Pathology of Pathology of Cardiovascular SystemCardiovascular System

Dr. Mohamad Nidal Khabaz Dr. Mohamad Nidal Khabaz

Valvular Heart Valvular Heart DiseasesDiseases

Valvular Heart DiseasesValvular Heart Diseases

Stenosis: failure of the valve to open completely, so Stenosis: failure of the valve to open completely, so impairing forward blood flow.impairing forward blood flow.

Insufficiency (Regurgitation): failure of the valve to Insufficiency (Regurgitation): failure of the valve to close completely so allowing reverse flow.close completely so allowing reverse flow.

Valve abnormalities: congenital or acquired.Valve abnormalities: congenital or acquired. The most common abnormalities are acquired The most common abnormalities are acquired

stenosis of the mitral and aortic valves.stenosis of the mitral and aortic valves. Valve abnormalities produce abnormal heart Valve abnormalities produce abnormal heart

sounds called murmurs.sounds called murmurs.

Valvular Heart Diseases: CausesValvular Heart Diseases: Causes

Mitral Stenosis: almost all due to rheumatic feverMitral Stenosis: almost all due to rheumatic fever Complications: Complications: Atrial fibrillationAtrial fibrillation (the commonest), (the commonest),

Systemic embolization, Pulmonary hypertension, Systemic embolization, Pulmonary hypertension, Right ventricular failure, Chest infectionsRight ventricular failure, Chest infections

Mitral Regurgitation:Mitral Regurgitation: mitral annulus:mitral annulus:

Dilatation : LV dilatation (Dilated Dilatation : LV dilatation (Dilated Cardiomyopathy) or repeated Myocardial Cardiomyopathy) or repeated Myocardial infarction infarction

Calcification: degenerative, chronic renal Calcification: degenerative, chronic renal failure (especially in elderly age group)failure (especially in elderly age group)

Valvular Heart Diseases: CausesValvular Heart Diseases: Causes Mitral Regurgitation:Mitral Regurgitation:

mitral leaflets:mitral leaflets: Shortening, rigidity, deformity (rheumatic heart Shortening, rigidity, deformity (rheumatic heart

disease)disease) Destruction of the leaflet: systemic lupus Destruction of the leaflet: systemic lupus

erythematosus, Trauma, infective endocarditis.erythematosus, Trauma, infective endocarditis. Myxomatous degeneration (Mitral valve Myxomatous degeneration (Mitral valve

prolapse)prolapse) chordae tendineaechordae tendineae

- Rupture: I.E., trauma, R.F., ischemia - Rupture: I.E., trauma, R.F., ischemia papillary musclespapillary muscles

- Dysfunction & Rupture: ischemia, dilatation.- Dysfunction & Rupture: ischemia, dilatation.

Valvular Heart Diseases: CausesValvular Heart Diseases: Causes

Aortic Stenosis Aortic Stenosis Calcific AS Calcific AS Rheumatic AS Rheumatic AS Congenital bicuspid aortic valveCongenital bicuspid aortic valve

Aortic RegurgitationAortic Regurgitation Rheumatic feverRheumatic fever Infective endocarditisInfective endocarditis TraumaTrauma Aortic root disease: dilatation of the ascending A.Aortic root disease: dilatation of the ascending A.

Marfan Syndrome, Syphilitic aortitisMarfan Syndrome, Syphilitic aortitis

Valvular Heart Diseases and Valvular Heart Diseases and Rheumatic FeverRheumatic Fever

The most common cause of acquired valvular The most common cause of acquired valvular disease in developed and underdeveloped disease in developed and underdeveloped countries is rheumatic fever (R.F.)countries is rheumatic fever (R.F.)

Now in the western world R.F. is being eradicated, Now in the western world R.F. is being eradicated, but its still the common cause (in addition to CAD but its still the common cause (in addition to CAD and degenerative calcific diseases).and degenerative calcific diseases).

R.F. can be presented in many ways:R.F. can be presented in many ways: arthritis without cardiac involvement arthritis without cardiac involvement rheumatic chorea (Sydenham's chorea) without rheumatic chorea (Sydenham's chorea) without

arthritis nor carditisarthritis nor carditis carditis with or without arthritiscarditis with or without arthritis

Acute Rheumatic FeverAcute Rheumatic Fever

Definition: an acute immunologically mediated, Definition: an acute immunologically mediated, inflammatory disease, which occurs as a sequel to inflammatory disease, which occurs as a sequel to group A (beta-hemolytic) streptococcal pharyngitis group A (beta-hemolytic) streptococcal pharyngitis after an interval of 1- 4 weeks.after an interval of 1- 4 weeks.

MultisystemMultisystem disease involving the heart, joints, disease involving the heart, joints, brain, cutaneous and subcutaneous tissues.brain, cutaneous and subcutaneous tissues.

PreventablePreventable disease disease Major Major public health problempublic health problem in heavily populated in heavily populated

underdeveloped and developing countries.underdeveloped and developing countries.

Rheumatic Fever: Incidence Rheumatic Fever: Incidence Occurs in only 3% of patients with group A Occurs in only 3% of patients with group A

streptococcal pharyngitis. Peak incidence: ages of streptococcal pharyngitis. Peak incidence: ages of 5-15 years. 5-15 years. Girls>boysGirls>boys

Why not all patients that have GAS throat infection Why not all patients that have GAS throat infection will have R.F.? (different incidence)will have R.F.? (different incidence)

Becaus there are microorganisms variables and Becaus there are microorganisms variables and host variables:host variables: Microorganism variables: only certain strains (M Microorganism variables: only certain strains (M

serotypes 1, 3, 5, 6, 14, 18, 24, 27, and 29) that serotypes 1, 3, 5, 6, 14, 18, 24, 27, and 29) that can produce the immunologically active Ag.can produce the immunologically active Ag.

Host variables: some will produce large amount Host variables: some will produce large amount of Abs after each infection but others don’t.of Abs after each infection but others don’t.

Rheumatic Fever-PathogenesisRheumatic Fever-Pathogenesis

Group A streptococcal(GAS) pharyngeal infectionGroup A streptococcal(GAS) pharyngeal infection Body produce antibodies against streptococci, Body produce antibodies against streptococci,

these antibodies cross react with human tissues these antibodies cross react with human tissues because of the antigenic similarity between M because of the antigenic similarity between M proteins of group A streptococci and human proteins of group A streptococci and human connective tissues (molecular mimicry) there is connective tissues (molecular mimicry) there is certain amino acid sequence that is similar certain amino acid sequence that is similar between GAS and human tissue.between GAS and human tissue.

Immunologically mediated inflamation & damage Immunologically mediated inflamation & damage (autoimmune disease) to human tissues which have (autoimmune disease) to human tissues which have antigenic similarity with streptococcal components antigenic similarity with streptococcal components like heart, joint, brain and connective tissues.like heart, joint, brain and connective tissues.

Bcs of the similsrity btw hyaluronic acid in GAS Bcs of the similsrity btw hyaluronic acid in GAS capsule and in the connective tissue of the joints, capsule and in the connective tissue of the joints, Ab produced agaist GAS capsule will start to attack Ab produced agaist GAS capsule will start to attack the joints and causes arthritis.the joints and causes arthritis.

M-protein in GAS cell wall and the myocardium are M-protein in GAS cell wall and the myocardium are similar, thus Ab produced against GAS cell wall will similar, thus Ab produced against GAS cell wall will attack heart and will cause carditis and so forth.attack heart and will cause carditis and so forth.

Rheumatic Fever-PathogenesisRheumatic Fever-Pathogenesis

There is no direct invasion to the tissue by the There is no direct invasion to the tissue by the microorganism, but it is an auotoimmune disease microorganism, but it is an auotoimmune disease that involves Ag-Ab interaction.that involves Ag-Ab interaction.

It must be pharyngeal infection not skin infection.It must be pharyngeal infection not skin infection. Always remember Always remember blood cultures of patients with blood cultures of patients with

rheumatic fever are sterilerheumatic fever are sterile.. Serological studies show elevated levels of Serological studies show elevated levels of

antibodies to streptococcal enzymes (streptolysin O antibodies to streptococcal enzymes (streptolysin O and DNAse B). and DNAse B).

Rheumatic Fever: Rheumatic Fever: Major ManifestationsMajor Manifestations

Fever, migratory polyarthritis, pancarditis, Fever, migratory polyarthritis, pancarditis, subcutaneous nodules, erythema marginatum of subcutaneous nodules, erythema marginatum of skin, and sydenham’s choreaskin, and sydenham’s chorea

Rheumatic Fever: Rheumatic Fever: Major ManifestationsMajor Manifestations

Carditis (pancarditis): all 3 layers are involvedCarditis (pancarditis): all 3 layers are involved Arthritis: migratory polyarthritis (large joints)Arthritis: migratory polyarthritis (large joints) Chorea: spasmodic, unintentional, jerky Chorea: spasmodic, unintentional, jerky

movements.movements. Subcutaneous nodule: painless, hard nodules Subcutaneous nodule: painless, hard nodules

beneath skin, over bony prominence, tendons and beneath skin, over bony prominence, tendons and joints.joints.

Erythema marginatum (rash): ring or crescent Erythema marginatum (rash): ring or crescent shaped, transient patches over trunk and limbs.shaped, transient patches over trunk and limbs.

Rheumatic Fever: Pathology Rheumatic Fever: Pathology The characteristic lesion is a disseminated focal The characteristic lesion is a disseminated focal

inflammatory foci known as ( Aschoff bodies )inflammatory foci known as ( Aschoff bodies ) A focus of fibrinoid necrosis surrounded by a A focus of fibrinoid necrosis surrounded by a

collection of lymphocytes, macrophages, few collection of lymphocytes, macrophages, few plasma cells plus modified histiocytes known as plasma cells plus modified histiocytes known as Anitschow cells (large amount of cytoplasm, Anitschow cells (large amount of cytoplasm, central nucleus, and prominent nucleolus), may central nucleus, and prominent nucleolus), may become multinucleated forming Aschoff giant become multinucleated forming Aschoff giant cells.cells.

Inflammatory infiltrates in many tissues (synovium, Inflammatory infiltrates in many tissues (synovium, joints, skin, and heart).joints, skin, and heart).

Eventual fate is fibrosis (common in cardiac tissues).Eventual fate is fibrosis (common in cardiac tissues).

Jones Criteria (Revised) for Guidance Jones Criteria (Revised) for Guidance in the Diagnosis of Rheumatic Fever in the Diagnosis of Rheumatic Fever

*The presence of two major criteria, or of one major and two minor criteria, indicates a high probability of acute rheumatic fever, if supported by evidence of

Group A streptococcal nfection.

Major Manifestation Minor Manifestations

Supporting Evidence of Streptococal Infection

Clinical Laboratory Carditis Polyarthritis

Chorea Erythema Marginatum

Subcutaneous Nodules

Previous rheumatic fever or rheumatic heart disease Arthralgia Fever

Acute phase reactants: Erythrocyte sedimentation rate, C-reactive protein, leukocytosis Prolonged P-R interval

Increased Titer of Anti-Streptococcal Antibodies ASO (anti-streptolysin O), others Positive Throat Culture for Group A Streptococcus Recent Scarlet Fever

Acute Rheumatic Carditis Acute Rheumatic Carditis (Pancarditis)(Pancarditis)

It is characterized by inflammatory changes It is characterized by inflammatory changes in all three layers of the heart. in all three layers of the heart.

Acute changes may resolve completely or Acute changes may resolve completely or progress to scarring and chronic valvular progress to scarring and chronic valvular deformities. deformities.

Acute Rheumatic Heart DiseasePathogenesis and Key Morphologic Changes

PancarditisPancarditis MyocardiumMyocardium

Scattered multiple foci of inflammation (Aschoff Bodies) Scattered multiple foci of inflammation (Aschoff Bodies) lie proximate to small vessels.lie proximate to small vessels.

Diffuse interstitial inflammatory infiltrates.Diffuse interstitial inflammatory infiltrates. EndocardiumEndocardium: Common, affect mostly mitral and : Common, affect mostly mitral and

aortic valves.aortic valves. Valves are edematous and thickened with foci of fibrinoid Valves are edematous and thickened with foci of fibrinoid

necrosis. (Aschoff nodules uncommon).necrosis. (Aschoff nodules uncommon). Formation of small vegetations “fibrinous clots” along the Formation of small vegetations “fibrinous clots” along the

lines of valve closure (Verrucous Endocarditis).lines of valve closure (Verrucous Endocarditis). PericardiumPericardium

Fibrinous Pericarditis: associated with serous or Fibrinous Pericarditis: associated with serous or serosanguinous pericardial effusion.serosanguinous pericardial effusion.

Aschoff Body in Acute Rheumatic Aschoff Body in Acute Rheumatic CarditisCarditis

Aschoff body in acute rheumatic carditis. Aschoff body in acute rheumatic carditis. Some large histiocytes with prominent Some large histiocytes with prominent

nucleoli, a prominent binuclear histiocyte, nucleoli, a prominent binuclear histiocyte, and central necrosis.and central necrosis.

Aschoff Body with “Caterpillar” Aschoff Body with “Caterpillar” NucleiNuclei

Verrucous Endocarditis Verrucous Endocarditis

Fibrinous PericarditisFibrinous Pericarditis

PancarditisPancarditisClinical ManifestationsClinical Manifestations

Symptoms: Symptoms: Pericardial friction rubs, Pericardial friction rubs, Weak heart sounds, Weak heart sounds, Tachycardia (rapid beating) and Tachycardia (rapid beating) and Arrhythmias.Arrhythmias.

In severe cases: myocarditis In severe cases: myocarditis cardiac cardiac dilation dilation functional mitral valve insufficiency functional mitral valve insufficiency or even congestive heart failure.or even congestive heart failure.

Chronic Rheumatic Heart Chronic Rheumatic Heart DiseasesDiseases

It is characterized by irreversible deformity of It is characterized by irreversible deformity of one or more cardiac valves. Usually mitral one or more cardiac valves. Usually mitral valve is abnormal in 95% of cases.valve is abnormal in 95% of cases.

Combined oartic and mitral valve disease is Combined oartic and mitral valve disease is present in 25% of cases. Aortic valve alone is present in 25% of cases. Aortic valve alone is rarely affected.rarely affected.

Pulmonary and Tricuspid valves are extremely Pulmonary and Tricuspid valves are extremely rare to be affected.rare to be affected.

Chronic Rheumatic Heart Chronic Rheumatic Heart DiseasesDiseases

Pathological changes: Pathological changes: Chronic scarring and calcification of the valve Chronic scarring and calcification of the valve

leaflets → stiff and thickened structure → leaflets → stiff and thickened structure → stenotic valve orifice and Improper closure stenotic valve orifice and Improper closure (regurgitation).(regurgitation).

Shortening and fusion of the chordae Shortening and fusion of the chordae tendineae.tendineae.

