Atherosclerosis (atheroma, Thrombosis & Embolism, Myocardial Infarction, Ischaemic Heart Disease & Angina, ACS & SCAD) Flashcards
What is an atheroma? Where does it form?
Atheroma = formation of focal elevated lesions (plaques)
Forms in the intima (innermost membrane) of large and medium-sized arteries
What are the consequences of arteromatous plaques in coronary arteries?
Plaques narrow the lumen —> ischaemia
Serious consequences:
- angina (chest pain due to reduced blood flow to heart muscles) due to myocardial ischaemia
- complications due to thromboembolism
What is the 2-step process of development of atheromatous plaque?
- Injury to endothelial lining of artery
2. Chronic inflammatory and healing response of vascular wall to agent causing injury
How does the endothelium get injured(2)? What are the consequences of this(3)?
Many causes including:
• Haemodynamic disturbances (turbulent flow)
• Hypercholesterolaemia (impairs endothelial function, lipoproteins can aggregate in intima and are modified by free radicals)
Consequences:
- accumulation of lipoproteins in vessel wall
- monocytes migrate into intima and transform into foamy macrophages
- platelets adhere
What are the 4 stages of atherogenesis?
Fatty streak:
- earliest significant lesion
- found in young children
- no clinical significance (may disappear)
Early atheromatous plaque:
- found in young adults and onwards
- smooth yellow patches in intima
Fully developed atheromatous plaque:
- central lipid core with fibrous tissue cap, covered by arterial endothelium
- inflammatory cells reside in fibrous cap
- highly thrombogenic (forms thrombus or clot when in contact with blood)
Complicated atheroma:
- haemorrhage into plaque (calcification)
- plaque rupture/fissuring
- thrombosis
Causes/risk factors of atheroma (6)
Hypercholesterolaemia is most important risk factor (causes plaque formation in absence of other known risk factors) Smoking Hypertension Diabetes mellitus Male Elderly
What are the signs of Hyperlipidaemia(3)?
Corneal Argus - deposit of cholesterol, phospholipds, triglycerides in arc on the iris
Tendon xanthomata - cholesterol deposits in tendons (often on knuckles and Achilles)
Xanthelasmata - yellow deposits of cholesterol underneath skin (usually on/around eyelids)
What are high grade plaque stenosis? What is stenoses atheromatous coronary artery? (What if its severe?)
Stenosis of 50-75% of vessel lumen —> critical reduction of blood flow in distal arterial bed —> reversible tissue ischaemia
E.g. stenoses atheromatous coronary artery = stable angina
Severe stenosis = unstable angina (ischaemic pain at rest)
What is acute atherothrombotic occlusion?
Ruptured plaque exposes thrombogenic plaque contents to blood stream —> coagulation cascade and thrombotic occlusion short time
What is a total atherothrombotic occlusion? With examples
Total occlusion —> irreversible ischaemia —> necrosis (infarction) of tissues
Examples:
- myocardial infarct (coronary artery) - stroke (carotid, cerebral artery) - lower limb gangrene (ileal, femoral, popliteal artery)
What is embolisation of the distal arterial bed?
Detachment of small thrombus fragments from thromboses atheromatous arteries —> embolise distal to ruptured plaque
Embolism occlusion of small vessels —> small infarcts in organs
(Common cause of stroke - cerebral infarct/TIA)
What is a ruptured atheromatous abdominal aneurysm?
Aneurysm - bulge in blood vessel
Media beneath atheromatous plaques gradually weakened —> gradual dilation of vessel
Vessel suddenly ruptures —> massive retroperitoneal haemorrhage (high mortality)
What are primary prevention measures for atheromatous plaques (5)?
Stop smoking Control blood pressure Weight loss Regular exercise Dietary modification
What are secondary prevention measures for atheromatous plaques?
Cholesterol lowering drugs (inhibits platelet aggregation to decrease risk of thrombosis on established atheromatous plaques)
What defects can occur in blood flow (2)?
Stasis - stagnation of flow
Turbulence - forceful, unpredictable flow
What is Virchow’s triad?
- Changes in blood vessel wall - e.g. atheromatous of coronary artery
- Changes in blood constituents - e.g. hyperviscosity
- Changes in pattern of blood flow - e.g. stasis (post-operatively), turbulence (atheromatous plaque)
What is a thrombosis
formation of a solid mass from the constituents of blood within the vascular system during life
What are common clinical scenarios of thrombosis (3)?
Deep vein thrombosis - blood clot developing in deep vein in body (usually leg)
Ischaemic limb - sudden decrease in limb perfusion that threatens viability of limb
Myocardial infarction
What are the 2 types of embolus?
Systemic thromboembolus
- travel to wide variety of sites: often lower limbs, brain - consequences dependent on: vulnerability of affected vessel to ischaemia, calibre of occluded vessel
Venous thromboembolus
- originate from deep venous thromboses - travel to pulmonary arterial circulation - consequences dependent on size of embolus - multiple over time —> pulmonary hypertension & right ventricular failure
Risk factors for DVT and pulmonary thromboembolism (7)
Cardiac failure Severe trauma/burns Post-op/post-partum (time after baby birth) Nephrotic syndrome Old age Oral contraceptive Bed rest/immobile
What are the types of embolus (9)
Fat (after major fractures)
Gas (decompression sickness - N bubbles lodge in capillaries)
Air (head and neck wounds, surgery, central venous catheter)
Tumour (spread of tumour)
Septic material (infective endocarditis)
Amniotic fluid (cause of collapse in childbirth)
Bone marrow (fractures - CPR)
Foreign bodies (sutures)
What is ischaemia?
