FY1 Calcium/Phosphate/
Magnesium Homeostasis
Funmi Awopetu
Senior Clinical Scientist
King George Hospital
Ca/P/Mg
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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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Intracellular signalling
Coagulation
Bone mineralization
Plasma membrane potential
Calcium Homeostasis
Parathyroid gland
Skeleton
Ca++
Kidneys
Intestine
Vitamin D
Calcium Metabolism
• Forms
– Free – 50%
– Bound – protein – 40%
– Complexed – 10%
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Hence adjusted for albumin
Acid base status
Calcium sensing receptor
PTH
Vitamin D
(calcitonin)
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
In vivo
• Tourniquet use and
venous occlusion
• Changes in posture
• Exercise
• Hyperventilation
• Alterations in protein
binding / complex
formation
In Vitro
• Inappropriate
anticoagulants
• Dilution with liquid
heparin
• Contamination with
calcium
• Spectrophotometric
interference
PTH
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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
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
• 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
• 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
• Contamination
95%
• Primary
hyperparathyroidism
• Malignancy (skeletal
involvement/PTHRP)
• Endocrine disorders –
hyper/hypothyroidism/acute
adrenal insufficiency
• FHH
• Renal failure
• Idiopathic hyperCa of
infancy
• Granulomatous
disorders (eg
sarcoidosis and TB)
• Chlorthiazide diuretics
• Lithium
• Milk alkali syndrome
• etc
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
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
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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
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
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Symptoms
Chvosteks and Trousseau’s signs
Neuromuscular excitability
Tetany
Paresthesia
Seizures
Causes of hypocalcaemia
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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
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Phosphate
Protein
1, 25 Vit D
Skeletal resistance to Vitamin D
Investigations
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Bone profile
Renal function
Mg
Vitamin D
? History (eg surgery to neck)
? PTH
Phosphate Metabolism
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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
Decreased renal excretion
– GFR
– Reabsorption
• hypoPTH
• Acromegaly
• Disodium etidronate
Increased intake
– Oral or IV
– P containing
laxatives/enemas
– Vit D intoxication
Cell Lysis
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Rhabdomyolysis
Intravascular haemolysis
Cytotoxic therapy
Leukaemia
Lymphoma
Transcellular shift
– Lactic acidosis
– Respiratory acidosis
– DKA
Hyperphosphataemia
• Exclude spurious
– delayed sample receipt
– haemolysis (HM2)
– anticoagulants EDTA/citrate – interfere with
complex formation during analysis
Hypophosphataemia
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Common
Muscle weakness
Respiratory failure
Decreased myocardial output
Rhabdomyolysis < 0.15mmol/L
Severe hypoP  haemolysis
Rickets/osteomalacia (chronic defy)
Wernicke’s encephalopathy
Hypophosphataemia
Intracellular shift
• Glucose
• Insulin
• Resp alkalosis
• Refeeding
Lowered renal P threshold
• Primary hyperPTH
• Renal tubular defects
• Familial
hypophospataemia
• Fanconi’s
Decreased absorption
• Increased loss
• Vomiting
• Diarrhoea
• Phosphate binding
antacids
• Decreased absorption
• Malabsorption
syndrome
• VitD defy
• Poor diet
Investigations
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? History
? Contamination ? Repeat
Bone profile
Renal function
Mg
? Vitamin D (?Ca)
? PTH (?Ca)
Magnesium Metabolism
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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
Symptoms
– Depressed neuromuscular system
– Depressed respiration
– Cardiac arrest
Causes
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Excessive intake
Antacids
Enemas
Parenteral therapy
Mg administration (RF)
Hypomagnesaemia
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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
Hypomagnesaemia
GI
Renal loss
• Prolonged nasogastric suction
• Chronic TPN
• Malabsorption
• Osmotic diuresis
(DM/mannitol)
• Bowel resection
• Hypercalcaemia
• Diarrhoea
• Alcohol
• Fistulas
• Drugs –
• Acute pancreatitis
diuretics/aminoglycosides/cispl
• Decreased intake
atin/cardiac glycosides
• Chronic vomiting
• Metabolic acidosis
Redistribution
(DKA/ETOH/starvation)
• DKA
• Renal disease
• Hungry bone disease
Questions?