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Metabolisme Kalsium

Hafiz Suwoto

Metabolisme Kalsium
• Kalsium adalah mineral terbanyak ditemukan
dalam tubuh manusia.
• Rata-rata seorang dewasa mengandung sekitar
1 kg, 99% diantaranya terdapat pada rangka.
• Cairan ekstrasel (ECF) mengandung sekitar
22.5 mmol, dimana sekitar 9 mmol terdapat
dalam serum.
• Lebih kurang 500 mmol kalsium mengalami
pertukaran diantara tulang rangka dengan ECF
selama waktu 24 jam. (Marshall, 1995).

Nilai Normal :
• Serum Kalsium mempunyai pengaturan yang
ketat dengan nilai normal total calcium 2.2-2.6
mmol/L (9-10.5 mg/dL) dan normal ionized
calcium 1.1-1.4 mmol/L (4.5-5.6 mg/dL). Kadar
kalsium darah ini diatur secara ketat terutama
kadar ionized calcium.
• Jumlah kalsium total berbeda sesuai dengan
kadar albumin, suatu protein dimana kalsium
dapat terikat.
• Efek biologis kalsium ditentukan oleh jumlah
ionized calcium, dan bukan oleh kadar total
kalsium. Ionized calcium diketahui ternyata tidak
berbeda dan paralel dengan kadar albumin, hal
ini berguna untuk pengukuran ion kalsium, bila
kadar albumin tidak normal tentu ditemukan
kelainan metabolisme kalsium meskipun kadar
kalsium total di plasma normal.

Kadar kalsium yang telah dikoreksi :
• Bila ditemukan kelainan pada kadar albumin, kadar kalsium
dapat ditentukan melalui suatu proses koreksi.
• Hal ini digunakan untuk menentukan kadar sebenarnya dari
total kalsium yang disebabkan oleh perubahan pada ikatan
kalsium-albumin. Hal ini memberikan perkiraan berapa
seharusnya kadar total kalsium bila kadar albumin berada
dalam kisaran normal.
– Kadar kalsium yang telah dikoreksi (mg/dl) = kadar total kalsium yang
terukur (mg/dl) + 0.8 (4.0 – kadar serum albumin terukur (g/dl))
– nilai 4.0 mempresentasikan nilai rata albumin.

• Bila terdapat hypoalbuminemia (kadar albumin < normal)
maka kadar kalsium yang telah dikoreksi akan lebih besar
dari pada kadar total kalsium terukur akan tetapi kadar
ionized calsium akan lebih rendah.

Sekitar 40% (10 mmol) diabsorpsi di lambung dan 5 mmol akan keluar dari tubuh bersama feces. Bila diet mempunyai kadar susu yang rendah termasuk bahan-bahan yang mengandung kalsium tinggi maka asupan dari diet akan rendah juga. karena dapat meningkatkan jumlah “calcium binding proteins”. .• • • • Sumber kalsium : Lebih kurang 25 mmol kalsium dikonsumsi oleh manusia pada diet yang normal. Sisanya akan diabsorpsi di usus halus. yang berperan pada absorpsi melalui apical membrane dari enterocytes di usus halus. Vitamin D merupakan ko-faktor penting pada proses “intestinal absorption of calcium”.

. • Kedua proses diatas distimulasi oleh hormon parathyroid (PTH).25-bisOH kolekalsiferol).Ekskresi : • Ginjal memfiltrasi sekitar 250 mmol per hari dan meresorbpsi kembali sekitar 245 mmol. sehingga kehilangan melalui urin hanya sekitar 5 mmol/l. • Ginjal juga berperan memproses vitamin D menjadi kalsitriol (1. yang merupakan bentuk aktif yang berperan membantu absorpsi di usus halus.

Dengan mempertahankan keseimbangan kalsium proses osteoporosis dapat dicegah.• • • • • Peran tulang pada metabolisme kalsium : Tulang berperan sebagai cadangan penyimpan kalsium terbesar karena 99% total kalsium tubuh terdapat di tulang. Calcium dapat dibebaskan dari tulang oleh hormon parathyroid . Calcitonin berperan menstimulasi masuknya kalsium ke dalam tulang meskipun prosesnya sendiri tidak dipengaruhi oleh calcitonin. . Rendahnya asupan kalsium dalam diet dapat menjadi faktor risiko pada perkembangan osteoporosis. Dalam keadaan normal sekitar 5 mmol mengalami pertukaran di tulang.

Kelenjar ini terdapat dibawah kelenjar thyroid.Organ-organ pengatur : • Organ pengatur terpenting adalah kelenjar parathyroid. . dan menghasilkan hormon parathyroid bila kadar kalsium darah menurun. • Sel-sel parafollicular dari kelenjar thyroid menghasilkan calcitonin bila kadar kalsium darah meningkat. • Akan tetapi dalam hal ini peran PTH lebih menentukan dalam pengaturan kadar kalsium darah.

