FY1 Calcium/Phosphate/ Magnesium Homeostasis Funmi Awopetu Senior Clinical Scientist King George...

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?