MATABOLISM OF CALCIUM & PHOSPHOROUS

1. Gandham. Rajeev

2. • Calcium metabolism
• Sources & RDA
• Factors affecting calcium absorption
• Biochemical functions
• Regulation of plasma calcium
• Disease states
• Case report
• Metabolism of phosphorous
• Sources & RDA
• Biochemical functions
• Disease states
• RGUHS questions

3. • Essential for
• Normal growth & maintenance of the body
• Calcification of bone
• Blood coagulation
• Neuromuscular irritability
• Acid-base equilibrium
• Fluid balance & osmotic regulation
• Daily requirement is >100 mg/day - macro minerals/macro elements
• Daily requirement is <100 mg/day - micro minerals/micro elements

4. Classification of minerals according to their essentiality
Major elements Minor elements
Calcium Iron
Magnesium Iodine
Phosphorous Copper
Sodium Manganese
Potassium Zinc
Chloride Molybdenum
Sulfur Selenium
Fluoride

5. Calcium metabolism
• Most abundant mineral.
• Total body calcium is about 1 to 1.5 kg.
• 99% is seen in bone together with phosphate & 1% in ECF
• Dietary Sources of calcium:
• Milk is a good source for calcium
• Egg, fish, cheese, beans, nuts, cabbage and vegetables are
good sources for calcium

6. Daily requirement of calcium
• Adult men & women = 500 mg/day
• Children’s = 1200 mg/day
• Pregnancy & lactation = 1500 mg/day
• Calcium in plasma is of 3 types
• Ionized or free or unbound calcium
• Bound calcium
• Complexed calcium

7. • Ionized or free or unbound calcium or diffusible: 5.5 mg/dl
• In blood, 50% of plasma calcium is free & is metabolically active
• It is required for
• Maintenance of nerve function
• Membrane permeability
• Muscle contraction
• Hormone secretion
• Bound calcium or non diffusible: 4.5 mg/dl
• 40% of plasma calcium is bound to proteins – albumin

8. • Complexed calcium: 1 mg/dl
• 10% of plasma calcium is complexed with anions including
bicarbonate, phosphate, lactate & citrate
• All the three forms of calcium in plasma remain in equilibrium
with each other.
• Normal Range:
• The normal level of plasma calcium is 9-11 mg/dl
• Urine calcium:100-250 mg/day

9. Absorption
• From upper small intestine - first & second part of duodenum.
• About 40% of dietary calcium is absorbed.
• Absorbed against a concentration gradient & requires energy.
• Requires a carrier protein, helped by calcium-dependent
ATPase.

10. Factors causing increased absorption
• Vitamin D:
• Calcitriol induces the synthesis of carrier protein (Calbindin)
in the intestinal epithelial cells & facilitates the absorption of
calcium
• Parathyroid hormone:
• It increases calcium absorption through increased synthesis
of calcitriol

11. • Acidity favors calcium absorption (enhance solubility of calcium)
• Amino acids:
• Lysine & arginine increases calcium absorption
• Amino acids increase the solubility of Ca-salts & thus its
absorption

12. Factors causing decreased absorption
• Phytates oxalates:
• Phytates & oxalates form insoluble Ca-salts & decreases the
absorption.
• High phosphate content will cause precipitation as calcium
phosphate.
• Alkaline condition is unfavorable for absorption.
• Calcium forms insoluble soaps with fatty acids
• Vitamin D deficiency states.

13. Biochemical functions
• Development of bones and teeth:
• Bone is regarded as a mineralized connective tissue
• Bones also act as reservoir for calcium
• The bulk quantity of calcium is used for bone & teeth formation
• Osteoblasts induce bone deposition & osteoclasts produce
demineralization.

14. • Muscles:
• Calcium mediates excitation & contraction of muscles
• Ca2+ interacts with troponin C to trigger muscle contraction
• Calcium activates ATPase, increases action of actin & myosin
and facilitates excitation-contraction coupling.
• Calcium decreases neuromuscular irritability.

15. • Nerve conduction:
• It is necessary for transmission of nerve impulses
• Blood coagulation:
• Calcium is known as factor IV in blood coagulation process
• Prothrombin contains γ-carboxyglutamate residues which are
chelated by Ca2+ during the thrombin formation.
• Calcium is required for release of certain hormones - insulin,
parathyroid hormone, calcitonin & vasopressin

16. • Activation of enzymes:
• Calmodulin is a calcium binding regulatory protein.
• Calmodulin can bind with 4 calcium ions & molecular weight of 17,000
• Calcium binding leads to activation of enzymes
• Enzymes activated by Calcium
• Glycogen synthase
• Pancreatic lipase
• Adenylate cyclase
• Glycerol 3-P-DH
• Pyruvate carboxylase
• PDH & Pyruvate kinase

17. • Second messenger:
• Calcium & cAMP are second messengers for hormones e.g.
epinephrine in liver glycogenolysis.
• Calcium serves as a third messenger for some hormones
e.g, ADH acts through cAMP & Ca2+
• Myocardium:
• Ca2+ prolongs systole.
• In hypercalcemia, cardiac arrest is seen in systole.

