BLOK HEMATOLOGI
Destruksi eritrosit tua, Besi Heme hrs tetap berada Sintesis Hemoglobin :
di SRE dlm bentuk Fe2+ - Heme
- Globin
Methemoglobin Reductase,
- Tetrapirol Bilirubin Defek Sintesis Heme
- Fe & Globin reutilisasi koensim NADH (dr EMP)
Defek Sintesis Globin
(Kualitatif & Kuantitatif)
Genetik : HbM
Akuisita : Oksidan
Copyright 2004, Medicine School of Shandong University HEMOGLOBINOPATHY
GSSG Oxidized Glutathione GSH Reduced Glutathione
Karakteristik struktur, isi & sifat
metabolisme eritrosit mendukung
fungsinya yaitu utk transport gas, ERITROSIT
yaitu mengangkut O2 dari paru ke
jaringan dan mengangkut CO2
dari jaringan ke paru
Cakram bikonkaf luas
permukaan relatif lebih besar
dibandingkan volume sel
Kandungan eritrosit : > 97%
volume adalah hemoglobin
(viskositas rendah
deformabilitas sel)
ATP dihasilkan secara anaerob,
shg eritrosit tidak
mengkonsumsi oksigen yg
diangkutnya
Copyright 2004, Medicine School of Shandong University
Eritrosit manusia tidak berinti
Kasus: SCA
Definisi: Eritrosit
yang memanjang
dan melengkung
dengan dua kutup
yang runcing.
Distribusi dalam
darah: normal tidak
ada
Perbesaran: 1000 x
Akibat:
Anemi sel sabit
Keuntungan: kebal
terhadap Malaria
Membran Eritrosit
Bersifat semipermeabel
Hidrofilik
Hidrofobik
Hidrofilik
STRUKTUR MEMBRAN
Mosaic
o > 50 jenis protein membran membentuk pola anyaman
asimetris di bagian dalam & luar membran
o Protein perifer dan protein integral (hidrofilik di luar,
hidrofobik di dalam)
Copyright 2004, Medicine School of Shandong University
LIPID BILAYER
Fosfolipid & glikolipid dg gugus polar hidrofilik di
permukaan eksternal & internal, gugus non polar
hidrofobik di tengah membran membran sbg
liquid sealer
A red cell in a low salt A red cell in a A red cell in a high salt
solution will swell and burst physiological salt solution will shrivel as water
as water flows into the more solution has normal flows out into the more
concentrated solution inside shape concentrated surrounding
the cell Copyright 2004, Medicine School of Shandong University solution
Jalur metabolisme utama eritrosit
Eritrosit memerlukan energi utk :
Mempertahankan deformabilitas & elastisitas membran
Rx2 enzimatik pembentukan ATP, mempertahankan besi dlm
keadaan tereduksi (Fe2+)
Transport ion Na, K, Ca keseimbangan osmotik intrasel
Jalur Pentose-
Phosphate/ Hexose- Juga dihasilkan NADPH
Monophosphate (HMP) G6PD mereduksi NADP (nicotinamide-adenine-
Shunt dinucleotide phosphate) mjd NADPH NADPH
mereduksi oxidized glutathione (GSSG) mjd btk
tereduksi (GSH) melindungi membran eritrosit &
Hb dr stress oksidatif
Anemia hemolitik
herediter
Pyruvate- - and -
Hereditary Hereditary G6PD
Spherocytosis Elliptocytosis
Ovalocytosis
Deficiency Kinase MetHbnemia Abnormal Hb thalassaemi
deficiency (Hb S, C, D, as
E, etc.)
Non
Immune immune
Autoimmune Alloimmune
(Warm type, (Transfusion Infection- Mechanical Miscelaneous
Drug-induced
Cold type, Reaction, induced trauma causes
PCH) HDN)
1) Hereditary
spherocytosis
(HS)
2) Hereditary
elliptocytosis
(HE)
Copyright 2004, Medicine School of Shandong University
HS HE
Merupakan kelainan genetik autosomal dominan,
Definisi ditandai dg defek membran eritrosit, mengakibatkan
membran menjadi kurang deformable dan mudah
pecah.
