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FY1 Calcium/Phosphate/ Magnesium Homeostasis. Funmi Awopetu Senior Clinical Scientist King George Hospital. Ca/P/Mg. Intro Calcium Phosphate Magnesium Investigations. Calcium. 99% present in skeleton (reservoir) Serum calcium 2.15-2.6 mmol/L Functions of calcium

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FY1 Calcium/Phosphate/ Magnesium Homeostasis

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Fy1 calcium phosphate magnesium homeostasis l.jpg

FY1 Calcium/Phosphate/ Magnesium Homeostasis

Funmi Awopetu

Senior Clinical Scientist

King George Hospital


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Ca/P/Mg

  • Intro

  • Calcium

  • Phosphate

  • Magnesium

  • Investigations


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Calcium

  • 99% present in skeleton (reservoir)

  • Serum calcium 2.15-2.6 mmol/L

  • Functions of calcium

    • Intracellular signalling

    • Coagulation

    • Bone mineralization

    • Plasma membrane potential


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Calcium Homeostasis

Parathyroid gland

Skeleton

Intestine

Ca++

Vitamin D

Kidneys


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Calcium Metabolism

  • Forms

    • Free – 50%

    • Bound – protein – 40%

    • Complexed – 10%

  • Hence adjusted for albumin

  • Acid base status

  • Calcium sensing receptor

  • PTH

  • Vitamin D

  • (calcitonin)


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Adjusted Calcium

Total Ca + ((44-Alb) x 0.015)

  • Advantages

    • Accounts for changes in alb conc

    • To calculate the expected Ca conc if the alb were normal

  • Limitations

    • Interpret with caution when H+ status abnormal

    • Not valid when alb very low eg <20


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Errors in Calcium measurement

  • In Vitro

  • Inappropriate anticoagulants

  • Dilution with liquid heparin

  • Contamination with calcium

  • Spectrophotometric interference

In vivo

  • Tourniquet use and venous occlusion

  • Changes in posture

  • Exercise

  • Hyperventilation

  • Alterations in protein binding / complex formation


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PTH

  • 84 aa

  • Synthesised by parathyroid gland

  • Bio activity in aa 1-34 (fragments)

  • Intact PTH T1/2 3-4 mins

  • Inhibited by

    • Hypercalcaemia (secretion)

    • 1,25D (synthesis)

  • Normal levels 1.3 – 6.8 pmol/L


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PTH

  • Bone resorption – to release Ca/P

    • Rapid release and longer term response – proliferation of osteoclasts

  • Kidney

    • distal tubule reabs of calcium (hypercalciuria)

    • Phosphaturia inhibits P reabs from prox tubule

  • Calcitriol ( intestine)


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    Vitamin D

    • Diet/UV sunlight (D2/D3)

    • 25 hydroxy D (liver)

    • 1,25 dihydroxy Vitamin D (kidney) – tightly regulated

    • Active form 1,25VitD

    • VitD action

      • Absorption of phosphate and calcium from intestine

      • PTH

    • 25OHD best measure – reflects sun and diet, long T1/2


    Hypercalcaemia l.jpg

    Hypercalcaemia

    • Increased flux of Ca2+ into the ECF from skeleton, kidney or intestine

    • Lethargy

    • Nausea

    • Vomiting

    • Bones, moans, groans and stones

    • Polyuria

    • Symptoms dependent on rate of increase


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    Causes of Hypercalcaemia

    • Contamination

    • Primary hyperparathyroidism

    • Malignancy (skeletal involvement/PTHRP)

    • Endocrine disorders – hyper-/hypothyroidism/acute adrenal insufficiency

    • FHH

    95%

    • Renal failure

    • Idiopathic hyperCa of infancy

    • Granulomatous disorders (eg sarcoidosis and TB)

    • Chlorthiazide diuretics

    • Lithium

    • Milk alkali syndrome

    • etc


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    Hyperparathyroidism

    • PTH Inappropriate to calcium level

    • Raised calcium with raised/normal PTH

    • ? Primary

    • ?Secondary/Tertiary

    • Primary - usually due to parathyroid adenoma (single/multiple)

    • Multiple - ? MEN

    • Treatment

      • High fluid intake

      • Surgery

      • Watch and wait

    • Side effects

      • Osteoporosis

      • Renal failure

      • Stones


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    FHH

    • Familial hypocalciuric hypercalcaemia

    • Autosomal dominant mutation in calcium sensing receptor  increased set point for calcium

    • Asymptomatic hypercalcaemia

    • Normal/slightly elevated PTH

    • Must differentiate from primary hyperparathyroidism

    • Low rate of calcium excretion in urine


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    Investigations

    • Bone profile

    • Renal function

    • PTH (>3 pmol/L inappropriate for hyperCa)

    • ? Primary HyperPTH or FHH

    • Urinary fractional calcium excretion

      • Fasting urine calcium x serum creatinine

        Urine creatinine

        < 25 umol/L FHH

        > 30 umol/L PHPT


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    Case

    • 51 year old woman investigated after ureteric colic shown on radiological examination to be due to Ca containing calculi.

