CVS pathology notes PDF

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Rebekah Mercer year 3 SBCP CVS pathology notes...

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Cardiovascular Pathology CVS revision Ischaemic and infarction Ischaemia: result of impaired blood flow or perfusion of tissues such that its deprived of vital nutrients, including oxygen. Reversible, depends on duration of ischaemia and metabolic demands of tissue. Infarction: death (necrosis) of tissues as result of ischaemia. Irreversible. Tissues vary in ability to repair and regenerate. Infarcts elicit inflam response. Factors effecting it: 

Nature of blood supply: lung and liver have biphasic circulation vs spleen and kidney have single supply Rate of development of occlusion: slow (adaption can occur) vs fast Vulnerability of tissue to hypoxia: neurones and myocardium (v vulnerable) vs skeletal muscle and fibroblasts (more resistant) Oxygen content of blood: anaemia (lower o2 carrying = susceptible) and hypoxia (eg at high altitude) vs normal

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Morphology of infarcts: varies depending on time since cessation of blood flow. Anatomical pattern of blood supply also effects appearance and sensitivity to infarct    

End artery – brain/heart Type and degree of anastomoses – heart/lower limb Vascular arcades – kidney/intestine Portal/other dual blood supply – liver/pituitary

Red infarct: due to blood presence

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Venous occlusion Loose tissues such as lung Tissues with dual circulation (lung & liver) Previous congested tissues Reperfusion damage

Pale infarct:

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Usual form in solid organs (heart, spleen, kidney) Single blood supply

Causes: often occur in occlusion eg thromobis/embolism with hyperviscosity 1. Things in lumen  Thrombosis  Embolism  Atheroma  Hyperviscosity  Steal 2. Things in wall

 Spasm  Vasculitis 3. Things outside wall  Compression Thrombosis Virchow’s triad: 1. Changes in intimal surface of vessel 2. Change in pattern of blood flow 3. Changes in blood constituents Genesis: preexisitng atheromatous plaque causes turbulence of flow. Loss of endothelial cells and exposure of collagen platelet activation - activation of clotting cascade and deposition of thrombus. This grows in the direction of flow = propagation Clinical effects: variable depending on

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 Vascular system involved  Speed of development  Availability of collateral flow  Sens of tissues to ischaemia Can be v severe:  Arterial thrombosis – in limb vessel eg femoral artery  Distal tissues become pale, cold, painful, pulseless and will ultimately undergo infarction – MI associated with coronary artery thrombus formation  Venous thrombosis (usually leg) – distal tissues become swollen, reddened and tender

Fate of thrombi: 1. 2. 3. 4.

Lysis and resolution = complete recanalization Organisation = scars causing occlusion of vessel Recanalization = scare and residual thrombus Embolism = kidney infarct

Embolism: mass of material (embolus) can move in vascular system and become lodged in some vessel and block lumen. Most emboli derived from thrombus. Most commonly pulm embolism from venous thrombosis in deep leg veins. Types:  

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**Thromboembolism** >90% Others: Atheromatous emboli Amniotic fluid (parturition – passes from foetal in maternal vasculatory system) Gas (trauma) Fat (trauma, esp fractured long bones) Tumour (metastasis)

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Foreign material (IV drug abusers) Infective agents (infected heart valves)

Origins of systemic arterial emboli:     

Atheromatous plaque with thrombus Valve vegetation Atrial thrombus Thrombus – old myocardial infarct (adynamic) Thrombus – recent MI

Effects of systemic arterial emboli:    

Central infarct (stroke) Renal infarct Ischaemic bowel Ischaemic foot – dry gangrene

Atheroma: deposition of material in intimal layers of vessels. Esp in high pressure vessels such as arteries. Composed of lipid deposits, macrophages, T lymphocytes, cholesterol, smooth muscle cells, fibrovascular connective tissue. Luminal narrowing = vascular insuff. Causes 30% hospital admission and 1/3 all deaths. Fibrous cap of atheromatous plaque. Fragmented and destroyed internal elastic lamina. Thinned media Normal layers of vessel: outside in 1. 2. 3. 4. 5. 6.

