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KULIAH PENGANTAR PRAKTIKUM BIOKIMIABLOK HEMATOLOGIBLOK HEMATOLOGI
DIAN ARININGRUM, dr, MKes, SpPK
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Tujuan pembelajaran1. Struktur dan fungsi membran eritrosit2. Metabolisme dan energetika eritrosit3. Aspek klinis dari defek struktur membran
dan defek metabolisme eritrosit4. Membrane disruption agent 5. Kalsium darah
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K nsep Dasar Me!ab l"sme Er"!r s"!- Tdk punya inti organela tdk bisa mensintesis protein
- Msh aktif se!ara metabolik AT" disintesis dr glikolisis anaerob
asuk sel se! facilitated di usion #glucosa transporter $ glu!ose
permease% sebagian insulin-
dependent &
'M" #(likolisis anaerob& AT") *aktat +A,
alur *uebering-/apoport
2)3-,"( regulasia0nitas b- 2
alur "entose-"hosphate
"eran ( ",% menghasilkan +A," reduksi (SS( m d (S
melindungi membran dr kerusakan
oksidatif
'+4 M "AT 6 anemiahemolitik
(SS( Oxidized Glutathione (S Reduced
7esi eme hrs tetapberada dlm bentuk
8e29
Methemoglobin /edu!tase)koensim +A, #dr 'M"&
,estruksi eritrosit tua)di S/'
- Tetrapirol 7ilirubin- 8e (lobin reutilisasi
(enetik : bMAkuisita : ksidan
Sintesis emoglobin :- eme- (lobin
• ,efek Sintesis eme•
,efek Sintesis (lobin#Kualitatif Kuantitatif&
'M (* 7 + "AT 6
Sumber energi : (lukosa
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Karakteristik struktur) isi sifat metabolisme eritrositmendukung fungsinya yaituutk transport gas$ ;akram bikonkaf luas
permukaan relatif lebihbesar dibandingkan?@
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Membran Er"!r s"!7ersifat semipermeabel
#$! s%ele! n#$! s%ele! n eritrosit merupakan
e aring yang dibentuk oleh protein0lamentosa yg kompleks
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'un&s" membran1& Mempertahankan bentuk sel2& Melindungi sel memungkinkan sel bertahan
thd stress selama melalui mikro
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STRUKTUR MEMBRAN
Lipid 43%: fosfolipid, olesterol, gli olipid
!rotein 4"% # le$ih dari 0 &enis protein'ar$ohidrat (%
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8luid-Mosai! "lasma Membrane8luid-Mosai! "lasma Membrane
Membran eritrosit mrpk struktur yg dinamis B
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'lu"d(M sa") M del
C 'lu"d $o Membran plasma berbentuk
!air pd suhu tubuh) krnkandungan fosfolipid tak enuh
o /asio kandungan asam lemaktak enuh : enuh pd bbrp tipe selberbeda2 Duiditas berbeda
C M sa") $o = 5E enis protein membran membentuk pola
anyaman asimetris di bagian dalam luar membrano "rotein perifer dan protein integral #hidro0lik di luar)hidrofobik di dalam&
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LIPID BILA*ER8osfolipid glikolipid dg gugus polar hidro0likdi permukaan eksternal internal) gugus non
polar hidrofobik di tengah membran membran sbg liquid sealer
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'LUIDITAS MEMBRAN
C "erubahan Duiditas mempengaruhi konformasi)orientasi) mobilitas dan clustering proteinmembran
C 8luiditas membran terutama ditentukan oleh
komposisi lipidC Kolesterol memegang peranan penting dalammempertahankan struktur matriks bilayer
C "eningkatan komponen kolesterol menurunkan
Duiditas membran
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8luiditas lapisan lipid bilayerditentukan oleh komposisinya
1. "an ang rantai asam lemak$ *ebih pendek gaya
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PROTEIN MEMBRAN PERI'ER
7erikatan ionik dg membran. Terlepas bila terpapar garamkonsentrasi tinggi) larutan dgkekuatan ionik sangat tinggiHrendah atau p ekstrim.
