![Body phosphate content
600 – 700 g in adult
(20 – 25 mol)
[1 mmol of phosphate= 30 mg]](https://image.slidesharecdn.com/phosphatehomeostasisitsrelateddisorders-171029061559/75/Phosphate-homeostasis-its-related-disorders-16-2048.jpg)
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Similar to Phosphate homeostasis & its related disorders
Phosphate homeostasis & its related disorders
- 1. Phosphate Homeostasis & ItsRelated Disorders Dr Ifat Ara Begum Associate Professor Dept of Biochemistry Dhaka Medical College, Dhaka
- 2. Introduction to phosphate Essentialto many vital physiological processes One of the important anion of ICF (140 meq/L)
- 3. Functions of phosphate Bonemineralization Participates in energy metabolism (storage & transfer of energy) Component of 1. Phospholipid, nucleotides & nucleic acid 2. 2,3-BPG & regulate oxygen transport
- 4. Contd Acts as Buffer& facilitates urinary acid excretion The component of intracellular 2nd messenger & participates in signal transduction Regulation of enzyme activity by covalent modification of enzyme Facilitates respiratory chain activity
- 5. Renal handling ofphosphate May be discussed under following headlines: I. Tubular load of phosphate II. Tubular reabsorption of phosphate III. Renal excretion of phosphate
- 6. i) Tubular loadof phosphate Tubular load equals to GFR X free Plasma phosphate concentration 100 - 200 mmol/day
- 7. ii) Tubular reabsorptionof phosphate 80 - 95% of tubular load i. From PCT: 70-80% by secondary active transport ii. From distal nephron : 10 - 20%
- 8. Contd Remember, Normally, phosphateis reabsorbed essentially from PCT & here, its reabsorption is inhibited by PTH Distal nephron reabsorbs phosphate only if hectic phosphate restriction in diet is imposed
- 9. Contd Process of tubularreabsorption of phosphate: Na+ - K+ pump keeps the intracellular Na+ concentration low So, Na+ from lumen diffuses to cell along with phosphate via Na-PO4 symporter Phosphate from cell goes to blood through basolateral border by diffusion
- 11. iii) Renal excretionof phosphate < 20% of tubular load It is <20 - 40 mmol/day
- 12. Contd Factors regulating renalphosphate excretion: 1. Dietary phosphate intake: If increases, renal phosphate excretion also increases. 2. Plasma phosphate concentration: If increases, renal phosphate excretion also increases.
- 13. Contd 3. PTH:It inhibits the Na-PO4 symporter & increases phosphate excretion by decreasing its reabsorption 4. Calcitonin: It increases the renal excretion of phosphate
- 14. Contd 5. Acid basestatus: In PCT of kidney, Na-PO4 symporter preferably entertains HPO4 -2 rather than H2PO4 - to be reabsorbed In acidosis, H2PO4 - predominates, so renal phosphate reabsorption decreases In alkalosis, HPO4 -2 predominates, so renal phosphate reabsorption increases
- 15. Phosphate homeostasis May bediscussed under following headings: Body phosphate content Distribution of phosphate Phosphate balance Daily turnover of phosphate & Regulation of phosphate balance
- 16. Body phosphate content 600– 700 g in adult (20 – 25 mol) [1 mmol of phosphate= 30 mg]
- 17. Distribution of phosphate I.80 - 85% in bone : Predominantly as calcium phosphate crystal (hydroxy apatite crystal) II. 15 - 20% in soft tissues III. 0.1% in ECF
- 18. Contd Plasma phosphate: 2.5 –4.5 mg% Forms of plasma phosphate: A. Organic: 70% B. Inorganic: 30%
- 19. Contd Inorganic phosphate: Ismeasured clinically as it is biologically active Represents the phosphate status of an individual Present in 3 forms in plasma: i. Free form (85%) ii. Protein bound form (10%) iii. As complex with cation (5%)
- 20. Phosphate balance Intake: 1400mg/day via milk/milk products, fish, meat, vegetables etc Output: 1400 mg/day via a) Urine: 900 mg/day b) Feces: 500 mg/day
