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Questions and Answers
What is the primary role of von Willebrand Factor (vWF) in platelet plug formation?
What is the primary role of von Willebrand Factor (vWF) in platelet plug formation?
Which statement correctly distinguishes the extrinsic and intrinsic pathways of blood clotting?
Which statement correctly distinguishes the extrinsic and intrinsic pathways of blood clotting?
What initiates the intrinsic pathway of coagulation?
What initiates the intrinsic pathway of coagulation?
Which factor is activated by thrombin in the intrinsic pathway?
Which factor is activated by thrombin in the intrinsic pathway?
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During the aggregation phase of platelet plug formation, which of the following occurs?
During the aggregation phase of platelet plug formation, which of the following occurs?
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Which statement best describes the role of thrombopoietin in blood cell production?
Which statement best describes the role of thrombopoietin in blood cell production?
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What would likely be a significant consequence of a deficiency in erythropoietin production?
What would likely be a significant consequence of a deficiency in erythropoietin production?
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Which process is primarily responsible for the removal of ruptured red blood cells from circulation?
Which process is primarily responsible for the removal of ruptured red blood cells from circulation?
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How does the structure of red blood cells facilitate their function in oxygen transport?
How does the structure of red blood cells facilitate their function in oxygen transport?
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Which of the following conditions could lead to hypoxia related to erythropoiesis?
Which of the following conditions could lead to hypoxia related to erythropoiesis?
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Which factor is activated by thrombin in the process of clot formation?
Which factor is activated by thrombin in the process of clot formation?
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What role does FXa play in the common pathway of coagulation?
What role does FXa play in the common pathway of coagulation?
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What is the primary function of plasmin in fibrinolysis?
What is the primary function of plasmin in fibrinolysis?
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In Haemophilia A, which pathway is assessed by prothrombin time (PT)?
In Haemophilia A, which pathway is assessed by prothrombin time (PT)?
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What initiates the extrinsic pathway of coagulation?
What initiates the extrinsic pathway of coagulation?
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What is the first step in the intrinsic pathway of blood clotting?
What is the first step in the intrinsic pathway of blood clotting?
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Which component is crucial for the adhesion step of platelet plug formation?
Which component is crucial for the adhesion step of platelet plug formation?
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What role does FXIa play in the intrinsic pathway of coagulation?
What role does FXIa play in the intrinsic pathway of coagulation?
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During the aggregation phase of platelet plug formation, what primarily occurs?
During the aggregation phase of platelet plug formation, what primarily occurs?
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Which of the following best describes the extrinsic pathway of coagulation?
Which of the following best describes the extrinsic pathway of coagulation?
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Study Notes
Vascular Spasm
- Arterioles constrict to reduce blood flow.
Platelet Plug Formation
- Exposure to extracellular matrix proteins is required.
- von Willebrand factor (vWF)
- Fibrinogen (converts to fibrin for blood clotting)
- Collagen
- Requires multiple steps:
- Adhesion
- Outside-in signaling - integrin activation
- Secretion
- Aggregation
- Thrombin production
Blood Clotting: Coagulation
- Extrinsic pathway:
- Initiated by tissue factor (TF) leaking from cells outside the bloodstream.
- Fewer steps and rapid.
- Intrinsic pathway:
- More complex and slower.
- Does not require outside tissue damage, e.g. caused by endothelial cell damage.
- Steps:
- Surface contact activates Factor XII (FXII).
- FXIIa activates Factor XI (FXI) and releases bradykinin (a vasodilator) from high molecular weight kininogen (HMWK).
- Calcium (Ca2+) and FXIa activate FIX, a serine protease.
- FIXa hydrolyses FX (with Ca2+, phosphatidylserine on activated platelets, and FVIIIa - the tenase complex).
- FVIII is a cofactor activated by thrombin from platelets.
- FX is activated, leading to the common pathway.
Blood Cell Formation (Haematopoiesis)
- Some myeloid stem cells differentiate into progenitor cells, while others and lymphoid stem cells develop directly into precursor cells.
- Progenitor cells cannot reproduce, they are committed to forming their designated cell type (e.g. CFU-E).
- Precursor cells (blasts) develop into the actual formed elements of blood over several divisions.
- Cytokines, colony-stimulating factors (CSFs), and interleukins (ILs) contribute to production and maturation.
- Erythropoietin (kidney) promotes red blood cell production.
- Thrombopoietin (liver) promotes platelet maturation.
