Cardiovascular Disease I (CVD I) Flashcards
What are the definitions of arteriosclerosis, atherosclerosis and atheroma (fibro-fatty plaques)?
Arteriosclerosis - ‘Hardening of the arteries’ – a generic term for the thickening and loss of elasticity of arterial walls
Multiple causes (including atheroma, age-related sclerosis and calcification).
Atherosclerosis - a specific form of arteriosclerosis (athere = porridge-like; sclerosis = hardness) due to atheroma
Worldwide, may contribute to up to 50% of all deaths
Atheroma (fibro-fatty plaques) - Athere – ‘porridge-like’; oma – ‘tumour’ - refers to plaques found particularly in elastic and medium-to-large muscular arteries.
These can protrude into and variably-obstruct the lumen and also weaken the underlying media
What are the risk factors for atheroma?
- Increasing age
- Sex hormone influences (M>F but this equalises by 8th decade)
- Genetics (‘Family History’ – probably polygenic)
- Hyperlipidaemia (esp. LDL-cholesterol)
- Hypertension (both systolic and diastolic levels are important)
- Cigarette smoking
- Diabetes mellitus
Outline the pathogenesis of atheroma formation.
- Chronic or repetitive endothelial injury / dysfunction - leads to increase permeability, leukocyte adhesion and thrombotic potential
- Accumulation of intimal lipid - phagocytosed by macrophages to form foam cells
- Smooth muscle cell migration to, and proliferation, in the intima - accompanied by changes in the ECM (accumulation of collagen and proteoglycan)
- Fibrosis forming a fibro-lipid plaque - inflammatory reaction including macrophages, lymphocytes, endothelial cells and smooth muslce cells
- Plaque injury – thrombosis and haemorrhage - stable plaque can become unstable - resulting in MI
Outline how a plaque can develop/evolve?
- Early plaque – confined to the intima – bulges out a little
- Advanced plaque – thin fibrous cap, dips out into the media - associated with weakening of the endothelial wall
- Complicated plaque – plaque that is likely to rupture driving thrombus formation
Which arteries are normally effected by atheroma formation?
Elastic and medium-to-large muscular arteries:
1. Abdominal aorta
2. Coronary arteries
3. Popliteal arteries
4. Descending thoracic aorta
5. Internal carotid arteries
6. Vessels of the circle of Willis
What are these images showing?
What are the complications associated with atheromas?
- Calcification of the plaque - hardening of the arteries
- Ulceration and plaque rupture - expose highly thrombogenic material and discharge micro-embolic debris (cholesterol emboli)
- Haemorrhage - rupture leading to a bleed into the plaque - expand the plaque/lead to further rupture
- Super-imposed thrombosis - fully/partially occlude the lumen
- Aneurysmal dilatation - dilation of the vessel - typical in abdominal aortic aneurysms
All of these can contribute to the vessel obstruction and downstream ischaemia
Note - exact effects will depend on the artery effected
- Intermittent claudication – cramping in the lower leg due to insufficient blood supply
- Gangrene - tissue death due to a lack of blood supply
What are the complications associated with atheromatous abdominal aortic aneurysms?
Sequelae:
1. Formation of an abdominal mass (pulsatile)
2. Impingement on adjacent structures eg ureter
3. Embolisation (atheroma or mural thrombus)
4. Vessel ostia obstruction - vessel openings
5. Rupture into the peritoneal cavity or retro- peritoneum with potentially massive (fatal) haemorrhage
What are the definitions of thrombus, thrombosis and haematoma?
- A thrombus is a solidification of blood constituents that forms within the vascular system during life
- Thrombosis is a pathological process - denotes the formation of thrombus within the uninterrupted vascular system
- Haematoma (blood clot) - Solidification of blood constituents outside the vascular system or after death
Key difference - intra vs. extra-vascular
What are the three drivers of thrombosis?