Chronic Rheumatic Heart Chronic Rheumatic Heart DiseasesDiseases

Clinical manifestations: depend on which Clinical manifestations: depend on which valve is involvedvalve is involved

Cardiac murmurs, Cardiac murmurs, Arrhythmia, Arrhythmia, Hypertrophy, Hypertrophy, Dilation, Dilation, Congestive heart failure,Congestive heart failure, Thromboembolic complications Thromboembolic complications Infective endocarditisInfective endocarditis

Chronic Rheumatic Mitral Chronic Rheumatic Mitral ValvulitisValvulitis

It is the most common cause of mitral stenosis It is the most common cause of mitral stenosis It causes stenosis > regurgitationIt causes stenosis > regurgitation Occurs in females > males.Occurs in females > males.

Mitral Stenosis:Mitral Stenosis: Leaflets are thick, rigid, and inter-adherent. And the Leaflets are thick, rigid, and inter-adherent. And the

orifice is narrowed “fish mouth” deformity.orifice is narrowed “fish mouth” deformity. Dilatation and hypertrophy of left atrium.Dilatation and hypertrophy of left atrium. Endocardium is thickened particularly above Endocardium is thickened particularly above

posterior mitral leaflet .posterior mitral leaflet . Lungs: firm and heavy (result of chronic passive Lungs: firm and heavy (result of chronic passive

congestion).congestion).

Chronic Rheumatic mitral Chronic Rheumatic mitral valvulitisvalvulitis

Mitral Regurgitation:Mitral Regurgitation: Valve leaflets are retracted Valve leaflets are retracted Left ventricular dilatation and hypertrophy.Left ventricular dilatation and hypertrophy.

Rheumatic mitral stenosis demonstrates Rheumatic mitral stenosis demonstrates diffuse fibrous thickening and distortion of the diffuse fibrous thickening and distortion of the valve leaflets, commissural fusion (arrow) "fish valve leaflets, commissural fusion (arrow) "fish

mouth" shape. mouth" shape.

Chronic Aortic ValvulitisChronic Aortic Valvulitis

Males > females and usually associated with mitral Males > females and usually associated with mitral valvulitis.valvulitis.

May occur in congenital bicuspid aortic valve (2%) May occur in congenital bicuspid aortic valve (2%)

Aortic stenosis:Aortic stenosis: Valve cusps are thickened, firm and adherent to Valve cusps are thickened, firm and adherent to

each other each other the aortic valve orifice is reduced to the aortic valve orifice is reduced to a rigid triangular channel.a rigid triangular channel.

Aortic stenosis increases the pressure load on left Aortic stenosis increases the pressure load on left ventricle causing hypertrophy.ventricle causing hypertrophy.

Subsequent left ventricular failure is associated Subsequent left ventricular failure is associated with dilation of the chamber.with dilation of the chamber.

Rheumatic aortic stenosis demonstrating Rheumatic aortic stenosis demonstrating thickening and distortion of the cusps with thickening and distortion of the cusps with

commissural fusion (rigid triangular channel)commissural fusion (rigid triangular channel)

Calcific Aortic Stenosis Calcific Aortic Stenosis degenerative calcific aorticstenosis degenerative calcific aorticstenosis

Degenerative changes in the cardiac valves are Degenerative changes in the cardiac valves are part of normal aging process, but it can develop to part of normal aging process, but it can develop to cause pathologic stenosis.cause pathologic stenosis.

The aortic valve leaflets are rigid and deformed by The aortic valve leaflets are rigid and deformed by calcified masses.calcified masses.

Fibrosis and calcification of the valve cusps lead to Fibrosis and calcification of the valve cusps lead to valve sclerosis.valve sclerosis.

The calcium deposits lie behind the valve cusps (at The calcium deposits lie behind the valve cusps (at the bases of the cusps).the bases of the cusps).

Calcific Aortic Stenosis Calcific Aortic Stenosis (degenerative calcific aortic stenosis) (degenerative calcific aortic stenosis)

The free edges of the cusps are usually not The free edges of the cusps are usually not affected. Calcific stenosis does not fuse the affected. Calcific stenosis does not fuse the cusps. cusps.

Symptom: severe cases may cause angina, Symptom: severe cases may cause angina, syncope (fainting), congestive heart failure, syncope (fainting), congestive heart failure, L.V. hypertrophy, sudden death due to L.V. hypertrophy, sudden death due to arrhythmia.arrhythmia.

Degenerative calcific aortic stenosis of a normal Degenerative calcific aortic stenosis of a normal valve having three cusps. valve having three cusps.

Nodular masses of calcium are heaped up within Nodular masses of calcium are heaped up within the sinuses of Valsalva (arrow). Note that the the sinuses of Valsalva (arrow). Note that the

commissures are not fused.commissures are not fused.

Mitral Valve ProlapseMitral Valve Prolapse

It is a common cardiac disorder (3-5% of adult It is a common cardiac disorder (3-5% of adult population, mainly females, ages 20-40 years).population, mainly females, ages 20-40 years).

It is usually an isolated problem but it may arise as a It is usually an isolated problem but it may arise as a complication of certain connective tissue disorders complication of certain connective tissue disorders (e.g. Marfan syndrome).(e.g. Marfan syndrome).

It has been reported as an isolated autosomal It has been reported as an isolated autosomal dominant condition that maps to chromosome 16p. dominant condition that maps to chromosome 16p.

Less commonly, as an x-linked recessive disorders.Less commonly, as an x-linked recessive disorders.

Mitral Valve ProlapseMitral Valve Prolapse

Most patients are asymptomatic Most patients are asymptomatic Some have palpitations and fatigue Some have palpitations and fatigue Some have atypical chest pain, and mid-systolic Some have atypical chest pain, and mid-systolic

click with a late systolic murmur.click with a late systolic murmur. The valve leaflets (posterior cusp) are soft and The valve leaflets (posterior cusp) are soft and

enlarged → ballooning of the leaflets into left atrium enlarged → ballooning of the leaflets into left atrium during systole. during systole.

Chordae tendineae are elongated, fragile and may Chordae tendineae are elongated, fragile and may rupture in severe cases. rupture in severe cases.

The valve annulus may be dilated.The valve annulus may be dilated.

Mitral Valve ProlapseMitral Valve Prolapse

Microscopic examinationMicroscopic examination Excessive amounts of loose, edematous, faintly Excessive amounts of loose, edematous, faintly

basophilic tissue within the middle layer (spongiosa) basophilic tissue within the middle layer (spongiosa) of the valve leaflets and chordae.of the valve leaflets and chordae.

ComplicationsComplications Mitral regurgitation and congestive heart failure. Mitral regurgitation and congestive heart failure. Sudden death caused by ventricular arrhythmias. Sudden death caused by ventricular arrhythmias. Infective endocarditis. Infective endocarditis.

Left ventricle demonstrates ballooning Left ventricle demonstrates ballooning with prolapse of the posterior mitral leaflet with prolapse of the posterior mitral leaflet

into the left atrium.into the left atrium.

EndocarditisEndocarditis

Infective Endocarditis (IE)Infective Endocarditis (IE)

Infection of the cardiac valves or the Infection of the cardiac valves or the endocardium, resulting in the formation of endocardium, resulting in the formation of vegetation (mass of thrombotic debris and micro-vegetation (mass of thrombotic debris and micro-organisms) on valve leaflets, mostly aortic and organisms) on valve leaflets, mostly aortic and mitral valves.mitral valves.

IE. is divided into two forms:IE. is divided into two forms: Acute Infective EndocarditisAcute Infective Endocarditis Subacute Infective EndocarditisSubacute Infective Endocarditis

Infective EndocarditisInfective Endocarditis

AcuteAcute SubacuteSubacute

OrganismOrganism High virulant High virulant staphylococcusstaphylococcus

Low virulant hemolytic Low virulant hemolytic streptococcusstreptococcus

ValveValve Normal and deformed Normal and deformed valvesvalves

Deformed valveDeformed valve

ProgressionProgression RapidRapid SlowSlow

ResponseResponse Little local reaction, Little local reaction, lession is destructivelession is destructive

Local inflammation, Local inflammation, lession is less lession is less destructivedestructive

ResolutionResolution Death (50%)Death (50%) Recovery (antibiotics)Recovery (antibiotics)

Infective EndocarditisInfective EndocarditisEtiology and PathogenesisEtiology and Pathogenesis

BacteremiaBacteremia Obvious hematogenous infection as with:Obvious hematogenous infection as with:

Intravenous drug abusers, Intravenous drug abusers, Elsewhere infection, Elsewhere infection, Previous dental, surgical or interventional Previous dental, surgical or interventional

procedure (urinary catheterization).procedure (urinary catheterization). Occult source of bacteremia Occult source of bacteremia

Small injuries to skin or mucosal surfaces such as Small injuries to skin or mucosal surfaces such as brushing the teeth.brushing the teeth.

Infective EndocarditisInfective EndocarditisEtiology and PathogenesisEtiology and Pathogenesis

Causative Organisms Causative Organisms

-Hemolytic (viridans) streptococci attacks -Hemolytic (viridans) streptococci attacks

deformed valves (50-60%).deformed valves (50-60%).

Staphylococcus aureus attacks healthy or Staphylococcus aureus attacks healthy or

deformed valves (intravenous drug abusers) (10-deformed valves (intravenous drug abusers) (10-

20%) .20%) .

Coagulase-negative staphylococci (S. epidermidis) Coagulase-negative staphylococci (S. epidermidis)

attacks prosthetic valve.attacks prosthetic valve.

Infective EndocarditisInfective EndocarditisRisk FactorsRisk Factors

Cardiac abnormalities: such as chronic valvular Cardiac abnormalities: such as chronic valvular

diseases and high pressure shunts within the heart diseases and high pressure shunts within the heart

(small ventricular septal defects). (small ventricular septal defects).

Prosthetic heart valves (10% to 20%).Prosthetic heart valves (10% to 20%).

Intravenous drug abusers (right side of the heart)Intravenous drug abusers (right side of the heart)

Pathology of Acute Pathology of Acute EndocarditisEndocarditis

Gross: vegetations may obstruct valve orifice and Gross: vegetations may obstruct valve orifice and cause rupture of the leaflets, cordae tendineae, or cause rupture of the leaflets, cordae tendineae, or papillary muscles. papillary muscles. May cause abscess in perivalvular tissue (ring May cause abscess in perivalvular tissue (ring

abscess).abscess). Vegetations may become systemic emboli Vegetations may become systemic emboli

infarcts (brain, kidneys, myocardium) and infarcts (brain, kidneys, myocardium) and abscesses.abscesses.

Micro: vegetations consist of large number of Micro: vegetations consist of large number of organisms, fibrin and blood cells. organisms, fibrin and blood cells.

Pathology of Subacute Pathology of Subacute Endocarditis Endocarditis

Gross: vegetations are firmer and less destructive Gross: vegetations are firmer and less destructive

(ring abscess uncommon).(ring abscess uncommon).

Systemic emboli may develop and cause Systemic emboli may develop and cause

infarcts, without abscesses.infarcts, without abscesses.

Micro: granulation tissue is seen at the base of the Micro: granulation tissue is seen at the base of the

vegetations.vegetations.

Later: fibrosis, calcifications and chronic Later: fibrosis, calcifications and chronic

inflammatory infiltrates.inflammatory infiltrates.

Infective EndocarditisInfective EndocarditisClinical ManifestationClinical Manifestation

Onset: gradual or explosive (organisms).Onset: gradual or explosive (organisms). Organism of low virulence cause low-grade fever, Organism of low virulence cause low-grade fever,

malaise, weight loss.malaise, weight loss. Organism of high virulence cause high fever, Organism of high virulence cause high fever,

shaking chills.shaking chills. Cardiac murmurs, enlargement of spleen, clubbing Cardiac murmurs, enlargement of spleen, clubbing

of digits (particularly in subacute cases), and of digits (particularly in subacute cases), and petechiae.petechiae.

Blood culture is important (only minority of cases Blood culture is important (only minority of cases remain negative).remain negative).

Infective EndocarditisInfective EndocarditisComplicationsComplications

Regurgitation leading to congestive heart failure.Regurgitation leading to congestive heart failure. Myocardial abscess (ring abscess).Myocardial abscess (ring abscess). Extension of infection to root of aorta (mycotic Extension of infection to root of aorta (mycotic

aneurysm).aneurysm). Systemic emboli, also pulmonary emboli in right-Systemic emboli, also pulmonary emboli in right-

sided endocarditis.sided endocarditis. Renal complications (glomerulonephritis and Renal complications (glomerulonephritis and

Infarction).Infarction).

Bacterial Endocarditis Remote Embolic Bacterial Endocarditis Remote Embolic EffectsEffects

Endocarditis of the mitral valveEndocarditis of the mitral valve(subacute, caused by streptococcus (subacute, caused by streptococcus

viridans) viridans)

Acute endocarditis of a congenitally Acute endocarditis of a congenitally bicuspid aortic valve with severe cuspal bicuspid aortic valve with severe cuspal

destruction and ring abscess (arrow).destruction and ring abscess (arrow).

Nonbacterial Thrombotic Endocarditis Nonbacterial Thrombotic Endocarditis (NBTE), Marantic Endocarditis(NBTE), Marantic Endocarditis

Characterized by sterile small nodules less than 5 Characterized by sterile small nodules less than 5 mm, (fibrin, platelets and other blood components) mm, (fibrin, platelets and other blood components) on the valve leaflets along the line of closure. on the valve leaflets along the line of closure.

The valve leaflets are normal, no inflammation or The valve leaflets are normal, no inflammation or fibrosis. fibrosis.

Mitral valve is the most common site, followed by Mitral valve is the most common site, followed by aortic valveaortic valve

It has been found to be associated with endothelial It has been found to be associated with endothelial abnormalities, deep venous thrombosis, and abnormalities, deep venous thrombosis, and malignancy (adenocarcinoma).malignancy (adenocarcinoma).

Libman-Sacks Endocarditis Libman-Sacks Endocarditis (LSE)(LSE)

Small sterile vegetations on ventricular or Small sterile vegetations on ventricular or both surfaces of mitral & tricuspid valves in both surfaces of mitral & tricuspid valves in some patients with Systemic Lupus some patients with Systemic Lupus Erythematosus.Erythematosus.

Nonbacterial Thrombotic Endocarditis (NBTE).Nonbacterial Thrombotic Endocarditis (NBTE).Nearly complete row of thrombotic vegetations Nearly complete row of thrombotic vegetations

along the line of closure of the mitral valve leaflets.along the line of closure of the mitral valve leaflets.

RHDRHD: row of small vegetations along the lines of closure of the : row of small vegetations along the lines of closure of the valve leaflets.valve leaflets.IEIE: large, irregular masses on the valve cusps that extend onto : large, irregular masses on the valve cusps that extend onto the cords. the cords. NBTENBTE: small, bland vegetations, usually attached at the line of : small, bland vegetations, usually attached at the line of closure. closure. LSELSE: has small or medium-sized vegetations on either or both : has small or medium-sized vegetations on either or both sides of the valve leaflets.sides of the valve leaflets.

