BIOKIMIA DARAH

SALMAH ORBAYINAH
2
DARAH
DARAH
PROTEIN
( alb, glob, fibr )
PLASMA
FAK PEMBEKUAN
LEUKOSIT
BUFFY-COAT
TROMBOSIT
ERITROSIT

4
Blood Cell Production
Formation & Destruction of RBCs
NUTRIEN ESENSIAL (Fe,
Asam Folat,Vit B12)
Besi
Asam folat
Vit B 12
Protein
eritrosit
eritrosit
Perkembangan optimal
Eritropoetik

7
ANEMIA
ANEMIA DEFISIENSI
DEFISIENSI BESI
BESI
KEGUNAAN ZAT BESI DALAM TUBUH
Pembentukan hemoglobin
Pertumbuhan
Bekerjanya bbrp macam enzim
Meningkatkan :
ketahanan terhadap infeksi
kemampuan usus menetralisir zat toksik
kemampuan belajar ( konsentrasi )
8
KEJADIAN DEFISIENSI BESI PADA ANAK

Negara maju : 20%

Negara berkembang / miskin: 30-80%
( terutama BALITA )

WHO ( INDONESIA )
2/3 ibu hamil : Hb rendah
Kejadian BBLR : 20%

50% Bayi lahir berisiko

9
Faktor predisposisi
Status hematologi ibu hamil
BBLR
Ketidak tahuan
Pemberian makanan Sosioekonomi
Perilaku pemberian makan
Infeksi menahun Jenis makanan
Infestasi parasit

10
METABOLISME BESI
Zat besi
Fe+++
Dalam makanan

Fe+++
HCL
lambung
Ferritin
Vit C
usus Fe++ Hemosiderin
Myoglobin
Transferin enzim
Sintesa Hb
( sumsum tulang )
11
METABOLISME BESI
Dietary Iron:
Iron is essential element and must be
precisely regulated.
On the lumen side of small intestine iron
is reduced from its ferric form(Fe3+) to
ferrous form(Fe2+).
Ferrous iron is then transported in
enterocytes by DMT1(divalent metal
transporter).
Iron can be either stored within the
enterocyte as ferritin or it can be
transferred across the basolateral
membrane to the plasma by
transport protein FERROPORTIN1 and
MTP1.
(Requires oxidation of Ferrous to
Ferric by hephaestin.)
TRANSPORT PROTEINS
DMT1 (Divalent Metal Transporter 1)
(Tranports from lumen into the
enterocytes)

FERROPORTIN1
(Transports from enterocytes to
circulation)
QUESTION????
Who is playing the central role in
IRON METABOLISM??
ANSWER
HEPICIDIN is the key regulator of iron
in our body.
What is HEPICIDIN??
Is a peptide hormone which was first
identified in human urine and plasma
in 2000.
Its molecular weight is 25 Kda.
Highly folded structure.
Present in inactive
form;prohepcidin(60aa) and its active
form is hepicidin(25aa).
HEPICIDN

25 Amino acid disulfide peptide.

Hepicidin, Primary regulator
Increased expression of hepicidin
leads to
Decrease iron absorption and release.
Mutation :Hemochromatosis
Increased expression:Iron deficiency
Hepicidin mRna expression is
increased by erythropoetin,hypoxia &
inflammation.
Also binds to ferroportin.
Ferroportin
The only cellular iron exporter in
vertebrates.
Present in macrophages,placenta
and the hepatocytes.
Mechanism of action of
hepicidin
The major mechanism of hepicidin is
THE REGULATION OF
TRANSMEMBRANE IRON TRANSPORT.
It binds to FERROPORTIN ,forms
hepicidin-ferroportin complex ,which
is degraded in the lysosomes and
iron is locked inside the cells(mainly
enterocytes,hepatocytes and
macrophages).
SO
Hepcidin lowers iron absorption in
the intestine ,lowers iron releasing
from hepatocytes and macrophages

Serum iron is
decreased.
Hepicidin Regulation
So when hepicidin levels are low ,iron exporting cells have abundant
ferroportin and thus releases iron into plasma.When hepicidin
concentration increases it binds to ferroportin and thus iron is retained
in the cells.
Regulation of Hepicidin
Hypoxia/Anemia
Inflammation
Regulation of Hepcidin synthesis by
anemia and hypoxia
Oxygen Hepcidin

Uptake of diet iron

Iron release from
hepatocytes
Iron release from
macrophages
Regulation of Hepcidin synthesis by
inflammation
Interleukin-6 Hepcidin

iron anemia of
chronic disease.
Generally when iron level
,ROS(Reactive oxygen species) that
leads to in thiobarbutyric acid
activation of NF Kappa proteins
activates IL-6 , hepicidin synthesis
Disease States
Hepcidin deficiency, physiological =
Haemochromatosis
Hepcidin excess anaemia of chronic
disease
The role of Hepcidin in hereditary
hemochromatosis
Hereditary hemochromatosis:
-excessive intestinal iron
absorption
-Saturation of transferrin
-Iron deposition in vital organs
Overall summary
Hepcidin
-Is a recently discovered liver produced
25 amino-acid peptide
-Is a regulator of iron metabolism that
controls iron absorption and
macrophage iron release.
-Is regulated by erythropoietic
needs( ) ,body iron stores( ) and
inflammation( )
Absorbing Iron From the
Diet

