Cardiovascular Pathology Flashcards
haemostasis
physiological process which is initiated when there is damage to a blood vessel to stop haemorrhage
rapid formation of a solid plug - platelets, fibrin and red blood cells
fibrinolysis
ensure haemostats plug doesn’t become too big
plasmin is formed and this breaks down insoluble fibrin to soluble products
thrombosis
occurs when there is inappropriate activation of haemostasis which overwhelms the capacity of the fibrinolytic system, resulting in the formation of a solid plug called a thrombus
thrombosis is PATHOLOGICAL
about a THROMBUS
composed of RBC, fibrin and platelets
forms within the CVS
forms in flowing blood
about a CLOT
composed of RBC and fibrin
NO platelets
forms outside the CVS (test tube, skin surface)
forms in stationary blood
what is virchow’s triad
endothelial injury (atherosclerosis, vasculitis, direct trauma)
abnormal blood flow (turbulence, stasis)
hyper coagulability (too many blood cells, coagulation factor defects)
most important risk for thrombosis in an artery
atherosclerosis
most important risk factor for thrombosis in a vein
stasis and hypercoagulability
complications of thrombosis
partial occlusion at the sire
complete occlusion at the site
embolism to a distant site
embolism
occlusion of a vessel by undissolved material that is transported in the blood stream
what will emboli originating in the venous system occlude?
pulmonary artery
what will emboli originating in the arterial system occlude?
a systemic artery
what is atherosclerosis?
a chronic inflammatory process affecting the intimal of arteries. it is characterised by the formation lipid-rich plaques in the vessel wall
risk factors for atherosclerosis
smoking
hypertension
diabetes mellitus
dyslipidaemia
development of atherosclerotic plaque
damage to endothelium
cells become dysfunctional
increased permeability, produce adhesion molecules and cytokines
attract inflammatory cells
monocytes differentiate into macrophages
produce free radicals that drive LDL oxidation to form oxidised LDL
form foam cells
foam cells produce growth factors that stimulate migration of smooth muscle cells from the media to intima
what is the fatty streak in atherosclerosis
Oxidised LDL accumulates within macrophages and smooth muscle cells just underneath the endothelial cells. Collections of lipid-laden macrophages sinng in the intimal layer may be visible as yellow elevations called fatty streaks. The fatty streak has no clinical significance but it is important because it may progress to an atherosclerotic plaque.
why does the atherosclerotic plaque form
due to attempt to heal by scarring
can be stable or unstable
complications of atherosclerosis
gradual enlargement of a stable plaque leading to luminal stenosis and reduced blood flow through the artery
sudden rupture of a vulnerable plaque
aneurysm formation
ischaemic heart disease
ischaemic heart disease is the term used to describe the spectrum of heart disease which result from coronary artery atherosclerosis
stable angina
occurs when there is an imbalance between supply and demand of O2/nutrients to the myocardium
results in myocardial ischaemia and cardiac type pain
acute coronary syndrome (ACS)
spectrum of clinical conditions which occur when there is a sudden severe reduction in myocardial perfusion leading to ischaemia and/or infarction
due to an acute/sudden change in a coronary artery atherosclerotic plaque causing sudden partial or complete occlusion
How is ACS identified
clinical fatures
ECG changes
cardiac troponin levels
the body’s response to MI
myocyte necrosis
acute inflammatory response
repair of the infarct
scar formation
short term complications of MI
ventricular fibrillation causing sudden death
other arrhythmias
acute cardiac failure or cariogenic shock
myocardium rupture
pericarditis
mural thrombus
long term complications of MI
recurrent MI
chronic congestive cardiac failure
Dressler’s syndrome
ventricular aneurysm formation
chronic ischaemic heart disease
Gradual enlargement of stable atherosclerotic plaques in coronary arteries leads to gradual luminal stenosis. This may cause low grade chronic myocardial ischaemia over a long period of time which results in progressive fine diffuse myocardial fibrosis ie. there is replacement of contractile myocardium by non- contractile scar tissue. Often this process is entirely asymptomatic because the remaining myocardium has enough time to undergo compensatory changes such as left ventricular hypertrophy. The compensatory changes mask the diffuse fibrosis and so the patient is asymptomatic.
