dr. Indriati Dwi Rahayu, M -...
Transcript of dr. Indriati Dwi Rahayu, M -...
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dr. Indriati Dwi Rahayu, M.Kes
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PENDAHULUAN
SEL-SEL
HEMATOPOIESIS
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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
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Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Composition of PLASMA
Formed
elements :
blood cells
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PLASMA
+55 % blood, homogen
Komposisi:
• +90 % water
• +10 % zat terlarut :
Garam anorganik : 0.9 %. Ex : Na, K, Ca
Zat organik : 2,1 %. Ex : As.amino, glukosa,
peptida, hormon, lipid
Protein plasma : 7 %. Ex; Albumin, Globulin
(α,β,γ) Fibrinogen, prothrombin
• The composition of plasma is usually an indicator of
the mean composition of the extracellular fluids in
general
KOMPONEN PADAT + 45 % : sel2 DARAH
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Blood products vs Protein Pharmacueticals
Ex :
• Factor VIII (for blood clotting-hemophilia)
• Factor IX (for blood clotting-hemophilia)
• Albumin (osmotic balance-kidney disease)
• Anti-thrombin III (for blood clotting)
What‘s next?
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The Problem with Proteins
(in vivo)
• Elimination by B and T cells
• Proteolysis by endo/exo peptidases
• Unwanted allergic reactions may develop (even
toxicity)
• Small proteins (<30 kD) filtered out by the kidneys
very quickly
• Loss due to insolubility/adsorption
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PENDAHULUAN
SEL-SEL DARAH
HEMATOPOIESIS
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RBC
EOSINOPHIL
BASOPHIL
NETROPHIL
LYMPHOCYTE
MONOCYTE
THROMBOCYTE
L
E
U
C
O
C
Y
T
E
S
sel2 DARAH
HARGA NORMAL
FUNGSI
STRUKTUR
KORELASI
KLINIS
!
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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%
- Populasi terbesar dalam darah
- Banyak memetabolisir obat
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- FUNGSI :
* untuk transpor O2 (oleh Hemoglobin)
* buffer asam-basa (oleh Hemoglobin)
* katalisator reaksi ( dg enzym karbonik anhidrase)
HEMOGLOBIN
** 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
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- STRUKTUR :
* Ф : 7 – 8 μm, (sediaan segar lebih besar; warna kuning
kehijauan)
* bikonkaf ; bag tengah: central pallor
* (matur) : inti dan organella (-)
* Bersifat fleksibel
* Cenderung saling melekat Rouleaux formation
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* Sitoplasma Isotonis; mengandung Hb. pH : 7,1 – 7,3
* Plasmalemma : tdd membran protein integral.
Mengandung reseptor2, carrier2, anzym2.
Dalam Spectrin
Luar Mengandung antigen
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- abnormalitas struktur:
* Anisositosis : RBC dalam ukuran bervariasi
* Makrositer : Ø > 9 µm
* Mikrositer : Ø < 6 µm
* Cabot ring = Howell Jolly body : fragmen inti. (> 1 %)
* Shadow/Ghost blood : pucat, bulat. Karena hemolisis.
* Crenated : mengkerut. Karena suasana hipertonis
* Spherocytosis : Spheroidal erythrocyte
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ASPEK FARMASI
- RBC sbg populasi terbesar
- Hb : dapat berinteraksi dg small diffussible ligands
terlibat dalam kontrol tekanan darah
- Banyak enzym dalam RBC dapat memetabolisme
berbagai jenis obat
- Bindingsite obat utama : Hb, protein, membran plasma
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RBC
EOSINOPHIL
BASOPHIL
NETROPHIL
LYMPHOCYTE
MONOCYTE
THROMBOCYTE
L
E
U
C
O
C
Y
T
E
S
sel2 DARAH
HARGA NORMAL
FUNGSI
STRUKTUR
KORELASI
KLINIS
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2. LEKOSIT
- jumlah normal: 6000 – 10.000 / μL
- dasar klasifikasi :
~ diameter
~ Bentuk inti
~ Ratio inti-sitoplasma
~ Pengecatan
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• Karakteristik umum :
- sel sejati inti & organella [+]
- gerak amuboid & diapedesis [+]
- berfungsi di jaringan ikat. Aliran darah hanya sebagai
sarana transportasi