18. Regulation of plasma calcium level
• Dependent on the function of 3 main organs
• Bone
• Kidney
• Intestine
• 3 main hormones
• Calcitriol
• Parathyroid hormone
• Calcitonin

19. Regulation of plasma calcium level by Calcitriol
• Role of calcitriol on bone:
• In osteoblasts of bone, calcitriol stimulates calcium uptake for
deposition as calcium phosphate
• At low calcium levels, calcitriol along with parathyroid
hormone increases the mobilization of calcium & phosphate
from the bone
• Causes elevation in the plasma calcium and phosphate

20. Role of calcitriol on kidneys
• Calcitriol minimizing the excretion of Ca2+ & phosphate by
decreasing their excretion & enhancing reabsorption.
• Role of calcitriol on intestine:
• It increases intestinal absorption of Ca2+ & phosphate.
• It binds with cytosolic receptor to form calcitriol-receptor complex
• Complex interacts with DNA leading to the synthesis of a specific
calcium binding protein
• This protein increases calcium uptake by intestine

21. Regulation by parathyroid hormone (PTH)
• PTH is secreted by two pairs of parathyroid glands.
• PTH (mol. wt. 95,000) is a single chain polypeptide, containing 84
amino acids.
• It is synthesized as prepro PTH, whch is degraded to proPTH &
finally to active PTH.
• The rate of formation & secretion of PTH are promoted by low
Ca2+ concentration.

22. Mechanism of action of PTH
• Action on the bone:
• PTH causes decalcification or demineralization of bone, a
process carried out by osteoclasts.
• This is brought out by pyrophosphatase & collagenase
• These enzymes result in bone resorption.
• Demineralization ultimately leads to an increase in the blood
Ca2+ level.

23. Action on the kidney
• PTH increases the Ca2+ reabsorption by kidney tubules
• It is most rapid action of PTH to elevate blood Ca2+ levels
• PTH promotes the production of calcitriol (1,25 DHCC) in the
kidney by stimulating 1- hydroxyaltion of 25-
hydroxycholecalciferol
• Action on the intestine:
• It increases the intestinal absorption of Ca2+ by promoting the
synthesis of calcitriol.

25. Calcitonin
• Calcitonin is a peptide containing 32 amino acids.
• It is secreted by parafollicular cells of thyroid gland.
• The action of CT on calcium is antagonistic to that of PTH.
• Calcitonin promotes calcification by increasing the activity of
osteoblasts.
• Calcitonin decreases bone resorption & increases the excretion
of Ca2+ into urine
• Calcitonin has a decreasing influence on blood calcium

26. Calcitonin, calcitriol & PTH act together

27. Hypercalcemia
• The serum Ca2+ level >11 mg/dl is called as Hypercalcemia.
• Causes:
• Hyperparathyroidism:
• Due to increased activity of parathyroid gland or PTH secreting
tumor
• Increase in calcium & ALP & decrease in phosphate levels.
• Excretion of calcium & phosphorous in urine.
• Determination of ionized Ca2+ (elevated to 6-9 mg/dl) is useful for
diagnosis of hyperparathyroidism

28. Clinical features of hypercalcemia
• Neurological symptoms:
• Depression, confusion, inability to concentrate
• Generalized muscle weakness
• Gastrointestinal problems
• Anorexia, abdominal pain, nausea, vomiting & constipation
• Renal feature: calcification of renal tissue
• Increased myocardial contractility & susceptibility to factures.

29. Hypocalcemia
• Decreased serum Ca2+ < 8.8 mg/dl is called as hypocalcemia
• Causes:
• Hypoproteinaemia:
• If albumin concentration in serum falls, total calcium is low
because the bound fraction is decreased
• Hypoparathyroidism:
• The commonest cause is neck surgery, idiopathic.

30. • Vitamin D deficiency:
• May be due to malabsorption or little exposure to sunlight
• Leads to bone disorders, osteomalacia & rickets
• Renal disease:
• In kidney diseases, the 1, 25 DHCC (calcitriol) is not synthesized
due to impaired hydroxylation

31. • Clinical features of hypocalcemia:
• Enhanced neuromuscular irritability
• Neurologic features
• Tingling, tetany, numbness (fingers & toes), muscle cramps
• Cardiovascular signs - abnormal ECG
• Cataracts.