• Osteoporosis dan osteomalacia juga merupakan kelainan yang disebabkan oleh gangguan pada metabolisme kalsium.Kelainan yang ditemukan pada metabolisme kalsium : • Hypocalcemia dan hypercalcemia merupakan kelainan yang sangat serius. • Renal osteodystrophy dapat terjadi sebagai konsekwensi dari chronic renal failure yang berhubungan dengan metabolisme kalsium. .

akan tetapi tropomyosin yang terdapat dalam struktur filamen actin akan memblok situs pengikatan pada protein actin sewaktu otot berada dalam keadaan relaksasi. • Bila kontraksi distimulasi oleh impuls saraf maka troponin yang terdapat dalam struktur filamen actin akan menggeser tropomiosin sehingga situs pengikatan pada actin terbuka dan dapat mengikat miosin. . Proses pembukaan situs pengikatan ini diregulasi oleh adanya ion Ca++. • Perubahan pada struktur filamen actin akan membentuk actomiosin dan kontraksi otot akan berlangsung.Peran Kalsium sebagai pengatur kontraksi otot : • Untuk terjadinya kontraksi otot miosin harus berikatan dengan actin.

Ca++ ion akan mengikat troponin yang selanjutnya mengikat tropomyosin dan membuka situs pengikatan pada protein actin. Arus polarisasi yang terjadi dengan segera ditransmisikan keseluruh serat otot oleh T tubuli dan menembus sampai ke sarcomer. Selanjutnya sisterna terminalis menjadi permeabel terhadap ion Ca++ dan akan membebaskan ion tersebut ke sarcomer. • Begitu terikat pada actin miosin akan memecah ATP dan membebaskan energi yang diperlukan untuk menarik filamen actin ke arah pusat sarcomer  kontraksi otot terjadi. • Sarcoplasmic reticulum sangat sensitif terhadap perubahan polarisasi itu. dan selanjutnya akan mengikat miosin. . Setiap T tubulus berada pada Z line. Perbedaan potensial antara bagian luar dan dalam akan mengalami pembalikan polarisasi.Pengaturan oleh ion kalsium berlangsung sbb: • Bila saraf motorik memicu timbulnya potensial aksi pada sel otot akan dihasilkan suatu senyawa pencetus berupa neurotransmiter.

troponin tidak dapat lagi mengikat tropomiosin. Menghilangnya ion Ca++. • Bila stimulasi saraf berhenti maka membran dari sisterna terminalis dengan cepat akan memompakan ion Ca++ bebas kemabali ke sisterna. sehingga tropomiosin akan kembali memblokir situs pengikatan miosin pada protein actin  kontraksi otot berhenti. .• Kontraksi otot ini akan terus berlanjut selama masih terdapat ion Ca++ bebas di dalam sarcomer.

. Skeletal dan otot kardiak kontraksinya diaktifkan bila ion Ca++ dibebaskan dari lumen SR ke sitosol melalui ryanodin reseptor. karena reseptor ini sangat sensitif terhadap alkaloid tumbuhan ryanodin.Ryanodine Receptor Kanal pembebasan ion Ca++ pada membran Retikulum sarkoplasmik sel otot (SR) disebut he ryanodine receptor.

leads to opening of ryanodinesensitive Ca++-release channels. Ca++ channel Voltage-gated Ca++ channels in the T tubule membrane interact with ryanodine receptors in the ++ Ca ryanodine closely apposed SR receptor membrane. by an action potential in the T tubule. cytosol SR lumen Activation of voltage-gated Ca++ channels. & then through the receptor's cytoplasmic assembly.extracellular space T tubules: invaginations of (T tubule lumen) voltage-gated muscle plasma membrane. passing through the transmembrane part of the ryanodine receptor. Ca++ moves from the SR lumen to the cytosol. .

Multiple biological functions of calcium • Cell signalling • Neural transmission • Muscle function • Blood coagulation • Enzymatic co-factor • Membrane and cytoskeletal functions • Secretion • Biomineralization .

5)/100 mls – Non diffusible .5-10.1kg – – – – – – 99% in bone 1% in blood and body fluids Intracellular calcium Cytosol Mitochondria Other microsomes Regulated by "pumps" • Blood calcium .5 mgs .Distribution of Calcium • Total body calcium.6.5 mgs – Diffusible .3.10mgs (8.

Bone Structure (cellular and non-cellular) • Inorganic (69%) – Hydroxyapatite .99% • 3 Ca10 (PO4)6 (OH)2 • Organic (22%) – Collagen (90%) – Non-collagen structural proteins • proteoglycans • sialoproteins • gla-containing proteins – α2HS-glycoprotein • Functional components • growth factors • cytokines .

