Flashcards in Cardiovascular II Deck (32)
The basic lesion is the fibro-fatty plaque in the intima of medium sized and large arteries. This consists of a core of tis- sue debris rich in lipids with a covering fibrous cap of connective tissue with varying degrees of cellular proliferation.
1) These are common in the young, even infants, and consist of intracellular lipid deposits, mainly in smooth muscle and macrophages.
2) They are seen initially in the aorta and subsequently in smaller arteries.
3) They are thought to be precursors of atherosclerotic plaques, and yet there is indirect evidence that the fatty streak can resolve
1) These are small, soft, blister-like elevations which are mainly translucent, but the central areas may be pale pink or grey.
2) They occur commonly in the aorta and larger vessels. They have a high fluid content and twice as much albumin and four times the fibrinogen and lipoprotein content as the normal intima.
3) As with the fatty streak, their relationship to subsequent athero- sclerotic plaques remains unproven.
1) Characteristic lesions of atherosclerosis
2) They have a lipid rich core with overlying fibrous cap on the luminal surface the anatomy and proportions of this are very variable.
3) This gives a pearly white lesion which, if cut into, may have little or no lipid (fibrous plaque).
4) The fibro-fatty plaque may cause the intima to be thicker than the media, which is frequently abnormally thin. This medial thinning may subsequently lead to aneurysm formation.
5) Plaques tend to be found at certain sites, but especially the lower abdominal aorta, coronary arteries, renal arteries, distal superficial femoral and popliteal, descending thoracic aorta, internal carotid and circle of Willis and internal iliac arteries.
6) Other arteries tend to be spared, especially those to the upper limbs.
Microscopic appearance of fibro-lipid plaques
Microscopically, plaques have three components:
1. Cells, mainly vascular smooth muscle cells (SMCs), macrophages and lymphocytes
2. Connective tissue fibres of collagen, elastin and proteoglycans
3. Lipids, mainly cholesterol and oxidised cholesterol in the form of low density lipoproteins. These are quite irritant and have been shown to cause severe inflammatory reactions in connective tissue and probably involve a similar response in the arterial wall, resulting in periarterial inflammation, fibrosis and lymphocyte infiltration.
See fibrofatty plaque diagram
Complications of plaques
1) Rupturing or ulceration of the luminal surface may occur. This may result in the fatty part discharging into the blood stream as so-called ‘cholesterol emboli’.
2) Thrombosis may occur over ulcerated or fissured plaques, which may extend, leading to arterial occlusion, particularly in the coronary circulation.
3) Haemorrhage may occur into a plaque because of breakdown of the overlying fibrous cap. This may balloon the plaque, narrowing the lumen or leading to its rupture.
4) Calcification frequently occurs, which may be patchy or extensive.
5) Extensive necrosis of the plaque may occur, which may also cause embolism of plaque material and may leave large areas of ulceration.
6) There may be thinning and weakening of the media, with associated loss of elastic tissue, which may result in aneurysmal dilatation.
There are essentially five important lipoproteins in the body, as follows:
1. Chylomicrons are only found in plasma after a fatty meal and are composed mainly of triglycerides.
2. Very low density lipoproteins (VLDL) mainly transport triglycerides and some cholesterol from the liver.
3. Intermediate density lipoproteins (IDL) are transient and derived from VLDL after it has been acted on by lipase.
4. Low density lipoproteins are derived from VLDL via the intermediate IDL. The level of LDL in the plasma is most strongly correlated with the development of atherosclerosis. LDL plays an important part in the transport of endogenous cholesterol into body cells. In the presence of activated monocytes and endothelial cells, free radicals oxidise LDL.
5. Oxidised LDL is itself toxic to endothelial cells, which compounds
the endothelial injury; it is also chemotactic
to monocytes and immobilises macrophages, which, along with smooth muscle cells, take it
up preferentially. Thus oxidised LDL makes up the greater part of the lipid content of atheroma. There is both theoretical and some experimental evidence to suggest that antioxidants may inhibit the formation of atherosclerosis although up to now they have not been to shown to affect clinical outcome.