• klasifikasi dengan pengecatan khusus diff.count
(hitung jenis)
• tipe utama : granulosit & agranulosit
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- Granulosit,
* = PMN (polymorpho nuclear)
* organella: [matur] Inti berlobus,
* TERDIRI DARI : Eosinofil, Basofil, da Netrofil
- Agranulosit
* mononuclear ; unsegmented
* TERDIRI DARI : Limfosit, Monosit
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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
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RBC
EOSINOPHIL
BASOPHIL
NETROPHIL
LYMPHOCYTE
MONOCYTE
THROMBOCYTE
L
E
U
C
O
C
Y
T
E
S
sel2 DARAH
HARGA NORMAL
FUNGSI
STRUKTUR
KORELASI
KLINIS
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• 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)
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STRUKTUR :
• Inti :
- chromatin padat
- p.u 2 lobus, sering tertutup granul
Peran :
* respon thd infeksi parasit
* modulasi proses inflamasi
* inaktivasi leukotrien & histamin
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RBC
EOSINOPHIL
BASOPHIL
NETROPHIL
LYMPHOCYTE
MONOCYTE
THROMBOCYTE
L
E
U
C
O
C
Y
T
E
S
sel2 DARAH
HARGA NORMAL
FUNGSI
STRUKTUR
KORELASI
KLINIS
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• Basofil :
- % WBC : 0-1 %
- karakteristik :
* kemampuan gerak amuboid & fagositosis terbatas
- Peran :
Memiliki reseptor Ig E dalam reaksi immediate
hipersensitivity;
menghasilkan mediator radang
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- Struktur :
* Φ :10-12 µm (lbh kecil dr netrofil)
* Sitoplasma :
- Granul mengandung heparin, histamin
* Inti :
p.u 3 lobus, bentuk S, sering tertutup granul
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RBC
EOSINOPHIL
BASOPHIL
NETROPHIL
LYMPHOCYTE
MONOCYTE
THROMBOCYTE
L
E
U
C
O
C
Y
T
E
S
sel2 DARAH
HARGA NORMAL
FUNGSI
STRUKTUR
KORELASI
KLINIS
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Netrofil :
- dominan, 60-70 %
- tidak dapat mitosis
- peran : first line pertahanan seluler : Fagositosis
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- karakteristik :
> gerak amuboid keluar pembuluh darah
~ makrofag aktif = microphage
> kemampuan mitosis [-]
> klasifikasi (menurut Schiling) :
~ Netrofil segmented (57 %)
Meningkat : shift to the right
- Netrofil nonsegmented (stab) (4%)
Meningkat : shift to the left
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STRUKTUR
• Φ : (sirkulasi) : 12 µm
(jaringan) : 20 µm
Inti :
• multilobus
• macam :
* hipersegmented ( >5 ) tua
* segmented
* stab
• [wanita] drumstick=Barr body,
mrpkn kromosom X inaktif
(menempel pada inti)
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RBC
EOSINOFIL
BASOFIL
NETROFIL
LIMFOSIT
MONOSIT
TROMBOSIT
HARGA NORMAL
FUNGSI
STRUKTUR
KORELASI
KLINIS
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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
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RBC
EOSINOFIL
BASOFIL
NETROFIL
LIMFOSIT
MONOSIT
TROMBOSIT
HARGA NORMAL
FUNGSI
STRUKTUR
KORELASI
KLINIS
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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 :
• mononuclear-phagocyte system cells in tissues;
• Phagocytosis
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The monocyte-macrophage system
tdd
• 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.
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Struktur :
- Φ: (sirkulasi) : 12-15 µm (jaringan) : 20 µm
-Sitoplasma : * warna biru keabu-abuan
- Inti : * p.u bentuk ginjal, eksentris
* Warna : ungu kemerahan
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RBC
EOSINOFIL
BASOFIL
NETROFIL
LIMFOSIT
MONOSIT
TROMBOSIT
HARGA NORMAL
FUNGSI
STRUKTUR
KORELASI
KLINIS
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PLATELET (thrombocyte=thromboplastid)
- Σ Normal : 200.000-400.000/Μl, lifespan : 8 hari
- Struktur :
Ø : 2-5 μm; dalam sediaan nampak berkelompok
Bentuk seperti cakram, biconvex
permukaan membran : Glycocalyx untuk adhesi
- Fungsi : CLOT FORMATION
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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.