Myocardial DiseasesMyocardial Diseases

Primary Myocardial Primary Myocardial DiseasesDiseases

A group of diseases intrinsic to myocardial fibers, A group of diseases intrinsic to myocardial fibers, including mainly:including mainly: Myocarditis: inflammatory conditions of the Myocarditis: inflammatory conditions of the

myocardium result in myocardium injurymyocardium result in myocardium injury Cardiomyopathies: primary non-infectious Cardiomyopathies: primary non-infectious

abnormalities in the myocardium.abnormalities in the myocardium. Dilated cardiomyopathyDilated cardiomyopathy Obstructive cardiomyopathyObstructive cardiomyopathy Restrictive cardiomyopathyRestrictive cardiomyopathy

MyocarditisMyocarditis

The heart may be of normal size, but more The heart may be of normal size, but more commonly it is dilated. commonly it is dilated.

The myocardium is flabby, pale and often contains The myocardium is flabby, pale and often contains small areas of hemorrhage. small areas of hemorrhage.

In most cases, myocarditis appears to be self-limitedIn most cases, myocarditis appears to be self-limited Clinical features range from an asymptomatic state Clinical features range from an asymptomatic state

to severe congestive heart failure at late stageto severe congestive heart failure at late stage Arrhythmia: lethal ventricular arrhythmias Arrhythmia: lethal ventricular arrhythmias

accounting for most sudden cardiac deaths.accounting for most sudden cardiac deaths.

Myocarditis: Major CausesMyocarditis: Major Causes

InfectionsInfections Immune-Mediated ReactionsImmune-Mediated Reactions

Myocarditis: Major CausesMyocarditis: Major Causes InfectionsInfections

Viruses: the most common cause in USA (e.g., Viruses: the most common cause in USA (e.g., coxsackievirus, echovirus). coxsackievirus, echovirus).

Chlamydia (e.g., C. psittaci)Chlamydia (e.g., C. psittaci) Rickettsia (e.g., R. typhi [typhus fever])Rickettsia (e.g., R. typhi [typhus fever]) Bacteria (e.g., Corynebacterium [diphtheria], Bacteria (e.g., Corynebacterium [diphtheria],

Neisseria [meningococcus], Borrelia [Lyme Neisseria [meningococcus], Borrelia [Lyme disease])disease])

Fungi (e.g., Candida)Fungi (e.g., Candida) Protozoa (e.g., Trypanosoma [Chagas disease], Protozoa (e.g., Trypanosoma [Chagas disease],

the most common cause in South America)the most common cause in South America) Helminths (e.g., trichinosis)Helminths (e.g., trichinosis)

Myocarditis: Major CausesMyocarditis: Major Causes

Immune-Mediated ReactionsImmune-Mediated Reactions Postviral and Poststreptococcal (rheumatic Postviral and Poststreptococcal (rheumatic

fever)fever) Systemic lupus erythematosusSystemic lupus erythematosus Drug hypersensitivity (e.g., methyldopa, Drug hypersensitivity (e.g., methyldopa,

sulfonamides)sulfonamides) Transplant rejectionTransplant rejection

Unknown : Sarcoidosis, and Giant cell myocarditisUnknown : Sarcoidosis, and Giant cell myocarditis

Myocarditis: MicroscopicallyMyocarditis: Microscopically

Viruses: edema and inflammatory infiltrate Viruses: edema and inflammatory infiltrate dominated by lymphocytes, myocyte degeneration dominated by lymphocytes, myocyte degeneration and necrosis.and necrosis.

Chronic cases: ventricular dilation, inflammation is Chronic cases: ventricular dilation, inflammation is less obvious, myocardial fibrosis becomes more less obvious, myocardial fibrosis becomes more prominent prominent

Parasites: the organism is demonstrable Parasites: the organism is demonstrable histologically, (Chagas disease, trypanosomes histologically, (Chagas disease, trypanosomes directly infect cardiac muscle fibers).directly infect cardiac muscle fibers).

Myocarditis: MicroscopicallyMyocarditis: Microscopically(Cont......)(Cont......)

Bacteria: neutrophilic infiltrate, and sometimes Bacteria: neutrophilic infiltrate, and sometimes abscess. abscess.

Cardiac transplant rejection: interstitial lymphocytes Cardiac transplant rejection: interstitial lymphocytes and myocyte degeneration.and myocyte degeneration.

Giant cell myocarditis is characterized by an Giant cell myocarditis is characterized by an inflammatory infiltrate in which multinucleated giant inflammatory infiltrate in which multinucleated giant cells are prominent. cells are prominent.

Lymphocytic Myocarditis: Lymphocytic Myocarditis: Dense mononuclear inflammatory cell Dense mononuclear inflammatory cell

infiltrate and associated myocyte injury.infiltrate and associated myocyte injury.

Hypersensitivity Myocarditis: Hypersensitivity Myocarditis: interstitial inflammatory infiltrate composed interstitial inflammatory infiltrate composed

largely of eosinophils and mononuclear largely of eosinophils and mononuclear inflammatory cells.inflammatory cells.

Giant Cell Myocarditis: Giant Cell Myocarditis: Mononuclear inflammatory infiltrate Mononuclear inflammatory infiltrate

(lymphocytes and macrophages), with (lymphocytes and macrophages), with extensive loss of muscle, and extensive loss of muscle, and

multinucleated giant cells, apparently multinucleated giant cells, apparently derived from muscle.derived from muscle.

Myocarditis: Myocarditis: Trypanosoma cruzi (Chagas disease). Trypanosoma cruzi (Chagas disease).

Intracellular organisms inside a myocyte, no Intracellular organisms inside a myocyte, no inflammatory reaction.inflammatory reaction.

CardiomyopathiesCardiomyopathies

CardiomyopathiesCardiomyopathies

Cardiomyopathies has been classified into three Cardiomyopathies has been classified into three forms:forms: Dilated Cardiomyopathy Dilated Cardiomyopathy Hypertrophic CardiomyopathyHypertrophic Cardiomyopathy Restrictive Cardiomyopathy Restrictive Cardiomyopathy

Dilated Cardiomyopathy Dilated Cardiomyopathy (DCM)(DCM)

Characterized by progressive cardiac hypertrophy, Characterized by progressive cardiac hypertrophy,

dilation and contractile (systolic) dysfunction dilation and contractile (systolic) dysfunction

(ineffective contraction, patients may have an (ineffective contraction, patients may have an

ejection fraction of less than 25%). ejection fraction of less than 25%).

Dilated Cardiomyopathy (DCM)Dilated Cardiomyopathy (DCM)

Exact cause is unknown in 90% of cases, but can Exact cause is unknown in 90% of cases, but can result from:result from: Viral myocarditis: presence of nucleic acids of Viral myocarditis: presence of nucleic acids of

coxsackievirus B and other enteroviruses. coxsackievirus B and other enteroviruses. Toxic chemicals: Toxic chemicals:

Alcohol abuse (ethanol toxicity)Alcohol abuse (ethanol toxicity) CobaltCobalt Chemotherapeutic agents (Doxorubicin).Chemotherapeutic agents (Doxorubicin).

Pregnancy: peripartum cardiomyopathy occurs Pregnancy: peripartum cardiomyopathy occurs late in pregnancy or several weeks post partum. late in pregnancy or several weeks post partum.

DCM: Genetic and familial conditionsDCM: Genetic and familial conditions Inherited genetic abnormalities are responsible for Inherited genetic abnormalities are responsible for

(20% to 30%) of cases of dilated cardiomyopathy. (20% to 30%) of cases of dilated cardiomyopathy. Mutations in genes coding for cytoskeletal proteins: Mutations in genes coding for cytoskeletal proteins:

Mutations in the dystrophin gene on X Mutations in the dystrophin gene on X chromosome (responsible for Becker and chromosome (responsible for Becker and Duchenne muscular dystrophy).Duchenne muscular dystrophy).

Abnormalities in genes encoding desmin, Abnormalities in genes encoding desmin, merosin, and dystrophin-associated proteins merosin, and dystrophin-associated proteins termed sarcoglycans.termed sarcoglycans.

Abnormalities in certain mitochondrial enzymes. Abnormalities in certain mitochondrial enzymes. Mutations in certain sarcomere protein genes (e.g., Mutations in certain sarcomere protein genes (e.g.,

β-myosin and cardiac troponin T). β-myosin and cardiac troponin T).

DCM: PathologyDCM: Pathology The heart is enlarged and flabby, weights 900 g (2-The heart is enlarged and flabby, weights 900 g (2-

3X normal), this is caused by dilation and 3X normal), this is caused by dilation and hypertrophy of all chambers.hypertrophy of all chambers.

Dilation and poor contractile function cause stasis of Dilation and poor contractile function cause stasis of blood in the cardiac chambers and predispose to the blood in the cardiac chambers and predispose to the development of fragile mural thrombi and development of fragile mural thrombi and subsequent emboli. subsequent emboli.

Microscopic features are non-specificMicroscopic features are non-specific Myocyte hypertrophyMyocyte hypertrophy Interstitial fibrosis, wavy fiber changeInterstitial fibrosis, wavy fiber change Scanty mononuclear infiltrate (sometimes)Scanty mononuclear infiltrate (sometimes)

DCM: Clinical FeaturesDCM: Clinical Features DCM is the most common form, accounting for about DCM is the most common form, accounting for about

90% of cases.90% of cases. Most common between ages of (20-60 years), men > Most common between ages of (20-60 years), men >

women. women. Most cases arise sporadically (except familial Most cases arise sporadically (except familial

cases).cases). Patients develop progressive congestive heart Patients develop progressive congestive heart

failure. failure. Prognosis is very poor (except peripartum DCM):Prognosis is very poor (except peripartum DCM):

50% die within 2yr, 75% within 5yr due to (CHF, 50% die within 2yr, 75% within 5yr due to (CHF, embolic complications or ventricular arrhythmias).embolic complications or ventricular arrhythmias).

Cardiac transplantation is the only mode of therapyCardiac transplantation is the only mode of therapy

DCM: Four-chamber dilation and DCM: Four-chamber dilation and hypertrophy. hypertrophy.

DCM: Histology demonstrating variable DCM: Histology demonstrating variable myocyte hypertrophy and interstitial myocyte hypertrophy and interstitial

fibrosisfibrosis

Hypertrophic Cardiomyopathy (HCM)Hypertrophic Cardiomyopathy (HCM) Asymmetric septal hypertrophy or Asymmetric septal hypertrophy or

Idiopathic hypertrophic subaortic stenosisIdiopathic hypertrophic subaortic stenosis

It is characterized by:It is characterized by: Myocardial hypertrophy which causes powerful Myocardial hypertrophy which causes powerful

contractions that rapidly expel blood from the contractions that rapidly expel blood from the ventricular cavities.ventricular cavities.

Abnormal (impaired) diastolic filling because of the Abnormal (impaired) diastolic filling because of the stiff, thick wall of the ventricle.stiff, thick wall of the ventricle.

The basic problem is an inability to fill a The basic problem is an inability to fill a hypertrophic left ventricle during diastole. Ejection hypertrophic left ventricle during diastole. Ejection is forceful but ineffective because the amount of is forceful but ineffective because the amount of blood in the left ventricle is greatly reduced.blood in the left ventricle is greatly reduced.

Hypertrophic Cardiomyopathy (HCM)Hypertrophic Cardiomyopathy (HCM) Asymmetric septal hypertrophy or Asymmetric septal hypertrophy or

Idiopathic hypertrophic subaortic stenosisIdiopathic hypertrophic subaortic stenosis

Pathogenesis:Pathogenesis: 50% of cases, HCM inherited as an autosomal 50% of cases, HCM inherited as an autosomal

dominant traitdominant trait Mutations in genes encoding sarcomeric contractile Mutations in genes encoding sarcomeric contractile

proteins.proteins. -myosin heavy chain (commonest 30%)-myosin heavy chain (commonest 30%) Troponin I and T, Troponin I and T, -tropomyosin, and myosin -tropomyosin, and myosin

light chains light chains Allelic heterogeneity Allelic heterogeneity

HCM: PathologyHCM: Pathology The heart weights 800 The heart weights 800

gm gm Hypertrophy of LV and Hypertrophy of LV and

interventricular septum interventricular septum “IVS”, without dilation “IVS”, without dilation (the left atrium may be (the left atrium may be dilated). dilated).

IVS is thicker than the IVS is thicker than the free (lateral) wall of the free (lateral) wall of the left ventricle.left ventricle.

IVS hypertrophy is most IVS hypertrophy is most evident in subaortic evident in subaortic regionregion

HCM: PathologyHCM: Pathology

It is often associated with ventricular outflow It is often associated with ventricular outflow

obstruction during systole which is caused by obstruction during systole which is caused by

abnormal anterior motion of the mitral valve leaflet abnormal anterior motion of the mitral valve leaflet

during systole.during systole.

This motion lead to recurrent, forceful contact This motion lead to recurrent, forceful contact

between the septum and the anterior mitral leaflet between the septum and the anterior mitral leaflet

causing thickening of the anterior mitral leaflet and causing thickening of the anterior mitral leaflet and

adjacent septal endocardium.adjacent septal endocardium.

HCM: PathologyHCM: Pathology

MicroscopicallyMicroscopically

Irregular arrangement Irregular arrangement

of hypertrophied of hypertrophied

abnormally branching abnormally branching

myocytes myocytes

Myocardial fibrosis (late Myocardial fibrosis (late

stage)stage)

HCM: ClinicalHCM: Clinical Characterized by: Characterized by:

Exertional dyspnea Exertional dyspnea Harsh systolic ejection murmur Harsh systolic ejection murmur Myocardial ischemia is common, and thus anginal Myocardial ischemia is common, and thus anginal

pain is frequent.pain is frequent. Ventricular arrhythmias and sudden death Ventricular arrhythmias and sudden death Increased risk of infective endocarditis Increased risk of infective endocarditis Later, progressive myocardial fibrosis may cause Later, progressive myocardial fibrosis may cause

congestive heart failure.congestive heart failure. Prognosis: varies with the genetic defect, so Prognosis: varies with the genetic defect, so

molecular diagnosis is usefulmolecular diagnosis is useful

Restrictive Cardiomyopathy Restrictive Cardiomyopathy (RCM)(RCM)

Characterized by primary decrease in ventricular Characterized by primary decrease in ventricular compliance, resulting in impaired ventricular filling compliance, resulting in impaired ventricular filling during diastole.during diastole.

The problem is a stiff and inelastic ventricle that can The problem is a stiff and inelastic ventricle that can be filled only with great effort, but the systole is not be filled only with great effort, but the systole is not forceful.forceful.

Myocardial contractility, although often normal early Myocardial contractility, although often normal early in the course of the disease, usually declines, in the course of the disease, usually declines, causing congestive heart failure in later stages.causing congestive heart failure in later stages.

Symptoms: fatigue, exertional dyspnea, chest pain, Symptoms: fatigue, exertional dyspnea, chest pain, and arrhythmiasand arrhythmias

It is the least common type of Cardiomyopathy.It is the least common type of Cardiomyopathy.

