required for vitamin D activation (stimulated by liter to milliequivalents per liter requires multiplication
decreased phosphate concentrations). by 1.8.
Even though phosphorus circulates in organic and inor-
PHYSICAL CHEMISTRY ganic forms, clinical laboratories typically measure inor-
ganic phosphate. Approximately 10% to 20% of the
Phosphorus exists in organic (phospholipidsandphosphate inorganic phosphate in serum is protein bound, and the
esters)andinorganic(orthophosphoricandpyrophosphoric remainder circulates as free anion or is complexed to
acids) forms in the body. Almost all serum phosphorus is sodium, magnesium, or calcium. The free and complexed
in the form of orthophosphate. Orthophosphoric acid fractions are available for ultrafiltration by the renal
is governed by the following set of equilibria: glomeruli.

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