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) –)
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.