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  • BLOOD BIOCHEMISTRYDisusun Oleh:dr. Husnil Kadri, M.Kes

    Biochemistry Departement Medical Faculty Of Andalas University Padang

  • BIOSINTESIS HEMOGLOBIN(PORFIRIN)

  • Struktur PorfirinPorfirin 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*

  • 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*

  • Sintesis Heme di Mitokondria85% sintesis heme terjadi dalam sel pembentuk eritrosit pada sumsum tulangHeme disintesis dari suksinil KoA + glisin.Piridoksal fosfat diperlukan untuk mengaktifkan glisin.

    *

  • Sintesis Heme di Mitokondria

    *

  • 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.

    *

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

  • 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 BloodWithdraw blood and place in tube12CentrifugePlasma (55% of whole blood)Formed elementsBuffy coat: leukocyctes and platelets (
  • Physical Characteristics of BloodAverage volume of blood:56 L for males; 45 L for females (Normovolemia)Hypovolemia - low blood volumeHypervolemia - high blood volumeViscosity (thickness) - 4 - 5 (where water = 1)The pH of blood is 7.357.45; x = 7.4Osmolarity = 300 mOsm or 0.3 OsmThis value reflects the concentration of solutes in the plasmaSalinity = 0.85%Reflects the concentration of NaCl in the bloodTemperature is 38C, slightly higher than normal body temperatureBlood accounts for approximately 8% of body weight

  • Components of Blood

    55% plasma 45% cells 99% RBCs< 1% WBCs and platelets

  • Blood PlasmaBlood plasma components:Water = 90-92%Proteins = 6-8%Organic nutrients glucose, carbohydrates, amino acidsElectrolytes sodium, potassium, calcium, chloride, bicarbonate Nonprotein nitrogenous substances lactic acid, urea, creatinineRespiratory gases oxygen and carbon dioxide

  • Formed ElementsFormed elements comprise 45% of bloodErythrocytes, leukocytes, and platelets make up the formed elementsOnly WBCs are complete cellsRBCs have no nuclei or organelles, and platelets are just cell fragmentsMost blood cells do not divide but are renewed by cells in bone marrow

  • Erythrocytes (RBCs)Biconcave discFolding increases surface area (30% more surface area)Plasma membrane contains spectrinGive erythrocytes their flexibilityAnucleate, no centrioles, no organellesEnd result - no cell divisionNo mitochondria means they generate ATP anaerobicallyPrevents consumption of O2 being transportedFilled with hemoglobin (Hb) - 97% of cell contentsHb functions in gas transportHb + O2 HbO2 (oxyhemoglobin)Most numerous of the formed elementsFemales: 4.35.2 million cells/cubic millimeterMales: 5.25.8 million cells/cubic millimeter

  • Erythrocytes (RBCs)Figure 17.3

  • Erythrocyte FunctionErythrocytes are dedicated to respiratory gas transportHemoglobin reversibly binds with oxygen and most oxygen in the blood is bound to hemoglobinComposition of hemoglobin A protein called globinmade up of two alpha and two beta chainsA heme moleculeEach heme group bears an atom of iron, which can bind to one oxygen moleculeEach hemoglobin molecule thus can transport four molecules of oxygen

  • Structure of HemoglobinFigure 17.4

  • HemoglobinSatu 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

  • HemoglobinOxyhemoglobin hemoglobin bound to oxygenOxygen loading takes place in the lungsDeoxyhemoglobin 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 TypesAll WBCs (leukocytes) have a nucleus and no hemoglobinGranular or agranular classification based on presence of cytoplasmic granules made visible by staininggranulocytes are neutrophils, eosinophils or basophilsagranulocytes 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 reactionNormal WBC countsneutrophils 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
  • Neutrophils (Granulocyte)Polymorphonuclear Leukocytes or PolysNuclei = 2 to 5 lobes connected by thin strandsolder cells have more lobesyoung 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 strandLarge, uniform-sized granules stain orange-red with acidic dyesdo not obscure the nucleusDiameter is 10 to 12 microns2 to 4% of circulating WBCs

  • Basophils (Granulocyte)Large, dark purple, variable-sized granules stain with basic dyesobscure the nucleusIrregular, s-shaped, bilobed nuclei Diameter is 8 to 10 micronsLess than 1% of circulating WBCs

  • Lymphocyte (Agranulocyte)Dark, oval to round nucleusCytoplasm sky blue in coloramount varies from rim of blue to normal amountSmall cells 6 - 9 microns in diameterLarge cells 10 - 14 microns in diameterincrease in number during viral infections20 to 25% of circulating WBCs

  • Lymphocytes

    B cells - responsible for humoral immunityT cells - responsible for cell mediated immunity

    B cells responsible for production of antibodies Receptor matches antigenCells multiplyAntibodies

  • T cellsCytotoxic T cells (Killer T cells)Bind to cytotoxic cells (eg infected by virus)SwellRelease toxins into cytoplasmHelper T cellsMost numerousActivate B cells, killer T cellsStimulate macrophagesSuppressor T cellsRegulate activities of other cell types

  • Monocyte (Agranulocyte)Nucleus is kidney or horse-shoe shapedLargest WBC in circulating blooddoes not remain in blood long before migrating to the tissuesdifferentiate into macrophagesfixed group found in specific tissuesalveolar macrophages in lungskupffer cells in liverwandering group gathers at sites of infectionDiameter is 12 - 20 micronsCytoplasm is a foamy blue-gray 3 to 8% o circulating WBCs

  • UNSUR SELULAR DALAM RESPON IMUNJalur limfoid yang membentuk limfosit dan subsetnyaJalur mieloid yang membentuk sel-sel fagosit mononuklear & polimorfonuklear (PMN).PMN terdiri dari: neutrofil, eosinofil, basofil

  • Platelets are fragments of mega-karyocytes

    Platelets function in the clotting mechanism by forming a temporary plug that helps seal breaks in blood vessels

    Platelets

  • 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

  • Protein PlasmaSebagian 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

  • Plasma ProteinsMore than 200

    Most abundantAlbumin - 4-5 g/100 mL- g-globulins - ~1 g/100 mLfibrinogen - 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

    - Penyakit hepar akan memperlihatkan rasio albumin/globulin yang menurun.

  • TransferinAdalah b1-globulin berbentuk glikoprotein yang disintesis di hepar.

    Berfungsi sebagai alat transpor besi (Fe3+)