Medical Uses of Haematopoietic Growth Factors
- Recombinant growth factors are used:
- Erythropoietin for kidney disease.
- Granulocyte colony-stimulating factor (G-CSF) for white blood cell formation after chemotherapy.
- Thrombopoietin for chemotherapy.
- Also used for clotting disorders and various neonatal disorders.
Red Blood Cells (Erythrocytes)
- Contain oxygen-carrying haemoglobin.
- Produce 2 million RBCs per second.
- Blood contains 5 million RBCs per microliter.
- Lack a nucleus and mitochondria, relying on anaerobic respiration.
- Flexible and bi-concave.
Function of Red Blood Cells
- Carry 5-8% of CO2 in the body bound physically to haemoglobin.
- Bind and carry nitric oxide (NO) for vasodilation and regulation of blood clot formation.
- Carbonic anhydrase creates carbonic acid, which dissociates into bicarbonate ions (HCO3-), important for buffer control and plasma carrying CO2.
Red Blood Cell Life Cycle
- RBCs are rapidly damaged in transit due to the lack of a nucleus and organelles for repair.
- The plasma membrane becomes fragile and may burst.
- Ruptured RBCs are removed by fixed macrophages.
- Their contents are recycled.
Iron Overload and Tissue Damage
- Fe2+ and Fe3+ bind to and damage cells.
- Plasma does not contain free iron.
- Iron-carrying proteins can become overloaded.
- Iron-dependent microbes can cause problems.
Erythropoiesis
- Red blood cell production starts in the red bone marrow (RBM) with the precursor cell type, pro-erythroblast.
- Cells divide several times, producing cells that make haemoglobin.
- Eventually, they differentiate into reticulocytes, which eject their nuclei.
- Reticulocytes pass into the blood and differentiate into red blood cells.
Erythropoiesis Problems
- Erythropoiesis sometimes cannot keep up with red cell demand.
- This can lead to hypoxia.
- Can be due to anemia or dietary deficiencies, circulatory problems, or blood doping.
Platelets
- Thrombopoietin causes haematopoietic stem cells to differentiate into megakaryoblasts, which produce megakaryocytes.
- Small, anucleate cells required for haemostasis.
- 150,000 - 400,000 per microliter.
- Life span 5-9 days.
Haemostasis
- Initiated by TF leaking into the blood from cells outside the bloodstream.
- Steps:
- FVII is activated by thrombin and FXa (from the intrinsic pathway).
- FVIIa and its cofactor TF (FIII) activate FX.
- FXa cleaves prothrombin (FII) on the surface of activated platelets (creating a prothrombinase complex with Ca2+, phospholipids, prothrombin, FXa, and FVa).
- FV is activated by small amounts of thrombin.
- Fibrinogen is converted to fibrin by thrombin.
- Thrombin also activates FXIII, which cross-links the fibrin clot.
Fibrinolysis for Clot Localization
- Clot plugs the ruptured area.
- Clot retraction is the tightening of the fibrin clot.
- Fibrin threads attached to damaged surfaces of the blood vessel contract as platelets pull on them, pulling the edges of the wound together.
- Fibrinolysis dissolves small, inappropriate clots, and dissolves clots as repair happens.
- Inactive plasminogen is incorporated into the clot.
- It is activated to plasmin by substances in the body tissue (thrombin and tissue plasminogen activator - t-PA).
- Plasmin digests fibrin threads and inactivates fibrinogen, prothrombin, FV, and FXII.
Haemophilia
- Haemophilia A (X-linked leading to FVIII deficiency):
- Extrinsic pathway (assessed by prothrombin time - PT) is normal.
- Intrinsic pathway (assessed by activated partial thromboplastin time - APTT) is abnormal.
- Affects approximately 1 in 5,000 males.
- Haemophilia B (Christmas disease, X-linked disorder leading to FIX deficiency):
- Affects approximately 1 in 30,000 males.
- Normal PT time, but abnormal APTT time.
Leukaemia
- Production of malignant white blood cells, suppressing production of all normal cells in the red bone marrow.
- Oncogenes: cause malignancy when mutated, leading to their activation (growth factors, receptors, DNA-binding proteins).
- Tumour suppressor genes: cause malignancy when mutated, leading to their suppression of growth.
- Types of leukaemia:
- Acute lymphoblastic leukaemia (ALL): short onset, derived from lymphoid stem cells. Most common in children.
- Acute myelogenous leukaemia (AML): affects all ages.
- Chronic lymphoblastic leukaemia (CLL): most common in adults (55+).