6. High density lipoproteins. There is an inverse relationship between the level of HDL and symptomatic atherosclerosis. This is because HDL is involved in a ‘reverse transport’ of cholesterol from cells and tissues to the blood stream, and then to the liver, where it is converted to free cholesterol. This is excreted in the bile, converted to bile acids or re-incorporated into plasma lipoproteins. Thus the higher the level of HDL the better (‘high helps!’).
Mitral valve disease: Stenosis
1. This may be caused by rheumatic endocarditis secondary to an immune response to β-haemolytic streptococci.
2. Mitral valve disease, may present in the second or third decades of life and quite often in pregnancy, when the altered haemodynamic physiology may cause atrial fibrillation and pulmonary oedema.
3. Clinicians should be aware of this risk during pregnancy in Asians.
4. It gradually causes left atrial hypertrophy, and then chronic passive congestion of the lungs (brown induration), with pulmonary oedema.
5. Treatment is now usually by balloon valvuloplasty; otherwise, surgical valvotomy or valve replacement may be required.
Mitral valve disease: Regurgitation
1. This may also be caused by rheumatic heart disease or endocarditis, but is more commonly due to mitral valve prolapse. This is also known as ‘floppy valve’.
2. It is due to a myxomatous degeneration of the mitral valve, and the enlarged mitral valve leaflets prolapse back into the atrium during systole. This is a common condition which gradually deteriorates with age.
3. The cause of the myxoid degeneration is not known but seems to be a connective tissue disorder. In the majority it is a chance finding on auscultation or echocardiogram and is of no clinical significance.
4. However, as it gets more severe, mitral regurgitation can develop with resultant congestive cardiac failure, arrhythmias, thrombosis behind the valve cusps and subsequent embolism.
5. Arrhythmias can occasionally cause sudden death.
Mitral valve repair may be required, which is more satisfactory than valve replacement, as the valve actually functions better, they do not need warfarin, provided they are in sinus rhythm, and there is less risk of SBE.
Aortic valve disease: Stenosis
1. This may be caused by rheumatic heart disease, when it is almost always accompanied by rheumatic mitral valve disease.
2. The vast majority of cases are due to age-related calcification with stenosis. This tends to come on in the 70s or 80s but may develop at a younger age in individuals with congenital bicuspid valve.
3. Nodules of calcium develop on the valve cusps and within the sinuses of Valsalva. Initially the left ventricle compensates by hypertrophy but, as the stenosis becomes more marked, patients may develop angina or syncopal attacks.
4. There is an increased risk of sudden death; thus when these symptoms develop, treatment is required urgently, with valve replacement.
Aortic valve disease: Regurgitation
This may be caused by the same factors as aortic stenosis but in addition may be due to:
1. Dissecting aortic aneurysm
2. Marfan’s syndrome
4. Ankylosing spondylitis
5. Still’s disease
6. Rarely to tertiary syphilis
Artificial heart valves
These are used sufficiently commonly that most general or orthopaedic surgeons will have patients, referred with other conditions, who have artificial heart valves.
There are two types:
1. Bioprostheses (usually made from porcine aortic valves) or mechanical valves constructed from metal and plastics.
2. There are a number of complications such as thromboembolism or infective endocarditis.
3. Thromboembolism is more likely with mechanical valves, and these patients require long-term warfarin anticoagulation.
4. When warfarin is stopped prior to surgery these patients should have intravenous heparin until shortly before surgery, which should be restarted as soon after as is considered safe.
Reperfusion syndrome: what is it?
The re-introduction of oxygenated blood after a period of ischaemia causes more damage than the ischaemia alone. The vascular endothelium is the site of damage, and neutrophils have been shown to be the prime mediator. It may occur after embolectomy, thrombolysis, repair of abdominal aortic aneurysm, or any vascular reconstruction.
