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ACP > CVS Pathology > Flashcards

CVS Pathology Flashcards

1
Q

Definition of Atherosclerosis

A
  1. Focal accumulation of lipids and proliferation of smooth muscle cells
  2. within the tunica intima of
  3. elastic, large and medium sized arteries
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2
Q

**Stages of Morphology of Atherosclerosis - features of fatty streaks, atheromatous plaque and complicated atheroma

A
  1. Fatty Streaks
    - linear, slightly raised yellow deposits within INTIMA
    - initial accumulation of cholesterol-laden macrophages
    (in virtually all children >10)
  2. Atheromatous Plaque
    - raised, localised lesion within intima
    - central necrotic core (cell debris, cholesteryl esters, foam cells) + overlying fibrous cap
    - main components:
    - - cell –> smooth muscle cells, foam cells (lipid-laden macrophages and SMC), T cells
    - - ECM (scar/chronic inflammation) –> collagen, elastic fibers, proteoglycans
    - - lipids –> intracellular and extracellular
  3. Complicated Atheroma
    - unstable plaque (thinner fibrous cap, larger lipid core, increase inflammation)
    - -> acute plaque changes: rupture/    ulceration inducing *thrombus formation and occlusion or haemorrhage into plaque which expands volume
    - -> atheroembolism: debris from ruptured plaque forming microemboli
    - -> aneurysm: pressure or ischaemic atrophy of intima causing structural weakening
    - -> *calcification
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3
Q

Risk factors for Atherosclerosis: non-modifiable (4), modifiable (5), uncertain (5)

A

Non-modifiable:
- age, male gender, post-menopausal female, **family history, genetic abnormalities

Modifiable:

  • hyperlipidemia, HT, DM
  • smoking
  • CRP

Uncertain/ additional risks:

  • obesity, metabolic syndrome
  • physical inactivity
  • stress (Type A personality)
  • high carb and trans-fat diet
  • chlamydia pneumoniae infection
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4
Q

Response-to-Injury Hypothesis of Atherosclerosis (6)

A
  1. Chronic endothelial injury e.g. HT, Hyperlipidemia, Smoking, Toxins, Viruses, Haemodynamic factors etc.
  2. Endothelial Dysfunction with increased permeability, platelet adhesion, monocyte adhesion and emigration into intima, (and leukocyte adhesion/ lipid insudation)
  3. Macrophages migrate to subendothelial space with proliferation of monocytes in response to chemotactic factors; macrophages ingest oxidised LDL –> foam cells
  4. Production of cytokines (IL-1, TNF) and growth factors (PDGF, FGF) from platelet adhesion, endothelial dysfunction and macrophages –> smooth muscle proliferation and migration from media to intima
  5. SMC and macrophages release further cytokines to elaborate and remodel ECM (collagen, elastin, proteoglycan)

–> SMC proliferation and ECM deposition are the major processes that convert fatty streak into a mature fibrofatty atheroma and account for progressive growth

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5
Q

Acute Plaque Changes: clinical significance, examples (3)

A

Clinical importance as they lead to increase in luminal obstruction

Rupture/ Fissuring
- exposing highly thrombogenic plaque constituents

Erosion/ Ulceration
- exposing thrombogenic subendothelial basement membrane to the blood

Haemorrhage into atheroma
- expanding its volume

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6
Q

Clinical Manifestations of Atherosclerosis: which organs, consequences (4)

A

In organs with rich blood supply, high level of oxygen demand during activity and large arteries

  • ischaemia (occlusion of vessels – claudication, chronic diabetic foot, AMI etc)
  • infarction
  • thromboembolism (debris from ruptured plaque become microemboli)
  • aneurysm (pressure or ischaemic atrophy of intima leading to loss of elastic tissue and structural weakening)
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7
Q

Hypertension definition, changes with age, cut-offs

A

Raised pressure in a vascular bed (systemic, pulmonary or portal)

  • bp increases with age, lower in pre-menopausal women but catches up and exceeds men in post-menopause
  • different criteria for different societies – around 130/80
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8
Q

Classification of Hypertension: primary vs secondary (prevalence and causes), benign vs malignant (definitions and complications)

A

Essential (Primary) HT - 90-95% cases

  • benign (90%)
  • malignant (10%)

Secondary HT

  • benign (80%)
  • malignant (20%)
  • due to renal, endocrine, vascular, neurogenic diseases

Benign = gradual increase in BP
Malignant = rapid elevation of BP, associated with direct end-organ damage (papilledema and retinal haemorrhage)
- may be complicated by LHF, hypertensive encephalopathy, deteriorating renal function

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9
Q

Pathology of Hypertension (benign and malignant)

A

For both benign and malignant HT:
- elastic and large muscular arteries – hypertensive atherosclerosis, aneurysms, acute dissections

  • medium sized muscular arteries – TM hyperplasia and hypertrophy, fibroelastic hyperplasia

Distinguishing features of benign and malignant HT are seen at small arteries and arterioles:

  • Benign
  • -> hyaline arteriosclerosis (ground-glass like, homogenous pink; also in aging and DM)
  • Malignant
  • -> hyperplastic arteriosclerosis (*onion skin like concentric muscular thickening of TM +/- intimal wall thickening with luminal reduction); also in HUS, progressive systemic sclerosis, toxaemia of pregnancy, chronic rejection
  • -> fibrinoid necrosis of arterioles (petechial haemorrhage with flea-bitten appearance)
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10
Q

