Cardiovascular pathology
Dr D S O’Briain October 2009
Week 6
Time
1.00pm
2.00pm
3.00pm
Disc ipline
Path
Pharm
Pharm
4.00pm
Week 6
Time
Clinical 1
9.00am
Micro
10.00am
Path
11.00am
Pharm
12 noon
1.00pm
Pharm
2.00pm
Clinical 2
3.00pm
4.00pm
Week 6
Time
9.00am
Path
Clinical 3
10.00am
Pharm
11.00am
Micro
12 noon
1.00pm
Clinical 4
2.00pm
Micro
3.00pm
Micro
4.00pm
Path
Disc ipline
Disc ipline
Path
CARDIOVASCULAR SYSTEM
Monday 05 October 2009
Topic: Hypertension and Isc haemia
Venue
Pathogenesis of Hypertension
WMLT
Modern Management of Hypertension
RSLT
Management of CVS Risk Overview &
RSLT
Smoking Cessation
Non Invasive Cardiology
RSLT
Tuesday 06 October 2009
Topic: General Principles of
Venue
Management
Infections in A&E
RSLT
Topic: Ischaemic Heart Disease
Pathogenesis of Ischaemic Heart
RSLT
Disease
Management of Ischaemic Heart
RSLT
Disease, MI
Lunch
CVS Risk: Lipid Lowering Therapy/
RSLT
Obesity
Chest pain: Approach to Cardiac
RSLT
Ischaemia
Topic: Valvular Heart Disease
Pathogenesis of Valvular Heart Disease
RSLT
Valvu lar Heart Disease
RSLT
Wednesday 07 October 2009
Topic: Peripheral Vasc ular Disease
Venue
Pathogenesis of Peripheral Vascular
RSLT
Disease
Anti-platelet Therapies
RSLT
Topic: General Principles of
Management
Surgical infections leg ulcers, wounds
RSLT
and dressings
The Ischaemic Leg: Painful Cold limbs
WMLT
Lunch
Topic: General Principles of
Management
Bacteraemia and line-associated
WMLT
infections
Topic: Myocarditis / Endocarditis
Endocarditis, Myocarditis & Pericarditis:
WMLT
A microbiological approach
Pathogenic basis of Endocarditis,
WMLT
Myocarditis & Pericarditis
Lecturer
DSOB
AM
MB or MH
Vinnie Maher
Lecturer
PGM
DSOB
JS
MB
tbc
DSOB
Mr Vincent Young
Lecturer
DSOB
JS
PGM
tbc
BOХC
TRR
DSOB
Week 6
Time
9.00am
10.00am
11.00am
Disc ipline
Micro
Clinical 5
12 noon
1.00pm
2.00pm
Path
Pharm
3.00pm
Pharm
4.00pm
Week 6
Time
Disc ipline
9.00am
10.00am
11.00am
12 noon
1.00pm
Clinical 6
Micro
Clinical 7
Path
Thursday 08 October 2009
Topic: Myocarditis/ Endo carditis
Venue
Free slot
Myocarditis & Pericarditis - is there a role WMLT
for Microbiology?
Sudden Death in young people and
RSLT
Cardiomyopathy
Lunch
Topic: Heart Failure, Cardiac Arrest
and Cardiogenic Shock
Pathogenesis of Cardiac Failure
RSLT
Management of Heart Failure including
RSLT
Acute Pulmonary Oedema
Management of Cardiac Arrhythmias
RSLT
and Cardiac Arrest
Free slot
Friday 09 October 2009
Topic: General Principles of
Venue
Management
SOB & Palpitations
Healthcare associated infections 1
RSLT
Wound care and management
CPC 1: Cardiova scular System
RSLT
Lunch
Lecturer
Dr Jerome Fennell
Dr Ross Murphy
VC
MB
MB
Lecturer
tbc
FRF
tbc
JOL/OS
Cardiovascular pathology
Systemic pathology
Topic: 2-5 min discussion, then summary panel
Segments:
1.
Hypertension (12 panels)
2.
Ischaemic heart disease (23 panels)
3.
Valvular heart disease: (14) Rheumatic fever, congenital heart disease
4.
Peripheral vascular disease: atherosclerosis (20), aneurysms (4) vasculitis
(7), vessels (3)
5.
Endocarditis, myocarditis, pericarditis:
6.
Pathogenesis of cardiac failure (Dr Crowley)
7.
CPC (Prof O’Leary)
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Hypertension
• High blood pressure is common and asymptomatic,
– 25% of population >140/90
•
Incidence increases: age, black, young males, older females
– More severe: younger, blacks.
• Consequences: Cardiac, cerebral and renal disease
Hypertension
•
Types:
Primary 95%
Secondary 5% (renal, vascular, endocrine)
•
Course:
Benign 95%
Accelerated (malignant) 5%
•
Compensated / decompensated.
BP = Cardiac output X peripheral vascular (arteriolar) resistance.
Factors: Blood volume, ECF volume, total body Na.
Regulation: renin-angiotensin-aldosterone system.
Terminology
How to say
"we have some ideas but we're not sure of the cause"
• primary
• ideopathic
• agnogenic
• cryptogenic
• essential
Essential Hypertension
Pathogenesis: Sodium retention and/or vasoconstriction
Upper limit of the continuous variable of blood pressure
Genetic factors (polygenic) :
Twin, sibling, familial, racial (blacks), animal (rat strains)
Rarely single gene defects for aldosterone metabolism, sodium resorption
•
•
Environment:
Exiled Chinese incidence increased: behavior, stress, obesity, OCT
Dietary sodium: animal study (rats), remote peoples exposed to salt
a) defect in Na excretion
b) defect in cell membrane Na or Ca transport
(Ca - phosphorylation - response to vasoconstrictors)
c) sympathetic response (stress, neurogenic factors)
Sodium Homeostasis
Total body sodium regulates blood volume and cardiac output
•
Influenced by:
Renin angiotensin system.
Blood volume -GFR - proximal tubule Na resorption.
Atrial natriuretic factor: inhibits (volume expansion -GFR -distal tubule Na
resorption).
•
Renal vasodepressors:
a) prostaglandins, b) kallikrein-kinin system, c) platelet activating factor.
Vasoconstrictors: angiotensin II, catechol amines, thromboxane, leukotriene, endothelin
Hypertension - Morphology
•
Adaptive response to pressure or volume overload:
•
Myocyte cytoplasm and nucleus enlarged.