Virchow’s Triad – all work together (at different levels) to lead to thrombosis
Usually one of the three dominates – usually all three contribute though – some instances this is not the case
How does endothelial injury contribute to thrombus formation? What are some common causes?
Endothelial integrity is the single most important factor especially in high-flow arterial scenarios - driver clot formation
Note - but the endothelium need not necessarily be physically disrupted to contribute to thrombosis; any perturbation in the dynamic balance of pro- and anti- thrombotic effects of endothelium can influence local clotting
How does abnormal blood flow contribute to thrombus formation?
Abnormal blood flow
1. Disrupts laminar flow (may be more likely for platelets to contact endothelium)
2. Prevents the dilution of clotting factors
3. Retards the inflow of inhibitors of clotting factors
4. Causes endothelial injury - promoting endothelial cell activation
You can have…
1. Turbulence - contributes to the development of arterial and cardiac thrombi
2. Stasis - Important in the formation of venous thrombi
How does hypercoagulability contribute to thrombus formation?
Refers to an alteration of the blood coagulation mechanism (particularly platelets and the clotting cascade) that in some way predisposes to thrombosis
May be….
1. Genetic - e.g. Mutations in factor V or prothrombin, Leiden mutaiton - resistant to protein C cleavage, etc.
2. Acquired - immobility, post-trauma or surgery, stasis and vascular injury
How do arterial and venous thrombi appear morphologically?
Arterial thrombi
- Usually occlusive
- May be mural - attached to the wall of blood vessel or cardiac chamber
- Occur anywhere but more frequent in:
a) Coronary
b) Carotid
c) Cerebral
d) Femoral
Venous thrombosis
- Also termed phlebothrombosis
- Not to be confused with thrombophlebitis
- Occurs typically in pelvic and leg veins in association with stasis
How do thrombi appear under the microscope?
What are the complications of arterial thrombosis?
Arterial occlusion
1. Loss of pulses distal to the thrombus
2. Area becomes cold, pale, painful
3. Eventually tissue dies and gangrene results
How do superficial and deep venous thrombosis differ?
Superficial (saphenous system)
- Congestion, swelling, pain, tenderness (rarely embolise - move)
Deep
- Foot and ankle oedema
- May be asymptomatic and recognised only when they have embolised (eg via IVC and right side of heart to the lung)
Can thrombosis occur both in th venous and arterial systems?
Yes both possible - can lead to occlusion of artery or veins
Embolism
Arterial – away from the heart (distal)
Venous – towards the heart (proximal)
What is the definition of an embolism?
An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin
99% of all emboli arise from thrombi (thromboembolism)
Unless otherwise qualified, the term embolus implies thromboembolism
What are examples of rare/less common forms of emboli?
Less common / rare forms of emboli include fragments of:
1. Bone or bone marrow
2. Atheromatous debris
3. Droplets of fat
4. Tumour cells
5. Foreign bodies (such as bullets)
6. Bubbles of air or nitrogen
What are five different types of embolism?
- Pulmonary embolism
- Systemic embolism
- Amniotic fluid embolism
- Air embolism
- Fat embolism
What is a pulmonary embolism? Where do the emboli normally come from?
Refers to an embolism, usually thrombo-embolism, that travels to the pulmonary arteries
Occlusion of a large or medium-sized pulmonary artery is almost always embolic in origin until proved otherwise
Most (95%) of pulmonary emboli arise in thrombi within the large deep veins of the lower leg - next most common pelvic veins
What effect does an emboli in the main pulmonary artery or a saddle embolus have?
Emboli lodged in the main pulmonary artery or at the birfurcation point - associated with instance collapse and sudden death
Their effect is to cause circulatory obstruction
Saddle embolus shown in the picture
What effect can medium and smaller emboli have?
Smaller emboli can travel out into the more peripheral pulmonary arteries
- If these are of intermediate size they may cause pulmonary infarction - deprive downstream tissues (particularly the case in patients with cardiac failure - normally bronchial artery supply can often sustain the lung parenchyma)
- If very small and recurrent, they may lead to pulmonary hypertension
In the presence of an inter-atrial or inter-ventricular defect (cross over) they may gain access to the systemic circulation - paradoxical embolism
List the complications associated with large, medium and small-sized pulmonary emboli.
