Cardiovascular pathology Flashcards
What is an aneurysm
Abnormal dilatation in an artery due to weakness on the vessel wall
What are the risk factors for AAA
*HTN
*Atherosclerosis
*Male, smoking, age >60, FHX, connective tissue disease, vasculitis, diabetes, trauma, congenital abnormalities of the aorta, infection, inflammation
Most common causes of AAA
Atherosclerosis, congential disease, mycotic, immunological, syphillis, trauma, salmonella
Morphological features of an AAA
*Localised dilatation of the abdominal aorta
*Usually between the renal arteries and bifurcation of the aorta into iliac arteries
Aneurysm often contains atheromatous ulcers covered with mural thrombi, with associated thinning and destruction of the media
Describe the pathogenesis of an aneurysm
*Occur when the structure or function of the connective tissue within the vascular wall is compromised
*Atherosclerotic plaque in the intima, compresses the media which cause degradation.
*This leads to cystic medial degeneration
*There is local inflammation, protelytic enzymes degrade the collagen, there is involvement of matrix metalloproteinases
*This results in loss of vascular smooth muscle cells, and inappropriate synthesis of non-elastic extracellular matrix
What are the clinical consequences of an aneurysm
*Painless mass
*Rupture- increased when diameter is >5cm. Can be retroperitoneal or intraperitoneal
*Obstruction-of branches such as mesenteric, vertebral or renal arteries
*Embolism of plaque or thrombus
*Impingement of plaque or compression of adjacent structures
*Infection or mycotic aneurysm
Risk of rupture of an AAA?
*<4m negligible
*4-5cm 1% per year
*5-6cm 11% per year
*>6cm 35% per year
What are thee risk factors for aortic dissection
*Male
*Age 40-60
*Hypertension
*Connective tissue disorder
*Iatrogenic- complication of arterial cannulation or coronary artery bypass
*Trauma
Describe the pathogenesis of an aortic dissection
*Hypertension with media hypertrophy as vasa vasorum and degeneration of the media
*and/or connective tissue disease (inherited or acquired)
*These cause weakness in the media
*Dissection begins with an intimal tear and the blood dissects into a tear in the media either distally or proximally within the media
How are dissections classifed?
- Stanford. Type A is proximal, type B distal
*Debakey
—>Type 1- ascending and descending
—>Type 2- ascending
—> Type 3- Descending only
Potential consequences of aortic dissection>
*Rupture back into the intima or out through the adventitia
*Rupture out or into the pericardial, pleural or peritoneal cavtities
*Cardiac tamponade, aortic insuffieciency via involvement of the aortic valve, MI, distal ischeamia and/ or spinal cord ischeamia via dissection into renal, mesenteric, formal or spinal vessels
*Death
What are the pathological consequence of aortic stenosis
*Concentric left ventricular hypertrophy
*LV outflow obstruction
*Angina/ myocardial ischeamia in the abscence of CAD
*Syncope
*Aortic dissection
*Heart failure
*Endocarditis (uncommon)
What are the causes of aortic stenosis
*Calcified/ degenerative
*Bicuspid
*Rheumatic heart disease
What clinical signs may differentiate calcific aortic stenosis from rheumatic aortic stenosis
*Rheumatic disease typically involves more than one valve
*Abscence of MS/MR and the abscence of Aortic regurgitation are more suggestive of calcific aortic stenosis
What are the predisposing factors for calcific aortic stenosis
*Age- over 70 for normal valve
*Wear and tear, chronic injury to the valve
*Bicuspid valve or other congential abnormality
*Hyperlipidaemia
*Hypertension
*Inflammation
What are the potential complications of congenital bicuspid aortic valve
*Major: calcification and stenosis
*Others: regurgitation, infective endocarditis, aortic dilatation, dissection
What are the systemic factors that lead to atherosclerosis
*Hypertension
*Hyperlipidaemia
*Smoking
*Hyperhomocysteninemia
*Infection
*Inflammation and inflammatory cystokines
What are local factors that lead to atherosclerosis
*Haemodynamic disturbanes i.e. turbulance at branch points
*Endothelial dysfunction
What arteries are most often affected by athersclerosis?
