Physiology + pathophysiology of clotting Flashcards
Semester 1 year 1
What is the blood?
A complex fluid of cellular components suspended in water ECF (plasma)
What are 3 components of blood?
-erythrocytes - red blood cells
-leukocytes - white blood cells
-platelets - involved in clotting
What is plasma?
A pale, watery solution of electrolytes, plasma, proteins, carbohydrates + lipids
What are the principle proteins in plasma?
-albumin
-fibrinogen
-immunoglobulins
-other plasma proteins in blood coagulation cascades
What are erythrocytes?
-most abundant cell (haematocrit)
-mainly composed of haemoglobin
What are the functions of erythrocytes?
-O2 carriage from lungs to systemic system
-CO2 carriage from tissues to lungs
-buffering of acids/bases
Describe the feedback mechanism for platelets
-platelets have receptor for thrombopoietin (TPO)
-abundant platelets bind TPO
-megakaryocytes not generated
-platelets not made
-receptors don’t bind to TPO
-TPO stimulates megakaryocyte production
-platelets generated
What is haemostasis?
The prevention of haemorrhage
How is haemostasis achieved?
-platelet plug - primary haemostasis
-clot formation - secondary haemostasis
What do platelets contain?
-mitochondria
-lysosomes
-peroxisomes
-alpha granules (VWF, fibrinogen, clotting factor, platelet derived growth factor)
-dense-core granules
What is the outer coat of platelets rich in?
Platelet receptors
What are the steps of platelet plug formation?
- platelet adhesion
- platelet activation
- platelet aggregation
- blood clot formation
Describe platelet adhesion
-a rapid temporary seal to prevent further blood loss
-plasma von Willebrand factor (VWF) binds to exposed collagen + platelet receptors
-binding of platelet receptors –> cascade of IC events –> activation
What does damage to the endothelium expose?
Subendothelial collagen (most thrombogenic)
Describe platelet activation
-secretion/exocytosis of dense and alpha granules
-secretion of platelet derived growth factor (PDGF)
-cytoskeletal changes
-expression of fibrinogen receptors
Describe platelet aggregation
-platelet fibrinogen receptors bind to plasma fibrinogen
-forms molecular bridges between platelets (aggregation)
-eventually actin + myosin contract (more compact platelet plug)
Describe blood clot formation
-slower, complex process involving cascade of clotting factors
-makes more permanent fibrin mesh
What are the 2 pathways for clotting?
-intrinsic pathway (slower)
-extrinsic pathway
When is the intrinsic pathway used for blood clotting?
Contact activation or surface damage
When is the extrinsic pathway used for blood clotting?
Trauma or inflammation
How is the intrinsic pathway for clotting initiated and describe the process
-initiated by factors in blood in contact with -ively charged membrane surface of activated platelets
-cascade of protease reactions
-end with activated factor Xa
How is the extrinsic pathway for clotting initiated and describe the process
-injury to endothelium allows tissue factor in subendothelial cells to become activated when blood factor VII in contact
-results in activated factor Xa
What is the common pathway from the 2 pathways for blood clotting?
-activated factor Xa
-enters common pathway to generate thrombin (enzyme) + produce stable fibrin
What happens as a result of the promotion of anti-thrombotic state?
-normal endothelial cells maintain normal blood fluidity
-paracrine factors inhibit platelet adhesion + aggregation
-many anti-coagulant factors
What is the promotion of pro-thrombotic state via?
-event of vascular damage
-hypoxia - expression of procoagulants
What does abnormal blood flow lead to injury of?
Turbulent blood flow leads to endothelial injury
What is turbulent flow caused by?
-local stenosis
-large radius
-high velocity
What can thrombus lead to?
Pathological conditions
