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BIOKIMIA

BLOK HEMATOLOGI

DIAN ARININGRUM, dr, MKes, SpPK


Danus Hermawan, dr
Jarot Subandono dr. MKes
Copyright 2004, Medicine School of Shandong University
Tujuan pembelajaran
1. Struktur dan fungsi membran eritrosit
2. Metabolisme dan energetika eritrosit
3. Aspek klinis dari defek struktur membran
dan defek metabolisme eritrosit
4. Membrane disruption agent
5. Kalsium darah

Copyright 2004, Medicine School of Shandong University


EMP (Glikolisis anaerob) ENZIMOPATHY anemia hemolitik
ATP, Laktat & NADH
Masuk sel sec facilitated diffusion Peran G6PD; menghasilkan NADPH
(glucosa transporter glucose reduksi GSSG mjd GSH melindungi 2,3-DPG regulasi
permease; sebagian insulin- membran dr kerusakan oksidatif afinitas Hb-O2
dependent)
Sumber energi : Glukosa
Jalur Pentose-Phosphate
Jalur Luebering-Rapoport

Konsep Dasar Metabolisme Eritrosit


- Tdk punya inti & organela tdk bisa mensintesis protein
- Msh aktif secara metabolik ATP disintesis dr glikolisis anaerob

Destruksi eritrosit tua, Besi Heme hrs tetap berada Sintesis Hemoglobin :
di SRE dlm bentuk Fe2+ - Heme
- Globin

Methemoglobin Reductase,
- Tetrapirol Bilirubin Defek Sintesis Heme
- Fe & Globin reutilisasi koensim NADH (dr EMP)
Defek Sintesis Globin
(Kualitatif & Kuantitatif)
Genetik : HbM
Akuisita : Oksidan
Copyright 2004, Medicine School of Shandong University HEMOGLOBINOPATHY
GSSG Oxidized Glutathione GSH Reduced Glutathione
Karakteristik struktur, isi & sifat
metabolisme eritrosit mendukung
fungsinya yaitu utk transport gas, ERITROSIT
yaitu mengangkut O2 dari paru ke
jaringan dan mengangkut CO2
dari jaringan ke paru
Cakram bikonkaf luas
permukaan relatif lebih besar
dibandingkan volume sel
Kandungan eritrosit : > 97%
volume adalah hemoglobin
(viskositas rendah
deformabilitas sel)
ATP dihasilkan secara anaerob,
shg eritrosit tidak
mengkonsumsi oksigen yg
diangkutnya
Copyright 2004, Medicine School of Shandong University
Eritrosit manusia tidak berinti

Kasus: SCA
Definisi: Eritrosit
yang memanjang
dan melengkung
dengan dua kutup
yang runcing.
Distribusi dalam
darah: normal tidak
ada
Perbesaran: 1000 x
Akibat:
Anemi sel sabit
Keuntungan: kebal
terhadap Malaria
Membran Eritrosit
Bersifat semipermeabel

Cytoskeleton eritrosit merupakan jejaring yang


dibentuk oleh protein filamentosa yg kompleks
Mekanisme adaptasi biologis
Copyright 2004, Medicine School of Shandong University
Fungsi membran
1) Mempertahankan bentuk sel
2) Melindungi sel & memungkinkan sel bertahan thd
stress selama melalui mikrovaskulatur (berubah
bentuk tanpa merubah komposisi sel)
3) Berperan penting dlm transport ke dalam & ke luar
sel :
a. Transport pasif (difusi, osmosis, facilitated
diffusion)
b. Transport aktif (ion-pumps, co-transport)
Copyright 2004, Medicine School of Shandong University
DINDING SEL
BUKAN SEKEDAR PEMBATAS SEL
BERPERAN JUGA UNTUK KOMUNIKASI ANTAR SEL
BERUPA LIPID BILAYER, BANYAK TERDAPAT
PROTEIN, DIANTARANYA PROTEIN RESEPTOR
DINDING SEL

