dr. Indriati Dwi Rahayu

dr. Indriati Dwi Rahayu

PENDAHULUAN SEL-SEL HEMATOPOIESIS



Umum - Special connective tissue •

Total volume: + 5 L, + 8 % body weight

•

Composition : √ plasma : tersebar unsur padat, protein, hormon √ unsur padat : blood cells

STAINING : Wright, Giemsa, Romanowsky, Leishman

~ Hematocrite

Composition of PLASMA

Formed elements : blood cells Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig 20.1

PENDAHULUAN SEL-SEL DARAH HEMATOPOIESIS

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sel2 DARAH RBC L E U C O C Y T E S

EOSINOPHYL BASOPHYL

NETROPHYL LYMPHOCYTE MONOCYTE

THROMBOCYTE

!

HARGA NORMAL FUNGSI STRUKTUR KORELASI KLINIS

KOMPONEN PADAT  45 % 1. Red Blood Cell = Erythrocyte - Normal value: 4 - 6 X 106 /μL - Life span : 120 hr  lien dan sum2 tulang - hematocrit : perkiraan volume eritrosit per unit volume darah. Harga normal : laki2 :40–50% ; wanita : 35–45%

- FUNGSI : * untuk transpor O2 (oleh Hemoglobin) * buffer asam-basa (oleh Hemoglobin) * katalisator reaksi ( dg enzym karbonik anhidrase) HEMOGLOBIN * Tdd 4 polipeptida, @ memiliki 1 Heme * Type (berdasar asam amino) 1. Hb A1 : 97 % 2. Hb A2 : 2 % 3. Hb F : 1 %. (pada neonatus 80%) 4. Hb S : abnormal dr Hb A  Sickle cell anemia

- STRUKTUR : * Ф : 7 – 8 μm, (sediaan segar lebih besar; warna kuning kehijauan) * bikonkaf ; bag tengah: central pallor * (matur) : inti dan organella (-) * Sitoplasma Isotonis; mengandung Hb

* Plasmalemma : tdd membran protein integral: Dalam  Spectrin Luar  Mengandung antigen * Bersifat fleksibel * Cenderung saling melekat  Rouleaux formation (hanya sementara)

- abnormalitas struktur: * Anisositosis : RBC dalam ukuran bervariasi * Poikilositosis : RBC bentuknya bervariasi

* Makrositer

: Ø > 9 µm

* Mikrositer

: Ø < 6 µm

* Cabot ring = Howell Jolly body : fragmen inti. (> 1 %) Pengecatan : Brilliant Cresyl Blue utk melihat sisa RER & ribosom pada retikulosit * Crenated : mengkerut. Karena suasana hipertonis * Spherocytosis : Spheroidal erythrocyte

KLINIS • Keluhan yg relevan : pucat • Anemia : Hb ↓ – may be caused by :  loss of blood (hemorrhage);  insufficient production of RBC by the bone marrow;  production of RBCs with insufficient hemoglobin, usually related to iron deficiency in the diet; or  accelerated destruction of blood cells. – Ex : Sickle cell anemia : The sickled erythrocyte is inflexible & fragile  shortened life span that leads to anemia. It increases the blood viscosity and can damage the walls of blood vessels, promoting blood coagulation. Blood flow through the capillaries is retarded or even stopped, leading to severe O2 shortage (anoxia) in tissues.

sel2 DARAH RBC


L E U C O C Y T E S

EOSINOPHYL

BASOPHYL NETROPHYL LYMPHOCYTE MONOCYTE

THROMBOCYTE

2. LEKOSIT - jumlah normal: 6000 – 10.000 / μL - dasar klasifikasi : ~ diameter ~ Bentuk inti ~ Ratio inti-sitoplasma ~ Pengecatan

• Karakteristik umum : - sel sejati  inti & organella [+] - gerak amuboid & diapedesis [+]

- berfungsi di jaringan ikat. Aliran darah hanya sebagai sarana transportasi - pada sediaan permanen ukuran lebih besar

- granul azurophilic, with lytic enzymes • klasifikasi dengan pengecatan khusus  diff.count (hitung jenis) • tipe utama : granulosit & agranulosit

