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

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Presentation on theme: "BLOOD COMPOSITION dr. Husnil Kadri, M.Kes Biochemistry Departement Medical Faculty Of Andalas University Padang."— Presentation transcript:

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

2 BIOSINTESIS HEMOGLOBIN (PORFIRIN)

3 Struktur Porfirin Porfirin adalah senyawa siklik yg dibentuk oleh 4 cincin pirol. Masing-masing cincin dihubungkan oleh 4 jembatan metenil (-HC=). Sifat khas porfirin adalah atom nitrogennya mampu mengikat ion logam. Contoh; - heme pada Hb mengikat Fe - klorofil pada tumbuhan hijau mengikat Mg 3

4 Beberapa Hemoprotein Protein Fungsi - Hemoglobin mengangkut oksigen di dalam darah - Mioglobin menyimpan oksigen di dalam otot - Sitokrom c keterlibatan pada rantai transpor elektron - Sitokrom P450 hidroksilasi xenobiotik - Katalase degradasi hidrogen peroksida - Triptofan pirolase oksidasi triptofan 4

5 Sintesis Heme di Mitokondria 85% sintesis heme terjadi dalam sel pembentuk eritrosit pada sumsum tulang Heme disintesis dari suksinil KoA + glisin. Piridoksal fosfat diperlukan untuk mengaktifkan glisin. 5

6 Sintesis Heme di Mitokondria 6

7 Pengaturan Sintesis Heme Enzim regulator adalah ALA-sintase. Heme bertindak sebagai regulator negatif (umpan balik negatif) sintesis enzim ALA- sintase. Jika heme meningkat, maka sintesis ALA-sintase akan menurun. 7

8 Porfiria Merupakan gangguan genetik biosintesis heme. Umumnya autosomal dominan, kecuali porfiria eritropoitik kongenital. Gejala; - nyeri abdomen - gangguan neuropsikiatri - fotosensitifitas kulit - bila berat = prototipe manusia srigala 8

9 Dasar Biokimia Porfiria Mutasi DNA Abnormalitas enzim pada sintesis heme Akumulasi ALA & PBG atau Akumulasi porfirinogen penurunan heme dlm sel & di kulit & jaringan tubuh Cairan tubuh Tanda & gejala Oksidasi spontan porfirinogen neuropsikiatrik menjadi porfirin Fotosensitifitas 9

10 Terapi Porfiria Hanya simptomatik. Represor ALA-sintase; - glukosa - hematin (bentuk hidroksida dari heme) -  -karoten untuk fotosensitifitas - preparat tabir surya Kontraindikasi; - preparat anestesi - alkohol - griseofulvin & barbiturat 10

11 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

12 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

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

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

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17 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

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

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20 Blood Plasma Blood plasma components: –Water = 90-92% –Proteins = 6-8% –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

21 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 blood cells do not divide but are renewed by cells in bone marrow

22 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 HbO 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

23 Erythrocytes (RBCs) Figure 17.3

24 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

25 Structure of Hemoglobin Figure 17.4

26 Hemoglobin Satu mol. Hb dewasa (HbA) mempunyai; - 4 gugus heme - Setiap heme mengandung 1 ion Fe subunit protein globin - Setiap subunit mengikat 1 mol. O mol. Globin mengikat 1 mol. CO 2 Subunit rantai terdiri dari 2  dan 2  -  masing-masing  =  141 asam amino -  masing-masing = 146 asam amino

27 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

28 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

29 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)

30 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

31 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

32 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

33 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

34 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

35 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

36 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

37 Emigration & Phagocytosis in WBCs

38 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

39 Platelets are fragments of mega- karyocytes 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 Platelets

40 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

41 Zone Electrophoresis of Plasma Proteins - + pI globulinsalbumin  

42 Protein Plasma 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

43 Plasma Proteins More than 200 Most abundant –Albumin g/100 mL -  -globulins - ~1 g/100 mL –fibrinogen g/100 mL

44 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

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

46 Transferin Adalah  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.

47 Ceruloplasmin Protein ini adalah  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.

48  -Globulins 20% of plasma proteins “  ” refers to electrophoretic mobility Represents a group of proteins of variable structure –immunoglobulins Main functional task is immunochemical –Antibodies - combine with specific antigens

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

50 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

51 Basic 4 chain structural unit –MW = 2x x27000 =

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53 Fibrinogen Coagulation Structure: –MW –Sequence of amino acids is known (3000) –4 y, 3 y structure 6 polypeptide chains, 2  (67,000), 2  (56,000), 2  (47,000)

54 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 Plasmin is end product of fibrinolytic system Clot needs to be removed Not needed forever Could embolize to lungs, brain

55 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.

56 Kepustakaan Marks, DB., Marks, AD., Smith CM Basic medical biochemistry: a clinical approach. Dalam: B.U. Pendit, penerjemah. Biokimia Kedokteran Dasar: Sebuah Pendekatan Klinis. Eds. J. Suyono., V. Sadikin., L.I. Mandera. Jakarta: EGC, 2000: Murray, RK Porfirin dan pigmen empedu. 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: Schumm, DE Essentials of biochemistry. Dalam: Moch. Sadikin, penerjemah. Intisari Biokimia. Jakarta: Bina Aksara, 1993:

57 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


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