ATHEROSCLEROSIS, THROMBOSIS AND EMBOLISM Flashcards
How many people fie each year due to hospital acquired Venous thrombone embolism?
32,000
we need to do VTE risk assessment on inpatients
Name the three layers of vessels
- Intima (Endothelial cell layer)
- Media (Smooth muscle layer)
- Adventitia (Fibrous connective tissue)
Describe the intima layer of blood vessels
It is made up of endothelial cells
Describe the media layer of blood vessels
It is a smooth muscle layer
Describe the adventitia layer of blood vessels
It is made up of fibrous connective tissue
Describe differences in the layers or arteries and veins
- In arteries media is much bigger than in veins
- Veins have a bigger lumen
- Veins have a larger adventitia than arteries
Where are endothelial cells found?
They are found don the interior surfaces of blood vessels and lymphatics and on the heart
What are endothelial cells on the heart called?
endocardium cells
What is the origin of endothelial cells?
Mesodermal origin
What are the functions of endothelial cells
- Barrier funcitons
- Involved in angiogenesis
- Mediation of coagulation
- Control of blood pressure
- Fluid filtration
Describe how endothelial cells carry our their barrier function
They have a semi selective barrier tat allows passage of white blood cells into and out of the blood
What can increase the permeability of endothelial cells?
Prolonged inflammation leads to increased permeability and tissue swelling
How do endothelial cells help mediate coagulation?
They have:
- Heparan sulphate which inactivates clotting cascade
- vWF which binds to stabilise factor VIII, binds to collagen linking platelets
How do endothelial cells help control blood pressure?
Through vasoconstriction and dilation
Name some disease where endothelial cell dysfunction is seen
- Diabetes
- Septic shock
- Hypertension
- Behcet’s
Other than disease what can cause endothelial cell dysfunction?
- Tobacco
- Air pollution
- Trans fat consumption
How can endothelial cell dysfunction be improved?
- Improved by smoking cessation
- Weight loss
- Improved diet
- Exercise
What is atheroma
It is the accumulation of intracellular and extra cellular lipid in the intimate of large and medium sized arteries
What is Atherosclerosis?
The thickening and hardening of arterial walls as a consequence of atheroma
Why do atheromas forms?
They form in repose to chronic endothelial cell damage
Why do atheromas mainly occur in arteries?
As blood is under much greater pressure in the arteries
Go through the steps of atheroma/ Atherosclerosis development
- Chronic endothelial cell injury
- Endothelial dysfunction
- Entrance of cholesterol rich LDLs in to intima
- Lipid engulfed by intima macrophages
- Formation of a flat yellow fat streak later forming raised yellow lipid plaques
- Extra cellular lipid deposits and collagen deposition leading to a fibrous cap over the lipids core (HARD yellow fatty plaque)
7 Ulceration of plaque - Predisposition of thrombus formation (Advanced complicated plaque formation)
Give some risk factors for atheroma/atherosclerosis
- High LDL / Low HDL diet
- Hypertension
- Diabetes
- Smoking
- Obesity
- Sedentary lifesyle
What is primary prevention of for atheroma/atherosclerosis?
It is aimed at delaying atheromatous formation or causing regression of established lesion in people who have never suffered serious complications
What is secondary prevention of for atheroma/atherosclerosis?
It is intended to precent recurrence of events such as myocardial infarction and stroke in patients who have already suffering a significant event
What does primary prevention of atheroma/atherosclerosis involve?
Essentially involved risk factor modification
What does secondary prevention of atheroma/atherosclerosis include?
Includes regular medication such as aspirin
When do early lesions of atheromas usually form?
Early lesion begin in 20s and 30s
Are atheromas reversible?
No they can’t be reversed and the disease is progressive
What can be used to stabilise plaque and prevent plaque rupturing blood vessels?
We can use drugs like lipid modifying agents such as statins
What can be used in cases where blood vessel rupture has occurred?
Antithromobtic agents may be used in case of rupture, leading to exposure of subendothelial extra-cellular
How do calcium antagonists affect atheromas?
