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FY1 Calcium/Phosphate/ Magnesium Homeostasis

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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

FY1 Calcium/Phosphate/ Magnesium Homeostasis

Funmi Awopetu

Senior Clinical Scientist

King George Hospital

ca p mg
Ca/P/Mg
  • Intro
  • Calcium
  • Phosphate
  • Magnesium
  • Investigations
calcium
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
calcium homeostasis
Calcium Homeostasis

Parathyroid gland

Skeleton

Intestine

Ca++

Vitamin D

Kidneys

calcium metabolism
Calcium Metabolism
  • Forms
    • Free – 50%
    • Bound – protein – 40%
    • Complexed – 10%
  • Hence adjusted for albumin
  • Acid base status
  • Calcium sensing receptor
  • PTH
  • Vitamin D
  • (calcitonin)
adjusted calcium
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
errors in calcium measurement
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
slide8
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
slide9
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)
vitamin d
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
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
causes of hypercalcaemia
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
hyperparathyroidism
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
slide14
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
investigations
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

slide16
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
hypocalcaemia
Hypocalcaemia
  • Symptoms
  • Chvosteks and Trousseau’s signs
  • Neuromuscular excitability
  • Tetany
  • Paresthesia
  • Seizures
causes of hypocalcaemia
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
chronic renal failure
Chronic Renal failure
  • Phosphate
  • Protein
  • 1, 25 Vit D
  • Skeletal resistance to Vitamin D
investigations20
Investigations
  • Bone profile
  • Renal function
  • Mg
  • Vitamin D
  • ? History (eg surgery to neck)
  • ? PTH
phosphate metabolism
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
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
hyperphosphataemia23
Hyperphosphataemia
  • Exclude spurious
    • delayed sample receipt
    • haemolysis (HM2)
    • anticoagulants EDTA/citrate – interfere with complex formation during analysis
hypophosphataemia
Hypophosphataemia
  • Common
  • Muscle weakness
  • Respiratory failure
  • Decreased myocardial output
  • Rhabdomyolysis < 0.15mmol/L
  • Severe hypoP  haemolysis
  • Rickets/osteomalacia (chronic defy)
  • Wernicke’s encephalopathy
hypophosphataemia25
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
investigations26
Investigations
  • ? History
  • ? Contamination ? Repeat
  • Bone profile
  • Renal function
  • Mg
  • ? Vitamin D (?Ca)
  • ? PTH (?Ca)
magnesium metabolism
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
Hypermagnesaemia

Symptoms

  • Depressed neuromuscular system
  • Depressed respiration
  • Cardiac arrest

Causes

  • Excessive intake
  • Antacids
  • Enemas
  • Parenteral therapy
  • Mg administration (RF)
hypomagnesaemia
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
hypomagnesaemia30
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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