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3. BONES
Ossification – Process of bone formation by
osteoblasts
Growth starts from 6th week after fertilization in
an embryo till 25 years of age
Grows in thickness throughout life, but after 25,
ossification functions primarily in bone
remodelling and repair
4. REQUIRMENT
For healthy and normal growth of bones, proper
amount of:
Vitamin D,C and A
Minerals like calcium, phosphorus and
magnesium
Hormones like PTH, GH and Calcitonin
are required
5.
6. ENZYMOLOGY
Clinical biology - body fluid, predominantly,
blood as most of the disease conditions are
diagnosed using the ↑ed or ↓ed levels of
enzymes in serum/plasma.
Plasma functional enzymes are secreted actively
into plasma whereas plasma non- functional
enzymes are increased during disease conditions
8. ALP
EC. 3.1.3.1
Non-specific enzyme hydrolysing aliphatic, aromatic or
heterocyclic compounds.
Optimum pH – between 9 and 10
Activator – magnesium and manganese
Constituent ion – zinc; produced by osteoblasts of bone, and is
associated with calcification process
Location – cell membranes (ecto-enzyme)
Function – associated with transport mechanisms in liver, kidney
and intestinal mucosa
Sialic acid content in ALP iso-enzyme makes it iso-forms due to
its synthesis during post- translational modification
9. CLINICAL MANIFESTATION
Normal serum value : 40 – 125 U/L
Upper normal in children is more, due to ↑ed osteoblastic
activity
Mild ↑ during pregnancy, due to placental iso-enzyme
production
Moderate ↑(2 to 3 times) during hepatic disease such as
infective hepatitis, alcoholic hepatitis or hepato cellular
carcinoma; Hodgkin’s lymphoma; congestive cardiac failure
or ulcerative colitis
Very high level(10-12 times upper limit) during extrahepatic
obstruction (obstructive jaundice) or cholestasis
Drastically high level(10-25 times upper limit) during bone
diseases such as Paget’s disease, rickets, osteomalacia,
osteoblastoma, hyperparathyroidism
12. CALCITRIOL (1,25- DHCC)
Biological active form of vitamin D
7-dehydrocholesterol , an intermediate in cholesterol
biosynthesis, on exposure to sun light is converted to
cholecalciferol (vitamin D3) in the skin. On several
hydroxylation, calcitriol(1,25-
DiHydroxyCholeCalciferol) is synthesised
Regulates the plasma levels of calcium and phosphate
Acts at 3 different level – intestine, kidney and bone.
13. RICKETS
Due to deficiency of vitamin D in children
Derived from an old English word ‘wrickken’ means
twist.
Characterized by bone deformities due to incomplete
mineralization, resulting in soft and pliable bones.
Weight bearing bones are bent to form bow-legs.
plasma level of calcitriol is decreased and ALP is
elevated
14.
15. OSTEOMALACIA
Due to deficiency of vitamin D in adult (adult
rickets)
Derived from Greek :osteon- bone; malakia –
softness
Demineralization of bones occurs, increasing
their susceptibility to fracture
Vitamin D is called as antirachitic vitamin
18. PARATHYROID HORMONE (PTH)
Causes demineralization of bone, carried out by
osteoclasts, by stimulating ↑ed activity of enzyme
pyrophosphatase and collagenase resulting in
bone reabsorption
this leads to an increase in the blood Ca level
Thus blood calcium level is maintained
associated with alterations in PTH
19. RENAL OSTEODYSTROPHY
Observed in patients with chronic renal failure
or with damage to renal tissues causing
impairment in the synthesis of calcitriol
Thus renal rickets is mainly due to ↓ed synthesis
of calcitriol in kidney
This does not respond to vit D, thus called as
vitamin D resistant rickets
Treated by administration of calcitriol
20.
21. OSTEOPOROSIS
Characterized by demineralization of bone
resulting in progressive loss of bone mass
Generally, elderly people (60+ yrs)of both sexes
are at the risk for osteoporosis
But predominantly occurs in post –menopausal
women.
This results in frequent bone fractures
22.
23. The ability to produce calcitriol from vit D is ↓ed with age,
particularly in postmenopausal women
Immobilized or sedentary individuals tend to decrease bone
mass while those on regular exercise tend to increase bone
mass
Deficiency of sex hormone(women) has been implicated in
the development of osteoporosis
Estrogen administration along with calcium
supplimentation (in combination with vit D)to
postmenopausal women reduces the risk factor
Higher dietary intake of Ca (<1.5g/day) is recommended for
elderly people
24.
25. OSTEOPETROSIS
Known as marble bone disease
Characterized by ↑ed bone density, due to
inability to resorb bone
Mostly observed in association with renal
tubular acidosis ( due to defect in the enzyme
carbonic anhydrase) and cerebral calcification
28. PAGET’S DISEASE
A chronic condition which interferes with the
body’s normal bone remodelling process
This can cause the affected bones to become
fragile and misshapen
Most commonly occurs in pelvis, skull, spine and
legs
29.
30. Complications includes:
Age : 40+yrs
Sex: Men are affected more
Family history
Fractures and deformities(Lathyrism)
Osteoarthritis
Neurological problems
Heart failure
Bone carcinoma
Hearing loss
31. Single site of bone is affected –
monostotic paget’s disease
Multiple sites of bone are affected
– polystotic paget’s disease
Bisphosphonate – medication also
used in osteoporosis- are the
mainstay of treatment
In several cases, surgery may be
necessary
Editor's Notes
Ectoenzyme- enzymes found outside of (or on the outer surface of )a cell