Physiology Note - Calcium and Phosphate Homeostasis

Dr Ch V Jyotsna
Assistant Professor, Critical Care
NRI Medical College
Guntur

CALCIUM AND PHOSPHATE HOMEOSTASIS

 

 

Calcium is a divalent cation and an essential element required for bone mineralization, muscle contraction, neuronal transmission, blood clotting and also functions as second messenger for hormone secretion and regulation. 99% of calcium is found within the bones and less than 1% is found intracellular with 0.1% of calcium in the extracellular fluid. Out of the calcium found in ECF, 50% is in ionized form which is the biologically active form and around 45% of calcium is protein bound and remaining is bound to anions like citrate, phosphate, sulphate and bicarbonate. Normal serum calcium levels are 8.5 – 10 mg/dl. Ionized calcium levels are 1.15-1.25 mmol/L. (Figure 1)

 

              In case of hypoalbuminemia, there is decrease in total body calcium where as ionized calcium remains unaffected.


 

CALCIUM HOMEOSTASIS


    Phosphorus is also an essential element required for bone mineralization. Major portion of phosphate is found within the bones (85%). Remaining 15% is found in the other tissues and less than 1% is found in extracellular fluid. It is component of adenosine triphosphate, energy source of cells and is also required for the formation of DNA and RNA. It helps in the formation of phospholipids, a component of cell membrane. It also required for enzyme activation. Normal serum phosphorus levels are 2.5-4.5 mg/dl. ( Figure 2)

 

 

Calcium is absorbed from small intestine which is vitamin D dependent. It is excreted from urine. With the net intestinal absorption of about 200 mg of calcium per day and renal excretion amounting to about 200 mg/day to maintain balance in a non-growing adult, 98% of the filtered calcium is reabsorbed by the tubules. It is mostly reabsorbed from proximal (80%) and distal (15%) tubules of nephron.

Dietary intake of phosphorus is approximately 20 mg/kg/day, of which more than half is absorbed. It is excreted in the urine, most of which is reabsorbed in the kidneys mainly in the proximal tubules.

CALCIUM – PHOSPHATE PRODUCT

              It is the product of total serum calcium levels and total serum phosphorus levels. This product is utilised in CKD patients to decide on the phosphate binders.

Calcium- phosphate product >55 à Sevelamer as phosphate binder

Calcium- phosphate product <55 à Calcium acetate as phosphate binder

 

Calcium and phosphate levels in the body are regulated by three hormones, parathyroid hormone, calcitonin and calcitriol and also Fibroblast growth factor- 23. It is regulated by kidneys, gut and parathyroid gland.

i)                    Parathyroid hormone (PTH) – It is a peptide hormone secreted by chief cells of parathyroid gland. These chief cells are sensitive to plasma calcium levels. Decrease in plasma calcium levels increases PTH secretion and vice versa. Parathyroid hormone increases bone osteoclastic activity and increases calcium levels. It also increases intestinal absorption of calcium and increases calcium reabsorption in kidneys. PTH secretion leads to phosphaturic effect and decreases the reabsorption of phosphate from kidneys by internalization of sodium phosphate co transporters.

ii)                  Calcitonin – It is produced by parafollicular C-cells of thyroid gland. It promotes osteoblastic activity in bones thereby decreasing serum calcium and phosphate levels. It reduces calcium reabsorption in kidneys and increases urinary calcium excretion. It also inhibits calcium absorption in the gut.

iii)                Calcitriol – Decreased levels of calcitriol stimulate osteoblast activity and inhibit osteoclast activity which decreases plasma calcium and phosphate concentrations. Decreased calcitriol levels also decreases the absorption of calcium and phosphate from the diet in the intestines which decreases plasma calcium and phosphate concentrations. Also decreased calcitriol levels in the kidneys, increases the excretion of calcium from the urine which decreases plasma calcium concentrations and vice versa.

iv)                Fibroblast growth factor-23 (FGF-23) – It is produced by bone cells and inhibits phosphate reabsorption in the kidneys thereby promoting phosphaturia and decreasing serum phosphate levels.

v)                  Insulin, thyroid, oestrogen and growth hormone promote phosphate reabsorption in kidneys.


 

 

PHOSPHATE HOMEOSTASIS

                                                         
 Recommended Reading

1. Marino, P. L. (2025). Maib05. Wolters Kluwer.
2. Yu E, Sharma S. Physiology, Calcium. [Updated 2023 Aug 14]. In: StatPearls
3. Taylor JG, Bushinsky DA. Calcium and phosphorus homeostasis. Blood Purif. 2009;27(4):387-94. doi: 10.1159/000209740. Epub 2009 Mar 23. PMID: 19299893.
4. Phosphate homeostasis in critical care Wadsworth, RL et al. BJA Education, Volume 16, Issue 9, 305 - 309
5. Lilly, C. M., Kelly, W. F., Irwin, R. S., & Boyle, W. A., III (2024). Irwin and rippe’s intensive care medicine, 9e

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