New myofibrils, filaments, mitochondria, ribosomes
(later degeneration, loss of myofibres, cell atrophy,
interstitial fibrosis)
•
Left ventricle: Concentric hypertrophy (normal LV
thickness 1.4 cm); dilates with decompensation
Hypertension - Effects
•
•
•
•
•
Compensation - none.
Decompensate - CCF
Thick wall: increases 02 requirement and diffusion distance
Dilation - eventually overstretches fibres
Myocyte degeneration and fibrosis - stiffness - impairs diastolic filling
(stroke volume)
• Atherosclerosis
Benign nephrosclerosis
Associations: age, diabetes, hypertension.
•
•
a) Arteriole walls thickened, hyaline, and lumen narrowed
Hyaline: plasma protein, lipids, basement membrane, intracellular matrix.
•
b) Fibroelastic hyperplasia (interlobular & arcuate arteries) - narrowing. Reduplication
of elastic lamina, increased fibromuscular tissue in media.
•
Secondary effects but may sustain & aggravate hypertension.
•
Effect - loss of tubules, interstitial fibrosis, damaged glomeruli, cortical narrowing,
granular kidney surface, mild reduction in size of kidney,
mild reduction in function and reserve.
Accelerated (malignant) hypertension
- Clinical
• Medical emergency; effects young, male, blacks
• CNS: papilloedema, visual effects, encephalopathy headaches, nausea,
vomiting, coma, fits
• CVS: failure
• Renal: proteinuria, haematuria (microscopic or gross), altered renal
function, later failure
50% mortality in 3 months untreated - 50% mortality in 5 years treated.
Death - uremia (CNS or CVS disease)
Hyperplastic arteriosclerosis Pathology
•
•
•
De novo.
On benign hypertension.
On renal disease (GN, reflux, scleroderma )
a) fibrinoid necrosis of arterioles (fibrin ± necrotising inflammation)
b) hyperplastic arteriolitis (arterioles and interlobular arteries) onion-skinning
with smooth muscle and collagen.
• Effect: narrowed arterioles, necrotic glomeruli, thrombosed capillaries, ischaemic
atrophy, infarction, high renin, endothelial injury (activated platelets, coagulation system
- thrombus).
Secondary Hypertension
(Mechanisms)
•
Renal
– a) Renin increase : renovascular
– b) Volume excess: acute GN
– c) Mixed.
•
Other (examples)
– Primary hyperaldosteronism ( blood volume)
– Phaeochromocytoma (vasoconstriction - (nor)adrenaline
– Oral contraceptives (renin angiotensin)
– Periarteritis nodosa (renin angiotensin)
Renal Artery Stenosis
Goldblatt. Hypertension proportional to constriction in one renal artery (Dog). Increased
renin from JGA; reverse with surgery or angiotension II antagonists. But secondary
renal changes may lead to persisting hypertension
•
•
70% have atheromatous plaque at origin of artery (males, diabetes, age) 2/3 curable
30% fibromuscular dysplasia (females,young) 90% curable Fibromuscular thickening
of intima, media or adventitia; multiple (or single) artery (or branches) unilateral (or
bilateral)
Morphology- In ischaemic kidney: ischaemic changes, JGA hyperplastic, arterioles normal.
In other kidney: hypertensive changes.
Clinical: (Bruit) IVP: small kidney, delayed function. Arteriogramvisualise stenosis, segmental beaded effect.
Measure renal vein renin.
Ischaemic Heart Disease
Imbalance in the supply and demand for oxygen (also
for nutrients and for removal of metabolites) in
cardiac muscle.
•
Increased demand: Exercise, emotion
•
Decreased supply:
Reduced oxygen (anaemia, cyanosis, carbon monoxide,
cigarettes).
Reduced coronary flow (atheroma, thrombus, spasm, shock).
Ischaemic Heart Disease
Epidemic
• Causes 80% of cardiac mortality
• Peaked in US in 1960s, 40% decline since
• Different patterns in some Western countries
• Cause of decline:
– Changing lifestyle (diet, smoking, exercise)
– Better therapy (CCU, thrombolysis, arrhythmia
therapy, CABG, angioplasty)
Atherosclerotic Coronary
Artery Disease: Distribution
• Narrowing of greater than 75% is clinically
significant
In 1/3 of patients one vessel is involved, in 1/3,
two vessels and in 1/3, three vessels.
• Sites: Proximal 2 cm of LAD and circumflex,
proximal 1/3 of right coronary artery.
• Less frequent: Secondary diagonal, obtuse,
marginal branches and posterior descending artery.
•
•
Rare: Intramyocardial branches
Atherosclerotic Coronary Artery
Disease:
Clinical Syndromes
•
•
•
•
•
Silent Infarct
Angina Pectoris
Myocardial Infarct
Chronic Ischaemic Heart Disease
Sudden Death
Angina Pectoris
•
Stable: Pain with exercise, emotion or other increases in demand.
– ST segment depressed—subendocardial ischaemia
•
Prinzmetal: Rest pain
– ST segment raised —transmural ischaemia.
– Due to spasm, (? cause: vasoconstrictive humoral factors, mast cells, nerves
– atherosclerosis usually present.
•
Unstable: Pain, increasing in duration and severity with less effort or at rest,
– (also called preinfarction angina or acute coronary insufficiency).
– Caused by: plaque enlarging, fissured, ulcerated, ruptured, vasospasm, platelet
aggregation and activation
Atherosclerotic Coronary Artery Disease
Vascular obstruction
• Plaque ulceration, fissure or rupture
–
–
–
–
•
platelets to adhere and become activated
thrombus forms (activated thrombin transforms fibrinogen to fibrin)
release of histamine, other vasoactive factors
microemboli may occur
Vasospasm: Demonstrated angiographically
– rarely causes infarct in absence of atheroma
– may rupture plaque, role of nerve supply and vasoactive factors
•
Other: Emboli, trauma, arteritis (SLE, PAN, etc), cocaine
(arrhythmia, spasm)
Myocardial Infarct - Coronary Artery
Lesions
• 90% of infarcts are supplied by an artery which has a thrombus over an
ulcerated or fissured plaque
• Platelets activated — aggregate to form thrombus (embolus) —
vasospasm, occlude.