Adventitia External elastic lamina Media Internal elastic lamina V thin intima Endothelium

Aetiology: exact cause unknown. Wide variation in appearance and effects. Well know risk factors. Major risk factors:      

Age (middle age and old) and sex (commoner in men but increasingly common in women after menopause) Hyperlipidaemia Smoking – modifiable Hypertension Diabetes mellitus Sedentary lifestyle – modifiable

Other risk factors:      

Lack of exercise Hyperuricaemia High carb intake Stress Obesity Soft water

Morphology: 3 types of lesion progressing from 1 to 3 1. Fatty streaks: linear elevations composed of lipid laden macrophages (foam cells) seen in 2030s. 2. Fibrolipid plaque: bigger lesion with fat and fibrosis and with fibroblasts present. Ingrowth of fibroblasts with deposits of collagen with formation of fibrosis occurring in 40-50s 3. Complicated lesion: - Narrowing - Endothelial erosion with thrombosis - Plaque rupture and fissuring (bleeding) – acute expansion of material and narrowing of vessel - Aneurysm formation due to weakening – seen in abdo aorta - Embolism Sites affected: tends to be high pressure vessels such as arterial tree but can occur in pulm vessels under pulm hypertension.  

Common in: lower abdo aorta/iliac > coronary > popliteal > desc thoracic aorta > int carotid and circle of willis Spared vessels (except at ostia – common atheromatous plaque due to turbulent flow): upper extremity > renal > mesenteric > aortic arch

Complications: 1. 2. 3. 4.

Narrowing Thrombus of plaque Fissuring and cracking with bleeding into plaque Aneurysm

Ischaemic Heart Disease Definition: spectrum of clinicopathological entities (including angina, MI or sudden death) in which there is an imbalance between demand for oxygen and its supply by the coronary arteries Mainly due to atheroma but other factors such as spasm and anaemia can contribute Epidemiology: commonest cause of death in western world + HF in UK. 150,000 deaths per annum in UK (out of 600,000 total). Huge health care burden with massive financial, social + personal cost. Aetiology:        

Familial factors Smoking ** most important signle preventable factor Diet Lifestyle Race (black > white – seen more in blacks) Age Gender (male > female) Obesity

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Diabetes mellitus Hypertension Hyperlipidaemia Stress – no hard evidence

Pathogenesis: under normal conditions the coronary artery blood flow is closely matched to huge aerobic metabolic demands of cardiac muscle. IHD occurs when blood supply becomes insufficient (can be combo of all 3):   

By reduction in blood supply (eg atheroma) Increased demand (eg muscle hypertrophy) Reduced oxygen carriage (eg anaemia)

Key points: 1. Changes in coronary arteries are common (atheroma, thrombosis, plaque haemorrhage, stenosis +/or occlusion) 2. Morphological appearances depend upon extent of infarction and elapsed time 3. Changes are spectrum from chronic ischaemic fibrosis through to acute infarction 4. With chronic ischaemia (asymptomatic or with angina) there may be some diffuse myocardial fibrosis 5. With sudden death there may be macroscopic changes or there can be nothing Spectrum: 

Angina: Reversible chest pain May be predictable and relate to increased exertion or unpredictable (unstable)  Myocardial infarction - Central crushing chest pain - Left arm + neck radiation - Complications  Sudden death – cardiac cause is first thing to consider -

Clinical spectrum: 

deposition of lipids, fat, fibroblasts, firbovascular CT in the intima = luminal narrowing (fixed coronary obstruction)  reduction in blood flow - on exercise increased oxygen demand of myocardium may not be met and angina pain will occur  plaque can undergo disruption - thrombus formation with platelet aggregation leading to further narrowing, scarring associated with healing (sever fixed coronary obstruction = chronic IHD)  acute event eg plaque disruption due thrombus - substantial increase in narrowing of lumen = unstable angina, acute subendocardial infarction or sudden death  if occlusion due to this = complete cessation of blood supply = MI or sudden death (insert image from slide 7) Acute MI:

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90% MIs are regional 3 commonest arteries affected: - LAD - RCA - LCC  Necrosis usually of left ventricle followed by inflam infiltration + fibrous repair (myocardium has no potential for regeneration)  Necrotic muscle release enzymes used routinely for diagnosis - amount of enzyme present in blood roughly proportional to amount of damage, different enzymes released with different time course so progression of events can be monitored by blood tests

Occlusion of different arteries leads to effects in different areas – ischaemia/infarction in different territories have different ECG changes + may be assoc with different complications   

RCA: inferior infarction, ECG = II, III, aVF, can involve post septum, can effect conduction system if prox to branches to that area or involves septum. L circumflex: lateral infarction, ECG = I, aVL + lateral chest leads LAD: most common, artery of sudden death, infarction in ant aspect. Ant chest lead ECG changes