Hidrofilik

Hidrofobik

Hidrofilik
STRUKTUR MEMBRAN

Lipid 43%: fosfolipid, kolesterol, glikolipid


Protein 49% - lebih dari 50 jenis protein
Karbohidrat 8%
Copyright 2004, Medicine School of Shandong University
Fluid-Mosaic Plasma Membrane

Membran eritrosit mrpk struktur yg dinamis


Copyright 2004, Medicine School of Shandong University
Fluid-Mosaic Model
Fluid
o Membran plasma berbentuk cair
pd suhu tubuh, krn kandungan
fosfolipid tak jenuh
o Rasio kandungan asam lemak tak
jenuh : jenuh pd bbrp tipe sel
berbeda2 fluiditas berbeda

Mosaic
o > 50 jenis protein membran membentuk pola anyaman
asimetris di bagian dalam & luar membran
o Protein perifer dan protein integral (hidrofilik di luar,
hidrofobik di dalam)
Copyright 2004, Medicine School of Shandong University
LIPID BILAYER
Fosfolipid & glikolipid dg gugus polar hidrofilik di
permukaan eksternal & internal, gugus non polar
hidrofobik di tengah membran membran sbg
liquid sealer

Copyright 2004, Medicine School of Shandong University


FLUIDITAS MEMBRAN
Perubahan fluiditas mempengaruhi konformasi, orientasi,
mobilitas dan clustering protein membran
Fluiditas membran terutama ditentukan oleh komposisi
lipid
Kolesterol memegang peranan penting dalam
mempertahankan struktur matriks bilayer
Peningkatan komponen kolesterol menurunkan fluiditas
membran

Copyright 2004, Medicine School of Shandong University


Fluiditas lapisan lipid bilayer ditentukan
oleh komposisinya
1. Panjang rantai asam lemak
Lebih pendek gaya van der Walls <<
makin cair
2. Kejenuhan rantai asam lemak
Makin tidak jenuh (asam lemak Cis rantai ganda)
makin cair
3. Kandungan kolesterol (rasio kolesterol:fosfolipid)
Makin tinggi kolesterol fluiditas <<
Copyright 2004, Medicine School of Shandong University
PROTEIN MEMBRAN PERIFER
Berikatan ionik dg membran.
Terlepas bila terpapar garam
konsentrasi tinggi, larutan dg
kekuatan ionik sangat tinggi/
rendah atau pH ekstrim. Lapisan
lipid bilayer tetap intact.
Menentukan viskoelastisitas
membran bentuk, stabilitas &
deformabilitas
Contoh : Spectrin, Ankyrin, Protein
band 4.1, Actin
Copyright 2004, Medicine School of Shandong University
PROTEIN MEMBRAN INTEGRAL
Tidak larut dlm air.
Tidak terlepas/ larut dlm paparan
garam konsentrasi tinggi (>100mM
NaCl).
Menyatu dg lapisan lipid bilayer
melalui interaksi hidrofobik protein-
lipid, hanya dpt terlepas bila tjd
kerusakan struktur lipid bilayer, mis
krn paparan detergen.

Biasanya berupa protein2 transmembran, kontak dg permukaan


dalam & luar.
Contoh : band 3 (transport channel utk glukosa & ion2),
Glycophorins A (sifat antigenik-gol drh ABO)
Copyright 2004, Medicine School of Shandong University
Copyright 2004, Medicine School of Shandong University
Fungsi Protein Membran
Enzymatic Signal binding Cellular Cell Recognition
Attachment Protein
Transport Protein
Protein proteins joining Protein

Channel Carry out Bind to Bind cells Glycoproteins Attach to


Proteins enzymatic chemical together (and glycolipids) cytoskeleton (to
channel for lipid reactions right messengers Tight junctions on extracellular maintain cell shape and
insoluble at the membrane (ex. hormones) Gap junctions surface serve as stabilize proteins)
molecules and and/or the extracellular
ions to pass when a substrate which sends a ID tags (which matrix (integrins
freely through binds to the message into the species, type of connect to both).
Carrier active site cell causing cell, individual). Extracellular Matrix
Proteins bind cellular reaction Carbohydrates protein fibers and
to a substance are short carbohydrates secreted
and carry it branched chains by cells and fills the
across of less than 15 spaces between cells
membrane, sugars and supports cells in a
change shape in tissue.
process Extracellular matrix can
influence activity inside
the cell and coordinate
the behavior of all the
Copyright 2004, Medicine School of Shandong University cells in a tissue.
SISTEM ENZIM MEMBRAN ERITROSIT

