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RULE OF 2/3
TOTAL BODY WEIGHT
1/3 SOLIDS
2/3 INTERSTITIAL
BLOOD
viscous fluid with a cellular portion and fluid portion I. Cellular Portion WBC platelets RBC II. Fluid Portion
Plasma
Serum without clotting factors
Properties of Blood
7 10 % of total body weight To = 36.5 C to 37.5 C pH = 7.35 7.45 Osmotic pressure = 7 8 atm Freezing point = -0.537C Sp. Gravity = 1.035 1.075 Viscosity = 4 5 x greater than water
Blood: Functions
I. Transport
A. Respiration
B. Nutrition C. Excretion
Blood: Functions
II. Regulatory
A. Blood pH
B. Body Temperature C. Body Hormones
Blood: Functions
III. Protective A. Infections (WBC) Bacterial Parasitic Viral Fungal
Blood: Functions
III. Protective
PLASMA PROTEINS
1. Fibrinogen
2. Gammaglobulin
3. Prothrombin 4. Blood grouping globulins
GENERALIZATIONS
Most plasma proteins are synthesized in the liver
GENERALIZATIONS
Many plasma proteins exhibit polymorphism Each plasma protein has a characteristic half-life Levels increase during acute inflammatory states or secondary to certain types of tissue damage
PLASMA PROTEINS
comprise the major parts of solids of plasma separation by Salting Out Method Na+ OR Ammonium Sulfate
PLASMA PROTEINS
Plasma CHON = 7.75 g/dl (6-8)
Albumin = 4.7 5.7 gm%
ALBUMIN
ALBUMIN
most abundant, most homogenous in electrophoresis MW - 69,000
Ellipsoidal in shape
150 Amstrom x 38 Amstrom small & compact
ALBUMIN
compact, small in size fast to travel in electrophoresis high solubility reactive groups in the molecule cause albumin to combine reversibly with a great diversity of anions and cations
ALBUMIN
N-terminal a.a. Asp
C-terminal a.a.
Leu human,dog & rabbit
ALBUMIN
Titration studies show molecule of albumin at ph 7.4
19 phenolic
22 guanidine groups
ALBUMIN
Major protein of human plasma 4.5g/dl Produced in the Liver 12 g/day 60% of Total Plasma Protein 75 80% of Plasma Oncotic Pressure Initially synthesized as PRE-PRO PROTEIN with a signal peptide
ALBUMIN
Decreased A:G Ratio Liver and Kidney Diseases Malnutrition
Binds various LIGANDS FFA, Calcium, Steroid Hormones Bilirubin, Tryptophan, Copper Drugs: Sulfonamides, Penicillin G Dicumarol, Aspirin
GLOBULIN
GLOBULIN
Fractions: A. Pseudoglobulin B. Euglobulin
glob IpH=5.06 glob IpH=5.12 transport (LP) transport (LP)
FIBRINOGEN
FIBRINOGEN: Factor 1
soluble plasma glycoprotein
46 nm in length
MW: 340,000
6 polypeptide chain
(A)2: (B)2;2
A2B2;2
FIBRINOGEN: Factor 1
end highly negatively charged (Asp & Glu residues A, B) B - (-) tyrosine O SO4 residue
Hence:
Contribute to its H2O solubility
Diagram Of Fibrinogen
Fibrin Polymerization
2 Glo 2 glyco
CHO
Unknown
Cerulo plasmin
Prothrombin Glo lipo protein
30
150,000
63,000
CHO
CHO
Copper transport
Blood clotting
Globulins Fibrinogen
150 th 340 th
CHO CHO
HAPTOGLOBIN
HAPTOGLOBIN
Plasma glycoprotein
MW = 100,000 daltons
Alpha-phoretic mobility
Irreversibly binds extracorpuscular Hgb in a tight non-covalent complex (Hb-Hp)
HAPTOGLOBIN
Hb Kidney Excreted in urine or precipitates in tubules (iron is lost) Kidney
Hb+Hp
Hb-Hp Complex
HAPTOGLOBIN
CERULOPLASMIN
CERULOPLASMIN
2-Globulin Serum Glycoprotein MW = 160,000 Carries 90% of Cu present in plasma (60% in RBC Superoxide Dismutase)
CERULOPLASMIN
Physiological functions of copper: 1. Oxidation of iron 2. Erythropoiesis and Leucopoiesis 3. Bone Mineralization
CERULOPLASMIN
Physiological functions of copper:
6. Catecholamine metabolism
