short notes for exam point of views depicting phosphorus disorders

1. Phosphorus
An adult body contains about 1 kg phosphate and it is found in every cell of the body. Most of
it (about 807o) occurs in combination with Ca in the bones and teeth. About 10 % of body P is
found in muscles and blood in association with proteins, carbohydrates and lipids. The remaining
10% is widely distributed in various chemical compounds.
Both in the monovalent and divalent state
(H2PO4-
and HPO42-
)
Ratio 1:1 = acidosis, 1:4 = pH 7.4 and 1:9 = alkalosis.
Inorganic : major component of hydroxyapatite in bone which play an important role in structural
support of the body.
Organic: most are incorporated into nucleic acids ,phospholipids, phosphoproteins and high
energy compounds involved in metabolism. Like ATP, creatine phosphates.
Biochemical functions
1. Phosphorus is essential for the development of bones and teeth.
2. lt plays a central role for the formation and utilization of high-energy phosphate compounds e.g.
ATP, GTP, creatine phosphate etc.
3. Phosphorus is required for the formation of phospholipids, phosphoproteins and nucleic acids
(DNA and RNA
4. It is an essential component of several nucleotide coenzymes e.g. NAD+, NADP+, pyridoxal
phosphate, ADP, AMP.
5. Several proteins and enzymes are activated by phosphorylation. Therefore has got role in
metabolism of proteins, fats and carbohydrates. Gene transcription and cell growth.
6. Phosphate buffer system is important for the maintenance of pH in the blood (around 7 .4) as
well as in the cells.
Serum Phosphate
The phosphate level of the whole blood is around a0 mg/dl while serum contains about 3- 4 mg/dl.
This is because the RBC and WBC have very high content of phosphate.
The serum phosphate may exist as free ions (40%) or in a complex form (50%) with cations such
as Ca2+
, Mg2+
, Na+
, K+
. About 10% of serum phosphate is bound to proteins.
Note: that the fasting serum phosphate levels are higher than the postprandial.
Clinical significance
Hypophophatemia (< 2.5 mg/dl)
May be caused by
1. A shift from ECF to ICF ( common)
2. Renal phosphate wasting
3. Decreased intestinal absorption
4. Loss from intracellular phosphate

2. Brief
A major etiology is carbohydrate –induced stimulation of insulin secretion >> transport of glucose
and phosphate into the cells. Where it is incorporated into the sugar phosphates and ATP.
Respiratory alkalosis >> increase in intracellular pH >> activates PFK and accelerates
glycolysis>> shift of phosphates into cells.
Any causes of excessive PTH secretion ( primary) and secondary hypothyroidism >> lowers the
renal threshold which causes the hypophosphatemia and phosphate depletion.
Also , lowered in Fanconi syndrome
X-linked hypophosphatemia rickets
Tumor induced osteomalacia.
Chronic alcoholism
Another disease called hungry bone syndrome.
Inadequate intestinal absorption due to malabsorption, malnutrition, vitamin D deficiency and
antacids that binds phosphorus
Aluminium and magnesium containing antacids causes hypo because phosphates binds with
antacids rendering it non absorables.
Treatment of DKA >> hypophosphatemia
Clinical manifestation depends on length and degree of deficiency.
Moderate : 1.5 to 2.4 mg/dl is usually not associated ( unless chronic, when osteomalacia or rickets)
Clinically : < 1.5 mg/dl because ATP, glycolysis , cellular function gets deranged.
Like muscle weakness, acute respiratory failure and decreased cardiac output.
At very low , < 1.0 mg/dl , rhabdomyolysis may occurs.
Also, 2,3 BPG is decreased >> tissue hypoxia >> because of increased affinity of HB for O2.
Severe hypophosphatemia ( < 0.5 mg/dl) : hemolysis of RBCs may occurs.
Mental confusion and frank coma also may be seen due to low ATP and tissue hypoxia.
Lastly, if it is chronic >. Impaired mineralization of the bone>> Rickets in children and
osteomalacia in adults.
Hungry bones syndrome
Fanconis syndrome: multiple defect in renal proximal tubular reabsorption, causing
glucosuria, phosphateuria,aminoaciduria,bicarbonate wasting,uric acid, water, sodium and
potassium , resulting hypokalemic metabolic acidosis associated with vitamin D resistant
metabolic bone disease.

3. Causes
Intracellular shift
Glucose: oral or intravenous
Insulin therapy
Alkalosis
Lowered renal phosphate threshold.
Primary and secondary hyperparathyroidism
Renal tubular defect
Familial hypophosphatemia
Fanconis syndrome
Decreased net intestinal absorption
Increased loss like vomiting and diarrhea
Phosphate binding antacids
Malabsorption syndrome
Vitamin D deficiency
Intracellular phosphate loss
Acidosis like ketoacidosis amd lactic acidosis
Hyperphosphatemia
Increase absorption: excess vitamin D
Increase cell lysis:
Release of intracellular phosphorus due to cell breakdown in case of rhabdomyolysis, intravascular
hemolysis and chemotherapy of certain malignancy.leukemia
Decrease excretion: renal failure, hypoparathyroidism and thyrotoxicosis
In acute or chronic renal failure>> decrease GFR>>reduces renal excretion of phosphate
>>hyperphosphatemia.
Moderate increase: Low PTH and PTH resistance (pseudo hypoparathyroidism)
Acromegaly( increased Growth Hormone) >> increased phosphate threshold caused by GH due to
which higher phosphate is seen in children.
Shift from ICF to ECF

4. Excessive oral, rectal or intravenous phosphate administration for the treatment of phosphate
depletion.
Acidosis>> hydrolysis of intracellular organic phosphate containing compound >> release of
phosphate into plasma.
Clinical manifestation
Rapid increase in serum phosphate>>hypocalcemia
Due to which symptoms like tetany, seizures and hypotension occurs.