homeostasis and coagulation

Question 1

clotting mechanisms

Answer 1

intrinsic- exposed collagen from injured blood vessel wall, test tube.
extrinsic- damaged tissue releases thromboplastin (converts prothrombin to thrombin)

Question 2

thrombin

Answer 2

activates protein C which is an inhibitor of the coagulation cascade. converted from thrombin.

Question 3

fibrin

Answer 3

non- globular protein involved in clotting blood. converted from fibrinogen by thrombin

Question 4

amplification cascade

Answer 4

thromboplastin and clotting factors convert inactive X to active X –> Active X converts prothrombin to thrombin –> fibrinogen is converted to fibrin by thrombin, and thrombin is also converted to XII and I –> fibrin, XIII and I form stable fibrin –> clot is formed

Question 5

platelets

Answer 5

non-nuclear cellular fragments
form mechanical plugs during blood vessel injury
adhesion and aggregation reactions:
adhesion: to subendothelial surface on damage/disease- due to binding to Von Willebrand’s factor
adhesion causes release reaction :ADP and thromboxane which promote platelet aggregation.
leads to platelet mass to plug area of endothelial damage- promotes coagulation reaction: -ve charges phospholipids on activated platelets which have adhered to site of damage to localize fibrin formation.
coagulation involved in: haemostasis- stopping blood loss through damaged vessels.

Question 6

adhesion in the coagulation cascade

Answer 6

Adhesion to exposed collagen in subendothelium. Collagen is very thrombogenic, responsible for the initiation of platelet adhesion. A number of adhesive receptors on the platelet surface membrane interact with collagen. Initial binding allows for other binding sites. Initiating transmembrane and intracellular signalling. Bind through von willerband factor VWF.

Question 7

platelet aggregation

Answer 7

Platelet adhesion at the site of vessel wall damage initiates activation events which activate aggregation. Adherent platelets undergo a dramatic shape change- irregular sphere- maximum surface area. Adherent platelets also secrete the contents of their storage granules by an exocidic process. This provides a high local concentration of effector molecules essential for platelet plug formation at the site of vascular injury aggregation agent- ADP. Platelet activation stimulation of thromboxane A2- another aggregation agent. Thrombin formed via coagulation pathway from prothrombin. Aggregation to endothelium stimulated via receptor-mediated Signal Transduction Events. Aggregation is an active metabolic process. By fibrinogen and vWF- binding of activated neighboring platelets. Allowing platelet aggregation to go ahead. Allows platelets to form a platelet plug.

Question 8

laboratory tests

Answer 8

-bleeding:
incisions to forearm with venous cuff
increased in platelet dysfunction/thrombocytopenia
-prothrombin time (INTERNATIONL NORMALISED RATIO INR)
time for coagulation following addition of thromboplastin. prolonged by abnormalities of Factors VII, X, V, II or I, liver disease or warfarin
- activated partial thromboplastin time (APTT)
examines ‘intrinsic pathway’. altered by changes in factors XII, XI, IX, VIII, X, V, II or I

Question 9

disorders of clotting and bleeding

Answer 9

thrombosis- unwanted blood cells.
venous: clots (thrombi) from in veins (DVT) due to stasis of blood. may travel to lungs -> pulmonary embolism.
atrial fibrilation: risk if TIA (transient ischaemic attack)

Question 10

virchow’s triad

Answer 10

• vascular endothelial injury
• alterations in blood flow (stasis)
• alterations in constitution of blood

Question 11

arterial thrombosis

Answer 11

arterial: form at atherosclerotic sites, lead to arterial blockage, ‘more’ of a platelet event:
heart - heart attack, MI
cerebral vessels (stroke)

Question 12

venous thrombosis

Answer 12

‘more’ of a platelet event

Question 13

haemophilia A

Answer 13

Genetic- carried on X-chromosome, so males XY most affected and female XX carriers.
low or lacking factor VIII of the clotting cascade. haemorrhage and prolonged bleeding. treat with factor VIII from blood donors or analogue of vasopressin (ADH) which increases patients factor VIII release

Question 14

haemophilia B

Answer 14

deficiency of factor IX. treated with prophylactic factor IX

Question 15

von Willebrand’s Disease

Answer 15

hereditary lack or defect in vWF. leads to increased bruising, nose bleeds, mucosal bleeding. Rx: analogue of vasopressin (ADH), factor VIII or vWF

Question 16

liver disease

Answer 16

reduced synthesis of clotting factors leads to increased bleeding- increased prothrombin time

Question 17

thrombocytopenia

Answer 17

reduced platelet number
spontaneous skin bleeding (purpura)
causes:
idiopathic
viral
drug-induced
toxins

Question 18

drug-induced thrombocytopenia

Answer 18

by immune mechanisms

treat with steroids (suppress immune response), in unresponsive splenectomy

Question 19

DID- Disseminated Intravascular Coagulation

Answer 19

large amounts of fibrin generated by procoagulant material such as amniotic fluid. vast consumption of clotting factors and platelets.
widespread thrombosis. give platelets and fresh frozen plasma.