Blood practical Flashcards
Blood’s transport function
1) deliver oxygen and nutrients to cells
2) Transport hormones to target organs
3) Remove metabolic waste products from cells
Regulatory function of blood
1) Absorb and distribute body heat
2) Maintain adequate fluid volume
Protective function of blood
1) Prevent blood loss via clotting
2) Prevent infection
Components of blood
Plasma- cell-free, contains proteins, ions and molecules.
Buffy coat- thin white layer seen between RBCs and plasma after centrifution. Contains platelets and leukocytes.
Erythrocytes- haematocrit or packed cell volume
Meaning of a reduced PCV
- Patient has fewer RBCs
- Blood therefore has a reduced carrying capacity than normal and HR and CO may increase to try and compensate.
- Reduced viscosity of blood
Structure of a platelet
Anucleate cells
Biconcave discs
Contain granules that contain substances crucial for haemostasis
Contain functional mitochondria
Initial function of platelets
Rapid response to vessel injury
Accumulate and bind to exposed collagen in wall and surrounding
How are platelets activated?
1) Exposed collagen binds via GP Ia/IIa (receptor for collagen)
2) soluble agonists released by activated cells such as
(1) ADP
(2) thromboxane A2 (TxA2)
(3) thrombin
trigger platelet activation through GPCR
How do activated platelets change function?
1) Change shape and spread across damaged tissue
2) Activated platelets aggregate (bind together)
3) Release chemical mediators to support haemostasis, promote further platelet activation and recruit adittional circulating platelets
4) Move phosphatidylserine (PS) lipids from the inner leaflet of their memebrane to the outer leaflet.
How do platelets change shape
Become activated then become star shaped and increase their surface area
Process of platelet aggregation
mediated by fibrinogen binding to platelet receptors GPIIIb / IIIa
Each fibrinogen molecule has 2 spatially distant binding sites for platelets and can therfore bind 2 at once. This cross linking sustains aggregation.
What chemical mediators do platelets produce?
Thromboxane (TxA2 )
ADP
Arachidonic acid
Thrombaxane TxA2
Produced by platelets during haemostasis
has prothrombotic properties by activating platelets
circulating fibrinogen binds thromboxane receptors on platelets activating them.
Vasoconstrictor
ADP (adenosine diphosphate)
Platelet agonist
causes platelet shape change, aggregation and generte thromboxane
Effect of platelets moving PS lipids
By flipping PS lipids from the inner leaflet of their membrane to the outside leaflet (Platelets) they are engaging in procoagulant activity.
Negatively charged PS provides a scaffold on wjich coagulation factors accumulate in a Ca2+ dependant manner.
Therefore, platelets help localise and activate coagulation factors at the site of injury
Platelet production
Thrombopoietin stimulates megakaryoblasts –> megakarypcyte –> plasma membrane invades cytoplasm, dividing it into compartments
Cell then ruptures and the compartments become cells
What part of the vessel are platelets found
Borders
3 steps of haemostasis
1) vascular spasm (vasoconstriction to reduce BF)
2) Platelet plug formation
3) Coagulation
Vascular spasm
Local vasoconstriction
Triggered by the damage itself as well as chemicals released by endothelial cells and platelets (e.g. serotonine and thromboxane)
3 steps of platelet plug formation
1) adhesion
2) activation
3) aggregation
adhesion step of platelet plug formation
platelets are slowed and captured at the site of injury by von Willebrand Factor (vWF simultaneosly bonds to collagen and platelets).
Platelet adhesion to collagen is mediated by the platelet receptor GpVI
Activation step of platelet plug formation
When platelets bind to collagen, they become activated (mediated by glycoprotein VI receptor)
Change shape and spread out
PS lipids relocate from the inner aspect of the platelet membrane to the outside, creating a negative framweork for the coagulation factors to stick to
Arachidonic acid
Produced by plateletes
converted to thromboxane A2 by COX and thromboxane synthase
Aggregation step of platelet plug formation
mediated by the binding of fibrinogen to activated GPIIb/IIIa on the surface of platelets thereby cross-linking them. As more platelets arrive in the circulation, they are activated by released ADP and TxA2, and aggregate to platelets already in the plug. This leads to the formation of a primary haemostatic plug.
Arterial thrombosis
platelet rich
responsible for the thrombi in coronary arteries
venous thrombosis
rich in fibrin
red thrombi due to the number of RBC trapped in
DVT and PE
Order of events from vessel injury to formation of stable blood thrombus
vessel injury
platelets adhere to sub-endothelial collagen
platelet activation
adherent platelets release bioactive mediators (ADP and TxA2)
platelet aggregation with formation of primary haemostatic plug
coagulation factors accumulate on activated platelets
conversion of prothrombin to thrombin
conversion of soluble fibrinogen to insoluble fibrin
Name 3 factors or receptors that help platelet adhesion to damaged tissue
Integrin a2B1
Glycoprotein Ib (GpIb)
von Willebrand factor
Thrombocytopaenia
high platelet count
thrombocytopenia
low platelet count
sign is petechiae
Prothrombotic factors
Long periods of immobility
Combined oral contraceptive pill
more…?
Anti-thrombotic factors
Vitamin k deficiency- some coagulation factors are dependant (II, VII, IX and X)
Haemophilias
Aspirin
