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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 – Intracellular signalling– Coagulation– Bone mineralization– Plasma membrane potential
Calcium Homeostasis
Skeleton Intestine
Kidneys
Parathyroid gland
Ca++
Vitamin D
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
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
• 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 • 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
95%
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
• 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
• Symptoms
• Chvosteks and Trousseau’s signs
• Neuromuscular excitability
• Tetany
• Paresthesia
• Seizures
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
• Phosphate
• Protein
• 1, 25 Vit D
• Skeletal resistance to Vitamin D
Investigations
• Bone profile
• Renal function
• Mg
• Vitamin D
• ? History (eg surgery to neck)
• ? PTH
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
Decreased renal excretion– GFR
– Reabsorption• hypoPTH
• Acromegaly
• Disodium etidronate
Transcellular shift– Lactic acidosis
– Respiratory acidosis
– DKA
Increased intake– Oral or IV
– P containing laxatives/enemas
– Vit D intoxication
Cell Lysis– Rhabdomyolysis
– Intravascular haemolysis
– Cytotoxic therapy
– Leukaemia
– Lymphoma
Hyperphosphataemia
• Exclude spurious– delayed sample receipt– haemolysis (HM2)– anticoagulants EDTA/citrate – interfere with
complex formation during analysis
Hypophosphataemia
• 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
Decreased absorption
• Increased loss
• Vomiting
• Diarrhoea
• Phosphate binding antacids
• Decreased absorption
• Malabsorption syndrome
• VitD defy
• Poor diet
Lowered renal P threshold
• Primary hyperPTH
• Renal tubular defects
• Familial hypophospataemia
• Fanconi’s
Investigations
• ? History
• ? Contamination ? Repeat
• Bone profile
• Renal function
• Mg
• ? Vitamin D (?Ca)
• ? PTH (?Ca)
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
Symptoms– Depressed neuromuscular system– Depressed respiration– Cardiac arrest
Causes– Excessive intake– Antacids– Enemas– Parenteral therapy– Mg administration (RF)
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
HypomagnesaemiaGI
• 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
Questions?