Atherosclerosis Flashcards
Atherogenesis definition
The process of forming atheromas/ atheromatous plaques
Components of atheromatous plaques
Central lipid core (w/ rim of foamy macrophages),
Fibrous tissue cap,
Covered by arterial endothelium
Main aetiological factor for atheroma
Hyperlipidaemia.
High levels of lipoproteins (especially LDL) irritate the arterial endothelium leading to injury.
Signs of major hyperlipidaemia
Premature corneal archus - white ring around iris
Tendon xanthomata - mobile nodules in knuckles/ Achilles
Xanthelasmata - yellowish deposits of cholesterol under the skin
Role of atheroma in coronary heart disease
Atheroma in coronary artery:
Stenosis –> reduction of blood flow –> reversible tissue ischaemia + angina
Total occlusion –> irreversible ischaemia –> tissue necrosis + myocardial infarction.
Role of atheroma in cerebrovascular disease
Atheroma in carotid/cerebral artery:
stenosis/ occlusion –> ischaemic stroke
Role of atheroma in peripheral arterial disease
Atheroma causing stenosis in ileal/ femoral/popliteal etc…artery
–> intermittent claudication (cramping pain in legs during exercise due to inadequate blood flow)
= most prominent symptom of PAD.
Process of arethomatous plaque formation
atherogenesis
- An irritant causes endothelial cell injury,
- LDL enters T. intima,
- Monocytes adhere to endothelium, migrate into T. intima, mature becoming macrophagesand phagocytose LDL,
- Macrophages die forming foam cells
- Activated platelets adhere to the injured endothelium and release growth factors,
- Growth factors cause intimal smooth muscle to proliferate and form a fibrous cap (enclosing the lipid core)
- smooth muscle cells lie down calcium
Results of endothelial cell injury to the endothelium
Increased permeability to LDL,
Enhanced expression of cell adhesion molecules
Increased thrombogenicity
Fatty streak
Earliest significant lesion of arteriosclerosis, begins in young children.
A yellow linear elevation of the intimal lining, comprised of lipid laden macrophages (foam cells).
No clinical significance, may disappear but for patients at risk, may form atheromatous plaques.
Consequences of atheroma on the artery
Reduced arterial radius = increased resistance
Reduced arterial compliance
= increased MAP
Pathophysiology of stable ischaemic heart disease
Mismatch between supply of O2 and metabolites to myocardium and myocardial demand for them.
Usually due to a reduction in coronary blood flow to the myocardium - coronary artery disease
Reasons for reduction of coronary blood flow
causing coronary artery disease
Obstructive coronary atheroma
Coronary artery spasm,
Coronary inflammation/arteritis
Other causes of stable ischaemic heart disease
other than reduction of coronary blood flow
Reduced O2 transport (anaemia),
Pathologically increased myocardial demand.
Angina definition
Cardiac chest pain associated with myocardial ischaemia (but without myocardial necrosis)
brought on by excess myocardial oxygen demand
e.g. exertion, cold weather, emotional stress, following heavy meal
Non-modifiable risk factors for coronary artery disease
Age,
Male,
Race (south Asian),
Family history/ genetic factors
Modifiable risk factors for coronary artery disease
Smoking, Diet and exercise, Diabetes mellitus (glycaemic control), Hypertenion (BP control), Hyperlipidaemia
Stable Angina SOCRATES
Site: Retrosternal Character: pressure/ tightness Radiation: Left neck/jaw/down arm Aggravated by: exertion/ emotional stress Relieved by: GTN/ physical rest.
Other symptoms of stable angina
apart from pain
Breathlessness on exertion,
Excessive fatigue on exertion,
Near syncope on exertion,
Signs of stable angina
Centripedal obesity, Xanthalasma and corneal arcus, Hypertension, Palpable abdominal aortic aneurysm, Arterial bruits, Absent/reduced peripheral pulses, Diabetic/hypertensive retinopathy.
Investigations of stable angina
ECG: Usually normal, can show LVH or evidence of previous MI
Bloods: FBC, lipid profile, fasting glucose, electrolytes, liver function, thyroid function, d-dimer.