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43
Blood
disorders
Infection
Bacteremia
Viremia
Septicemia
Puerperal fever
Malaria
Hemolytic anemia
Tumors
Leukemia
Myeloid
Lymphoid
Nutritional disorders
Iron deficiency anemia
Iron loading
Pernicious anemia
Vit K deficiency
Congenital disorders:
Thallasemias
Sickle cell anemia
Hemophilia
Trauma
Hemorrhagic
anemia
Aplastic anemia
Secondary disorders
Urinary system:
Erythrocytosis
Immune problems:
Hemolytic disease
of the newborn Degenerative disorders:
Excessive
coagulation
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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
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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 sel prekursor (blast) sel matur
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Sel Induk Hematoipoiesis pluripotensial
• derivat mesoderm, undifferentiated
• Bersifat mitosis aktif
• Bersifat pluripotent
• dapat membelah berulang, & selanjutnya
differensiasi menjadi sel2 darah matur
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• Berproliferasi, membentuk 2 jalur diferensiasi (2 stem
cell):
* Jalur Myeloid RBC, granulosit, monosit, Platelet
~ erythropoiesis
~ granulopiesis
~ monopoiesis
~ thrombopiesis
* Jalur lymphoid limfosit dan sel plasma
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Jalur Myeloid Jalur lymphoid
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Drug-induced Hematologic disorder
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Further readings :
Drug-Induced Hematologic Syndromes
DavidM.Mintzer, Shira N. Billet, and Lauren Chmielewski.
Adv Hematol. 2009;2009:495863.
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dr. Indriati Dwi Rahayu,M.Kes
Lab.Anatomi-Histologi FKUB
(SYSTEMA LYMPHOPOIETICA)
Pharmacist
edition
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Drainage cairan jaringan fluid balance
Mengangkut sel-imun & produknya, debris, benda asing
(ex : obat), lemak (dan material larut lemak)
Perlindungan dr pengaruh buruk materi asing yang
masuk
Sintesa limfosit & penghancuran antigen
– menunjang proliferasi & pemrograman prekursor
limfosit T [timus]
– menyaring limfe & pembentukan antibodi [limfonodus,
lien]
FUNGSI SISTEM LIMFATIK
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SISTEM IMUN
• NON SPESIFIK
– Fisik : kulit, mukosa, batuk, dll
– ‗Larut‘ : - Biokimia
- Sistem imun Humoral : komplemen, interferon
– Selular : Fagosit : MN, PMN,
NK cell
• SPESIFIK :
– Humoral : Sel B Antibodi
– Selular : Sel T
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SISTEM LIMFATIK terdiri dari :
(1) sistem pembuluh;
anyaman kapiler dari
berbagai organ dan
jaringan pembuluh limfe
vena besar
(2) Cairan limfe
(3) kelenjar limfe / limfoid
organ
tersusun atas sel-sel
limfatik
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Organisasi
sistem Limfatik
: Sel2 limfatik
: Struktur limfatik
: Organ limfatik
: Pembuluh limfatik (dgn cairan limfe di dalamnya)
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: Sel2 limfatik
: Struktur limfatik
: Organ limfatik
: Pembuluh limfatik (dgn cairan limfe di dalamnya)
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: Sel2 limfatik
: Struktur limfatik
: Organ limfatik
: Pembuluh limfatik
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SEL2 SISTEM LIMFATIK (outside the circulation)
Limfosit
NK cell
APC
Makrofag
Sel Plasma
Sel Retikuler
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Limfosit
• = sel mayoritas dalam sistem limfe
• dapat mengenali & memberi respon thd sel dan
substansi asing
• tidak dapat fagositosis
• Secara umum terdapat 2 jenis :
- Limfosit T (T-lymphocytes / T cell)
- Limfosit B (B-lymphocytes / B cell)
• klasifikasi berdasar komposisi permukaan sel &
reaksi thd Antigen
Limfosit NK cell APC Makrofag Sel Plasma Sel Retikuler
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Lymphocytes of Lymphoid
Organ
(T-cell (%) : B-cell (%))
Thymus
100 0
Bone Marrow
10 90
Spleen
45 55
Lymph Nodes
60 40
Blood
80 20
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T cell
• penanggungjawab imunitas seluler
• membawa reseptor Ag di permukaan reseptor
• memerlukan bantuan makrofag atau APC lain untuk respon optimal
• untuk aktivasi diperlukan kompleks Ag-MHC
• Sel Efektor :
* T-helper
* T-cytotoxic
* Supressor T-cell
Sel-sel organ limfatik
Limfosit NK cell APC Makrofag Sel Plasma Sel Retikuler
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B Lymphocytes (B cell)
• Penanggung jawab imun humoral
• punya Antigen di permukaan,
membawa Immunoglobulin(Ig) M & D
di membran
• perlu bantuan T-helper (CD4+) untuk
bereaksi thd Antigen
• Sel daughter :
- Plasma cell
- Memory cell
Sel-sel organ limfatik
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Sel Plasma
• merupakan hasil differensiasi sel B
efektor
• mensekresi Immunoglobulin (Ig)
• mikros : clock face nucleus
• ada di semua jaringan limfatik
Sel-sel organ limfatik
Limfosit NK cell APC Makrofag Sel Plasma Sel Retikuler
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Natural Killer cell
- = limfosit granular
- Tidak memiliki reseptor
- Dapat aktif tanpa
stimulasi (no memory)
Sel-sel organ limfatik
Limfosit NK cell APC Makrofag Sel Plasma Sel Retikuler
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APC (Antigen Presenting Cell)
• cells that display peptides associated with class II MHC
molecules to CD4+ TH cells (komplek antigen small component
presentation express on the cell surface)
• Tipe :
– Professional APC : constitutively express class II MHC
molecules
• = sel yg dpt menimbulkan aktivasi perkembangan limfosit
• Tdd : Dendritic cell, macrophage, & B-lymph.
