Biochemistry Departement Medical Faculty Of Andalas University

Presentasi berjudul: "Biochemistry Departement Medical Faculty Of Andalas University"— Transcript presentasi:

1 Biochemistry Departement Medical Faculty Of Andalas University
BLOOD COMPOSITION Dr. Husnil Kadri, M.Kes Biochemistry Departement Medical Faculty Of Andalas University Padang

2 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

3 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

4 Fungsi Utama Darah 8. Pengangkutan hormon & pengaturan metabolisme
9. Pengangkutan metabolit 10. Koagulasi

5 Components of Whole Blood
Plasma (55% of whole blood) Buffy coat: leukocyctes and platelets (<1% of whole blood) Formed elements Erythrocytes (45% of whole blood) 1 Withdraw blood and place in tube 2 Centrifuge Hematocrit Males: 47% ± 5% Females: 42% ± 5%

6

7

8 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) (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

9 Components of Blood 55% plasma 45% cells 99% RBCs
< 1% WBCs and platelets

10

11 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, urea, creatinine Respiratory gases – oxygen and carbon dioxide

12 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

13 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 + O 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

14 Erythrocytes (RBCs) Figure 17.3

15 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

16 Structure of Hemoglobin
Figure 17.4

17 Hemoglobin 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 Subunit rantai terdiri dari 2 a dan 2 b; - a masing-masing = 141 asam amino - b masing-masing = 146 asam amino

18 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

19 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

20 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 % (up if fungal/viral infection) eosinophil % (up if parasite or allergy reaction) basophil <1% (up if allergy reaction or hypothyroid)

21 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 microns 60 to 70% of circulating WBCs

22 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

23 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

24 Lymphocyte (Agranulocyte)
Dark, oval to round nucleus Cytoplasm sky blue in color amount varies from rim of blue to normal amount Small cells microns in diameter Large cells microns in diameter increase in number during viral infections 20 to 25% of circulating WBCs

25 B cells responsible for production of antibodies
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

26 T cells Cytotoxic T cells (Killer T cells) Helper 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

27 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 microns Cytoplasm is a foamy blue-gray 3 to 8% o circulating WBCs

28 Emigration & Phagocytosis in WBCs

29 UNSUR SELULAR DALAM RESPON IMUN
Jalur limfoid yang membentuk limfosit dan subsetnya Jalur mieloid yang membentuk sel-sel fagosit mononuklear & polimorfonuklear (PMN). PMN terdiri dari: neutrofil, eosinofil, basofil

30 Platelets Platelets are fragments of mega-karyocytes
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

31 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

32 Zone Electrophoresis of Plasma Proteins
- + globulins albumin g b a1 a2 pI 6.0 5.6 5.1 4.7

33 Protein Plasma Sebagian besar disintesis di hepar. Umumnya disintesis sbg preprotein pada poliribosom terikat membran. Preprotein akan mengalami modifikasi pascatranslasi. Hampir semuanya berupa glikoprotein, kecuali albumin. Bersifat polimorfisme (ciri bawaan pd populasi dgn sedikitnya 2 macam fenotipe). contoh; gol. Darah ABO

34 Plasma Proteins More than 200 Most abundant Albumin g/100 mL - g-globulins - ~1 g/100 mL fibrinogen g/100 mL

35 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

36 Albumin - Albumin juga dapat mengikat obat-an, seperti; sulfonamid, penisilin-G, dikumarol, aspirin - Penyakit hepar akan memperlihatkan rasio albumin/globulin yang menurun.

37 Transferin Adalah b1-globulin berbentuk glikoprotein yang disintesis di hepar. Berfungsi sebagai alat transpor besi (Fe3+) untuk dibawa ke jaringan. Jika besi tidak diikat oleh transferin, maka akan menjadi prooksidan.

38 Ceruloplasmin Protein ini adalah a2-globulin yang mengandung 90% Cu plasma. Tetapi 10% Cu terikat longgar pd albumin, sehingga mudah dilepas ke jaringan. Ceruloplasmin mengandung ferroksidase yang mengkatalisis ion Fe2+ --> Fe3+, karena hanya ion Fe3+ yang mampu berikatan dgn apotransferin.

39 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

40 Disintesis dalam sel plasma.
Imunoglobulin Plasma Disintesis dalam sel plasma. Sel plasma adalah turunan Sel-b yang mensintesis dan mensekresikan imuno- globulin sebagai respon terhadap pajanan berbagai antigen. Semua imunoglobulin mengandung paling kurang 2 rantai ringan dan 2 rantai berat.

41 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

42 Basic 4 chain structural unit
MW = 2x x27000 = Constant - same amino acid sequence for all of the molecules Variable - varies between molecules- results in specificity of molecules Two heavy and two light chains joined by disulfide bonds. Variable region - red - binds the antigen Constant region (black) can activate complement pathway or attach the Ab to cells such as macrophages

43 The basic antibody unit is a monomer, IgA is a dimer and IgM is a pentamer

44 Fibrinogen Coagulation Structure: MW Sequence of amino acids is known (3000) 4y, 3y structure 6 polypeptide chains, 2a (67,000), 2b (56,000), 2g (47,000)

45 Blood coagulation (clotting)
Function: Blood coagulation (clotting) Fibrinogen Fibrin Thrombin Fibrin Degradation (FDP) Plasmin Plasmin is end product of fibrinolytic system Clot needs to be removed Not needed forever Could embolize to lungs, brain Coagulation - very important consideration when processing blood outside of the body Structure must incorporate the ability to be easily broken down after clotting What is a clot and how does it form from the polymerization of fibrinogen? Overhead from Brash’s notes next

46 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.

47 Kepustakaan Harbut, C. 150 Blood. Download Rand, ML., Murray, RK 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: Simpson, S. Chapter 19 Blood. Download Sheardown, H. Blood Biochemistry. McMaster University. Download