Transcript Blood

BLOOD COMPOSITION
Dr. Husnil Kadri, M.Kes
Biochemistry Departement
Medical Faculty Of Andalas University
Padang
Fungsi Utama Darah
1. Respirasi;
pengangkutan O2 dan CO2
2. Nutrisi;
pengangkutan hasil absorpsi usus
3. Ekskresi;
pengangkutan sisa metabolik ke ginjal,
paru-paru, kulit, & usus
Fungsi Utama Darah
4. Keseimbangan asam-basa
5. Keseimbangan air;
antara sirkulasi darah dan jaringan
6. Pengaturan suhu tubuh
7. Pertahanan terhadap infeksi;
oleh sel darah putih & antibodi
Fungsi Utama Darah
8. Pengangkutan hormon &
pengaturan metabolisme
9. Pengangkutan metabolit
10. Koagulasi
Components of Whole Blood
Plasma
(55% of whole blood)
Buffy coat:
leukocyctes and
platelets
(<1% of whole blood)
1 Withdraw blood
2 Centrifuge
and place in tube
• Hematocrit
• Males: 47% ± 5%
• Females: 42% ± 5%
Erythrocytes
(45% of whole blood)
Formed
elements
Physical Characteristics of Blood
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Average volume of blood:
– 5–6 L for males; 4–5 L for females (Normovolemia)
– Hypovolemia - low blood volume
– Hypervolemia - high blood volume
Viscosity (thickness) - 4 - 5 (where water = 1)
The pH of blood is 7.35–7.45; x = 7.4
Osmolarity = 300 mOsm or 0.3 Osm
– This value reflects the concentration of solutes in the plasma
Salinity = 0.85%
– Reflects the concentration of NaCl in the blood
Temperature is 38C, slightly higher than “normal” body
temperature
Blood accounts for approximately 8% of body weight
Components of Blood
– 55% plasma
– 45% cells
• 99% RBCs
• < 1% WBCs and platelets
Blood Plasma
• Blood plasma components:
– Water = 90-92%
– Proteins = 6-8%
• Albumins; maintain osmotic pressure of the blood
• Globulins
– Alpha and beta globulins are used for transport purposes
– Gamma globulins are the immunoglobulins (IgG, IgA, etc)
• Fibrinogen; a clotting protein
– Organic nutrients – glucose, carbohydrates,
amino acids
– Electrolytes – sodium, potassium, calcium,
chloride, bicarbonate
– Nonprotein nitrogenous substances – lactic acid,
Formed Elements
• Formed elements comprise 45% of
blood
• Erythrocytes, leukocytes, and platelets
make up the formed elements
– Only WBCs are complete cells
– RBCs have no nuclei or organelles, and
platelets are just cell fragments
• Most formed elements survive in the
bloodstream for only a few days
• Most blood cells do not divide but are
renewed by cells in bone marrow
Erythrocytes (RBCs)
• Biconcave disc
– Folding increases surface area (30% more surface area)
– Plasma membrane contains spectrin
• Give erythrocytes their flexibility
• Anucleate, no centrioles, no organelles
– End result - no cell division
– No mitochondria means they generate ATP anaerobically
• Prevents consumption of O2 being transported
• Filled with hemoglobin (Hb) - 97% of cell contents
– Hb functions in gas transport
• Hb + O2
HbO2 (oxyhemoglobin)
• Most numerous of the formed elements
– Females: 4.3–5.2 million cells/cubic millimeter
– Males: 5.2–5.8 million cells/cubic millimeter
Erythrocytes (RBCs)
Figure 17.3
Erythrocyte Function
• Erythrocytes are dedicated to respiratory gas
transport
• Hemoglobin reversibly binds with oxygen and
most oxygen in the blood is bound to
hemoglobin
• Composition of hemoglobin
– A protein called globin
• made up of two alpha and two beta chains
– A heme molecule
• Each heme group bears an atom of iron, which can bind to
one oxygen molecule
• Each hemoglobin molecule thus can transport four
molecules of oxygen
Structure of Hemoglobin
Figure 17.4
Hemoglobin
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Satu mol. Hb dewasa (HbA) mempunyai;
- 4 gugus heme
- Setiap heme mengandung 1 ion Fe2+
- 4 subunit protein globin
- Setiap subunit mengikat 1 mol. O2
- 1 mol. Globin mengikat 1 mol. CO2
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Subunit rantai terdiri dari 2 a dan 2 b;
- a masing-masing = 141 asam amino