CXR: differential diagnosis
Exercise tolerance test: Shows ST segment depression on exertion
Myocardial perfusion imaging: Tracer seen at rest, not at stress
Invasive coronary angiogram/ cardiac catheterisation: shows occlusion
Exercise tolerance test
Can confirm diagnosis of angina with:
- typical symptoms
- ST segment depression
Myocardial perfusion imaging
Radionuclide tracer injected, images obtained at stress and at rest.
Tracer seen at rest, but not stress = ischaemia
Tracer not seen at rest or stress = infarction
Localises ischaemia,
assesses size of area affected.
coronary angiography/ cardiac catheterisation
Radio-opaque contrast is injected into coronary arteries with a catheter and visualised on an x-ray.
shows sites, distribution and nature of atheromatous disease - enabling best treatment decision.
Drug treatment of stable angina
influencing disease progression
STATINS: Reduce LDL cholesterol deposition
ACE INHIBITORS: Stabilise endothelium and reduce plaque rupture
ASPIRIN: Protects endothelium and reduces platelet aggregation
Drug treatment of stable angina
Symptom relief
Druds that decrease myocardial demand (HR, contractility, afterload):
β-blockers,
CCBs,
nitrates(e.g. GTN),
K+ channel activators (prevent influx of Ca2+ to smooth muscle = coronary vasodilation), e.g. nicorandil)
Percutaneous Transluminal Coronary Angioplasty (PTCA)/
Percutaneous Coronary Intervention (PCI)
A balloon catheter is inserted through femoral/ brachial artery into the coronary artery with stenosis.
The balloon is inflated to compress the blockage and widen the artery. A stent may also be used to keep the vessel open.
Coronary Artery Bypass Grafting (CABG)
- The left internal thoracic artery is diverted to the left coronary artery.
- A great saphenous vein is removed and used to join the aorta to the obstructed artery, immediately after the obstruction.
Virchow’s Triad
3 Factors causing thrombosis:
Changes in blood vessel wall,
Changes in blood constituents,
Changes in the pattern of blood flow.
Relationship between atheroma and thrombosis
Arterial thrombosis is most commonly superimposed on atheroma.
Changes in the blood vessel wall that could lead to thrombosis
ATHEROMA
atheroma = occlusion = turbulent flow/stasis = endothelial damage = thrombus
Changes in blood constituents that could lead to thrombosis
HYPERVISCOSITY
-e.g. from dehydration
HYPERCOAGULABILITY
- thrombophilia,
- pregnancy,
- drugs e.g. OCP,
- Diseases
Changes in blood flow that could lead to thrombosis
STASIS
- aeroplane,
- post-op
TURBULENCE
- atheroma,
- aortic aneurysm
Process of thrombosis
Endothelial injury = collagen exposed
- -> platelets adhere to collagen
- -> thrombin converts fibrinogen to fibrin
- -> fibrin mesh formed over platelet plug
= Further turbulence
–> damages endothelium + causes platelet deposition
= growth of thrombus
Sources of systemic/arterial thromboemboli
Mural thrombus (formed in heart chamber),
Aortic aneurysm,
Atheromatous plaques,
Valvular vegetations,
Source of venous thromboemboli
Deep venous thrombi
most common type, often cause pulmonary thromboembolism
Types of embolus
Systemic/ arterial (thromboembolus), Venous (thromboembolus), Fat, Gas, Air, Tumour, Trophoblast (in pregnancy), Septic material, Amniotic fluid, Bone marrow, Foreign bodies
Ischaemia definition
Relative lack of blood supply to tissue/ organ leading to inadequate O2 supply to meet the needs of the tissue/organ
Types of hypoxia
Hypoxic - low inspired O2/ low PaO2
Anaemic - abnormal blood
Stagnant - abnormal delivery
Cytotoxic - abnormal at tissue level
Hypoxia definition
Diminished availability of O2 to body tissues
Infarction definition
Ischaemic necrosis within a tissue/ organ in living body produced by occlusion of the arterial supply or venous drainage
*Cell death due to ischaemia
Effects of infarction
Tissue dysfunction,
Pain,
Physical damage
Supply issues leading to ischaemic heart disease
Coronary artery atheroma, Cardiac failure (flow), Low pulmonary function, Pulmonary oedema, Anaemia, Previous MI
Process of infarction
relative lack of O2 supply
- -> anaerobic metabolism
- -> ATP depletion
- -> (loss of myocardial contractility)
- -> cell death
- -> liberation of enzymes
- -> breakdown of tissue
Transmural infarction
Ischaemic necrosis affecting full thickness of the myocardium
Subendocardial infarction
Ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart
probably non-STEMI
Reparative process in myocardial infarction
Cell death
- -> Cell membranes breakdown (=coagulative necrosis)
- -> Proteins leak out
- -> Neutrophils lyse dead muscle cells
- -> Neutrophils die
- -> Macrophages phagocytose debris
- -> Granulomatous inflammation (angiogenesis + fibroblasts lay down collagen)
- -> Fibrosis = scar tissue - non-contractile
Acute coronary syndrome (ACS)
Any sudden cardiac even due to myocardial ischaemia
e.g. Unstable angina, Non-STEMI, STEMI, Sudden Cardiac Death.
