What is haemostasis?
The stopping of bleeding.
When does physiological thrombosis often occur?
After a trauma (cut/injury).
What is important for physiological thrombosis?
Vessel wall structure and integrity.
What does a cross section of an artery contain?
Inner lumen with endothelial cells- these make a basal lamina to sit on. Around basal lamina are the SMC surrounded by the interstitial collagen fibres. The lumen contains RBC, WBC, platelets and plasma.
What does the lumen contain?
RBC, WBC, platelets and plasma.
What does plasma consist of?
Water, other molecules and proteins.
What factors does plasma contain?
Clotting factors.
What is serum?
Plasma without clotting factors.
Where are clotting factors produced?
Liver but some in epithelial cells.
How are clotting factors often named?
Roman numerals.
How do clotting factors work and what do they result in?
They are an amplification system resulting in the production of thrombin.
What does thrombin do?
Promotes the conversion of soluble fibrinogen into insoluble fibrin.
What does fibrin form?
A fibrin meshwork of strands.
What is the precursor of thrombin?
Prothrombin- activated by clotting factor amplification system.
What is the clotting factor amplification cascade stimulated by?
Initial trauma.
What does initial trauma result in?
Exposure of interstitial collagens to plasma.
Exposure of a molecule called tissue factor (TF).
What happens to the vessel after trauma?
Blood leaks out of the trauma defect and comes into contact with the interstitial collagen fibres. Plasma clotting factors can then be activated because they are in contact with interstitial collagens. Tissue factor is also released from SMC- TF can now bind a particular clotting factor and activate the amplification cascade.
What does plasma have to do to activate clotting factors?
Contact interstitial collagens.
Where is tissue factor released from?
Smooth muscle cells.
What does tissue factor do?
Binds a particular clotting factor to activate amplification cascade.
How are clotting factors activated in terms of structure?
Many are serine proteases- this means they have a serine amino acid in them and they cleave other clotting factors to form the active molecule.
What does the clotting cascade lead to?
The conversion of prothrombin to active thrombin which stimulates the conversion of soluble fibrinogen into insoluble fibrin.
What is the end-point of the clotting cascade?
The production of insoluble fibrin strands which form a meshwork.
Where are platelets produced?
Bone marrow.
What type of cells are platelets produced from?
Megakaryocyte.
What characterises megakaryocytic and how are they formed?
Characterised by large size and many nuclei- formed through excessive nucleic division without cytoplasmic cell division.
How do platelets bud off from the megakaryocyte?
Bud off as cytoplasmic extensions.
What does trauma to a vessel lead the platelets to do?
Come into contact with the interstitial collagens.
What do platelets do in response to trauma?
Adhere together to close the trauma-induced gap. (And release clotting factors).
What is coagulation by definition?
The solidification of blood.
What are the 2 types of coagulation?
Thrombus formation
Clot formation
Where does thrombus formation occur?
Flowing blood.
What does a thrombus contain?
Platelets and meshwork of fibrin strands
What colour is a thrombus?
Pale/cream coloured
Why does thrombus formation occur in flowing blood?
Platelets have molecules on their surface which allow adherence to interstitial collagen even when blood is flowing past them.
Where does clot formation occur?
Stagnant blood.
How does clot formation occur?
Blood leaks out from vessel and becomes stagnant (stationary). Within the stagnant blood, the clotting cascade is activated.
What does a clot contain?
RBC and meshwork of fibrin strands.
What colour is a clot?
Red (due to RBC).
What is clot formation an example of?
Haemostasis.
Summarise the process after trauma.
Trauma occurs, results in BV defect.
Blood leaks out of lumen- plasma/IS collagen exposure
Stagnant blood can form clot, flow can form thrombus.
Blood vessel always vasoconstricts to preserve BF.
What grows into the wound and what does this form?
New vessels (angiogenesis)- forms granulation tissue.
What do capillaries formed in the granulation tissue do?
Oxygenate the wound and keep it alive.
How is a thrombus physiologically removed?
Protein called plasminogen is converted into plasmin. Plasmin cuts up fibrin into smaller fragments for removal.
What is the removal of a thrombus called?
Thrombolysis.
What does the thrombolytic system depend on?
The plasminogen being converted into plasmin
Plasmin cutting up the fibrin into smaller fragments for removal.
What is the thrombolytic system usually in balance with?
In balance with the clotting system- plasmin generation will limit the extent of the evolving thrombus.
When are thrombosis/clotting physiological?
Wound repair/healing
Female menstruation
What does Virchow’s Triad address?
The three predisposing situations that may result in thrombus formation.
What is Virchow’s Triad?
Changes in the intimal surface of the vessel
Changes in pattern of blood flow through the vessel
Changes in the constituents of blood in vessel
When does pathological thrombosis occur?
In the absence a trauma.
What are the coronary arteries?
Main cardiac arteries which supply blood to the heart.
What does smoking cigarettes do to platelets?
Increases ‘stickiness’- they find it easier to aggregate. Sticker platelets increases the likelihood of a thrombosis occuring.
How does the impact of smoking relate to Virchow’s Triad?
Demonstrates an example of 3- alteration in blood constituents.
What do smoking and high lipid concentration act as a predisposition to?
Atheroma formation in the coronary arteries.
What is atherosclerosis?
Disease of coronary arteries in which there is a resulting build-up of lipid under the intimal surface of the vessel.
