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2.1. Biokimia Darah PDF
2.1. Biokimia Darah PDF
ASPECT OF BLOOD
IntroducHon
Qs related to Blood
Anak saya waktu disunat darahnya susah berhenH,
kenapa ya dok?
Tiap kali saya sikat gigi keluar darah, kenapa ya dok?
Hidung adik saya sering mimisen. Kenapa ya dok?
Tekanan darah saya rendah. Apa saya harus makan
sate kambing terus dok?
Kadar Hemoglobin (Hb) paman saya kurang. Kata
dokter harus ditransfusi. Apa kalau kurang darah
harus ditransfusi dok?
Anak saya kurang darah, apa harus diberi lauk haH &
ampela terus dok?
Fer$lized
ovum
Zygote
Teaching aims
By the end of the lecture, students would be
able to understand & describe various
biochemical aspects of blood
Reference:
Murray K et al. 2000. Harpers Biochemistry,
25th ed & other lecture sources
Core topics
Introduction
Composition and main functions of blood
Plasma and its proteins
Hemostasis and thrombosis
Hemoglobin synthesis and degradation
IntroducHon
Blood is a liquid tissue circulates in
what is virtually a closed system of blood
vessels
Blood consists of solid elements (RBC,
WBC & platelets) suspended in a liquid
medium called plasma critical for the
maintenance of health
FuncHons
Respiration
Nutrition
Excretion
Maintenance of normal acid-base balance
Regulation of water balance
Regulation of body temperature
Composition
Solid elements : RBC, WBC, Platelets
Liquid medium : plasma consisting of water,
electrolytes, metabolites, nutrients, proteins,
hormones, etc.
Water & electrolyte composition of
plasma is practically the same as that of all
extracellular fluids
Once the blood has clotted (coagulated),
the remaining liquid phase (called serum)
lacks of the clotting factors (including
fibrinogen)
Composition of Blood
19-13
Leukocyte (WBC)
There are 3 groups :
granulocytes (polymorphonuclear leukocytes
= PMNs):
Neutrophils
Basophils
eosinophils
monocytes
lymphocytes
Platelets (Thrombocytes)
cell-like parHcles smaller than RBCs and
WBCs.
Help with cloing process by gathering
at bleeding site and clumping together
to form a plug that helps seal the blood
vessel.
H&A
Tr-A
Ps
r u
e b
c s
u t
r a
s n
o c
r e
H
Tr-H
Antigen
Tr-B
O
H&B
hh
Precursor
substance
Glucose
Precursor
Substance
(stays the
same)
Galactose
N-acetylglucosamine
Galactose
Source: cls.umc.edu/COURSES/.../ABOsystem.ppt
Glucose
H antigen
Galactose
N-acetylglucosamine
Galactose
Fucose
cls.umc.edu/COURSES/.../ABOsystem.ppt
cls.umc.edu/COURSES/.../ABOsystem.ppt
Glucose
Galactose
N-acetylglucosamine
Galactose
Fucose
N-acetylgalactosamine
cls.umc.edu/COURSES/.../ABOsystem.ppt
Glucose
Galactose
N-acetylglucosamine
Galactose
Fucose
Galactose
A
Group O
Many H
antigen sites
Group A
Fewer
H antigen
sites
GeneHcs
The H antigen is found on the RBC with
the Hh or HH genotype, but NOT from
the hh genotype
The A antigen is found on the RBC with
the Hh, HH, and A/A, A/O, or A/B
genotypes
The B antigen is found on the RBC with
the Hh, HH, and B/B, B/O, or A/B
genotypes
H anHgen
Certain blood types possess more H
antigen than others:
Greatest
amount of H
O>A2>B>A2B>A1>A1B
cls.umc.edu/COURSES/.../ABOsystem.ppt
Least
amount of H
Plasma proteins
Total plasma protein approx. 7.0-7.5 g/dl
A complex mixture of simple & conjugated
proteins such as glycoproteins & various types
of lipoproteins, thousands of antibodies
Can be separated by:
sodium or amm. sulfate into three major
groups fibrinogen, albumin & globulins
electrophoresis using cellulose acetate into
five bands albumin, 1, 2, & globulin
Cont.
Concentration of plasma protein is important in
determining the distribution of fluid between
blood & tissues
Osmotic pressure (oncotic pressure) exerted by
plasma protein is approx. 25 mm Hg.
Hydrostatic pressure in arterioles is approx.
37 mm Hg a net outward force of about 11
mm Hg drives fluid out into interstitial spaces.
Hydrostatic pressure in venules is approx. 17
mm Hg a net force of about 9 mm Hg
attracts water back into circulation
Cont.
The above pressures are often referred to
as the Starling forces.
If plasma protein concentration is markedly
diminished (eg. due to severe protein
malnutrition fluid is not attracted back
into the intravascular compartment and
accumulates in extravascular tissue spaces
oedema
Cont.
Most plasma proteins are synthesized in the
liver
Plasma proteins are generally synthesized
on membrane-bound polyribosomes
Almost all plasma proteins are
glycoproteins
Many plasma proteins exhibit polymorphism
Cont.
albumin for bilirubin, FFA, ions, metals,
metheme, steroids, other hormones, variety
of drugs
Ceruloplasmin contains Cu but albumin is
more important in physiological transport of
Cu
Corticosteroid-binding globulin (transcortin)
Haptoglobin binds extracorpuscular Hb
Liproproteins (chylomicron, VLDL, LDL,
HDL)
Cont.
