EKA AGUSTIA RINI

RICKETS
 Disorder of mineralization of
the bone matrix / osteoid in
growing bone
 Involved : growth plate
Newly trabecular formed
Cortical bone
Osteomalacia
After cessation of growth
Involves only a bone, not the growth plate
 rakhitis
Gangguan mineralisasi matriks tulang / osteoid dalam pertumbuhan
tulang
Terlibat: plat pertumbuhan
Baru terbentuk trabekular
Tulang kortikal

Osteomalacia
Setelah berhentinya pertumbuhan
Melibatkan hanya tulang, bukan lempeng pertumbuhan
 Risk factors
 Living in northern latitudes (<30o);
 Dark skinned children;
 Decreased exposure to sunlight
 Maternal vitamin D deficiency;
 Diets low in calcium, phosphorus and vit. D
 Prolonged parenteral nutrition in infancy with
an inadequate supply of intravenous calcium
and phosphate;
 Intestinal malabsorption
 Faktor risiko
Tinggal di garis lintang utara (<30o);
Anak berkulit gelap;
Berkurangnya paparan sinar matahari
Kekurangan vitamin D ibu;
Diet rendah kalsium, fosfor dan vit. D
Nutrisi parenteral berkepanjangan pada masa
bayi dengan suplai kalsium dan fosfat
intravena yang tidak mencukupi;
Malabsorpsi usus
Defective production of
1,25(OH)2D3
 Hereditary type I vitamin D-resistant (or
dependent) rickets (mutation which abolishes
activity of renal hydroxylase);
 Familial (X-linked ) hypophosphataemic rickets –
renal tubular defect in phosphate transport;
 Chronic renal disease;
 Fanconi syndrome (renal loss of phosphate)
 Target organ resistance to 1,25(OH)2D3-
hereditary vitamin D-dependent rickets type II
(due to mutations in vitamin D receptor gene).
 Produksi cacat 1,25 (OH) 2D3
Rakhitis tipe I yang resisten terhadap vitamin D (atau dependen)
(mutasi yang menghapus aktivitas hidroksilase ginjal);
Familial (X-linked) hypophosphataemic rickets - defek tubulus ginjal
dalam transport fosfat;
Penyakit ginjal kronis;
Sindrom Fanconi (kehilangan ginjal fosfat)
Targetkan resistensi organ terhadap 1,25 (OH) 2D3 - herediter
vitamin D tergantung rakhitis tipe II (karena mutasi pada gen
reseptor vitamin D).
Calcium homeostasis - PTH
action
-ve feedback
PTH

Decreased 1,25-(OH)2D
Ca Clearance

Increased
Resorption

Increased
Ca Absorption

Serum
Ca2+
 Homeostasis Kalsium - aksi PTH
 Vitamin D Metabolism

VitD3 25-OH-D3
7 Dehydrocholesterol VitD3 (cholecalciferol) (calcidiol)
Skin

Calcium absorption

1,25-(OH)2-D3 25-OH-D3
(calcitriol) (calcidiol)
Resorption
 PTH Response to
Hypocalcemia
-ve feedback Ca2+
Plasma
PTH
Ca2+
Increase
Plasma
1,25-(OH)2D H2PO4-

Renal Excretion

Ca2+
Renal Excretion

Ca2+
GIT absorption
Resorption
Role of Calcium

 Bone Growth
 Blood Clotting
 Maintenance of trans membrane potential
 Cell replication
 Stimulus-contraction & stimulus-contracting coupling
 Second messenger process
 Peran Kalsium

Pertumbuhan tulang
Pembekuan darah
Pemeliharaan potensi membran trans
Replikasi sel
Stimulus-kontraksi & kopling kopling-
stimulus
Proses messenger kedua
Intestine:

 Increases calcium binding protein

 Active transport in the jejunal cells
 Phosphorus ions absorption through specific
phosphate carrier
 Alkaline phosphatase (AP) synthesis
 ATP-ase sensibility to calcium ions
 Usus:?
Meningkatkan protein pengikat kalsium
Transportasi aktif di sel jejunum
Penyerapan ion fosfat melalui pembawa
fosfat spesifik
Sintesis alkali fosfatase (AP)
Sensibilitas ATP-ase terhadap ion kalsium
Factors in Calcium
Homeostasis
 Ca++ sensing receptor (CaSR)
 membrane protein that binds Ca++
 determines the set-point for PTH secretion.
 Parathyroid hormone (PTH)
 84 amino acid peptide
 increases calcium concentration
 calcium reabsorption in the kidney
 calcium resorption from bone
 intestinal calcium absorption via renal formation
1,25-diOH-D).
 Faktor-faktor dalam Homeostasis Kalsium
Ca ++ sensing receptor (CaSR)
protein membran yang mengikat Ca ++
menentukan titik setel untuk sekresi PTH.
Hormon paratiroid (PTH)
84 peptida asam amino
meningkatkan konsentrasi kalsium
reabsorpsi kalsium di ginjal
resorpsi kalsium dari tulang
penyerapan kalsium usus melalui pembentukan ginjal
1,25-diOH-D).
Factors in Calcium
Homeostasis
 Vitamin D (1,25-diOH-D).
 absorption / reabsorption of calcium
(intestines, bone, and kidney).
 Calcitonin.
 32 amino acid peptide
 Secretion if serum calcium (antagonist PTH)
 inhibits osteoclast activity bone calcium resorption
 Faktor-faktor dalam Homeostasis Kalsium

Vitamin D (1,25-diOH-D).
penyerapan / reabsorpsi kalsium (usus, tulang,
dan ginjal).
Kalsitonin
32 peptida asam amino
Sekresi jika kalsium serum (antagonis PTH)
menghambat aktivitas osteoklas resorpsi
kalsium tulang
 Calcium metabolism
Skeleton
25 mmol/day

25 Mol (99%)
Gut

Kidney

13 mmol/d
300 mmol/day

2.20 mmol/L
(30mmol)
3 mmol/d
290 mmol/day

Plasma/ICF

10 mmol/day
15 mmol/day
Calcium Distribution in
Plasma

Ionised Calcium
~1.0 mmol/L

Total Calcium
~2.0 mmol/L

Bound Calcium
~0.95 mmol/L

Complexed Calcium
~0.05 mmol/L
Pathophysiology of Calcium
 Disorders of homeostatic regulators
 PTH
 vitamin D
 Disorders of the skeleton
 bone metastases
 Disorders of effector organs
 gut - malabsorption
 kidney
 Diet
 Patofisiologi Kalsium

Gangguan pengatur homeostatik

PTH
vitamin D
Gangguan kerangka
metastasis tulang
Gangguan organ efektor
usus - malabsorpsi
ginjal
Diet
 Breast milk contains 30-50IU/liter, cow’s
milk 20-30IU/l, egg yolk contains 20-
50IU/10gr.
 80% of the vitamin D is absorbed in the
small intestine in the present of normal
biliary secretion.
 Vitamin D reaches the blood through
thoracic duct along with chilomicrons.
 ASI mengandung 30-50IU / liter, susu sapi 20-
30IU / l, kuning telur mengandung 20-50IU /
10gr.
80% vitamin D diserap di usus kecil pada saat
sekresi empedu normal.
Vitamin D mencapai darah melalui saluran
thoraks disertai dengan chilomicron.
 Calcium regulation in the blood is as follows:
 Vitamin D2 in the food (exogenous) + vitamin D3
(skin, endogenous) =<liver microsomes
 =<25(OH) D3 =< Mitochondrial kidney tubules
membrane activated 3 forms:
 24,25 (OH)2 D3; 1,24,25 (OH)2 D3; 1,25 (OH)2 D3
!!! last more active.
 In placental macrophage of pregnancy women
are present 1,25(OH)2 D3
 Regulasi kalsium dalam darah adalah sebagai
berikut:
Vitamin D2 dalam makanan (eksogen) +
vitamin D3 (kulit, endogen) = <mikrosom hati
= <25 (OH) D3 = <membran tubulus
mitokondria ginjal diaktifkan 3 bentuk:
24,25 (OH) 2 D3; 1,24,25 (OH) 2 D3; 1,25 (OH)
2 D3 !!! terakhir lebih aktif
Pada plasenta makrofag wanita hamil hadir
1,25 (OH) 2 D3
 Serum calcium : narrow physiological
range
 Result of complex interaction process
vitamin D, parathyroid hormone (PTH),
and the calcium sensing receptor.
 Serum calcium
 50% free (ionized)
 40% protein bound (80% albumin & 20%
globulin)
 10% complexed (phosphate, citrate,
bicarbonate, lactate)
 Kalsium serum: rentang fisiologis yang
sempit
Hasil proses interaksi kompleks vitamin D,
hormon paratiroid (PTH), dan reseptor
penginderaan kalsium.
Kalsium serum
50% bebas (terionisasi)
40% protein terikat (80% albumin & 20%
globulin)
10% dikomplekskan (fosfat, sitrat,
bikarbonat, laktat)
 Physiology of PTH

