Blood Physiology Lecture 5 Flashcards
Hemostasis is the _____
prevention of blood loss
_____ are important in hemostasis
platelets
platelets are found in the middle _______
“buffy coat” mixed with the white blood cells
Why is hemostasis necessary? (3)
- Pro-hemostatic factors prevent blood loss
-Anti-hemostatic factors are factors which keep the blood fluid
-Our body tries to maintain a state where blood can circulate smoothly, without
formation of unnecessary clots
Steps of homeostasis (3):
- Vasoconstriction , Vascular Spasm
- Primary Hemostasis or platelet plug formation
- Secondary Hemostasis or blood clotting/coagulation
Steps of homeostasis:1. Vasoconstriction Vascular Spasm
A ruptured blood vessel contracts to minimize blood loss at the site of the cut
(Factors which trigger vasoconstriction:)
- An injury stimulates pain receptors that activate nerve endings that are directly affected by the cuts, causing vasoconstriction
-Injury to blood vessel smooth muscle, causing vasoconstriction
-Local injury to the platelets causes the release of serotonin, which acts
as a vasoconstrictor
Steps of homeostasis: 2. Primary Hemostasis or platelet plug formation
-Platelets aggregate to form a platelet plug or a white thrombus (It is known as white thrombus because platelets are colorless cells)
Steps of homeostasis: 3. Secondary Hemostasis or blood clotting/coagulation
-If the bleeding does not stop after the formation of the white thrombus, blood clotting enzymes are activated to form a stronger gel-like clot at the cut site. This is known as red thrombus as it is reddish in color.
The word thrombus refers to _______
a blood clot
3 steps of the formation of platelets
- Platelets originate from the pluripotent stem cells of the bone marrow
- Pluripotent stem cells are converted to cells called megakaryocytes
- Platelets are pinched off from the cytoplasmic part of megakaryocytes
Platelets contain organelles such as _______
Vesicles called alpha granules and dense granules
Platelets do not contain a ________
nucleus
Things platelets contain (5)
- Vesicles called alpha granules, and dense granules
- Glycogen for energy
- Contractile proteins actin and myosin
- Surface glycoproteins which act as receptors
- Canaliculi
Contents of Alpha Granules (4)
-Adhesive protein von Wilebrand factor
-growth factors
-some blood clotting factors
-cytokines
Contents of Dense Granules (3)
-ADP and ATP
-5-hydroxytryptamine (serotonin)
-calcium
Alpha granules contain _______
large molecules
Denses granules contain ______
small molecules
Platelet Plug Formation (Primary Hemostasis) steps (3):
- Adhesion
- Activation of Platelets
- Aggregation of Platelets
Platelet Plug Formation (Primary Hemostasis) steps: Adhesion
-Platelets must adhere to a surface in the process of hemostasis
-Normally do not stick to the smooth surface of blood vessels but an injury to blood vessels disrupts the endothelial layer and exposes the underlying collagen
-Platelets adhere to the collagen tissue using von Willebrand factor
- von Willebrand factor is a protein secreted by platelets and
endothelial cells
-Once secreted, von Willebrand factor can change conformation
and bind to platelets
- von Willebrand factor forms a bridge between the damaged
vessel wall and the platelets
Platelet Plug Formation (Primary Hemostasis) steps: Activation of Platelets:
- Binding of platelets to collagen triggers the release of chemicals from their storage granules (ADP and serotonin)
- ADP and serotonin act locally on the platelets to change metabolism, shape, and expression of receptors on the surface of the platelet
Platelet Plug Formation (Primary Hemostasis) steps: Aggregation of Platelets:
New platelets to adhere to old ones by a positive feedback effect which rapidly
forms a platelet plug inside the vessel
Platelet Plug steps (5)
-von Willebrand factor is secreted by platelets and endothelial cells and binds to exposed
collagen molecules in the damaged blood vessel wall, changes its own conformation and
becomes bound to platelets
-von Willebrand factor forms a bridge between the damaged vessel wall and the
platelets
-The activated platelets express a fibrinogen receptor on their surface, which can bind to
fibrinogen, a plasma protein, and other platelets to form a network, or lattice-like
structure, which ultimately forms the plug
-During this process the activated platelets also secrete thromboxane A2 and ADP, which
attract more platelets to the cut site, and the aggregation continues
-After the plug is formed, the plug can contract using its contractile proteins actin and
myosin to tighten the plug and seal the cut site
Adhesion of platelets triggers ________
activation of platelets
Once platelets are activation they secrete the compounds: (2)
- Serotonin (5HT) and ADP
- Thromboxane A2
What does serotonin do when it is secreted from activate platelets
It acts as a vasoconstrictor
What does ADP do when it is secreted from activated platelets
it plays a role in further platelet aggregation
What does Thromboxane A2 do when it is secreted from activated platelets?