- Granulosit, * = PMN (polymorpho nuclear) * organella: [matur] Inti berlobus, Golgi,mitokondria, free ribosom,RER * specific granules dan azurophilic granules; * TERDIRI DARI : Eosinofil, Basofil, dan Netrofil - Agranulosit * mononuclear ; unsegmented * granul azurophilic ONLY * TERDIRI DARI : Limfosit, Monosit

Keluhan yang relevan : - Infeksi

- Keganasan - Efek samping obat

Leukocytosis • An increase in the number of circulating leukocytes occurs as a normal protective reaction in a variety of pathological

conditions, especially in response to infections. • Pathological leukocytosis : leukocyte count more than 11 x 109/1 (11. 000/mm3)

• Drug involved : ex : corticosteroid, litium

Leukopenia the total blood leukocyte count : less than 4 x 109/1 (4000/mm3) Drug involved : ex : Minocycline, clozapine

Granulocytopenia (neutropenia) This is a general term used to indicate an abnormal reduction in the numbers of circulating granulocytes (polymorphonuclear leukocytes), commonly called neutropenia because 40 to 75% of granulocytes are neutrophils. A reduction in the number of circulating granulocytes occurs when production does not keep pace with the normal removal of cells


EOSINOPHYL

BASOPHYL

HARGA NORMAL FUNGSI

NETROPHYL

STRUKTUR KORELASI KLINIS

LYMPHOCYTE MONOCYTE

THROMBOCYTE

• Eosinofil : - % WBC : 1-4 % - Karakteristik : * >> di sirkulasi saat reaksi alergi & infeksi parasit * gerak diapedesis [+] * kemampuan fagositosis terbatas, t.u kompleks Ag-Ab * responsif dengan pemberian steroid ( = Thorn test)

STRUKTUR : • Φ : (sirkulasi) : 9 µm (jaringan) : 14 µm

-

Sitoplasma : * granul lebih besar, refraktil, uniform * granul mengandung lisozym khusus (peroxidase, acid

fosfatase, cathepsin, ribonuclease, Eosinophilic antiparasitic agent) + azurophilic • Inti :

- chromatin padat - p.u 2 lobus, sering tertutup granul

- Peran : * respon thd infeksi parasit * modulasi proses inflamasi * inaktivasi leukotrien & histamin

KLINIS : Eosinophilia : associated with allergic reactions and helminthic (parasitic) infections. Corticosteroids can produce a rapid decrease in the number of blood eosinophils, probably by interfering with

their release from the bone marrow into the bloodstream

Eosinopenia  sepsis marker (?)


EOSINOPHYL

BASOPHYL

HARGA NORMAL FUNGSI

NETROPHYL


LYMPHOCYTE MONOCYTE

THROMBOCYTE

• Basofil : - % WBC : 0-1 % - karakteristik :

* mirip mast cell, kecuali ultrastrukturnya * kemampuan gerak amuboid & fagositosis terbatas

- Peran :  dalam reaksi immediate hipersensitivity;

 menghasilkan mediator radang

- Struktur : * Φ :10-12 µm (lbh kecil dr netrofil) * Sitoplasma : - kurang padat - ukuran granul bervariasi, granul spesifik gelap

- Granul mengandung heparin, histamin * Inti : chromatin padat, lebih pucat

p.u 3 lobus, bentuk S, sering tertutup granul

KLINIS cutaneus basophil hypersensitivity : penumpukan extravaskular karena inflamasi


EOSINOPHYL

BASOPHYL

HARGA NORMAL FUNGSI

NETROPHYL


LYMPHOCYTE MONOCYTE

THROMBOCYTE

Netrofil : - dominan, 60-70 %

- tidak dapat mitosis - peran : first line pertahanan seluler : Fagositosis

- karakteristik : > gerak amuboid  keluar pembuluh darah  ~ makrofag aktif = microphage > kemampuan mitosis [-] > 2 macam granule ( specific & azurophilic) > klasifikasi (menurut Schiling) : ~ Netrofil segmented (57 %) Meningkat : shift to the right

- Netrofil nonsegmented (stab) (4%) Meningkat : shift to the left

STRUKTUR • Φ : (sirkulasi) : 12 µm (jaringan) : 20 µm

• Sitoplasma : - warna : salmon-pink - Granul spesifik : Alkaline phosphatase, lysozym, Laktoferin kolagenase, protein antibacterial nonenzimatik (ex; Phagocytin) - Granul Azurofilik : Acid phosphatase, myeloperoxidase, protein antibakterial kationik, dll - >> glikogen