0.1.0.2.3 mgs phosphate .5.5 mgs – Albumin bound .5 mgs – Ionized .0.8 – Globulin bound .5 mmoles/L) • Non diffusible .6 mgs citrate .0.10mgs/100 mls(2.2 mgs other – Close to saturation point • tissue calcification • kidney stones .Blood Calcium .3 – Complexed .2 mgs • • • • bicarbonate .3.6.7 • Diffusible .

5 g/d) • Primarily in duodenum – 15-20% absorption • Adaptative changes – – – – • low dietary calcium growth (150 mg/d) pregnancy (100 mg/d) lactation (300 mg/d) Fecal excretion .Diet • Dietary calcium – Milk and dairy products (1qt = 1gm) Dietary supplements – Other foods • Other dietary factors regulating calcium absorption – Lactose – Phosphorus Calcium Absorption (0.4-1.

calbindins) – calcium regulating membranomes • Ion exchangers • Passive diffusion .g..Mechanisms of GI Calcium Absorption • Vitamin D dependent • Duodenum > jejunum > ileum • Active transport across cells – calcium binding proteins (e.

transcellular – Passive .1% filtered load .250 mg/day – 0.Urinary Calcium • Daily filtered load – 10 gm (diffusible) – 99% reabsorbed • Two general mechanisms – Active .5 .paracellular • Proximal tubule and Loop of Henle reabsorption – Most of filtered load – Mostly passive – Inhibited by furosemide • Distal tubule reabsorption – 10% of filtered load – Regulated (homeostatic) • • • • • stimulated by PTH inhibited by CT vitamin D has small stimulatory effect stimulated by thiazides Urinary excretion – 50 .

25(OH)2D .inhibit excretion • furosemide .Regulation of Urinary Calcium • Hormonal .tubular reabsorption – PTH .stimulate excretion Other Routes of Excretion • Perspiration • Lactation .decreases excretion (clearance) – CT .decreases excretion • Diet – Little effect – Logarithmic • Other factors – Sodium .increases excretion – Phosphate .increases excretion (calciuretic) – 1.thiazides vs loop • thiazides .decreases excretion – Diuretics .

Disorders of Calcium and Phosphate Metabolism .

Abnormalities of phosphate balance 4.Outline 1. Example cases . Review of calcium and phosphate metabolism 2. Abnormalities of calcium balance 3.

Major Mediators of Calcium and Phosphate Balance • Parathyroid hormone (PTH) • Calcitriol (active form of vitamin D3) .

Role of PTH • • • • • Stimulates renal reabsorption of calcium Inhibits renal reabsorption of phosphate Stimulates bone resorption Inhibits bone formation and mineralization Stimulates synthesis of calcitriol Net effect of PTH  ↑ serum calcium ↓ serum phosphate .

Regulation of PTH Low serum [Ca+2]  Increased PTH secretion High serum [Ca+2]  Decreased PTH secretion .

Role of Calcitriol • Stimulates GI absorption of both calcium and phosphate • Stimulates renal reabsorption of both calcium and phosphate • Stimulates bone resorption Net effect of calcitriol  ↑ serum calcium ↑ serum phosphate .

Regulation of Calcitriol .

Overview of Calcium-Phosphate Regulation .

most of the calcium in the body exists as the mineral hydroxyapatite. phosphate) To estimate the physiologic levels of ionized calcium in states of hypoalbuminemia: [Ca+2]Corrected = [Ca+2]Measured + [ 0. Ca10(PO4)6(OH)2. Calcium in the plasma: 45% in ionized form (the physiologically active form) 45% bound to proteins (predominantly albumin) 10% complexed with anions (citrate.Different Forms of Calcium At any one time.8 (4 – Albumin) ] . sulfate.

Overview of Biochemical Homeostasis .

Overview of Calcium Balance .

Etiologi Hypercalcemia Increased GI Absorption Milk-alkali syndrome Elevated calcitriol Vitamin D excess Excessive dietary intake Granuomatous diseases Elevated PTH Hypophosphatemia Increased Loss From Bone Increased net bone resorption Elevated PTH Hyperparathyroidism Malignancy Osteolytic metastases PTHrP secreting tumor Increased bone turnover Paget’s disease of bone Hyperthyroidism Decreased Bone Mineralization Elevated PTH Aluminum toxicity Decreased Urinary Excretion Thiazide diuretics Elevated calcitriol Elevated PTH .