Hemopexin
Retinol-binding protein
Sex hormone-binding globulin
Thyroid-binding
Transferrin
Transthyretin (formerly pre albumin, binds
T4 & forms a complex with Retinol-binding
protein)
Cont.
Haptoglobin:
A plasma glycoprotein that binds
extracorpuscular Hb in a tight
noncovalent Hb-Hp complex
Prevent loss of free Hb into kidney
Its plasma levels are of some
diagnostic use low level in
hemolytic anemias
Cont.
Transferrin:
a 1-globulin, a glycoprotein, synthesized
in liver
Plays an important role in the bodys
metabolism of iron (two mol of Fe3+ per
mole of transferrin) diminishes potential
toxicity of free iron
Plasma concentration is approx. 300 mg/
dL can bind 300 g of iron per dL (Total
Iron Binding Capacity of plasma)
Ceruloplasmin (Cp)
2-globulin
Binds copper (Cu)
Exhibits a copper-dependent oxidase activity
Low levels of Cp are associated with Wilson
disease
Tissue levels of Cu & certain other metals
are regulated in part by metallomethionins
(small protein found in the cytosol of cells
particularly liver, kidney & intestine)
1-Antiproteinase (1-antitrypsin)
Synthesized by hepatocytes &
macrophages
Principal serine protease inhibitor of
human plasma inhibits trypsin,
elastase & certain other proteases
Deficiency of this protein has a role in
certain cases (approx. 5%) of
emphysema
2-Macroglobulin
A large plasma glycoprotein
Comprises 8-10% of the total plasma
protein in human
Synthesized by a variety of cell types,
including monocytes, hepatocytes &
astrocytes.
Binds many proteinases (an important
panproteinase inhibitor)
Binds many cytokines
Immunoglobulin
Play a major role in the bodys defence
mechanism
Synthesized by B lymphocytes
Immunoglobulin (Ig)
A group of proteins involved in mediating
immune response in higher organisms
In gamma globulin fraction of serum
Very heterogeneous
Similar in different species
106 different antibodies may be produced
in human adult
Ig structure
Tetramer :
* a pair of light chains (two identical
=kappa or =lambda chains)
* a pair of heavy chains (two identical
=alpha, =gamma, =delta, =epsilon or
=mu chains)
Light chain has one variable region (VL) &
one constant region (CL)
Heavy chain has one variable region (VH)
and three (, , ) or four (, ) constant
regions
22 22
4 %
IgA
22 22 10 %
IgM
22 22
15 %
IgD
IgE
22 22
18 %
22 22
18 %
Ig funcHonal groups
N terminal of H & L chains (VL/VH & CL /CH1)
=> antigen binding fragment
C terminal of L chain (CL) => interchain
disulphide bond
C terminal of H chain (CH) particularly C 2 &
C 3 * and C 4 of IgM & IgE) constitute the Fc
fragment responsible for class specific
effector function => complement fixation or
placental transfer, cell surface binding etc
Thrombi
Three types of thrombi:
White thrombus
Red thrombus
Disseminated fibrin deposit in very
small blood vessels or capillaries
F I : Fibrinogen
F II : Prothrombin
F III : Tissue factor
F IV : Ca2+
F V : Proaccelerin, labile factor,
accelerator (Ac-) globulin
F VII : Proconvertin, serum prothrombin
conversion accelerator (SPCA),
cothromboplastin
Intrinsic pathway
Involves factors XII, XI, IX, VIII, & X as
well as prekallikrein, HMW kininogen,
Ca2+ & platelet phospholipids results
in the production of factor Xa.
Commences with the contact phase in
which prekallikrein, HMW kininogen, F
XII & F XI are exposed to a negatively
charged activating surface.
Intrinsic pathway
PK
HK
XII
XIIa
HK
XI
Ca 2+
Extrinsic pathway
VII
XIa
VIIa/Tissue factor
IX
VIII
Ca 2+
IXa
Ca 2+
PL
VIIIa
X
V
Xa
Va
Prothrombin
Ca 2+
PL
Thrombin
Prothrombin
Thrombin
XIII
Fibrinogen
XIIIa
Fibrin monomer
Fibrin polymer
Cross-linked
Fibrin polymer
Extrinsic pathway
Also leads to activation of F X but by
different mechanism.
Involves tissue factor, F VII, F X & Ca2+
and results in the production of F Xa
It is initiated at the site of tissue injury
with the expression of tissue factor on
endothelial cells
Some notes
Levels of circulating thrombin must be
carefully controlled achieved in 2 ways:
Feedback mechanism through a
cascade of enzymatic reactions for the
conversion of prothrombin to thrombin
Inactivation of any thrombin formed by
circulating inhibitors (the most important
of which is antithrombin III)
Some notes(cont.)
Endogenous activity of antithrombin III is
greatly potentiated by the presence of
heparin
Coumarin anticoagulants (eg. Warfarin)
inhibit vit.K-dependent carboxylation of F II,
VII. IX & X
Fibrin clots are dissolved by plasmin
(circulates in plasma in the form of its
inactive zymogen, plasminogen)
Some notes(cont.)
Activators of plasminogen are found in
most body tissues e.g.
tissue plasminogen activator (alteplase,
t-PA) is a serine protease that is
released into circulation from vascular
endothelium under condition of injury or
stress & is catalytically inactive unless
bound to fibrin (recombinant t-PA is used
therapeutically as a fibrinolytic agent as
is Streptokinase
Urokinase (precursor: prourokinase)
TERIMAKASIH
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