Anda di halaman 1dari 31

Metabolisme Calcium-Tulang

Metabolisme Ca
• Bagaimana perjalanan atau perubahan calcium
mulai dari intake – absorbsi – sirkulasi – Tulang
dan eckresi.
• Calcium atom, ion keluar masuk: gut, blood
plasma, interstitial fluid, intracellular fluid, dan
bone.
• Plasma calcium homeostasis : Mekanisme
pengaturan kadar ion calcium dalam darah tetap
dalam batas normal (very narrow limit)
Struktur tulang
• Organik :
– Collagen: 1 collagen type : protein (90%)
– proteoglikan, fosfatase
• An-organik : Ca, Posfat dan air
– calcium-rich crystals : hydroxyapatite
(Ca10[PO4]6[OH]2)
– Microarchitecture: reservoir of calcium
– Osteoid: noncalcified organic matrix
Cristal Apatite
• Komplek kation, Ca2+ - anion HPO4 2–,
CO3 2–, OH– dan F–
–carbonate apatite Ca10(PO4)6CO3
–hydroxyapatite Ca10(PO4)6 (OH)2
–fluoroapatite Ca10(PO4)6F2
• Dewasa: > 1 kg calcium disimpan
pada tulang
Calcium
• extracellular calcium (Ca2+ : 5 mmol/L
– very rigidly controlled.
– Kadar Ca : mitochondria - endoplasmic
reticulum
• intracellular (Ca2+ ) : 0.05–10 mmol/L.
• normal total calcium of 2.2-2.6 mmol/L (9-
10.5 mg/dL)
Calcium Sirkulasi
• ionized Ca2+: 1.3-1.5 mmol/L
(4.5-5.6 mg/dL, active form
(50% of total calcium).
• protein-bound: albumin (40%);
Ca2+ buffer
• Complexed : citrate dan
phosphate: (10%).
Absorpsi Calcium
Fungsi Calcium
• Bone component: 1–1.5 kg Ca2+ (98%)
mineral bone
• Signaling substance: Ca2+ ions, sebagai
second messengers pada signal
transduction pathways:
– exocytosis
– muscle contraction
– cofactors in blood coagulation
• Enzymes Co –factor
• Proteins bind Ca2+ via oxygen ligands,
Calcium

• calcium sensors : efek biokimia Ca2+sbg


second massengger dalam cytoplasm
(Ca2+ binding proteins) : annexins,
calmodulin, and troponin C in muscle
– Calmodulin: mengikat 4 Ca2+ ion
• Ca2+ ion : regulasi aktifitas enzym,
pompa ion dan komponen otot rangka.
Enzymes and proteins regulated by
calcium or calmodulin.
Pengaturan homeostasis calcium

• Parathyroid hormone (PTH)


• Vitamin D
– 25-hydroxycholecalciferol (25(OH)D3) :
cadangan vit D hepar
– 1,25(OH)2D3: Meningkatkan Ca dan
posfat serum
• Calcitonin menghambat osteoclastic bone
resorption
Hormonal regulation of Ca2+ metabolism
Bone remodeling
• Bone : strukture dinamis melalui siklus
remodeling : resorption deposition
• Remodeling: adaptasi terhadap perubahan
beban dan hormonal
• renewed annually.
Bone remodeling

• Mineralization : Deposit Ca2+ dalam tulang dan mobilisasi


Ca diatur oleh hormon ( maturasi dan aktifitas osteosit)
• Osteoblast : deposit collagen, Ca2+ dan phosphate,
(new bone )
• Osteoclasts : sekresi H+ ions dan collagenase untuk
melarutkan tulang (bone remodeling).
• Osteoblast dan osteoclast: cytokines dan growth
factors.
• bone formation and bone breakdown : balance.
Bone remodeling
• Hormon: calcitriol, parathyroid dan calcitonin
• PTH: memicu pelepasan Ca2+ melalui perantara cytokine
dilepaskan oleh osteoblas
• Cytokines: memicu perkembangan prekusor ostoeclast
menjadi mature
• Calcitonin : menghambat prekusor osteoclast sejalan
dengan cytokine, memicu osteoblast
• Osteoporosis: women menopause (reduction in estrogen
levels)
• Estrogens normal:
• menghambat pemetangan osteoclas
Calcitonin
• Calcitonin:
• polypeptide hormone (32-amino acid)
• parafollicular cells (C cells) kelenjer
thyroid apabila Ca2+ darah meningkat
• IP3: Inositol 1,4,5-trisphosphate (inositol
trisphosphate): second messenger
berikatan - receptors endoplasmic
reticulum (ER) sehingga efflux Ca2+ dari
ER ke cytoplasm.
Parathyroid hormon
• PTH: 84-amino acid polypeptide hormone
• parathyroid gland, sekresi bila low blood
Ca2+ levels.
• PTH: meningkatkan Ca2+ dalam darah
dengan memicu pembentukan osteoclast:
releasing bone calcium and phosphate into
the blood
Vitamin D
• Vitamin D3: a secosteroid formed dengan
bantuan UV light pada 7-dehydrocholesterol.
• vitamin D bentuk aktif: hormone 1,25-
dihydroxycholecalciferol (calcitriol) pada
ginjal
• Berikatan dengan nuclear receptors pada
intestine, bone dan kidney untuk
pembnetukan calcium-binding proteins.
Maintaining bone mass - the bone remodeling
cycle.

Resorption and formation of bone by osteoclasts and osteoblasts is coupled


Calcitriol

• steroid hormone
– Bone formation melalui differensiasi osteoblast
– Anak : calcitriol < N gangguan mineralisasi
– Overdose vitamin D (cholecalciferol),
precursor calcitriol, (hypervitaminosis)
Calcium homeostasis
• Ca2+metabolism: balanced in healthy adults.
• 1 g Ca2+ : lebih kurang 300 mg di resorbsi.
• Jumlah yang sama diekresi.
• The amounts of Ca2+ released from bone and
deposited in it per day are much smaller.
• Milk and milk products, especially cheese, are
particularly rich in calcium.
Some Metabolic and Genetic Diseases Affecting Bone
and Cartilage
Dwarfism Often due to a deficiency of growth hormone, but has many other
causes.
Rickets Due to a deficiency of vitamin D during childhood.
Osteomalacia Due to a deficiency of vitamin D during adulthood.
Hyperparathyroidism Excess parathormone causes bone resorption.
Osteogenesis imperfecta Due to a variety of mutations in the COL1A1 and COL1A2 genes
affecing the synthesis and structure of type I
collagen.
Osteoporosis Commonly postmenopausal or in other cases is more gradual and
related to age; a small number of cases are due
to mutations in the COL1A1 and COL1A2 genes and possibly in the
vitamin D receptor gene
Osteoarthritis A small number of cases are due to mutations in the COL1A genes
Several chondrodysplasias Due to mutations in COL2A1 genes
Pfeiffer syndrome1 Mutations in the gene encoding fibroblast growth receptor 1
(FGFR1)
Jackson-Weiss) and Crouzon Mutations in the gene encoding FGFR2
syndromes1
Achondroplasia and
thanatophoric dysplasia2
CLINICAL CORRELATION
• Malignancies or hyperparathyroidism : Hypercalcemia :
kidney stones
• Osteoporotic : Estrogen decrease
• Genetic conditions:
• familial hypocalciuric hypercalcemia
• hyperparathyroidism.
• Osteomyelitis
• osteosarcoma