– Nonprofessional APC : can be induced to express class II MHC
molecules
• =sel yg dpt distimulasi utk presentasi antigen dlm fungsi
efektor
• Ex : endothelial cells, astrocytes, epithelial cells, fibroblast
Sel-sel organ limfatik
Limfosit NK cell APC Makrofag Sel Plasma Sel Retikuler
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APC (Antigen Presenting Cell)
Sel-sel organ limfatik
Limfosit NK cell APC Makrofag Sel Plasma Sel Retikuler
By convention, APC usually refers to a cell that displays antigens to T lymphocytes.
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Makrofag
• komponen mononuclear phagocyte system
• memfagositosis kompleks antigen, memperkuat
antigenisitas
• memfagositosis kompleks Ag-Ab
• mendindingi sinus vaskuler
• tersebar di organ limfatik & jaringan limfatik
• tersebar di jaringan ikat longgar
SEL2 SISTEM limfatik
Limfosit NK cell APC Makrofag Sel Plasma Sel Retikuler
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Sel Retikuler
• stellata, prosesus beranyaman
• Type :
– Sel Retikuler mesenchymal juga sbg APC
– Sel Retikuler epithelial supportive
• di thymus
• = nurse cell
Sel-sel organ limfatik
Limfosit NK cell APC Makrofag Sel Plasma Sel Retikuler
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: Sel2 limfatik
: Struktur limfatik
: Organ limfatik
: Pembuluh limfatik
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• = kumpulan limfosit2, berbentuk sferis
aggregat2 limfatik sub unit fungsional
• Tdd dr Germinal center & mantle zone
• Nodulus primer
– saat prenatal
– Germinal center [-]
– Ag [-]
NODULI LIMFATISI (Lymphatic nodule)
GAMBARAN KHUSUS
(SPECIAL FEATURES)
Nodulus sekunder
setelah lahir
= bentuk aktif dr nodulus
primer oleh paparan Antigen
Terdapat Germinal Centre
banyak limfoblast
Sbg tempat sel memori (in
‗cap‘)
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.......special features
GERMINAL CENTRE
• Daerah yang nampak pucat, berada di tengah suatu
noduli limfatici (Lymphatic nodule)
- timbul setelah lahir
- Hilang timbul sesuai stimulasi antigen
- Tempat diferensiasi B-cell
- [-] - s/d akan lahir
- bila antigen [-]
- thymectomy saat lahir
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GERMINAL CENTRE
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: Sel2 limfatik
: Struktur limfatik
: Organ limfatik
: Pembuluh limfatik
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1. Sel
Sel Utama : Limfosit T & B
Sel lain : - Sel plasma - Sel retikuler
- APC - Makrofag
2. Jaringan (struktur) Limfatik
a. Loose lymphatic tissue limfosit tidak tersusun
rapat.