 Resorption: free Ca2+, orthophosphate, Mg, citrate,

Bone hydroxyproline,osteocalcin.

 Calcium absorption indirectly through vit D

GIT metabolism

 phosphate excretion via proximal tubules

Inhibits bicarbonate reabsorption metabolic acidosis
Kidney favours calcium ionization bone resorption &
dissociation of calcium from plasma protein binding sites
 Causes of rickets
Vit. D deficiency Lack of adequate sunlight
Unsupplemented breast-fed infant.
Total parenteral nutrition (TPN)

Ca deficiency Lack of dietary Ca

Inadequate Ca in TPN
Phosphat def. Breast-fed infant
Inadequate PO4 in TPN
 Causes of rickets
Vit. D Lack of adequate sunlight
deficiency Consumption of diet low in
fortified foods
Unsupplemented breast-fed
infant.
Total parenteral nutrition
(TPN)
Ca Lack of dietary Ca
deficiency Inadequate Ca in TPN
UV / increased sunlight
exposure
Vit D2
Vit D2 for premature
Vit D2 in TPN / oral
Ca 700 mg/day
Ca in prmature / TPN

Phosphat Breast-fed infant

def. Inadequate PO4 in TPN
CLINICAL MANIFESTATIONS

Rickets may develop in any age of an infant,

more frequent at 3-6mo, early in
prematures.
 The first signs of hypocalcaemia are CNS
changes- excitation, restlessness,
excessive sweated during sleep and
feeding, tremors of the chin and
extremities.
 MANIFESTASI KLINIS
Rickets dapat berkembang di usia bayi mana
pun, lebih sering pada usia 3-6 hari, sebelum
prematur.
Tanda pertama hipokalsemia adalah
perubahan SSP - eksitasi, kegelisahan,
keringat berlebihan saat tidur dan makan,
tremor dagu dan ekstremitas.
 Skin and muscle changes- pallor, occipital
alopecia, fragile nails and hair, muscular
hypotony,motor retardation.
 Complications- apnoea, stridor, low
calcium level with neuromuscular
irritability (tetany).
 CNS changes are sometimes interpreted
as CNS trauma and the administration of
the
 Perubahan kulit dan otot-pucat, alopecia
oksipital, kuku rapuh dan rambut, hipotetis
berotot, retardasi motor.
Komplikasi-apnea, stridor, tingkat kalsium
rendah dengan iritabilitas neuromuskular
(tetany).
Perubahan SSP kadang ditafsirkan sebagai
trauma SSP dan administrasi
ACUTE SIGNS