RCM: CausesRCM: Causes

Endomyocardial fibrosis (the most common cause) Endomyocardial fibrosis (the most common cause) accounts for up to 10% of cases of childhood heart accounts for up to 10% of cases of childhood heart disease in tropical areas.disease in tropical areas.

Eosinophilic endomyocardial fibrosis (Löffler Eosinophilic endomyocardial fibrosis (Löffler syndrome), is rare. syndrome), is rare.

Genetic factors are not clearly defined, but may Genetic factors are not clearly defined, but may account for some cases (desmin mutations) account for some cases (desmin mutations)

Additional important causes: amyloidosis, Additional important causes: amyloidosis, endocardial fibroelastosis, hemochromatosis, endocardial fibroelastosis, hemochromatosis, radiation injury to the heart.radiation injury to the heart.

RCM: PathologyRCM: Pathology

Tropical endomyocardial fibrosis and Löffler Tropical endomyocardial fibrosis and Löffler syndrome: syndrome: The atria are dilated, and the ventricles of The atria are dilated, and the ventricles of

normal sizenormal size The endocardium is thick and solid (left The endocardium is thick and solid (left

ventricle).ventricle). Microscopically: dense fibrosis in endocardium Microscopically: dense fibrosis in endocardium

& myocardium. & myocardium.

RCM: Pathology (Cont...)RCM: Pathology (Cont...)

Eosinophilic endomyocardial fibrosis: Eosinophilic endomyocardial fibrosis: infiltration by eosinophils (early stages).infiltration by eosinophils (early stages).

Endocardial fibroelastosis (uncommon):Endocardial fibroelastosis (uncommon): Occurs mostly in children < 2 years of age, Occurs mostly in children < 2 years of age, Abundant fibroelastic tissue in the Abundant fibroelastic tissue in the

endocardium revealing porcelain-like endocardium revealing porcelain-like appearance).appearance).

PericarditisPericarditis

PericarditisPericarditis Primary: uncommon, mostly viral and sometimes by Primary: uncommon, mostly viral and sometimes by

other organisms (pyogenic bacteria, mycobacteria other organisms (pyogenic bacteria, mycobacteria and fungi).and fungi).

Secondary to: Secondary to: Acute myocardial infarction, cardiac surgery, or Acute myocardial infarction, cardiac surgery, or

radiation to the mediastinum.radiation to the mediastinum. Associated with systemic disorders, mostly with Associated with systemic disorders, mostly with

uremia, rheumatic fever, systemic lupus uremia, rheumatic fever, systemic lupus erythematosus (SLE), and metastatic erythematosus (SLE), and metastatic malignancies (bloody effusions).malignancies (bloody effusions).

Pericarditis OutcomesPericarditis Outcomes

Pericarditis may Pericarditis may Cause immediate hemodynamic complications if Cause immediate hemodynamic complications if

a significant effusion is presenta significant effusion is present Resolve without significant sequelaeResolve without significant sequelae Progress to a chronic fibrosing process. Progress to a chronic fibrosing process.

Acute Pericarditis: MorphologyAcute Pericarditis: Morphology

In uremia, and acute rheumatic fever: the exudate is In uremia, and acute rheumatic fever: the exudate is fibrinous and impart a shaggy irregular pericardial fibrinous and impart a shaggy irregular pericardial surface (bread and butter pericarditis).surface (bread and butter pericarditis).

Viral pericarditis Viral pericarditis fibrinous exudate. fibrinous exudate. Acute bacterial pericarditis Acute bacterial pericarditis fibrinopurulent fibrinopurulent

exudate.exudate. TuberculosisTuberculosis caseous materials and hemorrhagic caseous materials and hemorrhagic

pericarditis pericarditis Pericardial metastases: irregular nodules with a Pericardial metastases: irregular nodules with a

shaggy fibrinous exudate and a bloody effusion .shaggy fibrinous exudate and a bloody effusion .

Fibrinous Pericarditis Fibrinous Pericarditis

The pericardial surface shows strands The pericardial surface shows strands of pink fibrin extending outward. of pink fibrin extending outward. There is underlying inflammation.There is underlying inflammation.

Chronic Pericarditis: Chronic Pericarditis: MorphologyMorphology

Ranges from delicate adhesions to dense fibrotic Ranges from delicate adhesions to dense fibrotic scars. scars.

In extreme cases the heart cannot expand normally In extreme cases the heart cannot expand normally during diastole, a condition called constrictive during diastole, a condition called constrictive pericarditis.pericarditis.

Pericarditis: ClinicalPericarditis: Clinical

Atypical chest pain (worse on reclining), Atypical chest pain (worse on reclining), Friction rub.Friction rub. Significant exudate Significant exudate signs and symptoms of signs and symptoms of

cardiac tamponade cardiac tamponade faint distant heart sounds, faint distant heart sounds, distended neck veins, declining cardiac output, and distended neck veins, declining cardiac output, and shock.shock.

Chronic constrictive pericarditis Chronic constrictive pericarditis venous venous distension and low cardiac output.distension and low cardiac output.

Pericardial EffusionsPericardial Effusions Accumulation of fluid in the pericardium, fluid nature Accumulation of fluid in the pericardium, fluid nature

varies with cause, major types and their causes are: varies with cause, major types and their causes are: Serous: congestive heart failure, Serous: congestive heart failure,

hypoalbuminemiahypoalbuminemia Serosanguineous: blunt chest trauma, Serosanguineous: blunt chest trauma,

malignancymalignancy Chylous: mediastinal lymphatic obstructionChylous: mediastinal lymphatic obstruction Fibrinous / Serofibrinous: RF, connective tissue Fibrinous / Serofibrinous: RF, connective tissue

diseases, MI and post-MI, trauma & uremiadiseases, MI and post-MI, trauma & uremia Blood (Hemopericardium): ruptured aortic Blood (Hemopericardium): ruptured aortic

aneurysms, ruptured myocardial infarcts, aneurysms, ruptured myocardial infarcts, penetrating traumatic injury to the heart. penetrating traumatic injury to the heart.

Cardiac TumorsCardiac Tumors Heart tumor are rareHeart tumor are rare Metastatic Neoplasms: metastases may reach the Metastatic Neoplasms: metastases may reach the

heart via lymphatic, venous, or arterial channels. heart via lymphatic, venous, or arterial channels. seen in up to 10% of patients dying of seen in up to 10% of patients dying of

disseminated cancer, mostly involving disseminated cancer, mostly involving pericardium. pericardium.

The most common primary neoplasms that The most common primary neoplasms that metastasize to the heart are:metastasize to the heart are: carcinomas of the lung and breast, carcinomas of the lung and breast, malignant melanomas, malignant melanomas, lymphomas & leukemias. lymphomas & leukemias.

Cardiac tumorsCardiac tumors

Primary tumors include:Primary tumors include:

Myxoma: is commonest heart tumor in adults, Myxoma: is commonest heart tumor in adults,

benign, 90% in Lt atrium. They appear as sessile or benign, 90% in Lt atrium. They appear as sessile or

pedunculated gelatinous mass covered by pedunculated gelatinous mass covered by

endotheliumendothelium

Microscopically: multinucleated stellate (Star-Microscopically: multinucleated stellate (Star-

shaped) cells, edema and mucoid stroma.shaped) cells, edema and mucoid stroma.

Cardiac tumorsCardiac tumors RhabdomyomaRhabdomyoma

Common (infancy and children)Common (infancy and children) Associated with tuberous sclerosisAssociated with tuberous sclerosis Grossly: myocardial masses project into the Grossly: myocardial masses project into the

ventricular lumen solitary or multifocal. ventricular lumen solitary or multifocal. Microscopically: eosinophilic, polygonal cells Microscopically: eosinophilic, polygonal cells

(contain large, glycogen-rich cytoplasmic (contain large, glycogen-rich cytoplasmic granules). granules).

Lipoma, and Papillary Elastofibromas, Lipoma, and Papillary Elastofibromas, Sarcomas: Angiosarcomas, and Rhabdomyo-Sarcomas: Angiosarcomas, and Rhabdomyo-

sarcomas.sarcomas.

Vascular DiseasesVascular Diseases

VasculitisVasculitis

Inflammation of blood vessels of any size, Inflammation of blood vessels of any size, affecting one or few vessels in a limited affecting one or few vessels in a limited area or it could be systemic affecting area or it could be systemic affecting multiple organ systems.multiple organ systems.

VasculitisVasculitis Mostly immune reaction related:Mostly immune reaction related:

Immune complexes.Immune complexes.

(SLE, cryoglobulinemic vasc.)(SLE, cryoglobulinemic vasc.)

(hypersensitivity) (hypersensitivity)

(viral infection, hepatitis) (viral infection, hepatitis) Antineutrophil cytoplasmic antibodies (ANCAs).Antineutrophil cytoplasmic antibodies (ANCAs).

p-ANCAs (perinuclear p-ANCAs (perinuclear myeloperoxidase) myeloperoxidase)

(microscopic polyangiitis, Churg-Strauss (microscopic polyangiitis, Churg-Strauss syndrome)syndrome)

c-ANCAs (cytoplasmic c-ANCAs (cytoplasmic proteinase 3) proteinase 3)

(Wegener granulomatosis)(Wegener granulomatosis)

VasculitisVasculitis Mostly immune reaction related:Mostly immune reaction related:

Immune complexes.Immune complexes. Antineutrophil cytoplasmic antibodies (ANCAs).Antineutrophil cytoplasmic antibodies (ANCAs). Antiendothelial Cell Antibodies: induced by Antiendothelial Cell Antibodies: induced by

defects in immune regulation (SLE, Kawasaki)defects in immune regulation (SLE, Kawasaki) Infection Infection

Classification of Classification of Vasculitis Vasculitis

Based on Based on PathogenesisPathogenesis

Direct Infection

Bacterial (e.g., Neisseria)

Rickettsial (e.g., Rocky Mountain spotted fever)

Spirochetal (e.g., syphilis)

Fungal (e.g., aspergillosis, mucormycosis)

Viral (e.g., herpes zoster-varicella)

Immunologic

Immune complex-mediated

Infection-induced (e.g., hepatitis B and C virus)

Henoch-Schönlein purpura

Systemic lupus erythematosus and rheumatoid arthritis

Drug-induced

Cryoglobulinemia

Serum sickness

Antineutrophil cytoplasmic autoantibody-mediated

Wegener granulomatosis

Microscopic polyangiitis (microscopic polyarteritis)

Churg-Strauss syndrome

Direct antibody attack-mediated

Goodpasture syndrome (anti-glomerular basement membrane antibodies)

Kawasaki disease (antiendothelial antibodies)

Cell-mediated

Allograft organ rejection

Inflammatory bowel disease

Paraneoplastic vasculitis

Unknown

Giant cell (temporal) arteritis

Takayasu arteritis

Polyarteritis nodosa (classic polyarteritis nodosa)

Classification of vasculitisClassification of vasculitis

The systemic vasculitides are classified on the The systemic vasculitides are classified on the basis of the basis of the Size and Size and Anatomic site of the involved blood vessels,Anatomic site of the involved blood vessels, Histologic characteristics of the lesion, andHistologic characteristics of the lesion, and Clinical manifestations. Clinical manifestations.

There is considerable clinical and pathologic There is considerable clinical and pathologic overlap among these disorders,overlap among these disorders,

Classification of vasculitisClassification of vasculitis

Polyarteritis nodosa: Polyarteritis nodosa: Medium - sized & small arteries.Medium - sized & small arteries.

Wegener’s granulomatosis: Wegener’s granulomatosis: Arterioles,venules,capillaries and small blood Arterioles,venules,capillaries and small blood

vesseles.vesseles. Microscopic polyarteritis (hypersensitivity Microscopic polyarteritis (hypersensitivity

vasculitis): vasculitis): Venules, capillaries & arterioles.Venules, capillaries & arterioles.

Temporal (giant cell,cranial) arteritis: Temporal (giant cell,cranial) arteritis: Mainly affects large blood vesseles.Mainly affects large blood vesseles.

Giant Cell (Temporal) ArteritisGiant Cell (Temporal) Arteritis

The most common of the vasculitis, is an acute The most common of the vasculitis, is an acute and chronic, often granulomatous inflammation of and chronic, often granulomatous inflammation of arteries of large to small size (mainly in the head-arteries of large to small size (mainly in the head-especially the temporal arteries but also the especially the temporal arteries but also the vertebral and ophthalmic arteries (Blindness). vertebral and ophthalmic arteries (Blindness).

Lesions have also been found in other arteries Lesions have also been found in other arteries throughout the body, including the aorta (giant cell throughout the body, including the aorta (giant cell aortitis).aortitis).

Giant Cell (Temporal) Arteritis:Giant Cell (Temporal) Arteritis:MorphologyMorphology

Characteristically, segments of affected arteries Characteristically, segments of affected arteries develop nodular thickenings with reduction of the develop nodular thickenings with reduction of the lumen and may become thrombosed. lumen and may become thrombosed.

Common variant: Common variant: granulomatous inflammation of the inner half of granulomatous inflammation of the inner half of

the media centered on the internal elastic the media centered on the internal elastic membrane marked by membrane marked by a lymphocytic infiltrate, a lymphocytic infiltrate, multinucleate giant cells, multinucleate giant cells, fragmentation of the internal elastic lamina, fragmentation of the internal elastic lamina, macrophages are seen close to the damaged macrophages are seen close to the damaged

elastic lamina. elastic lamina.

Giant Cell (Temporal) Arteritis Giant Cell (Temporal) Arteritis (Morphology Cont..)(Morphology Cont..)

Less common pattern, a nonspecific panarteritis Less common pattern, a nonspecific panarteritis with a mixed inflammatory infiltrate (lymphocytes, with a mixed inflammatory infiltrate (lymphocytes, macrophages, neutrophils and eosinophils). macrophages, neutrophils and eosinophils).

Healed stage of both of these patterns reveals Healed stage of both of these patterns reveals collagenous thickening of the vessel wall; collagenous thickening of the vessel wall; organization of the luminal thrombus sometimes organization of the luminal thrombus sometimes transforms the artery into a transforms the artery into a fibrous cordfibrous cord. .

Giant Cell (Temporal) Arteritis:Giant Cell (Temporal) Arteritis: Pathogenesis Pathogenesis

Evidence points to a T-cell-mediated immune Evidence points to a T-cell-mediated immune response to an unknown, possibly vessel wall, response to an unknown, possibly vessel wall, antigen. antigen.

Supporting this hypothesis are a granulomatous Supporting this hypothesis are a granulomatous inflammatory response with the presence of CD4+ inflammatory response with the presence of CD4+ T cells.T cells.