7. Melanin formation
8. Myelin Formation
9. Glucose homeostasis
10.Antioxidant protection of cells
inactivates -1 antitrypsin
increase proteolytic destruction of lung tissue emphysema
HEMOSTASIS
HEMOSTASIS VASOCONSTRICTION
Modifying Signal
Inactive Enzyme A
10x
Active Enzyme A
Amplification 10x
Inactive Enzyme B
10x
Active Enzyme B
Amplification 100x
Inactive Enzyme C
10x
Active Enzyme C
Amplification 1000x
ACTION OF PLATELETS
COLLAGEN vWF
LIPOPROTEINS
FACTOR V 20%
ADP
Arachidonic Acid
Cyclooxygenase
Endoperoxidase
Thromboxane synthetase Prostacyclin synthetase
Thromboxane A2
Prostacyclin (PGI2)
Thromboxane B2 (platelets)
ANTIPLATELET DRUGS
ASPIRIN / NSAIDS
Inhibits thromboxane synthesis by blocking cycloxygenase Used in prophylaxis and treatment of MI, TIA and other thrombotic events
ANTIPLATELET DRUGS
TICLOPIDINE (Ticlide 500mg)
Inhibits ADP Formation
Prevents TIA, for patients who cant tolerate aspirin
ANTIPLATELET DRUGS
CLOPIDOGREL (PLAVIX 75 mg)
A. Inhibits the ADP pathway B. Both are used for people with stent
ANTIPLATELET DRUGS
CILOSTAZOL (PLETAAL)
A. Inhibits Phosphodiesterase use especially with people with intermittent claudication
ANTIPLATELET DRUGS
DIPYRIDAMOLE
Inhibits phophodiesterase increasing cAMP Used in prevention of thrombosis in artificial heart valves
ANTIPLATELET DRUGS
SOLUDEXINE (VESSEL DUE-F)
ANTIPLATELET DRUGS
SULFINPYRAZONE
Mechanism unknown
Rarely Used
COAGULATION PATHWAY
Factor I
Factor II
Fibrinogen
Prothrombin
Factor III
Factor IV
Tissue Factor
Ca++
Factor VII
Factor XIII
ZYMOGENS OF SERINE PROTEASES Factor IX Activated by Factor XIa in the presence of Ca++ Factor VII Activated by thrombin in the presence of calcium
ZYMOGENS OF SERINE PROTEASES Factor II Activated on surface of activated platelets by prothrombinase complex (Ca++, Factors Va and Xa)
COFACTORS
Factor VIII
- Activated by thrombin
COFACTORS
Factor V
- Activated by thrombin
COFACTORS
Factor III (Tissue Factor)
- Lipoprotein found on the surfaces of extravascular cells that acts as a cofactor for factor VII
T
H R O M B I
COO-
PROTEIN C
THROMBOMODULIN Protein on the surface of endothelial which then activates Protein C cells binds thrombin
THROMBI N THROMBOMODULIN
Va
VIIIa
FIBRIN CLOT
NH3+
FIBRINOPEPTIDE (A OR B)
NH2-CO-CH2-CH2FIBRIN (GLUTAMINYL)
NH+
FIBRIN-CH2-CH2-CH2-CH2-NH-C-CH2-CH2-FIBRIN
FIBRINOLYSIS
TPA
FIBRIN CLOT
PLASMIN
Arg Val FIBRIN
SOLUBLE FRAGMENTS
t.PA
t.PA PLASMIN
PAI-1 PAI-2
INHIBITORS
THROMBOLYTIC AGENTS
ALTEPLASE (tPA)
Large human protein, MW50,000 Produced in bacteria through recombinant DNA
THROMBOLYTIC AGENTS
ANISTREPLASE
APSAC (Anisoytated Plasminogen Streptokinase Activator Component)
THROMBOLYTIC AGENTS
STREPTOKINASE
Obtained from bacterial cultures Forms a complex with plasminogen prior to conversion
THROMBOLYTIC AGENTS
UROKINASE
Extracted from cultured human kidney cells
PLASMINOGEN ACTIVATION VARIOUS STIMULI (+) BLOOD PROACTIVATOR tPA, UROKINASE BLOOD ACTIVATOR (+) (+) (-) ANTIACTIVATORS INHIBITION
(-)
AMINOCAPROIC ACID TRANEXAMIC ACID
STREPTOKINASE
(+)
ACTIVATOR PROACTIVATOR ANISTREPLASE Arg Val
PLASMIN
(+)
ACTIVITY OF HEPARIN
HEPARIN
+
THROMBIN
XII a
XI a
Xa
IX a
VITAMIN K CYCLE
WARFARIN COUMARIN
PROTEIN CARBOXYLASE
VITAMIN K EPOXIDE / VITAMIN K(O) + H3O+ FACTORS II, VII, IX, X PROTEIN C / S
PROERYTHROBLAST
MEGAKARYOCYTES N. MYELOCYTES
ERYTHROCYTE
THROMBOCYTES
PRE B CELL
B LYMPHOBLAST
PMN
B CELL
MONOCYTE EOSINOPHIL
BASOPHIL
T LYMPHOBLAST
T CELL