They may reduce foam cell production
Name the 4 main sites atheromas occur
- Aorta
- Coronary arteries
- lilac and popliteal arteries
- Internal carotis arteries
How is the aorta affected by atheromas?
- Can weakening of the walls
- This leads to aortic aneurysms (due to dilation of aorta)
- Risk of aorta rupturing increases
How are the coronary arteries affected by atheromas?
- Artery lumen narrows leading to reduced blood flow causing ischaemia (angina)
OR - Thrombus fors over plaque leading to occlusion of lumen causing infarction
How are lliac and popliteal arteries
affected by atheromas?
Lumen of the arteries narrow reducing blood flow causing ischaemia (intermittent claudication, gangrene)
How are the interns carrots arteries affected by atheromas?
An emboli can throw off and travel to the brain
This emboli blocks blood flow to the brain and can cause ischaemia (if transient) or infarction (or stroke)
What is thrombus?
It is a structured solid mass or plug of blood constituent formed within the heart of blood vessels during life
What is thrombosis ?
The process of thrombus formation
This can be considered to the inappropriate activation of the normal ischaemia (if transient) or infarction (TIA or stroke)
Where can thrombus happen?
It can occur anywhere waiting the cardiovascular system
Name the 3 types of thrombus
- Arterial
- Cardiac
- Venous
Where does arterial thrombus occur?
Usually at sits of endothelial injury or turbulence
Name some common sites where arterial thrombus occurs
- Coronary arteries
- Cerebral arteries
- Femoral arteries
What is cardiac thrombus sometimes called?
Mural thrombi
Where does cardiac thrombus occur?
Over areas of endomyocardial injury
Can also occur with arrhythmias and cardiomyopathy
What are the potential outcomes of thrombus ?
Propagation
Embolism
Dissolution
Organisation/ recanalisation
Where does venous thrombus occur?
Usually occurs at sites of vascular stasis
Vast majority occur in the veins of the lower limbs
What are the potential outcomes of thrombus ?
Propagation
Embolism
Dissolution
Organisation/ recanalisation
What are predisposing conditions to thrombus called?
Hyper coagulable conditions
Name some genetic Hyper coagulable conditions
- Protein C or S deficiency
- Antithrombin III deficiency
- Factor V mutations
- Prothrombin mutations
What do genetic Hyper coagulable conditions affect?
They prevent the bodies ability to carry out the clotting cascade
Name some environmental Hyper coagulable conditions
- Stasis eg Prolonged bed rest and long haul flights
- Atherosclerosis
- Smoking
- Atrial fibrillation
- Prosthetic heart valves
- Myocardial infarction
- vasculitis
- Neoplasia
- Oral contraceptives
- Disseminated intravascular coagulation
What is protein C?
It is a vitamin K dependent glycoprotein
What is another name for protein C?
Autothrombin IIA
What does protein C do?
Inactivated factor Va and VIII a
What does protein C deficiency increase?
It increases risk of clotting
What is protein S?
It is a vitamin K dependent glycoprotein
It is a co factor protein that works with protein C
What does protein S do?
It helps to inactivate Va and VIII a
What is antithrombin III?
It is a glycoprotein produced in the liver
Can antithrombin III deficiency be inherited?
Yes it is inherited in 1/2000 - 1/5000 people
Can antithrombin III be acquired?
Yes due to liver failure
What can antithrombin II deficiency lead to?
Can lead to increased clotting
What does antithrombin III target?
It targets the activated forms of Factor II, VII IX, X, XI, XII,
Name the most common mutation found in European populations
Factor V mutations
What can factor V mutations sometime see called?
Leuiden disease
Ho many British Caucasians are though tot have factor V Leiden?
Approx 10%
What is the link beteen deep vein thrombosis/ pulmonary embolism and factor V mutation?
Upo 30% of patients who develop thrombosis to a pulmonary embolism have a factor V mutation
How do people get mutated Facto Vs?
It is inherited so people may get passed on the mutated form of clotting factor V
What problems arise if someone has a mutated factor V protein?
The mutated form of factor V is not as easily de activated by protein C resulting in increased risks of clotting
How is stasis a Hyper coagulable condition?
if coagulation become activated when you are sedentary for a long period of time then they are not cleared out as easily and also platelets start clumping together
How is atherosclerosis a Hyper coagulable condition?