However, eventually the myocardium decompensates and there is onset of progressive chronic heart failure.
ishcaemic strokes
80% of strokes
caused by sudden occlusion of a cerebral artery leading to a sudden reduction in blood flow to part of the brain leading to infarction of brain tissue
most commonly due to rupture of an atherosclerotic plaque in the internal carotid artery
types of aneurysm
saccular - spherical shape, bulge out of the side of the vessel
fusiform - spindle shape, involving all the circumference of vessel
false aneurysm - expanding pulsatile haematoma in a continuity with a vessel lumen, NOT lined by the endothelium
common complications of AAAs
rupture (la place’s law)
thrombosis and embolism
AAA screening
invites men from the age of 65
men with a small or medium aneurysm are followed up to see if the aneurysm gets bigger
men with a large aneurysm are referred to a vascular surgeon to discuss options - open surgery, EVAR or conservative management
medium sized PE
causes occlusion of a segmental pulmonary artery
leads to a VQ mismatch
causes respiratory compromise
pleuritic chest pain SOB haemoptysis pleural rub crackles effusion
VTE prevention
major cause of hospital deaths
LMWH
anti embolism stockings
patients should be encouraged to mobilise as early as possible
patients should be given information about VTE risk on admission and discharge
Wells criteria
clinical symptoms of DVT (3)
other diagnoses less likely than PE (3)
heart rate >100 (1.5)
previous DVT or PE (1.5)
haemoptysis (1)
immobilisation or surgery within past 4 weeks (1.5)
malignancy (on treatment, treated in last 6 months, palliative) (1)
PE likely if more than 4 points, PE unlikely if 4 or less
would do a d dimer if it is LESS than 4. if tis more then do a CTPA
D-dimer in PE diagnosis
D-dimers are cross-linked fibrin degradation products formed by the action of plasmin.
D-dimers are raised in PE but also in many other conditions eg. post operatively, MI, stroke, trauma, pregnancy.
Thus, a raised D-dimer is not useful in making a positive diagnosis of PE since it is not very specific.
A normal (negative) D-dimer is useful since it has a >90% NPV for PE ie. >90% of patients with a negative D-dimer do not have a PE.
PE imaging
CT pulmonary angiogram is the NICE recommended radiological investigation for suspected PE.
[If CTPA is not appropriate (eg. allergy to contrast media, renal impairment), then a ventilation:perfusion (V:Q) scan can be considered.
For a CPTA, radiocontrast is injected into the circulation and a CT scan is performed. The blood vessels are filled with blood mixed with contrast and so appear white. A thrombus will appear as a dark area (a ‘filling defect’) because it formed before the contrast was administered. Thus, the thrombus does not contain contrast and appears dark.
Massive PE
Massive PE is due to a massive embolus occluding a proximal pulmonary artery or the pulmonary artery bifurcation (‘saddle embolus’).
As a consequence, blood cannot enter the lungs, which causes a sudden
increase in resistance to pulmonary blood flow and results in sudden
pulmonary hypertension.
The right side of the heart does not have time to compensate for this sudden increase in pressure in the pulmonary circulation, and so there is onset of acute right heart failure (cor pulmonate).
In addition, blood cannot pass through the lungs, which results in decreased filling of left side of heart and therefore decreased left ventricular output. This presents as haemodynamic compromise in the form of shock, collapse and sudden death. On examination there is tachycardia, hypotension, raised JVP, RV heave, normal chest examination, low 02 sats.
recurrent small PEs
A third presentation of pulmonary embolism is in the form of recurrent small PEs.
Each individual episode is usually subclinical (ie. does not result in symptoms) but over time the multiple small emboli occlude arterioles resulting in gradual occlusion of the pulmonary arterial bed, leading to the gradual development of pulmonary hypertension.
Because the onset is gradual, the heart has time to undergo compensatory right ventricular hypertrophy.
Eventually the right ventricle will decompensate and right heart failure (cor pulmonale) ensues.
most common causes of cor pulmonale
COPD
pulmonary fibrosis
recurrent small PEs
Right Heart Failure
Right heart failure is much less common than left heart failure.
By convention, the term ‘right heart failure’ is usually reserved for cases developing in the absence of left- sided heart failure ie. we don’t use the term ‘right heart failure’ when the right heart failure is secondary to left heart failure.