Giant Cell (Temporal) Arteritis:Giant Cell (Temporal) Arteritis: Clinical Features Clinical Features

Rare before the age of 50 (F:M = 2:1) .Rare before the age of 50 (F:M = 2:1) . Symptoms are constitutional fever, fatigue, weight Symptoms are constitutional fever, fatigue, weight

loss-without localizing signs or symptoms loss-without localizing signs or symptoms The diagnosis depends on biopsy and histologic The diagnosis depends on biopsy and histologic

confirmation.confirmation. Treatment with anti-inflammatory agents is Treatment with anti-inflammatory agents is

remarkably effective.remarkably effective.

Temporal (giant cell) arteritis. Temporal (giant cell) arteritis. Giant cells at the degenerated internal Giant cells at the degenerated internal

elastic membrane in active arteritis and elastic membrane in active arteritis and intimal thickening.intimal thickening.

Temporal (giant cell) arteritis. Temporal (giant cell) arteritis. Elastic tissue stain demonstrating focal Elastic tissue stain demonstrating focal

destruction of internal elastic membrane (arrow) destruction of internal elastic membrane (arrow) and intimal thickening (IT) characteristic of long-and intimal thickening (IT) characteristic of long-

standing or healed arteritis.standing or healed arteritis.

Polyarteritis Nodosa (PAN) Polyarteritis Nodosa (PAN)

Systemic vasculitis (segmental transmural Systemic vasculitis (segmental transmural necrotizing inflammation) of small or medium-sized necrotizing inflammation) of small or medium-sized muscular arteries (muscular arteries (but not arterioles, capillaries, or but not arterioles, capillaries, or venulesvenules), typically involving kidneys, heart, liver, ), typically involving kidneys, heart, liver, and gastrointestinal tract, and gastrointestinal tract, but sparing the pulmonary but sparing the pulmonary circulation.circulation.

Individual lesions may involve only a portion of the Individual lesions may involve only a portion of the vessel circumference with preference for branching vessel circumference with preference for branching points. points.

Polyarteritis Nodosa (PAN)Polyarteritis Nodosa (PAN)(Cont...) (Cont...)

Inflammatory process causes segmental erosion Inflammatory process causes segmental erosion with weakening of the arterial wall which may cause with weakening of the arterial wall which may cause aneurysm or rupture. aneurysm or rupture.

Impairment of perfusion, causing ulcerations, Impairment of perfusion, causing ulcerations, infarcts, ischemic atrophy, or hemorrhages. infarcts, ischemic atrophy, or hemorrhages.

Sometimes the lesions are exclusively microscopic Sometimes the lesions are exclusively microscopic with no gross changes. with no gross changes.

Polyarteritis Nodosa (PAN):Polyarteritis Nodosa (PAN):Histologically Histologically

The acute phase demonstrates neutrophils, The acute phase demonstrates neutrophils, eosinophils, and mononuclear cells and is eosinophils, and mononuclear cells and is frequently accompanied by fibrinoid necrosis. The frequently accompanied by fibrinoid necrosis. The lumen may become thrombosed. lumen may become thrombosed.

Later, the acute inflammatory infiltrate disappears Later, the acute inflammatory infiltrate disappears and is replaced by fibrous thickening of the vessel and is replaced by fibrous thickening of the vessel wall that may extend into the adventitia. wall that may extend into the adventitia.

Firm nodularity sometimes marks the lesions. Firm nodularity sometimes marks the lesions. All stages of activity may coexist in different vessels All stages of activity may coexist in different vessels

or even within the same vessel. or even within the same vessel.

Polyarteritis Nodosa:Polyarteritis Nodosa:Clinical Course Clinical Course

> young adults <, Acute, subacute, or chronic and is > young adults <, Acute, subacute, or chronic and is frequently remittent and episodic. frequently remittent and episodic.

Malaise, fever of unknown cause, and weight loss; Malaise, fever of unknown cause, and weight loss; hypertension, abdominal pain and melena (bloody hypertension, abdominal pain and melena (bloody stool), diffuse muscular aches and pains, and stool), diffuse muscular aches and pains, and peripheral neuritis. peripheral neuritis.

Renal involvement is often prominent and a major Renal involvement is often prominent and a major cause of death. cause of death. There is no glomerulonephritisThere is no glomerulonephritis because small vessel involvement is absent. because small vessel involvement is absent.

Polyarteritis Nodosa:Polyarteritis Nodosa:Clinical Course Clinical Course

30% of PAN patients have hepatitis B antigen in 30% of PAN patients have hepatitis B antigen in their serum. their serum.

There is no association with ANCA. There is no association with ANCA. Poor prognosis: death if not treated, but therapy with Poor prognosis: death if not treated, but therapy with

corticosteroids and cyclophosphamide results in corticosteroids and cyclophosphamide results in remissions or cures in 90%. remissions or cures in 90%.

Clinical diagnosis by biopsy of the suspected area of Clinical diagnosis by biopsy of the suspected area of involvement. involvement.

Polyarteritis nodosa with segmental fibrinoid Polyarteritis nodosa with segmental fibrinoid necrosis and thrombotic occlusion of the lumen of necrosis and thrombotic occlusion of the lumen of this small artery. Note that part of the vessel wall at this small artery. Note that part of the vessel wall at

the upper right (arrow) is uninvolved.the upper right (arrow) is uninvolved.

Wegener’s GranulomatosisWegener’s Granulomatosis

Necrotizing vasculitis characterized by the triad of:Necrotizing vasculitis characterized by the triad of: Acute necrotizing granulomas of the upper Acute necrotizing granulomas of the upper

respiratory tract (ear, nose, throat), or the lower respiratory tract (ear, nose, throat), or the lower respiratory tract (lung) or both.respiratory tract (lung) or both.

Necrotizing or granulomatous vasculitis affecting Necrotizing or granulomatous vasculitis affecting small to medium-sized vessels (capillaries, small to medium-sized vessels (capillaries, venules, arterioles, and arteries), mostly in the venules, arterioles, and arteries), mostly in the lungs and upper airways.lungs and upper airways.

Renal disease (focal necrotizing, often crescentic, Renal disease (focal necrotizing, often crescentic, glomerulonephritis).glomerulonephritis).

Limited forms, or more widespread WG (eye, skin).Limited forms, or more widespread WG (eye, skin).

Wegener’s GranulomatosisWegener’s Granulomatosis

PathogenesisPathogenesis Immunologic mechanisms of Cell Mediated type.Immunologic mechanisms of Cell Mediated type. > 95% c-ANCA positive.> 95% c-ANCA positive. May be hypersensitivity to an inhaled agent.May be hypersensitivity to an inhaled agent.

Clinical pictureClinical picture overlaps with PAN and overlaps with PAN and ococccurs urs more in males more in males

peak 5th decadepeak 5th decade

Diagnosis (Lung biopsy)Diagnosis (Lung biopsy) Prognosis: 80% die within a yearPrognosis: 80% die within a year

90% respond to treatment90% respond to treatment

Wegener granulomatosis. Wegener granulomatosis. There is inflammation (vasculitis) of a small artery There is inflammation (vasculitis) of a small artery along with adjacent granulomatous inflammation, along with adjacent granulomatous inflammation, in which epithelioid cells and giant cells (arrows) in which epithelioid cells and giant cells (arrows)

are seen. are seen.

Micoscopic Polyangiitis Micoscopic Polyangiitis (Microscopic Polyarteritis, Hypersensitivity, (Microscopic Polyarteritis, Hypersensitivity,

or Leukocytoclastic Angiitis)or Leukocytoclastic Angiitis) Necrotizing vasculitis: (Arterioles, capillaries, Necrotizing vasculitis: (Arterioles, capillaries,

venules). All lesions tend to be of the same age.venules). All lesions tend to be of the same age. Involve Involve

skin (palpable purpura), skin (palpable purpura), mucous membranes, mucous membranes, lungs (capillaritis: hemoptysis), lungs (capillaritis: hemoptysis), brain, heart, brain, heart, GI (bowel pain or bleeding), GI (bowel pain or bleeding), kidneys (necrotizing glomerulonephritis: kidneys (necrotizing glomerulonephritis:

hematuria, proteinuria), and hematuria, proteinuria), and muscle (muscle pain or weakness).muscle (muscle pain or weakness).

Micoscopic Polyangiitis Micoscopic Polyangiitis (Microscopic Polyarteritis, Hypersensitivity, (Microscopic Polyarteritis, Hypersensitivity,

or Leukocytoclastic Angiitis)or Leukocytoclastic Angiitis)

Precipitating cause: immunologic reaction to an Precipitating cause: immunologic reaction to an antigen antigen drug: penicillin drug: penicillin microorganisms: strept ococcusmicroorganisms: strept ococcus heterlogous proteins and tumor antigens.heterlogous proteins and tumor antigens.

Removal of the offending agent improve the caseRemoval of the offending agent improve the case p-ANCAs are present in 70-80% of patients.p-ANCAs are present in 70-80% of patients.

Micoscopic Polyangiitis Micoscopic Polyangiitis (Microscopic Polyarteritis, Hypersensitivity, (Microscopic Polyarteritis, Hypersensitivity,

or Leukocytoclastic Angiitis)or Leukocytoclastic Angiitis)

Morphology Morphology The transmural necrotizing lesions of microscopic The transmural necrotizing lesions of microscopic

polyangiitis often resemble those of PAN with polyangiitis often resemble those of PAN with segmental fibrinoid necrosis of the media. segmental fibrinoid necrosis of the media.

Macroscopic infarcts similar to those seen in PAN Macroscopic infarcts similar to those seen in PAN are uncommon. are uncommon.

In some lesions the change is limited to infiltration In some lesions the change is limited to infiltration with neutrophils, which become fragmented as they with neutrophils, which become fragmented as they follow the vessel wall, giving rise to the term follow the vessel wall, giving rise to the term leukocytoclastic angiitis.leukocytoclastic angiitis.

Leukocytoclastic vasculitis in a skin. Leukocytoclastic vasculitis in a skin. Fragmentation of neutrophil nuclei in and Fragmentation of neutrophil nuclei in and

around vessel walls.around vessel walls.

Kawasaki’s diseaseKawasaki’s disease(mucocutaneous lymph node syndrome)(mucocutaneous lymph node syndrome)

Acute illness of infants and children characterized by Acute illness of infants and children characterized by fever, lymphadenopathy, skin rash, oral/ conjunctival fever, lymphadenopathy, skin rash, oral/ conjunctival erythema.erythema.

Associated with an arteritis affecting large, medium-Associated with an arteritis affecting large, medium-sized, and small vessels. sized, and small vessels.

Its clinical significance stems from the involvement of Its clinical significance stems from the involvement of coronary arteries.coronary arteries.

20% have coronary vasculitis, often with aneurysm.20% have coronary vasculitis, often with aneurysm. Histology like PANHistology like PAN Etiology ; unknown, it is self-limited disease, rarely Etiology ; unknown, it is self-limited disease, rarely

fatal(1%) due to complications of coronary fatal(1%) due to complications of coronary involvement.involvement.

Thromboangiitis Obliterans Thromboangiitis Obliterans (Buerger’s disease)(Buerger’s disease)

Distinctive disease leads to vascular insufficiency, Distinctive disease leads to vascular insufficiency, is characterized by segmental, thrombosing, acute is characterized by segmental, thrombosing, acute and chronic inflammation of medium and small and chronic inflammation of medium and small arteries, (tibial and radial arteries and adjacent arteries, (tibial and radial arteries and adjacent veins and nerves). veins and nerves).

It almost always affects males (ages 20 to 40 ) who It almost always affects males (ages 20 to 40 ) who have a history of smoking or chewing tobacco, have a history of smoking or chewing tobacco, however, a higher percentage of women and however, a higher percentage of women and people over the age of 50 have been recognized to people over the age of 50 have been recognized to have this disease.have this disease.

May leads to gangrene. May leads to gangrene.

Thromboangiitis Obliterans Thromboangiitis Obliterans (Buerger’s disease)(Buerger’s disease)

Pathogenesis: derivative of tobacco or tobacco Pathogenesis: derivative of tobacco or tobacco smoke may cause endothelial cell injury or incite an smoke may cause endothelial cell injury or incite an immunologic reaction in predisposed persons.immunologic reaction in predisposed persons.

Microscopically, acute and chronic inflammation Microscopically, acute and chronic inflammation permeates the arterial walls, accompanied by permeates the arterial walls, accompanied by thrombosis of the lumen, which may undergo thrombosis of the lumen, which may undergo organization and recanalization. organization and recanalization. The thrombus contains small microabscesses The thrombus contains small microabscesses

with a central focus of neutrophils surrounded by with a central focus of neutrophils surrounded by granulomatous inflammationgranulomatous inflammation

Thromboangiitis obliterans (Buerger disease)Thromboangiitis obliterans (Buerger disease)

The lumen is occluded by a thrombus containing The lumen is occluded by a thrombus containing two abscesses (arrows). The vessel wall is two abscesses (arrows). The vessel wall is infiltrated with leukocytes.infiltrated with leukocytes.

ArteriosclerosisArteriosclerosis

ArteriosclerosisArteriosclerosis

Hardening of arteries (Thickening and loss Hardening of arteries (Thickening and loss of elasticity of arterial walls).of elasticity of arterial walls).

Three patternThree pattern Atherosclerosis Atherosclerosis Monckeberg Monckeberg ArteriolosclerosisArteriolosclerosis

Monckeberg Medial Calcific SclerosisMonckeberg Medial Calcific Sclerosis

Focal dystrophic Calcific deposits in the Focal dystrophic Calcific deposits in the mediamedia. . It occurs in old age group >50 in:It occurs in old age group >50 in:

Small to medium-sized muscular arteries ofSmall to medium-sized muscular arteries of Lower limb Lower limb Head and neck Head and neck Pelvis (especially the uterine arteries).Pelvis (especially the uterine arteries).

Of unknown etiology and of little clinical Of unknown etiology and of little clinical significancesignificance

There is higher incidence in diabetic individuals.There is higher incidence in diabetic individuals.

Monckeberg Medial Calcific SclerosisMonckeberg Medial Calcific Sclerosis

No lumenal narrowing, No ischemic and embolic No lumenal narrowing, No ischemic and embolic phenomenaphenomena

In advanced cases, In advanced cases, stenosis and atheroma may stenosis and atheroma may occur, but occur, but the lumen usually remains patent the lumen usually remains patent (open), and (open), and vessels may become rigid and lose vessels may become rigid and lose their distensibility their distensibility leading to "pipe-stem" rigidity.leading to "pipe-stem" rigidity.

Calcified arteries may be visualized on Calcified arteries may be visualized on radiographs.radiographs.

Histology: Ring like or plate calcification in media.Histology: Ring like or plate calcification in media. Asymptomatic, however, it may co-exist with Asymptomatic, however, it may co-exist with

atherosclerosis.atherosclerosis.

Monckeberg's Medial Calcific SclerosisMonckeberg's Medial Calcific SclerosisCalcification affects only the media. Calcification affects only the media.

ArteriolosclerosisArteriolosclerosis

Affects small arteries and arteriolesAffects small arteries and arterioles Cause thickening of vessel walls with luminal Cause thickening of vessel walls with luminal

narrowing that may induce ischemic injury, and is narrowing that may induce ischemic injury, and is best demonstrated in the renal arterioles.best demonstrated in the renal arterioles.