Reperfusion syndrome: pathology
1. 98% of oxygen is broken down by the mitochondria, undergoing tetravalent reduction and producing high energy phosphate groups.
2. Approximately 2% of oxygen metabolism takes place by univalent reduction, and as a result a series of highly reactive, toxic, oxygen free radicals are formed.
3. Neutrophils in the act of phagocytosis produce large amounts of free radicals which facilitate the ‘killing process’. If this process were unregulated an overwhelming amount of tissue damage would occur.
4. An enzyme, superoxide dismutase (SOD), catalyses the reduction of superoxide radicals to hydrogen peroxide, and this too is removed by a series of enzymes.
5. Cell cytoplasm also has a number of antioxidants such as ascorbic acid and cystine which further limit free radical activity.
6. During ischaemia there is an increased generation of highly reactive metabolites. These may initiate a cascade of reactions which release other oxygen free radicals within the endothelial cells and may overcome the cells’ protective mechanisms.
7. The main pathological effect of oxygen free radicals is the generation of chemotactic agents resulting in direct migration of activated neutrophils into the reperfused tissue, with consequent injury. The damaged endothelial cells become more permeable.
Reperfusion syndrome: Neutrophil involvement
1) When neutrophils enter reperfused tissue they become activated and increase their synthesis of oxygen free radicals and proteolytic enzymes.
2) They induce injury by adhering to the endothelium at two sites: firstly, the precapillary sphincter, which may result in the capillaries becoming blocked by white cells, and secondly, postcapillary venules, where they induce injury by secretion of proteolytic enzymes such as elastase.
3) For vascular injury to occur, neutrophils must be present and must adhere to the endothelium.
Local effects of reperfusion syndrome
1) Limb swelling due to increased capillary permeability
2) Compartment syndrome as a result of the swelling;
3) Impaired muscle function due to ischaemia
4) Muscle contracture – may develop later if the
Effects of reperfusion syndrome (immediate)
1) Hyperkalaemia due to leakage of potassium from the damaged cells; this may result in cardiac arrhythmias
2) Acidosis due to the buildup of acidic metabolites
3) Myoglobinaemia due to breakdown of muscle cells,
which can result in acute tubular necrosis.
Effects of reperfusion syndrome (48 hours)
When the area of ischaemic tissue is large there may be serious widespread consequences:
1) Lung neutrophil sequestration, which may lead to pulmonary oedema and subsequently to ARDS
2) Renal neutrophil sequestration, which may lead to increased vascular permeability and to acute renal failure
3) Gastrointestinal endothelial oedema, which may lead to increased gastrointestinal vascular permeability and endotoxic shock.
An aneurysm is an abnormal localised dilatation of an artery or chamber of a heart due to weakening of the wall.
1. true – where the wall is formed by one or more of the layers of the affected vessel; and
2. false – where the wall is formed by connective tissue which is not part of the vessel wall.
True aneurysms may be:
1. fusiform – which is a dilatation due to a segment of the vessel wall affected around the whole circumference; or
2. saccular – where only part of the circumference is involved. It is thought these may be slightly more likely to rupture.
‘Berry’ aneurysms These are due to a congenital defect in the media at the junctions of vessels around the circle of Willis. They are the most common cause of subarachnoid haemorrhage, and although they can occur in young people the commonest age of presenta- tion is about 50 years. There is an increased incidence in patients with hypertension.
Atheromatous aneurysms The most common site is the abdominal aorta, and the next most common sites are popliteal and femoral arteries.
Abdominal aortic aneurysm (AAA): Risk factors are smoking and hypertension
The main complication is rupture, which may be intraperitoneal and accompanied by rapid death or retroperitoneal. Here they may leak, the blood pressure falls and a haematoma forms, holding the situation for anything from a few hours to a few days or even weeks. This situation is frequently described as a leaking abdominal aortic aneurysm.
Histologically the main findings are atrophy of the medial smooth muscle cells and destruction of the elastic fibres and replacement with collagen.