Have acute and subacute clinical signs

 Craniotabes – acute sign of rickets,
osteolyses detected by pressing firmly over
the occipital or posterior parietal bones, ping-
pong ball sensation will be felt. Large anterior
fontanella, with hyperflexible borders, cranial
deformation with asymmetric occipital
flattening.
 TANDA AKUT
Memiliki tanda klinis akut dan subakut
Craniotabes - tanda akut rakhitis, osteolitik
yang terdeteksi dengan menekan kuat di atas
tulang parietal oksipital atau posterior,
sensasi bola pingpong akan terasa.
Fontanella anterior besar, dengan batas
hyperflexible, deformasi kranial dengan
asimetris oksipital merata.
 SUBACUTE SIGNS

 Subacute signs are all the following: frontal

and temporal bossing
 False closure of sutures (increase protein
matrix), in the X-ray craniostenosis is absent.
 Maxilla in the form of trapezium, abnormal
dentition.
 TANDA SUBACUTE
Tanda-tanda subakut adalah sebagai berikut:
penguasaan frontal dan temporal
Penutupan jahitan palsu (meningkatkan
matriks protein), pada radang kraniostenosis
sinar-X tidak ada.
Maxilla dalam bentuk trapezium, gigi tidak
normal.
 Late dental evolution, enamel defects in
the temporary and permanent dentition.
 Enlargement of costo-chondral junctions-
“rickets rosary”
 Thorax, sternum deformation, softened
lower rib cage at the site of attachment of
the diaphragm- Harrison groove.
 Evolusi gigi yang terlambat, cacat enamel
pada gigi sementara dan permanen.
Pembesaran sambungan costo-chondral-
"rickets rosario"
Thorax, deformasi sternum, tulang rusuk
bawah yang melunak di tempat pelekatan
diafragma - alur Harrison.
Subacute signs

 Spinal column- scoliosis, lordosis, kyphosis.

 Pelvis deformity, entrance is narrowed (add to
cesarean section in females)
 Extremities- palpated wrist expansion from
rickets, tibia anterior convexity, bowlegs or
knock kness legs.
 Deformities of the spine, pelvis and legs result in
reduced stature, rachitic dwarfism.
 Delayed psychomotor development (heat
holding, sitting, standing due to hypotonia).
 Tanda subakut
Skoliosis tulang belakang, lordosis, kifosis.
Cacat Pelvis, pintu masuk menyempit (tambahkan ke seksio sesarea
pada wanita)
Ekstremitas - ekspansi pergelangan tangan terluar dari rakhitis,
konveksi anterior anterior tibia, bowleg atau kaki ketukan.
Kelainan bentuk tulang belakang, panggul dan tungkai
menyebabkan perawakannya berkurang, dwarfisme rachitis.
Perkembangan psikomotor yang tertunda (menahan panas, duduk,
berdiri karena hipotonia).
LABORATORY DATA

 Serum calcium level (N=2.2-2.6mmol/l). At the level

<2.0mmol/l convulsions sets in.
 Phosphorus normal (1.5-1.8mmol/l). Normal ratio of Ca :
P= 2:1; in rickets become 3:1; 4:1.
 Serum 25(OH)D3 (N=28+2.1ng/ml); and
1,25(OH)2D3(N=0.035+0.003ng/ml)
 Serum alkaline phosphatase is elevated <500mmol/l.
 Thyrocalcitonin can be appreciated (N=23.6+3.3pM/l)
Serum parathyroid hormone (N=598+5.0pM/l)
In urine: Aminoaciduria <1.0mg/kg/day
 Urinary excretion of 3’5’ cyclic AMP
 Decreased calcium excretion (N=50-150mg/24h)
 DATA LABORATORIUM
Tingkat kalsium serum (N = 2,2-2,6 mmol / l). Pada level
<2,0mmol / l konvulsi masuk
Fosfor normal (1,5-1,8 mmol / l). Rasio normal Ca: P = 2:
1; dalam rakhitis menjadi 3: 1; 4: 1.
Serum 25 (OH) D3 (N = 28 + 2.1ng / ml); dan 1,25 (OH)
2D3 (N = 0,035 + 0,003ng / ml)
Serat alkalin fosfatase meningkat <500mmol / l.
Thyrocalcitonin dapat diapresiasi (N = 23,6 + 3.3pM / l)
Serum hormon paratiroid (N = 598 + 5,0pM / l)
Dalam urin: Aminoaciduria <1.0mg / kg / hari
Ekskresi urin AMP siklik 3'5 '
Penurunan ekskresi kalsium (N = 50-150mg / 24h)
Radiological findings

Only in difficult diagnostic cases.