32. Rickets
• Rickets is a disorder of defective calcification of bones.
• This may be due to a low levels of vitamin D in the body or
due to a dietary deficiency of Ca2+ & P or both.
• The concentration of serum Ca2+ & P may be low or normal
• An increase in the activity of alkaline phosphatase is a
characteristic feature of rickets.

34. Osteoporosis
• Characterized by demineraIization of bone resulting in the
progressive loss of bone mass.
• After the age of 40-45, Ca2+ absorption is reduced & Ca2+
excretion is increased; there is a net negative balance for Ca2+
• After the age of 60, osteoporosis is seen
• There is reduced bone strength & an increased risk of fractures.
• Decreased absorption of vitamin D & reduced levels of
androgens/estrogens in old age are the causative factors.

36. Case report
• A 5 year old girl had bone deformities such as bow legs and pigeon
chest. She had delayed eruption of teeth. The girl was from a strict
vegetarian family and she used to take very low amount of milk.
Interpret the following laboratory findings.
Investigations Report
Serum calcium 8.5 mg/dl
Serum inorganic phosphate 2.2 mg/dl
Serum alkaline phosphatase 175 IU/L
Serum calcitriol 12 pg/ml (Reference Range: 15 – 60 pg/ml)

37. Gandham. Rajeev

38. • Human body contains - 1 kg of phosphorous
• Body distribution:
• 80% of phosphorous is found in bones & teeth in combination
with calcium.
• 15% of phosphorous is present in soft tissues, as a component of
phospholipids, phosphoproteins, nucleic acids & nucleoproteins.
• 1% is found in ECF, as inorganic form

39. Dietary sources and RDA
• The food rich in calcium is also rich in phosphorous
• i.e. milk, cheese, beans, eggs, cereals, fish & meat
• Milk is good source of phosphorous
• RDA:
• Adults: 800 mg/day
• During pregnancy and lactation: 1,200 mg/day
• Ca : P of 1:1 is recommended

40. Biochemical functions
• Phosphorous is essential for formation of bones & teeth
• It is a constituent of hydroxyapatite in bone & provides structural
support.
• Formation & utilization of high energy phosphate compounds
like
• ATP, ADP, GTP, Creatine phosphate, etc. contains phosphorous.
• Essential for the formation of
• Phospholipids, phosphoproteins, nucleic acids, nucleotides

41. • Component of nucleotide coenzymes – NAD+, NADP, ATP, ADP
• Several enzymes & proteins are activated by phosphorylation
& dephosphorylation.
• Phosphate buffer system is important for maintenance of
blood pH
• Formation of phosphate esters - glucose-6-p.

42. Absorption
• 90% of dietary phosphorous is absorbed from small intestine.
• Absorption is stimulated by both PTH & calcitriol.
• Excretion:
• 500 mg of phosphate is excreted through urine per day
• Renal threshold for phosphorous is 2 mg/dl.
• Normal range:
• Plasma phosphorous: 2.5 to 4.5 mg/dl in adults
• In children’s: 5.0 to 6.0 mg/dl

43. • Calcium & phosphorous have reciprocal relationship.
• In particular, if phosphate rises, calcium falls.
• Fasting phosphate levels are higher
• Postprandial decrease of phosphorous is due to the utilization of
phosphorous for metabolism.

44. Hypophosphataemia
• Serum inorganic phosphate concentration <2.5 mg/dl is called as
Hypophosphataemia
• Causes:
• Decreases intake, Decreased absorption, Increased loss:
• In the treatment of Diabetes the effect of insulin in causing the shift of
glucose into cells also enhances the transport of phosphate into cells, which
may result into hypophosphataemia

45. • Renal rickets is associates with low phosphate & increased ALP
concentration.
• Congenital defect of tubular phosphate reabsorption, e.g. Fanconi’s
syndrome, in which phosphate is lost.
• Symptoms:
• Symptoms:
• Hemolytic anemia, weakness, bone fractures, Muscle pain.
• Rickets in children’s & osteoporosis in adults may develop.

46. Hyperphosphataemia
• Increase in serum inorganic phosphate levels than the normal
levels is called as hyerphosphataemia
• Causes:
• Increased intestinal absorption, decreased renal excretion,
cellular release of phosphorous.
• Symptoms:
• Chronic renal failure, soft tissue calcification.

47. RGUHS Questions
1. Explain the sources, daily requirement, absorption,
biochemical functions & disorders of calcium metabolism.
2. Blood calcium homeostasis.
3. Rickets & osteoporesis.
4. Metabolism of phosphorous.