b. Dense lymphatic tissue limfosit membentuk
aggregat ( lymphatic nodules/follicle)
3. Organ Limfatik
Ex : Limfonodus, Lien, Timus
KOMPONEN ORGAN LIMFATIK:
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• organ limfatik sentral (Primary) :
pembentukan limfosit tidak tergantung antigen
supply T-cell netral atau prekursor limfosit B ke organ
& jaringan perifer
Tdd : Timus dan sumsum tulang
• organ limfatik perifer (Secondary):
pembentukan limfosit tergantung antigen sel2
imunokompeten, bereaksi thd Antigen spesifik
Tdd : Limfonodus, lien, tonsil, aggregat limfatik tidak
berkapsul
Klasifikasi jaringan & organ limfatik :
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KARAKTERISTIK :
* >> limfosit
• kerangka anyaman serabut & sel retikuler
ORGAN LIMFATIK
Thymus
L I E N
LIMFONODUS
TONSIL
AGGREGAT
LIMFATIK TIDAK
BERKAPSUL
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• organ limfatik berkapsul terkecil & terbanyak
• tersebar dalam kelompok2 di sepanjang pembuluh limfe
di leher, axilla, abdomen, pangkal paha, dan thorax
• fungsi :
– sbg filter limfe
– ‗menangani ‗ antigen & debris seluler
– penambahan immunoglobulin
LIMFONODUS
Thymus L I E N LIMFONODUS TONSIL AGGREGAT LIMFATIK
TIDAK BERKAPSUL
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Struktur
• bentuk seperti kacang
• Tdd cortex dan medulla
• Kapsul trabekula antara nodulus di cortex
• pembuluh darah & pembuluh limfe efferent di hilum
• Pembuluh limfe afferent melalui permukaan convex
• terdapat HEV (High Endothelial Venules), yang dihuni sel T
LIMFONODUS
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CORTEX :
• limfosit tersusun padat
• germinal center [+]
• limfosit tergantung di anyaman jaringan ikat retikuler
LIMFONODUS
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ALIRAN LIMFE
limfe pembuluh afferent
sinus subcapsular
sinus peritrabekular
anyaman anastomose di sinus2 medullary
pembuluh limfe efferent
hilum
LIMFONODUS
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• Penyaringan limfe
– limfe afferent membawa debris seluler & antigen
‘ditangani‘ oleh makrofag & sel2 dendritik folikuler
di sinus2
– limfosit mengalami : kontak dg APC & makrofag di
sinus2
– keluar dr sinus masuk parenchym
LIMFONODUS
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T I M U S (Thymus)
• Hanya membentuk prekursor sel T
• Temporer --mengalami involusi dg pertambahan
umur
T I M U S L I E N LIMFONODUS TONSIL AGGREGAT LIMFATIK
TIDAK BERKAPSUL
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ANATOMI : Thymus
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Histofisiologi timus
• pembentukan T-limfosit
( prekursor dibentuk di sum-sum tulang) cortex timus
(= thymocyte)
menghilangkan sel2 prematur yang teraktivasi & menjadi
Antigen ―self‖‘
kemampuan mengenali antigen
TIMUS
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• Blood-timus barrier
– tersusun dari :
1. sel endothelial (+ occluding junction)
2. Basal lamina endothel
3. jaringan ikat
4. Basal lamina sel retikuler epithelial
5. sel retikuler epithelial (+desmosom)
– hanya di cortex
– memisahkan thymocyte yang sedang proliferasi dg
aliran darah, untuk mencegah masuknya materi
antigenik mempertahankan supply sel induk
‗naïve‘ yang siap diprogram
TIMUS-Histofisiologi
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Histofisiologi timus (cont)
• Thymocyte :
proliferasi thymocyte limfosit T
kebanyakan akan mengalami apotosis difagositosis oleh
makrofag
p.u tidak bisa bereaksi terhadap antigen
They migrate toward the medulla as they mature
Mature T cells exit the thymus via venules and efferent
lymphatic vessels from the thymic medulla.
The T cells then migrate to secondary lymphoid structures.
TIMUS
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L I E N
fungsi :
• tempat pembentukan limfosit teraktivasi
• pertahanan thd benda asing
• tempat destruksi RBC tua
• penyimpanan darah
• berperan dalam metabolisme besi
• Sbg organ hematopoiesis fetal.
Thymus L I E N LIMFONODUS TONSIL AGGREGAT LIMFATIK
TIDAK BERKAPSUL
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Struktur
• kapsul jaringan ikat padat trabekula splenic pulp
• Pulpa :
white pulp (pulpa putih; pulpa alba): * Noduli Limfatici
(Corpusculum Malpighi)
Red pulp (Pulpa merah; pulpa rubra):
Marginal zone :
• Membentuk penghubung antara pulpa merah dan
pulpa putih
• pembuluh limfe afferent [-], HEV [-]
LIEN
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• Di hipokhondrium; dg sedikit
sampai epigastrium.