Most often associated with hypertension and Most often associated with hypertension and diabetes mellitus.diabetes mellitus.

Two anatomic variantsTwo anatomic variants Hyaline arteriolosclerosisHyaline arteriolosclerosis Hyperplastic arteriolosclerosisHyperplastic arteriolosclerosis

Hyaline ArteriolosclerosisHyaline Arteriolosclerosis Characterized by Characterized by

Diffuse, homogeneous, pink hyaline thickening of Diffuse, homogeneous, pink hyaline thickening of the walls of arterioles.the walls of arterioles.

Loss of underlying structural detail and narrowing Loss of underlying structural detail and narrowing of the lumenof the lumen

Occurs typically in elderly patients. Occurs typically in elderly patients. Advanced lesions are seen in persons with Advanced lesions are seen in persons with

diabetes mellitus and/or with hypertension.diabetes mellitus and/or with hypertension. Hyaline arteriolosclerosis is typically seen in Hyaline arteriolosclerosis is typically seen in

kidneys. kidneys.

Hyaline ArteriolosclerosisHyaline Arteriolosclerosis

Endothelial injury causes leakage of plasma Endothelial injury causes leakage of plasma

components across vascular endothelium, and components across vascular endothelium, and

excessive extracellular matrix production by smooth excessive extracellular matrix production by smooth

muscle cells.muscle cells.

This process is associated with lumenal narrowing This process is associated with lumenal narrowing

that may induce ischemic injurythat may induce ischemic injury

Afferent & efferent arterioles in kidneyAfferent & efferent arterioles in kidney→→benign benign

nephrosclerosisnephrosclerosis

Hyaline ArteriolosclerosisHyaline ArteriolosclerosisMarkedly thickened arteriole to the lower right of Markedly thickened arteriole to the lower right of

this glomerulusthis glomerulus

Hyaline ArteriolosclerosisHyaline ArteriolosclerosisArteriolar wall is hyalinized and the lumen is Arteriolar wall is hyalinized and the lumen is

markedly narrowedmarkedly narrowed

Hyperplastic ArteriolosclerosisHyperplastic Arteriolosclerosis

Concentric laminated (onion skin) arteriolar Concentric laminated (onion skin) arteriolar thickening with reduplicated basement membrane thickening with reduplicated basement membrane and smooth muscle cells proliferation.and smooth muscle cells proliferation. Commonly associated with Commonly associated with malignant malignant

hypertensionhypertension Leads to lumenal narrowingLeads to lumenal narrowing Frequently associated with fibrinoid necrosis Frequently associated with fibrinoid necrosis

(necrotizing arteriolitis).(necrotizing arteriolitis). Later, the vascular walls hypertrophy due to Later, the vascular walls hypertrophy due to

hyperplasia of SMCs and sometimes this occurs hyperplasia of SMCs and sometimes this occurs along with necrosis of the vessel wall. along with necrosis of the vessel wall.

Hyperplastic ArteriolosclerosisHyperplastic ArteriolosclerosisOnion skin appearanceOnion skin appearance

Narrow LumenNarrow Lumen

Onion Skin ThickeningOnion Skin ThickeningOf arterioles.Of arterioles.

Hyperplastic ArteriolosclerosisHyperplastic Arteriolosclerosis(Onion-Skinning) causing luminal obliteration (arrow)(Onion-Skinning) causing luminal obliteration (arrow)

Hyperplastic ArteriolosclerosisHyperplastic ArteriolosclerosisFibrinoid necrosisFibrinoid necrosis

Atherosclerosis (ATH)Atherosclerosis (ATH)

Systemic disease at multiple sites affects vital Systemic disease at multiple sites affects vital

organs, in which ATH is revealed at:organs, in which ATH is revealed at:

Elastic arteriesElastic arteries

Large arteriesLarge arteries

Medium sized arteries.Medium sized arteries.

It is common worldwide, almost everyone in U.S is It is common worldwide, almost everyone in U.S is

subject to ATH if they live long enough. Accounting subject to ATH if they live long enough. Accounting

for about 50% of all deaths in West.for about 50% of all deaths in West.

The characteristic lesion of ATH is called The characteristic lesion of ATH is called atheromaatheroma

ATH: Atheroma (ATH: Atheroma (fibrofatty plaques) fibrofatty plaques)

Atheroma is focal Atheroma is focal lesion of intima, that is lesion of intima, that is

characterized by intimal deposition of lipids, characterized by intimal deposition of lipids,

intruding into the lumen (0.3 to 1.5 cm in intruding into the lumen (0.3 to 1.5 cm in

diameter), diameter),

Atheroma leads to intimal thickening, scarring, and Atheroma leads to intimal thickening, scarring, and

reducing the lumen size causing stenosis, which reducing the lumen size causing stenosis, which

ends with ischemia and infarction.ends with ischemia and infarction.

Atheroma: Gross Atheroma: Gross

Atheroma consist of lipid core covered by a firm Atheroma consist of lipid core covered by a firm white fibrous cap, and have three main white fibrous cap, and have three main components:components: Cells: including SMCs, macrophages, Cells: including SMCs, macrophages,

leukocytesleukocytes Extracellular matrix, including collagen, elastic Extracellular matrix, including collagen, elastic

fibers, and proteoglycansfibers, and proteoglycans Intracellular and extracellular lipid.Intracellular and extracellular lipid.

Around the lesions, there is neovascularization.Around the lesions, there is neovascularization.

Foam cells are large lipid-laden cells that derive predominantly Foam cells are large lipid-laden cells that derive predominantly from blood monocytes (tissue macrophages), but SMCs can from blood monocytes (tissue macrophages), but SMCs can also absorb lipid to become foam cells.also absorb lipid to become foam cells.

Two type of atheromatous plaques Two type of atheromatous plaques Soft plaques (abundant lipid). Soft plaques (abundant lipid). Solid or fibrous plaques (SMCs and fibrous tissue).Solid or fibrous plaques (SMCs and fibrous tissue).

AtheromaAtheroma

Plaques change and progressively enlarge Plaques change and progressively enlarge through through Cell death and degeneration,Cell death and degeneration, Synthesis and degradation of extracellular Synthesis and degradation of extracellular

matrix,matrix, Organization of thrombus.Organization of thrombus. Atheroma often undergo calcification. Atheroma often undergo calcification.

Complication: rupture (ulceration or erosion), Complication: rupture (ulceration or erosion), hemorrhage, thrombosis, aneurysmal dilationhemorrhage, thrombosis, aneurysmal dilation

Large BV :Large BV : Abdominal aorta Abdominal aorta Iliac Iliac

In descending orderIn descending order Coronary Coronary PoplitealPopliteal CarotidCarotid Circle of Willis.Circle of Willis.

Vessels of the upper Vessels of the upper extremities are usually extremities are usually spared, spared,

The severity of AS in one The severity of AS in one artery does not predict its artery does not predict its severity in anotherseverity in another

Atherosclerosis: ComplicationsAtherosclerosis: Complications Major consequencesMajor consequences

Coronary arteries: IHD (myocardial infarction)Coronary arteries: IHD (myocardial infarction) Cerebrovascular system: Cerebral infarction Cerebrovascular system: Cerebral infarction

(stroke)(stroke) Aorta: Hypertension and aneurysm formationAorta: Hypertension and aneurysm formation Peripheral vascular systemPeripheral vascular system

Decreased perfusion to extremities (gangrene Decreased perfusion to extremities (gangrene of the legs)of the legs)

More consequences (diminished arterial perfusion)More consequences (diminished arterial perfusion) Mesenteric occlusion, Sudden cardiac death, Mesenteric occlusion, Sudden cardiac death,

Chronic IHD, Ischemic encephalopathyChronic IHD, Ischemic encephalopathy

Atherosclerosis: Fatty streaksAtherosclerosis: Fatty streaks Fatty streaks, (composed of foam cells), are not Fatty streaks, (composed of foam cells), are not

significantly raised and thus do not cause any significantly raised and thus do not cause any disturbance in blood flow. disturbance in blood flow.

They begin as multiple yellow, flat spots (fatty They begin as multiple yellow, flat spots (fatty dots) less than 1 mm, then combine into dots) less than 1 mm, then combine into elongated streaks. elongated streaks.

Fatty streaks appear in the aortas of children Fatty streaks appear in the aortas of children regardless of geography, race, sex, or regardless of geography, race, sex, or environment. environment.

Coronary fatty streaks begin to form in Coronary fatty streaks begin to form in adolescence.adolescence.

The relationship of fatty streaks to atherosclerotic The relationship of fatty streaks to atherosclerotic plaques is uncertain.plaques is uncertain.

Gross views of atherosclerosis in the aorta.Gross views of atherosclerosis in the aorta.A. Mild atherosclerosis composed of fibrous plaques, A. Mild atherosclerosis composed of fibrous plaques,

one of which is denoted by the arrow.one of which is denoted by the arrow.B. Severe disease with diffuse, complicated lesions.B. Severe disease with diffuse, complicated lesions.

Morphologic typesMorphologic types

Fatty dotsFatty dots Atheroma Plaques Complicated Atheroma Plaques Complicated

Histologic features of atheromatous plaque Histologic features of atheromatous plaque in the coronary artery.in the coronary artery.

Histologic features of Histologic features of atheromatous plaque in the atheromatous plaque in the coronary artery.coronary artery.

The plaque shown in A, The plaque shown in A, stained for elastin (black) stained for elastin (black) demonstrating that the demonstrating that the internal and external elastic internal and external elastic membranes are destroyed membranes are destroyed and the media of the artery and the media of the artery is thinned under the most is thinned under the most advanced plaque (arrow).advanced plaque (arrow).

Histologic features of Histologic features of atheromatous plaque in the atheromatous plaque in the coronary artery.coronary artery.

The junction of the fibrous The junction of the fibrous cap and core showing cap and core showing scattered inflammatory cells, scattered inflammatory cells, calcification (broad arrow), calcification (broad arrow), and neovascularization (small and neovascularization (small arrows)arrows)

Atherosclerosis: Atherosclerosis: Risk FactorsRisk Factors

Non-modifiable risk factors (Constitutional)Non-modifiable risk factors (Constitutional)

Age, Sex, GeneticsAge, Sex, Genetics

Modifiable risk factors (Major)Modifiable risk factors (Major)

Hyperlipidemia, Hypertension, Smoking, Hyperlipidemia, Hypertension, Smoking,

DiabetesDiabetes

Modifiable risk factors (Other)Modifiable risk factors (Other)

Diet (obesity), life style (stress), personal habits Diet (obesity), life style (stress), personal habits

(lack of regular exercise) (lack of regular exercise)

AtherosclerosisAtherosclerosisConstitutional Risk FactorsConstitutional Risk Factors

Age: it is clinically evident after middle age, between Age: it is clinically evident after middle age, between

ages 40-60 increases the incidence of MI 5 fold.ages 40-60 increases the incidence of MI 5 fold.

Sex: men > premenopausal women, but men = women Sex: men > premenopausal women, but men = women

by 7by 7thth-8-8thth decades ( decades (↓↓ postmenopausal estrogen). postmenopausal estrogen).

Genetics: familial predisposition (polygenic)Genetics: familial predisposition (polygenic)

Well-defined hereditary genetic derangement in Well-defined hereditary genetic derangement in

lipoprotein metabolism (familial lipoprotein metabolism (familial

hypercholesterolemia)hypercholesterolemia)

Familial clustering of other risk factors: hypertension Familial clustering of other risk factors: hypertension

or diabetesor diabetes

Atherosclerosis: Major Risk FactorsAtherosclerosis: Major Risk Factors

Hyperlipidemia (HypercholesterolemiaHyperlipidemia (Hypercholesterolemia))

LDL increases the risk of ATH.LDL increases the risk of ATH. HDL has a protective effect (negative risk factor). HDL has a protective effect (negative risk factor).

It mobilizes the cholesterol from tissues to liver, It mobilizes the cholesterol from tissues to liver, It is increased by exercise and ethanol use It is increased by exercise and ethanol use

High dietary intake High dietary intake Bad fats: cholesterol and saturated fats (egg yolk, Bad fats: cholesterol and saturated fats (egg yolk,

animal fats, and butter) animal fats, and butter) Good fats such as omega-3 fatty acids (fish oils), Good fats such as omega-3 fatty acids (fish oils),

unsaturated fats)unsaturated fats) Low ratio of saturated to polyunsaturated fats Low ratio of saturated to polyunsaturated fats

lowers risk.lowers risk.

Atherosclerosis: Major Risk FactorsAtherosclerosis: Major Risk Factors

Hypertension Hypertension Hypertension: Men ages 45-62 with (BP 169/95) Hypertension: Men ages 45-62 with (BP 169/95) →↑→↑

X 5 of IHD than men with (BP 140/90). X 5 of IHD than men with (BP 140/90). Cigarette smoking increases the incidence and Cigarette smoking increases the incidence and

severity of ATH in M &F and dseverity of ATH in M &F and decreasesecreases HDL HDL 1 pack +/day for years1 pack +/day for years→↑→↑ X2-3 of death rate X2-3 of death rate

from IHDfrom IHD Diabetes mellitusDiabetes mellitus

Induces hypercholesterolemiaInduces hypercholesterolemia MI (X 2) MI (X 2) strokestroke gangrene (X100- 150gangrene (X100- 150))

Atherosclerosis: Other Risk FactorsAtherosclerosis: Other Risk Factors

Decrease physical activity (lack of regular exercise) Decrease physical activity (lack of regular exercise) Life style (competitive, stressful with type A Life style (competitive, stressful with type A

personality)personality) Obesity (decrease HDL)Obesity (decrease HDL) Multiple risk factors have multiplicative effect.Multiple risk factors have multiplicative effect. ATH may develop in absence of known risk factor.ATH may develop in absence of known risk factor.