Remember, overall, the most common cause of RHF is as a consequence of LHF, when it is called congestive heart failure (or biventricular heart failure).
acute RHF
Acute right heart failure is much less common than acute left heart failure.
The most common cause of acute right heart failure is a massive pulmonary embolism causing sudden blockage of a major pulmonary artery or the pulmonary bifurcation (saddle embolus):
• the pressure in the pulmonary arterial system rises dramatically ie. development of pulmonary
hypertension. The right heart does not have time to undergo compensatory changes and so cannot generate enough force to maintain an output. This results in acute right heart failure, which presents clinically as circulatory collapse, shock and/or instantaneous death.
A myocardial infarction involving the right ventricle but sparing the left ventricle is another important (but less common) cause of acute right heart failure.
what is pulmonary hypertension
Pulmonary hypertension refers to an increase in blood pressure in the pulmonary vasculature (pulmonary arteries, veins and capillaries). It is defined as a resting mean pulmonary artery pressure at or above 25 mmHg (normal is in the range of 18-25mmHg).
chronic RHF
Chronic right heart failure is much less common than chronic left heart failure.
The clinical features of chronic right heart failure are shown in the diagram opposite.
Preceding the development of chronic right failure, the right ventricle is damaged slowly over a period of time.
commonest causes of slow damage to he right ventricle
lung diseases
(COPD, pulmonary fibrosis, recurrent small PEs)
damage the RV by causing pulmonary HTN - compensatory changes in early stages but eventually decompensated resulting in RHF
what is cor pulmonale
Cor pulmonale is the term used to indicate right heart failure due to lung disease (including diseases of the pulmonary vessels):
• massive PE → acute cor pulmonale.
• COPD, pulmonary fibrosis or recurrent small PEs → chronic cor pulmonale.
The link between lung disease and the development of right heart failure is that the lung disease causes pulmonary hypertension (ie. increased pressure in the pulmonary circulation).
classification of hypertension
primary/essential - ~95%
secondary - ~5%
causes of secondary hypertension
chronic renal disease coarctation of aorta endocrine disease drugs pregnancy cushing's syndrome acromegaly
effects of HTN on vessels
accelerates atherosclerosis
accelerates arteriosclerosis
hyaline arteriosclerosis
hyperplastic arterioscerlosis
what is arteriosclerosis?
hardening of an artery or arteriole
hypertensive heart disease
HTN has a number of adverse effects on the heart
- accelerates coronary artery atherosclerosis (worsens IHD)
- causes LVH
may manifest in a number of ways including MI/ischaemia, arrhythmias, progressive LHF
hypertensive renal disease
Progressive hyaline arteriosclerosis in the renal arterioles causes chronic and progressive renal ischaemia. This results in tubular atrophy, interstitial fibrosis and progressive glomerular sclerosis. In turn this leads to the development of progressive chronic kidney disease (CKD).
A vicious cycle is established: hypertension causes CKD which in turn worsens the hypertension. Ultrasound will show small kidneys - they are small because of atrophy and fibrosis.
other complications of HTN
retinal changes intracerebral haemorrhage (haemorrhage stroke) subarachnoid haemorrhage
what is malignant/accelerated hypertension
Malignant/accelerated hypertension
This is a clinicopathological syndrome characterised by a markedly raised diastolic blood pressure (usually >130-140mmHg) and end organ damage.
It occurs in less than 1% patients with primary hypertension but more commonly in cases of secondary hypertension (especially when due to renovascular disease).
Malignant hypertension usually affects younger people with hypertension; new cases usually present at 30-40yr of age.
The underlying pathogenesis is poorly understood.