• Deaths under 4 hours — 90% have thrombus; over 12 hours — 60%
have thrombus (thrombolysis)
• 10% without thrombus: (usually have severe atherosclerosis) Spasm,
platelet aggregates, emboli (mural thrombus, endocarditis,
paradoxical), arteritis, cocaine, tachycardia or arrhythmia
Evolution of infarct
• 4 hours: No morphological changes (subtle ultrastructural
changes).
• 8 hours: Oedema, myocytolysis, contraction band necrosis,
wavy fibres.
• 24 hours: Grossly pale, acute inflammatory infiltrate.
• Days: Infarct becomes clearly defined grossly, centre
softens, a hyperaemic rim appears, granulation tissue
appears.
• Weeks: Organisation proceeds leaving an organised scar by
about six weeks.
Myocardial Infarct, Morphology
•
Experimentally after 20 minutes of occlusion
–
•
Infarct size:
–
•
ischaemic necrosis begins in the subendocardium (least collaterals and vessels most
compressible)
Proportional to extent and duration of ischaemia, collateral supply, metabolic
demands; may be transmural or subendocardial.
Infarct site:
– Left ventricle (If adjacent, right ventricle is involved in 25%, adjacent atrium in 5%)
–
•
Isolated right ventricle in 1% (usually following marked right ventricle hypertrophy and strain).
Distribution:
– LAD (50%) Anterior 2/3 septum, anterior wall, apex.
– RCA (35%) Posterior wall and septum.
– LCA (15%) Lateral left ventricular wall
•
Infarcts are usually single
–
may extend (retrograde thrombus, vasospasm, arrhythmia), reperfusion injury.
Cardiac Enzymes
• Creatine Kinase
– MB isoenzyme specific for
heart
– Rises 4-8h, peaks 18h, falls
2-3d
• Troponin T or I
– Similar start, remain for 714d
Myocardial Infarct, Clinical
• Asymptomatic (15%).
• Symptomatic (60%).
– Sudden pain, crushing character, retrosternal, radiation (left shoulder, arm,
jaw), associated sweating, nausea, vomiting, dyspnoea, indigestion.
• Sudden death (25%).
• ECG:
– new Q waves, ST and T wave abnormalities, arrhythmias
– evolving pattern, 20% are non-specific or silent.
• Enzymes:
– Soluble cytoplasmic enzymes (CK 4h-4d, Troponin I and T 4h-14d
• Image: Echo (mural dyskinesia), Angiography, perfusion scintography,
MRI.
Effects of Myocardial
Infarction
• Decompensation:
– Muscle is dead, injured, stunned, disorganised,
•
Infarct dyskinesia:
– May cause aneurysm, mural thrombus, embolism.
•
Infarct rupture:
– tamponade, septal shunt.
•
Papillary muscle infarct or rupture
– mitral valve dysfunction
• Arrhythmias provoked in injured tissue
• Haemorrhagic pericarditis.
Myocardial infarct — complications
• Uncomplicated (15%)
• Sudden death (25%)
• Arrhythmia
– (sinus brady-, tachy-cardia, ventricular tachycardia, PVC, V fibrillation,
asystole, block)
•
•
•
•
•
•
Left ventricular failure (60%)
Pump failure (40% of myocardium damaged)
Shock (10%)
Rupture (free wall, septum, papillary muscle)
Thromboembolism
Mortality 35% in one year (50% sudden, 25% in hospital. 10% die
each subsequent year.
Percutaneous Transluminal
Coronary Angioplasty
•
Mechanisms
–
–
–
•
Early closure
–
–
–
–
–
•
Plaque compression—redistribute soft contents (most human plaques are hard)
Plaque fracture—breaking, cracking, splitting;
Stretching of plaque-free wall (70% of all, 24% severe plaques, are eccentric)
Spasm
Thrombus
Dissection with large intimal flap
Relaxation of overstretched wall of eccentric plaque
Subintimal bleed (concurrent thrombolysis)
Late chronic stenosis (20-50%)
–
–
Fibrocellular intimal proliferation
Progression of plaque
Myocardial Infarct,
Demography
• Age (only 5% under 40)
• Male (risk x 6 under 45, less when older)
• Smoker (risk x 5, proportional to number
smoked)
• Other: personality (type A: increased risk),
exercise and moderate alcohol protect
• Western countries: risk was high, now
falling
Chronic Ischaemic Heart
Disease
Insidious congestive cardiac failure
(possibly remote myocardial infarct or angina)
• Findings: possibly: left ventricular dilation, murmur,
calcification
• Morphology: patchy fibrosis, old infarcts
• ECG: Normal, bundle branch block or non -specific
changes
Sudden Cardiac Death
• Ischaemic heart disease (at least 75% stenosis)
– occluding thrombus in 1/2, new infarct in 1/4, old infarct in 1/3
• Other coronary artery disease: anatomic anomalies, embolism, arteritis,
dissection
• Myocardial disease: hypertrophic obstructive cardiomyopathy, right
ventricular dysplasia, myocarditis, amyloid, sarcoid
• Valve disease: aortic valve stenosis, floppy mitral valve infective
endocarditis.
• Conduction defects
• Electrolyte abnormalities
Congestive Cardiac Failure
State resulting from impaired cardiac function and resulting in insufficient
output for the metabolic requirements of tissues and organs
A) Excess Load.
B) Decreased pumping ability.
•
Muscle fibre
–
–
.
–
–
a) death
b) dysfunction
Decreased output - Forward failure.
Damming back - Backward failure.
Cardiac Failure - Compensation
• Dilation: produces increased force of contraction and
stroke volume (Starling)
• Hypertrophy
• Increased blood volume
• But increased muscle mass and blood volume require more
work — excess dilation — reduced efficiency
No morphological difference between compensated and non-compensated
heart — look for hypoxic and congestive effects remote from the heart
Left Ventricular Failure
•
Heart:
– Hypertrophy and dilation of left ventricle (except mitral stenosis)
•
Lungs:
– Congestion, oedema of lung and pleural space
– Dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, cough with frothy bloodtinged sputum
•
Kidney:
– Decreased perfusion (ischaemic tubular changes)
– renin angiotensin aldosterone system (increased NaCl, H20, ECF and blood
volume)
•
Brain:
– Hypoxia — irritable, decreased concentration and attention span, stupor, coma
Right Ventricular Failure
Secondary to
A) Left ventricular failure
B) Other causes: cor pulmonale, cardiomyopathy, constrictive pericarditis, tricuspid and pulmonary valve
disease
•
Liver:
–
–
•
Enlarged, chronic passive congestion (nutmeg)
if severe: central necrosis with fibrosis result in cardiac sclerosis (cardiac cirrhosis)
Spleen:
–
•
Enlarged, congested, dilated sinusoids and fibrotic walls
Kidney:
–
•
Congested
Subcutis:
–
•
Oedema, anasarca
Pleura:
–
•
Effusion (especially on right)
Portal System:
–
Congestion of GIT, spleen; ascites
Heart Failure
Organ
LV Failure RV Failure
Effect
Lung
+++
+
Oedema, cough, dyspnoea.
