BY PAUL GEDEON
Pathophysiology of phosphate balance.
Physiological function of phosphate
- *Relatively high concentration in ICF
- Role in cellular signaling (cAMP etc.)
- Phosphorylation to activate or deactivate enzymes as cofactors Buffer of bodily fluids
- Component of bones
- Nucleic acids (DNA, RNA)
- ATP, GTP
Regulation of phosphate level
- PTH: Secretion stimulated by high serum phosphate which decreases activity of NaPi transporter leading to phosphaturia. Note: PTH will have effect on both calcium and phosphate so don’t forget about calcium in all this!
- Absorbed in GI via same NaPi transported that is present in kidney; stimulatted by Vitamin D.
- FGF-23:Exact effect still debated but concentration of FGF-23 is proportional to PTH, Vit D and phosphate level. FGF-23 acts to inhibit Vit D action (negative feedback) and stimulate renal loss of phosphate.
Hypophosphatemia (<0.81 mmol/l)
- EC to IC shift o Respiratory alkalosis = H shifted out of cells and into blood in exchange for phosphate, lowering the serum phosphate
- Refeeding syndrome = recovery from malnutrition or chronic alcoholism causes using up of phosphate in rebuilding “damaged” metabolism o Recovery from diabetic ketoacidosis
- Admin of any substances that stimulates glycolysis (which uses phosphate) e.g insulin,
- Bone reservoir disturbance o Hungry bone syndrome (explained in hypocalcemia): After surgical removal of parathyroids to treat osteitis fibrosa cystica, there is rapid deposition of phosphate and calcium to form new bone.
- Excretion disturbance in kidney (congenital vs acquired) o PHPT = increased PTH causes phosphaturia o Hyper FGF-23 (x-linked hypophosphatemic rickets) = phosphaturia
- Fanconi syndrome = Proximal tubular defect causing loss of bicarbonate (RTA-2) and other ions.
- NaPi transported defect
- Osmotic diuresis = in diabetic patients with significant glucosuria, loss of not only water but other ions including phosphate.
- Intake disturbance o Fasting o Alcoholism
- Antacids (with Ca, Al, Mg) = complexation with phosphate will decrease blood phosphate
- Chronic diarrhea or steatorrhea
- Vit D deficiency = low intestinal Pi and calcium absorption
*Depletion of IC ATP = no energy for cellular metabolic function, leading to various consequences
- Hematological o Hemolytic anemia
- Reduced 2,3-BPG = decreased oxygen carrying capacity since normally 2,3-DPG regulates affinity of oxygen to hemoglobin.
- Decreased leukocyte migration o Platelet dysfunction
- Neuromuscular o CNS: Irritability, confusion, coma
- Peripheral neurons: Paresthesia, increased nerve conduction velocity
- Muscle weakness: proximal myopathy, dysphagia, ileus, respiratory failure
- Bone = osteomalacia
- Cardiovascular o Impaired muscle function o CMP
- Renal dysfunction o Falling GFR
- Abnormal tubular transport (loss of Ca, Ng, bicarbonate and glucose)
- IC to EC shift (extensive tissue destruction) o Tumor lysis syndromeo Rhabdomyolysis (extensive skeletal muscle breakdown) o Hemolysis o Fulminant hepatitis o Bowel infarction
- Acidosis = H moved into cell and phosphate moved out in exchange
- Bone reservoir disturbance o Osteoporosis
- CKD as a mineral and bone disorder
- Excretion problems (kidney) o Renal failure (most common cause) = due to falling GFR
- PTH resistance = no stimulation of phosphaturia in kidney o HypoPTH
- Intake problems o Per os, IV load
- Vit D intoxication
- Phosphate enemas
- Short term o Hyperphosphatemia inhibits Vit D activation (hydroxylation) causing Hypocalcemia leading to tetany.
- Long term o Ectopic calcification
o Secondary hyperPTH and development of CKD mineral and bone disorder.