Vascular disturbances 2

Question 0

What are the elements of haemostasis?

Answer 0

1. Platelets
2. Blood vessel- wall and endothelium
3. Clotting factors
   Dysfunction➡ bleeding/thrombis

Question 1

What is haemostasis?
What is a haemorrhage?
Thrombosis?

Answer 1

Haemostasis- Arrest of bleeding, blood coagulation and vessel repair
Haemorrhage= ineffective haemostasis
Thrombis= inappropriate/ excessive blood coagulation

Question 2

Describe the resolution of haemorrhage at the tissue level

Answer 2

• RBC, WBC and plasma proteins released into tissue
• RBC broken down into heme and globin by macrophages
• Hb in circulation is transported to liver
• globin is broken down in macrophages into amino acids
• plasma proteins are released into tissues
• fibrinogen converted to fibrin
• fibroblasts are activated leading to collagen formation and tissue repair.

RBC, WBC + plasma proteins releases into tissues
RBC➡ heme + globin (tissues + circulation)
Tissues:macrophages

Slide 11, 12, 13

1) Haemorrhage into an area release many RBC’s and much plasma along with a few other cell types
2) RBC break down releasing (heme +globin)
3) in the tissue, fixed and circulating macrophages will be attracted to enter the sure if haemorrhage to mop up debris and phagocytosed the RBC
4) the haemoglobin is phagocytosed red cells in the macrophages to (iron + biliverdin)-green colour of bruise. Iron is stored intracellularly in macrophages as (ferretinand haemosideran➡ biliverdin (orange-brown) is further metabolised to bilirubin then released into the circulation, to be transported by albumin to the liver and then excreted in bile.

5) haemoglobin that is released into the circulation is bound by plasma proteins and transported to the liver for recycling into bilirubin and then excreted as bile.
6) globin is broken down within macrophages into amino acids, which are recycled,
7) the plasma proteins released during haemorrhage include fibrinogen. Once these proteins become extra vascular, fibrinogen converts to fibrin. The presence of fibrin encourages fibroblasts to enter and produce collagen and form fibrous connective tissue (ie fibrosis) it also causes more phagocytes to migrate there

Question 3

Give me an overview of haemostasis

Answer 3

Slide 15
Or written on paper lecture

1. Tissue injury
2. Activation of intrinsic and extrinsic pathways
   
   3. Extrinsic ➡ release if tissue factor from endothelial cells into circulation
      A) activation of factor 7➡ triggers cascade
      B) activation of factor 10➡ common pathway
3. Intrinsic pathway
   A)tissue damage and exposure to collagen
   B) when C comes in contact with blood ➡activates factor 12➡ already in circulation➡ once factor 12 comes into contact with collagen ➡cascade of Intrinsic pathway
   C) factor 11, 9 and 8 are activated then factor 10➡ then common pathway
4. Common pathway:
   A) Factor 10 is activated
   B) thrombin A and Factors 5,8, 11 and 13
   C) fibrin (bodies glue for platelets covers hole, and glues damaged tissue.
   D) fibrin activates fibroblasts and inflammatory response

Common pathway:
Factor 10 then
Throw a (thrombin A) star (factor 5) which spooks the octopus (8) which jumps on some skis (11) then enters a spaceship (13) the spaceship shits its self coz its had to much fibre (fibrin) the shit that lands in the water activates an inflammatory response and fibroblast activation.

Question 4

Describe the differences you would see In anti thrombotic endothelial cells and Prothrombotic endothelial cells
Slide 17

Answer 4

Antithrombotic:

• anti platelet
• fibrinolytic factors
• anticoagulant ion factors
• vasodilators

Prothrombotic:

• platelet co-factors
• anti-fibrinolytic factors
• coagulant factors
• vasoconstrictors

Question 5

Platelets in haemostasis
Adhesion? 
Secretion?
Primary haemostasis? 
Secondary? 
Fibrin?

Answer 5

• Prothrombotic
• responsible for primary haemostasis (3stages)
• adhesion, secretion and aggregation

Platelets bind to the extra cellular matrix via a vonwilibrans factor bridge
-vWF is realised from endothelial cells when they are damaged

Question 6

Describe the process in Primary haemostasis

1. Adhesion
2. Platelet secretion

Primary and secondary haemostasis

Answer 6

• Prothrombotic
• responsible for primary haemostasis (3stages)
• adhesion, secretion and aggregation

Adhesion:

• platelets bind to ECM via vWF bridge
• vWF is released from endothelial cells in response to damage

Secretion:
-adhesion triggers synthesis and secretion of a variety of substances to promote platelet adhesion and facilitate platelet aggregation

Primary haemostasis:
-platelet aggregation. Platelet adhesion and secretion leads to platelet shape change and aggregation= formation of the primary haemostatic plug (reversible)

Secondary haemostasis: activation of coagulation pathways glues the platelet plug together with fibrin= formation of secondary haemostatic plug (irreversible)

Fibrin:

• stabilises the platelet plug
• encourages fibroblastic proliferation and organisation= important for resolution of thrombus
• increases inflammatory response

Platelets bind to the extra cellular matrix via a vonwilibrans factor bridge
-vWF is realised from endothelial cells when they are damaged

Platelet adhesion triggers the synthesis and secretion of a variety of substances to promote platelet adhesion Nd facilitate platelet aggregation (= platelets sticking to each other)

Question 7

Clotting factors= inactive pro-enzymes within the circulation (liver)
-once activated a cascade of reactions is triggered which ultimately results in the formation of fibrin.
Fibrin acts to:

Answer 7

• stabilise platelet plug (=formation of the secondary haemostatic plug
• encourages fibroblastic proliferation and organisation➡ important in the resolution of the thrombus
• • inflammatory response