Notes on Hemostatic Mechanisms

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What causes blood vessel constriction?

When arteries or arterioles are damaged, the circular smooth muscles in their walls contract. This is caused by damage to smooth muscle by substances released from activated platelets and reflexes by pain receptors. In particular, these chemicals are serotonin and thromboxane A2.

Summary of platelet structure and function:

• Form from megakaryocysts in red bone marrow.

• Disc shaped, no nucleolus and have vesicles.

• Their granules contain various chemicals.

• Aged platelets removed by macrophages in spleen and liver.

• Activated by thrombin.

Clotting (coagulation) factors: What are they, where are they synthesized, what vitamin is needed for the synthesis of some of them, how are they activated?

Clotting involves several factors. They include calcium ions, several inactive enzymes synthesized by the liver, and chemicals released by platelets and damaged blood vessels. Vitamin K is needed by some of them.

Coagulation cascade:

It is a sequential enzymatic activation of clotting factors with positive feedback.

Extrinsic pathway:

• Faster than intrinsic.

• Tissue factor (thromboplastin) leaks into blood from outside to blood vessels and initiates formation of prothrombinase.

• Fewer clotting steps.

Role of Thrombin:

Thrombin, in the presence of calcium ions, converts soluble fibrinogen to loose insoluble fibrin threads. Thrombin also activates factor XIII to strengthen fibrin threads.

List the mechanisms involved in hemostasis:

• Vascular Spasm.

• Platelet plug formation.

• Blood clotting (coagulation).

Describe the platelet release reaction and its role in the platelet plug formation:

When platelets aggregate, the become activated and interact with each other, and release chemicals. This is called platelet release reaction.

What is the difference between serum and plasma?

Serum is the left over liquid that forms after blood clots. Serum = Plasma clotting proteins. Plasma is the straw-colored liquid left when formed elements are separate from blood.

Different test tubes are required for collection of plasma and serum. A plasma tube is used to collect blood for a Full Blood Count (for example). What is in the plasma test tube?

Plasma contains proteins, water and other solutes.

Biochemically, most coagulation factors are inactivated enzymes. What are enzymes? How do these enzymes become activated?

Most of these enzymes are synthesized in the liver and are known by Roman numerals, for example, clotting factor X. They become activated at various stages of the blood-clotting cascade.

What organ produces most of the clotting factors? What happens to clotting when this organ fails?

The liver produces most clotting factors. Clotting is hindered when the liver fails.

Which pathway is more important in vivo (in the human body): the intrinsic or extrinsic pathway?

Extrinsic pathway is more important.

Describe the role of Vitamin K in coagulation:

It is required for the synthesis of four clotting factors: II, VII, IX and X. Vitamin K deficiency causes hemorrhagic disease.

Blood normally does not clot while in blood vessels. Why not? List the mechanisms that prevent coagulation from becoming uncontrolled:

Blood does not clot in vessels because:

• Substances called anticoagulants are present in blood. Eg., antithrombin, heparin, activated protein C, warfarin.

• Blood vessels make it hard for clotting agents to become adtivated by themselves.

The fibrinolytic system dissolves small clots in a process called fibrinolysis. Plasminogen is incorporated into a clot, then the clot is dissolved.

Why is factor X important?

Factor X links the extrinsic and intrinsic pathways.

What is von Willebrand factor (vWF) and what are its functions?

• It causes platelets adhere to each other.

• Causes platelets adhere to damaged subendothelium.

• Prevent degradation of factor VIII: C in plasma.

Additional Reading:

Basic Pathology

1. Cell Injury
2. Inflammation and Repair
3. Immunopathology
4. Water, Electrolyte, Acid-Base, Hemodynamic Disorders
5. Genetic and Developmental Disorders
6. Environmental Pathology
7. Nutritional Disorders
8. Neoplasia
9. Vascular Disorders
10. Heart Disorders
11. Red Blood Cell Disorders
12. White Blood Cell Disorders
13. Lymphoid Tissue Disorders
14. Hemostasis Disorders
15. Blood Banking and Transfusion Disorders
16. Upper and Lower Respiratory Disorders
17. Gastrointestinal Disorders
18. Hepatobiliary and Pancreatic Disorders
19. Kidney Disorders
20. Lower Urinary Tract and Male Reproductive Disorders
21. Female Reproductive and Breast Disorders
22. Endocrine Disorders
23. Musculoskeletal Disorders
24. Skin Disorders
25. Nervous System Disorders
26. Notes on Tissue Regeneration
27. A Table of Bleeding Disorders
28. FAQ on Structure and Function of Red Blood Cells
29. FAQ on Components of Blood
30. Notes on Hemostatic Mechanisms
31. What is Fever?
32. What is Edema?
33. FAQ on Blood Pressure
34. FAQ on principles of fluid and flow dynamics of Blood
35. Causes of Thrombocytopenia
36. Squamous cell carcinoma of head and neck mucosa
37. Four tumors which never metastasize to the brain
38. What is caustic injury?
39. What causes Peripheral Edema?

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