What do atheromas result in?
Abnormal blood flow- both slow and turbulent blood flow can be recognised.
What does slow blood flow predispose to?
Fibrin and platelet clumping.
How does atheroma formation relate to Virchow’s Triad?
Example of 1/2- change in intimal surface of vessel, disruption to blood flow.
What else can rupture through the intimal surface of a vessel?
Lipid / collagen.
What happens when platezleytsand fibrin are exposed to lipid/collagen/turbulent flow.
Thrombus formation.
What does a thrombus do in the coronary artery?
Blocks cardiac blood flow.
Why does a clot form behind the thrombus?
Because blood flow is stagnant.
What aspect of Virchow’s Triad can lead to thrombosis?
All three.
What are the consequences of blocking an artery?
Complete/partial obstruction of artery means that threes reduced or no flow past the blockage. The tissue supplied by this artery will receive less BF and less oxygen.
What is it called when a tissue receives less blood flow?
Ischaemia.
What is it called when the tissue supplied becomes less oxygenated?
Hypoxia.
What is deoxygenated tissue described as?
Ischaemic / hypoxic.
What characterises ischaemic tissue?
Pain.
How can blockages cause tissue death?
Significant blockage causes obstruction to blood flow. Ischaemia leads to hypoxia resulting in localised area of cell death.
What is a localised area of dead tissue called?
Infarct / infarction.
What is the process of any tissue dying called?
Necrosis.
What name is reserved for tissue death due to ischaemia?
Ischaemic necrosis.
What is an infarct in the heart called?
Coronary artery thrombosis.
What is an infarct in the brain called?
Cerebral artery thrombosis.
What is an infarct in the gut called?
Mesenteric artery thrombosis.
What is embolism?
Embolism involves a mass of material moving in the vascular system and being able to become lodged in a vessel and block its lumen.
What are most emboli derived from?
Thrombi / clots.
What is the term given to the embolism of thrombi/clots?
Thromboembolism.
How does a pulmonary embolism occur?
Sluggish flow in deep veins leads to thrombosis/clot formation. Clot breaks off and travels through circulatory system through heart to pulmonary artery.
Name 2 other forms of embolism.
Marrow embolism
Air embolism
What is circulatory shock?
Profound circulatory failure causing the perfusion of vital organs.
What are the 3 types of circulatory shock?
Hypovalaemic
Cardiogenic
Septic
What is perfusion?
Passage of blood/other fluid through blood vessels/channels.
Why should the term ‘shock’ be used with caution around patients?
Does not bear psychological or electrical reference.
Is a normal blood pressure reading arterial or venous?
Arterial.
What is a normal blood pressure reading?
120/80
What does normal blood pressure rely on?
Enough blood in system
Smooth muscle in vessels having a certain tone
Heart pumping blood
Why must there be enough blood in the system?
If there isn’t enough, the vessel will collapse and the blood pressure will become low than unrecordable.
Why must smooth muscle have a certain tone?
If tone is decreased, the vessel will dilate. If enough vessels are affected then the blood pressure will fall.
Why must the heart be pumping blood?
If it doesn’t pump enough blood, the blood pressure will fall.
How does the body detect blood flow/pressure?
Carotid bodies.
What are the carotid bodies?
Primary detection mechanism of blood flow/pressure/oxygenation.
Where are the carotid bodies?
2 carotid bodies on either side of the neck occurring at the bifurcation (splitting) of the carotid arteries.
What do carotid bodies respond to?
Partial pressure of oxygen.
How does the partial pressure of oxygen relate to blood pressure?
If the blood pressure drops, so does the partial pressure of oxygen.
How do carotid bodies respond to low blood pressure?
Send nerve signals to the brainstem to activate the sympathetic nervous system.
What does the sympathetic nervous system primarily do in response to low blood pressure?
Tells heart to pump faster/harder- increases heart rate.
What is the physiological response to low blood pressure?
Increase of heart rate.
What are the secondary functions of the sympathetic nervous system following carotid body-brainstem activation?
Increased vascular tone in the limbs and abdomen, resulting in blood being pushed up to chest and head- circulation focused round vital organs.
Adrenal glands secrete adrenaline- stimulates heart to beat even harder and faster.
Why does the sympathetic nervous system stimulate increased vascular tone in the limbs and abdomen?
Pushes blood to chest/head- circulation is focused around the vital organs.
Why does the sympathetic nervous system stimulate adrenaline production in the adrenal glands?
Adrenaline encourages the heart to beat faster- adds to increased heart rate.
What is hypervolaemic shock?
Hypervolaemic shock occurs when there is insufficient blood pumping in the body to maintain blood pressure.
What do the effects of carotid bodies display in terms of clinical presentation?
Malaise
Rapid breathing
Fast heart rate
Pale, sweaty skin
What is cardiogenic shock?
Cardiogenic shock occurs as a result of cardiac inability to maintain blood pressure- not just due to insufficient blood.
What is septic shock?
Septic shock occurs when bacteria enters the blood.
Bacteremia= entry
Septicemia = growth
What causes the extremity within septic shock?
Vasodilation in excess.
What are the complications of shock?
Decreased perfusion of blood
Decreased perfusion of kidneys (both initially reversible but then severe).
What is a brain injury due to shock called?
Ischaemic infarction of brain tissue.
What is a renal injury due to shock called?
Ischaemic necrosis of renal tubules.