What are systemic emboli? What are the common causes?
Systemic emboli - refers to emboli that travel through the systemic arterial circulation
- 80-85% arise from thrombi within the heart
- Less common sources include thrombi developing in relation to:
1. Ulcerated atherosclerotic plaques
2. Aortic aneurysms
3. Infective endocarditis
4. Artificial heart valves and aortic grafts
What is the main consequence of arterial emboli? What are the major sites where they lodge?
Arterial emboli almost always cause infarction
Major sites for systemic emboli to lodge are:
1Lower extremities (commonest)
2. The brain
3. Viscera (mesenteric, renal, splenic arteries)
4. Upper limbs (much less common)
What is the definition of an infarct?
Infarct (Latin: infarcire = to stuff) - area of ischaemic necrosis (lack of oxygen driving tissue/cell death) caused by occlusion of arterial supply or venous drainage in a particular tissue
What is the definition of an necrosis?
Necrosis - Refers to a spectrum of morphological changes that follow cell death in living tissue, largely resulting from the progressive action of enzymes on the lethally injured cells
What are the causes of infarction?
Thrombosis and thromboembolism account for the vast majority
Other causes include:
1. Vasospasm
2. Expansion of atheroma
3. Compression of a vessel
4. Twisting of the vessels through torsion (eg testis or bowel)
5. Traumatic rupture
What factors influence the development of an infarct?
- Nature of the vascular supply - Single (e.g. spleen) or dual (e.g. lung, small bowel)
- Rate of development of occlusion - Rapid occlusion more likely to cause infarction
- Vulnerability of affected tissue to hypoxia - More metabolically active tissues more vulnerable e.g. heart
- Oxygen content of blood - Hypoxia increases risk
What does the histopathology of an infarction look like?
- Ischaemic coagulative necrosis (minutes - days) - Liquefactive necrosis in the central nervous system
- Inflammatory response (hours - 7 days)
- Reparative response (1 - 2 weeks)
- Scarring (2 weeks - 2 months)
Can a lack of venous drainage cause an infarction?
Yes, lack of venous drainage – pressure rises – eventually arterial supply can’t get in as the pressure is too high
What are three requirements that are required for the coagulation cascade?
Require phospholipid surface, calcium present and optimal temperature
Note - coagulation cascade is driven by large enzyme macro-molecular complexes
1. Extrinsic tenase
2. Intrinsic Tenase
3. Prothrombinase
What is the haemostatic balance?
Physiological balance between bleeding and clotting – repair small little damages (occurs constantly) and bleeding
Can’t have too little or too much clotting - finely tuned system
What is the epidemiology of Venous Thromboembolism (VTE)?
Common – incidence 1 per 1000
May present as as sudden death - pulmonary embolism
30% of patients develop recurrent venous thrombosis after a primary incidence of VTE
28% develop post thrombotic syndrome – longer term consequences not only acute (death)
Mortality of promptly diagnosed and adequately
treated pulmonary embolism (PE) is 2%
A major international health problem - 5x the number of deaths compared to the number of ALL hospital acquired infections
What are the risk factors of venous thromboembolism?
- Age – increased risk with age
- Obesity – 2-3 fold increase in obese patients
- Varicose veins
- Previous VTE
- Family history of VTE
- Thrombophilia – heritable factors for thrombosis
- Cancer – ovarian and lung cancers
- Other thrombotic states - Heart failure, infarction, stroke, etc.
- Hormone therapy
- Pregnancy
- Immobility – travel, hospitalization, etc.
Is venous thromboembolism frequently unrecognised?
Yes - 80% of DVT are clinically silent - mainly times they are only found when people present with a PE
What are the different types of venous thrombosis?
