pp darah 2009
DESCRIPTION
kuliahTRANSCRIPT
![Page 1: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/1.jpg)
BIOKIMIA LEUKOSIT DAN
TROMBOSIT
![Page 2: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/2.jpg)
LEKOSIT
Jumlah : 5000 – 10000 / mm3Terdiri dari :1. Fagosit : netrofil, eosinofil, basofil &
monosit2. Imunosit : limfosit
Umur : 9 hari- Mitosis & diferensiasi : 2 – 3 hari - Maturasi : 5 – 7 hari - Netrofil matur : 6-10 jam di sirkulasi
kmd keluar ke jaringan mati
![Page 3: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/3.jpg)
Granulopoesis
Granulopoiesis stimulasi hormonal oleh 2 gol cytokine (dihasilkan terutama oleh makrofag & sel T) :1. Interleukin2. Colony Stimulating factor (CSF)
![Page 4: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/4.jpg)
NETROFIL
Granula primer : Muncul pd tahap Promyelosit
Fungsi : Fagositosis Masa hidup di sirkulasi : 10 jam 40 – 70% lekosit Sitoplasma : kaya lisosom (mgd enzim2 degradatif) Phosphorilasi oxydative moderate, menghas NADPH pbtk
ROS* Sumber energi : glukosa; jalur glikolisis aerob & pentose-
phosphate
Granula sekunder (spesifik) : Muncul mulai tahap myelosit
*ROS Reactive Oxygen Species bakterisid
![Page 5: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/5.jpg)
Granula PrimerMyeloperoxidaseDefensinLysozyme ElastaseLainnya
BPICathepsin GAlkaline phosphataseProteinase 3-glucuronidase-fucosidasePhospholipases A2, C, D-mannosidase
Enzim2 Netrofil
Granula SekunderLactoferrin Lysozyme CollagenaseLainnya
GelatinaseVitamin B12-binding proteinCD11b/CD18, CD11c/CD18 (integrins)Complement receptor 3 (CR3)HistaminasePlasminogen activator
![Page 6: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/6.jpg)
Netrofil memiliki mekanisme oxidative & non-oxidative utk menghancurkan bakteri
mechanisms of killing
Sistem NADPH oxidase, kompleks enzim membran, mereduksi O2 mjd superoxide anion (02-), hydrogen peroxide (H2O2), & hydroxyl radical (OH) = Oxidative burst
Halida H2O-MPO katalisasi pbtk radikal hipoklorit (hypochlorous radical = HOCL.) dr H2O2 & Cl- membunuh bakteri dg cara halogenasi atai peroksidasi
![Page 7: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/7.jpg)
EOSINOFIL
Granula sitoplasma besar, tercat eosin (merah) isi enzim hidrolitik & basic protein
BASOFIL
1 – 3% Di sirkulasi 18 jam ke jar
trtm kulit & mukosa ( 6 hari)
Peran : - Fagositosis kompleks antigen- antibodi; - Respon alergi; - Pertahanan thd parasit; - Removal fibrin selama inflamasi
0 – 1% Isi granula : heparin
(antikoagulan) & histamin (vasodilator)
Di jaringan berdiferensiasi mjd mast cell
Mempunyai tempat ikatan dg IgE
Granula sitoplasma besar, tercat basofilik (biru tua), menutupi inti
![Page 8: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/8.jpg)
MONOSIT
Jumlah 2 – 8% Stlh dilepas dr sumsum tulang 20 – 40 jam
di sirkulasi keluar ke jaringan diferensiasi mjd MAKROFAG fungsi fagosit, umur bbrp bulan – tahun
Makrofag di jaringan mjd bagian dr sistem Retikuloendotelial (SRE) : - Hati sel Kupffer - Ginjal sel mesangial - Otak mikroglia - Kulit sel langerhans - Sumsum tulang, lien, paru
Makrofag juga berperan sbg Antigen Presenting Cell (APC)
3m
![Page 9: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/9.jpg)
Makrofag sbg Antigen-Presenting Cells (APC)
• B cells & macrophages, display antigens to T cells
(Major histocompatibility complex)
![Page 10: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/10.jpg)
LIMFOSIT
Merupakan sel yg kompeten sec imunologis, respon bersifat spesifik thd antigen tertentu
2 jenis : 1. Limfosit T imunitas seluler thd bakteri, virus, protozoa, jamur, transplantasi organ 2. Limfosit B Imunitas humoral, sintesis antibodi
Natural killer cells (NK cell) : menyerang sel asing (mikroorganisma, sel tumor) sec langsung
![Page 11: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/11.jpg)
trombosit
![Page 12: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/12.jpg)
HEMOSTASIS – KONTROL PERDARAHAN
Menghentikan perdarahan (kapiler & arteri kecil)(kapiler & arteri kecil)
Spasme vaskulerSpasme vaskulerPbtk sumbat trombositPbtk sumbat trombositKoagulasiKoagulasi
Sel endotel
Trauma Sumbat trombosit
FASE VASKULER FASE TROMBOSIT FASE KOAGULASI
![Page 13: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/13.jpg)
Yang memegang peran utama dlm Hemostasis :
1.1. Sel endotel Sel endotel integritas pembuluh integritas pembuluh darahdarah
2.2. Kualitas & kuantitas TrombositKualitas & kuantitas Trombositsumbat trombosit (Hemostasis primer)sumbat trombosit (Hemostasis primer)