Popliteal and femoral aneuryms
Popliteal and femoral aneuryms
While popliteal aneurysms may rupture, they far more commonly develop thrombus on the walls of the aneurysm, and repeated small emboli may break off. This tends to destroy the runoff vessels gradually, so that, when the aneurysm finally thromboses, there is quite frequently no suitable runoff to which to perform a bypass.
Femoral aneurysms cause fewer problems.
These are most commonly associated with subacute infective endocarditis, although they may be due to any bacteraemia. Salmonella is one of the more common organisms responsible. In the major vessels, they are more likely to occur at sites where the vessel is already diseased with atheroma. They tend to be saccular, with weakness of the wall at the site of infection. They may thrombose or rupture and should, therefore, be treated if the patient is fit enough.
Rare now. They tend to involve the thoracic aorta. Microscopically, there is endarteritis of the vasa vasorum, with the inflammatory process extending into the media and causing ischaemia which damages the vessel wall.
Dissecting aneurysms (acute aortic dissection)
The thoracic aorta is the most common artery affected. Blood enters the diseased media which splits into two layers. Blood may then enter this false lumen, which tends to cut off the blood supply to branches along its route. The condition is caused by medionecrosis – which may be associated with Marfan’s syndrome, but by no means all the patients have this. There is a strong association with hypertension.
Once the dissection has occurred, it tends to rupture – either back into the main lumen of the artery, in which case the patient may survive for some time, or externally with rapid demise of the patient. When this condition involves the ascending aorta, it may dissect across a coronary ostium, leading to myocardial infarction, or across the aortic valve, causing aortic regurgitation.
False aneurysm (pulsating haematoma)
This results from a small tear in the artery which is followed by haematoma the wall of which becomes organised and will hold the aneurysm for some time before it ruptures.
These are due to injury with a small defect and usually they can be repaired simply by controlling the artery, closing the defect and evacuating the haematoma. Alternatively they may be treated under ultrasound (US) control by direct pressure with the US probe or by injecting thrombin into the sac watching closely on the US screen.
These are sometimes known as aneurysmal varices. These may be traumatic, or more commonly may follow formation of an AV fistula for renal dialysis. Here an artery is anastomosed to a vein in order to get a fast flow of blood in a superficial vessel suitable for needling to put blood through the kidney machine. Occasionally the flow is so good that aneurysmal dilatation gradually develops. They are associated with a raised venous pressure dis- tally and may also result in a degree of distal ischaemia due to ‘steal’ of the blood back up the veins.
A varicose vein is one which is tortuous and dilated and associated with local valvular incompetence. Varicose veins of the legs are extremely common, occurring in 10–20% of the population, with an increased incidence over the age of 50. They are said to be commoner in women, although a recent survey for the Vascular Surgical Society showed they were more common in men but that women consulted their doctors about them more often!
Varicose veins may be associated with:
1) poor support of the venous wall, which may be due to a familial tendency (approximately 40% of patients have a family history); in addition obesity and advancing age tend to result in loss of support of the vein; also prolonged dependent position
as in patients with jobs that involve sitting or
standing still for long periods.
2) Increased pressure within the lumen, which may
be caused by a venous thrombosis, pregnancy, or tumour masses pressing on the veins.
Varicose veins: Clinical
By far and away the most common vein affected is the great saphenous, with incompetence, initially at the saphenofemoral junction, which gradually works its way down as the vein stretches and affects the next valve down.
The next most common site is the short saphenous followed by incompetent valves in the veins which perforate the deep fascia connecting the superficial with the deep venous system
Varicose veins: Complications
2) Venous eczema (mild irritation and rash);
4) Venous pigmentation due to haemosiderin
5) Haemorrhage, which will be made worse by a
proximal tourniquet and should be treated by local
pressure and elevation; and
6) Venous stasis ulcer (longstanding venous stasis
ulcers may become malignant – Marjolin’s ulcer).