Causes damage to vessel wall and leads to thinning of lumen
How is smoking a Hyper coagulable condition?
Increases prothrombotic biomarkers
How is atrial fibrillation a Hyper coagulable condition?
Leads to blood pooling
How is having a prosthetic heart valve a Hyper coagulable condition?
Negatively charged may activate intrinsic pathway this may lead to the formation of an imperfect surface which leads to increased adhesion
How is Myocardial infarction a Hyper coagulable condition?
Causes damage to heart wall
How is Vasculitis a Hyper coagulable condition?
Causes damage to vessel walls
How is Neoplasia a Hyper coagulable condition?
Leads to malignancy induced abnormal coagulation and fibrinolysis, damage to endothelial cells, co-morbidities
How are oral contraceptives a Hyper coagulable condition?
They increase circulating fibrinogens
How is Disseminated intravascular coagulation a Hyper coagulable condition?
It leads to a widespread activation of clotting cascade secondary to other processes such as malignancy, sepsis, trauma
This leads to release of pro coagulants
How can we clinically prevent thrombosis
By prescribing:
- Aspirin
- Heparin
- Warfarin
Or by carrying out Thrombolysis
How is aspirin used to prevent thrombosis?
used for primary and secondary prevention of CVA and MI
How Is heparin used to prevent thrombosis?
It is injected into patients to prevent post operative deep vein thrombosis
How Is warfarin used to prevent thrombosis?
It prevents thrombi in patients with atrial failure or protethic heart values
What is Thrombolysis
It is used to treat thrombosis
Name the main drug involved in Thrombolysis
reptokinase and tissue-type plasminogen activator (TPA) which activate the body’s natural fibrinolytic system to break down thrombus, and minimise myocardial damage.
How can we treat thrombosis
Rivaroxaban/apixaban/betrixaban
Clopidogrel
What are Rivaroxaban/apixaban/betrixaban
They are oral anti coagulants used in place of warfarin to prevent lots Q
What do Rivaroxaban/apixaban/betrixaban target?
They target factor X in the clotting cascade
What is Clopidogrel?
It is an anti-platelet medication similar uses to aspirin.
What is Virchow’s Triad
3 factors predisposing to thrombosis
Name the 3 corners of Virchow’s Triad
- Changed in constituents of blood
- Changes in vessel wall
- Change int eh pattern of blood flow
How can blood constitutes change?
Coagulation potential can increase due to OCP and other drugs as well as pregnant
Who is at risk of increased coagulation potential
Women takin the pill (12 in 100,00)
What increases the risk of increased coagulation potential?
- Obesity
- Personal history
- sedentary lifestyle
- Increased age
- Smoking
What` can cause changes to vessel walls?
- Atheroma
- Trauma
- Inflammation
- Neoplasia
What can lead to changes to the pattern of blood flow?
Stasis or turbulent blood flow – due to narrowing (eg from atheroma)
What is an embolus?
It is an abnormal mass of material (solid or gas) which is carried in the blood stream from one part of the circulation to another
This impacts vessels whose calibre is too small to allow the embolus to pass
How can an emboli cause damage?
It can get loges anywhere in the vascular tree depending on the site od origin
Whta is a pulmonary embolism?
An embolus lodged in the pulmonary vessels
Where does the embolus in Pulmonary Thromboembolism originate?
Originates from a detached piece of thrombus sitting in a deep vein of the leg.
How and where does the embolus in Pulmonary Thromboembolism travel too?
Travels via venous system to the right heart, then out through pulmonary artery.
It Lodges in pulmonary arterial tree
Where does the embolus in Systemic Thromboembolism originate?
Originated from detached piece of mural thrombus or left heart valvular vegetation.
How and where does the embolus in systemic Thromboembolism travel too?
It travels via the aorta into the systemic arterial circulation
It can get lodged in arteries leading to lower limbs, brain, kidneys or gut
Where does the embolus in cerebral Thromboembolism originate?
originates from detached piece of thrombus in a common carotid artery
How and where does the embolus in cerebral Thromboembolism travel too?