Inti : • chromatin padat

• multilobus • macam : * hipersegmented ( >5 )  tua * segmented * stab • [wanita] drumstick=Barr body, mrpkn kromosom X inaktif (menempel pada inti)

KLINIS : An increased number of band neutrophils in the blood indicates a higher production of neutrophils, probably in response to a bacterial infection. ( Immature neutrophils that have recently entered the blood circulation have a nonsegmented nucleus in the shape of a horseshoe (band forms))

RBC EOSINOFIL BASOFIL NETROFIL

LIMFOSIT MONOSIT TROMBOSIT


Limfosit :  % wbc :20 – 25 %  di luar pembuluh darah :

organ limfatik & jaringan ikat

 Dapat berRESIRKULASI  terbagi dalam 2 kelas : limfosit T (most) & B

 Peran : sesuai jenis sel. sel T : berperan dalam immunitas seluler sel B : berperan dalam immunitas humoral; berdiferensiasi menjadi Sel Plasma;  menghasilkan Imunoglobulin  ! TIDAK DAPAT FAGOSITOSIS

 Struktur : * Φ: Kecil 6 – 8 µm Med-besar :8-18 µm * Sitoplasma : [kecil] :dekat inti tipis, basofil pucat, warna biru kehijauan >> ribosom; Organella lain << (tidak khas) [med-besar] : lebih banyak, (lain sama)

 Inti : [kecil] : - Bulat / pipih, dengan indentasi 1 sisi

- heterochromatis padat - warna : biru s/d hitam- keunguan [med-besar] : lebih besar kurang heterocromatis warna : ungu kemerahan

CLINICAL CORRELATION AIDS • HIV-infected adolescents and adults categorizes persons on the basis of clinical conditions associated with HIV infection and CD4+ T lymphocyte counts

SEVERE COMBINED IMMUNODEFICIENCY • The SCID syndrome is characterized by gross functional impairment of both humoral and cell-mediated immunity and by susceptibility to devastating fungal, bacterial, and viral infections




Monosit (large mononuclear leucocyte) : - % WBC : 3 – 8 % - Karakteristik :

hanya di darah Di luar sirkulasi  fagositosis kemampuan resirkulasi [-]

gerak pseudopodia seperti octopus, dg inti di

depan

- Peran : • Generation of mononuclear-phagocyte system cells in tissues; • phagocytosis and digestion of protozoa and virus and senescent cells

The monocyte-macrophage system consists of the body's complement of monocytes and macrophages. Some macrophages are mobile whereas others are fixed. These include: • histiocytes in connective tissues • microglia in the brain • Kupffer cells in the liver • alveolar macrophages in the lungs • sinus-lining macrophages (reticular cells) in the spleen, lymph nodes and thymus gland • mesangial cells in the glomerulus of nephrons in the kidney • osteoclasts in bone.

Struktur : - Φ: (sirkulasi) : 12-15 µm (jaringan) : 20 µm -Sitoplasma : * warna biru keabu-abuan * >> granul azurofilik * >> mitokondria & golgi & RER

* Ribosom bebas << - Inti : * p.u bentuk ginjal, eksentris * lebih pucat (kromatin lebih halus)

* 2-3 nucleoli * Warna : ungu kemerahan

CLINICAL CORRELATION • Monocytopenia occurs with acute infections, with stress, and after treatment with glucocorticoids. Monocytopenia also occurs in aplastic anemia, hairy cell leukemia, acute myeloid leukemia, and as a direct result of myelotoxic drugs. • Monocytosis is associated with tuberculosis, brucellosis, subacute bacterial endocarditis, Rocky Mountain spotted fever, malaria, and visceral leishmaniasis (kala azar). Monocytosis also occurs with malignancies, leukemias, myeloproliferative syndromes, hemolytic anemias, chronic idiopathic neutropenias, and granulomatous diseases such as sarcoidosis, regional enteritis, and some collagen vascular diseases.