Morphology of Hypertension - heart (3), kidneys (benign 6, malignant 3), CNS (4)

A

HT mainly affects blood vessels, heart, kidney (c.f. urogenital flashcards), CNS

Heart:

  • CONCENTRIC left ventricular hypertrophy (pressure effect evenly distributed)
  • coronary atherosclerosis (IHD)
  • congestive heart failure

Kidney:
- benign nephrosclerosis –> narrowing of cortex, finely granular cortex with retention cysts, thickening and prominence of interlobular arteries, hyaline arteriosclerosis of renal arterioles, tubular atrophy and glomerular sclerosis

  • malignant NEPHROSCLEROSIS –> petechial haemorrhages, fibrinoid necrosis, HYPERPLASTIC ARTERIOSCLEROSIS

CNS: (more details in CNS lectures)

  • occlusive atherosclerotic vascular disease
  • atheroembolic cerebral infarction
  • lacunae
  • hypertensive ENCEPHALOPATHY
  • CHARCOT-BOURCHARD aneurysm
  • Binswanger’s Disease
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11
Q

**Aneurysm definition and classifications by aetiology (6), risk factors (3), general pathogenesis (3)

A

Definition: localised, permanent dilatation of artery or vein
(pseudo-aneurysm = ruptured vessel wall creating haematoma bound externally by adherent extravascular tissues)

Classification by aetiology:
- atherosclerotic, syphilitic, mycotic, berry, capillary micro-aneurysm (Charcot-Burchard), traumatic (arteriovenous)

Risk factors:

  • atherosclerosis (AAA)
  • HT (ascending aortic aneurysm)
  • weakening vessel wall e.g. vasculitis, trauma, congenital

Pathogenesis (weakened vessel wall):

  • abnormal connective tissue synthesis e.g. Marfan’s
  • excessive connect tissue degradation e.g. MMPs in inflammation disrupting lamellar units
  • loss of SMC: ischaemic due to atherosclerosis (increase diffusion distance) or narrowing of vasa vasorum in HT
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12
Q

Pathogenesis of Aneurysms: atherosclerotic, syphilitic and mycotic

A

Atherosclerotic

  • inflammatory reaction towards intimal atheroma
  • enzymes released from macrophages –> fragmentation of elastic fibres
  • weakening of media
  • common in AAA

Syphilitic

  • infection of vasa vasorum in ascending aorta by treponema pallidum –> vasculitis (endarteritis obliterans with plasma cell infiltrate)
  • ->ischaemic damage to media –> fibrosis and loss of elastic tissue causing weakness and dilatation

Mycotic

  • bacterial or fungal infection with septic embolus, extension of suppuration or direct infection
  • enter media via vasa vasorum to cause weakening of arterial wall
  • mostly affects cerebral arteries (but possible anywhere)
  • IE most common cause
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13
Q

Pathogenesis of aneurysms: berry, capillary micro-aneurysm, traumatic

A

Berry
- congenital defect with fibrous replacement of media
- most frequent type of intracranial aneurysm –> typically at CIRCLE OF WILLIS anterior communicating artery - SAH if rupture
(a/w PKD)

Capillary Micro-aneurysm

  • HT and DM vascular disease
  • segmental weakening and dilatation of vessel walls, commonly at MCA especially lenticular-striate branch
  • precursor of primary hypertensive intracerebral haemorrhage (Charcot-Burchard) usually occurring at basal ganglia, cerebellum, brainstem

Traumatic (arteriovenous)

  • pathological communication between artery and vein secondary to traumatic injury
  • leading to weakening of arterial wall
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14
Q

Classification of aneurysm by shape, location (and likely cause)

A

Berry: small spherical (1-1.5cm)
Saccular: large spherical (5-20cm)
Fusiform: spindle
–> gross descriptions not specific for any disease

Abdominal AA
- HYPERTENSION

Thoracic AA

  • Syphilis, Marfan syndrome, Takayasu arteritis
  • chest mass, AR murmur, LHF
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15
Q

Manifestations of AAA (6)

A
  1. Pulsatile, expansile mass (mostly infrarenal)
  2. Rupture with catastrophic haemorrhage – complication of hypertension –> hypovolemic shock
  3. Pressure effect on adjacent structures e.g. ureter, vertebra
  4. Vascular occlusion through direct effect of atheroma or formation of mural thrombus
  5. Dilatation of aorta root with regurgitation
  6. Thrombo-embolism
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16
Q

Aortic Dissection definition, epidemiology and aetiology (4)

A

Dissection of blood along laminar planes of media due to tear in aortic intima
- formation of blood filled channel within the aortic wall

Epidemiology and Aetiology:

  • **HYPERTENSIVE patient (atherosclerotic)
  • Male, 40-60 years old
  • Abnormality in connective tissue e.g. Marfan’s, Ehler Danlos syndrome
  • rarely in pregnancy (increased risk at 3rd trimester)
  • trauma
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17
Q

Pathology of Aortic Dissection (3)

A

Cystic medial necrosis – prominent loss of elastic fibres with mucinous degeneration