*apisan lipid bilayer tetapinta!t.Menentukan
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PROTEIN MEMBRAN INTEGRAL
Tidak larut dlm air. Tidak terlepasH larut dlmpaparan garam konsentrasitinggi #=1EEmM +a;l&.Menyatu dg lapisan lipid bilayermelalui interaksi hidrofobikprotein-lipid) hanya dpt terlepasbila t d kerusakan struktur lipidbilayer) mis krn paparandetergen.7iasanya berupa protein2 transmembran) kontak dg
permukaan dalam luar.;ontoh;ontoh : band 3 #transport channel )t gl) osa * ion2+(ly!ophorins A # sifat antigeni #gol drh -.+
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'un&s" Pr !e"n Membran
Transp r!Pr !e"n
En+$ma!")Pr !e"n
Signal binding proteins
Cellular joining
#ellRe) &n"!" n
Pr !e"n Attachment
# annelPr !e"ns $!hannel forlipid insolublemole!ules andions to passfreely through#arr"erPr !e"ns $bind to asubstan!e and!arry it a!rossmembrane)!hange shapein pro!ess
;arry outen+$ma!")rea)!" ns right at themembraneJhen asubstrate binds
to the a!ti
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8asilitasi pergerakan substrat dari keluarsel1. !a-"-#$%ase transport aktif +a
#keluar sel& K #masuk sel&2. &a-Mg-#$%ase calcium pump
transport ;a keluar sel - bila ;a intraselterlalu tinggi ggn deformabilitas
Mempertahankan besi dlm keadaan
tereduksi Menghasilkan AT" +A," Sintesis heme
SISTEM EN-IM MEMBRAN ERITROSIT
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Molekul keluar masuk sel dg :'. %assi(e $ransport : di usi) facilitated di usion ) osmo). #cti(e $ransport : endositosis) pinositosis) fagositosis
Ba&a"mana m le%ul ber&era% %eluar masu%sel .
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Fhat is ,i usionN
,i usion is the net mo
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Fhat is 8a!ilitated ,i usionNC 'a)"l"!a!ed d"/us" n "s ! e ne! m 0emen! 1
m le)ules 1r m a "& ) n)en!ra!" n ! a l 2) n)en!ra!" n ith the aid o! channel orcarrier proteins 3
C I ns 4Na 5 , K 5 , #l (6
C Su&ars 4Glu) se6C Am"n A)"dsC Small 2a!er s luble
m le)ulesC 7a!er 41as!er ra!e6
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Molekul a"r bergerak dari larutan dg konsentrasi solute lebirendah menu u konsentrasi lebih tinggi melalui membransemi permeabel
OSMOSIS
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Te%anan Osm !"% Te%anan Osm !"% C ,ihasilkan oleh Lat terlarut *solute+ dalam
larutanC Merupakan tekanan yg men!egah molekul air
memasuki larutan dengan konsentrasi solutelebih tinggi
C Meningkat bila umlah partikelterlarut bertambah
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H 2 D H$p ! n"), H$per! n"), and Is ! n") S lu!" nsA/e)! ! e 7a!er M 0emen! 1 a #ell.
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Dlm lar "s ! n"s Dlm lar "p ! n"s Dlm lar "per! n"s
Tek osmotik larutan samadng tek osmotik intraeritrosit
PsoluteQ G PsoluteQ lar0siologis tek. osmotik G
molekul air bergerakmemasuki eritrosit eritrosit bengkak pe!ah#hemolisis&
PsoluteQ= PsoluteQ lar0siologis tek. osmotik
molekul air bergerakkeluar eritrosit eritrokisut #krenasi&
,isebut sbg larutan0siologisB
(lukosa 5.E@ atau +a;lE.>E@
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A red !ell in a high salt
solution Jill shri
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alur metabolisme utama eritrositC 'ritrosit memerlukan energi utk :
Mempertahankan deformabilitas elastisitas membran/ 2 enLimatik pembentukan AT") mempertahankan besidlm keadaan tereduksi #8e 29 &
Transport ion +a) K) ;a keseimbangan osmotik intrasel
Tdpt 2 alur metabolisme utama eritrosit :1.(likolisis anaerob # alur 'mbden-MeyerhofH 'M"& energi
sbg AT" #1 molekul glukosa 2 AT"&2. e ose Monophosphate # M" Shunt H alur "entose
"hosphate& +A, +A," sbg daya pereduksi
NADH : Nicotinamide Adenin Dinucleotide; NADPH : Nicotinamide Adenin Dinucleotide Phosphate
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Lueber"n&(Rap p r! S un!
He8 se M n p sp a!eS un! 4HMP69 Pen! se
P sp a!