Kidney
+
++
Fluid retention, decreased
perfusion.
Brain
++
+
Hypoxia.
Liver
-+
+++
Enlarged, congested.
Spleen
-+
+++
Enlarged, congested.
Portal
-+
++
Ascites, GIT congestion.
+++
Oedema.
Subcutis - +
Cor Pulmonale
Right ventricular enlargement secondary to disordered structure or function
of lungs
Causes:
•
•
•
Lung parenchymal disease: COAD, pulmonary fibrosis, cystic fibrosis
Vascular disease: pulmonary embolism, vasculitis
Chest disorders: Kyphoscoliosis, obesity, neuromuscular disorders
Effect: Narrowing of pulmonary vascular bed (hyperviscosity-polycythemia)
•
Pulmonary hypertension -> cor pulmonale: acute (due to eg pulmonary embolism) -or
chronic). Right ventricular wall hypertrophies then dilates and fails
Rheumatic fever
Acute recurrent inflammation associated with
reaction to streptococcal infection.
Occurs 1-5 weeks after Group A, ß haemolytic
streptococcal infection, mainly children (5-15
years)
Rheumatic Fever, Jones Criteria
Major criteria of Jones
•
•
•
•
•
Polyarthritis — sequential involvement of large joints
Erythema marginatum
Subcutaneous nodules
Sydenham's chorea — rapid purposeless movements.
Carditis
Also (minor criteria): fever, arthralgia, previous rheumatic fever, prolonged PR
interval, acute phase reactants (ESR, CRP or WCC increased)
Jones (AHA): 2 major or 1 major and 2 minor criteria: high probability of rheumatic fever.
Recent streptococcal infection increases probability
Rheumatic Fever, Pathogenesis
• 1. Follows streptococcal infection but lesions sterile
• 2. Streptococcal antibodies — anti streptolysin 0 (AS0) &
hyaluronidase
• 3. Most frequent after severe streptococcal infections
• 4. Recur with repeated streptococcal infection
• 5. 99.9% decline in incidence—better living conditions, antibiotics,
organism has changed.
• 6. Individual susceptibility — genetic.
Rheumatic Fever, Pathogenesis
Aetiology :
•
Cross reaction
• Hyaluronate of humans—streptococcal capsule.
• Streptococcal membrane—muscle sarcolemma
• Streptococcal M protein—cardiac myosin
• Autoimmune - antiheart antibody (but ? cross reaction)
Pathology:
• Aschoff Body: Fibrinoid necrosis surrounded by mononuclear cells with Anitschkew
cells (with caterpillar nucleus)
• Pericarditis (bread &butter)
• Myocarditis
• endocarditis (verrucae on lines of closure) & McCallum's patches.
• Heal by scarring - distort valve
Rheumatic Fever:
Cardiac involvement
Acute - in 2/3 of children, 1/3 of adults.
Pericarditis, arrhythmias (atrial fibrillation), prolonged PR interval, auricular
thrombus, cardiac dilation (MI murmur). Valve involvement (MI, AI),
(death 1%))
Chronic - if first attack severe or when very young.
• MV in 2/3, MV & AV 1/4, TV (Few), PV rare
• Valve fibrosis, calcification, fused commissures (fish mouth) &
chordae.
• Mitral stenosis: LA dilation, auricular thrombus, pulmonary
congestion, RVH
Congenital Heart Disease Varieties
a) Shunts: Chamber (or vessel) to chamber (or vessel).
•
Right to left - Early cyanosis, clubbing, hypertrophic osteoarthropathy,
polycythemia (cerebral thrombosis).
•
Left to right - cyanose tardive. Increased pulmonary flow with vascular
sclerosis, pulmonary hypertension, reversed flow (right to left).
• Shunt complication. paradoxical embolism, infected embolism, infective
endocarditis.
b) Obstruction: Non-cyanotic. Failure to thrive, retarded development, intercurrent
diseases of childhood.
c) Malposition: Ectopia, dextrocardia (isolated or other anomalies) situs inversus
totalis (Kartagener; sinusitis, bronchiectasis, immotile cilia).
Congenital Heart Disease - Early
Cyanosis
1. Tetralogy of Fallot
•
•
VSD, overriding aorta, right ventricular outflow obstruction, RVH.
Outflow obstruction (infundibular, valve, supravalve) dictates severity.
2.
•
Transposition (multiple combinations with atria, ventricles, vessels)
3.
•
•
Truncus arteriosus
4.
Tricuspid Atresia
Mixing essential: ASD in all, most also have PDA, or VSD.
Common aorta & PA
Usually other cardiac defects
Congenital Heart Disease
Late Cyanosis—septal development
1. Ventricular septal defect
• Development of septum (week 5-6): common ventricle divided by muscular &
membranous septum
2. Atrial septal defect
• Development of septum (week 4): atrial canal closed by septum primum,
(ostium primum). Valve effect allows RA-LA flow, closes at birth
3. Patent ductus arteriosus
• Ductus closes day 1-2 (High 02, low PGE)
Congenital Heart Disease Late Cyanosis
Ventricular septal defect
Size dictates effect:
• Small — 5mm: (Roger), well tolerated, 50% close spontaneously,
loud murmurs & thrill, endocarditis
• Large: pulmonary hypertension, shunt reverses
Atrial septal defect
Ostium primum defect (5%). Often Down's syndrome
Ostium secundum (90%). Often other defects
Patent ductus arteriosus
•
•
90% PDA isolated (important for survival in other forms of CHD).
Machinery murmur, systolic thrill. LVH, dilated PA
Congenital Heart Disease Obstructive
1. Coarctation of Aorta - systolic murmur & thrill
–
–
Preductal: infants, (PDA) RVH with cyanosis of lower body
Postductal: adults (PDA in 50%)
» hypertension in upper body insufficiency (claudication, cold) in
lower body.