Longitudinal or oblique intimal tear usually occurring within 10cm of aortic valve –> blood can extend distally or retrograde within outer and middle third of media

  • -> intramural haematoma
  • -> “double barrel” appearance
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18
Q

Classification of Aortic Dissection and Complications (4)

A

Stanford Classification (DeBakey no longer used)

Type A:

  • more common
  • ascending aorta +/- descending aorta
  • absent radial pulse (subclavian artery impinged), retrograde dissection into aortic root
  • 75% mortality
  • Tx: surgery, intensive anti-hypertensives

Type B:

  • descending aorta (beyond subclavian artery)
  • 25% mortality
  • Tx: conservative (anti-hypertensive)

Complications:

  • rupture through adventitia – massive haemorrhage in cavities (hemomediastinum) – MC CAUSE OF DEATH
  • cardiac tamponade (hemopericardium) – retrograde extension of dissection
  • ischaemia – extension of dissection in various arteries (MI, ischemic stroke, AKI, ischemic leg)
  • AR
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19
Q

Ischaemic Heart Disease: definition, most common cause, risk factors

A

Reduction or cessation of blood supply to the myocardium leading to an imbalance in myocardial O2 demand and supply from coronary arteries

  • Most common cause is coronary atherosclerosis (CHD)
  • less prevalent in central and South America, Asia and Africa but increasing incident recently

Risk factors:

  • same as those for atherosclerosis (reduce supply)
    • age, sex, hyperlipidemia, DM, smoking, HT etc.
  • ventricular hypertrophy, hyperthyroid (increase demand)
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20
Q

Clinical Manifestations of IHD (3 main categories)

A

Typical/ Stable Angina Pectoris

  • narrowing of vessel causing pain on exertion
  • chronic IHD – progressive HF due to ischaemic injury from prior infarctions or chronic low-grade ischaemie

Angina pectoris is intermittent chest pain due to inadequate perfusion, typically atherosclerotic disease with >70% fixed stenosis

Acute Coronary Syndromes

  • unstable angina pectoris (>90% occlusion) – fissure or rupture of atherosclerotic plaque triggering formation of mural thrombus (not necessarily occlusive); chest pain without exertion
  • non STEMI
  • STEMI – AMI from acute thromboses after plaque disruption, OCCLUSION

Sudden Cardiac Death
- lethal arrhythmias – typically without significant acute myocardial damage

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21
Q

Pathophysiology of IHD (3)

A
  1. Blood supply insufficient for myocardial demand
    - decreased supply – e.g. atherosclerotic obstruction (ischaemic if obstruction >75%), decreased blood volume
    - increased demand – e.g. ventricular hypertrophy, hypertension, tachycardia
  2. High metabolic activity of cardiac muscles
    - reliance on aerobic metabolism (mitochondria >30% volume of myocardial fibres; poor reserve of high energy phosphates) – decreased O2 e.g. pneumonia/ CHF, decreased O2 carrying capacity e.g. anaemia
    - low tissue ATP and accumulation of lactic acid –> cell death –> rapid loss of contractility
  3. Subendocardial myocardium vulnerable to ischaemia
    - last area to receive blood from epicardial coronary arteries
    - subendocardial plexus compressed during systole so flow limited to diastole
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22
Q

Pathogenesis of IHD: atherosclerotic (6), non-atherosclerotic (3), others (1)

A

Coronary Atherosclerosis (most common)

  • acute plaque changes consisting of rupture, ulceration, intra-plaque haemorrhage –> subendothelial collagen and thrombogenic necrotic material exposed
  • platelets adhere and activated
  • platelets aggregate to form micro thrombi (mechanical occlusion) and release TXA2 to induce vasospasm and thrombosis
  • tissue factors activate coagulation cascade to add to thrombus
  • thrombus can expand to occlude vessel within minutes

Non-atherosclerotic (<10%)

  • embolism from vegetations on the aortic or mitral valves, AF (embolisation from mural thrombi)
  • coronary arteritis (vasculitis) e.g. Kawasaki’s disease, polyarteritis nods, giant cell arteritis
  • others e.g. cocaine abuse (spasm), traumatic injury
  • Haemodynamic alterations such as hypotension, shock, tachycardia
23
Q

Acute Myocardial Infarction: *definition, subendocardial vs transmural, macroscopic vs microscopic

A
  • Irreversible ischaemic necrosis of defined area of myocardium due to reduction of myocardial blood supply
  • M>F, increase with age, same risk factors as for atherosclerosis
  • subendocardial (inner 1/3) or transmural (full thickness)

Subendocardial usually due to transient ischaemia, Q wave absent
Transmural usually with chronic atherosclerosis and acute thrombosis, STEMI and Q wave present

  • macroscopic (mostly) vs microscopic
    • microscopic infarcts in the setting of small vessel occlusions that don’t show diagnostic ECG changes (due to non-atherosclerotic causes of occlusion)
24
Q

Coronary circulation of the heart: arteries and their areas of supply (3)

A

Left anterior descending artery - 50% incidence; high mortality

  • anterolateral wall of LV
  • anterior 2/3 of IV septum
  • apex

Left circumflex artery - 20%

  • small area of lateral wall of LV
  • 10% have left dominant supply of PDA

Right coronary artery - 30%

  • 90% have right dominant supply of PDA (supply AV node)
  • posterior wall of LV - PDA
  • posterior 1/3 of IV septum - PDA
  • RV

Filled with blood in diastole; tachycardia reduces filling time –> predispose to ischaemia
Collateral perfusion may develop if occlusion occurs at sufficiently slow rate –> if this collateral supply is occluded then can cause infarct!