Me!Hbredu)!ase
pa! 2a$
Embden(Me$er 1
Pa! 2a$ 4EMP6
alur *uebering $ /apoportmenghasilkan :,;(DPG #2)3-,iphosphogly!erate& mbtkkomplek dg b #1 : 1& mengatur a0nitas b thd 2
Menghas NADPH akti0tas (lutathionreduktase #reduksi (SS(m d (S & (S utkdekomposisi 2 2 # 2 2== pbtk Met b&+A," uga diperlukan olMet b reduktase utkmempertahankan besi tetadalam keadaan tereduksi
b#8e 39 & b#8e 29 &Met b
redu!tase
+A,
'M" ugamenghasilkan NADH
yg diperlukan olehenLim
Methemoglobin
redu,tase utkmereduksi Met b
(- -",
"yru
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uga dihasilkan +A,"( ", mereduksi +A," # nicotinamide-
adenine-dinucleotide phosphate & m d +A +A," mereduksi oxidized glutathione
#(SS(& m d btk tereduksi #(S & melindungi membran eritrosit b dr stress
oksidatif
alur "entose-"hosphateH exose-
Monophosphate* M%+ hunt
alur M"H "entose "hosphate
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ASPEK KLINISC Maintenan!e of hgb fun!tion reOuires a!ti
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ASPEK KLINIS
$ Met gb /edu!tase "athJay - maintains ironin the redu!ed fun!tional state.
C There are 2 pathJays) the +A, and the+A," redu!tase pathJays. They are
dependent upon +A, and +A,"respe!ti
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AS"'K K* + S : ANEMIA HEMOLITIK
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AS"'K K* + S : ANEMIA HEMOLITIK
!C5 : !aro6ys al Cold 5e oglo$in)ria517 : 5e olytic 1isease of the 7e $orn5US : 5e olytic#Ure ic Syndro e88! : 8hro $otic 8hro $ocytopenic !)rp)ra19C : 1ise inated 9ntravasc)lar Coag)lation!75 : !aro6ys al 7oct)rnal 5e oglo$in)ria
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Abnormalitas umlah atau struktur proteinmembran
1& ereditarysphero!ytosis
# S&2& ereditary
ellipto!ytosis
# '&
AS"'K K* + S : De1e% membran er"!r s"!
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HS HE
De>n"s"Merupakan kelainan genetik autosomaldominan) ditandai dg defek membran eritrosit)mengakibatkan membran men adi kurangdeformable dan mudah pe!ah.
E!" l &"Ankyrin dan Spe!trin
Spe!trin) protein I.1)
protein I.2
M r1 l &"
'ritrosit berukuranlebih ke!il) lebihbulat #tidakbikonkaf&*ebih fragil
•'ritrosit berbentukelips
ASPEK KLINIS @ de1e% en+"m
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Stress ksidatif1. Antimalaria : "rimakuin
2. Sulfonamide3. +itrofuranI. "hena!etin5. Uit K sintetis
. +aphthalene #moth balls&?. Makanan : ka!ang fa. Ketoasidosis diabetik
'pisode hemolitik
ekstra
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ksidasi 8e 29 m d 8e 39 pbtk Methemoglobin tidak mampu mengika
+ormal : Selama fase deoksigenasi b 1 $ 3@ bteroksidasi m d Met b tiap hari direduksi kembalioleh enLim Methemoglobin reduktase # Met&breduction path a% &
- /nstable emoglobins #herediter&- ,e0siensi Met b- reductase- -
M !H MOG"O#$% M
b#8e 39 & b#8e 29 &Methemoglobinredu!tase
+A, #dr. alur 'M"&
Defek pada Jalur Reduksi Methemoglobin
ASPEK KLINIS @ de1e% en+"m er"!r s"!
d 1 % +"
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ASPEK KLINIS @ de1e% en+"mer"!r s"!
'ritrosit mempertahankan
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ASPEK KLINIS
C Kandungan asam lemak kolesterol diit adanyapenyakit2 yang mempengaruhi metabolismekolesterol #penyakit hati empedu) ggn enLim&mempengaruhi komposisi asam lemak kolesterolmembran perubahan bentuk membran #seltarget) a!antho!yte& gangguan Deksibilitas
deformabilitas eritrosit sur
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ASPEK KLINISC Adanya komponen
protein di bagian luarmembran eritrositbermuatan negatif #Letapotential& tdk
menempel satu sama lain;eta potential is the potential difference$et een the dispersion edi) and thestationary layer of fl)id attached to thedispersed particle
high eta potential ill confer sta$ility, i e , thesol)tion or dispersion ill resist aggregation
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• !er)$ahan o posisi protein plas a a an en)r)n aneta potential rouleaux eritrosit pening atan L=1
C nDamasi peningkatan kadar 0brinogen rouleaux eritrosit
C Multiple Myeloma sintesis globulin oleh selplasma ↑ rouleaux eritrosit
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>left : itho)t he olysis+ red $lood cell s)spension >0 % sheep /-Cs in saline+, see s red andopa?)e> iddle : itho)t he olysis+ /-Cs sedi ented spontaneo)sly for @0 in 7ote that the s)pernatant is
not colored>right : he olysis+ /-C s)spension treated ith the he olysin of S. pyogenes at 3AC for 30 in$eco e transparent $y he olysis
'M * S S '/ T/ S T
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Tube mLs3 C
Na#l
mLsd"s!"lled
2a!er
Na#l # n)34C6
1 E.E 1E.E E emolisis total2 >.E 1.E E.2 emolisis total3 V.E 2.E E.I emolisis sebagianI ?.5 2.5 E.5 Tidak ter adi
hemolisis
5 ?.E 3.E E. Tidak ter adihemolisis
.5 3.5 E.? Tidak ter adihemolisis
? .E I.E E.V Tidak ter adihemolisis
V 5.5 I.5 E.> Tidak ter adihemolisis isotonis
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Tes! 'ra&"l"!asOsm !"% Er"!r s"!