» Large collateral vessels: intercostal, axillary, mammary with rib
notching
2. Pulmonary stenosis
3. Aortic stenosis
Top 3 (50%) —VSD, PDA, ASD: late cyanosis
Middle 3 — non-cyanotic
Bottom 4 — Fallot etc: early cyanosis
Other Valve Diseases
Calcific aortic stenosis
– bicuspid (1% of population)
– rheumatic or normal valve becomes calcified - sclerotic, later stenotic.
• Result: systolic murmur, LVH, CCF; angina, syncope, sudden death
Mitral annular calcification
• asymptomatic, seen on imaging (rarely regurgitation, stenosis,
arrhythmias, thrombi, infection)
Mitral valve prolapse
• Ballooned (floppy) valve with myxoid degeneration of valve
fibrosa
• 7% of population, peak young females (in Marfan syndrome,
abnormal fibrillin gene)
• Asymptomatic - mid systolic click late systolic murmur
• Minority: chest pain, dyspnoea, fatigue, psychiatric symptoms
• Benign (Rarely: infective endocarditis, mitral insufficiency,
arrhythmias, emboli with infarction, sudden death)
Malignant carcinoid syndrome
Plaques of fibrous tissue on valve and endocardium of right ventricle outflow tract
•
Syndrome:
– Flushing, cramps, nausea, vomiting, diarrhoea (100%)
– Cardiac disease (50%)
– Asthma (33%)
•
Syndrome occurs in less than 1% of all carcinoids but in 10% of carcinoids
with large hepatic metastases (rarely: with ovarian or lung carcinoids)
• Mediators: 5HT, kallikrein, bradykinin, histamine, prostaglandins
• Metabolism: in liver, monoamine oxidases of lungs
Prosthetic valves
Types
• A) Mechanical occluders
• B) porcine or bovine bioprostheses
Complications in 5-10% (emboli 3%, infection 1%) per patient year
• Paravalvular leak
• Thromboembolism: (anticoagulate mechanical valves) emboli, infection,
obstruct movement of valve
• Infections: at tissue interface (ring abscess), also at cusp in bioprosthesis
• Deterioration: Bioprostheses, calcification and degeneration in 25%
• Also: Haemolysis, fibrous tissue ingrowth effecting function
Atheromatous Plaque,
Macroscopic
• Fibrous cap (white), deeper portion (grumous, yellow).
• 3 - 15 mm diameter, raised, coalesce.
• Scanty to numerous
• Distribution: Abdominal aorta> coronary > popliteal >
descending thoracic >internal carotid > circle of Willis.
• Spared: upper extremities, renal, mesenteric (except ostia).
Atheromatous Plaque
Histology
• Fibrous cap: Smooth muscle, WBC, connective tissue,
collagen, elastic, proteoglycan.
• Core: lipid debris, cholesterol, cholesterol esters, foam
cells ( smooth muscle and macrophage), fibrin, plasma
proteins, T-cells.
• Periphery: neovascularisation, chronic inflammation.
Effects of Atheromatous Plaque
Different effects in narrow (coronary) and wide (aorta) vessels
Clinically silent
Most plaques have no effect.
Calcification: Identify on imaging.
Complicated plaques
Fissure
Ulcerate: atheroemboli.
Thrombose: occlude, embolise
Haemorrhage: occlude.
Consequences
Stenose: Ischaemia, atrophy.
Occlude (by thrombus or haemorrhage): Infarct.
Aneurysm: pressure effects, leak (rupture)
Fatty streak
Possible precursor of atheroma.
• Spot (1mm), Streak (1x10mm).
• Composition: Macrophages filled with lipid (foam cells) later smooth
muscle cells with lipid droplets, extracellular lipid, T-lymphocytes,
proteoglycans, collagen, elastin.
• Incidence: More frequent with high milk/fat diet:
• 10% first decade, 30% third decade,
• May recede, persist or convert to fibrous plaque
• Distribution: Aorta - unlike atheroma, Coronary arteries - like
atheroma.
Intimal Cushion
• White areas of diffuse intimal thickening composed of
intimal smooth muscle and matrix (little collagen, no
lipid), gelatinous lesion.
• Degenerate effect of blood pressure and time.
• But occur at ostia (atheroma sites).
Monckeberg’s Calcific Medial
Sclerosis
•
•
•
•
•
Calcification of medium or small
arteries
Both sexes, over 50
Arteries: Femoral, radial, ulnar, genital.
Cause: vasotonic factors, adrenaline,
nicotine.
Effect: none, visible in imaging
Arteriolosclerosis
•
Hyaline change in vessel walls.
•
•
Pathogenesis - plasma leakage, smooth muscle matrix.
Associations - hypertension, diabetes, age.
•
•
•
Benign - hyaline narrowing.
Hyperplastic - onion skin (fibrinoid necrosis).
Sites: Kidney, gall bladder, intestine, periadrenal,
pancreatic.
Atherosclerosis Risk Factors
Hyperlipidemia.
LDL.
Hypertension: 160/95 Vs 140/90,- Risk X 5. Increases: Atheroma, IHD, CVD. Risk decreases with
therapy.
Cigarettes: More AS, more sudden death, Risk increased by 70-200%. Decreases after cessation.
Diabetes: More AS, MI x 2, Increased CVD, PVD risk increased x 8-150.
Other: Physical activity, stress, obesity, oral contraceptives, hyperuricemia, high CHO intake, male, age,
family history, homocystinemia.
Multiple Factors:
More than additive.
Theories of Atherogenesis
• Virchow - imbibation
• Rokitansky - encrustation
Role of lipid in Atherosclerosis
1. Found in plaque
2. Experimentally raised lipid -> AS
3. Hyperlipidemias -> AS
4. Populations with high lipids -> high AS
rate
5. Treat hyperlipidemia - decrease AS.
Risk of Atherosclerosis
•
•
High: Raised LDL (70% cholesterol), triglyceride and VLDL.
Low: Raised HDL.
•
Risk increases with increased cholesterol level (risk x 5 with cholesterol
increase 220 to 265)
•
•
Increased intake cholesterol and triglycerides - increases serum cholesterol.