Atherosclerosis: Other Risk FactorsAtherosclerosis: Other Risk Factors(Cont…)(Cont…)

Hyperhomocystenemia: homocysteine increases Hyperhomocystenemia: homocysteine increases

platelet adhesion and coagulation abnormalities, platelet adhesion and coagulation abnormalities,

resulting in increased arterial and venous clots, resulting in increased arterial and venous clots,

leading to strokes and heart attacksleading to strokes and heart attacks

Can be caused by low intake of Folic acid, Can be caused by low intake of Folic acid,

vitamin B vitamin B

Atherosclerosis – PathogenesisAtherosclerosis – PathogenesisThe Response to Endothelium Injury HypothesisThe Response to Endothelium Injury Hypothesis

1. ATH is considered to be a chronic inflammatory 1. ATH is considered to be a chronic inflammatory response of the arterial wall initiated by injury to the response of the arterial wall initiated by injury to the endothelium (focal areas of chronic endothelial endothelium (focal areas of chronic endothelial injury (slight), because of injury (slight), because of derivatives of cigarette smoke, derivatives of cigarette smoke, homocysteine, homocysteine, viruses and other infectious agents, viruses and other infectious agents, hyperlipidemiahyperlipidemia

Atherosclerosis – PathogenesisAtherosclerosis – PathogenesisThe Response to Endothelium Injury HypothesisThe Response to Endothelium Injury Hypothesis

2. Result in endothelial dysfunction that causes 2. Result in endothelial dysfunction that causes ↑↑endothelial permeability, endothelial permeability, enhanced leukocyte adhesion enhanced leukocyte adhesion alteration in expression of EC gene products alteration in expression of EC gene products

(ICAM-1) & (VCAM-1) that mediate adhesion of (ICAM-1) & (VCAM-1) that mediate adhesion of circulating monocytes, lymphocytes and platelets. circulating monocytes, lymphocytes and platelets. (thrombotic potential)(thrombotic potential)

Atherosclerosis – PathogenesisAtherosclerosis – PathogenesisThe Response to Endothelium Injury HypothesisThe Response to Endothelium Injury Hypothesis

3.Depositions of lipoproteins in the vessel wall, mainly 3.Depositions of lipoproteins in the vessel wall, mainly

LDL with its high cholesterol content. Then LDL with its high cholesterol content. Then

modification of lesional lipoproteins by oxidation.modification of lesional lipoproteins by oxidation.

4.Adhesion of blood monocytes (and other 4.Adhesion of blood monocytes (and other

leukocytes) to the endothelium, followed by their leukocytes) to the endothelium, followed by their

migration into the intima and their transformation migration into the intima and their transformation

into macrophages and foam cells. into macrophages and foam cells.

5.Adhesion of platelets.5.Adhesion of platelets.

Atherosclerosis – PathogenesisAtherosclerosis – PathogenesisThe Response to Endothelium Injury HypothesisThe Response to Endothelium Injury Hypothesis

6. Release of factors from activated platelets and 6. Release of factors from activated platelets and

macrophages that cause migration of SMCs from macrophages that cause migration of SMCs from

media into the intima. media into the intima.

7. Proliferation of SMCs in the intima, and elaboration 7. Proliferation of SMCs in the intima, and elaboration

of extracellular matrix, leading to accumulation of of extracellular matrix, leading to accumulation of

collagen and proteoglycans. collagen and proteoglycans.

8. Enhanced accumulation of lipids both within cells 8. Enhanced accumulation of lipids both within cells

(macrophages and SMCs) and extracellularly. (macrophages and SMCs) and extracellularly.

Atherosclerosis - Pathogenesis Atherosclerosis - Pathogenesis The Role of Endothelial InjuryThe Role of Endothelial Injury

Determinants of endothelial alterationsDeterminants of endothelial alterations Homodynamic disturbances Homodynamic disturbances Effects of hypercholesterolemiaEffects of hypercholesterolemia Tendency for plaques to occur at ostia of exiting Tendency for plaques to occur at ostia of exiting

vessels, branch points and along the posterior vessels, branch points and along the posterior wall of the abdominal aorta (where there are wall of the abdominal aorta (where there are disturbed flow patterns).disturbed flow patterns).

Atherosclerosis - Pathogenesis Atherosclerosis - Pathogenesis The Role of LipidsThe Role of Lipids

Evidence linking hypercholestrolemia & ATHEvidence linking hypercholestrolemia & ATH Increased LDL cholesterol levels, decreased Increased LDL cholesterol levels, decreased

HDL cholesterol levels, and increased levels of HDL cholesterol levels, and increased levels of the abnormal Lp(a) the abnormal Lp(a)

Lipids in atheromas (plaques) are plasma-Lipids in atheromas (plaques) are plasma-derived cholesterol and cholesterol esters.derived cholesterol and cholesterol esters.

Relationship between increased LDL level and Relationship between increased LDL level and the severity of ATHthe severity of ATH

Atherosclerosis - Pathogenesis Atherosclerosis - Pathogenesis The Role of Lipids ( Cont…)The Role of Lipids ( Cont…)

Genetic or acquired conditions result in Genetic or acquired conditions result in hypercholesterolemia. hypercholesterolemia. familial hypercholesterolemiafamilial hypercholesterolemia diabetes mellitusdiabetes mellitus hypothyroidismhypothyroidism nephrotic syndromenephrotic syndrome alcoholismalcoholism

Lowering levels of serum cholesterol by diet or Lowering levels of serum cholesterol by diet or drug slows the rate of progression of ATH, and drug slows the rate of progression of ATH, and causes regression of plaques.causes regression of plaques.

Atherosclerosis - Pathogenesis Atherosclerosis - Pathogenesis The Role of Lipids (mechanisms) The Role of Lipids (mechanisms)

Hyperlipidemia, may directly impair EC function Hyperlipidemia, may directly impair EC function

through increased production of oxygen free through increased production of oxygen free

radicals (in macrophages or EC) that deactivate radicals (in macrophages or EC) that deactivate

nitric oxide (the major endothelial-relaxing factor).nitric oxide (the major endothelial-relaxing factor).

Free radicals induce chemical changes of lipid in Free radicals induce chemical changes of lipid in

the arterial wall by oxidizing LDL, leading to:the arterial wall by oxidizing LDL, leading to:

Accumulation of lipoproteins (mainly LDL or Accumulation of lipoproteins (mainly LDL or

oxidized LDL) in intima at sites of increased oxidized LDL) in intima at sites of increased

endothelial permeability.endothelial permeability.

Atherosclerosis - Pathogenesis Atherosclerosis - Pathogenesis The Role of Lipids (mechanisms)The Role of Lipids (mechanisms)

Role of oxidized LDL in atherogenesisRole of oxidized LDL in atherogenesis Oxidized LDL is ingested through scavenger Oxidized LDL is ingested through scavenger

receptor of macrophages thus forming foam receptor of macrophages thus forming foam cells.cells.

Increases monocytes accumulation in lesion Increases monocytes accumulation in lesion (adhesion)(adhesion)

Stimulates release of GF & cytokinesStimulates release of GF & cytokines Oxidized LDL is cytotoxic to ECs and SMCsOxidized LDL is cytotoxic to ECs and SMCs Oxidized LDL can induce endothelial cell Oxidized LDL can induce endothelial cell

dysfunctiondysfunction

The Role of The Role of Monocytes, Macrophages and PlateletsMonocytes, Macrophages and Platelets

Adhesion of monocytes to ECs, then migration into Adhesion of monocytes to ECs, then migration into the intima, followed by transformation into the intima, followed by transformation into macrophages which engulf lipoproteins largely macrophages which engulf lipoproteins largely oxidized LDL to become foam cells.oxidized LDL to become foam cells. Macrophages produce IL-1 & TNF which increase Macrophages produce IL-1 & TNF which increase

adhesion of leukocytesadhesion of leukocytes Macrophages produce toxic O2 speciesMacrophages produce toxic O2 species Macrophages elaborate GF that contribute in Macrophages elaborate GF that contribute in

SMC proliferation.SMC proliferation. Adhesion of plateletsAdhesion of platelets Release of factors from activated platelets and Release of factors from activated platelets and

macrophages that cause migration of SMCs from macrophages that cause migration of SMCs from media into the intima.media into the intima.

Atherosclerosis - PathogenesisAtherosclerosis - Pathogenesis

The Role of Smooth Muscle Cell ProliferationThe Role of Smooth Muscle Cell Proliferation Proliferation of SMCs in the intima and elaboration Proliferation of SMCs in the intima and elaboration

of ECM, leading to accumulation of collagen and of ECM, leading to accumulation of collagen and

proteoglycans.proteoglycans.

Convert fatty streak into a mature fibrofatty Convert fatty streak into a mature fibrofatty

atheroma and contribute to the progression of atheroma and contribute to the progression of

ATH.ATH.

Enhanced accumulation of lipids both within cells Enhanced accumulation of lipids both within cells

(macrophages and SMCs) and extracellularly.(macrophages and SMCs) and extracellularly.

Ischemic Heart Ischemic Heart DiseasesDiseases

Ischemic Heart Diseases (IHD)Ischemic Heart Diseases (IHD)

A group of closely related syndromes caused by an A group of closely related syndromes caused by an imbalance between the myocardial oxygen imbalance between the myocardial oxygen demands and blood supply.demands and blood supply. It accounts for 80% of cardiac death and nearly It accounts for 80% of cardiac death and nearly

1/3 of all deaths in developed countries .1/3 of all deaths in developed countries . The most common cause of IHD is luminal The most common cause of IHD is luminal

narrowing of the C.A. by atherosclerosis and the narrowing of the C.A. by atherosclerosis and the following contributing factors: following contributing factors: Acute plaque changes Acute plaque changes Coronary artery thrombosis Coronary artery thrombosis Coronary artery vasospasmCoronary artery vasospasm

Ischemic Heart Diseases (IHD) Ischemic Heart Diseases (IHD)

Clinical syndromes of IHDClinical syndromes of IHD

Angina pectorisAngina pectoris

Myocardial infarctionMyocardial infarction

Sudden cardiac deathSudden cardiac death

Chronic IHDChronic IHD

Angina Pectoris (AP)Angina Pectoris (AP)

Characterized by episodic attacks of crushing or Characterized by episodic attacks of crushing or squeezing substernal pain, radiating to precordium squeezing substernal pain, radiating to precordium and left arm.and left arm.

Types of AnginaTypes of Angina Typical stable APTypical stable AP Prinzmetal or variant anginaPrinzmetal or variant angina Unstable Angina (preinfarction angina or Unstable Angina (preinfarction angina or

crescendo angina)crescendo angina)

Angina Pectoris (AP)Angina Pectoris (AP)

Typical stable APTypical stable AP Chest pain associated with exertion, stress Chest pain associated with exertion, stress

and emotion.and emotion. Usually there is fixed atherosclerotic Usually there is fixed atherosclerotic

narrowing (75%) of C.A (stenosis).narrowing (75%) of C.A (stenosis). Relieved by rest and nitroglycerine. Relieved by rest and nitroglycerine.

Angina Pectoris (AP)Angina Pectoris (AP)

Prinzmetal or variant anginaPrinzmetal or variant angina Occurs at rest, less frequently related to effortOccurs at rest, less frequently related to effort Caused by C.A. spasm usually near Caused by C.A. spasm usually near

atherosclerotic plaque.atherosclerotic plaque. Respond to nitroglycerineRespond to nitroglycerine

Angina Pectoris (AP)Angina Pectoris (AP)

Unstable Angina (preinfarction angina or Unstable Angina (preinfarction angina or crescendo angina)crescendo angina) More frequent, more intense and provoked by More frequent, more intense and provoked by

less effort or emotionless effort or emotion Increased frequency of anginal pain and Lasts Increased frequency of anginal pain and Lasts

longerlonger Caused by acute plaque change with Caused by acute plaque change with

superimposed partial thrombosis or vasospasmsuperimposed partial thrombosis or vasospasm Nitroglycerine is required more but it is less Nitroglycerine is required more but it is less

effectiveeffective

What is your diagnosisWhat is your diagnosis

Severe, crushing substernal chest pain, which Severe, crushing substernal chest pain, which may radiate to the neck, jaw, epigastrium, may radiate to the neck, jaw, epigastrium, shoulder, or left arm. shoulder, or left arm.

This pain lasts several hours to days and is not This pain lasts several hours to days and is not significantly relieved by nitroglycerin. significantly relieved by nitroglycerin.

The pulse is generally rapid and weak The pulse is generally rapid and weak Patient is diaphoretic (sweating) with short Patient is diaphoretic (sweating) with short

breathing (dyspnea). breathing (dyspnea).

Myocardial Infarction (MI)Myocardial Infarction (MI)

An area of myocardial necrosis caused by local An area of myocardial necrosis caused by local ischemia.ischemia.

Acute MI is the most common cause of death in Acute MI is the most common cause of death in the west. 1.5 million MI/ year in USA, with 1/2 the west. 1.5 million MI/ year in USA, with 1/2 million deaths, 50% do not reach hospital.million deaths, 50% do not reach hospital.

Ages 45-54, M>F (Risk factors same as of Ages 45-54, M>F (Risk factors same as of atherosclerosis).atherosclerosis).

Myocardial Infarction (MI)Myocardial Infarction (MI)

Pathogenesis Pathogenesis Most acute MIs are caused by coronary artery Most acute MIs are caused by coronary artery

thrombosis.thrombosis. Important contributing factors are:Important contributing factors are:

Acute plaque changes followed by Acute plaque changes followed by thrombosis.thrombosis.

Vasospasm Vasospasm and platelet aggregation may and platelet aggregation may contribute to coronary artery occlusion.contribute to coronary artery occlusion.

Acute myocardial infarction (MI)Acute myocardial infarction (MI)

MI typically begins in the subendocardial region MI typically begins in the subendocardial region and extends over the next (3-6) hours to involve and extends over the next (3-6) hours to involve the mid- and subepicardial areas of the the mid- and subepicardial areas of the myocardium myocardium

Two types of M ITwo types of M I Transmural: full thickness infarction > 2.5 cm in Transmural: full thickness infarction > 2.5 cm in

diameter caused by sever atheroma with acute diameter caused by sever atheroma with acute plaque changes leading to complete occlusion.plaque changes leading to complete occlusion.

Subendocardial: limited to inner 1/3 of wall Subendocardial: limited to inner 1/3 of wall thickness, caused by ischemia due to diffuse thickness, caused by ischemia due to diffuse coronary atherosclerosis (stenosis).coronary atherosclerosis (stenosis).

Morphology of MIMorphology of MI

Size of MI depends on segment of C.A. blocked Size of MI depends on segment of C.A. blocked and collateral circulationand collateral circulation

The location of MI depends on site of occlusion and The location of MI depends on site of occlusion and type of coronary circulationtype of coronary circulation Left anterior descending coronary artery (LAD) Left anterior descending coronary artery (LAD)

(40%- 50%)(40%- 50%) Anterior and apical LV+ ant 2/3 of IVSAnterior and apical LV+ ant 2/3 of IVS

Right coronary artery (RCA) (30% - 40%)Right coronary artery (RCA) (30% - 40%) Posterior LV + post 1/3 of IVS( in right Posterior LV + post 1/3 of IVS( in right

dominance)dominance) Left circumflex coronary artery LCA (15% - 20%)Left circumflex coronary artery LCA (15% - 20%)

Lateral LV + post wall ( in left dominance)Lateral LV + post wall ( in left dominance)

0-12 hours0-12 hours There are no morphological changes yet.There are no morphological changes yet.

12-18 hours12-18 hours Coagulation necrosis begins, the cytoplasm of the necrotic myocytes becomes Coagulation necrosis begins, the cytoplasm of the necrotic myocytes becomes eosinophilic, loss of cross striations, pyknosis and karyorrhexis. Wavy eosinophilic, loss of cross striations, pyknosis and karyorrhexis. Wavy

fiber change at the periphery of the infarct. fiber change at the periphery of the infarct.