• Antara fundus gaster –
diafragma
ANATOMI
LIEN
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LIEN : sirkulasi
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Mekanisme aliran darah
mencapai sinus
• Closed theory
– Dinding kapiler berlanjut
sebagai dinding sinusoid
• Open theory
– Ujung kapiler di Billroth
cord darah keluar,
disaring oleh cord
dinding sinusoid (via
fenestrae)
LIEN : sirkulasi
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TONSIL
Macam :
• T.palatina (D-S)
• T.pharyngeal
• T.lingual
Thymus L I E N LIMFONODUS TONSIL AGGREGAT LIMFATIK
TIDAK BERKAPSUL
Ring of Waldeyer
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Tonsila palatina/faucial
• 2 buah, di dinding lateral oropharynx, di bawah palatum
molle
• ditutupi epithel squamous complex dg kornifikasi
• mengandung noduli limfatisi, p.u dengan germinal center
• crypte 10-20 mengandung sel epithel yg desquamasi,
limfosit, dan bakteri
• kapsul jaringan ikat padat : tebal, parsial berfungsi
sebagai barrier untuk mencegah penyebaran infeksi
TONSIL
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Tonsila pharyngeal
• tunggal, midline nasopharyx posterior
• kapsul lebih tipis
• crypte [-]
• kapsul jaringan ikat tipis, parsial
• bila hipertrofi adenoid
TONSIL
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TONSIL
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Tonsila lingualis
• lebih kecil, jumlah lebih banyak
• di pangkal lidah, belakang papilla circumvalata
• ditutupi epithel squamous complex dg sedikit kornifikasi
• germinal center [+]
• Kapsul tidak jelas
(Juncq,Paulsen)
TONSIL
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TONSIL
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AGGREGAT LIMFATIK TIDAK BERKAPSUL • mrpkn noduli limfatisi
dalam kelompok kecil
atau soliter
• contoh :
– Berkelompok : Peyer‘s
patches di IT
– Soliter : tersebar di
mukosa GIT, UT, UG
• dapat diselubungi selapis
sel retikuler pipih
• kapsul jaringan ikat [-]
Thymus L I E N LIMFONODUS TONSIL AGGREGAT LIMFATIK
TIDAK BERKAPSUL
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• MALT ( Mucosa Associated Lymphatic Tissue).
– BALT (Bronchial Associated Lymphatic Tissue).
– GALT (Gut Associated Lymphatic Tissue).
– SALT (Skin Associated Lymphatic Tissue).
AGGREGAT LIMFATIK TIDAK BERKAPSUL
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dari perut turun ke kaki…
dari perut naik ke tangan….
dari perut ke kepala….
dari perut ke semuanya…..
la la la la…la..la…
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Sistem Limfatik
vs
OBAT
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system limfatik sebagai :
• jalur alternative cairan jaringan ke sirkulasi
• target obat
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• Ex target :
– Limfosit
– Jalur sistem limfatik
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Peluang aplikasi :
• infeksi
• inflamasi
• deteksi metastase tumor
• Vaksin
• Kanker
• Carrier / prodrug
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Jalur pemberian :
• oral.
Faktor :
• GALT
• M-cell
• Parenteral : i.m, sc, ip
– i.m & S.c : endocytosis & difusi pasif……ditentukan
banyak faktor*
– i.p
Melalui cisterna chylii
(or mesenteric lymph nodes vena hepar).
Small mol.
large mol.
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Faktor obat I.m / s.c :
Sulit ditentukan via kapiler/limfatik
Area of the drug depot
Volume injeksi
Konsentrasi obat
pH
Pergerakan tubuh
Anatomis
Kondisi jaringan
Molecular weight (MW)
1000 - >16.000 limfatik
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– Syarat
• Lipid base
lipofilik , t.u MW: 1.000 - 16.000
* long chain fatty acid & TG
* unsaturated fatty acid
• Carrier :
– Nanoparticle
– Liposome
– Microspherere
• Prodrug. Ex : MMC-D (mitomycin-C dextran; anti tumor)
Colloidal
drug delivery
system
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reference :
Panyam, J., Kumar, V., and Mishra, B. (1999) Recent trends in drug
delivery systems: Lymphatic drug targeting and transportation. Acta
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