Blood physiology 4

(( Transfusion ))

-The most common reason for transfusion is decreased blood volume .
-If a patient becomes severely anemic it may be no longer possible to treat this by simply improving the diet & to add iron , B12 or folic acid supplement . It may be necessary to give a blood transfusion .
-The blood for a blood transfusion is taken under sterile conditions .
-Acid citrate is added to prevent the blood from clotting , & glucose ( dextrose ) added to feed the red cells (ACD= acid citrate dextrose blood , -CPD= citrate phosphate (to maintain the level of 2,3 – DPG) , dextrose blood) .
-The WBCs do not survive for more than a few hours when the blood is taken for a blood transfusion & a transfusion of stored blood can therefore not be used to increase the number of white cells in the circulation .
-It is very important that none of the blood transfusion apparatus should contain any soap or detergent because these substances dissolve the outer fatty membrane of the RBC’s , & will thus destroy the cells .
-The blood is stored at 4C0 & care must be taken to ensure that the temperature does not fall below freezing point because this would destroy the RBC’s , due to the formation of ice crystals .


-If blood of one blood group is transfused to a recipient of another blood group , a transfusion reaction is likely to occur in which the RBC’s of the donor blood are agglutinated .
-It is very rare that the transfused blood ever causes agglutination of the recipient’s cells for the following reason :-
-The plasma portion of the donor blood immediately becomes diluted by all the plasma of the recipient , thereby decreasing the titer of the infused agglutinins to a level too low to cause agglutination . On the other hand , the infused blood does not dilute the agglutinins in the recipient’s plasma to major extend .
-Therefore , the recipient’s agglutinins can still agglutinate to donor cells .
-Harmful effects or even death can result from a blood transfusion if the donor’s RBC’s become agglutinated by antibodies in the recipient’s plasma .
-If a donors RBC’s do not contain any A or B antigen , they of course can not be clumped by anti – A or anti – B antibodies for this reason the type of blood that contains neither A nor B antigens – namely type O blood - can be used as donor blood without the danger of anti – A or anti – B antibodies clumping its red blood cells . -Type O blood is therefore called universal donor blood .
-While universal recipient blood is type AB , it contains neither anti – A nor anti – B antibodies in its plasma . Therefore it cannot clump any donor’s RBC’s containing A or B antigens .
-So it is very important to maintain the life must know the groups of blood before making transfusion of blood between two person to prevent the clotting of blood & subsequently prevent the death .

-Red cell fragility

-The osmotic fragility of freshly taken red cells reflects their ability to taken up water without lysis & is determined by their volume to surface area ratio .
-The ability of the normal RBC’s to withstand hypotonicity results from its biconcave shape which allows the cell to increase its volume by about 70% before the surface membrane is stretched .
-Once this limit is reached , lysis occurs . The increase in osmotic fragility is a property of the spheroidal shape of the cell .
-Spherocytes which have a decreased surface to volume ratio demonstrate an increased osmotic fragility .
-Since RBC’s in solutions with a lower osmotic pressure , they swell , becoming spherical rather than disk shaped , & eventually lose their hemoglobin (hemolysis) which dissolves in the plasma , coloring it red .
-When osmotic fragility is normal , red cells begin to hemolyze when suspended in 0.45% (may be 48%) saline , & hemolysis is complete in 0.35% (may be 0.33%) saline .
-In hereditary spherocytosis , the cells are spherocytic in normal plasma & hemolyze more readily than normal cells in hypotonic sodium chloride solutions .



-(( Hemostasis & blood coagulation ))

-The term hemostasis means prevention of blood loss .
-Whenever a vessel is reptured , hemostasis is achieved by several different mechanism including :-

-(1):- Vascular spasm .
-(2):- Formation of platelet plug .
-(3):- Blood coagulation .
-(4):- Growth of fibrous tissue into the blood clot to close the hole in the vessel permanently .

-(1) Vascular spasm:-
-Immediately after a blood vessel is cut or reptured , the wall of the vessel contracts , this lead to reduce the flow of blood from the vessel rupture .
-The contraction results from both nervous reflexes & local myogenic spasm .
-The nervous reflexes are initiated by pain impulses originating from the traumatized vessel or from nearby tissues .


-(2) Formation of the platelet plug:-
-The second mechanism for hemostasis is formation of the platelet plug .
-Platelets repair of vascular opening is based on several important functions of the platelet
it self :-
-When platelets come in contact with a damaged vascular surface , such as the collagen fibers in the vascular wall or a damaged endothelial cells , they immediately change their characteristics .
-They begin to swell , they assume irregular forms with numerous irradiating processes protruding from their surfaces .
-They become sticky so that they stick to the collagen fibers , & they secrete large quantities of ADP (adenosine diphosphate) & enzymes that cause formation of thromboxane A2 in the plasma which used to induce platelet aggregation .
-So these accumulation of platelet lead to form a platelet plug .
-This is loose plug but it is usually able in blocking the blood loss if the vascular opening is small . But if there is a large hole , a blood clot in addition to the platelet plug is required to stop the bleeding.

-(3) Blood coagulation:-
-The third mechanism for hemostasis is formation of the blood clot . The clot begins to develop in (15 to 20) seconds if the trauma of vascular wall has been sever & in one to two minutes if the trauma has been minor .