Travels in the arterial system to the brain where it lodges somewhere in the cerebral vasculature
What can cerebral Thromboembolism cause?
Stroke
Where does the embolus in Lower Limb / Renal Thromboembolism originate?
Originated from detached piece of thrombus in abdominal aorta
How and where does the embolus in Lower Limb / Renal Thromboembolism travel too?
Lodges in rate renal arteries or arteries in the lower limbs
What is a paradoxical embolism?
An embolism that originates in systemic veins and enters systemic arterial circulation
Describe the route of a paradoxical embolism
due to presence of an inter-atrial or inter-ventricular defect, embolism passes from right heart to left heart, and out via the aorta to the systemic arterial circulation.
What is Ischaemia?
Impaired vascular perfusion of an area of tissue thus depriving it of viral nutrients especially oxygen
Where can Ischaemia occur?
- Coronary arteries leading to angina
- ileac, femoral & popliteal arteries (LEGS) lading to intermittent claudication
- mesenteric arteries (gut) leading ischaemic bowel
What is infarction?
Death (necrosis) of an area of issue due to ischaemia
Where can infarction occur?
- Heart
- BRAIN cerebrovascular accident causing a stroke
- Gut (bowel infarction)
What is Ischaemia and infarction frequently associated with ?
the development of atherosclerosis.
How can atherosclerosis lead to Ischaemia and infarction
If an atherosclerotic plaque ruptures, thrombus forms on the surface which can occlude blood flow.
Occasionally bits of thrombus can break off and occlude other blood vessels downstream (embolism).
what can Ischaemia and infarction be caused by?
- Atherosclerosis
- Thrombosis
- Embolism
- Obstruction of venous drainage
What is shock in a medical scenario
is a life-threateningmedicalcondition of low bloodperfusionto tissues resulting in cellular injury and inadequate tissue function
Name the 4 Amin types of shock
- Cardiogenic shock
- Obstructive
- Hypovolaemic shock
- Distributive shock
What can shock cause?
- Inadequate perfusion leading to cell hypoxia and energy deficiency
- Lactic acid production and fall in pH due to anaerobic metabolism
- Metabolic acidosis leading:
A. to Cell memb dysfunction and failure of Na pump
4. Intracellular lysosome release leading to Toxic substances enter circulation
5. These cause Capillary endothelium damaged
6 Destruction, dysfunction and cell death
B. Vasoconstriction causing Failure of pre-capillary sphincters
4. This leads to Peripheral pooling of blood
What are the signs and symptoms of cariogenic shock
- Distended jugular veins due to increased venous pressure
- Weak or absent pulse
- Arrhythmia
- Reduced blood pressure
What is cariogenic shock caused by?
Often caused by things which prevent the heart pumping effectively
What are the signs and symptoms of obstructive shock
- Cardiac Tamponade
- Pulmonary Embolism
- Aortic Stenosis
What is obstructive shock caused by?
Due to obstruction in blood flow outside the heart
What are the signs and symptoms of hypovolaemic shock
- Rapid, weak thready pulse
- Tachycardia
3 .Cool, clammy skin – vasoconstriction
4 .Hypothermia - Thirst and xerostomia
- Cold, mottled skin
What is hypovolaemic shock caused by?
Due to insufficient fluid circulation
Usually due to haemorrhage in adults, vomiting and diarrhoea in children.
Can also be caused by burns (fluid loss) and excess urine (diabetes mellitus and insipidus)
What does disruptive shock include
Infectious, anaphylaxis and neurogenic causes.
What can disruptive shock cause?
massive dilatation leading to hypotension
Which disease is linked with disruptive shock
Typically present with SIRS (Systemic Inflammatory Response Syndrome)
What does Anaphylaxis cause?
Causes mass vasodilation – hypotension and increased capillary permeability
What is the treatment fro a patient in medical shock?
- ABCDEs first
- Oxygen and bolus of fluids – normal saline is fine as first measure, then consider RBCs
- Meds – vasopressors if hypotension not improved with fluids
What is the prognosis of a paint suffering from medical shock
Prognosis is poor – mortality 70-90% with cardiogenic, 30-50% with septic shock