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BLOOD COMPOSITION. dr. Husnil Kadri , M.Kes Biochemistry Departement Medical Faculty Of Andalas University Padang. BIOSINTESIS HEMOGLOBIN (PORFIRIN). Struktur Porfirin. Porfirin adalah senyawa siklik yg dibentuk oleh 4 cincin pirol.

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blood composition

BLOOD COMPOSITION

dr. HusnilKadri, M.Kes

Biochemistry Departement

Medical Faculty Of Andalas University

Padang

struktur porfirin
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

beberapa hemoprotein
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 mitokondria
SintesisHemediMitokondria
  • 85% sintesis heme terjadi dalam sel pembentuk eritrosit pada sumsum tulang
  • Heme disintesis dari suksinil KoA + glisin.
  • Piridoksal fosfat diperlukan untuk mengaktifkan glisin.
pengaturan sintesis heme
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.
porfiria
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

dasar biokimia porfiria
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

terapi porfiria
Terapi Porfiria
  • Hanya simptomatik.
  • Represor ALA-sintase;

- glukosa

- hematin (bentuk hidroksida dari heme)

- b-karoten untuk fotosensitifitas

- preparat tabir surya

  • Kontraindikasi;

- preparat anestesi

- alkohol

- griseofulvin & barbiturat

fungsi utama darah
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 darah1
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 darah2
Fungsi Utama Darah

8. Pengangkutan hormon &

pengaturan metabolisme

9. Pengangkutan metabolit

10. Koagulasi

components of whole blood
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)

Withdraw blood and place in tube

Centrifuge

1

2

  • Hematocrit
    • Males: 47% ± 5%
    • Females: 42% ± 5%
physical characteristics of blood
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 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
Components of Blood
  • 55% plasma
  • 45% cells
    • 99% RBCs
    • < 1% WBCs and platelets
blood plasma
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
formed elements
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
erythrocytes rbcs
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
erythrocyte function
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 oxygenmolecule
      • Each hemoglobin molecule thus can transport four molecules of oxygen
hemoglobin
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

hemoglobin1
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
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
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
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
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
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
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
slide34
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
slide35
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
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
unsur selular dalam respon imun
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

platelets
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
protein plasma
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
Zone Electrophoresis of Plasma Proteins

+

-

globulins

albumin

g

b

a1

a2

pI

6.0

5.6

5.1

4.7

protein plasma1
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

plasma proteins
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
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

albumin1
Albumin

- Albumin juga dapat mengikat obat-an,

seperti; sulfonamid, penisilin-G,

dikumarol, aspirin

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

transferin
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.
ceruloplasmin
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.

g globulins
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
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.
classes of immunoglobulins
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
slide51
Basic 4 chain structural unit
    • MW = 2x55000 +2x27000 = 160000
fibrinogen
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)
slide54

Thrombin

Fibrinogen

Fibrin

Plasmin

Fibrin

Degradation (FDP)

Function:

  • Blood coagulation (clotting)
  • Plasmin is end product of fibrinolytic system
  • Clot needs to be removed
    • Not needed forever
    • Could embolize to lungs, brain
haptoglobin
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
Kepustakaan
  • Marks, DB., Marks, AD., Smith CM. 1996. 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: 612 - 4.
  • Murray, RK. 2003. 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: 342 - 9.
  • Schumm, DE. 1992. Essentials of biochemistry. Dalam: Moch. Sadikin, penerjemah. Intisari Biokimia. Jakarta: Bina Aksara, 1993: 147.
kepustakaan1
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 20-05-2007.