- b masing-masing = 146 asam amino
Hemoglobin
• Oxyhemoglobin – hemoglobin bound to oxygen
– Oxygen loading takes place in the lungs
• Deoxyhemoglobin – hemoglobin after oxygen
diffuses into tissues (reduced Hb)
• Carbaminohemoglobin – hemoglobin bound to
carbon dioxide
– Carbon dioxide loading takes place in the
tissues
WBC Anatomy and Types
• All WBCs (leukocytes) have a nucleus and
no hemoglobin
• Granular or agranular classification based
on presence of cytoplasmic granules made
visible by staining
– granulocytes are neutrophils, eosinophils or
basophils
– agranulocytes are monocyes or lymphocytes
Differential WBC Count
• Detection of changes in numbers of circulating
WBCs (percentages of each type)
– indicates infection, poisoning, leukemia,
chemotherapy, parasites or allergy reaction
• Normal WBC counts
– neutrophils 60-70% (up if bacterial infection)
– lymphocyte 20-25% (up if viral infection)
– monocytes 3 - 8 % (up if fungal/viral infection)
– eosinophil 2 - 4 % (up if parasite or allergy reaction)
– basophil <1% (up if allergy reaction or hypothyroid)
Neutrophils (Granulocyte)
• Polymorphonuclear Leukocytes or Polys
• Nuclei = 2 to 5 lobes connected by thin
strands
– older cells have more lobes
– young cells called band cells because of
horseshoe shaped nucleus (band)
• Fine, pale lilac practically invisible granules
• Diameter is 10-12 microns
• 60 to 70% of circulating WBCs
Eosinophils (Granulocyte)
• Nucleus with 2 or 3 lobes connected by
a thin strand
• Large, uniform-sized granules stain
orange-red with acidic dyes
– do not obscure the nucleus
• Diameter is 10 to 12 microns
• 2 to 4% of circulating WBCs
Basophils (Granulocyte)
• Large, dark purple, variable-sized
granules stain with basic dyes
– obscure the nucleus
• Irregular, s-shaped, bilobed nuclei
• Diameter is 8 to 10 microns
• Less than 1% of circulating WBCs
Lymphocyte (Agranulocyte)
• Dark, oval to round nucleus
• Cytoplasm sky blue in color
– amount varies from rim of blue to normal
amount
• Small cells 6 - 9 microns in diameter
• Large cells 10 - 14 microns in diameter
– increase in number during viral infections
• 20 to 25% of circulating WBCs
Lymphocytes
– B cells - responsible for humoral immunity
– T cells - responsible for cell mediated
immunity
• B cells responsible for production of
antibodies
– Receptor matches antigen
– Cells multiply
– Antibodies
• T cells
– Cytotoxic T cells (Killer T cells)
• Bind to cytotoxic cells (eg infected by virus)
• Swell
• Release toxins into cytoplasm
– Helper T cells
• Most numerous
• Activate B cells, killer T cells
• Stimulate macrophages
– Suppressor T cells
• Regulate activities of other cell types
Monocyte (Agranulocyte)
• Nucleus is kidney or horse-shoe shaped
• Largest WBC in circulating blood
– does not remain in blood long before migrating to the
tissues
– differentiate into macrophages
• fixed group found in specific tissues
– alveolar macrophages in lungs
– kupffer cells in liver
• wandering group gathers at sites of infection
• Diameter is 12 - 20 microns
• Cytoplasm is a foamy blue-gray
• 3 to 8% o circulating WBCs
Emigration & Phagocytosis in WBCs
UNSUR SELULAR DALAM RESPON IMUN
1. Jalur limfoid yang membentuk limfosit
dan subsetnya
2. Jalur mieloid yang membentuk sel-sel
fagosit mononuklear & polimorfonuklear
(PMN).
PMN terdiri dari:
neutrofil, eosinofil, basofil
Platelets
• Platelets are fragments of megakaryocytes
• Their granules contain serotonin, Ca2+,
enzymes, ADP, and platelet-derived
growth factor (PDGF)
• Platelets function in the clotting
mechanism by forming a temporary plug
that helps seal breaks in blood vessels
• Platelets not involved in clotting are kept
inactive by Nitric Oxide (NO) and
prostaglandins
Protein Plasma
- Bagian utama unsur padat dalam plasma.
- Konsentrasi total protein plasma + 7-7,5 g/dl.
- Berbagai protein plasma dapat dipisahkan
menurut karakteristik kelarutannya.