Fasilitasi pergerakan substrat dari & keluar sel


1. Na-K-ATPase transport aktif Na (keluar sel)
& K (masuk sel)
2. Ca-Mg-ATPase calcium pump transport
Ca keluar sel - bila Ca intrasel terlalu tinggi
ggn deformabilitas

Mempertahankan besi dlm keadaan tereduksi


Menghasilkan ATP & NADPH
Sintesis heme

Copyright 2004, Medicine School of Shandong University


Bagaimana molekul bergerak keluar masuk sel ?
Molekul keluar masuk sel dg :
1. Passive Transport : diffusi, facilitated diffusion, osmosis
2. Active Transport : endositosis, pinositosis, fagositosis

Copyright 2004, Medicine School of Shandong University


What is Diffusion?
Diffusion is the net movement of
molecules from a high
concentration to a low concentration
until equally distributed.
Diffusion rate is related to
temperature, pressure, state of
matter, size of concentration
gradient, and surface area of
membrane.

Gases (oxygen, carbon dioxide)


Water molecules (rate slow due to polarity)
Lipids (steroid hormones)
Lipid soluble molecules (hydrocarbons, alcohols, some vitamins)
Small noncharged molecules (NH3)
Copyright 2004, Medicine School of Shandong University
What is Facilitated Diffusion?
Facilitated diffusion is the net movement of
molecules from a high concentration to a low
concentration with the aid of channel or carrier
proteins.

Ions (Na+, K+, Cl-)


Sugars (Glucose)
Amino Acids
Small water soluble
molecules
Water (faster rate)

Copyright 2004, Medicine School of Shandong University


OSMOSIS

Molekul air bergerak dari larutan dg konsentrasi solute lebih rendah


menuju konsentrasi lebih tinggi melalui membran semi permeabel
Copyright 2004, Medicine School of Shandong University
Tekanan Osmotik
Dihasilkan oleh zat terlarut (solute) dalam larutan
Merupakan tekanan yg mencegah molekul air
memasuki larutan dengan konsentrasi solute
lebih tinggi

Meningkat bila jumlah


partikel terlarut
bertambah

Copyright 2004, Medicine School of Shandong University


How Do Hypotonic, Hypertonic, and Isotonic Solutions
Affect the Water Movement of a Cell?

Copyright 2004, Medicine School of Shandong University


Dlm lar isotonis Dlm lar hipotonis Dlm lar hipertonis
Tek osmotik larutan sama dng [solute] < [solute] lar [solute]> [solute] lar fisiologis
tek osmotik intra eritrosit fisiologis tek. osmotik < tek. osmotik > molekul
molekul air bergerak air bergerak keluar eritrosit
Disebut sbg larutan fisiologis memasuki eritrosit eritrosit eritrosit kisut (krenasi)
bengkak & pecah (hemolisis)
Glukosa 5.0% atau NaCl 0.90%
NaCl 0,9% disebut garam
fisiologis, pembuka dan
penutup transfusi

Copyright 2004, Medicine School of Shandong University


Eritrosit udem Eritrosit normal Crenated cell

A red cell in a low salt A red cell in a A red cell in a high salt
solution will swell and burst physiological salt solution will shrivel as water
as water flows into the more solution has normal flows out into the more
concentrated solution inside shape concentrated surrounding
the cell Copyright 2004, Medicine School of Shandong University solution
Jalur metabolisme utama eritrosit
Eritrosit memerlukan energi utk :
Mempertahankan deformabilitas & elastisitas membran
Rx2 enzimatik pembentukan ATP, mempertahankan besi dlm
keadaan tereduksi (Fe2+)
Transport ion Na, K, Ca keseimbangan osmotik intrasel

Tdpt 2 jalur metabolisme utama eritrosit :


