BloodBlood

Week 7Week 7

Dr. Walid DaoudDr. Walid Daoud

A. ProfessorA. Professor

AnemiaAnemia________________________________________________________

Anemia is decrease in O2 carrying capacity Anemia is decrease in O2 carrying capacity of blood due toof blood due to::

11 - -Decreased number of RBCsDecreased number of RBCs::

. . Less than 4.5 million/mmLess than 4.5 million/mm33 in males in males..

. . Less than 3.9 million/mmLess than 3.9 million/mm33 in females in females..

22 - -Decreased Hb content of bloodDecreased Hb content of blood::

. . Less than 13.5 g/dl in malesLess than 13.5 g/dl in males..

. . Less than 11.5 g/dl in femalesLess than 11.5 g/dl in females..

Classification & Causes of AnemiaClassification & Causes of Anemia__________________________________________________________According to size of RBCs & Hb contentAccording to size of RBCs & Hb content::

I-Normocytic Normochromic AnemiaI-Normocytic Normochromic Anemia::

Both size of RBCs & Hb content are normal Both size of RBCs & Hb content are normal but RBCs number is decreased but RBCs number is decreased..

CausesCauses::

--Acute blood lossAcute blood loss (Hemorrhagic anemia) (Hemorrhagic anemia)..

--Bone marrow depressionBone marrow depression (Aplastic anemia) (Aplastic anemia)..

- - Breakdown of RBCsBreakdown of RBCs (Hemolytic anemia)(Hemolytic anemia)..

Classification & Causes of AnemiaClassification & Causes of Anemia________________________________________________________

II-Microcytic Hypochromic Anemia or II-Microcytic Hypochromic Anemia or Iron Deficiency Anemia Iron Deficiency Anemia::

Both size of RBCs and Hb contents are Both size of RBCs and Hb contents are less than normal less than normal..

CausesCauses::

- - Decreased iron intake in dietDecreased iron intake in diet..

- - Failure of iron absorptionFailure of iron absorption..

- - Chronic blood lossChronic blood loss..

Classification & Causes of AnemiaClassification & Causes of Anemia__________________________________________________________

III-Macrocytic Hyperchromic Anemia or III-Macrocytic Hyperchromic Anemia or Megaloblastic Anemia Megaloblastic Anemia::

Both size of RBCs and Hb content are Both size of RBCs and Hb content are more than normal more than normal..

CausesCauses::

- - Vitamin BVitamin B1212 deficiency deficiency..

- - Folic acid deficiencyFolic acid deficiency . .

Platelets or ThrombocytesPlatelets or Thrombocytes________________________________________________________

Non-nucleated, granulated bodies, 2-4 µm in Non-nucleated, granulated bodies, 2-4 µm in diameterdiameter..

Normal platelet countNormal platelet count::

150,000-450,000150,000-450,000//mmmm33

Decreased platelet count (Thrombocytopenia)Decreased platelet count (Thrombocytopenia)..

Increased platelet count (Thrombocytosis)Increased platelet count (Thrombocytosis)..

Formation of PlateletsFormation of Platelets________________________________________________________

Pluripotential stem cell in bone marrowPluripotential stem cell in bone marrow ↓ ↓ iinterleukinnterleukin

CFU-MCFU-M ↓ ↓ GM-CSFGM-CSF

MegakaryocyteMegakaryocyte↓ ↓ thrombopoietinthrombopoietin

PlateletsPlatelets

CFU-M = CFU-M = Colony forming unit-megakayocyteColony forming unit-megakayocyte . . GM-CSF=GM-CSF=Granulocye-monocyte colony stimulating factorGranulocye-monocyte colony stimulating factor..

Structure of PlateletsStructure of Platelets______________________________________________________A. Platelet membraneA. Platelet membrane..B. Platelet cytoplasmB. Platelet cytoplasm::

11 - -Beneath membrane:Beneath membrane: microtubules & ptn microtubules & ptn..22 - -Intracellular organellesIntracellular organelles::

33 - -Glycogen granulesGlycogen granules..44 - -Enzymes for synthesis of prostaglandinsEnzymes for synthesis of prostaglandins..

55 - -GranulesGranules:: . . Dense granulesDense granules.. . . Alpha granulesAlpha granules . .

HemostasisHemostasis______________________________________________________It means stoppage of bleeding from an It means stoppage of bleeding from an injured blood vesselinjured blood vessel..

Hemostatic process consists ofHemostatic process consists of::

I- Local vasoconstriction of injured blood I- Local vasoconstriction of injured blood vessel vessel..

II- Temporary hemostatic plug formationII- Temporary hemostatic plug formation..