25
Q

Progression of myocardial necrosis: first site, “at risk” area, earliest detectable feature

A

Necrosis begins in myocardium beneath endocardial surface i.e. subendocardium (coronary arteries run an epicardial course) –> wavefront of cell death move through myocardium with extended ischaemia

Area that depends on occluded vessel = “at risk” myocardium

The very narrow zone of myocardium immediately beneath endocardium is spared because it can be oxygenated by diffusion from ventricle

Earliest detectable feature of myocyte necrosis is disruption of sarcolemmal membrane –> leakage of intracellular macromolecules –> basis of blood tests to detect irreversible myocyte damage

26
Q

Pathology of AMI: first 4 hours

A

Following occlusion, contractile function is lost within 2 minutes as aerobic metabolism ceases and lactic acid accumulates (ultrastructural changes e.g. glycogen depletion, cellular and mitochondrial swelling)

***Gross changes not apparent for the first 12 hrs
Microscopic changes not apparent until 12-18 hrs

<30 minutes

  • reversible ischaemia
  • histology: normal
  • clinically: angina relieved by nitroglycerin, fast and weak pulse, sweating, ST depression, cardiac enzymes normal

> 30 minutes

  • irreversible ischaemia
  • histology: wavy fibres at edges of infarct
  • clinically: AMI, chest pain not received by nitroglycerin, ST elevation, cardiac enzymes elevated

1 hr

  • histology: edema
  • clinically: cardiogenic shock (if massive >40% infarcted) –> hypotension and dyspnea due to pulmonary edema; sudden cardiac death

4 hrs

  • triphenyl tetrazolium chloride (TTC) fails to stain infarcted myocardium because of LDH leakage –> area of infarct unstained and old scars appear white and glistening
  • histology: typical features of coagulative necrosis
27
Q

Pathology of AMI: from 12 hrs

A

12 hrs

  • grossly: myocardial mottling (red-blue discolouration) because of trapped blood
  • histology: pyknosis, karyorrhexis, myocyte HYPEREOSINOPHILIA, loss of cytoplasmic cross striations

1 day
- histology: neutrophil infiltration (acute inflammation)

3-7 days:

  • grossly: pale firm well defined region with hyperaemic rim
  • histology: inflammatory infiltrates (neutrophils peak at 5-6 days), macrophages and granulation tissue first appear at margins on day 4
  • clinically: ventricular rupture –> haemopericardium –> cardiac tamponade –> papillary muscle tear –> mitral regurgitation with new murmur

7 days
- histology: macrophage infiltration

2 weeks

  • grossly: yellow, soft, sunken area with red-purple hyperaemic rim (progressive replacement by granulation tissue) by day 10
  • histology: fibrosis, compensatory myocyte hypertrophy

2 months
- gross: scarring complete – thin firm greyish white dense fibrous tissue –> unable to distinguish age of scar
(healing occurs from borders towards the centre as it requires migration of inflammatory cells and ingrowth of new vessels from margins)

28
Q

Clinical Course of AMI (3), causes of sudden cardiac death (4), ***complications of AMI (8)

A 
Sudden cardiac death (arrhythmia, cardiogenic shock, thromboembolism (cerebral), ventricular rupture)
Uncomplicated cases (10%)
Complicated cases (90%)

Heart conduction:
- lethal arrhythmias most common - 75% cases (VF as most common cause of SUDDEN CARDIAC DEATH)

Cardiac muscle/wall:

  • progressive LVHF with pulmonary oedema (remaining viable muscles have increased workload - chronic IHD) - 60%
  • cardiogenic shock - 10%
  • ventricular rupture causing haemopericardium and cardiac tamponade

Pericardium:

  • pericarditis
  • Dressler’s syndrome (post-infarction fever, pericarditis, pleurisy, pneumonitis due to auto Ab against damaged pericardial Ag - Type II HSR or viral infection; can occur between 10 days to 2 years post MI) - 1-4%

Blood:
- thromboembolism (reduced contractility causing stasis and endocardial damage exposing thrombogenic surface) - up to 40%

Papillary muscle:
- papillary muscle/chordae tendinae rupture (acute mitral regurgitation –> acute heart failure) - 1-5%

(SUDDEN DEATH: arrhythmia, cardiogenic shock, tamponade, papillary muscle rupture
Ineffective pumping: mural thrombus and embolism
Healing: pericarditis, ventricular dilation and aneurysm, progressive HF)

29
Q

Reperfusion in AMI: definition, ideal timing, earliest detectable feature of myocyte necrosis, recovery

A

Restoration of blood flow to ischaemic myocardium by coronary interventions e.g. thrombolysis, angiplasty, stent placement, CABG

Myocardial injury is potentially reversible for 30 minutes after onset –> need rapid diagnosis to permit early intervention and salvage as much “at risk” myocardium as possible
- greater chance if within 3 hrs