1.Glikolisis anaerob (Jalur Embden-Meyerhof/ EMP) energi sbg
ATP (1 molekul glukosa 2 ATP)
2.Hexose Monophosphate (HMP Shunt / Jalur Pentose Phosphate)
NADH & NADPH sbg daya pereduksi

NADH : Nicotinamide Adenin Dinucleotide; NADPH :Copyright


Nicotinamide Adenin
2004, Medicine Dinucleotide
School of ShandongPhosphate
University
EMP juga menghasilkan Embden-Meyerhof
NADH yg diperlukan Pathway (EMP)
oleh enzim Hexose Monophosphate Shunt
Methemoglobin (HMP)/ Pentose Phosphat
reduktase utk mereduksi G-6-PD
MetHb
GSSG

Menghas NADPH utk


aktifitas Glutathion reduktase
(reduksi GSSG mjd GSH) GSH
utk dekomposisi H2O2 (H2O2
MetHb
>> pbtk MetHb)
reductase
pathway ** NADPH juga diperlukan oleh
MetHb reduktase utk
NADH mempertahankan besi tetap
Hb(Fe3+) Hb(Fe2+) dalam keadaan tereduksi
MetHb Luebering-Rapoport Shunt
reductase
Jalur Luebering Rapoport
menghasilkan 2,3-DPG (2,3-
Diphosphoglycerate) mbtk
** Pyruvate-Kinase
komplek dg Hb (1 : 1)
mengatur afinitas Hb thd O2
G-6-PD = Glucose-6-Phosphate Dehydrogenase Copyright 2004, Medicine School of Shandong University
Jalur HMP/ Pentose Phosphate

Jalur Pentose-
Phosphate/ Hexose- Juga dihasilkan NADPH
Monophosphate (HMP) G6PD mereduksi NADP (nicotinamide-adenine-
Shunt dinucleotide phosphate) mjd NADPH NADPH
mereduksi oxidized glutathione (GSSG) mjd btk
tereduksi (GSH) melindungi membran eritrosit &
Hb dr stress oksidatif

Copyright 2004, Medicine School of Shandong University


ASPEK KLINIS
Maintenance of hgb function requires active RBC
metabolic pathways for ATP production. ATP is
required for:
Maintaining hgb in the reduced form
Membrane integrity and deformability
Maintaining the RBC intracellular volume
Producing adequate amounts of NADH, NADPH,
and GSH
RBCs generate energy almost exclusively from the
anaerobic breakdown of glucose - 4 metabolic
pathways are important for maintaining cellular
energetics.
Copyright 2004, Medicine School of Shandong University
ASPEK KLINIS
MetHgb Reductase Pathway - maintains iron in the
reduced functional state.
There are 2 pathways, the NADH and the
NADPH reductase pathways. They are
dependent upon NADH and NADPH respectively.
In the absence of the enzymes or NADH and
NADPH, metHgb, which can't transport O2, is
formed.

Copyright 2004, Medicine School of Shandong University


Jalur Luebering-Rapoport
Luebering-Rapoport shunt - causes the
accumulation of 2,3 DPG which is important in
decreasing the hgb affinity for O2 during O2
unloading.

Menghasilkan midproduct 2,3-DPG

Regulasi afinitas Hb thd O2

Akumulasi 2,3-DPG akan


menurunkan afinitas Hb
thd O2 O2 dilepas ke
jaringan
Copyright 2004, Medicine School of Shandong University
ASPEK KLINIS : ANEMIA HEMOLITIK

Anemia hemolitik
herediter

Membrane Enzyme Hemoglobin


defect defect defect

Pyruvate- - and -
Hereditary Hereditary G6PD
Spherocytosis Elliptocytosis
Ovalocytosis
Deficiency Kinase MetHbnemia Abnormal Hb thalassaemi
deficiency (Hb S, C, D, as
E, etc.)