PLATELET (thrombocyte=thromboplastid) - berasal dr ―budding’ megakariosit di sumsum tulang - Σ Normal : 200.000-400.000/Μl, lifespan : 8 hari

- Fungsi : CLOT FORMATION • Primary aggregation—Discontinuities in the endothelium,  platelet aggregation  platelet plug

• Secondary aggregation—Platelets in the plug release an adhesive glycoprotein and ADP.  increasing the size of the platelet plug. • Blood coagulation -- cascade, giving rise to a polymer, fibrin  thrombus.

- Struktur : 

Ø : 2-5 μm; dalam sediaan nampak berkelompok



Bentuk seperti cakram, biconvex



pd sediaan segar : tidak berwarna



permukaan membran : Glycocalyx untuk adhesi



tepi : hyalomere,warna biru pucat. Terdapat marginal bundle



central : dense granulomere, Terdapat mitokhondria, granul glikogen, dan granul2 warna ungu. Jenis granul : δ, α, λ

CLINICAL CORRELATION THROMBOCYTOPENIA This is defined as a blood platelet count below 150 x 109/1 (150 000/mm3) but spontaneous capillary bleeding does not usually occur unless the count falls below 30 x 109/1 (30 000/mm3). Thrombocytopenia results from one or more of three processes: (1) decreased bone marrow production; (2) sequestration, usually in an enlarged spleen; and/or (3) increased platelet destruction. Disorders of production may be either inherited or acquired.

THROMBOCYTOSIS Thrombocytosis is almost always due to (1) iron deficiency; (2) inflammation, cancer, or infection (reactive thrombocytosis); or (3) an underlying myeloproliferative process [essential thrombocythemia or polycythemia vera or, rarely, the 5q-myelodysplastic process

Cells Eosinofil Netrofil

Level UP Down

Terminology

Limfosit

UP down

Eosinophilia Netropenia (AGRANULOCYTOSIS) NEUTROPHILIC LEUKOCYTOSIS Lymphocytosis Lymphopenia

Monosit

UP down

Monocytosis Monocytopenia

UP

Example Parasitic infection typhoid fever

TBC infeksi akut, stres, dan setelah pengobatan dengan glukokortikoid

Bacterial infections viral infections, malignancies complication of corticosteroid therapy immunodeficiency states

Agranucytosis Trombosit

RBC ALL

UP

thrombosytosis

(1) kekurangan zat besi, (2) peradangan, kanker, atau infeksi (trombositosis reaktif)

down

thrombocytopenia

DHF

UP

Erythrocytosis

Hct ↑

down

anemia

>>>>>

down

Pancytopenia = Aplastic anemia

• MCV : mean cell volume, is a measure of the average red blood cell volume • MCH : mean cell hemoglobin, is the average mass

of hemoglobin per red blood cell in a sample of blood • MCHC : mean corpuscular hemoglobin concentration, a measure of the concentration of hemoglobin in a given volume of packed red blood cells

• RDW : red blood cell distribution width. measure of the variation of red blood cell (RBC) volume • LED = laju endap darah

PENDAHULUAN SEL-SEL HEMATOPOIESIS

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HEMATOPOIESIS = proses sintesa sel2 darah Terdiri dari proliferasi dan differensiasi sel2 induk

hematopoiesis

Tahap : Sel induk pluripotensial  Sel induk (stem cell)  sel progenitor (CFU)  sel prekursor (blast)  sel matur

Sel Induk Hematoipoiesis pluripotensial • derivat mesoderm, undifferentiated

• Bersifat mitosis aktif • Bersifat pluripotent • dapat membelah berulang, & selanjutnya differensiasi menjadi sel2 darah matur

• Berproliferasi, membentuk 2 jalur diferensiasi (2 stem cell): * Jalur Myeloid  RBC, granulosit, monosit, Platelet ~ erythropoiesis ~ granulopiesis

~ monopiesis ~ thrombopiesis * Jalur lymphoid  limfosit dan sel plasma

Colony forming cell: (~ sel progenitor) - = sel pembentuk koloni

- sebagai pembentuk koloni2 tipe2 sel darah tertentu - differensiasi menjadi sel induk unipoten ( ex : ECFC membentuk RBC, LCFC membentuk limfosit, dst)

Jalur Myeloid

Jalur lymphoid

Available at @

Available @ : indri.lecture.ub.ac.id anatomi.lecture.ub.ac.id

dr. Indriati Dwi Rahayu

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