Omega 3 fatty acids (fish) protective
How Hyperlipidemia may
damage intima
More serum LDL, more cellular penetration.
•
•
•
LDL with proteoglycan - avid uptake.
LDL modified - lysosomal uptake.
LDL - directly damages endothelial cell.
• Oxidised lipoproteins: Endothelial injury, smooth
muscle injury, foam cells - scavenger receptor,
chemotactic.
Intimal dysfunction
• Cause: Mechanical, Haemodynamic stress,
Immune complex, Radiation, Chemotherapy.
• Association: Hypertension, Stress,
Cigarettes.
• Effect: Increased intimal permeability,
adhesion, smooth muscle proliferation,
atheroma (if hyperlipidemia )
Macrophage
• Family: Monocyte, histiocyte, macrophage, epithelioid cell,
giant cell, granuloma
•
Monocytes adhere, migrate, phagocytose
• Have scavenger receptor - modified VLDL receptor (Lipid
internalised, hydrolysed, esterified -> lipid droplet).
•
Monocytes produce: IL-1, TNF (increased adhesion),
chemotaxis factors, toxic O2, PDGF, TGF beta -> smooth muscle
Smooth muscle proliferation
• Origin: From media (or myointima)
•
Stimulus: PDGF (from platelets, macrophages,
endothelial and smooth muscle cells), FGF, EGF,
TGF.
• Inhibit: Heparin, TGF-B.
• Result: Smooth muscle cells produce
extracellular matrix and foam cells
(atheroma)
Arterial Injury
Permeability increases.
Adhesion of platelets, monocytes
Factors released
Smooth muscle migrates to intima, proliferates and produces
extracellular matrix, collagen, elastin, proteoglycans
Monocytes - phagocytose
Lipid deposited
Other Theories of
Atherogenesis
• Primary smooth muscle proliferation: monoclonal
growth (as a form of leiomyoma)
• Cause: Exogenous (hydrocarbon, virus),
endogenous (cholesterol)
• Experimentally: Plaques in Marek chicken virus,
anthracycline, herpes mRNA in plaque
Aneurysms
• Localised abnormal dilation of vessel.
• Types: Saccular, fusiform, cylindroid, dissection.
• Complications: Pressure, thrombus, rupture.
• Aetiology: Atherosclerosis, cystic medial necrosis,
syphilis, trauma (arteriovenous aneurysm), PAN,
infections, (mycotic), congenital (berry).
Atherosclerotic Aneurysm
• Males of 50+, frequently (50%) hypertensive
• Abdominal aorta (between renal artery and aortic biforcation).
(Thoracic aorta, renal, mesenteric arteries)
• Complications;
•
Rupture (if >6 cm, 50% rupture in 10 years)
•
surgical mortality 50% (unruptured 5%)
•
Compression - ureter, vertebrae
•
Occlusion (thrombus, pressure)
•
Embolism
•
Abdominal mass
Syphilis
Obliterative endarteritis of vasa vasorum
Medial destruction with fibrosis (causes tree barking or wrinkling of intima and
dilation of vessel). Aortic valve dilated with rolled thickened cusps
Secondary atherosclerosis usual
•
•
•
•
•
•
•
Complications
Mediastinal encroachment
Respiratory effects in lung and airway
Swallowing impairment
Cough (recurrent laryngeal nerve)
Pain (involvement of vertebrae and ribs)
Cardiac effects
Dissecting Haematoma
(Aneurysm)
Males x 3 , aged 40 to 60, Females often young, pregnant and hypertensive.
Haematoma between middle and outer 1/3 of vessel enters through 4-5 cm
transverse intimal tear.
Type A - Within 10cm of aortic valve.
Type B - Distal to subclavical artery.
Haematoma dissects proximal, distal or reenters lumen.
Pain - back, radiates progressively.
Rupture into pericardial, pleural or peritoneal cavity.
Narrowing of vessels - cerebral or coronary insufficiency.
Dissecting Haematoma
(Aneurysm)
Cause: Hypertension - mechanical stress
Cystic medial necrosis: basophlic mucoid pools with fragmented elastic,
abnormal collagen, elastin,
proteoglycan
Marfan, abnormal collagen cross links. Structural effects in retina, lens,
joint, aorta, abnormal height
Therapy: Surgery, hypotensive therapy.
Arteritis
Arteritis (vasculitis, angiitis).
Cause: Bacterial, irradiation, toxin, trauma, collagen disease.
Immune pathogenesis:
Resemble arthus phenomenon, serum sickness (immune complex disorders)
Found in SLE, Mixed cryoglobulinemia(IgG,M,Complement)
Virus Ag/Ab complex, IgG+C. HBsAg-antibody complex
Drugs
Cytotoxic Ab to endothelial cells (SLE) to activated endothelial cells
(Kawasaki)
c-ANCA (PAN, Wegeners), p-ANCA (microscopic PAN, Churg Strauss)
T cells + granulomas; cell mediated immunity
Arteritis
• Periarteritis nodosa (PAN)
• Leukocytoclastic vasculitis
• Temporal arteritis
• Wegener’s granulomatosis
• Allergic granulomatosis
• Lymphomatoid granulomatosis
• Raynaud’s
• Buerger’s
• Takayasu’s
• Kawasaki’s
Periarteritis Nodosa, Pathology
• Classic type involves medium or small vessels (except lung).
• Kidney 85%, heart 75%, liver 65%, GI 50% (also pancreas, testes,
skeletal muscle, skin).
• Involves sharply localised segments of vessels especially branching
points.
• Stages (may coexist):
• Acute - fibrinoid necrosis (of segments), leukocytes, aneurysm
formation, thrombus.
• Healing - fibroblastic reaction - nodules, macrophages, plasma cells,
organised thrombus
• Healed - fibrotic (elastic stains).
Periarteritis Nodosa, Clinical
• Ill young adult, (male x 3), fever, malaise, weak, raised
WCC, PUO, weight loss.
• Renal failure, haematuria, hypertension, albuminuria.
• Abdominal pain, melaena.
• Muscle aches and pains, peripheral neuritis.
• Investigate: Hepatitis B Ag 30%, ANCA, Arteriography nodules (aneurysms)
• Biopsy: Kidney, skin.
• Therapy: Steroid and cyclophosphamide cure 90%.