-Mechanism of blood coagulation:-

-Basic theory:-
-Over (30) different substances that effect blood coagulation have been found in the blood & tissues , some promoting coagulation which are called procoagulants , & others inhibiting coagulation which are called anti coagulants .
-Whether or not the blood will coagulate depends on the degree of balance between these two groups of substances .
-Normally the anticoagulants predominate & the blood dose not coagulate but when a vessel is reptured the activity of the procoagulants in the area of the damage become much greater than that of anticoagulants & then a clot dose develop.


-General Mechanism:-

-The clotting takes place in three essential steps:-

-First:- Thromboplastin formation via the extrinsic system & the intrinsic system .

-Second:- Thrombin formation .

-Third:- The thrombin acts as an enzyme to convert fibrinogen into fibrin (fibrin formation) .


-Conversion of prothrombin to thrombin (Thrombin formation) :-

-After prothrombin activator (thromboplastin) has been formed as a result of rupture of the blood vessel or as a result of damage .
-The prothrombin activator can then cause conversion of prothrombin to thrombin , which in turn causes polymerization of fibrinogen molecules into fibrin .
-Prothrombin is a plasma protein , alpha 2 – globulin , having aMW of 68,700 . It is present in normal plasma concentration of about 15 mg per 100 ml .
-It is unstable protein that can split easily into smaller compounds , one of which is thrombin .
-The thrombin has aMW of 33 , 700 almost exactly half that of prothrombin .
-Vitamin K is required by the liver for normal formation of prothrombin (stimulates liver cells to increase their synthesis of prothrombin).

-Effect of prothrombin activator (thromboplastin) to form thrombin from prothrombin :-

-As in below the conversion of prothrombin to thrombin occur under the influence of prothrombin activator & calcium ions.
-The rate of formation of thrombin from prothrombin is almost directly proportional to the quantity of prothrombin activator .
-The rapidity of clotting process is proportional to the quantity of thrombin formed .

Prothrombin
Extrinsic or intrinsic
Prothrombin activator Ca+2
thromboplastin) Thrombin

Fibrinogen Fibrin monomer
Ca+2
Fibrin
stabilizing factor
Fibrin threads

[ Conversion of prothrombin to thrombin & polymerization of fibrinogen to form fibrin threads ]

-Conversion of fibrinogen to fibrin :-
-Thrombin is a protein enzyme with proteolytic activity .
-It acts on fibrinogen to remove two low molecular weight peptides from each molecule of fibrinogen , forming a molecule of fibrin monomer which has the automatic capability of polymerizing with other fibrin monomer molecules .
-Therefore, many fibrin monomer molecules polymerize within second into long fibrin threads that form the reticulum of the clot .
-In the early stages of this polymerization, the fibrin thread are not cross-linked with each other & the result clot is weak & can be broken easily .
-So another process occurs during the following few minutes that greatly strength the fibrin reticulum .
-This involves a substance called fibrin stabilizing factor that is normally present in small a mount in plasma .
-Before fibrin stabilizing factor that can have effect on the fibrin threads it must it self be activated & then this process lead to form covalent cross - linked bonds between the adjacent fibrin threads .
-The fibrin threads adhere to damaged surfaces of blood vessels , therefore the blood clot which composed of a mesh work of fibrin threads running in all directions & entrapping blood cells & plasma becomes adherent to any vascular opening & there by prevents blood loss .

-Clot retraction :-
-With in few minutes after a clot is formed , it begins to contract & usually expresses most of the fluid from the clot within (30 to 60) minutes , this fluid expressed is called the serum because of its fibrinogen & most of the other clotting factor have been removed .
-Platelets are necessary for clot retraction to occur , there fore , failure of clot retraction if the number of platelets in the circulating blood is low .
-Further more , platelets entrapped in the clot continue to release procoagulants substances one of which is fibrin stabilizing factor that causes more & more cross linking bonds between the adjacent fibrin threads .
-As the clot retracts , the edges of broken blood vessel are pulled together .

-Formation of prothrombin activator (thromboplastin)
-There are two basic ways in which prothrombin activator can be formed :-
-(1) Extrinsic pathway :-
-Begins with truma to the vascular wall or to the tissue outside the blood vessels .


-(2) Intrinsic pathway :-

-That begins in the blood it self .
-In both the extrinsic & intrinsic pathways a series of different plasma protein , especially beta – globulins play major roles . These are called clotting factors .


-The extrinsic mechanism for initiating clotting :-
-The extrinsic mechanism occurs according to the following three basic steps :-

-(1) Release of tissue factor & tissue phospholipid :-

-The traumatized tissue releases two factors that set the clotting process into motion .
These are:-
-A) Tissue factor:-
- Which is proteolytic enzyme .
-B) Tissue phospholipids :-
-Which are mainly phospholipids of the tissue cells membranes .

-(2) Activation of factor X to form activated factor X – role of factor V11 & tissue factor :-
-The tissue factor complexes with blood coagulation factor V11 & this complex , in the presence also of tissue phospholipids , act enzymatically on factor X to form activated factor X .
-(3) Effect of activated factor X to form prothrombin activator – role of factor V :-

-The activated factor X complexes immediately with the tissue phospholipids released from the traumatized tissue & also with factor V to form complex called prothrombin activator (thromboplastin) .
-With in a few seconds this splits prothrombin to form thrombin , & the clotting process proceeds as has been explained






(1)


(2) X activated X

V
(3)
Prothrombin activator Ca+2
Prothrombin Thrombin
Ca+2


((The extrinsic pathway for initiating blood clotting ))