The characteristic histological lesion is hyperplastic arteriolosclerosis (see diagram on page 4). There is also fibrinoid necrosis of small arteries and arterioles.
clinical consequences of malignant hypertension
actue LVF stroke acute renal failure blurred vision hypertensive encephalopathy microangiopathic haemolytic anaemia and disseminated intravascular coagulation
clinical presentation of aortic dissection
tearing pain between the shoulder blades
hypertension
asymmetrical pulses
major risk factors for aortic dissection
hypertension
abnormal media eg marfans, EDS
pregnancy
what is aortic dissection?
occurs when there is a tear in the intimal. a split forms in the media and blood tracks in the newly formed ‘false lumen’
classification of aortic dissection
type A: involves the ascending aorta - immediate surgical repair
type B: does not involve the ascending aorta - medical management
complications of aortic dissection
compromised blood flow
stroke
MI
cardiac tamponade if ruptures into pericardium
aortic regurgitation
if ruptures into thoracic or abdominal cavity may cause exsanguination
ischaemia
about valve stenosis
failure of a valve to open completely → impede forward flow.
stenosis is virtually always caused by a chronic process.
The chronicity of the process allows time for compensatory changes in heart, blood vessels and other organs.
about valve regurgitation
failure of a valve to close completely → reverse flow occurs.
regurgitation may be caused by an acute or chronic process.
aortic stenosis - common causes
cusp calcification of a bicuspid valve
age related calcification of a tricuspid valve
post rheumatic fever valve disease
pathophysiology of aortic stenosis
Blood flow across the aortic valve is impeded during systole. As a consequence, a significantly elevated left
ventricular pressure is necessary to drive blood into the aorta.
Since AS develops over a chronic course, the LV is able to compensate by undergoing hypertrophy in response to the high systolic pressure it must generate to maintain output.
ie. gradual development of LV outflow obstruction causes gradual pressure overload of LV and results in
compensatory LV hypertrophy.
However, the hypertrophy reduces the compliance of the ventricle. The resulting elevation of diastolic LV pressure also causes LA hypertrophy in order to fill the ‘stiff’ LV
As a consequence of the compensatory changes, there is a long asymptomatic period.
Eventually the heart decompensates and there is deterioration in cardiac function, leading to the the development of symptoms.
clinical presentation of aortic stenosis
syncope
angina
dyspnoea
aortic stenosis type of murmur
ejection systolic murmur
common causes of mitral regurgitation
LV dilatation mitral valve prolapse infective endocarditis post RF papillary muscle rupture post MI ischaemia due to coronary artery atheroma
acute mitral regurgitiation
Mitral regurgitation of sudden onset is usually due to infective endocarditis or rupture of a papillary muscle after a myocardial infarction.
When there is sudden onset of mitral regurgitation, the heart does not have time to undergo compensatory changes.
As a consequence, blood flows back into the left atrium, causing the pressure in the LA to rise.
The high pressure in the LA is transmitted backwards into the pulmonary circulation and the high pressure in the pulmonary circulation causes transudation of fluid from the circulation into the lung interstitium and alveoli (pulmonary oedema) ie. acute left heart failure.
chronic mitral regurgitation
Mitral regurgitation of gradual onset may be due to dilatation of the mitral valve ring, mitral valve prolapse, post-rheumatic fever or papillary muscle ischaemia.
When there is gradual onset of mitral regurgitation, the heart has time to undergo compensatory changes:
• the LA dilates so that it can accommodate the back flow of blood without a substantial increase in LA pressure.
• the LV undergoes hypertrophy, which mitigates the effects of regurgitation.
These compensatory changes maintain cardiac output at near-normal levels and so the patient may be asymptomatic for many years.
Eventually, the left hypertrophied LV begins to decompensate (ie. its function deteriorates) and there is development of progressive left ventricular failure.
mitral valve prolapse
Mitral valve prolapse (MVP) is the most common cause of mitral regurgitation.
It is common with an incidence of approximately 5%, mainly women.
MVP is usually an isolated finding but it may be found as a complication of genetic disorders of connective tissue synthesis eg. Marfan’s syndrome, Ehlers-Danlos syndrome.
In MVP the normal dense collagen and elastin matrix of the valve is replaced with loose myxomatous connective tissue containing abundant glycosaminoglycans (so-called ‘myxomatous degeneration’). The leaflets become enlarged and one of the leaflets ‘prolapses’ back into the LA during systole.
what is infective endocarditis
Infective endocarditis refers to infection of part of the endocardium, usually the endocardial surface of a valve (but the atrium or ventricle can be affected).
It is a serious disease with a high mortality (untreated approx 100%, treated approx 10-30%).
what are the causes of infective endocarditis?