'Osmotic(ragilit% Test)
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'/', TA/6 S" '/ ;6T S Sasil $es 0ragilitas Osmoti, 1ritrosit
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'W" SX/' T ; 'M ;A* S *U'+TSC ' posure measurements in !ombination Jith
analysis of haematologi!al parameters may be atool for early dete!tion of !ellular !hanges in theblood !aused by e posure to sol
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' posure to to i! metalsC *ead poisoning
C 'rythro!ytes as an important target of lead to i!ityC After ingestion or inhalation) lead mole!ules enters
the bloodstream Jhere it is predominantly bound toerythro!yte proteins) !ause proteolysis and disruptionof /7; membrane.
C *ead alters lipid metabolism) enhan!es lipidpero idation and de!reases !ell membrane Duidity.
C *ead may be responsible !ausing osmoti! !hange inblood hen!e osmoti! fragility is the reason forhemolysis.
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S+AK' U'+ MC Snake
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KALSIUMKALSIUMC 8ungsi struktural mineral tulang gigiC
8ungsi regulasi :- econd messenger
ker a hormon- Kontraksi otot
- Konduksi syaraf - "embekuan darah- Kofaktor utk akti
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TRANSPORT KALSIUM DLMTRANSPORT KALSIUM DLMDARAHDARAH
Kalsium ekstraseluler intraseluler hanya 1@ dr total
kalsium tubuhKalsium intraseluler : E.EEE1konsentrasi kalsiumekstraseluler
Konsentrasi kalsiumekstraseluler intraseluler
diatur dg ketat,lm darah kalsium berada dlm3 bentuk :
0ree #ionized &calcium #5E@& fungsional
Terikat pd albumin #IE@&
Kompleks dg bikarbonat) sitratatau fosfat #1E@&
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P RA% &A"'$(M )*aP RA% &A"'$(M )*a 2+2+ dlm hem stasisdlm hem stasis
C Trtm di alur intrinsik alur bersamaC ;a :5 sbg koenLim) berikatan dg faktor koagulasi
mengaktifkan faktor koagulasi punyaakti0tas enLimatik% memungkinkan ikatan faktorkoagulasi pd membran fosfolipid trombositterakti
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KONTROL HOMEOSTASIS KALSIUM & FOSFAT
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KONTROL HOMEOSTASIS KALSIUM & FOSFAT
"'/X7A A+ KA A/ KA*S XM A/A"'/X7A A+ KA A/ KA*S XM A/A
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"'/X7A A+ KA,A/ KA*S XM ,A/A"'/X7A A+ KA,A/ KA*S XM ,A/ACarpopedal SpasmH"p %alsem"a
C Tetani otot *carpopedal spasm+
C ,ilatasi antung∀ ↑ permeabilitas membran selC (gn pembekuan darah
H"per%alsem"aC ,epresi sistem syaraf) ↓ reDeC Kelemahan ototC (gn motilitas usus) konstipasi
C "embentukan kristal kalsium fosfat
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Koreksi kadar ;al!iumC "erubahan kadar albumin 1 gramHd*
perubahan kadar kalsium serum E.V mgHd*C Kadar albumin serum normal 3.5 - 5.E gHdlC 7ila tidak m"sd"a&n s"s "per%alsem"am"sd"a&n s"s "per%alsem"a
;al!ium terkoreksi Albumin R
Serum )al)"um 5 4 (album"n6 F 3
;ontoh: ;a 3 mgHd* Alb 2.5 gHd*:R 1E.5 9 P#I $ 2.5& W E.VQ R 3J mgHd*
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SA'ET* PRE#AUTIONSA'ET* PRE#AUTIONC angan ber!anda) membau botol) men!ampur-!ampur
reagen yg tdk diinstruksikan utk di!ampur.C 7erhati-hatilah bila beker a dg bahan u i yang berasal
dr bahan biologis darah) krn kemungkinan adanyakuman atau
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8he &o)rney of a tho)sand iles$egins ith a single step 2.
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