III-Blood clot formationIII-Blood clot formation . .

HemostasisHemostasis______________________________________________________I- Local vasoconstrictionI- Local vasoconstriction::

11 - -Nervous reflexNervous reflex..

Initiated by pain sensationInitiated by pain sensation..

22 - -Local myogenic contractionLocal myogenic contraction..

Due to direct damage of blood vesselsDue to direct damage of blood vessels..

33 - -Chemical substancesChemical substances..

Serotonin and thromboxane ASerotonin and thromboxane A2 2 liberatedliberated

from platelets cause vasoconstrictionfrom platelets cause vasoconstriction..

HemostasisHemostasis______________________________________________________II- Temporary Hemostatic Plug FormationII- Temporary Hemostatic Plug Formation::

11 - -Platelet adhesionPlatelet adhesion..

22 - -Platelet activationPlatelet activation..

33 - -Release reactionRelease reaction..

44 - -Platelet aggregationPlatelet aggregation..

55 - -Platelet procoagulant activityPlatelet procoagulant activity..

66 - -Platelet fusionPlatelet fusion..

HemostasisHemostasis______________________________________________________

III- Blood Coagulation (Blood Clotting)III- Blood Coagulation (Blood Clotting)::

Properties of Blood Coagulation FactorsProperties of Blood Coagulation Factors::

GroupGroupFibrinogenFibrinogenProthrombinProthrombinContactContact

FactorsFactors

SynthesisSynthesis

StorageStorage

Consumption Consumption by clottingby clotting

I,V,VIII,XIIII,V,VIII,XIII

All in liverAll in liver

V and VIII V and VIII lose theirlose their

activityactivity

All are All are consumedconsumed

II, VII, IX, XII, VII, IX, X

StableStable

Only II is Only II is consumedconsumed

XI, XIIXI, XII

StableStable

Not Not consumconsum

HemostasisHemostasis______________________________________________________

The clotting mechanismThe clotting mechanism::

The loose platelet plug changes to blood clotThe loose platelet plug changes to blood clot::

11--Fibrinogen forms a loose then tight fibrin clot Fibrinogen forms a loose then tight fibrin clot catalyzed by factor XIII and Ca catalyzed by factor XIII and Ca22++..

22--Thrombin converts fibrinogen to fibrinThrombin converts fibrinogen to fibrin..

33--Active factor X converts prothrombin to Active factor X converts prothrombin to thrombin thrombin..

44--Factor X is activated by either extrinsic or Factor X is activated by either extrinsic or intrinsic pathways intrinsic pathways . .

HemostasisHemostasis______________________________________________________A. Intrinsic PathwayA. Intrinsic Pathway::In vivo (in plasma) or in vitro (glass of tube)In vivo (in plasma) or in vitro (glass of tube)..

- -Activation of factor XII by HMW kininogen Activation of factor XII by HMW kininogen and kallikrein in plasma and kallikrein in plasma . .

- -XIIa activates factor XIXIIa activates factor XI.. - -XIa activates factor IXXIa activates factor IX..

- -IXa forms a complex with VIIIa & activates IXa forms a complex with VIIIa & activates factor X in presence of phospholipids (PF3) factor X in presence of phospholipids (PF3)

and Caand Ca22++..

HemostasisHemostasis______________________________________________________

B- Extrinsic PathwayB- Extrinsic Pathway::

Initiated only Initiated only in vivoin vivo by tissue thromboplastin by tissue thromboplastin (TPL, factor III); they are group of tissue (TPL, factor III); they are group of tissue phospholipoprotein released from damaged phospholipoprotein released from damaged vascular and connective tissuesvascular and connective tissues..

- -TPL activates factor VIITPL activates factor VII..

- -VIIa directly activates factor X in presence VIIa directly activates factor X in presence of Ca of Ca2+2+ TPL and phospholipids (PL) and TPL and phospholipids (PL) and indirectly through activation of factor IXindirectly through activation of factor IX..

HemostasisHemostasis______________________________________________________Common Part in Both PathwaysCommon Part in Both Pathways::

- -Xa converts prothrombin to thrombinXa converts prothrombin to thrombin.. - -Thrombin transforms soluble fibrin to Thrombin transforms soluble fibrin to

insoluble fibrin insoluble fibrin.. - -Thrombin in presence of CaThrombin in presence of Ca2+2+ activates activates

factor XIII which stabilizes fibrin clot factor XIII which stabilizes fibrin clot . . - -Contraction of actin, myosin and Contraction of actin, myosin and

thrombosthenin of platelets causes clot thrombosthenin of platelets causes clot retraction and squeezes serum outretraction and squeezes serum out . .