- Deep venous thrombosis (DVT)
- Pulmonary embolus (PE)
- Cerebral, mesenteric, axillary, splanchnic, splenic
Any vein can get a thrombosis – however, the distribution/incidence varies – e.g. rare in renal veins or upper limb
What are the clinical features of lower limb DVT?
How do clinicians predict the liklihood that a patient has a DVT?
Well’s pre-test probability (clinical likelihood) of DVT
Well’s Scores - Stratifies patients into low-, intermediate- or high-probability categories
Online survey
What types of clinical investigations are used to investigate potential DVT?
- Use of D-dimer (breakdown product of fibrinogen/fibrin) as a negative predictor of venous thromboembolism - indicates that there are elevated levels of clot formation
If D-dimer is negative it strongly indicates that there is no DVT but a positive D-dimer is indicative but not absolute - used to rule out DVT
- Venous ultrasonography – gold standard
- Higher sensitivity and specificity for proximal DVTs - less sensitive for leg/calf DVTS - Contrast venography - Very rarely performed
What are the clinical features of a pulmonary embolism?
What investigations are performed to diagnose a pulmonary embolism?
- X-ray is used to exclude other diagnoses – doesn’t diagnose PE directly
- Main types of imaging
a) V/Q scan
b) CT-pulmonary angiogram (gold standard) - Heart strain suspected – Echocardiogram
What is the principle behind the venous thromboembolism (VTE) treatment?
-
Rapid initial anticoagulation
a) parenteral anticoagulant: heparin, low molecular weight heparin, fondaparinux,
OR
b) direct oral anticoagulant (DOAC)
Aim: to reduce the risk of thrombus extension and fatal pulmonary embolism - stop thrombus expanding and spread (does not dissolve clot) -
Extended therapy
a) Orally active anticoagulant : vitamin K antagonist
OR
b) Direct oral anticoagulant
Aim: to prevent recurrent thrombosis and chronic complications such as post-phlebitic syndrome - treat with an active anticoagulant – prevent recurrent thrombosis and chronic complications
Normally use Low MW heparin or direct oral anticoagulant
What clotting factors are typically targetted by drugs?
Many different targets but factor Xa is the main target more many drugs
Compare and constrast the use of UFH and LMWH in VTE treatment.
UFH - used when there is a high risk of bleeding - can be reversed
Note - LMWH due to the reduction in chain length there is reduced capacity to inhibit thrombin compared with UFH.
UFH - short half life + can be reversed using protamine
What mechanical methods are available to prevent venous thrombosis?
Mechanical:
1. Mechanical foot pumps
2. Graduated compression stockings - TED stocking – properly applied – aid the venous return to the heart
Summary of the treatments used to treat venous thrombosis?
Outline the impacts that hypertension has on the heart?
- Left ventricular hypertrophy - increase mass predicts excess cardiac mortality, predisposes people to chronic heart failure and is associated with sudden death (arrythmias)
- Fibrosis - increased scarring
- Contribute to the patogenesis of coronary artery atheroma and ischaemic heart disease
Outline the impacts that hypertension has on the kidney?
- Cause nephrosclerosis (loss of nephrons)
- Hypertension causes hardening of arteries (hyaline arteriosclerosis) which in turn drives loss of nephrons - downstream ischaemia
- Proteinuria - loss of proteins
- Chronic renal failure - Rapid rises in blood pressure can be associated with acute renal failure (‘malignant’ hypertension)
What are three drivers/causes of cornary artery disease?
- Atheroma-related coronary artery disease (by far the most common) - atherosclerosis - results in…
- Progressive stenosis
- Haemorrhage into a plaque
- Thrombosis
- These may cause ‘acute coronary syndromes’ (angina, acute MI and sudden death) - Emboli e.g. from inflamed aortic valve (endocarditis) - emboli can also arise (i.e. from aortic valve) and lodge into coronary artery
- Vasculitis - auto-immune disorders
What are some complications associated with acute MI?