Usually bacterial
- Streptococci, usually S. viridans (40-50%) – weakly pathogenic. - Staphylococci eg. S. aureus (20-30%) – highly pathogenic.
S. aureus is the most common cause in iv drug users; usually affecting the tricuspid valve. • other bacteria eg. gram negative bacteria such as E. coli.
• less commonly fungi eg. Candida, Aspergillus.
- typically immunocompromised, iv drug users and patients with indwelling venous lines.
what is the pathogenesis of infective endocarditis
Bacteria are delivered to the heart during an episode of bacteraemia. This may be due to an event as trivial as tooth brushing or associated with a more invasive procedure such as surgery. As a consequence of the bacteraemia, the organisms adhere to and invade the valve.
The endocardium is normally resistant to infection, so for infection to occur:
• either there must be highly pathogenic organisms (eg. S. aureus) colonising a normal valve.
• or weakly pathogenic organisms (eg. S. viridans) colonising an abnormal valve eg. prosthetic valve, mitral
or aortic regurgitation, mitral valve prolapse.
As the organisms replicate they become enmeshed within layers of platelets and fibrin on the valve surface, forming vegetations.
what is a vegetation?
a thrombus containing microorganisms
complications of endocarditis
disturbance of valve function
embolism
formation of antigen-antibody immune complexes
investigations of infective endocarditis
blood cultures (at least 3 sets from different sites, taken a minimum of 1 hour apart and before starting antibiotics)
echocardiography (TOE will identify vegetations and any complications)
How many of Duke’s criteria is needed for diagnosing endocarditis
two major
one major and three minor
five minor
Duke’s major criteria
positive blood cultures
evidence of endocardial involvement noted on echo (new valvular regurgitation, abscess, vegetations)
Duke’s minor criteria
predisposing valvular or cardiac abnormality
fever >38
vasculitic phenomena
embolic phenomena
microbiologicalevidence - positive blood culture but does not meet major criteria
suggestive echocardiographic findings
acute left heart failure
In acute left heart failure there is a sudden major insult to the left side of the heart.
There is no time for compensation, and cardiac output falls catastrophically. The sudden failure of the LV leads to severe congestion in the pulmonary venous system and rapid accumulation of fluid in the alveolar spaces and interstitium. This causes pulmonary oedema and presents as severe breathlessness.
In the worst cases, there is underperfusion of organs and development of cardiogenic shock.
chronic left heart failure
Chronic left heart failure is by far the most common form of heart failure; it is almost always due to chronic left ventricular failure.
The left ventricle is damaged slowly over a period of time. The commonest causes of slow damage to the left ventricle are:
• chronic ischaemic heart disease (due to coronary artery atherosclerosis). • systemic hypertension.
• valvular (mitral/aortic) heart disease.
Because the damage occurs slowly, there is enough time for compensatory myocardial hypertrophy to occur. This maintains cardiac output and prevent symptoms of heart failure.
Eventually the myocardium becomes irreversibly damaged and the left ventricle decompensates leading to chamber dilatation and falling cardiac output.
Heart decompensation
Patients with chronic heart failure may decompensate if their heart is stressed.
Patients with chronic heart failure frequently experience episodes of acute worsening in their symptoms. This is often described as ‘acute decompensation’ and is very commonly seen in routine practice when a concurrent illness (often only a trivial infection) places additional burden on a critically failing heart and pushes the patient into acute failure.
Most patients with chronic heart failure experience a relapsing and remitting course, with periods of stability interspersed with episodes of decompensation.
diagnosing LVF
• History and Examination • ECG (usually abnormal) • CXR (cardiomegaly)
• Echocardiography
• can confirm systolic or diastolic dysfunction.
• it may identify the underlying cause eg. aortic or mitral valve disease. • B type natriuretic peptide (BNP) plasma levels
• BNP is a hormone secreted by ventricular myocytes in response to volume and pressure overload of the LV. Its normal function is to promote a salt and water diuresis by the kidney.
• BNP plasma levels are useful because low levels effectively rule out the diagnosis of LVF.
• in contrast, in the correct clinical context, high BNP plasma levels make the diagnosis of LVF very
likely.
Investigations to identify the underlying cause of the heart failure are also important.