Copyright 2004, Medicine School of Shandong University


ASPEK KLINIS : ANEMIA HEMOLITIK
Anemia
hemolitik
akuisita

Non
Immune immune

Autoimmune Alloimmune
(Warm type, (Transfusion Infection- Mechanical Miscelaneous
Drug-induced
Cold type, Reaction, induced trauma causes
PCH) HDN)

PCH : Paroxysmal Cold Hemoglobinuria HUS, TTP, DIC


HDN : Hemolytic Disease of the Newborn PNH
Cardiac hemolysis
HUS : Hemolytic-Uremic Syndrome Venom
Thermal damage
TTP : Thrombotic Thrombocytopenic Purpura Toxin
Osmotic damage
DIC : Diseminated Intravascular Coagulation Organ dysfunction
External factor
PNH : Paroxysmal Nocturnal Hemoglobinuria Copyright 2004, Medicine School of Shandong University
ASPEK KLINIS : Defek membran eritrosit

Abnormalitas jumlah atau struktur protein membran

1) Hereditary
spherocytosis
(HS)

2) Hereditary
elliptocytosis
(HE)
Copyright 2004, Medicine School of Shandong University
HS HE
Merupakan kelainan genetik autosomal dominan,
Definisi ditandai dg defek membran eritrosit, mengakibatkan
membran menjadi kurang deformable dan mudah
pecah.

Spectrin, protein 4.1,


Etiologi Ankyrin dan Spectrin protein 4.2

Eritrosit berukuran
lebih kecil, lebih bulat Eritrosit berbentuk elips
Morfologi
(tidak bikonkaf)
Lebih fragil

Copyright 2004, Medicine School of Shandong University


ASPEK KLINIS : defek enzim eritrosit
Defisiensi Glucose-6-phosphate Stress Oksidatif :
1. Antimalaria : Primakuin
dehydrogenase (G-6-PD) 2. Sulfonamide
3. Nitrofuran
4. Phenacetin
Antioksidan
5. Vit K sintetis
6. Naphthalene (moth balls)
7. Makanan : kacang fava
8. Infeksi
Antioksidan 9. Ketoasidosis diabetik

Episode hemolitik
ekstravaskuler akut
HMP Shunt mrpk satu2nya
stlh paparan oksidan,
penghasil NADPH utk eritrosit
tbtk Heinz bodies
Copyright 2004, Medicine School of Shandong University
ASPEK KLINIS : defek enzim eritrosit
Glycolysis- generates 90% of the required ATP- the
breakdown of 1 glucose generates 2 ATP and 2
NADH.
5 - 10% of the glucose is metabolized by Hexose
monophosphate shunt (pentose phosphate shunt).
It produces NADPH and GSH which protect the RBC
from oxidative injury.
If the concentrations of these are too low, the
globin will denature and precipitate in the cell.
This is seen as Heinz bodies which attach to the
membrane causing membrane damage and RBC
destruction.
Copyright 2004, Medicine School of Shandong University
ASPEK KLINIS : defek enzim eritrosit
Defek pada Jalur Reduksi Methemoglobin
Normal : Selama fase deoksigenasi Hb 1 3% Hb
teroksidasi mjd MetHb tiap hari direduksi kembali oleh enzim
Methemoglobin reduktase (MetHb reduction pathway)
Oksidasi Fe2+ mjd Fe3+ pbtk Methemoglobin tidak mampu mengikat O2

NADH (dr. jalur EMP)


Hb(Fe3+) Methemoglobin
Hb(Fe2+)
reductase

- Unstable Hemoglobins (herediter)


- Defisiensi MetHb-reductase METHEMOGLOBINEMIA
- Obat-obat yg mengoksidasiCopyright
Hb 2004, Medicine School of Shandong University
ASPEK KLINIS : defek enzim eritrosit
Eritrosit mempertahankan volume & homeostasis air
dg pengaturan konsentrasi Na+ & K+ oleh pompa
kation yg memerlukan ATP.
ATP juga diperlukan oleh pompa Ca2+ utk
mencegah tertimbunnya Ca2+ di dalam sel.
Jika sel kekurangan ATP timbunan Na+ dan Ca2+
intraseluler, kekurangan K+ & air dehidrasi sel,
ggn deformabilitas eritrosit survival & umur
eritrosit

