Unit 3: Patho & Treatment - Acute Coronary Syndrome Flashcards
What do coronary heart disease, hypertension, heart failure, diabetes and peripheral arterial disease all have in common?
All of these pathologies have:
A tendency to co-exist in the same individual
To be associated with shared risk factors
Are associated with atherosclerosis
What are the 3 layers of a normal blood vessel?
Intima
Media/tunica media
Adventitia/tunica externa
What is the function of each layer?
Intima - inner layer, composed of a single layer of endothelial cells resting on a connective tissue basement layer. This endothelium is a physical barrier between the internal vessel wall structure and the circulating blood. Endothelium has 2 important functions:
- Secrete vasoactive substances – nitric oxide and prostacyclin which both produce vasodilation and endothelin which promotes vasoconstriction.
- Secrete anticoagulants including prostacyclin which physically repels platelet cells and prevents them from attaching to the endothelial wall.
Media/tunica media - thickest layer of the arterial wall. Lies between the intima and the adventitia. Is composed mainly of smooth muscle cells (SMCs) within a matrix of collagen, proteoglycans & elastin fibres.
Adventitia/tunica externa - the external wrapping of the arterial wall structure and has protective functions. It is largely made of densely packed collagen fibres
Define atherosclerosis
A combination of changes in the intima consisting of the accumulation of lipids, other blood constituents and fibrous tissue, accompanied by changes in the media of the vessel
Is the most common underlying cause of all cardiovascular disease (stroke, peripheral vascular disease (PVD))
What 2 conditions must be present in order for the formation of plaque to occur in a blood vessel?
a. High levels of circulating Low Density Lipoproteins (LDLs) – which are composed of 50% cholesterol which can equate to 2-3 thousand cholesterol molecules per LDL molecule.
b. Damage/irritation to the endothelium due to;
1. high levels of frictional or shearing forces (most usually secondary to high BP),
2, high levels of blood glucose or insulin (as in diabetes),
3. micro-organisms (e.g. a secondary consequence of systemic viral or bacterial illness which may even have been quite minor i.e tooth caries or sore throats)
4. inflammatory mediators (as is seen in obesity, diabetes & auto-immune conditions e.g. RA),
5. toxins & irritants (commonly including bacterial toxins, & nicotine - smoking)
Outline how an atheroma forms in damaged blood vessels.
Damaged endothelial cells release cell adhesion molecules which attract monocytes and platelets to the area which bind to the affected endothelium and cross the arterial wall to enter the intima. As monocytes leave the blood system to enter the tissues they change and become marcophages and release Free radicals or reactive oxygen species (ROS).
LDLs also enter into the sub-intimal wall structure. The lipid / cholesterol carried by the LDLs then become oxidized by ROS.
Macrophages ingest the oxidised LDLs and become bloated causing the macrophages to alter their structure & function & become foam cells. The process of engulfing LDLs is associated with the release of more ROS which attracts more monocytes (which then change to macrophages / foam cells) and LDLs to the site in a positive feedback loop of recruitment. The collection of foam cells and LDLs increases over time. The platelet cells and the foam cells in the intima both release a number of chemical substances including growth factors.
Growth factors diffuse across the internal elastic laminae to affect smooth muscle cells (SMCs) in the tunica media. Some of these SMCs cross into the intima via the gaps. Once in the intima SMCs proliferate and collagen and elastin fibres are also secreted. A localised mass begins to form within the wall structure – the plaque/ atheroma
Over time LDLs continue to accumulate and the plaque enlarges and forms a mature plaque. A fibrous cap forms over the plaque protecting it from the stress of passing blood flow
How does the atheroma affect blood flow in the blood vessel?
It obstructs blood flow and causes turbulence in the blood flow
How does ageing degenerate the atheroma?
- Fibrous cap covering the plaque starts to fissure as a prelude to plaque rupture. When a plaque ruptures contact occurs between the collagenous material within the plaque and the platelets within the vessels blood flow.
- A haemostatic response is immediately triggered (haemostasis) - blood clot forms at the site of rupture. Hence a thrombus now forms right on top of the ruptured plaque.
- The thrombus can cause total or near-total vessel occlusion, compromising the viability of the tissues which rely on that blood supply.
What would indicate that a person may be at their ischaemic threshold? Define ischaemic threshold
The point at which blood flow and demand become uncoupled in this way is known as the ischaemic threshold.
When a person becomes symptomatic it may indicate they are at their ischaemic threshold;
1. The atheroma grows large enough to seriously occlude a vessel lumen lowering the ischaemic threshold so that it impacts on their normal activities
- When the individual steps up their activity levels and the tissues supplied by the affected artery increase their demand for blood flow (O2), which the compromised vessels cannot meet
What is the function of the coronary arteries?
How many coronary arteries exist?
They supply nutrients and oxygen to the cardiac muscle fibres through its own blood supply called the coronary circulation
2 - left and right (supplying RV wall, SAN, AVN, Bundle of His) coronary arteries which arise from the root of the aorta
What are the different types or angina?