Restoration of flow can prevent some necrosis and retain some function but return of function to the myocardium may be delayed for hours to days (post-ischaemic ventricular dysfunction/ stunning with persisting biochemical abnormalities) and reperfusion injury may occur

30
Q

Reperfusion Injury: 5 mechanisms, morphology (2)

A
  • haemorrhage due to leakage through damaged vessels (accounts for >50% of ultimate infarct size)
  • endothelial swelling and leukocyte aggregation occluding capillaries and limiting reperfusion of critically injured myocardium (“no-reflow”)
  • *oxidative stress – free radicals from leukocytes and endothelial cells accumulate (cellular antioxidant mechanism compromised by ischaemia)
  • *Ca overload – impaired Ca cycling and depletion of ATP
  • mitochondrial dysfunction – increase permeability to proteins leading to swelling and rupture –> release mitochondrial components that promote apoptosis
  • local activation of complement by IgM Ab deposited in ischaemic tissues (increase inflammation and injury)

Pathology:

  • Grossly – haemorrhagic infarcts due to injured vasculature
  • Histology – CONTRACTION BANDS (intensely eosinophilic intracellular stripes) from myocyte sarcomere hyper contraction when exposed to Ca from plasma (and absence of ATP to initiate relaxation) –> altered morphology
31
Q

Chronic Ischaemic Heart Disease: definition, associations, causes of death (3)

A

Progressive congestive heart failure secondary to long term ischaemic myocardial injury

  • a/w history of angina (stable) +/- MI
  • insidious development as compensatory mechanisms of heart begin to fail

Morphology:

  • LV dilation and hypertrophy
  • evidence of scarring from previous infarcts
  • patchy fibrous thickening of endothelium
  • histology: myocardial hypertrophy, diffuse subendocardial myocyte vacuolisation (sublethal ischemic injury), fibrosis

Causes of death;

  • arrhythmia
  • congestive HF
  • AMI
32
Q

Sudden Cardiac Death: definition, causes (4), mechanism of death (1)

A

Unexpected death within 1 hour of onset of cardiac symptoms or from cardiac causes without symptoms

IHD most common cause
Other causes: myocardial disease (myocarditis, cardiomyopathy causing LHF and cardiogenic shock), valvular disease (MV prolapse and papillary muscle rupture), conduction system abnormalities (VT/VF cause ischemia), thromboembolism from MI

Most common mechanism of death = VF e.g. triggered by myocardial ischaemia induced irritability

33
Q

Myocarditis definition and aetiologies (3 main categories)

A

Non-ischaemic myocardial inflammation resulting in injury to myocardial fibres

Aetiology:

  • Infections – **viral most common e.g. Coxsackie virus, influenza; chlamydia, corynebacterium, candida etc
  • Immune – post-infectious e.g. post-viral, post-streptococcal acute rheumatic fever; SLE, drug HSR e.g. methyldopa, transplant rejection
  • Unknown – sarcoidosis, giant cell arteritis
34
Q

Myocarditis Pathology: 3 phases

A

Pathology:
Acute Phase –
- grossly: dilated heart; flabby, pale myocardium with small areas of haemorrhages
- mononuclear infiltrates (LYMPHOCYTES) and histiocytes, congestion
- direct destruction of cardiomyocytes by virus-mediated lysis –> OEDEMATOUS myocardium, myocardial fibre necrosis

Subacute Phase –
- immune dysregulation with molecular mimicry between viral and cardiac Ag

Chronic Phase –
- development of dilated cardiomyopathy
with marked ventricular dilatation due to extensive myocardial injury
- diffuse pericellular myocardial fibrosis

(Other variant: hypersensitivity myocarditis, giant cell myocarditis, chagas myocarditis)

35
Q

Myocarditis Clinical Manifestations (5) and Outcomes (3)

A

Typically young, hx of flu/ viral infection
Dyspnea (most common), chest pain, fever, persistent tachycardia and palpitations, congestive heart failure

Outcomes:

  • self-limiting with complete resolution
  • progressive deterioration to dilated cardiomyopathy
  • death or cardiac transplantation (in cases of intractable heart failure, arrhythmias)
36
Q

*Cardiomyopathy definition

A

Heart diseases resulting from a primary abnormality in myocardium

Excluding heart disease due to CAD, IHD, HT, myocarditis, valvular disease etc. (all secondary)

37
Q

Dilated and *Hypertrophic Cardiomyopathies: definition, LVEF, causes, histology features, clinical outcomes

A

Dilated/ Congestive Cardiomyopathy (most common - 90%)

  • progressive cardiac dilation and contractile dysfunction
  • LVEF <40%
  • causes: genetic (20-50%), alcohol (direct toxicity and decrease thiamine), haemochromatosis, drug doxorubicin
  • histology (non-specific): interstitial thrombosis, intracardiac mural thrombi, myocyte hypertrophy
  • Hypertrophic Cardiomyopathy
  • MC cause of death in young athletes
  • asymmetric (eccentric) marked hypertrophy of IVS relative to LV/RV (IVS>LV/RV) and diastolic dysfunction
  • left ventricular outflow tract obstruction in 1/3 due to systolic anterior motion of mitral valve (HOCM)
  • LVEF 50-80%
  • histology: characteristic myocardial fibre DISARRAY (causing myocyte hypercontractilty –> unable to relax); interstitial fibrosis, LV outflow tract plaque (anterior MV leaflet contacts septum during systole), thickened septal vessels
  • causes: genetic (100%)