Etiologi Hypocalcemia Decreased GI Absorption Poor dietary intake of calcium Impaired absorption of calcium Vitamin D deficiency Poor dietary intake of vitamin D Malabsorption syndromes Decreased conversion of vit. D to calcitriol Liver failure Renal failure Low PTH Hyperphosphatemia Decreased Bone Resorption/Increased Mineralization Low PTH (aka hypoparathyroidism) PTH resistance (aka pseudohypoparathyroidism) Vitamin D deficiency / low calcitriol Hungry bones syndrome Osteoblastic metastases Increased Urinary Excretion Low PTH s/p thyroidectomy s/p I131 treatment Autoimmune hypoparathyroidism PTH resistance Vitamin D deficiency / low calcitriol .

Overview of Phosphate Balance .

Etiologi Hyperphosphatemia Increased GI Intake Fleet’s Phospho-Soda Decreased Urinary Excretion Renal Failure Low PTH (hypoparathyroidism) s/p thyroidectomy s/p I131 treatment for Graves disease of thyroid cancer Autoimmune hypoparathyroidism Cell Lysis Rhabdomyolysis Tumor lysis syndrome .

Etiologi Hypophosphatemia Decreased GI Absorption Decreased dietary intake (rare in isolation) Diarrhea / Malabsorption Phosphate binders (calcium acetate. and alcholism) During treatment for DKA . anorexia. Al & Mg containing antacids) Decreased Bone Resorption / Increased Bone Mineralization Vitamin D deficiency / low calcitriol Hungry bones syndrome Osteoblastic metastases Increased Urinary Excretion Elevated PTH (as in primary hyperparathyroidism) Vitamin D deficiency / low calcitriol Fanconi syndrome Internal Redistribution (due to acute stimulation of glycolysis) Refeeding syndrome (seen in starvation.

5-10.Case 1 Mrs. Labs are as follows: Calcium (total) – 11. Her exam is unremarkable.8 g/dL (normal ~ 3. T is a 59 year old woman with a past medical history significant for hypertension who comes for a routine clinic visit.8 mg/dL (normal ~ 2.9 mg/dL (normal ~ 8.0-4.2 mg/dL) Phosphate – 1.3 mg/dL) Albumin – 3.5-5.0 g/dL) PTH – 124 pg/mL (normal ~ 10-60 pg/mL) Creatinine – 1.2 mg/dL . but later in the interview describes chronic fatigue and a mildly depressed mood. She initially states that she has no symptomatic complaints.

In the ER. The seizures stop with low dose IV diazepam.2 meq/L Calcium (total) – 6.2 mg/dL) (normal ~ 2.5-5. but was admitted for mild alcoholic hepatitis and marked malnutrition. Later that day.8 mg/dL Phosphate – 0. G is a 40 year old man with a history of alcoholism.Case 2 Mr.3 mg/dL CK – 3500 U/L (normal ~ 8. he complained of feeling fatigued and weak. His mental status cleared up about 8 hours after admission.5-10. Stat labs are sent: Sodium – 136 meq/L Potassium – 3.0 g/dL) .3 mg/dL) (normal ~ 3.8 g/dL Creatinine – 1.0-4. He had not seen a doctor for 15 years before police brought him to the ER after finding him confused and disheveled behind a local convenience store. During morning rounds on hospital day #2. he was thought to be confused simply due to intoxication.7 mg/dL Albumin – 1. the nurses find him seizing.

7 meq/L PTH . Stat labs are ordered from clinic: Sodium – 138 meq/L CBC. he reports feeling fatigued.2 g/dL Calcium (total) – 13. PT/PTT – WNL Potassium – 3.8 mg/dL (baseline creatinine = 1. Upon further obtaining further history.1 mg/dL Phosphate – 1.Pending Magnesium – 1. H is a 74 year old man with a past history significant for hypertension and COPD from smoking 2 packs per day for the last 40 years.Case 3 Mr. and chronically thirsty for several weeks.3 mg/dL Creatinine – 2.8 mg/dL Albumin – 2. He presented to an urgent pulmonary clinic appointment with 2 months of increased cough and 5 days of “mild” hemoptysis. His exam is significant for bilateral rhonchi (no change from baseline lung exam) and absent reflexes.1) . nauseous.

who is brought to the ER by her mother after she noted her to be acting bizarrely for the past several weeks. screen – Negative Urine pregnancy .Negative .8 mg/dL Urine tox.9 mg/dL Phosphate – 4.1 meq/L Magnesium – 2.4 mg/dL Albumin – 4. who recommends checking routine labs: Sodium – 142 meq/L Potassium – 4.Case 4 Miss L is a 16 year old woman with no significant past medical history.3 mg/dL Calcium (total) – 6.2 g/dL Creatinine – 0. a psychiatry consult is asked to see the patient. Thought to be actively psychotic.

Sekian dan Terima Kasih .