Copyright 2004, Medicine School of Shandong University


ASPEK KLINIS

Kandungan asam lemak & kolesterol diit & adanya


penyakit2 yang mempengaruhi metabolisme kolesterol
(penyakit hati & empedu, ggn enzim) mempengaruhi
komposisi asam lemak & kolesterol membran
perubahan bentuk membran (sel target, acanthocyte)
gangguan fleksibilitas & deformabilitas eritrosit survival
dan umur eritrosit

Copyright 2004, Medicine School of Shandong University


ASPEK KLINIS
Adanya komponen protein di
bagian luar membran
eritrosit bermuatan negatif
(zeta potential) tdk
menempel satu sama lain

Zeta potential is the potential difference


between the dispersion medium and the
stationary layer of fluid attached to the
dispersed particle.
A high zeta potential will confer stability, i.e., the
solution or dispersion will resist aggregation.
When the potential is low, attraction exceeds
repulsion and the dispersion will break and
flocculate
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Perubahan komposisi protein plasma akan menurunkan
zeta potential rouleaux eritrosit peningkatan LED
Inflamasi peningkatan kadar fibrinogen rouleaux
eritrosit
Multiple Myeloma sintesis globulin oleh sel plasma
rouleaux eritrosit

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HEMOLISIS ERITROSIT

(left : without hemolysis) red blood cell suspension (0.5% sheep RBCs in saline), seems red and
opaque.
(middle : without hemolysis) RBCs sedimented spontaneously for 60 min. Note that the supernatant is
not colored.
(right : hemolysis) RBC suspension treated with the hemolysin of S. pyogenes at 37C for 30 min,
become transparent by hemolysis.
Copyright 2004, Medicine School of Shandong University
When there is a decrease in the surface
area to the cell volume, as in the
spherocyte, the osmotic fragility is
increased. The resistance of such cells
to hypotonic solutions is decreased.
In cells as the fragmentosit and target
cell, where the surface area relationship
to the volume of the cell is increased
over that typified in the normal
erythrocyte, then there is an increased
resistance to hypotonic solutions. Such
cells have a decreased osmotic fragility.
Copyright 2004, Medicine School of Shandong University
Tube mLs mLs NaCl Conc.
1.0% distilled (%)
NaCl water
1 0.0 10.0 0 Hemolisis total
2 9.0 1.0 0.2 Hemolisis total
3 8.0 2.0 0.4 Hemolisis sebagian
4 7.5 2.5 0.5 Tidak terjadi hemolisis
5 7.0 3.0 0.6 Tidak terjadi hemolisis
6 6.5 3.5 0.7 Tidak terjadi hemolisis
7 6.0 4.0 0.8 Tidak terjadi hemolisis
8 5.5 4.5 0.9 Tidak terjadi hemolisis
(isotonis)
9 5.0 5.0 1.0 Krenasi
10 4.5 5.5 1.0 Krenasi
Copyright 2004, Medicine School of Shandong University
Test Fragilitas
Osmotik Eritrosit
(Osmotic Fragility
Test)

Copyright 2004, Medicine School of Shandong University


HEREDITARY SPHEROCYTOSIS
Hasil Tes Fragilitas Osmotik Eritrosit

100
80
% Hemolysis

60
40
20
0
0,3 0,4 0,5 0,6
NaCl (% of normal saline)

Normal HS
Copyright 2004, Medicine School of Shandong University
EXPOSURE TO CHEMICAL SOLVENTS
Exposure measurements in combination with analysis of
haematological parameters may be a tool for early
detection of cellular changes in the blood caused by
exposure to solvents, before the appearance of clinical
symptoms.

Copyright 2004, Medicine School of Shandong University


Exposure to toxic metals
Lead poisoning
Erythrocytes as an important target of lead toxicity
After ingestion or inhalation, lead molecules enters the
bloodstream where it is predominantly bound to
erythrocyte proteins, cause proteolysis and disruption of
RBC membrane.
Lead alters lipid metabolism, enhances lipid peroxidation
and decreases cell membrane fluidity.
Lead may be responsible causing osmotic change in blood
hence osmotic fragility is the reason for hemolysis.