Genetic defect in dilated cardiomyopathy involving proteins of cytoskeleton pre-dominantly vs. genetic defects in hypertrophic cardiomyopathy encode proteins of sarcomere

Clinical complications:

  • progressive heart failure
  • sudden death
  • AF, arrhythmias
  • stroke
38
Q

Restrictive and Arrhythmogenic Cardiomyopathies: definition, LVEF, causes

A

Restrictive Cardiomyopathy (least common)

  • primary diastolic dysfunction due to reduced compliance (with decreased filling of ventricles and dilation of atria)
  • LVEF 45-90%
  • causes: amyloidosis (most common), radiation-induced interstitial fibrosis, idiopathic

Arrhythmogenic RV Cardiomyopathy

  • progressive fibroadipose replacement of ventricular myocardium causing severely thinned RV wall
  • inherited AD, with variable penetrance
  • primarily in young
  • RVF and various arrhythmias, especially V-tach and VF
39
Q

Hypertensive Heart Disease: 2 types, causes, manifestations, pathology (3)

A

Systemic

  • left sided
  • due to chronic pressure overload
  • concentric LVH –> can decrease diastolic filling with time –> LA dilation
  • dilation if CHF develops with volume overload in late stage
  • pathology: transverse diameter of myocytes is increased, prominent nuclear enlargement and hyperchromasia (boxcar nuclei), intercellular fibrosis

Cor pulmonale

  • right sided
  • due to pulmonary HT
  • acute: RV dilation (develops faster than hypertrophy)
  • chronic: RV hypertrophy + dilation (if ventricular failure develops)
  • atheromatous plaques in pulmonary arteries

Morphology of Hypertension: Concentric ventricular hypertrophy, coronary atherosclerosis, CHF

40
Q

Ventricular Hypertrophy

A

Concentric

  • sarcomeres duplicate in parallel to long axis
  • mechanism = increase afterload
  • causes: HT, AS, (10% HCM c.f. asymmetric)

Eccentric

  • sarcomeres duplicate in series
  • mechanism = increase preload
  • causes:
    • LVH – MR, AR, left-to-right shunt e.g. VSD
    • RVH – TR, PR
41
Q

Pericarditis: aetiologies (5), pathology (2), presentation (4), treatment (2)

A

Inflammation of pericardium

Aetiology:

  • idiopathic (most common)
  • infection – similar to pathogens that cause myocarditis
  • drugs – similar to myocarditis e.g. methyldopa
  • uraemia
  • malignancy – lung most common, breast

Pathology:

  • fibrinous inflammation with pericardial effusion
  • dense scar tissue with dystrophic calcification –> constrictive pericarditis (most commonly due to TB, previous open-heart surgery)

Presentation:

  • fever, tachycardia
  • chest pain, relieved on leaning forward
  • pericardial friction rub
  • pericardial effusion (muffled heart sound, Kussmaul sign, pulsus paradoxus)

Treatment:

  • underlying cause
  • pericardiocentesis (if there is effusion)
42
Q

Normal anatomy of heart valves: function, anatomy of types of valves, mechanism for ensuring efficient flow

A

Function: unidirectional blood flow (open with appropriate caliber, competent)

AV valves

  • leaflets with attachment to ventricle via tendinous cords and papillary muscles
  • mechanism: papillary muscle contraction during systole; total area of leaflets > orifice with overlap during systole

Semilunar valves

  • 3 leaflets attaching to ventricle-arterial junction (in an arc)
  • mechanism: semilunar cusps with arc shape attachment –> act as hanging basket to hold blood and allow time for blood to flow into coronary arteries; total area of leaflets > orifice
43
Q

Abnormal functions of heart valves and mechanisms

A

Stenosis (causing hypertrophy) and regurgitation (causing dilatation - congestive - and hypertrophy)

Mechanisms of stenosis:

  • fusion of commissure
  • thickening of leaflets (fibrosis/calcification)

Mechanisms of regurgitation:

  • abnormality of annulus – dilation
  • abnormality of leaflet e.g. cusp retraction (fibrosis) or expansion (myxoid change), cusp perforation/ destruction (IE)
  • abnormality of tendinous cord e.g. chordal shortening/ lengthening/ rupture
  • abnormality of papillary muscle – dysfunction (ischaemia/ infarction)
44
Q

Common causes of specific heart valve dysfunctions, 4 main aetiologies

A

MS and AS

  • fusion of commissure due to post-inflammatory scarring: RF
  • degenerative calcification of AS

MR

  • leaflet abnormalities: RF, IE, MV prolapse
  • tensor apparatus abnormalities: papillary muscle or tendinous cord rupture
  • LV/annulus abnormalities: myocarditis, DCM, mitral ring calcification

AR

  • leaflet abnormalities: RF, bicuspid AV
  • tensor apparatus abnormalities: degenerative aortic root dilation
  • aortic diseases: Marfan, RA, ankylosing spondylitis

4 main aetiologies of heart valve diseases:

  • congenital
  • degenerative
  • post-inflammatory
  • post-infective
45
Q

Congenital Heart Valve Disease: prevalence, cause, effects, associations, complications (3)

A

Bicuspid AV

  • 1-2% normal population at birth
  • may be familial
  • aortic root enlargement at commissural and supra-aortic levels
  • a/w coarctation (narrowing) of aorta, patent ductus arteriosus, ventricular septal defect

complicated by predisposition to late degenerative changes:
- AR, AS, IE

46
Q

Degenerative Heart Valve Disease: Aortic sclerosis – definition, pathogenesis (2), complications

A

Senile calcific aortic sclerosis

  • calcific deposits within aortic cusps and aortic sinuses (not involving free edges)
  • may extend to anterior mitral leaflet occasionally (usually normal)
  • pathogenesis: degenerative wear and tear + dystrophic calcification
  • pathogenesis: chronic injury by hyperlipidemia, HT, inflammation etc.
  • sequelae and complications: AS
47
Q

Degenerative Heart Valve Disease: Mitral valve prolapse – definition, pathology, associated conditions (4), complications (6)

A

Systolic prolapse of mitral leaflet >2mm into left atrium above the annulus plane – “floppy” valve
+/- resulting MR
F>M 7:1

Pathology:

  • a primary form of myxomatous degeneration (deposition of mucoid onto MV) –> ballooning leaflets enlarged, thick; tendinous cords elongated
  • histology: thinning of fibrosa layer of valve with expansion of middle spongiosa layer due to mucoid material
  • concomitant tricuspid lesion in 20-40%

Associated conditions: (connective tissue disorders)
- Marfan’s syndrome, osteogenesis imperfecta, ASD, pulmonary emphysema, cystic medial necrosis of aorta

Sequelae and Complications:

  • MR, IE –> rupture tendinous cord
  • Lambl’s papillary excrescences (small thrombi formed endocardial surfaces at valve contact margins, may embolise)
  • small platelet thrombi at sites of cusp contact –> retinal embolisation and stroke
48
Q

Mitral ring annular calcification: appearance, site, complications

A

Horseshoe shaped calcified ridge on ventricular surface of mitral valve
- calcific deposits in angle between leaflets and ventricular wall (incorporating chordal attachments on leaflets)

sequelae and complications:
- generally does not affect valvular function unless severe –> MR due to immobilisation, MS, conduction disturbance due to impingement of AV node

49
Q

Post-inflammatory Valve Disease: Acute Rheumatic Fever - *definition (3), pathogenesis and pathology (5), presentation of carditis (6)

A

Acute, *immunologically mediated *multi-system disease *secondary to group A streptococcal pharyngitis

  • 3% of infections (genetic susceptibility)
  • most often in children

Pathogenesis:

  • Type II HSR: Ab against M proteins of streptococci cross react with tissue glycoprotein in the heart, joint and other tissues
  • -> onset of symptoms 2-3 weeks after infection
  • -> absence of bacteria in lesions

Pathology:

  • exudative and inflammatory response affecting connective tissue and basement membrane
  • early phase: fibrinoid necrosis, oedema of connective tissue, increase in acid mucopolysaccharide
  • intermediate phase: ASCHOFF BODIES (fibrinoid necrosis surrounded by T cells, plasma cells and histiocytes)
  • late phase: organisation and fibrosis

Carditis –> Pancarditis

  • Aschoff bodies in all 3 layers of the heart
  • myocardium with diffuse interstitial inflammatory infiltrates with scattered Aschoff bodies
  • Endocardium with fibrinoid necrosis and fibrin deposition along lines of closure –> fibrous thickening (McCallum’s Patch) –> form 1-2mm verrucous vegetations with no bacteria (valvulitis)
  • pericardium with fibrinous pericarditis (exudate) and effusion
50
Q

Acute Rheumatic Fever Diagnosis, complications (6), prognosis, causes of death

A

Diagnosis – JONES’ CRITERIA
- Major: carditis, migratory polyarthritis, chorea, erythema marginatum, subcutaneous nodules

  • Minor: fever, arthralgia, previous RF, increase acute phase reactants (ESR/CRP/WBC), prolonged PR interval on ECG

Dx = 2 major OR 1 major + 2 minor
with evidence of preceding streptococcal infection e.g. increase ASOT, +ve throat culture, recent scarlet fever

Clinical presentations: as in Jones’

Sequelae and Complications:

  • chronic rheumatic heart disease
  • –> accumulation of previous inflammation and scarring - replace Aschoff bodies - causing irreversible deformity of valves
  • –> leaflet thickening, commissural fusion and shortening, thickening and fusion of chordae tendinae
  • –> stenosis (buttonhole) > regurgitation – mainly affect mitral valve
  • –> pressure or volume overload – increases predisposition to IE
  • -> LA pressure overload in MS leads to dilation which precipitates AF –> increase formation of large mural thrombi and also eventually leads to CHF
  • adhesive pericarditis

Prognosis and Causes of Death

  • poor prognosis if significant murmur, cardiomegaly, CHF; previous repeated episodes
  • main causes of death: cardiac failure, subacute IE, thromboembolism (mural thrombi or septic emboli)

Treatment:

  • Penicillin/Erythromycin x10 days
  • Prednisone if severe carditis
51
Q

Post-infective Valve Disease: Infective Endocarditis - causes, types (2), pathogenesis (2), pathology (5)

A

Microbial invasion and implantation on heart valves

  • acute = infection of previously normal valve by high virulence org e.g. s. aureus – high moratity
  • 50-60% subacute = infection of previously damaged valve by lower virulence org e.g. s. viridans – insidious, good recovery
    (s. aureus can attacked damaged valves too)

Pathogenesis:
- transient bacteraemia –> tooth brushing, dental extraction, IVDA, manipulation of genitourinary tract
- underlying heart lesion –> valvular disease, high pressure shunts within heart, valvular replacements
(turbulent blood flow damages valve –> fibrin and platelet adhere –> trap circulating micro-organism –> fibrin encases vegetation)

Heart valves are avascular so infection is difficult to treat!!

Pathology:
Acute IE
- bulky friable lesions (yellow) containing fibrin, micro-organisms and inflammatory cells
- destruction of valves, rupture of chordae tendinae and papillary muscles
- erode into myocardium –> ring abscess
- shedding of emboli with formation of micro-abscess where they lodge –> septic infarcts

Subacute IE

  • more firm vegetation, less valve destruction and myocardium involvement
  • chronic inflammation, granulation tissue at base, fibrosis, calcification
52
Q

Infective Endocarditis Diagnosis and reasons for rejecting IE Dx (3)

A

Diagnosis: DUKE CRITERIA
Pathologic criteria: (either +ve = definite)
- +ve micro-organisms in a vegetation
or
- pathologic lesions (histological confirmation of active infection)

Major clinical criteria: (both+ve = definitive)

  • blood culture positive x2 (for typical pathogens e.g. viridians strep, s. aureus, enterococci)
  • ECHO +ve for endocardial involvement (oscillating intracardiac mass on valve, abscess, new partial dehiscence of prosthetic valve) or new valvular lesion

Minor clinical criteria:

  • predisposing heart condition or IVDA
  • fever >38 celsius
  • vascular: Janeway lesions, conjunctival haemorrhage, major arterial emboli, mycotic aneurysm, septic pulmonary infarcts
  • immunologic: Osler’s nodes, Roth’s spot, rheumatoid factor, GN
  • microbiological: +ve blood culture but not meeting major criteria
  • ECHO: consistent with IE but not major criteria

Definitie IE

  • either pathologic criteria
  • 2 major criteria or 1 major + 3 minor or 5 minor

Possible IE
- 1 major + 1 minor or 3 minor

Rejected IE

  • firm alternate diagnosis for manifestations
  • resolution of manifestations with antibiotic therapy for <4 days
  • no pathologic evidence of IE at surgery or autopsy
53
Q

Infective Endocarditis Clinical Manifestations (4), prognosis and complications

A

Constitutional symptoms due to continuos bacteraemia

  • low grade fever, malaise, weight loss (low virulence)
  • high fever, chills, septicaemia (acute IE)

Cardiac Manifestations
- changing murmur, heart failure, heart block, arrhythmias

Septic embolisation

  • systemic e.g. kidney, spleen, blood vessels, brain
  • pulmonary

Circulating Immune complex deposition

  • cutaneous – splinter haemorrhage, Janeway lesions (painless, haemorrhagic), petechiae, Osler’s nodes (red, raised, tender nodules), Roth spots
  • renal – GN

Prognosis depends on infecting organisms and complications

  • s. viridians 98% recovery with antibiotics
  • s. aureus and enterococci 60-90%

Complications with poor prognosis
- GN, septicemia, arrhythmias, systemic embolisation

54
Q

Heart Failure: cause, DDx, compensation and decompensation, LHF causes and consequences, RHF causes and consequences, histologies

A

Can be caused by both systolic and diastolic dysfunction
Ddx: liver disease, renal failure, thyroid diseases, anaemia

Frank starling –> increase EDV –> dilate heart and increase fibre stretching –> contract more forcibly to compensate for dysfunction –> compensated HF

Dilation increases wall tension and O2 demand unable to meet body demands –> papillary muscle dysfunction, mitral regurgitation, LA dilation –> decompensation

LHF

  • MC due to IHD/CHD, HT, AV/MV disease, cardiomyopathy
  • LVH and dilation, myoctype hypertrophy
  • IHD causes HF by infarction (decrease contractility and CO), longer term hypertrophy (altered interstitial matrix and arrhythmia), ischaemia (hypocontractile myocardium decreasing systolic function) – vice versa: HF can exacerbate ACS as cardiomegaly increase O2 demand of the heart hence increasing chance of ACS
  • pulmonary congestion, oedema and pleural effusion – SOB, orthopnea, PND
  • reduced peripheral perfusion: confusion, AKI
  • —> interstitial (eosinophilic) transudates, alveolar septal edema and edema fluid in alveolar space, congested capillaries

RHF

  • MC due to LHF (pul HT increase burden)
  • congestive hepatomegaly, portal HT with subsequent congestive splenomegaly
  • transudative effusion at pleural space but no pulmonary oedema
  • pedal and sacral oedema
  • —> Nutmeg liver (centrilobular zone - zone 3 - necrosis)

ACP (27 decks)

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