FY1 Calcium/Phosphate/ Magnesium Homeostasis

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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 lt20

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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

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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 (gt3 pmol/L inappropriate for hyperCa)
• ? Primary HyperPTH or FHH
• Urinary fractional calcium excretion
• Fasting urine calcium x serum creatinine
• Urine creatinine
• lt 25 umol/L FHH
• gt 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 Trousseaus signs
• Neuromuscular excitability
• Tetany
• Paresthesia
• Seizures

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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

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Hyperphosphataemia

• Decreased renal excretion
• GFR
• Reabsorption
• hypoPTH
• Acromegaly
• Disodium etidronate

• Cell Lysis
• Rhabdomyolysis
• Intravascular haemolysis
• Cytotoxic therapy
• Leukaemia
• Lymphoma

• Transcellular shift
• Lactic acidosis
• Respiratory acidosis
• DKA

• Increased intake
• Oral or IV
• P containing laxatives/enemas
• Vit D intoxication

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Hyperphosphataemia

• Exclude spurious
• delayed sample receipt
• haemolysis (HM2)
• anticoagulants EDTA/citrate interfere with
  complex formation during analysis

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Hypophosphataemia

• Common
• Muscle weakness
• Respiratory failure
• Decreased myocardial output
• Rhabdomyolysis lt 0.15mmol/L
• Severe hypoP ? haemolysis
• Rickets/osteomalacia (chronic defy)
• Wernickes encephalopathy

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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
• Fanconis

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Investigations

• ? History
• ? Contamination ? Repeat
• Bone profile
• Renal function
• Mg
• ? Vitamin D (?Ca)
• ? PTH (?Ca)

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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

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Hypermagnesaemia

• Symptoms
• Depressed neuromuscular system
• Depressed respiration
• Cardiac arrest
• Causes
• Excessive intake
• Antacids
• Enemas
• Parenteral therapy
• Mg administration (RF)

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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/cardia
  c glycosides
• Metabolic acidosis (DKA/ETOH/starvation)
• Renal disease

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Questions?