Stable angina/angina pectoris (SAP)/classic angina i.e. the atheroma is stable (it is not rupturing - may become unstable angina if atheroma becomes vulnerable)
Variant angina
Silent angina
Unstable stable (part of the acute coronary syndrome and heart attacks)
Define angina
A pain/discomfort in the chest/adjacent areas due to a transient inadequate myocardial perfusion leading to hypoxia for a short time
Blood flow is obstructed by an atheroma, damage to the endothelium leads to a loss of nitric oxide (which contribute to vasodilation)
It is causes the ischaemic threshold to be reached. This relies on the size of the atheroma, the degree of physical activity undertaken and the aerobic fitness of the individual (skeletal muscle)
What type of pain is associated with angina?
Referred pain
Myocardium becomes hypoxic and it releases chemical mediators - adenosine, bradykinins which stimulate SNS afferents and produce APs along symapthetic afferents to thoracic spine which synapse with ascending tracts and with afferents coming from somatic sensory system. This blurs information & brain cannot distinguish if the pain is coming form visceral organs like the heart or if its coming from the somatic system
What are the 4 clinical markers of stable angina?
- location of pain
- neck (especially left), lower jaw, may radiate into both arms&shoulders & fingers (left), behind sternum, over both sides of chest (left) - Character of pain
- intense, heavy weight, “discomfort”, squeezing feeling/pressing/tight band, often indistinguishable from heart attack - Relationship of pain to stress
- occurs with stress - physical/emotional i.e. emotion, eating, exercise, extreme cold
- is diagnosed by ECG - Duration of pain
- < 5mins
- rarely > 5-10 mins
Name the associated symptoms of angina
Anxiety
SNS/PSN response - faintness & nausea or tachycardia & diaphoresis (abnormal sweating)
Women are more likely to get associated symptoms than classic symptoms of angina
What part of the ECG does angina affect?
S-T segment - quiet point between ventricular depolarisation and repolarisation
Various forms of ST-segment depression:
(a) horizontal
(b) a down-sloping ST segment
(c) up-sloping
Horizontal and down-sloping indicate ischaemia. Up-sloping is a poor indicator of ischaemia
A descent of >1millimetre is indicative of myocardial ischaemia (a mismatch between supply and myocardial demand)
How is stable angina diagnosed?
- A blood test which is looking for negative cardiac enzymes as these enzymes indicate myocardial fibre death which occurs in myocardial infarction (heart attack) not SAP
- Exercise tolerance test (ETT) (modified Bruce protocol) (on a bike with 12 leads of ECG - it looks at what point the patient hits ischaemic threshold- a diagnostic test for stable angina
- Angiogram - dye is inserted into coronary arteries to investigate where is atheromas are in the coronary artery
How would you manage stable angina pectoris (SAP)?
What are the goals for the treatment of SAP?
- General management
- physical activity + cardiac rehabilitation, lifestyle/behavioural modification - Pharmacology
- Surgical - percutaneous coronary intervention (PCCI) i.e. balloon angioplasty +/- DES (drug eluting stent) - used for a discrete atheroma. Or coronary artery by-pass grafting (CABG) for multiple atheromas
Goals:
- Symptomatic relief
- Reduce frequency of angina episodes
- Slow disease progression to reduce the risk of cardiovascular disease (CVD) events such as acute myocardial infarction (AMI)
Describe the 6 different types of anti-ischaemic drugs used to treat angina
- ST Nitrates - GTN
- provides immediate symptomatic relief
- increases;
rapid VD of coronary arteries (increases myocardial perfusion)
systemic venodilation (VD) (decreases pre-load) - veins act as storage vessels rather than vessels that return blood to the heart
arterial VD (decreases after-load) - Longer acting nitrates
- reduce incidence of anginal episode
- cause vasodilation of coronary arteries - Beta blockers (-olol)
- block sympathetic receptors on heart i.e. pacemaker cells in the intrinsic conducting system, cell membrane of ventricular muscle fibres. This causes max and resting HR to decrease and limits SV
30bpm (beats per minute) need to be taken off the patients age to account for the beta blocker in order to calculate HRmax: HRmax = 220 - age - beta blocker. Beta blockers artificially lower HR by 20-40bpm. Its very important that the patient understands and uses the Borg RPE scale - Ca2+ antagonists (-pine)
- decrease Ca2+ influx, CICR and SV (reduces metabolic demand/blood needed from the coronary arteries)
- blocking Ca2+ causes vasodilation, increases blood flow through coronary arteries
- blocking Ca2+ channels in systemic arteries& veins limits vasoconstriction (produces vasodilation -> reduces TPR -> reduces afterload),
blocking Ca2+ on veins reduces venous return and preload - Anti-platelet therapy
- decrease platelets sticking to endothelial and sticking to each other (tenacity) - Anti-atheroma
- statins
- lower LDLs
Name a beta blocker drug
- olol
Bisoprolol
Name a Ca2+ channel blocker
- pine
Felodipine
Name an LDL reducer drug
-statin
Atorvastatin