Temporal arteritis
• Granulomatous inflammation of small and medium sized cranial
arteries
• Morphology: giant cell reaction to fragmented elastic in vessel wall
with polys and lymphocytes. Later thrombus formation and intimal
fibrosis. Segmental involvement; biopsy is negative in 40%.
• Clinical: aged, female, high ESR, headache, local tenderness, facial
pain, visual loss (40%). May involve aortic arch, GI tract,
myocardium, CNS
•
Association; polymyalgia rheumatica (flu-like illness with muscle stiffness.
•
Cause: ? Cell mediated immunity to arterial antigen.
• Responds to steroids
Wegener’s Granulomatosis
Acute necrotising granulomatous inflammation of upper and lower respiratory tract with
focal necrotising vasculitis.
Glomerulonephritis:.
• Clinical: males in 5th decade
•
95% pneumonitis with nodular or cavitating infiltrate
•
90% chronic sinusitis
•
75% mucosal ulceration of nasopharnyx
•
80% renal disease
.
»
80% die in one year,t. 90% respond to cyclophosphamide
Pathogenesis: ANCA, Occasionally immune complexes found, cell mediated immunity role.
Raynaud
Raynaud’s Disease.
• Vasospastic disorder of young women, onset: cold, emotion.
• Involves fingers, hands, nose and feet which become white, blue and
red.
• Benign: Secondary arterial thickening, tropic skin changes (atrophy,
ulcers).
Raynaud’s phenomenon.
• Vasospastic changes in extremities due to:
• Atherosclerosis, connective tissue diseases, Buerger’s disease,
Buerger’s Disease (Migratory
Thrombophlebitis)
• Segmental thrombotic acute & chronic inflammation
of intermediate and small vessels (arteries, veins and
nerves)
• Involves males, strong association with tobacco
smoking
• Pain, vascular insufficiency of lower limbs gangrene, Raynaud phenomenon
Varicose Veins
• Dilated tortous veins (legs, portal system),female, fat, familial,
increase with age
• Aetiology: Posture, pregnancy, tumours, poor support (superficial
veins surrounded by fat)
• Pathology: Valves distorted and damaged, vein elastica degeneration
and calcification and fibrosis (phlebosclerosis), luminal thrombus
• Effect: Leg congestion, oedema, heavyness, pain, stasis dermatitis,
tropic changes, ulcer
Thrombophlebitis (Deep
venous thrombosis)
Predisposition: CCF, cancer, pregnancy, bed-rest, immobilisation, postoperative.
Effects:
Local: Deep leg veins (periprostatic, pelvis) inflamed - oedema, dilated
surrounding veins, dusky cyanosis, pain on pressure or dorsiflexion.
Asymptomatic.
Pulmonary embolism.
Lymphatics
– Inflammation: Lymphangitis, lymphadenitis
•
Obstruction: tumour, surgery, radiation, inflammation,
filiariasis. Results in oedema with fibrosis, brawny induration,
peau d’orange, ulceration.
• Leak: chylothorax, chylous ascites.
• Lymphoedema praecox: Females 10-25 years, lower limb. ?
cause
• Milroy’s disease: Lymphoedema from birth, mendelian,
abnormal lymphatics.
Vascular Tumours
Benign
• Haemangioma; capillary, cavernous
• glomus, telangiectasia, spider naevus, granuloma pyogenicum, naevus
flammeus (simple birthmark), port-wine stain (disfiguring birthmark) Lindau
von Hipple, Sturge Weber, Osler Weber Rendau
Malignant.
• Haemangioendothelioma, haemangiopericytoma
• Angiosarcoma: High grade malignancy Skin, soft tissue, breast, liver
– (arsenic, thorotrast, PVC) .
• Kaposi’s sarcoma: immune deficiency, herpes virus HHV8
Infective endocarditis
Microbiological colonisation of valve.
(Similar effect: Colonisation of endocardium, aorta, aneurysms)
Valve lesion
– Abnormal valves: Rheumatic (especially: small shunt, jet lesions), congenital
(VSD, PDA, Fallot), mitral prolapse, calcific stenosis (bicuspid), prosthetic valves,
catheters
– Normal valves
Risk
– In neutropenia, immunodeficiency, immunosuppression, IVDU
Seeding
– Infection, surgery, dentist, IVDU. trivial injury, transient gut or mouth seeding
Infective endocarditis
Microbiological colonisation of valve. (Similar effect: Colonise endocardium,
aorta, aneurysms)
Valve lesion
– Abnormal valves: Rheumatic (especially: small shunt, jet lesions), congenital
(VSD, PDA, Fallot), mitral prolapse, calcific stenosis (bicuspid), prosthetic valves,
catheters
– Normal valves
Risk
– In neutropenia, immunodeficiency, immunosuppression, IVDU
Seeding
– Infection, surgery, dentist, IVDA. trivial injury, transient gut or mouth seeding
Infective Endocarditis: Organisms
Organisms
– 65% streptococcal: alpha haemolytic (viridens), bovis, faecalis
– 25% staphylococcus aureus.
• Others: S. pneumoniae, GNB (E.Coli, N. gonorrhoea).
– 10% sterile.
Precipitating factors:
• agglutinating antibodies, adhesion factors, platelet-fibrin deposits on
valve.
Infective Endocarditis: Clinical
•
•
•
•
•
•
Systemic: fever, fatigue, weight loss, flu-like illness, chills.
Murmur (changing in acute, absent in 10%).
Emboli: subungual, retina (Roth spots); to brain, spleen, kidney
(lung).
Metastatic abscess (in acute): cerebral, meninges, renal.
Renal: Embolic infarct, focal or diffuse glomerulonephritis.
Cardiac: valve stenosis or incompetence, abscess, graft dehiscence,
pericarditis
Infective endocarditis: course
• Acute (days) :
– virulent organism, large invasion, low resistance. On normal or
prosthetic valve, IVDU, catheter. Large ulcerating vegetation,
perforate, erode valve.
• Chronic (months) :
– low virulence, partial healing.
Endocarditis, other forms
Non-Bacterial thrombotic endocarditis
•
•
•
•
•
1-5mm, fibrin, on leaflet (lines of closure), sterile.
marantic (chronic debilitating disease); or following catheter.
Associated with DVT or pulmonary embolus (hypercoagulable states)
Mucinous carcinomas (may secrete procoagulant)
Complication: (Rare), emboli, infarct, infection.
Libman Sacks —SLE (and antiphospholipid syndrome).