Remember there are anatomical variations Time scale: 1. In first 24hrs no much to see: at 6hrs may be ECG changes but no gross or histological features. On EM may see swollen mitochondria 2. Over 24hrs: inflammatory reaction at edges, myocytes will lose striations (seen in light microscopy) 3. Several days to weeks: dead myocytes removed by macrophages, after weeks healing by repair, organisation +progressive fibrosis leading to formation of fibrous scar tissue 4. Several months: scar will mature + be akinetic segment. May be weak + deffo wont contract Complications: DARTH VADER: Death, arrhythmias, rupture, tamponade, heart failure Valve disease, aneurysm of ventricle, dresslers, embolism, recurrence Complication Sudden death Arrhythmias Angina Cardiac failure Mitral incompetence (may contribute to cardiac failure) Pericarditis

Interval Within hours First few days Variable Variable Any time

Mechanism Arrhythmias – often VF Damage to conducting system Ischaemia Muscle necrosis and arrhythmias Papillary muscle damage

2-4 days

Transmural infarct with pericardial inflam (manifests as chest pain + assoc with heart

Cardiac rupture – likely to cause acute death Mural thrombosis Ventricular aneurysm

3-5 days

Dresslers syndrome – c

Late

1 week or more Late

Myocardial rupture: - early - mechanism = muscle necrosis plus acute inflam - mycomalacia cordis - where = ventricle wall to give acute haemopericardium (and usually sudden death), septum to give left to right shunt, papillary muscle to give mitral incompetence    -

failure) Wall weakening following muscle necrosis (and removal of damaged tissue by macrophages) + acute inflam Ischaemia + endothelial damage Muscle necrosis due to scar tissue + or arrhythmia ProAutoimmune

Ventricular Aneurysm: - late - mechanism = dilation of fibrous scar - effects = dyskinetic segment, heart failure, mural thrombosis (and all its complications)

Treatment can prolong life + improve quality Lifestyle changes + cholesterol reduction Long term prognosis depends on no. of key factors: Age Extent of coronary artery disease Severity of symptoms Pumping ability of heart

Hypertension Arterial BP is measure of force exerted on arterial walls by circulating blood. Traditionally measured in right brachial artery in upper arm. Usually measured in mmHg (could be pascals, atmospheres, torr) Methods of measuring BP:    

Ambulatory BP monitoring – most accurate: wear cuff for 24 hours and BP measured on several occassion Home BP monitoring Clinic BP measurement Shopping centre measurement

Diagnostic threshold:

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Systolic 140mmHg and Diastolic 90 mmHg Cut off points appropriate and vary depending on method of measurement. Always check latest guidelines

Major risk factor for stroke, MI, HF, chronic kidney disease, cog decline and premature death Untreated can cause vascular and renal damage leading to treatment resistant state. Been estimated that 2mmHg rise in systolic is associated with increased risk of mortality from heart disease (7%) and stroke (10%) 25% adults in UK have it. 50% over 60 have it, with ageing pop prevalence increasing Causes: 1. Primary/essential: 90% all cases. No single (organic) physical cause but there are no. of risk factors. Risk factors: - Old age - Fam history - African or Caribbean origin - High amount of salt in food - Lack of exercise - Overweight - Smoking - Excess alcohol - Stress - Urban dwelling 2. Secondary: Specific cause can be identified - Renal:  Parenchymal: substance of kidney  Diabetic nephropathy  Chronic glomerulonephritis – AI chronic inflame of renal glomeruli  Polycystic kidney disease – genetic disease: multiple cysts in kidney  Chronic tubulointerstitial nephritis – chronic inflam of tubules and tissue between tubules (interstitium)  Hypertensive renal disease (result of hypertension)  renovascular disease:  renal artery stenosis – decrease in blood flow through one or both of main renal arteries or their branches  stenosis usually due to: o atherosclerosis: 90% cases. Primarily in patients >50 (more often men). Effects aortic orifice or proximal segment of renal artery. Chronic progressive stenosis tends to become clinically evident after 10yr atherosclerosis = renal atrophy and chronic kidney disease

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o fibromuscular dysplasia (not like precancer) – pathological thickening arterial wall most often distal main renal artery or intrarenal branches o younger adults = women 20-50 chronic progressive stenosis causes refractory hypertension and may lead to chronic kidney disease diagnosis by imaging

 Endocrine: Adrenal cortex:  High Aldosterone – aldosteronoma (benign tumour of adrenal gland)  High cortisol – Cushings (once symptomatic): o Ectopic ACTH due to lung cancer o Pituitary microadenoma (benign) o Adrenal adenoma (benign) o Meds (corticosteroids) Adrenal medulla:  High (nor)adrenaline – phaeochromocytoma (tumour of adrenal gland medullar – maj of cases are benign but small no. are malignant, hard to differentiate between benign and malignant) - Coarctation of aorta: congenital narrowing of aorta. Reduced blood flow to lower half of body = high BP in arms and low in the lower half of body. - Meds – NSAIDs, oral contraception, steroids - Pregnancy -