Copyright 2004, Medicine School of Shandong University


SNAKE VENOM
Snake venom is a complex mixture of proteolytic enzymes,
peptidases proteinases, phospholipases and neurotoxins that are
able to cause serious damage to the musculoskeletal, blood clotting,
cardiopulmonary, renal and central nervous systems.
Hemotoxic effects induce hemolysis, fibrinogen proteolysis, and
thrombocytopenia, which, along with activation of plasminogen, can
lead to a bleeding diathesis in severe envenomation.
Phospholipase A2 catalyzes the hydrolysis of phosphoglycerides
creating phospholipids, which have detergent properties with a
highly polar hydrophilic head and a hydrophobic tail and therefore
they are capable of damaging cell membranes by breaking the
continuity of its bilayer lipid.

Copyright 2004, Medicine School of Shandong University


KALSIUM
Fungsi struktural mineral tulang & gigi
Fungsi regulasi :
- Second messenger
kerja hormon
- Kontraksi otot
- Konduksi syaraf
- Pembekuan darah
- Kofaktor utk aktivasi enzim
- Aktifitas sekretorik
klj eksokrin & endokrin
Copyright 2004, Medicine School of Shandong University
TRANSPORT KALSIUM DLM DARAH
Kalsium ekstraseluler &
intraseluler hanya 1% dr total
kalsium tubuh
Kalsium intraseluler : 0.0001
konsentrasi kalsium ekstraseluler
Konsentrasi kalsium ekstraseluler
& intraseluler diatur dg ketat
Dlm darah kalsium berada dlm 3
bentuk :
Free (ionized) calcium (50%)
fungsional
Terikat pd albumin (40%)
Kompleks dg bikarbonat, sitrat
atau fosfat (10%)

Copyright 2004, Medicine School of Shandong University


PERAN KALSIUM (Ca2+)
dlm hemostasis
Trtm di jalur intrinsik & jalur bersama
Ca2+ sbg koenzim, berikatan dg faktor koagulasi &
mengaktifkan faktor koagulasi punya aktifitas
enzimatik; memungkinkan ikatan faktor koagulasi
pd membran fosfolipid trombosit teraktivasi
Antikoagulan in vitro mrpk Ca-chelating agents
(Sitrat, EDTA, Oksalat) mengikat Ca2+

Copyright 2004, Medicine School of Shandong University


Copyright 2004, Medicine School of Shandong University
KONTROL HOMEOSTASIS KALSIUM & FOSFAT

Copyright 2004, Medicine School of Shandong University


PERUBAHAN KADAR KALSIUM DARAH
Hipokalsemia Carpopedal Spasm
Tetani otot (carpopedal spasm)
Dilatasi jantung
permeabilitas membran sel
Ggn pembekuan darah (Ca faktor -
pembekuan darah ke berapa?)

Hiperkalsemia
Depresi sistem syaraf, reflex
Kelemahan otot
Ggn motilitas usus, konstipasi
Pembentukan kristal kalsium fosfat
Copyright 2004, Medicine School of Shandong University
Koreksi kadar Calcium
Perubahan kadar albumin 1 gram/dL
perubahan kadar kalsium serum 0.8 mg/dL
Kadar albumin serum normal 3.5 - 5.0 g/dl
Bila tidak misdiagnosis hiperkalsemia

Calcium terkoreksi Albumin =

Serum calcium + [(4 -albumin) X 0.8]

Contoh: Ca 10.5 mg/dL & Alb 2.5 g/dL:


= 10.5 + [(4 2.5) X 0.8] = 11.7 mg/dL
Copyright 2004, Medicine School of Shandong University
SAFETY PRECAUTION
Jangan bercanda, membau botol, mencampur-campur
reagen yg tdk diinstruksikan utk dicampur.
Berhati-hatilah bila bekerja dg bahan uji yang berasal dr
bahan biologis darah, krn kemungkinan adanya kuman atau
virus yg berbahaya spt HIV, Hepatitis B dan hepatitis C.
Selalu gunakan sarung tangan karet.
Hindari kemungkinan tertusuk jarum.
Cuci segera tangan atau anggota badan yang kontak
dengan bahan biologis menggunakan sabun.

Copyright 2004, Medicine School of Shandong University


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