31
How Cells Get their Iron from the
Body

32
KEBUTUHAN TERHADAP BESI

5 10 mgr / hari
Meningkat pada :
Bayi
Pertumbuhan
Prasekolah
meningkat
Remaja / pubertas
Penyakit infeksi

Sangat sedikit
Pengeluaran besi Deskuamasi: sel-sel kulit, sal cerna
Keringat, urine & empedu
49
Derajat
Derajat Defisiensi
Defisiensi Besi
Besi

PRELATEN LATEN LANJUT

Cadangan tak ada ( ANEMIA)
Cadangan besi kurang
Besi serum kurang
Besi serum masih normal
Feritin kurang Cadangan tak ada
Feritin kurang
Belum anemia Besi serum rendah
Belum anemia
Feritin sangat kurang
Timbul gejala

50
MANIFESTASI
MANIFESTASI KLINIK
KLINIK
Lesu, letih Kulit kering
Pucat Lidah : atropi papil
Mudah terangsang Pembesaran jantung
Nafsu makan kurang Bising sistolik fungsional

Konsentrasi kurang
Prestasi sekolah menurun

51
LABORATORIUM
LABORATORIUM

Darah tepi : Lab lainnya :

Hb rendah
Mikrositer, Hematokrit rendah
Hipokrom SI menurun, TIBC meningkat
Anisositosis, Ferritin menurun
Poikilositosis Saturasi transferin
FEP ( Free erytrhrocyt Phorphyrin )

52
PENGOBATAN
PENGOBATAN
Pengobatan kausal
Pemberian preparat besi :
Ferro sulfat, fosfat, fumarat
Suplementasi besi
Fortifikasi besi
Transfusi darah

53
TRANSFUSI
TRANSFUSI DARAH
DARAH
Tidak sering dilakukan
Indikasi khusus :
Keadaan umum yang buruk
Infeksi berat ( Bronkopneumonia )
Gagal jantung
Pemberian transfusi: sedikit dan berulang

54
 ANEMIA DEFISIENSI Vit B12 dan
asam folat
ANEMIA MEGALOBLASTIK
Anemia dg abnormalitas fungsional dan
morfologi spesifik dari eritroblast sumsum
tulang mengakibatkan maturasi inti relatif
lebih lambat dibanding sitoplasmanya.
Penyebab:
1. Defisiensi vit B12
2. Defisiensi asam folat
3. Metabolisme vit B12 dan asam folat yg
abnormal.
ANEMIA DEFISIENSI Vit B12 dan
folat
Vit B-12 dan asam folat merupakan
komponen penting dlm pembentukan DNA,
diperlukan dlm tahap penyediaan bahan
baku dan enzim untuk sintesis DNA.
Defisiensi B-12 dan folat akan menyebabkan
sintesis DNA menjadi abnormal, karena
pada saat yg sama produksi RNA berjalan
normal, sedang produksi DNA abnormal
maka pematangan inti dan sitoplasma mjd
tdk seimbang. Maturitas inti lambat maka
pembelahan sel tertunda sehingga ukuran
sel menjadi lebih besar dari normal
sehingga disebut megaloblast.
 Morfologi Darah Tepi Anemia
Megaloblastik

ERITROSIT
MAKROSITIK

HIPERSEGMENTASI
NETROFIL
ANEMIA DEFISIENSI Vit B12
ANEMIA PERNISIOSA
Suatu keadaan dimana absorbsi vit B-12
sangat menurun akibat kegagalan atau
penurunan faktor intrinsik sehingga terjadi
gangguan sintesis eritrosit.
Absorbsi vit B-12 di gastrointestinal
memerlukan beberapa faktor:
1. Vit B-12 harus dilepaskan dr makanan
oleh digesti peptik dlm lambung yg
diperantarai asam hidrokloride yg
dilepaskan oleh sel parietal lambung.
ANEMIA DEFISIENSI Vit B12
2. Faktor intrinsik yg disekresikan oleh sel
parietal, dimana faktor intrinsik
membentuk kompleks dg vit B-12
kemudian mentransportnya ke dalam
usus.
Morfologi sel darah merah menyerupai
anemia megaloblastik.
 KLASIFIKASI ANEMIA BERDASAR
MORFOLOGI ERITROSIT

Klasifikasi berdasarkan kandungan Hb dalam

eritrosit, ukuran eritrosit, angka eritrosit.
1. Anemia Normositik Normokromik
Warna dan ukuran eritrosit dalam batas
normal.
Terjadi pada: perdarahan akut, anemia
hemolitik, penyakit sumsum tulang,
penurunan pacuan eritropoietin (peny. Ginjal).
KLASIFIKASI ANEMIA BERDASAR
MORFOLOGI ERITROSIT (2)

2. Anemia Makrositik Normokromik

Terjadi pada: A. Megaloblatik, A.
Pernosiosa.
3. Anemia Mikrositik Hipokromik
Terjadi pada ADB (Anemia Defisiensi besi)
Metabolisme Asam Folat