Eritrosit berukuran
lebih kecil, lebih bulat Eritrosit berbentuk elips
Morfologi
(tidak bikonkaf)
Lebih fragil
Episode hemolitik
ekstravaskuler akut
HMP Shunt mrpk satu2nya
stlh paparan oksidan,
penghasil NADPH utk eritrosit
tbtk Heinz bodies
Copyright 2004, Medicine School of Shandong University
ASPEK KLINIS : defek enzim eritrosit
Glycolysis- generates 90% of the required ATP- the
breakdown of 1 glucose generates 2 ATP and 2
NADH.
5 - 10% of the glucose is metabolized by Hexose
monophosphate shunt (pentose phosphate shunt).
It produces NADPH and GSH which protect the RBC
from oxidative injury.
If the concentrations of these are too low, the
globin will denature and precipitate in the cell.
This is seen as Heinz bodies which attach to the
membrane causing membrane damage and RBC
destruction.
Copyright 2004, Medicine School of Shandong University
ASPEK KLINIS : defek enzim eritrosit
Defek pada Jalur Reduksi Methemoglobin
Normal : Selama fase deoksigenasi Hb 1 3% Hb
teroksidasi mjd MetHb tiap hari direduksi kembali oleh enzim
Methemoglobin reduktase (MetHb reduction pathway)
Oksidasi Fe2+ mjd Fe3+ pbtk Methemoglobin tidak mampu mengikat O2
(left : without hemolysis) red blood cell suspension (0.5% sheep RBCs in saline), seems red and
opaque.
(middle : without hemolysis) RBCs sedimented spontaneously for 60 min. Note that the supernatant is
not colored.
(right : hemolysis) RBC suspension treated with the hemolysin of S. pyogenes at 37C for 30 min,
become transparent by hemolysis.
Copyright 2004, Medicine School of Shandong University
When there is a decrease in the surface
area to the cell volume, as in the
spherocyte, the osmotic fragility is
increased. The resistance of such cells
to hypotonic solutions is decreased.
In cells as the fragmentosit and target
cell, where the surface area relationship
to the volume of the cell is increased
over that typified in the normal
erythrocyte, then there is an increased
resistance to hypotonic solutions. Such
cells have a decreased osmotic fragility.
Copyright 2004, Medicine School of Shandong University
Tube mLs mLs NaCl Conc.
1.0% distilled (%)
NaCl water
1 0.0 10.0 0 Hemolisis total
2 9.0 1.0 0.2 Hemolisis total
3 8.0 2.0 0.4 Hemolisis sebagian
4 7.5 2.5 0.5 Tidak terjadi hemolisis
5 7.0 3.0 0.6 Tidak terjadi hemolisis
6 6.5 3.5 0.7 Tidak terjadi hemolisis
7 6.0 4.0 0.8 Tidak terjadi hemolisis
8 5.5 4.5 0.9 Tidak terjadi hemolisis
(isotonis)
9 5.0 5.0 1.0 Krenasi
10 4.5 5.5 1.0 Krenasi
Copyright 2004, Medicine School of Shandong University
Test Fragilitas
Osmotik Eritrosit
(Osmotic Fragility
Test)
100
80
% Hemolysis
60
40
20
0
0,3 0,4 0,5 0,6
NaCl (% of normal saline)
Normal HS
Copyright 2004, Medicine School of Shandong University
EXPOSURE TO CHEMICAL SOLVENTS
Exposure measurements in combination with analysis of
haematological parameters may be a tool for early
detection of cellular changes in the blood caused by
exposure to solvents, before the appearance of clinical
symptoms.
Hiperkalsemia
Depresi sistem syaraf, reflex
Kelemahan otot
Ggn motilitas usus, konstipasi
Pembentukan kristal kalsium fosfat
Copyright 2004, Medicine School of Shandong University
Koreksi kadar Calcium
Perubahan kadar albumin 1 gram/dL
perubahan kadar kalsium serum 0.8 mg/dL
Kadar albumin serum normal 3.5 - 5.0 g/dl
Bila tidak misdiagnosis hiperkalsemia