How our body prevents blood loss? | Stages of clot formation | hemostasis

How our body prevents blood loss? 

Introduction

     Normally, in small blood vessels, on a daily basis, thousands of injuries occur but still non of blood is leaked into the tissue spaces. Its all bcoz of the physiological process that occurs normally in the body, that is called Hemostasis.

Why normally clot formation not occur? 

     Normally, Blood flows smoothly in the vessels without forming clots. Its bcoz their are certain factors that acts as an anticoagulant, and inhibits the clotting factors. Few are given below:

• Thrombomodulin is a factor that is secreted by the endothelium of blood vessels, that binds thrombin with itself. Then Thrombin activates the Protein-C that inactivates the clotting factor-V and factor-VIII.
• Endothelial cells releases a chemical called Nitric Oxide, that binds Prostacyclin (PGI2), then prostacyclin inhibits the aggregation of platelets.
• Heparin Sulfate, a molecule, is attached with the Endothelial walls, in heparin sulfate, Antithrombin is attached that inactivates the clotting factor-II, factor-IX and factor-X.

     These all factors works normally so that clot formation can not occur. If an injury occurs, then the above given factors will not be secreted, that leads to the activation of all clotting factors, so ultimately clot formation occur.

What is Hemostasis?

     Hemo means blood and stasis means stop, collectively this term means the localized stop of blood leakage. It is a physiological process that normally occurs thousands of times in the body daily. It involves four steps that are given below:

1) Vascular Spasm

2) Platelet plug formation

3) Blood clot formation (Blood coagulation)

4) Lysis of Clot 

Vascular Spasm

     When the endothelial injury occurs, damaged tissue release the Endothelin that comes down to the smooth muscles of vessels and cause their contraction, that leads to the Vasoconstriction.

     If smooth muscles or collagen fibers are exposed due to injury, then a protective response is called the Myogenic mechanism in which smooth muscles contract that causes vasoconstriction.

     As the inflammation occurs that leads to the release of number of factors that sensitize the noci receptor, that cause the Vasoconstriction.

     As long as the spasm lasts, the platelet plug formation starts and in the last formed.

Platelet Plug Formation

     As the endothelial surface is damaged, so the platelets come in contact with that tissues, platelet changes its characteristics like it swells, contractile proteins contract. Platelets adhere to collagen and vWF (These traumatized tissues secretes vWF). As the glycoprotein membrane of platelet binds with vWF, the release of ADP and Platelet activation factor occur. 

     The enzymes present in platelet forms Throboxane A2 that attract more platelets and form a platelet plug. This mechanism successfully block the blood if small blood vessel is ruptured. Thus mechanism is very important as thousands of small blood vessels are ruptured daily.

Blood Coagulation

     This is the third mechanism of clot formation, that occurs after 15-20 seconds approx: if injury is severe or after 1-2 minutes if injury is minor. This coagulation occur through a cascade of reactions that are divided into two pathways, named:

1. Intrinsic Pathway
2. Extrinsic Pathway

Intrinsic Pathway

      As the aggregation of platelets ends, the clotting factor-XII comes in contact with that platelet plug, its activated as their is negative charge on platelet plug surface. The factor -XII activates factor -XI, then it activates factor -IX, then factor -IX andfactor -VIII combines in the presence of Ca ions and activates factor -X. factor -X with factor -V, Platelet phospholipids and Ca ions leads to the formation of Prothrombin Activator.

Extrinsic Pathway

     The damaged tissue secretes a factor called tissue factor (factor -III) that activates factor-VII, then factor-VII leads to the activation of factor -X. factor -X with factor -V, Platelet phospholipids and Ca ions forms Prothrombin activator.

Conversion of Prothrombin to Thrombin

     Prothrombin is an unstable molecule that is splited into two parts with the help of Prothrombin activator, one part is Thrombin. Prothrombin is continually formed by liver, and utilized in the coagulation. 

     Liver disease leads to the decrease production of prothrombin. As Vit-K is also required for normal activation of prothrombin, so its deficiency also leads to the prothrombin problem.

Conversion of Fibrinogen to Fibrin

     Thrombin is a protein enzyme that acts on Fibrinogen and removes four polypeptides from 1 molecule to form one fibrin monomer, that automatically polymerized to form a network. But that bonding in network is of weak noncovalent bond. The same thrombin activates factor -XIII, that is the fibrin stabilizing factor, that makes the bonding covalent and 3 dimensional strong.

Blood Clot and Clot Retraction

     The blood clot is the entrament of blood cells, platelets and plasma through fibrin network, the whole is called Blood clot.

     After the formation of clot, it begins to contract and the fluids are expressed from the clot, those are the serum. If the contraction can not occur, it means that there is decrease of platelets. Platelets directly contribute towards this by starting contraction of all contractile proteins. 

     As the clot retracts, the edges will be pulled together and it also contributes to hemostasis.

Lysis of Clot

     As the clot also contains the plasminogen with the plasma proteins, and damaged tissues slowly secretes a factor called tissue Plasminogen Activator that converts the plasminogen to plasmin.

     Plasmin also digests other clotting factors like fibrinogen, factor -V, factor -VIII, factor -II and  factor -XII. Result is that the whole clot is digested.

Positive Feedback Mechanism

     Once the clot is formed, it leads to its extension to its surrounding. Its just bcoz of the proteolytic action of Thrombin on other clotting factors. Thrombin also enhances further conversion of prothrombin to thrombin. Thrombin also acts on other factors that increases the Prothrombin Activator and coagulation continuous till the blood loss is stopped.

Role of Ca ions

     The Ca ions have also an important role in coagulation as they are of very importance in Intrinsic pathway. Except starting two steps, the whole pathway needs Ca ions for moving forward and activating other factors. 

     Ca ions are released from the Ca stores present in the Mitochondria, Endoplasmic Reticulum and Golgi Apparatus of Platelets.

Conclusion

     Daily, thousands times our blood vessels are ruptured inside, but still we don't feel the process taking place in our body, that is Hemostasis. Its looks easy, but it is not. Take exercises daily and have a wonderful diet so that the whole process can undergo smoothly.