Sudden Cardiac Death (SCD)
Death caused by sudden and unexpected cardiac arrest
Myocardial Infarction definition
major/minor
Cell death in the myocardium due to ischaemia
MAJOR MI = due to complete coronary artery occlusion
MINOR MI = due to a partial/ transient complete coronary artery occlusion
Symptoms of Myocardial Infarction
main + associated
Chest pain/discomfort:
- severe, not “agony”
- may radiate to neck/arm
May be associated with:
- nausea
- sweating
- dyspnoea
Signs of Myocardial Infarction
on examination
May look very unwell/ fine,
Often no specific features to find,
CHECK:
- HR
- BP
- Murmurs
- Crackles
ECG changes after an MI
Complete coronary occlusion –> ST elevation –> Q waves after 3 days
Partial coronary occlusion –> no ST elevation (+ T-wave inversion) –> No Q waves
Location of MI caused by coronary occlusions in different coronary arteries
RCA = inferior/posterior
Anterior interventricular coronary artery = anterior
Circumflex = lateral/posterior
Detecting Posterior MIs
Usually caused by a RCA occlusion, so may see inferior changes.
Opposite changes are seen in opposite leads
Biomarker tests following MI
Myocyte death = membrane ruptures = proteins (cardiac biomarkers) leak out.
Most useful biomarkers = Cardiac troponin I & T
*There can be other causes of troponin rise!!
Diagnosis of MI
- detection of cell death = elevated troponin
- AND one of…
- symptoms of ischaemia
- New ECG changes,
- Evidence of coronary problem on angiogram,
- other evidence for new cardiac damage
Thrombolytic therapy mechanism
Serine proteases that convert plasminogen to plasmin (a natural fibrinolytic)
Strengths of thrombolytic therapy
Works well if given early, especially with aspirin.
Used if PCI not possible within 2 hours
Weaknesses of thrombolytic therapy
Increases risk of bleeding/haemorrhage:
- don’t give if recent stroke or previous intracranial bleed,
- Caution of recent surgery, on warfarin or severe hypertension.
May not work, especially if given late.
Aspirin therapy (mechanism and benefit)
Aspirin inhibits platelet production of thromboxane,
(thromboxane stimulates platelet aggregation and vasoconstriction)
Daily aspirin reduces risk of MI and death in patients with ischaemic heart disease
Common complications of MI
Arrhythmia, Cardiogenic shock, Myocardial rupture, Papillary muscle dysfunction, Acute VSD
Cardiogenic shock
Inadequate circulation of the blood due to ventricular failure
Cardiac rehabilitation
Exercise programmes,
Information sessions,
Addresses risk factors
Beta blockers in MI treatment
Reduce myocardial oxygen demand by lowering HR and myocardial contractility.
Reduces mortality following acute MI and reduces risk of secondary MI in survivors.
