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

Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig 20.1

Composition of PLASMA

Formed

elements :

blood cells

PENDAHULUAN

SEL-SEL DARAH

HEMATOPOIESIS

RBC

EOSINOPHYL

BASOPHYL

NETROPHYL

LYMPHOCYTE

MONOCYTE

THROMBOCYTE

L

E

U

C

O

C

Y

T

E

S

sel2 DARAH

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

Anemia : Hb ↓

may be caused by :

– loss of blood (hemorrhage);

– insufficient production of erythrocytes by the bone marrow;

– production of erythrocytes 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 and fragile and has a 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.

RBC

EOSINOPHYL

BASOPHYL

NETROPHYL

LYMPHOCYTE

MONOCYTE

THROMBOCYTE

L

E

U

C

O

C

Y

T

E

S

sel2 DARAH

HARGA NORMAL

FUNGSI

STRUKTUR

KORELASI

KLINIS

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, da Netrofil

- Agranulosit

* mononuclear ; unsegmented

* granul azurophilic ONLY

* TERDIRI DARI : Limfosit, Monosit

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)

Leukopenia

the total blood leukocyte count : less than 4 x 109/1 (4000/mm3).

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 or when the life

RBC

EOSINOPHYL

BASOPHYL

NETROPHYL

LYMPHOCYTE

MONOCYTE

THROMBOCYTE

L

E

U

C

O

C

Y

T

E

S

sel2 DARAH

HARGA NORMAL

FUNGSI

STRUKTUR

KORELASI

KLINIS

• 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

RBC

EOSINOPHYL

BASOPHYL

NETROPHYL

LYMPHOCYTE

MONOCYTE

THROMBOCYTE

L

E

U

C

O

C

Y

T

E

S

sel2 DARAH

HARGA NORMAL

FUNGSI

STRUKTUR

KORELASI

KLINIS

• 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

RBC

EOSINOPHYL

BASOPHYL

NETROPHYL

LYMPHOCYTE

MONOCYTE

THROMBOCYTE

L

E

U

C

O

C

Y

T

E

S

sel2 DARAH

HARGA NORMAL

FUNGSI

STRUKTUR

KORELASI

KLINIS

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 non-

enzimatik (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

HARGA NORMAL

FUNGSI

STRUKTUR

KORELASI

KLINIS

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

RBC

EOSINOFIL

BASOFIL

NETROFIL

LIMFOSIT

MONOSIT

TROMBOSIT

HARGA NORMAL

FUNGSI

STRUKTUR

KORELASI

KLINIS

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.

RBC

EOSINOFIL

BASOFIL

NETROFIL

LIMFOSIT

MONOSIT

TROMBOSIT

HARGA NORMAL

FUNGSI

STRUKTUR

KORELASI

KLINIS

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 Level Terminology Example

Eosinofil UP Eosinophilia Parasitic infection

Netrofil Down Netropenia

(AGRANULOCYTOSIS)

typhoid fever

UP NEUTROPHILIC

LEUKOCYTOSIS

Bacterial infections

Limfosit UP Lymphocytosis viral infections, malignancies

down Lymphopenia complication of corticosteroid therapy

immunodeficiency states

Monosit UP Monocytosis TBC

down Monocytopenia infeksi akut, stres, dan setelah pengobatan

dengan glukokortikoid

Agranucytosis

Trombosit UP thrombosytosis (1) kekurangan zat besi, (2) peradangan,

kanker, atau infeksi (trombositosis reaktif)

down thrombocytopenia DHF

RBC UP Erythrocytosis Hct ↑

down anemia >>>>>

ALL 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

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 @

Anatomi FKUB

TERIMA KASIH