HemostasisHemostasis______________________________________________________Important notesImportant notes::

- -Extrinsic pathway is very rapid (15 sec.) Extrinsic pathway is very rapid (15 sec.) while intrinsic pathway is slow (1-6 min.) while intrinsic pathway is slow (1-6 min.)..

- -Injury of a blood vessel will trigger both the Injury of a blood vessel will trigger both the intrinsic system intrinsic system by exposed collagenby exposed collagen and and extrinsic system extrinsic system by tissue thromboplastinby tissue thromboplastin..

- -In test tube, clotting occurs only by intrinsic In test tube, clotting occurs only by intrinsic system by glass or addition of collagen system by glass or addition of collagen..

- -In intravenous thrombosis, clotting occurs In intravenous thrombosis, clotting occurs via intrinsic system by exposure of clotting via intrinsic system by exposure of clotting

factors to subendothelial collagen factors to subendothelial collagen..

Anticoagulant MechanismsAnticoagulant Mechanisms________________________________________________________

Limiting reactions:Limiting reactions: prevent blood clotting in prevent blood clotting in healthy blood vessels and breakdown any healthy blood vessels and breakdown any clots already formedclots already formed..

A.General:A.General:1-1- Smooth vascular endotheliumSmooth vascular endothelium..

22 - -Rapid flow of bloodRapid flow of blood..

33 - -HeparinHeparin..

B.Specific:B.Specific:1-1- Thromboxane AThromboxane A2 2 & Prostacyclin& Prostacyclin..

22 - -Antithrombin IIIAntithrombin III..

33 - -Fibrinolytic systemFibrinolytic system..

The Fibrinolytic SystemThe Fibrinolytic System________________________________________________________Thrombomodulin binds thrombin to form Thrombomodulin binds thrombin to form thrombomodulin-thrombin system which thrombomodulin-thrombin system which activate protein Cactivate protein C which causes which causes::

--Inactivation of factor Va and VIIIaInactivation of factor Va and VIIIa..

--Inactivation of inhibitor of tissue plasminogen Inactivation of inhibitor of tissue plasminogen activator (t-PA), ↑ formation of plasminactivator (t-PA), ↑ formation of plasmin..

Plasmin (fibrinolysin)Plasmin (fibrinolysin) is an enzyme formed is an enzyme formed from plasminogen. It lyses fibrin & fibrinogen from plasminogen. It lyses fibrin & fibrinogen forming fibrin-degradation products (FDP) forming fibrin-degradation products (FDP) which inhibits thrombinwhich inhibits thrombin..

AnticoagulantsAnticoagulants________________________________________________________

Substances used to prevent blood clottingSubstances used to prevent blood clotting..

A- In vitro anticoagulants:A- In vitro anticoagulants: in a test tube in a test tube::

11--Removal of CaRemoval of Ca22++: :

. . Oxalates: precipitates CaOxalates: precipitates Ca22++ . .

. . Citrates: binds CaCitrates: binds Ca2+2+ by deionizing them by deionizing them

22--Silicon:Silicon: prevents activation of factor XII prevents activation of factor XII..

33--HeparinHeparin..

AnticoagulantsAnticoagulants________________________________________________________B- In vivo anticoagulants:B- In vivo anticoagulants: inside the body inside the body::

HeparinHeparinDicumarolDicumarol

OriginOrigin

ActionAction

Site of Site of actionaction

OnsetOnset

DurationDuration

RouteRoute

AntidoteAntidote

Mast cell & basophilMast cell & basophil

Facilitates action of Facilitates action of thrombinthrombin..

In vivo and vitroIn vivo and vitro

RapidRapid

ShortShort

I.V. and I.MI.V. and I.M..

Protamine sulphateProtamine sulphate

PlantPlant

Competitive inhibition Competitive inhibition of vitamin K in liverof vitamin K in liver , ,

↓ ↓factors II, VII, IX, Xfactors II, VII, IX, X..

Only in vivoOnly in vivo..

SlowSlow

LongLong

OralOral

Vitamin KVitamin K

Abnormalities of HemostasisAbnormalities of Hemostasis________________________________________________________

1-Thrombocytopenic purpura: S.C. hemorrhage

↓ -Platelets count below 50,000 / mm3.

- Bleeding time is prolonged..

2-Vitamin K deficiency: due to:

-Decreased formation: absent intestinal flora .

- Decreased absorption: bile duct obstruction.

3-Hemophilia: congenital sex-linked disease

-Hemophilia A: absence factor VIII .

- Hemophilia B: absence factor IX.

- Hemophilia C: absence factor XI .