Contraindications of beta blockers in MI treatment
Asthma Bradycardia Heart block Coronary vasospasm Cocaine use ↑ risk cardiogenic shock ( Systolic BP<120, HR>110, age>70yrs)
Goals of pharmacological treatment of myocardial infarction
- Increase Myocardial O2 Supply:
- coronary vasodilation - Decrease Myocardial O2 Demand:
- decrease HR
- decrease BP
- decrease preload/ myocardial contractility
Drugs for prevention of MI and Angina
Beta-blockers,
ACE inhibitors,
Aspirin,
Simvastatin (lipid-lowering therapy),
Clopidogrel (mechanism)
Inhibits platelet aggregation
Heparin (mechanism)
Inactivates thrombin (converts fibrinogin to fibrin)
Risk factors for stroke
MODIFIABLE:
- High BP
- Atrial fibrilation
NON-MODIFIABLE:
- Age
- Race
- Family history
Stroke investigations
Blood tests - FBC, Lipids, ECG - For possible cause CT - Better for haemorrhagic (shows blood) MRI - Better for ischaemic Carotid doppler - shows carotid stenosis Echo - shows clots in heart
Acute treatments for stroke
Thrombolysis,
Aspirin,
Hemicraniectomy,
Thrombectomy (clot retrieval)
Hemicraniectomy
Part of the skull is temporarily removed to allow the brain to swell following a stroke without increasing intercranial pressure.
Treatment for primary + secondary prevention of stroke
Clopidogrel or Aspirin \+ Statin \+ BP drugs (even if normal BP)
*Carotid Endarterectomy (surgical removal of atheromatous plaque)
Aortic aneurysm disease definition
Dilatation of all layers of the aorta, leading to an increase in diameter of >50%
(abdominal aorta >3cm)
Symptoms of abdominal aortic aneurysm
nearing rupture
May be asymptomatic
Increasing back pain
tender abdominal aortic aneurysm
Clinical presentation of abdominal aortic aneurysm rupture
Abdominal/back/flank pain
Painful pulsatile mass
Hypoperfusion
Haemodynamic instability (shock)
Unusual presentations of AAA
Distal embolisation Aortocaval fistula Aortoenteric fistula Ureteric occlusion Duodenal occlusion
Carotid endarterectomy
Prophylactic surgical removal of an atheromatous plaque from a carotid artery
Complications (weaknesses) of carotid endarterectomy
Wound infection Bleeding Scar Anaesthetic risks Nerve damage Perioperative stroke
Strengths of carotid endarterectomy
+ when should it be done
Lower risk of stroke than from stenting
Should be offered for all symptomatic patients with >70% stenosis (but not if complete occlusion)
Positives of iodinated contrast agents
Differential x-ray attenuation Inert Stable in selected body compartments Painless Easy to use Cheap Localises in the vascular system
*All qualities of the ideal vascular contrast agent
Problems with iodinated contrast
MAJOR REACTIONS:
- renal dysfunction
- disturbance of thyroid metabolism
- disturbance of clotting
- seizures
- pulmonary oedema
- Contrasts should only be administered by those who can recognise and treat potential reactions
Carbon dioxide as a contrast agent
A negative contrast agent
Used in angiography
Useful in patients with poor renal function or sensitivity to iodinated contrast agents
Compression ultrasound
A normal vein has low pressure and is compressible
A DVT vein is full of thrombus and is not
Radionuclide imaging of vascular disturbances is used for…
Perfusion
Blood loss
Advantages of CT
Gives information about other structures
Sensitive
IV injection only
Limitations of CT
Radiation dose
High contrast dose
Expensive
Main contraindication of contrast agents
Renal failure
May induce contrast nephropathy
Renal function should be checked before administering the contrast if the patient is likely to have renal impairment
Doppler ultrasonography
Ultrasound scanning that uses the doppler effect to image the movement of blood
B mode ultrasound scanning
Shows a still plane through the body
Also called “2D mode”
M mode ultrasound scanning
Many pulses are emitted in quick succession creating an ultrasound “video”
Housenfield Unit/ CT Number
An arbitrary unit of the X-ray attenuation of structures viewed on CT
e.g. water = 0, compact bone = >1000
CT window width
The range of Housenfield units displayed. Tissues outside the range are shown as black or white
Maximum width = a wider range of densities represents one shade of grey. Contrast appears very low, used to view regions with wide ranges of density
Smaller width = a smaller range of densities is represented by a shade of grey. Subtler differences in density can be distinguished,
CT window level
The Housenfield unit at the centre of the window width. Should be higher to view denser tissues
Spiral (helical) CT
The scanner scans the body in a spiral path.