Clinical manifestation: target order complications 1. CVS 

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LVH – symmetrical = concentric (asymmetrical LVH in hypertrophic cardiomyopathy – unrelated to hypertension. Genetic disease and can cause sudden death in young adults) Atherosclerosis – asymmetrical narrowing of the lumen of larger vessels bu lipid accumulation in the intima Arteriosclerosis – symmetrical narrowing of lumen of smaller vessels by deposition of protein within wall of blood vessels Haemorrhagic stroke: often results from rupture of small cerebral microaneurysm that have been weakened, primarily by chronic arterial hypertension

2. Kidneys: hypertensive nephrosclerosis  Benign hypertensive arteriolar nephrosclerosis is progressive renal impairment caused by chronic poorly controlled hypertension  Benign hypertensive arteriolar nephrosclerosis results when chronic hypertension damages small blood vessels, glomeruli, renal tubules and interstitial tissues  Can result in progressive chronic kidney disease 3. Retina: hypertensive retinopathy  In Long term or v severe high BP  Thickened BV walls  reduced blood flow  ischaemia and infarction Mechanisms 1. Damaged blood vessels  bleeding 2. Loss of vision Valve Disease Rheumatic fever – virtually extinct in developed countries (v unlikely to encounter it in this country) but still remains in 3rd world (esp in subtropic regions and assoc with socioeconomic factors such as overcrowding). Occurs most freq in kids due to throat infection with group A haemolytic streptococci. Latency period of 2-6 wks before symptoms develop. Diagnostic criteria: 

Major Carditis Polyarthritis Sydenham’s chorea Erythema marginatum Subcut nodules  Minor - Fever - Arthralgia - Lab abnormalities eg raised CRP -

ECG abnormalities: prolonged PR interval Evidence of strep infection

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Pathogenesis: molecular mimicry – immunological cross reaction to components of bacterial wall and structural components of heart muscle. Not direct bacterial infection of heart. Hallmark = pancarditis. Present with pleural effusion and fibrous pericarditis which manifest as audible rub may develop myocarditis which involves lesion know as aschoff body (central core of collagen surrounded by giant cells. Bordered by peculiar cells with long bar of central chromatic called antischkow cells form in pericardium of hear and in perivascular distribution) – many will develop endocarditis. Swollen valves infiltrated by inflammatory cells and small vegetations on valve leaflets. Valvular heart disease:   -

Stenosis Thickened and/or calcified Obstruction to flow Incompetence Also called regurg or insufficiency Lose normal function and leak

(mitral valve disease produces a combo of the 2) Causes: 

Age related changes: - Calcification - Functional changes  Rheumatic fever  Floppy valves  Congenital defects  Infective endocarditis  Miscellaneous

Aortic: 

Stenosis - Causes  Calcific degeneration  Rheumatic fever  Bicuspid aortic valve (at birth) - Complications  LVH  Angina  Syncope  LV failure

 Sudden death  incompetence - causes  aortic root dilatation = pulls cusps apart  valve regurgitation  rheumatic valve disease Mitral:  -

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stenosis: causes:  rheumatic fever complications  pulm hypertension  left atrial and right ventricular hypertrophy incompetence causes  floppy valve o mitral valve leaflet expanded = balloons and projects back into left atrium o causes regurg jet of blood from left ventricle into left atrium – dilates left atrium dilates and can cause AF o due to myxoid degeneration of substance of valve leaflet  rheumatic fever  dilated mitral valve annulus  papillary muscle dysfunction Complications  Diverse effects

Infective endocarditis: microorganism invades the bloodstream and settles on thrombus in the valves leaflet = vegetation *acute or chronic disease resulting from infection of focal area of endocardium* usually over heart valve, may involve endocardial surface of atrium or ventricle or intimal surface of aorta or a congenital defect (eg VSD) Classified by causative organsism. Although uncommon it is life threatening condition of great importance! Where do organisms come from: anywhere     

Oropharynx: streptococci veridans (dental procedures) Skin: staph A coagulase -ve (cannulation and surgery) GIT: gram -ve or enterococci (endoscopy) UG tract: same as GIT (cystoscopy and prostatectomy) IV drug abuse: wide range including pseudomonas and fungi

Vegetations: friable mass of varying size on valves. Contain relevant organisms. Mix of organisms, platelets, fibrin and inflame cells. Organisms plus assoc inflame and repair events may seriously damage the valve and promote: altered haemodynamics and thrombosis (virchows triad) Predisposing factors:    

Structural cardiac abnormalities – esp due to regurg flow thr...