- Sudden death
- Dysrhythmias
- Persistent pain - necrosis
- Angina
- Cardiac failure - ventricular dysfunction/dysrhythmias
- Mitral incompetence - papillary muscles dysfunction/necrosis
- Pericarditis
- Cardiac rupture - weakend wall by necrosis
- Mural thrombosis - abnormal endothelial surface
- Ventricular aneurysm - stretching of newly formed scar tissue
What are the three general causes of heart failure?
Pressure overload
Hypertension (pulmonary or systemic) - leads to hypertophy - impairs normal heart function
Valve disease e.g. aortic stenosis
Volume overload
Valve disease e.g. aortic incompetence
Intrinsic cardiac disease
Ischaemic heart disease
Primary heart muscle disease
Myocarditis
Pericardial disease
Conducting system disorders
Note - actual heart failure may be a combination
How does left and right ventricular failure normally present?
What do the Q, R and S wave in the QRS complex represent? What does the PR interval represent?
Q wave – activation of the intra-ventricular septum – from left to right
R wave – Depolarization from the base to the apex of the heart
S – wave – activation going up the walls of the left and right ventricles
PR interval – length of time between sinus node firing and AV node firing – something wrong with AV node – results in increase PR interval
What is a respiratory sinus arrythmia?
Sinus arrythmia - Sinus node fires at a variable rate
Normal physiological change – during inspiration there is an increase in volume of thorax as well as the heart – resulting in decrease pressure – resulting in more blood being drawn in - autonomic nervous system responds by increasing heart rate
Hence, this results in fluctuations between inspiration and expirations
a) Speeds up during inspiration
b) Slow down during expiration
This effect is mediated by changes in parasympathetic activity (vagus nerve)
What is sinus tachycardia? What are the physiological and pathological causes?
Sinus node fires > 100 per minute
Physiological causes:
anxiety, exercise
Pathological causes:
fever, anemia, hyperthyroidism, heart failure
shock (sepsis, bleeding, anaphylaxis)
almost any acute medical emergency
What is sino-atrial disease? What is is physiologically characterised by? What types of ECGs can it produces?
A degenerative condition affecting the atria, including the sinoatrial (SA) and atrioventricular (AV) nodes
Characterised by patchy atrial fibrosis, atrial dilatation and altered conduction
Common in individuals age > 70 years
What is 1st degree AV nodal block?
Consistent delay in PR interval (more than 1 large square) – 1st degree AV nodal block – usually symptomless
What are the two types of second degree AV nodal block?
Grade 2 AV nodal block
Mobitz type 1 – increasing PR interval leading to a skipped beat – due to disease of AV node
Mobitz type 2 – normal rhythm followed by sudden QRS drop (can be multiple) – indicates bundle of his bundle block – more serious – long pauses and blackouts
What is grade three AV nodal block?
Grade 3 AV nodal block/Complete heart block
Complete dissociation between atrial and ventricular rhythm (different rhythms)
P wave appears randomly (can be superimposed)
QRS complexes – broad and abnormal – indicating that the ventricles are activating spontaneously
What are the causes of AV-nodal block?
Anything that damages and inteferes with the AV node.
What does the following ECG show?
Atrial fibrillation
Irregular and rapid atrial activity with normal/narrow QRS complexes
What does the following ECG show?
Atrial flutter
Saw-tooth pattern – regular and rapid activity
Normal/narrow QRS complexes
What are the causes of atrial fibrillation and flutter?
Both atrial flutter and fibrillation cause similar symptoms
What are the treatments for atrial fibrillation/flutter?
What does the following ECG show?
Ventricular tachycardia – broad QRS, absence of P waves, abnormal axis for QRS, fast heart rate – common in patients with a previous MI/scarring in the heart
Note ST segment is elevated but in a broad QRS we can’t interpret the ST segment
What does the following ECG show?
Ventricular fibrillation
No organized P waves and no organized QRS complexes – cardiac arrest
What are the treatments for ventricular fibrillation?