 X-ray of the distal ulna and radius: concave
(cupping) ends; normally sharply, Fraying
rachitic metaphyses and a widened epiphyseal
plate.
 Osteoporosis of clavicle, costal bones, humerus.
 Greenstick fractures.
 Thinning of the cortex, diaphysis and the cranial
bones.
 Temuan radiologis
Hanya dalam kasus diagnostik yang sulit.
Sinar-X dari ulna dan radius distal: ujung
cekung (bekam); biasanya tajam, Fraying
metafisis rachitik dan piring epiphyseal yang
melebar.
Osteoporosis pada klavikula, tulang kosta,
humerus.
Fraktur Greenstick
Penipisan korteks, diaphysis dan tulang
kranial.
EVOLUTION

The evolution is slow with spontaneous healing

at the age of 2-3 years.
If treated can be cured in 2-3mo with the
normalization of the skeletal and the cellular
system.
Gibbous, palatal deformity and the narrow
pelvis may persist.
 EVOLUSI
Evolusi lambat dengan penyembuhan
spontan pada usia 2-3 tahun.
Jika dirawat dapat disembuhkan dalam 2-
3mo dengan normalisasi rangka dan sistem
seluler.
Gibbous, kelainan bentuk palatal dan panggul
yang sempit dapat terjadi.
DIFFERENTIAL DIAGNOSIS

 Osteogenesis imperfecta, chondrodystrophy,

congenital diseases- CMV, rubella, syphilis.
 Chronic digestive and malabsorption
disorders.
 Hereditary Fanconi’s disease, phosphorus
diabetes, renal tubular acidosis.
 PERBEDAAN DIAGNOSA
Osteogenesis imperfecta, chondrodystrophy,
penyakit bawaan - CMV, rubella, sifilis.
Gangguan pencernaan dan malabsorpsi
kronis.
Penyakit Fanconi herediter, diabetes fosfor,
asidosis tubulus ginjal.
Slide 3 of 21
 Radiology
Thinning of cortex
Widening, cuping metaphyses
Decreased bone density

Biochemistry

Ca serum : low / N
ALP increased
PTH increased
 Radiologi

Penipisan korteks
Pelebaran, cuping metaphyses
Berkurangnya kepadatan tulang

Biokimia

Serum Ca: rendah / N

ALP meningkat
PTH meningkat
PROPHILAXIS IN RICKETS

 Specific antenatal prophylactic dose

administration : 500-1000IU/day of vitamin
D3 solution at the 28-th week of pregnancy.
 The total dose administered is 135000-
180000IU. In term infants prophylactic intake
of vitamin D2 700IU/d started at 10 days of
age during the first 2 years of life; in
premature the dose may increase to
1000IU/day.
 PROPHILAXIS DALAM RICKET
Pemberian dosis profilaksis antenatal
spesifik: 500-1000IU / hari larutan vitamin D3
pada minggu ke 28 kehamilan.
Dosis total yang diberikan adalah 135000-
180000IU. Pada bayi yang diberi asupan
profilaksis vitamin D2 700IU / hari dimulai
pada usia 10 hari selama 2 tahun pertama
kehidupan; Pada dosis prematur bisa
meningkat menjadi 1000IU / hari.
PROPHILAXIS IN RICKETS

