Calcium, phsophate and magnesium

• calcium
  • 2.10-2.60 mmol/L
• phosphate
  • 0.8-1.4 mmol/L
• magnesium
  • 0.75-1.00 mmol/L
• alkaline phophatase
• 30-130 iu/L (dep on age/gender)

• involves PTH, calcitriol/1,25 dihyroxylcholecalciferol/1,25 DHCC/1,25 hydroxylvitamin D3)
  • also GH, TH, adrenals steriods, sex hormones
• PTH increases calcium levels (and decr phosphate)
  • bones: activates osteoclasts to break down bone matrix
    • also acts on FGF23 which decr PO4 reabs in kidney
  • kidney: incr calcium reabsorption + incr phosphate excretion
    • PTH directly incr 1-alpha hydroxylase so incr 25(OH)D3 to 1,25(OH)2D3 (active vit D)
  • small intestine: 1,25(OH)2D3 incr absorption of calcium and PO4

NB vitamin D 

• cholecalciferol/vitamin D3 from diet or from UVB reaction from cholesterol precursor in epidermis
  • hydroxylation in ER of liver hepatocytes by 25 hydroxylase > 25-OH cholecalciferol
  • hydroxylation in kidney by 1-alpha hydroxylase > 1,25(OH)2 cholecalciferol = active

• 1.5kg in body
  • 98% in skeleton
  • 1% in ECF
  • also in skeletal muscle, skin, liver, CNS
• of plasma calcium:
  • ultrafilterable- 53%
    • complexed - 6% > phosphate - 1.5 / citrate - 1.5% / bicarb - 3%
    • protein bound - 47% > albumin - 37% / globulin - 10%
  • ionised- 47% 
    • "free" calcium- regulates feedback mechanisms therefore phsyiologically important
  • labs measure total=free + bound
    • low albumin conc may cause decr in total but free will remain normal(ish)
    • acidosis (lactic/DKA etc) causes Ca be ionised away from albumin
  • calcium correction
    • +/- 0.02 mmol'L calcium for each 1g/L albumin above or below 40g/L albumin
      • NB doesn't work once albumin >25g/L

• membrane bound glycoprotein enyzyme
• produced from liver, bone, intestine and placenta
  • high ALP- bone or liver source?
    • electrophoresis, but slow and inpractical
    • measure gamma GT
      • = membrane bound glycoprotein enzyme found only in liver
      • if gamma GT incr then liver is source of high ALP
  • bonce specific ALP reflects osteoblast activity, incr in:
    • osteomalaica
    • Paget's disease
    • bone metastases
    • hyperparathyroidism

• causes:
  • common (rememeber!)
    • primary hyperparathyroidism (incr PTH)
    • malignancy (low PTH)
    • artefact (low PTH)
      • poor venepuncture>venous stasis
      • hyperproteinaemia (e.g. bc myeloma)
  • rare
    • vitamin D toxicity (low PTH)
    • prolonged immobilisation (low PTH)
    • thiazide diuretics (low PTH)
    • adrenal failure (low PTH)
    • sarcoid (low PTH)
    • lithium
    • familial hypocalcuric hypercalcaemia (low PTH)
    • milk alkali (low PTH)

• acute symptoms "moans, bones, groans and stones":
  • nocturia and polyuria
  • renal colic
  • mental impairment
• chronic symtpoms:
  • bone pain
  • anorexia
  • nausea and vomiting
  • drowsiness > coma
• renal findings
  • renal calculi
  • nephrocalcinosis
• bone findings
  • subperiosteal erosions
  • pathological fractures
  • demineralisation + cysts

• primary = incr secretion of PTH
  • single or multiple adenoma (~95%)
  • parathyroid hyperplasia 
  • parathyroid carcinoma (rare)
• secondary = incr PTH due to hypocalcaemia
  • renal failure (due to failure of 1-hydroxylation)
  • vitamin D deficiency (failure to absorb Ca)
  • drugs
    • phosphate/bisphosphate
  • medullary carcinoma of the thyroid (rare)
• tertiary = result of prolonged secondary hyperparathyroidsim, no longer relies on feedback- get hypercalcaemia
  • renal transplantation after prolonger dialysis
  • multiple endocrine neoplasia
    • MEN I
    • MEN II
      • pheochromocytoma (= neuroendocrine tumour of chromaffin cells in adrenal medulla)

• artefact
  • wrong collection tube- not purple (EDTA) or blue (INR, cont. citrate)
• hypoalbuminaemia
• acute/chronic renal failure
• vitamin D deficiency
  • osteomalacia
  • rickets
• acute pancreatitis
• hypomagnasaemia
• hypoparathyroidism (usually surgical)

• tetany
  • spasms of hands, feet, larynx and overactive neurological reflexes due to lowered action potential threshold 
  • NB may be due to decr ionised calcium in alkalosis w/ no marked hypocalcaemia in tests
  • latent (=early/milder)
    • Chvostek's sign
      • spasm of facial muscles elicited by tapping face to excite facial nerve
    • Trousseau's sign
      • carpal spasm elicited by compressing upper arm, causing ischaemia in peripheral nerves (e.g. w/ BP cuff)
  • spontaneous
    • carpopedal spasm
    • muscle cramps
    • parasthesia, fits
    • hypotension

• Causes
  • intracellular shifts
    • incr glucose, insulin, respiratory alkalosis
  • decr renal phosphate threshold
    • 1 or 2 hyperparathyroidism, renal tubular defects
  • decr intestinal absorption
    • vomiting, diarrhoea, phosphate binding antacid
    • malabsorption, vitamn D deficiency
  • intracellular phosphate loss
    • keto/lactate acidosis
• Clinical findings
  • muscle weakness
    • acute resp failure, derc CO, reduced 2-3 DPG
  • neuro symptoms
    • neuromuscular hyperexcitability, latent tetany
  • skeletal
    • impaired mineralisation

• causes
  • decr renal exrection
    • decr GFR
    • incr tubular reabs (hypoparathyroidism, acromegaly, etidronate- bisphosphate for ostpor)
  • phosphate intake
    • IV, laxative, phosphate enema 
      • NB esp care needed in elderly w/ decr GFR
  • extracellular phosphate load
    • transcellular shift
      • lactic, resp or DK acidosis
    • cell lysis
      • rhabdomyloysis (crush injury), haemolysis (G6P def), cytotoxic therapy, haem ca
• findings
  • acute= tetanty (b/c hypocalc), seizures, hypotension
  • chronic= 2 hyperparathyroidism (b/c PT gland stim)
    • soft tissue calcification (kidneys, cornea, skin)

• causes:
  • acute renal failure
  • severe DKA
  • Addison's disease
  • supplement (longterm TPN)
• clinical findings
  • loss of deep tendon reflexes
  • incr PR interval > cardiac arrest
  • but only really a problem if Mg > 2.0 mmol/L as otherwise cleared wuickly by kidneys

• causes:
  • GI
    • NG suction, bowel resection, diarrohoea, acute pancreatitis
  • renal loss
    • DM, chronic parenteral fluid therapy, hypercalcaemia, alcohol
  • renal disease
    • pylenephritis, acute tubular necrosis (fiuretic phase), post renal transplant
  • drugs
    • diuretics, aminoglycosides, amphotericin (haem malignancy), ciclosporin (imm suppr)
• clinical findings:
  • hyperirritability
  • tetany
  • convulsions
  • ECG change- AF
  • impairment of PTH secretion