Images are more detailed and can be taken in a shorter time
Causes of venous valvular failure
valvular/venous incompetence
Surgical or traumatic disruption of the valve
DVT: ↑ pressure
Pregnancy: Hormonal changes cause vein and valve weakness. Enlarges uterus causes mechanical obstruction = ↑ pressure
Large pelvic tumour: A mechanical obstruction = ↑ pressure
Varicose veins investigations
DOPPLER ULTRASOUND:
Shows dynamic blood flow
TOURNIQUET TEST:
TAP TEST:
Tapping the saphenous vein at the knee will be felt at the saphenofemoral junction if the valves in between are incompetent
Chronic venous insufficiency investigations
Ultrasound: shows flow/reflux
Ankle-brachial pressure index: excludes arterial disease where BP is lower in the leg
CT/MR Venography: Shows detailed venous anatomy
Varicose veins treatment
- Endovenous/endothermal treatment:
A heat/ laser catheter causes fibrosis and occlusion of the vein - Ultrasound guided foam sclerotherapy:
A chemical foam causes fibrosis and occlusion of the vein - Open surgery:
The vein is stripped out
If intervention unsuitable (DVT, pregnancy): Compression hosiery
Lymphoedema
Pooling of lymph fluid in the tissue (usually lower limbs) due to improper lymphatic drainage.
Can be primary (genetic) or secondary, due to: - malignancy - surgery - radiotherapy - infection
Treatment is elevation and drainage
Stages of symptoms of arterial occlusive disease
Stage 1: Asymptomatic
Stage 2: Claudication on exertion
Stage 3: Pain at rest, mostly in feet
Stage 4: Necrosis/ gangrene of the limb
Signs of arterial occlusive disease
Ulceration
Pallor
Hair loss
Surgical interventions for arterial occlusive disease
Angioplasty
Surgical bypass
Amputation
Embolectomy
Demand issues leading to ischaemic heart disease
High intrinsic demand
Exertion
Stress
Clinical consequences of ischaemia
MI
TIA (Transient ischaemic attack)
Cerebral infarction
Peripheral vascular disease
Beta blocker ADRs
Fatigue
Lethargy
Bradycardia
Bronchospasm
Aspirin ADRs
GI bleed
Nitrovasodilators ADRs
Headache
Hypotension (“GTN syncope”)
Rate limiting CCBs ADRs
Ankle oedema
Flushing
Headache
Vasodilating CCBs ADRs
Reflex tachycardia
Ankle oedema
Flushing
Headache
ACEI ADRs
Cough
First dose hypotension
Renal impairment
Purpose of coronary interventions in SIHD and angina
Symptomatic treatment
Prevention of MI
Pathophysiology of valvular incompetence
Once one valve fails, venous pressure increases, the distal vein dilates causing further valvular incompetence
Treatment of chronic venous insufficiency
Wound care
Elevation
Compression bandaging
Shockwave therapy (for ulcers)
Symptoms of varicose veins
Burning Itching Heaviness Tightness Swelling Discolouration Phlebitis (red lines) Bleeding Disfiguration Eczema Ulceration
Signs of varicose veins
Twisting and bulging visible and palpable veins
Oedema
Symptoms of chronic venous insufficiency
Swelling Heaviness Pain Itching Varicose veins Discolouration
Signs of chronic venous insufficiency
Oedema
Telangiectasia (spider veins)
Eczema
Hyperpigmentation
Lipodermatosclerosis (hypodermis inflammation)
Ulceration (breach in skin btw/ knee and ankle)
Haemosiderin pigmentation
Indications of ultrasound
Used for anatomical + functional vascular imaging
No radiation
Quick
Non-invasive
Methods of administration of contrast agents
Parenteral e.g:
- CT (coronary) angiogram
- Ultrasound
- Radionucleide imaging
- CT
Catheterisation e.g:
- coronary angiography/ cardiac catheterisation
Tourniquet test
Leg is raised above heart level so vein drains
A tourniquet is applied above upper thigh to compress superficial (not deep) veins
Patient stands
- If superficial veins distal to tourniquet refill <20 seconds = deep valvular incompetence
Tourniquet is released after 20 seconds
*If sudden refilling of superficial veins now = superficial venous incompetence