Relative lack of blood supply to tissue/organ leading to inadequate O2 supply to meet needs of tissue/organ
4 types of hypoxia
- Hypoxic - low inspired O2 level/normal inspired O2 but low PaO2
- Anaemic - normal inspired O2 but abnormal blood
- Stagnant - normal inspired O2 but abnormal delivery (occlusion of vessel)
- Cytotoxic - normal inspired O2 but abnormal at tissue level
What are the supply (5) and demand (2) causes of ischaemic heart disease?
Supply: Coronary artery atheroma Cardiac failure (flow) Pulmonary function (e.g. pulmonary oedema) Anaemia Previous MI Demand: Heart has high intrinsic demand Exertion/stress
Clinically correlate atheromatous stages to conditions
Established atheroma in coronary artery = stable angina
Complicated atheroma in coronary artery = unstable angina
Complicated ruptured plaque —> thrombosis —> ischaemia/infarction
Atheroma in aorta —> aneurysm
Functional effects of ischaemia
Blood/O2 supply fails to meet demand due to insufficient supply or too high a demand (or both)
Effects of acute and chronic ischaemia
Acute - sudden decrease in limb perfusion that threatens viability of limb
Chronic - peripheral arterial disease resulting in reduced blood flow to limbs (commonly lower)
Biochemical and cellular effects of ischaemia
Insufficient O2 to meet demand therefore aerobic metabolism —> anaerobic metabolism —> cell death
Different tissues have variable O2 requirements and are variably susceptible to ischaemia - dependent on metabolic rate
What is a myocardial infarction?
Coronary arterial obstruction —> decreased blood flow to region of myocardium —> ischaemia + rapid myocardial dysfunction —> myocyte death
What is the time scale of myocardial ischaemia
Seconds = anaerobic metabolism & onset of ATP depletion
<2minutes = loss of myocardial contractility (—> heart failure)
Few minutes = ultrastructural changes (myofibrillar relaxation, cell and mitochondrial swelling) potentially reversible
20-30minutes = severe ischaemia —> irreversible damage
20-40minutes = myocyte necrosis
1hour = injury to microvasculature
How is a myocardial infarction diagnosed?
Detection of cardiac cell death = positive cardiac biomarkers (troponin levels increase significantly- STEMI, not so much NSTEMI)
AND one of:
- Symptoms of ischaemia
- New ECG changes
- Evidence of coronary problem on coronary angiogram or autopsy
- Evidence of new cardiac damage on another test
What are non-coronary causes of troponin rise?
Arrhythmia Pulmonary embolism Cardiac contusion Sepsis Anaemia
(Elevated troponin levels on own just indicate some degree of myocardial cell injury)
What does the ECG tell you about myocardial infarction? What does this indicate?
If there is ST elevation (STEMI) in ECG there will be complete coronary occlusion
If there is ST depression, T wave inversion or normal there may be a partial coronary occlusion
Modifiable and non-modifiable risk factors of stable angina
Modifiable:
Smoking
Lifestyle - exercise and diet
Diabetes mellitus (glycemic control reduces CV risk)
Hypertension (BP control reduces CV risk)
Hyperlipidaemia (lowering reduces CV risk)
Non-modifiable: Age Gender Family history Genetic factors
What is angina
a discomfort in the chest and/or adjacent areas associated with myocardial ischaemia but without myocardial necrosis
What is the pathophysiology of stable angina
Mismatch between supply of O2 and metabolites to myocardium and myocardial demand for them
Commonly due to reduction in coronary artery blood flow to the myocardium (most common cause is coronary atheroma)
What presenting features make angina likely?
Site of pain (retrosternal)
Character of pain (tight band/pressure/heaviness)
Radiation sites (neck/jaw/down arms)
Aggravating (exertion/emotional stress)
Relieving factors (rapid improvement with glycerol trinitrate)
What presenting features make angina unlikely?
Sharp/stabbing pain (more likely pleuritic or pericardial)
Associated with body movements or respiration
Very localised
Superficial with/or without tenderness
No pattern to pain (particularly if often occurring at rest)
Begins some time after exercise
Lasts hours
What are the 4 degrees of stable angina activity?
- ordinary physical activity doesn’t cause angina – symptoms only on significant exertion
- slight limitation of ordinary activity – symptoms on walking > 1 flight of stairs or 2 blocks
- marked limitation – symptoms on walking only 1-2 blocks or 1 flight of stairs
- symptoms on any activity – getting washed/dressed causes symptoms
What are the types of myocardial infarcts (3)?
Transmural infarction
Subendocardial infarction
Acute infarcts
What is a transmural infarction
Ischaemic necrosis affecting full thickness of myocardium
What is a subendocardial infarction
Ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart
What is an acute infarct?
Acute infarcts classified according to whether there is elevation of the ST segment on the ECG
What are some complications of myocardial infarction (8)?
Sudden death Angina Arrhythmias Cardiac failure Cardiac rupture (ventricular wall, septum, papillary muscle) Reinfarction Pericarditis Pulmonary embolism
Name 2 acute coronary syndromes
Myocardial infarction
Unstable angina pectoris
Name 2 stable coronary artery diseases
Angina pectoris
Silent ischaemia
What is stable coronary artery disease?
Arises due to mismatch in myocardial blood/oxygen supply and demand
Attacks of angina may be precipitated by anything which increases heart rate, stroke volume or blood pressure
What is demand ischaemia? What are determinants of demand ischaemia (4)?
Ischaemia during stress (physical/emotional)
Determinants of demand ischaemia: Heart rate Systolic blood pressure Myocardial wall stress Myocardial contractility
What is supply ischaemia? What are determinants of supply ischaemia (4)?
Ischaemia at rest
Determinants of supply: Coronary artery diameter and tone Collateral blood flow Perfusion pressure Heart rate (duration of diastole)
What are acute coronary syndromes?
Collection of symptoms related to a problem with coronary arteries