• 1-4mm, fibrin & necrotic debris overlying fibrinoid necrosis.
• Anywhere in leaflet - MV & TV, may be multiple. Also lesions in
myocardium, pericardium and vessels
Myocarditis.
Pathology:
Clinical:
Leucocyte infiltration and myocyte degeneration or necrosis.
Heart is normal sized or enlarged.
Patchy haemorrhagic foci, pale flabby myocardium.
May involve one or several chambers.
Normal peri- and endocardium.
Asymptomatic.
Fatigue, dyspnoea, palpitations, chest discomfort, fever.
Arrhythmia.
Sudden onset congestive cardiac failure, murmur
(dilated AV valves).
Myocarditis, Aetiology.
•
Viral: Coxsachie A, B, ECHO, polio, influenza A, B, HIV.
–
•
•
•
Occurs days to weeks after a respiratory or neurological infection (is occasionally primary).
Cell mediated immunity (activated macrophages, CD8 lymphocytes), cells attack viruscontaining myocytes.
T. Cruzi: South American Trypanosomiasis (Chagas disease). Myocarditis in 80%, 10% die acutely.
Trichinosis, Lyme disease (borrelia borgdorferi).
Other: other infections, collagen diseases, drugs, transplant, sarcoid,
Cardiomyopathy
Non-inflammatory heart muscle disease of unknown
cause.
• Exclude: Inflammatory, hypertensive, congenital,
valve and pericardial disease.
• Primary :
Dilated (congestive) — more than 90%
Hypertrophic
Restrictive (obliterative) — rare
• Secondary.
Dilated (Congestive)
Cardiomyopathy
Heart
–
–
–
–
weight increased
4 chamber dilation
mural thrombi left ventricle (also right ventricle, atria)
valves and coronary arteries normal
Biopsy: Fibre hypertrophy, focal fibrosis, endocardial thickening, foci of inflammatory cells, (normal in
1/4).
Clinical: Relentless congestive failure, 25% five year survival.
Associations:
•
•
•
•
•
•
•
Alcohol: Direct effect, thiamine deficiency, cobalt.
Peripartum: Nutritional, hypertensive, metabolic effects,
occurs in poor multiparous women, regresses in 50%.
Genetic: dystrophin gene defect in 30%
Post Viral: Evidence of remote myocarditis.
Iron
Arrhythmogenic RV dysplasia, familial (ch 14 defect)
Hypertrophic Cardiomyopathy
Also termed: Asymmetric septal hypertrophy (ASH), Ideopathic
hypertrophic subaortic stenosis (IHSS), Hypertrophic obstructive
cardiomyopathy (HOCM)
• Heart enlarged, predominantly left ventricle, basal part (occasionally
other chambers predominate), Asymmetric or symmetric, bananashaped cavity, outflow obstructed by muscle (a disorder of diastole).
• Endocardial thickening, mural plaques, mitral valve thickening,
• Intramural coronary arteries.
• Microscopy: Myocyte hypertrophy, disarray of cells and
myofilaments in 50% of septum, interstitial fibrosis
Hypertrophic Cardiomyopathy
Clinical:
•
•
•
•
Young adult
Asymptomatic,
Sudden death (with exercise)
Dyspnoea, angina, dizzyness, congestive failure, atrial fibrillation, auricular
thrombus, emboli, infected endocarditis (mitral valve).
Pathogenesis: Autosomal dominant (50%)—abnormal sarcomeric genes: beta myosin heavy chain (in one
third), cardiac troponin T, tropomyosin, myosin binding protein C
Increased left ventricle wall thickness and decreased compliance decreases volume of ventricle (decreased
stroke volume), obstructs mitral valve, and obstructs outflow, (dilation of congestive failure may
improve function).
Restrictive Cardimyopathy
•
•
•
•
Amyloid.
Sarcoid.
Radiation
Endomyocardial fibrosis: Children, young adults,
Africa.
Heart transplantation
• 2500 transplants yearly, most for IHD and DCM, 5 year survival 6085%
•
Immediate failure (d 1-10): surgical factors, Hyperacute rejection
•
Acute rejection, d 1-100
•
•
•
•
Graft atherosclerosis
Kidney: cyclosporine toxicity
Infections: 60% of deaths in first year (CMV, toxoplasmosis,)
Malignancy:
–
–
A) Skin basal and squamous carcinomas, other carcinomas
B) Lymphoproliferative disorder: EBV related, B-cell, high grade
Pericardial fluid
Effusion: Non-inflammatory, low protein, few cells.
•
Serous (congestive failure, hypoproteinaemia)
•
Serosanguinous (trauma, resuscitation)
•
Chylous (lymphatic rupture)
•
Cholesterol
Exudate: Inflammatory, High protein, cells.
•
Acute: Serous, serofibrinous, fibrinous, purulent,
suppurative, haemorrhagic, caseous.
•
Chronic: Obliterative, adhesive, constrictive.
Acute Pericarditis
Serous: usually non-bacterial (collagen diseases, uremia, tumour).
Serofibrinous/fibrinous: (eg: myocardial infarct, collagen disease)
Fibrin resolves or organises (adhesive pericarditis). Clinically:
Friction rub, pain, systemic febrile reaction, signs of congestive failure.
Purulent/suppurative: usually bacterial, direct spread from empyema,
pneumonia, endocarditis
Haemorrhagic: Tuberculosis, malignancy
Chronic Pericarditis
• Obliterative pericarditis (incidental post-mortem finding).
• Adhesive mediastinopericarditis: previous suppuration, caseation,
cardiac surgery, radiation. Heart is bound to surrounding structures.
Develops marked hypertrophy.
• Constrictive pericarditis: Ideopathic or following suppuration or
caseation. Small quiet heart, reduced output, congested veins, pulsus
paradoxus.
Cardiac Tumours
Secondary (in 5% of tumour autopsies).
• Primary site: Lung, breast, melanoma, lymphoma, leukaemia.
• Usually asymptomatic
• in pericardium (pericarditis, effusion)
• in myocardium (arrhythymias, obstruction, congestive failure)
Primary (rare)
Myxoma: Most in atria, especially left
Effects: systemic reaction, syncope, sudden death, embolism.
Lipoma
Papillary elastofibroma: Organised thrombus with papillary projections on valve leaflets
Rhabdomyoma: muscle hamartoma, children, tuberous sclerosis, may obstruct.