 WHO recommendation for rickets prophilaxis

in a children coming from unfavorable
conditions and who have difficult access to
hospitals is 200000IU vitamin D2 i/muscular,
 On the 7day, 2, 4, 6 month- total dose
800000IU. In case of the necessary
prolongation 700IU/day till 24mo are given.
 Rekomendasi WHO untuk rangsets
prophilaxis pada anak-anak yang berasal dari
kondisi yang tidak menguntungkan dan yang
memiliki akses sulit ke rumah sakit adalah
200000IU vitamin D2 i / otot,
Pada 7 hari, 2, 4, 6 bulan - dosis total
800000IU. Dalam hal pemberian waktu yang
diperlukan 700IU / hari sampai 24mo
diberikan.
SPECIFIC TREATMENT IN RICHETS

 The treatment is with vitamin D3 depending

on the grade.
 In grade I- 2000-4000IU/day for 4-6weeks,
totally 120000-180000IU.
 In grade II- 4000-6000IU/day for 4-6 weeks,
totally 180000-230000IU.
 In grade III- 8000-12000IU/day for 6-8 weeks,
totally 400000-700000IU.
 PERAWATAN KHUSUS DI RICHETS
Perawatannya adalah dengan vitamin D3
tergantung kelasnya.
Di kelas I-2000-4000IU / hari untuk 4-6
minggu, total 120000-180000IU.
Di kelas II - 4000-6000IU / hari selama 4-6
minggu, benar-benar 180000-230000IU.
Di kelas III-8000-12000IU / hari selama 6-8
minggu, total 400000-700000IU.
SPECIFIC TREATMENT IN RICHETS

 Along with vitamin D, calcium is also

administered (40 mg/kg/day for a term baby,
 80 mg/kg/day for a premature baby); also
indicate vitamin B&C preparations.
 From the 7-th day of the treatment massage can
be started. Intramuscular administration
 of ATP solution in case of myotonia 1ml/day is
preferred.
 PERAWATAN KHUSUS DI RICHETS
Seiring dengan vitamin D, kalsium juga
diberikan (40 mg / kg / hari untuk satu istilah
bayi,
80 mg / kg / hari untuk bayi prematur); juga
menunjukkan persiapan vitamin B & C.
Dari hari ke 7 perawatan pijat bisa dimulai.
Administrasi intramuskular
Larutan ATP dalam kasus myotonia 1ml /
hari lebih diutamakan.
Vit D. def;
TPN : 0,5 ug/kg/day
Oral: 400-800 IU daily

Ca deficiency;
Premature: 75-150 mg/dl
Oral :200 mg/kg/day
IV : solution 20 mg/dl
RICKETS COMPLICATIONS

 Rickets tetany in result of low concentration

of serum calcium (<2mmol/l), failure of the
PTH compensation and muscular irritability
occur.
 Hypervitaminosis D
 KOMITE RICKETS
Rickets tetany akibat rendahnya konsentrasi
kalsium serum (<2mmol / l), kegagalan
kompensasi PTH dan iritabilitas otot terjadi.
Hipervitaminosis D
HYPERVITAMINOSIS D

 Symptoms develop in hypersensitivity to vitamin

D children or after1-3mo of high doses intakes of
vitamin D; they include hypotonia, anorexia,
vomiting, irritability, constipation, polydipsia,
polyuria, sleep disorder, dehydration. High
serum level of acetone, nitrogen and
 Ca<2.9mmol/l are found. Increase calcium
concentration in urine may provoke
incontinence, renal damage and calcification.
 HYPERVITAMINOSIS D
Gejala berkembang pada hipersensitivitas pada anak-anak vitamin D
atau setelah konsumsi asupan vitamin D dosis tinggi; Mereka
termasuk hipotonia, anoreksia, muntah, mudah tersinggung,
konstipasi, polidipsia, poliuria, gangguan tidur, dehidrasi. Tingkat
serum tinggi aseton, nitrogen dan
Ca <2.9mmol / l ditemukan. Meningkatkan konsentrasi kalsium
dalam urin dapat memicu inkontinensia, kerusakan ginjal dan
kalsifikasi.