    • Serum Calcium 2.95 mmol/L

    • Phosphate 0.7 mmol/L

    • PTH 10 pmol/L

    • Bone radiographs normal

    • Serum urea, albumin ALP normal


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    Hypocalcaemia

    • Symptoms

    • Chvosteks and Trousseau’s signs

    • Neuromuscular excitability

    • Tetany

    • Paresthesia

    • Seizures


    Causes of hypocalcaemia l.jpg

    Causes of hypocalcaemia

    • Contamination

    • Hypoalbuminaemia

    • Chronic renal failure

    • Magnesium deficiency

    • Hypoparathyroidism (/pseudo)

    • Vitamin D deficiency (or resistance)

    • Acute haemorrhagic and edematous pancreatitis

    • Hungry bone syndrome


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    Chronic Renal failure

    • Phosphate

    • Protein

    • 1, 25 Vit D

    • Skeletal resistance to Vitamin D


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    Investigations

    • Bone profile

    • Renal function

    • Mg

    • Vitamin D

    • ? History (eg surgery to neck)

    • ? PTH


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    Phosphate Metabolism

    • 85% present in skeleton

    • Serum inorganic phosphate 0.84-1.45 mmol/L

    • 10% protein bound, 35% complexed, rest free

    • Integrity of bone

    • Oxygen delivery

    • Muscle contraction

    • Role in ATP (energy), nucleotides, NADP, cell membranes, gene transcription, cell growth

    • Balance maintained primarily by kidneys


    Hyperphosphataemia l.jpg

    Hyperphosphataemia

    Decreased renal excretion

    • GFR

    • Reabsorption

      • hypoPTH

      • Acromegaly

      • Disodium etidronate

    • Cell Lysis

      • Rhabdomyolysis

      • Intravascular haemolysis

      • Cytotoxic therapy

      • Leukaemia

      • Lymphoma

    • Increased intake

      • Oral or IV

      • P containing laxatives/enemas

      • Vit D intoxication

    • Transcellular shift

      • Lactic acidosis

      • Respiratory acidosis

      • DKA


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    Hyperphosphataemia

    • Exclude spurious

      • delayed sample receipt

      • haemolysis (HM2)

      • anticoagulants EDTA/citrate – interfere with complex formation during analysis


    Hypophosphataemia l.jpg

    Hypophosphataemia

    • Common

    • Muscle weakness

    • Respiratory failure

    • Decreased myocardial output

    • Rhabdomyolysis < 0.15mmol/L

    • Severe hypoP  haemolysis

    • Rickets/osteomalacia (chronic defy)

    • Wernicke’s encephalopathy


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    Hypophosphataemia

    • Decreased absorption

    • Increased loss

      • Vomiting

      • Diarrhoea

      • Phosphate binding antacids

    • Decreased absorption

    • Malabsorption syndrome

    • VitD defy

    • Poor diet

    Intracellular shift

    • Glucose

    • Insulin

    • Resp alkalosis

    • Refeeding

    • Lowered renal P threshold

    • Primary hyperPTH

    • Renal tubular defects

    • Familial hypophospataemia

    • Fanconi’s


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    Investigations

    • ? History

    • ? Contamination ? Repeat

    • Bone profile

    • Renal function

    • Mg

    • ? Vitamin D (?Ca)

    • ? PTH (?Ca)


    Magnesium metabolism l.jpg

    Magnesium Metabolism

    • 55% present in skeleton

    • 1% of total body Mg extracellular

    • Serum Mg 0.7-1.0 mmol/L

    • Cofactor for enzymes

    • Required for ATP (MgATP)

    • Glycolysis

    • Cell replication

    • Protein biosynthesis

    • PTH increases renal tubular reabs of Mg

    • Homeostasis maintained - control of excretion


    Hypermagnesaemia l.jpg

    Hypermagnesaemia

    Symptoms

    • Depressed neuromuscular system

    • Depressed respiration

    • Cardiac arrest

      Causes

    • Excessive intake

    • Antacids

    • Enemas

    • Parenteral therapy

    • Mg administration (RF)


    Hypomagnesaemia l.jpg

    Hypomagnesaemia

    • Common in inpatients

    • Usu assoc with hypoK and hypoP

    • Increased neuromuscular excitability

    • Causes impaired PTH secretion

    • PTH end organ resistance

    • Oral K not retained if patient also Mg deficient

    • Assoc. with Ca defy with overlapping symptoms

    • HypoCa and HypoK unresponsive to supplementation should prompt Mg measurement


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    Hypomagnesaemia

    • GI

      • Prolonged nasogastric suction

      • Malabsorption

      • Bowel resection

      • Diarrhoea

      • Fistulas

      • Acute pancreatitis

      • Decreased intake

      • Chronic vomiting

    • Redistribution

      • DKA

      • Hungry bone disease

    • Renal loss

      • Chronic TPN

      • Osmotic diuresis (DM/mannitol)

      • Hypercalcaemia

      • Alcohol

      • Drugs – diuretics/aminoglycosides/cisplatin/cardiac glycosides

      • Metabolic acidosis (DKA/ETOH/starvation)

      • Renal disease


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    Questions?


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