- Metode pemisahan tsb antara lain;
1. Salting-out (Na2SO4 23%, dll)
2. Elektroforesis
Zone Electrophoresis of Plasma
Proteins
+
globulins
g
pI
6.0
b
a1 a2
5.6
5.1
albumin
4.7
Protein Plasma
1. Sebagian besar disintesis di hepar.
2. Umumnya disintesis sbg preprotein pada
poliribosom terikat membran. Preprotein
akan mengalami modifikasi pascatranslasi.
3. Hampir semuanya berupa glikoprotein,
kecuali albumin.
4. Bersifat polimorfisme (ciri bawaan pd
populasi dgn sedikitnya 2 macam fenotipe).
contoh; gol. Darah ABO
Plasma Proteins
• More than 200
• Most abundant
– Albumin - 4-5 g/100 mL
- g-globulins - ~1 g/100 mL
– fibrinogen - 0.2-0.4g/100 mL
Albumin
- Merupakan protein utama dalam plasma.
- Mempertahankan 75-80% tekanan osmotik.
- Berfungsi mengikat berbagai macam ligand,
seperti; asam lemak bebas, Ca, Cu, Zn,
hormon steroid, bilirubin, metheme
Albumin
- Albumin juga dapat mengikat obat-an,
seperti; sulfonamid, penisilin-G,
dikumarol, aspirin
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Penyakit hepar akan memperlihatkan rasio
albumin/globulin yang menurun.
Transferin
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Adalah b1-globulin berbentuk glikoprotein
yang disintesis di hepar.
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Berfungsi sebagai alat transpor besi (Fe3+)
untuk dibawa ke jaringan.
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Jika besi tidak diikat oleh transferin, maka
akan menjadi prooksidan.
Ceruloplasmin
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Protein ini adalah a2-globulin yang
mengandung 90% Cu plasma.
Tetapi 10% Cu terikat longgar pd albumin,
sehingga mudah dilepas ke jaringan.
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Ceruloplasmin mengandung ferroksidase
yang mengkatalisis ion Fe2+ --> Fe3+,
karena hanya ion Fe3+ yang mampu
berikatan dgn apotransferin.
g-Globulins
• 20% of plasma proteins
• “g” refers to electrophoretic mobility
• Represents a group of proteins of
variable structure
– immunoglobulins
• Main functional task is immunochemical
– Antibodies - combine with specific
antigens
Imunoglobulin Plasma
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Disintesis dalam sel plasma.
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Sel plasma adalah turunan Sel-b yang
mensintesis dan mensekresikan imunoglobulin sebagai respon terhadap pajanan
berbagai antigen.
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Semua imunoglobulin mengandung paling
kurang 2 rantai ringan dan 2 rantai berat.
Classes of Immunoglobulins
• IgG – Identifies microorganisms for
engulfment or lysis
• IgE – Inhibits parasite invasion; involved in
allergic reactions
• IgD – Unknown
• IgA – Basis for passive immunity provided by
breast milk, agglutinates infectious agents in
secretions outside the body, present in tears,
mucous
• IgM – Identifies microorganisms for
engulfment or lysis
• Basic 4 chain structural unit
– MW = 2x55000 +2x27000 = 160000
Fibrinogen
• Coagulation
• Structure:
– MW 340 000
– Sequence of amino acids is known
(3000)
– 4y, 3y structure
• 6 polypeptide chains, 2a (67,000),
2b (56,000), 2g (47,000)
Function:
– Blood coagulation (clotting)
Fibrinogen
Fibrin
Thrombin
Plasmin
Fibrin
Degradation (FDP)
Plasmin is end product of fibrinolytic system
Clot needs to be removed
Not needed forever
Could embolize to lungs, brain
Haptoglobin
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Merupakan glikoprotein plasma yang
mengikat hemoglobin ekstrakorpuskular.
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Membentuk komplek Hb-Hp (HemoglobinHaptoglobin).
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Hb ekstrakorpuskular merupakan hasil
penguraian + 10% Hb yang dilepas ke dlm
sirkulasi.
Kepustakaan
•
Harbut, C. 150 Blood. Download 19-10-2010.
http://www.cerritos.edu/charbut/AP150/lec_otl/150%20Blood.ppt
•
Rand, ML., Murray, RK. 2003. Protein plasma, imunoglobulin, dan pembekuan
darah. Dalam: Andry Hartono, penerjemah. Harper’s Biochemistry. 25th ed. Eds.
R.K. Murray, D.K. Granner, P.A. Mayes, V.W. Rodwell. McGraw-Hill Companies,
New York: 702 - 11.
•
Simpson, S. Chapter 19 Blood. Download 19-10-2010.
•
Sheardown, H. Blood Biochemistry. McMaster University. Download 20-052007.