Calcium, phsophate and magnesium

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  • Created by: z
  • Created on: 27-02-16 13:39

Ranges

  • 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)
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Calcium homeostasis

  • 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
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Calcium distribution

  • 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
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Alkaline phosphatase

  • 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
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Hypercalcaemia

  • 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)
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Hyper: symptoms and findings

  • 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
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Hyperparathyroidism

  • 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)
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Hypocalcaemia: causes

  • 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)
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Hypocalcaemia: clinical signs

  • 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
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Hypophosphataemia: causes and findings

  • 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
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Hyperphosphataemia: causes and findings

  • 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)
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Magnesium excess (>1 mmol/L)

  • 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
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Magnesium deficiency (

  • 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
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