- Chronic myelogenous leukaemia (CML): prolonged onset, derived from myeloid stem cells. Mostly in adults.
- Causes often unknown but can be radiation or chemotherapy, genetics (Down syndrome), environmental factors, or viral infections (e.g. Epstein-Barr virus).
Bone Marrow Transplant
- Replacement of cancerous or abnormal red bone marrow with healthy red bone marrow.
- Patient RBM is destroyed by chemotherapy and whole-body radiation.
- Healthy RBM can come from a donor or patient if in remission.
- Marrow migrates to red bone marrow cavities and multiplies.
- Can create graft-vs-host disease.
- Patients need to stay on immunosuppressants.
Haemostasis
- Vascular spasm: Arteries and arterioles constrict reducing blood flow.
-
Platelet plug formation: Requires exposure to:
- Von Willebrand factor
- Fibrinogen
- Collagen
- Requires several steps:
- Adhesion
- Outside-in signalling
- Secretion
- Aggregation
- Thrombin production
-
Blood clotting: Coagulation
- Extrinsic pathway: Fewer steps, rapid, initiated by tissue factor.
- Intrinsic pathway: More complex, slower, does not require tissue damage.
Coagulation Pathways
-
Extrinsic Pathway:
- Tissue factor (TF) leaks into the blood from cells outside the bloodstream.
- FVII is activated by thrombin and FXa from the intrinsic pathway.
- FVIIa and TF activate FX.
-
Intrinsic Pathway:
- Surface contact activates FXII.
- FXIIa activates FXI and releases bradykinin.
- Ca2+ and FXIa activate FIX.
- FIXa hydrolyses FX along with Ca2+, phosphatidylserine, and FVIIIa.
- FVIII is a cofactor activated by thrombin.
-
Common Pathway:
- FX activates the common pathway.
- FXa cleaves prothrombin on the surface of activated platelets.
- FV is activated by thrombin.
- Fibrinogen is converted to fibrin by thrombin.
- Thrombin activates FXIII which cross-links the fibrin clot.
Fibrinolysis
- Dissolves small clots and dissolved clots as sites of repair.
- Inactive plasminogen incorporated into the clot.
- Activated to plasmin by substances in body tissue (thrombin, t-PA).
- Plasmin digests fibrin threads and inactivates fibrinogen, prothrombin, FV, and FXII.
Haemophilia
-
Haemophilia A: X-linked leading to FVIII deficiency.
- Normal extrinsic pathway.
- Abnormal intrinsic pathway.
- Affects 1 in 5000 males.
-
Haemophilia B: "Christmas disease", X-linked disorder leading to FIX deficiency.
- Normal PT time but abnormal APTT.
- Affects 1 in 30 000 males.
Blood Groups
- The surface of RBCs contains glycoproteins and glycolipids acting as antigens.
Blood Cell Formation
- All marrow is red in newborns, converted to yellow over time.
- Haematopoiesis occurs in red bone marrow.
- Pluripotent stem cells: Found in red bone marrow and can differentiate into any cell.
- Myeloid stem cells: Develop in red bone marrow and give rise to platelets, RBCs, monocytes, neutrophils, eosinophils, and basophils.
- Lymphoid stem cells: Begin development in red bone marrow, end in lymphatic tissues and give rise to lymphocytes.
Leukaemias
- Production of malignant WBC cells, suppress production of all normal cells in the red bone marrow.
- Can cause bleeding problems and anaemia.
- Acute lymphoblastic leukaemia: Short onset, derived from lymphoid stem cells, most common in children.
- Acute myelogenous leukaemia: Affects all ages.
- Chronic lymphoblastic leukaemia: Most common in adults (55+).
- Chronic myelogenous leukaemia: Prolonged onset, derived from myeloid stem cells, mostly in adults.
Bone Marrow Transplant
- Replacement of cancerous or abnormal red bone marrow with healthy red bone marrow.
- Patient's red bone marrow destroyed by chemotherapy and whole body radiation.
- Healthy red bone marrow can be from a donor or the patient if in remission.
- Marrow migrates to red bone marrow cavities and multiples.
- Can create graft vs. host disease.
- Patients need to stay on immunosuppressants.
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Description
This quiz explores the intricate processes involved in blood clotting, including vascular spasm, platelet plug formation, and the coagulation pathways. You'll learn about key components such as von Willebrand factor and the intrinsic and extrinsic pathways. Test your understanding of how these mechanisms work together to prevent excessive bleeding.