- 21. Contd Intestinal absorption ofphosphate: 60 – 70% of dietary phosphate is absorbed from intestine by vitamin D & PTH Intestinal absorption matches with renal excretion in steady state
- 22. Contd From intestine, phosphateis absorbed : Actively through transcellular route by Na-PO4 symporter stimulated by vitamin D & Passively through paracellular route
- 24. Phosphate turnover Available phosphatein intestine: 1600 mg 1. Diet (1400 mg/day) 2. Various intestinal secretion (200 mg/day)
- 25. Contd From intestinal lumen, 1100 mg of phosphate is absorbed by PTH & vitamin D (with net absorption of 900 mg) which joins ECF phosphate pool of pool 600 – 700 mg Remaining 500 mg of phosphate from intestinal lumen is excreted with stool
- 26. Contd ECF phosphate poolis in reversible equilibrium with soft tissue phosphate pool & bone phosphate pool at a definite turnover rate From ECF , 900 mg calcium is excreted through urine daily to match with the intestinal absorption
- 28. Contd Renal excretion ofphosphate is regulated by PTH Bony phosphate turnover is regulated by PTH & vitamin D
- 29. Regulation of phosphatebalance
- 30. Contd Remember, The neteffect of : 1. Calcitriol : Hypercalcemia & Hyperphosphatemia. Calcitriol directly can suppress PTH secretion 2. PTH: Hypercalcemia but hypophosphatemia 3. Calcitonin: Hypocalcemia & hypophosphatemia
- 31. ↓ Plasma PO4 ↑Calcitrio l ↑ intestinal Calcium absorption ↑ intestinal PO4 absorptio n ↓PTH ↓ bone resorptio n ↓ PO4 excretion ↑ Calcium excretion No change / slight ↑ in plasma calcium Serum PO4 comes back to normal
- 32.
- 33. Abnormalities of phosphate homeostasis 2types of abnormalities: 1. Hyperphosphatemia 2. Hypophosphatemia
- 34. 1. Hyperphosphatemia An electrolytedisturbance in which there is abnormally elevated level of phosphate in blood >4.5 mg% Often, calcium levels are lowered (hypocalcemia) due to precipitation of phosphate with the calcium in tissues.
- 35. Contd Causes may belisted under following headings: Impaired renal excretion: RF Increased phosphate intake/absorption: dietary intake,↑ ingestion of phosphate containing supplement/bowel preparations etc Release from intracellular store: Rhabdomyolysis, tumorolysis etc
- 36. Contd Endocrinopathies: Hypoparathyroidism, Resistanceto PTH Shift from intracellular to extracellular compartment: Metabolic acidosis, lactic acidosis, DKA Genetic diseases: Familial tumoral calcinosis
- 37. Contd (Explanation onshift) Metabolic acidosis causes phosphorus to shift out of cells. In lactic acidosis, glycolysis is decreased, which decreases intracellular utilization of phosphate in the generation of ATP. In DKA, glycolysis is impaired and hyperglycemia can shift phosphate out of cells via osmotic drag.
- 38. 2. Hypophosphatemia An electrolytedisturbance in which there is abnormally low level of phosphate in blood <2.5 mg%
- 39. Contd Causes may belisted under following headings: Increased renal excretion: Hyperparathyroidism, metabolic acidosis etc Decreased phosphate intake/absorption: Poor intake, malabsorption, vitamin D deficiency/resistance, diarrhoea, steatorrhea etc
- 40. Contd Shift fromextracellular to intracellular compartment: : Respiratory alkalosis, elevated serum insulin or glucose levels Genetic diseases: Autosomal dominant hereditary hypophosphatemic rickets (ADHR), X-linked hypophosphatemic rickets (XHR) etc
- 41. Contd (Explanation onshift) In respiratory alkalosis, CO2 decreases in the extracellular space, causing intracellular CO2 to freely diffuse out of the cell. This drop in intracellular CO2 causes a rise in cellular pH which has a stimulating effect on glycolysis.
- 42. Contd Since the processof glycolysis requires phosphate (the end product is ATP), the result is a massive uptake of phosphate into metabolically active tissue (such as muscle) from the serum. So hypophosphatemia develops