phosphate Flashcards
What forms of phosphate exist in the body?
Organic
- ATP, DNA, RBC and mostly as PO43
Inorganic (Pi)
Match the following (extrapoints for structures)
- 85%
- 1%
- 14%
A. ICF
B. Bones
C. ECF
1B
- formed as hydroxyapatite crystals
2C
- Mostly inorganic:inorganic form of HPO42- and H2PO42- with a ratio of 4:1
3A
- inorganic or organic forms (ATP, DNA, RBC and mostly as PO43-)
What forms does phosphate have in ECF?
The inorganic phosphate in the ECF can be protein bound (10%), complexed with Ca2+/Mg2+ (35%), or free (55%)
Function of phosphate
functions including ATP formation, phospholipids, intracellular metabolic pathways, tissue oxygenation, acid excretion, bone mineralisation and nucleic acid synthesis.
What factors affect phosphate homeostasis?
Vit D, FGF-23 and PTH are the main ones.
- Others: acid-base status, corticosteroids, GH, thyroxine, insulin, calcitonin, dopamine, serotonin
What does Vit D, FGF23 and PTH do in terms of phosphate?
PTH
- act to release phosphate using bone storage
VitD
- act to increase intestine reabsorption
Both PTH and FGF23 have negative effect on kidney reabsorption of phosphate and increases its excretion.
Where does renal reabsorption take place?
80-95 is reabsorbed in the PCT using Na/PO3 co transporters
- acid-base status, corticosteroids, GH, thyroxine, insulin, calcitonin, dopamine, serotonin
What effect does PTH has?
Stimulates the conversion of 25-OH to 1,25diOH vitamin D - to release phosphate from bone
- act on the kidney by reducing NPT2a/c expression to increase phosphate excretion
What effect does FGF23 has?
FGF23 is released by osteocytes and osteoblasts. Acts to inhibit the conversion of 25-OH to 1,25diOH vitD to decrease absorption of phosphate.
- FGF23 act on the kidney to reduce NPT2a expression cauisn increased phosphate excretion
What symptoms will patients with mild, severe and chronic hypophosphataemia have?
Mild - no signs
Chronic - rickets/osteomalacia
Severe - hematopoietic, muscular, nervous and GI systems
Describe the severe (hypophosphataemia) symptoms in detail
Haemopoietic system - decreased2,3-BPG in RBC (reduced oxygen release - hypoxia), increased red cell fragility (haemolysis), abnormal platelet function
- Muscular system: decrease in contractility of the diaphragm, heart, skeletal muscle (can lead to respiratory failure), and/or rhabdomyolysis
- Nervous system: decreased energy available to the brain, in the form on lethargy, confusion, seizure and possibly comas
- GI problems: smooth muscle breakdown
What causes hypophosphataemia?
Inadequate absorption from the intestine, redistribution into cells or bones, or increased urinary phosphate loss
Describe how inadequate intake causes hypophosphataemia
Malnutrition, alcoholism, malabsorption, Vit D deficiency, or use of antiacids
Describe how redistribution into the bone causes hypophosphataemia
Seen in hungry bones syndrome where rate of bone formation is greater than breakdown.
Describe how redistribution into cells causes hypophosphataemia
Seen in refeeding syndrome, DKA recovery, alkalosis, increased muscle uptake
Describe how increased loss causes hypophosphataemia
Either GI or renal
GI- diarrhoea
Renal - alcohol, hyperparathyroidism, fanconi, post kidney transplant
What is refeeding syndrome?
Redistribution of K
- Periods of malnutrition, followed by intake of carbohydrates
- Intracellular ions (Mg2+, PO3-, K+) have leaked from cells and been lost in the urine during malnutrition but following intake they are rapidly taken up by cells due to insulin release
What is respiratory alkalosis?
Redistribution of K
- (hyperventilation and H+ ICF decrease)This activates a phosphofructokinase which increases the phosphorylation of glucose to allow phosphate to be rapidly taken up
What are some FGF-23 related conditions?
In renal failure FGF23 increases causing hyperphosphataemia and hypophosphataemic rickets.
Range of genetic disorders associated with elevated FGF23
- X-linked hypophosphataemic rickets (XLH)
- AD hypophosphataemic rickets (ADHR)
- AR hypophosphataemic rickets (ARHR)
- Tumour induce osteomalacia
Briefly explain what X-linked hypophosphataemic rickets (XLH) is?
Mutation to PHEX gene causing renal phosphate wasting due to the actions of FGF23
Briefly explain what AD hypophosphataemic rickets (ADHR) is?
Mutation in FGF-23 at is cleavage site that prevents proteolysis
Briefly explain what AR hypophosphataemic rickets (ARHR) is?
Mutation to DMP1 gene encoding a restraining FGF23 protein
Describe the investigations for hypophosphateamia
Review clinical details: IV treatment, history of alcoholism/eating disorders, drugs, any renal impairment/transplant.
Repeat phosphate according to glucose/insulin throughout the day.
Further assessment includes:
- U&E: renal function
- bone profile
- Mg measurement
- pH
- Urine phosphate
- urine amino acids
- Urine AA and glucose
- PTH/FGF23/vitD
How is the reabsorption of phosphate assessed?
A paired fasting 2nd void urine & blood for calculations of TmP/GFR. This tells us renal tubular maximum reabsorption of phosphate per litre of GFR
- TRP<0.86 phosphate reabsorption is maximal and relationship is linear