*Lower abdominal aorta
*Coronary arteries
*Popliteal arteries
*Internal carotids
*Vessels of the circle willis
Outline the steps involved in the pathogenesis of atherosclerosis
*Endothelial injury and dysfunction
*LDL accumulation and oxidation in the vessel wall
*Monocyte adhesion and migration into the intima and transformation into foam cells and macrophages
*Platelet adhesion
*Smooth muscle cell migration from media to intima
*Smooth muscle proliferation into the intima
*Enhances lipid accumulation within the intimal cells
Describe the difference between a stable and unstable plaque
*Stable: Dense collagen, thick fibrous cap, minimal inflammation, small atheromatous core
*Unstable: Thin fibrous cap, increased inflammation, large lipid core
How does an atherosclerotic plaque suddenly causes symptoms
*Rupture, ulceration or erosion of the intimal surface of the plaque exposes the blood to underlying thrombogenic substance and triggers thrombosis. The thrombus can partially or completely occulde the lumen and lead to downstream ischeamia
*Haemorrhage into plaque via rupture of the fibrous cap can cause intra-plaque expanding volume haemorrhage which occulde the vessel
*Atheroembolism-plaque rupture can discharge atherosclerotic debris into the bloodstream producing microemboli
*Aneurysm formation- via atherosclerosis induced pressure atrophy of underlying media, causing weakness of vessel wall, dilatation and potentially rupture of the vessel
What is the definition of cardiomyopathy
*Heterogenous group of diseases of the myocardium
*Associated with the mechanical and/or electrical dysfunction
*Usually inappropriate ventincular hypertrophy or dilatation
*Divided into primary (congenital or acquired) or secondary (where myocardium is affected as a component of systemic, multisystem disorder
What are the types of cardiomyopathy and some causes of each type>
*Hypertrophic-75% genetic, autosomal dominant
*Dilated- Alcohol, myocarditis (infective, autoimmune), ischaemic, drugs (chemotherapy), idiopathic, peripartum, genetic
*Restrictive-Infiltrative i.e. amyloidosis, sarcoidosis; non-infiltrative i.e idiopathic, scleroderma
How do dilated and hypertrophic cardiomyopathy differ?
*Dilated- cardiac dilatation, poor LVEF (<40%) systolic dysfunction/impaired contractility
*Hypertrophic-myocardial hypertrophy, normal high LVEF, impaired complaince (diastolic dysfunction)
What are some of the pathological consequences of dilated cardiomyopathy?
*Valve dysfunction (mitral and tricuspid most common)
*Mural thrombi with embolisation
*Arrythmia
*Atrial fibrillation
*Death from progressive failure
What are the pathological features of hypertrophic cardiomyopathy
*Macroscopic: Hypertrophy without dilatation, asymmetrical hypertrophy, LV outflow obstruction
*Microscopic: Myocyte hypertrophy, disarray of myocytes and intertisital fibrosis
What are the complications of HOCM
Atrial fibrillation, congestive cardiac failure, sudden cardiac death
What is cor pulmonale
Right sided heart failure that is not due to left sided heart failure
*Acute-massive PE
*Chronic-chronic lung disease
What are the common causes of cor pulmonale
*Anything that causes pulmonary hypertension
*Diseases of pulmonary parenchyma-COPD, fibrosis, bronchiectasis
*Disease of pulmonary vessels-Pulmonary HTN, recurrent PE, pulmonary arteritis
*Disorders of chest movement-marked obesity, kyphoscoliosis, neuromuscular disorders
*Disorders causing pulmonary artery constriction-hypoxaemia, metabolic acidosis, chronic sleep apnoea, altitude sickness
What are the major morphological features of pulmonary hypertension
*Pulmonary congestion is minimal but systemic and portal systems may be engorged
*Heart-Right ventricle hypertrophy and dilatation, leftward bulging of septum
*Liver/portal system-hepatomegaly, centrilobular necrosis, congestive splenomegaly
*Effusions and ascites within pleural, pericardial and peritoneal spaces
*Subcutaneous oedema in peripheries and dependent portions of the body
What factors predispose to infective endocarditis?
Host factors
*Bactereamia-reccent dental work, loss of skin integrity
*IVDU
*Immunodeficiency
*Dru induced immunosupression
*Malignancy
*Neutropeania
*Diabetes
*Alcohol excess
Cardiac factors
*Degenerative MV prolapse
*Calcific aortic stenosis
*Bicuspid aortic valve
*prosthetic valves
*Congential valve defects
*Rheumatic heart disease
What organisms commonly causes endocarditis?
*Strep viridians
*Staph aureus
*Staph epidermidis
*Enterococci
*Gram negative bacilli
*HACEK organisms (haemophilis, actinocacilius, cardiobacterium, eikinella, kingella)
*Fungal
What are the complications of endocarditis
Local- erosion/ destructions of tissue/valves. Also abscess formation
Systemic
-Septic infarcts to brain, lung, kidneys
-Myoctic aneurysm
-embolic phenomena-janeway lesions, roth spots (retina)
-Immune mediated glomerulonephritis
What is heart failure
When the cardiac function is impaired and/or the heart is unable to maintain a cardiac output sufficient to meet the bodys metabolic needs
What are the classifications types of heart failure
*Systolic dysfunction (inability to contract)
-Myocardial ischaemia
-Acute MI
-pressure of volume overload (hypertension)
-Dilated cardiomyopathy
*Diastolic dysfunction (inadequate filling)
-LV hypertrophy
-myocardial fibrosis
-Amuloidosis
-pericarditis
*Other
-Arrhythmias
-valvular disese
-outflow obstruction i.e AS
-Regurgitant flow
-HOCM
What are the clinical features of heart failure
*respiratory-dyspnoea, orthopnoea, PND, APO, pleural effusions
*Cardiac- third heart sounds or gallop rhythm, displaced apex beat, atrial fibrillation, murmur, JVP elevation
*Renal-activations of the RAAS resulting in fluid retention, peripheral oedema and AKI
*CNS-confusion secondary to hypoxia
*Hepatic-engorgement, ascities, cirrhosis (late)
What are the pathological changes seen in the liver caused by heart failure?