It promotes further platelet aggregation and vasoconstriction of the vascular smooth muscle which will reduce blood flow to the cut site
Upon platelet activation, __________ exposed on the surface of the platelet
aid in the conversion of ________ to thrombin, which acts to promote further platelet _________
- Phospholipids
- Prothrombin
- Aggregation
Why does the plug not expand along the undamaged endothelium of the blood vessel?
Adjacent undamaged endothelial cells synthesize and release prostacyclin, and nitric oxide which inhibit the spread of the platelet plug along undamaged endothelium
Prostacyclin function:
Inhibits platelet aggregation
Nitric Oxide Function
inhibits platelet adhesion, activation and aggregation
The innate response of inflammation occurs within seconds of the initiation of ______. Following some time lag, chemicals are released from the blood vessel wall which start the process of healing by initiating the formation of the ________ at the site of the cut.
- Injury
- Platelet Plug
Membrane damage, or a disturbance in the cell membrane, initiates the production of _____ acid from membrane _______.
- Arachidonic
- Phospholipids
What happens in the lipoxygenase pathway?
Arachidonic acid is converted to leukotrienes by the enzyme lipoxygenase, and
these chemicals then initiate inflammatory responses of swelling
What happens in the cyclooxyrgenase pathway (2):
- Arachidonic acid is converted to a prostaglandin by an enzyme known as cyclooxygenase or COX
2.Platelets and endothelial cells both have the cyclooxygenase enzyme, but they have different isoforms, or variants, of the enzyme. As a result, the hemostatic responses will vary. The prostaglandins play a role in hemostatic effects that help to prevent blood loss.
Generally, the acute inflammatory response precedes _______ effects
hemostatic
Aspirin is prescribed to prevent ________________
clot formation in patients that have a potential risk for heart attacks
In the cyclooxyenase pathway, ________ is produced from membrane _______ as a results of membrane rupture and ________
- arachidonic acid
- phospholipids
- injury
What are the two isoforms of the cyclooxyrgenase enzyme?
COX 1
COX 2
Healthy endothelial cells are subject to ________
the action of the COX 2 enzyme
What does the COX 2 activity in healthy endothelial cells result in?
the synthesis of prostacyclin and this has an
anti-hemostatic effect. The prostacyclin synthesized from arachidonic acid keeps the plug from expanding to adjacent undamaged endothelial cells.
Platelets are subject to ________
the action of the COX 1 enzyme
COX 1 in platelets produces ________
thromboxane A2 and has a pro-hemostatic effect, or
favors the formation of a platelet plug
__________ can inhibit the actions of both COX-1 and COX-2
Aspirin
What happens when COX-1 is inhibited in the platelets?
the chances of producing thromboxane A2 are completely blocked. Platelets are non-nucleated cells and once their enzyme is inhibited, the actions of the COX 1 enzyme are completely blocked, as they cannot synthesize new COX 1 enzyme.
What happens when COX-2 in healthy endothelial cells?
healthy endothelial cells will eventually start synthesizing new COX-2 enzymes as they are nucleated. COX-2 enzymes then convert arachidonic acid to prostacyclin.
When may low dose aspirin may be used in patients?
When they have an increased risk of a heart attack, to prevent clot formation
Aspirin can block the _________ only and block all the __________ pathways;
- COX 1
- pro-hemostatic
_______ pathways can overcome the inhibition of aspirin to make ______ and keep the vessels _______ and decrease _______ aggregation
- COX 2
- Prostylactin
- Vasodilator
- Platelet
