Ca2+ / Phosphate Balance Flashcards
Where is phosphate reabsorbed?
By which transporter?
Proximal tubule
85% is reabsorbed via the NaPi2a/NaPi2c cotransporters here
5 Functions of Ca2+
- bone growth/remodelling
- secretion e.g. of NTs
- muscle contraction
- blood clotting
- 2ndry messenger
4 steps of bone remodelling
- stem cell differentiation to osteoclasts
- reabsorption of bone
- MO/Mononuclear cell mopping up debris
- Laying down new osteoid by osteoblasts
3 hormones favouring osteoclast activation
3 hormones favouring osteoblast activation
osteoclast + : thyroxine, vit A, PTH
osteoblast + : oestrogens, androgens, PTH
Where in parathyoid glands is PTH made?
Chief cells
If calcium is low, the parathyroids detect this and respond by…
releasing more PTH
4 actions of PTH…
- stimulates osteoblasts to produce M-CSF and RANK ligand to increase bone reabsorption
- increases Ca2+ reabsorption in the DCT
- increases phosphate excretion
- stimulates conversion of cholecalciferol into active 1,25-dehydroxy vitamin D3 “calcitriol” in the kidney via increasing the enzyme 1 a hydroxylase
3 actions of Vitamin D in Calcium homeostasis…
- increases Ca2+ absorption in the GUT
- synergies with PTH on bone
- stimulates CaBP synthesis (ca binding protein)
- inhibits PTH synthesis and 1-a hydroxylase
Causes of Hypercalcemia
- Hyperparathyroidism
- Cancer
- Hypervitaminosis (D)
- Increased bone turnover
Cause of Primary Hyperparathyroidism
- Chief cells no longer recognise calcium is high
- due to single adenoma causing inability to switch off PTH
- or diffuse hyperplasia
Secondary vs. Tertiary Hyperparathyroidism
2ndry is a compensatory hyperfunctioning of parathyroid glands due to hypocalemia, peripheral PTH resistance, renal insufficiency, vit D deficiency..
whereas 3ary is following 2ndry when despite the underlying abnormality having been corrected corrected, the glandular hyperfunctioning continues
Hormonal causes of Hypercalcemia due to malignancy: 3 examples
- metastatic solid tumours
- osteoclast activating factor (lymphoma, myeloma)
- PTH-RP from lung tumours, lymphoma, myeloma
- PTH from small cell lung carcinoma
How may inflammatory markers e.g. from granulomatous diseases, lead to raised calcium?
Macrophages express 1-a hydroxylase which activates vitamin D3 consequently Ca2+ levels rise
How can immobilisation cause hypercalcemia?
Bone is laid down along lines of stress via release of piezoelectricity (from pressure+latent heat) which osteoblasts are sensitive to. Without this you get an imbalance of bone remodelling
Which asymptomatic condition is a loss of function mutation in CaSR (calcium sensing receptor) gene.
FHH-Familial Hypocalciuric Hypercalcemia
List 5 classic hypercalcemia symptoms.
- Neurologic: decreased conc, confusion, fatigue
- Renal: polyuria, nephrocalcinosis, DI
- MSK: weakness, bone pain, osteoporosis
- CVS: short QT interval, HT, bradycardia
- GIT: anorexia, nausea, constipation, peptic ulcer
Hypercalcemia sign in the eye
Keratinosis-milky calcium deposit ring around pupil
Hypercalcemia, 3 scan investigations
- SestaMBI Scan (localise adenoma both - thyroid = para)
- Neck Ultrasound, Renal Tract Ultrasound
- DEXA (bone density)
5 Hypercalcemia treatments
- saline rehydration (dilute so kidneys can clear Ca)
- furosemide (Ca excretion)
- pamidronate infusion (binds to hydroxyapetite crystals so osteoclasts cant)
- calcitonin
- prednisolone (steroid to decrease infammatory causes)
- dialysis
Where is calcitonin made and what is its action?
C cells of thyroid gland
oppose action of PTH (decrease Ca)
What is the calcimimetic cinacelet used to treat?
Hypercalcemia e.g. for 2dry hyperPTH as it binds to the parathyroid calcium sensing receptor and decreases calcium release
3 Causes of HYPOcalcemia with Low PTH
- hypoparathyroidism
- pseudohypoparathyroidism
- activating mutation of the Ca Sensing R
3 Causes of HYPOcalcemia with High PTH
- vitamin D deficiency (renal/liver disease or resistance)
- poor dietary calcium
- malabsorbtion
1 and 2dry HYPOparathyroidism
1ary can be congenital/autoimmune
2nry can be post neck surgery/trauma or from radioiodine
3 factors contributing to low vit D due to poor sunlight exposure
- suncream
- obesity
- lattitde
- skin pigmentation
What is calcium chelation/precipitation?
Citrate in blood (e.g.transfusions) is a cheletic agent so it binds to Ca2+ and takes it out of circulation having an anti-coagulant effect and lowering plasma calcium levels.
(calcium is vital in the clotting cascade, ^this decreases chance of clot formation)
5 common symptoms of HYPOcalcemia
2 Acute manifestations
2 Chronic Manifestations
Common: muscle cramps, paraesthesia, SOB due to bronchospasm, confusion, seizures, Chvostek’s (facial nerve tap->contraction) and Trosseau’s sign
Acute: Syncope, congestive HF
Chronic: Dry skin, coarse hair, itching
3 signs/symptoms of vit D3 deficiency
- aches/pains in bones
- proximal myopathy
- low phosphate
- children: knocked knees/bow legs