-Nutmeg liver
-Centrilobular necrosis (from central hypoxia)
-Centrilobular fibrosis
-crirrhosis
How is hypertension classified
*Primary (or essential)
*Secondary
What factors are thought to contibute to primary or essential HTN
*Multiple genetic polymorphisms and interacting enviromental factors
*Genetic-familial, multiple gene foci, genetic disorders altering NA handling
*Vasocontristritive influence-structual changes cause increased peripheral vascular resistance which leads to HTN
*Enviromental factors-stress, obesity, smoking, lack of physical activity and high salt intake
What are the long term consequences of essential HTN
*HTN is a major factor for atherosclerosis
*CAD
*Cerebrovascular disease
*Aortic dissection
*renal failure
*cardiac hypertrophy + failure
*Multi-infarct dementia
*Retinal changes
That are some causes of secondary HTN?
*Renal
-Acute GN
-CKd
-PCKD
-renal artery stenosis
-renal vasculitis
-renin producing tumours
*Endocrine
-adrenocortical hyperfuntion-cushings, hyperaldosteronism, CAH, conn syndrome
-exogenous hormones-gluccocoritcods, oestrogens, MAOis, sympathomimetics
-pheochromoctoma
-actomegaly
-Hypo or hyperthyroidism
-Pregnancy induced HTN
*Cardiovascular
-Aortic coartation
-increased intravascular volume
-High cardiac output
*Neurological
-OSA
-raised ICP
*Psychogenic
-Acute stress
-surgery
-pain
What are the clinical features of malignant hypertension
Severe HTN with systolic over 200, diastolic over 120, plus features of end organ dysfunction, such as
-renal failure
-encephalopathy
-CVS abnormalities
-retinal haemorrhages/ papilloedema
-often superimposed on previous benign HTN
-rapidly rising BP
What morphological changes are seen in hypertensive heart disease
*Thickened LV wall
*no dilatation
*Left atrial enlargement
*Increased weight of the heart
What are the pathological consequence of hypertensives heart disease
*Stiff ventricle
*Impaired diastolic filling
*Atrial dilatation and atrial fibrillation
*Heart failure
*Sudden cardiac death
What is acute coronary syndrome
ACS is a clinical manifestation of ischeamic heart disease and can present as unstable angina, NSTEMI, STEMI, or sudden cardiac death
Describe the pathogenesis of myocardial infarction due to atherosclerosis
*Acute plaque change
-Rupture/fissuring/erosions/ulceration or haemorrhage into the atheroma
*Thrombus formation
-Platelet adhesion, aggregation and microthrombi formation
-platelet release of mediators causing vasospasms
-Activation of cogulation cascade leading to thrombus
*Vasocontriction, stimulated by:
-circulating adrenergic agonists
-locally released platelet contents
-endothelial dysfunction causing reduced NO
-perivascular inflammatory mediators
*Vessel occulsion, leading to:
-Decreased myocardial blood flow
-myocyte necrosis
After an acute MI, what complications might a patient have?
*Contractile dysfunction causing hypotension and shock
*Arrhythmias i.e sinus bradycardia, AF, heart block, tachycardia, VT, VF
*Myocardial rupture: ventricular free wall, septum, papillary muscles
*Ventricular aneurysm
*Pericarditits or dreslers syndrome
*Infarct explansion
*Papillary muscle dysfunction
*Progressive heart failure
Describe the rime course of myocardial injury after acute coronary occlusion?
Reversible
-Cessation of aerobic metabolism (immediately)
-loss of contractility (2mins)
-decreased ATP production (down to 50% in 10 minutes, 10% in 40 mins)
-Lactic acid production
-Structural changes-cell and mitochondrial swelling, myofibrillar relaxation
Irreversible (20-40 minutes)
-Myocyte injury, sarcolemma distruption, cell membrane rupture (>30mins)
-initially subendocardial and then transmura myocyte death
-microvascular injury (1hr)
-coagulation necrosis (>2hr)
Describe the clinical feature of pericarditis
*Chest pain-typically positional, pleurtic
*Fever
*Congestive cardiac failure
*Pericardial friction rub
*constrictive pericarditis-muffled heart sounds, raised jvp
What are the causes of pericarditis
*Infectious- viral, pyogenic bacteria, TB, fungal
*Immune mediated- rheumatic fever,SLE, scleroderma, post cardiotomy, dresslers syndrome post MI, drug hypersensitivity
*Others: MI, uraemia, neoplastic, trauma, radiation
What types of pericardial fluid exudate occur?
*Serous-non infectious inflammation i.e SLE, viral, uraemia, tumours
*Fibrinous-post MI, trauma, post surgery but also sometimes infectious
*Purulent/supprative- bacterial invasion from local infection, lymphatic or blood seeding, surgical
*Haemorrhagic-rupture, dissection
*Caseous-TB
