Calcium Metabolism and

Regulation
Calcium in the plasma :
Biological function of calcium
• Required for Activation of enzymes :
Either directly ( e.g succinate dehydrogenase , pancreatic
lipase ) or
as an important intracellular signaling molecule (second
messenger)
• Required for Muscle contraction :
Ca binding to troponin is required
for interaction of actin and myosin
filaments for muscle contraction

• Excitation of nerves
• Required for Blood clotting
Prothrombin contains gamma carboxyglutamate
residues which binds to Calcium during coagulation
Sources: milk, egg, fish, vegetables(broccoli ,but
not spinach), cereals.

Daily requirement:

Adult- 500mg/day
Children- 1200mg/day
Pregnancy & lactation-
1500mg/day
Absorption :-first & second part of duodenum
• absorption requires a carrier protein , helped
by calcium dependent ATPase.
Excreted : feces and urine.
CALBINDIN
Regulation of Plasma Calcium
Homeostasis of blood calcium is dependent on
Function of three main organ :
1. Bone 2. Kidney 3. Intestine
Function of three main hormone
1. PTH 2. Vit D 3. Calcitonin
FACTORS CAUSING INCREASED
ABSORPTION

1. Parathyroid hormone increases absorption of

Calcium
2. Calcitriol (1,25 dihydroxycholecalciferol)
INDUCES synthesis of Ca binding protein
---CALBINDIN required for absorption of
Calcium in the intestine
FACTORS CAUSING DECREASED ABSORPTION

1.Calcitonin decreases Ca absorption

2. Phytates (cereals) & Oxalates (leafy vegetables) forms

insoluble salts and interferes with Ca absorption.

3.High content of dietary phosphates results in the

formation of Ca phosphates. Dairy
foods.Beans.Lentils.Nuts.Bran cereals.Oatmeal.Colas
and other drinks with phosphate additives.
Clinical Conditions Related to Plasma Calcium
Level Alterations
Hypo Calcemia : Causes Include

Hypoparathyroidism : due to neck surgery , or due to

Magnesium deficiency
Vit D deficiency : dietary deficiency , malabsorption or
little exposure to sunlight
Renal Disease : kidneys fail to synthesise Calcitriol due
to imapired hydroxylation >> no calcitriol for
regualtion
Clinical features of Hypo Calcemia :
[-Neuromuscular excitability]

Low EC Calcium =
increases Neuronal excitability=
Neuromuscular irritabilty &
Muscle spasm
Early symptom : numbness , tingling sensation –
fingers ,toes
If Ca fall Progresses/severe : manifested as
Spasm in limb = Tetany
Bronchial spasm = wheezing
Vocal cord spasm = voice change
Carpopedal spasm
Hyper calcemia Causes Include :
1. Hyperparathyroidism : usually PTH adenoma
2. Malignancy : with or without Bone metastasis

Clinical Features [ Neuromuscular excitability]

High EC calcium = reduces neuronal excitability
Confusion .lethargy .muscle weakness and
constipation
Cardiac : Arrythmias
 Summary blood Calcium
: PTH & Vitamin D

Hypocalcemia Hyper calcemia

• Hypo parathyroidism • Hyper parathyroidism

• Vit D deficiency • Malignancy (with or
• Renal Disease (failure without bone metastasis )
in Calcitriol synthesis )
Phosphorous
Functions
1. Constituent of bone and teeth : inorganic
phosphate is a major constituent of
hydroxyapatite in bone
2. Acid Base Regulation : Mixture of HPO4 and
H2PO4 constitutes the phosphate buffer
3. Energy storage and transfer reactions :
High energy compounds eg. ATP , ADP ,
Creatine p
4. Essential constitutent : phospholipid in cell
membrane , nucleic acid and nucleotides
5. Regulation of enzyme activity :
Phosphorylation and de Phosphorylation of
enzymes modify the actitvity of many
enzymes
Dietary requirement
• 500mg/day

Source: Milk, cereals,

leafy vegetables,
meat, eggs.

RDA : 800 mg/day

men + women
Absorption: Occurs from jejunum
Excretion : by kidney through urine as
NaH2PO4

Regulation :
plasma [Phosphate] is controlled by the kidney
PTH decreases the reabsorption of phosphorous
from the tubules thereby causing increased
excretion of phosphorous in urine
Vit D increases phosphate absorption
Serum level of phosphorous = 2.5-4.5 mg/dl

Clinical Conditions Related to plasma phosphorous

concentration
Hypophosphatemia < 2.5mg/dl
Causes of Hypophosphatemia :
1. Increased renal excretion : due to
Hyperparathyroidism : High PTH increases phosphate
excretion by the kidney and ,
Renal tubular disorder : Fanconis syndrome
phosphate is lost from body
2. Vit D deficiency
Clinical symptoms :
as phosphate is an important component of ATP ,
cellular function is impaired >>> muscle pain
and weakness
If hypophostaemia is chronic ;
rickets in children or osteomalacia in adults may
develop
Calcium Phosphosrus

PTH
Hyper phosphatemia
Causes : Decreases E xcretion
1. Renal failure (most common cause)
2. Hypoparathyroidism : Low PTH decreases
phosphate excretion by the kidneys and leads to high
serum concentration
• Clinical symptoms : clinically very imp
Hyper phosphatemia may cause a decrease in serum
calcium concentration ; Hence
Tetany and seizures
Magnesium
• Total body content is 25g (4th most abundant )

• 55 % : in Bones
complexed with Ca and Phosphorous

• And is present mainly in Intra cellular Fluid

• With a small proportion in the ECF
Serum Mg : 0.8-1.2mmol/l
70% exist in free state (ionic)
30% is bound to protein(25% with albumin & 5% with
globulin ).
 Functions
• Role in Enzyme action
Magnesium is involved as a co factor and as
an activator to a wide range of enzymes
involved in
Oxidative phosphorylation , glycolysis , cell
replication , nucleotide metabolism , and many
ATP dependent
reactions
Neuromuscular Excitability
Mg exerts an effect on neuromuscular excitability
similar to Calcium
it helps to maintain the electrical potential in
nerves and muscle .

• High levels depresses nerve conduction

• Low levels may produce tetany
(hypomagnasemic tetany)
Constituents of bone and teeth
About 70% of body Mg is present as Apatites in
bones , dental enamel and dentines

Magnesium influences the secretion of PTH by

the parathyroid gland .
 Dietary Sources
• Mg is widely distributed in vegetables
• Found in porphyrin group of chlorophyll of
green vegetables
• Found in almost all animal tissues
• Other imp sources are cereals,beans,leafy
vegetables and fish
RDA of adult
man is 350 mg /day
Women is 300mg/day

Absorption : 30-40 % small intestine

Excretion : feces , sweat and urine

Hypermagnesemia : uncommon

• Occasionally in Renal failure

Most common clinical manifestation :
At 2.5 -5.0 mmol/L : cardiac conduction is
affected
At > 7.5 mmol/L : respiratory paralysis and
cardiac arrest
• Hypomagnaesemia :
Causes : general nutritional insufficiency
Intestinal malabsorption
Severe vomiting , Diarrhoea

Clinical manifestation
Similar to Hypocalcemia ?? HOW
impaired neuromuscular function such as tetany ,
hyper irritability , tremor, convulsions and muscle
weakness