3.3. Kaskade Koagulasi Fibrin Kaskade Koagulasi Fibrin (Hemostasis sekunder)(Hemostasis sekunder)
- Faktor koagulasi
- Inhibitor koagulasi
- Ion kalsium
4. Sistem fibrinolitik
![Page 14: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/14.jpg)
TROMBOPOESIS
![Page 15: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/15.jpg)
TROMBOSIT
150 – 450 x 103 / mm3 Diameter 2.5 u Umur : 7 – 10 hari Diproduksi di sumsum tulang melalui fragmentasi
sitoplasma megakariosit (1 megakariosit 4000 trombosit)
Produksi trombosit dikendalikan oleh mekanisme humoral yaitu hormon Trombopoietin
Trombopoietin disintesis oleh hati (>>>) & ginjal Fungsi : adhesi, sekresi, agregasi pembentukan
sumbat trombositRetikulum
Endoplasma
Trombosit
Eritrosit
Fragmentasi sitoplasma megakariosit mjd pecahan2 trombosit
Megakariosit
![Page 16: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/16.jpg)
STRUKTUR TROMBOSITSistem kanalikuler
terbuka
Mitochondria
Sistem tubular menyimpan kalsiumkalsium
Area Submembran mikrofilamen mbtk sitoskeleton elastisitas
Granula alfa :Granula alfa :- Protein adhesive- Faktor koagulasi- Cytokine- Growth factors- Fibrinogen
Granula Granula Densa :Densa :- ATP- ADP- 5-HT- Serotonin- Ca2+- Pyrophosphate
Reseptor glikoprotein (GPGP) di permukaan adhesi & agregasi (GP Ib/IX, IIb/IIIa)
Membran, dilapisi fosfolipidfosfolipid
(Energi dr fosforilasi oksidatif & glikolisis anaerob)
Granula glikogen
![Page 17: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/17.jpg)
TROMBOSIT (cont’d)
Stlh kontak dg matriks subendotel, trombosit mengalami 3 reaksi :1. Adhesi & perubahan bentukAdhesi & perubahan bentuk
- Trombosit menempel pd kolagen subendotel- Stimulasi oleh von Willebrand Factor (vWF) & reseptor
glycoprotein (GP Ib-IX/ Integrin)
Projeksi sitoplasma memudahkan kontak antar trombosit
![Page 18: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/18.jpg)
PEMBEKUAN DARAH (KOAGULASI)
• Merupakan sistem amplifikasi biologis
• Prokoagulan aktivasi oleh proteolisis faktor koagulasi aktif (bersifat enzim) mengaktifkan prokoagulan berikutnya
CASCADE KOAGULASI
Pembentukan fibrin
![Page 19: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/19.jpg)
Kaskade Koagulasi
dipicu oleh Faktor Jaringan yg dilepas oleh jaringan yg rusak
Va, Xa, Ca2+, PL , PF3Kompleks Protrombinase(Aktivator Protrombin)
VIIIa, IXa, Ca2+, PL Kompleks Tenase(Aktivator Faktor X)
dipicu oleh paparan kolagen
remain until a component is consumed
(PK, HMWK)
HMWK
activeVIII
Active VV
Ca2+, PL, PF3
![Page 20: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/20.jpg)
FibrinolisisKoagulasi
HEMOSTATIC BALANCE
TROMBOSIS PERDARAHAN
ATIIIClotting FactorsTissue factor*2-Antiplasmin
Fibrinolytic System
TM, Prot. C
PAI-1TFPI
Prot. S
PROCOAGULANT ANTICOAGULANT
![Page 21: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/21.jpg)
SISTEM FIBRINOLITIK
• Bekuan darah dilisiskan oleh Plasmin
– Berasal dr plasminogen (proenzim; tdk aktif)
• Koagulasi dpt dicegah dg pemberian antikoagulan atau obat2 fibrinolitik
– Antikoagulan (heparin, warfarin, hirudin)
– Obat fibrinolitik (t- PA, streptokinase & urokinase)
– Antiagregasi trombosit (Aspirin, inhibitor reseptor GP IIb-IIIa)
![Page 22: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/22.jpg)
HEMOFILIA
Defek genetik penurunan sintesis bbrp faktor koagulasi
Faktor VIII berkurang Hemofilia A Faktor IX berkurang Hemofilia B Faktor XI berkurang Hemofilia C Gejala : Gangguan pembekuan darah pasca
trauma - Hematoma- Hemartros- Perdarahan gusi- Perdarahan pasca cabut gigi- Perdarahan pasca sirkumsisi- Perdarahan gastrointestinal- Perdarahan otak
Terapi : substitusi faktor koagulasi cryopresipitat, konsentrat, FVII sintetis (DNA rekombinan)
![Page 23: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/23.jpg)
GANGGUAN KOAGULASI AKUISITA
• Peny Hati :
– Sintesis faktor koagulasi – Fibrinolisis – Trombositopenia
• Disseminated Intravascular Coagulation (DIC) :– Aktivasi koagulasi oleh suatu aktivator
– Komplikasi obstetri (IUFD, solusio plasenta), infeksi (sepsis), shock, keganasan, trauma berat
– Koagulasi >> faktor koagulasi & trombosit terkonsumsi perdarahan
– Clot organ2 iskemia, infark, failure
![Page 24: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/24.jpg)
![Page 25: PP Darah 2009](https://reader035.vdocuments.pub/reader035/viewer/2022062404/5529c1a3550346646e8b4593/html5/thumbnails/25.jpg)
“ Teachers open the door, but you must enter by yourself “