Patho - 4th Asessment - Disorders Of Calcium, Phosphate - 2007

Electrophoresis of 4th Year Medical Students Microbiolog y Pathology

Neurosciences

Pharmacology

September

June

DISORDERS OF CALCIUM, PHOSPHATE AND MAGNESIUM METABOLISM PROF.S.O.OLUSI

Objectives of this lecture : To understand : • The physiology of calcium, phosphate and magnesium homeostasis in man. • The laboratory assessment of calcium status. • Disorders of calcium, phosphate and magnesium metabolism and their investigations in the clinical chemistry laboratory.

A BRIEF REVIEW OF THE PHYSIOLOGY OF CALCIUM HOMEOSTASIS

: .1Distribution • More than 99% of calcium in the body is found in bone complexed with phosphate as hydroxyapatite. • The remaining 1% is found in the ECF especially blood where it is important in muscle contraction and neurotransmitter release. • The total calcium concentration in plasma varies between 2.20-2.60 mmol/L.Of this, 45% circulates as free calcium ions;40% is bound to protein, mostly albumin, and 15% is bound to anions such as bicarbonate, citrate, phosphate and lactate. • It is the ionized free calcium ions that is physiologically active. • Since the concentrations of citrate, bicarbonate, lactate, phosphate and albumin can change dramatically in disease or after surgery, the concentration of plasma calcium can also change.

CALCIUM - REGULATING HORMONES Two hormones (parathyroid hormone and calcitriol) regulate the .concentration of calcium in the ECF

FUNCTIONS OF CALCIUM

LABORATORY ASSESSMENT OF CALCIUM CONCENTRATION

Plasma total calcium is usually measured in the laboratory although .there are ion - selective electrodes that can measure ionized calcium Changes in plasma albumin concentration will affect total calcium .levels without affecting the ionized calcium concentration Various formulae have been derived to calculate the calcium concentration when the plasma albumin level lies outside the reference : range.One such formula is = )Albumin ] <40 g/L : Corrected calcium )mmol/L ] ) ]Ca]+0.02*)40- ]Albumin] = )Albumin ] >40g/L : Corrected calcium )mmol/L ] )Ca]+0.02* ) ]Albumin] -40]

DISORDERS OF CALCIUM METABOLISM - HYPERCALCAEMIA Hypercalcaemia occurs when the plasma calcium concentration is above the upper reference range (2.60mmol/L).It is a common laboratory finding. The causes of hypercalcaemia are :

FLOW DIAGRAM FOR INVESTIGATION OF HYPERCALCAEMIA

HYPOCALCAEMIA

.Low serum calcium (below 2.2 mmol/L).Relatively uncommon : Clinical Features

(increased excitability of neuromuscular tissue (tetany i) –) ii) – laryngeal stridor and seizures) iii) – prolongation of the QT and ST intervals in ECG) iv) – heart block) v) – congestive heart failure) vi) – calcification of the based ganglia) } vii) – psychiatric disturbances) in long standing hypocalcaemiaviii) – cataracts } in children – abnormal dental development ix) –)

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Differential diagnosis of Hypocalcaemia

Flow diagram for investigation of hypocalcaemia

PHOSHATE : Physiology The majority of phosphate within the body is found in the cells ,where it serves as an important component of phospholipids / phosphoproteins, nucleic acids and nucleotides.Phosphorylation dephosphorylation reactions are important in the regulation of .enzyme activity The hormonal control of phosphorous homeostasis is shown below

PLASMA PHOSPHATE CONCENTRATIONS • Plasma phosphate concentrations change with age.Highest levels are found in infants.Throughout childhood and adolescence, plasma phosphate concentrations remain higher than in adults. • In adulthood, a decline in fasting plasma phosphate concentrations is seen in men after the age of 40 but not in women. • Plasma phosphate does not change during pregnancy, but is elevated during lactation. • Plasma phosphate concentrations exhibit diurnal variation.Levels are very much higher in the mid - afternoon than in the early morning. • Plasma phoshate rises immediately after a meal but falls subsequently as phosphate enters the cell.

DISORDERS OF PHOSPHATE METABOLISM - HYPERPHOSPHATAEMIA The major causes of hyperphosphataemia ( a plasma phosphate concentration greater than 1.4mmol/L ) are shown in the table.

DISORDERS OF PHOSPHATE METABOLISM - HYPOPHOSPHATAEMIA Hypophosphataemia can arise by 3 mechanisms : 2. inadequate phosphate absorption from the intestine 3. shifts of phosphate from extracellular fluid into cells 4. abnormal urinary phosphate losses

When plasma concentrations fall below 0.35mmol/L, the acute syndrome of phosphate deficiency may develop.The major manifestations of this syndrome are listed in the following table.

MAGNESIUM METABOLISM

Majority of body magnesium is found in bones.Only about is found in plasma.Thus the measurement of plasma 0.5% .magnesium does not accurately reflect total body magnesium About 60% of magnesium in plasma is ionized and about .is complexed with bicarbonate, citrate or phosphate 15% .The remaining25% is bound to protein pricipally albumin Plasma concentrations are therefore influenced by plasma albumin and plt.Plasma magnesiumconcentrations are not .age or sex dependent

The hormonal regulation of plasma magnesium is shown in the following figure

DISORDERS OF MAGNESIUM METABOLISM - HYPERMAGNESAEMIA

The normal adult plasma magnesium concentration is 0.8-1.0 mmol/L.Significant hypermagnesaemia is uncommon.Cardiac .conduction is affected at concentrations of 2.5 - 5.0 mmol/L Concentrations greater than 7.5 mmol/L cause respiratory paralysis and cardiac arrest.This type of hypermagnesaemia .may be seen in renal failure

DISORDERS OF MAGNESIUM METABOLISM - HYPOMAGNESAEMIA

CLINICAL FEATURES • tetany (with normal or decreased calcium) • agitation, delirium • ataxia, tremor, choreiform movements and convulsions • muscle weakness, cardiac arrythmias.