BLOOD COMPOSITION Dr Husnil Kadri M Kes Biochemistry
BLOOD COMPOSITION Dr. Husnil Kadri, M. Kes Biochemistry Departement Medical Faculty Of Andalas University Padang
Fungsi Utama Darah 1. Respirasi; pengangkutan O 2 dan CO 2 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 • 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 p. H of blood is 7. 35– 7. 45; x = 7. 4 • Osmolarity = 300 m. Osm or 0. 3 Osm – This value reflects the concentration of solutes in the plasma • Salinity = 0. 85% – Reflects the concentration of Na. Cl 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 (Ig. G, Ig. A, 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 O 2 being transported • Filled with hemoglobin (Hb) - 97% of cell contents – Hb functions in gas transport • Hb + O 2 Hb. O 2 (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 • Satu mol. Hb dewasa (Hb. A) mempunyai; - 4 gugus heme - Setiap heme mengandung 1 ion Fe 2+ - 4 subunit protein globin - Setiap subunit mengikat 1 mol. O 2 - 1 mol. Globin mengikat 1 mol. CO 2 • 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, Ca 2+, 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 (Na 2 SO 4 23%, dll) 2. Elektroforesis
Zone Electrophoresis of Plasma Proteins + globulins g p. I 6. 0 b a 1 a 2 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 m. L - g-globulins - ~1 g/100 m. L – fibrinogen - 0. 2 -0. 4 g/100 m. L
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 - Penyakit hepar akan memperlihatkan rasio albumin/globulin yang menurun.
Transferin • Adalah b 1 -globulin berbentuk glikoprotein yang disintesis di hepar. • Berfungsi sebagai alat transpor besi (Fe 3+) untuk dibawa ke jaringan. • Jika besi tidak diikat oleh transferin, maka akan menjadi prooksidan.
Ceruloplasmin • Protein ini adalah a 2 -globulin yang mengandung 90% Cu plasma. Tetapi 10% Cu terikat longgar pd albumin, sehingga mudah dilepas ke jaringan. • Ceruloplasmin mengandung ferroksidase yang mengkatalisis ion Fe 2+ --> Fe 3+, karena hanya ion Fe 3+ 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 • Disintesis dalam sel plasma. • Sel plasma adalah turunan Sel-b yang mensintesis dan mensekresikan imunoglobulin sebagai respon terhadap pajanan berbagai antigen. • Semua imunoglobulin mengandung paling kurang 2 rantai ringan dan 2 rantai berat.
Classes of Immunoglobulins • Ig. G – Identifies microorganisms for engulfment or lysis • Ig. E – Inhibits parasite invasion; involved in allergic reactions • Ig. D – Unknown • Ig. A – Basis for passive immunity provided by breast milk, agglutinates infectious agents in secretions outside the body, present in tears, mucous • Ig. M – Identifies microorganisms for engulfment or lysis
• Basic 4 chain structural unit – MW = 2 x 55000 +2 x 27000 = 160000
Fibrinogen • Coagulation • Structure: – MW 340 000 – Sequence of amino acids is known (3000) – 4 y, 3 y structure • 6 polypeptide chains, 2 a (67, 000), 2 b (56, 000), 2 g (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 • Merupakan glikoprotein plasma yang mengikat hemoglobin ekstrakorpuskular. • Membentuk komplek Hb-Hp (Hemoglobin. Haptoglobin). • 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/AP 150/lec_otl/150%20 Blood. ppt • Rand, ML. , Murray, RK. 2003. Protein plasma, imunoglobulin, dan pembekuan darah. Dalam: Andry Hartono, penerjemah. Harper’s Biochemistry. 25 th ed. Eds. R. K. Murray, D. K. Granner, P. A. Mayes, V. W. Rodwell. Mc. Graw-Hill Companies, New York: 702 - 11. • Simpson, S. Chapter 19 Blood. Download 19 -10 -2010. • Sheardown, H. Blood Biochemistry. Mc. Master University. Download 20 -052007.
- Slides: 47