18-72 hours18-72 hours The area shows a slight pallor. Neutrophils begin to show up and peak about 3 The area shows a slight pallor. Neutrophils begin to show up and peak about 3 days and subsequently diminish. Hemmhorage is rare because MIs are days and subsequently diminish. Hemmhorage is rare because MIs are ischemic by definition. contraction bands at the periphery of the infarct ischemic by definition. contraction bands at the periphery of the infarct

produced by hypercontraction of myofibrils in dying cells. produced by hypercontraction of myofibrils in dying cells.

4-7 days4-7 days The infarct will appear pale firm with a hyperemic boarder. Macrophages, The infarct will appear pale firm with a hyperemic boarder. Macrophages, fibroblasts and capillaries first appear at the margins then begin to migrate fibroblasts and capillaries first appear at the margins then begin to migrate

into center. Macrophages begin to phagocytize the necrotic myocytes.into center. Macrophages begin to phagocytize the necrotic myocytes.

10 days10 days The necrotic area is yellow, soft; the granulation tissue is visible grossly at the The necrotic area is yellow, soft; the granulation tissue is visible grossly at the edge of the infarct as a red-purple zone. Collagen fibers are seen and many edge of the infarct as a red-purple zone. Collagen fibers are seen and many

macrophages with remnants of myocytes.macrophages with remnants of myocytes.

4-8 weeks4-8 weeks Vascularity diminishes and most infarcts have been replaced by dense scar Vascularity diminishes and most infarcts have been replaced by dense scar tissue. The ventricular wall is thinned, firm, and gray at the site of the tissue. The ventricular wall is thinned, firm, and gray at the site of the

healed infarct healed infarct

Myocardial Infarct, early changes Myocardial Infarct, early changes (Wavy Fibers)(Wavy Fibers)

Early Acute Myocardial Infarct Early Acute Myocardial Infarct (Few PMN’s)(Few PMN’s)

Acute Myocardial InfarctAcute Myocardial InfarctCoagulative NecrosisCoagulative Necrosis

Organizing Myocardial InfarctOrganizing Myocardial InfarctGranulation TissueGranulation Tissue

Old Myocardial InfarctOld Myocardial Infarct(Collagen Scar)(Collagen Scar)

Organizing Myocardial InfarctOrganizing Myocardial Infarct

Complications of MIComplications of MI Infarcted papillary muscle rupture is most common Infarcted papillary muscle rupture is most common

at third day. It causes acute left ventricular failure at third day. It causes acute left ventricular failure and is associated with a high mortality rate.and is associated with a high mortality rate.

External rupture usually towards the end of the week External rupture usually towards the end of the week 1 as blood dissects through the myocardium. It 1 as blood dissects through the myocardium. It causes hemopericardium and cardiac tamponade. It causes hemopericardium and cardiac tamponade. It can also dissect through the IV septum. can also dissect through the IV septum.

Mural thrombi are potential sources for systemic Mural thrombi are potential sources for systemic emboli.emboli.

Acute pericarditis occurs in (15%) of patients with MI Acute pericarditis occurs in (15%) of patients with MI within 2 to 4 days.within 2 to 4 days.

Ventricular aneurysm is a late complicationVentricular aneurysm is a late complication

Complications of MIComplications of MI

After infarction about 25% of patients experience After infarction about 25% of patients experience sudden death due to fatal arrhythmia.sudden death due to fatal arrhythmia.

If patients survive the acute event, 80% to 90% If patients survive the acute event, 80% to 90% develop complications.develop complications. Arrhythmias (75% - 95%)Arrhythmias (75% - 95%) Left ventricular failure with mild to severe Left ventricular failure with mild to severe

pulmonary edema (60%) pulmonary edema (60%) Cardiogenic shock (10%) if infarct > 40% of LV Cardiogenic shock (10%) if infarct > 40% of LV

mass.mass. Thromboembolic phenomena (15%-49%).Thromboembolic phenomena (15%-49%).

MI - MI - Laboratory diagnosis Laboratory diagnosis

Creatine kinase (MB fraction) rises within 4‑6 Creatine kinase (MB fraction) rises within 4‑6

hours, peaks early and is normal within 4 days. hours, peaks early and is normal within 4 days.

LDH rises in about 24 hours, peaks in 3‑6 days LDH rises in about 24 hours, peaks in 3‑6 days

and may be abnormal for 14 days. The most and may be abnormal for 14 days. The most

sensitive is the ratio of LDH1 to LDH2 (normally < sensitive is the ratio of LDH1 to LDH2 (normally <

1.0 ; ratio "flipped" in infarction).1.0 ; ratio "flipped" in infarction).

Troponin I & T, Troponin I & T, troponin levels remain elevated for troponin levels remain elevated for

4 to 7 days after the acute event 4 to 7 days after the acute event

Sudden cardiac deathSudden cardiac death

Unexpected death from cardiac causes within one Unexpected death from cardiac causes within one

hour of the onset of symptoms.hour of the onset of symptoms.

Majority are complication of IHD.Majority are complication of IHD.

75 - 95 % have marked coronary atherosclerosis.75 - 95 % have marked coronary atherosclerosis.

Ultimate cause of death is fatal arrhythmias.Ultimate cause of death is fatal arrhythmias.

Sudden cardiac deathSudden cardiac deathCoronary Artery Diseases

Coronary atherosclerosis

Developmental abnormalities (anomalous origin, hypoplasia)

Coronary artery embolism

Other (vasculitis, dissection)

Myocardial Diseases

Cardiomyopathies

Myocarditis and other infiltrative processes

Right ventricular dysplasia

Valvular Diseases

Mitral valve prolapse

Aortic stenosis and other forms of left ventricular outflow obstruction

Endocarditis

Conduction System Abnormalities

Hypertensive heart disease (HHD)Hypertensive heart disease (HHD)

Basics for diagnosisBasics for diagnosis History of hypertensionHistory of hypertension Left ventricular hypertrophy in the absence of Left ventricular hypertrophy in the absence of

other causes accounting for hypertrophyother causes accounting for hypertrophy The stimulus for hypertrophy is pressure overloadThe stimulus for hypertrophy is pressure overload

Hypertensive heart disease (HHD)Hypertensive heart disease (HHD)

Stages of HHDStages of HHD

Compensated HHD:Compensated HHD:

With hypertrophy an adequate cardiac output With hypertrophy an adequate cardiac output

is maintained.is maintained.

Decompensated HHD:Decompensated HHD:

Thickness of muscle wall increase demand for Thickness of muscle wall increase demand for

oxygen, decrease compliance, and role of oxygen, decrease compliance, and role of

hypertension on atheroma, all contribute to hypertension on atheroma, all contribute to

decompensated HHD and eventual dilatation.decompensated HHD and eventual dilatation.

Hypertensive heart disease (HHD)Hypertensive heart disease (HHD)

GrossGross Compensated stage ..... Concentric hypertrophyCompensated stage ..... Concentric hypertrophy Decompensated stage ......... DilatationDecompensated stage ......... Dilatation

Both stages, heart weight increasedBoth stages, heart weight increased Histology: Large fibers with large nuclei, later Histology: Large fibers with large nuclei, later

interstitial fibrosis.interstitial fibrosis.

Hypertensive heart disease (HHD)Hypertensive heart disease (HHD)

Causes of death in HHDCauses of death in HHD CHFCHF Increased risk of sudden cardiac deathIncreased risk of sudden cardiac death Renal disease , strokeRenal disease , stroke

Drug control leads to regression of hypertrophy.Drug control leads to regression of hypertrophy.

AneurysmsAneurysms

AneurysmsAneurysms

Abnormal dilations of blood vessel or the heart. Abnormal dilations of blood vessel or the heart. Develop where there is marked weakening of Develop where there is marked weakening of the wall (congenital, infections, trauma, the wall (congenital, infections, trauma, systemic diseases).systemic diseases).

True aneurysms (Atherosclerotic, syphilitic, True aneurysms (Atherosclerotic, syphilitic, congenital vascular aneurysms and the left congenital vascular aneurysms and the left ventricular aneurysm) are of two shapes: ventricular aneurysm) are of two shapes: Fusiform and Saccular.Fusiform and Saccular.

Aneurysms (Cont…)Aneurysms (Cont…)

False aneurysm is a tear in the vascular wall False aneurysm is a tear in the vascular wall leading to an extravascular hematoma that leading to an extravascular hematoma that freely communicates with the intravascular freely communicates with the intravascular space (pulsating hematoma). space (pulsating hematoma). Aortic dissection (dissecting hematoma), Aortic dissection (dissecting hematoma),

patients with hypertension or with patients with hypertension or with abnormality of connective tissue that affects abnormality of connective tissue that affects the aorta (Marfan syndrome). the aorta (Marfan syndrome).

Complications: Thrombosis, Embolism, RuptureComplications: Thrombosis, Embolism, Rupture

Proximal aortic dissection Proximal aortic dissection demonstrating a small, oblique demonstrating a small, oblique intimal tear (demarcated by the intimal tear (demarcated by the probe), allowing blood to enter probe), allowing blood to enter the media, creating an the media, creating an intramural hematoma (narrow intramural hematoma (narrow arrows).arrows).

Note that the intimal tear has Note that the intimal tear has occurred in a region largely occurred in a region largely free from atherosclerotic free from atherosclerotic plaque, and that propagation of plaque, and that propagation of the intramural hematoma is the intramural hematoma is arrested at a site more distally arrested at a site more distally where atherosclerosis begins where atherosclerosis begins (broad arrow).(broad arrow).

Abdominal Aortic Aneurysm (AAA)Abdominal Aortic Aneurysm (AAA)CausesCauses

Atherosclerosis causes arterial wall thinning Atherosclerosis causes arterial wall thinning

through medial destruction. through medial destruction.

Cystic medial degeneration of the arterial media Cystic medial degeneration of the arterial media

Focal loss of elastic and muscle fibers in the Focal loss of elastic and muscle fibers in the

aortic media and replacement by cystic spaces aortic media and replacement by cystic spaces

filled with myxoid material (hypertension, filled with myxoid material (hypertension,

Marfan’s syndrome)Marfan’s syndrome)

Abdominal Aortic Aneurysm (AAA)Abdominal Aortic Aneurysm (AAA)SitesSites

Common site is abdominal aorta below the renal Common site is abdominal aorta below the renal

arteries and above the bifurcation of the aorta. But arteries and above the bifurcation of the aorta. But

the common iliac arteries, the arch, and descending the common iliac arteries, the arch, and descending

parts of the thoracic aorta can be involved.parts of the thoracic aorta can be involved.

AAAs are saccular or fusiform, and thrombus AAAs are saccular or fusiform, and thrombus

frequently fills at least part of the dilated segment . frequently fills at least part of the dilated segment .

Abdominal Aortic Aneurysm (AAA)Abdominal Aortic Aneurysm (AAA)

Two variants: Inflammatory AAAs and Mycotic Two variants: Inflammatory AAAs and Mycotic AAAs AAAs

Males > 50 years old, (50% of patients are Males > 50 years old, (50% of patients are hypertensive).hypertensive).

Complications: depend primarily on location and Complications: depend primarily on location and size:size: Rupture into the peritoneal cavity or Rupture into the peritoneal cavity or

retroperitoneal tissues with massive hemorrhage. retroperitoneal tissues with massive hemorrhage. Obstruction of a vessel, particularly of the iliac, Obstruction of a vessel, particularly of the iliac,

mesenteric, renal, or vertebral branches. mesenteric, renal, or vertebral branches. Embolism from atheroma or mural thrombus. Embolism from atheroma or mural thrombus. Pressure on an adjacent structure (ureter or Pressure on an adjacent structure (ureter or

vertebrae). vertebrae).

Abdominal aortic aneurysm that ruptured.Abdominal aortic aneurysm that ruptured.

A. Cross-section of aortic media with marked elastin A. Cross-section of aortic media with marked elastin fragmentation and formation of areas devoid of elastin that fragmentation and formation of areas devoid of elastin that resemble cystic spaces, from a patient with Marfan syndrome. resemble cystic spaces, from a patient with Marfan syndrome. <cystic medial necrosis><cystic medial necrosis>

B. Normal aortic media, showing the regular layered pattern of B. Normal aortic media, showing the regular layered pattern of elastic tissue. elastic tissue.

In both A and B the tissue section is stained to highlight elastin In both A and B the tissue section is stained to highlight elastin as black.as black.

Aortic Dissection (Dissecting Aortic Dissection (Dissecting Hematoma)Hematoma)

Entry of blood into the arterial wall, through an Entry of blood into the arterial wall, through an intimal tear, usually in the aortic arch, dissecting the intimal tear, usually in the aortic arch, dissecting the media between the middle and outer third, causing media between the middle and outer third, causing massive hemorrhage.massive hemorrhage. Aortic dissection (dissecting hematoma), occurs Aortic dissection (dissecting hematoma), occurs

in patients with hypertension (90%) or with in patients with hypertension (90%) or with abnormality of connective tissue that affects the abnormality of connective tissue that affects the aorta (Marfan syndrome).aorta (Marfan syndrome).

Dissection of the aorta or other branches Dissection of the aorta or other branches (coronary) may occur during or after pregnancy (coronary) may occur during or after pregnancy (rare). (rare).

Histologic view of the dissection demonstrating Histologic view of the dissection demonstrating an aortic intramural hematoma (asterisk). Aortic an aortic intramural hematoma (asterisk). Aortic elastic layers black and blood red in this section, elastic layers black and blood red in this section, stained with Movat stain.stained with Movat stain.

Aortic Dissection (Dissecting Aortic Dissection (Dissecting Hematoma)Hematoma)

Sudden onset of severe pain, beginning in the Sudden onset of severe pain, beginning in the anterior chest, radiating to the back, and moving anterior chest, radiating to the back, and moving downward as the dissection progresses. (Not MI).downward as the dissection progresses. (Not MI).

Aortic dissections are classified into two types:Aortic dissections are classified into two types: Proximal lesions: more common (dangerous), Proximal lesions: more common (dangerous),

involving the ascending aorta or both the involving the ascending aorta or both the ascending and the descending aorta (called type ascending and the descending aorta (called type A). A).

Distal lesions begin distal to the subclavian artery Distal lesions begin distal to the subclavian artery (called type B) (called type B)

Aortic dissections are classified into two types: A and B.

Aortic Dissection (Dissecting Hematoma)Aortic Dissection (Dissecting Hematoma)ComplicationComplication

The most common cause of death is rupture of the The most common cause of death is rupture of the dissection outward into any of the three body dissection outward into any of the three body cavities (pericardial, pleural, or peritoneal).cavities (pericardial, pleural, or peritoneal).

Retrograde dissection into the aortic root can cause Retrograde dissection into the aortic root can cause disruption of the aortic valve causing cardiac disruption of the aortic valve causing cardiac tamponade, aortic insufficiency, and myocardial tamponade, aortic insufficiency, and myocardial infarction.infarction.

Extension of the dissection into the great arteries of Extension of the dissection into the great arteries of the neck or into the coronary, renal, mesenteric, or the neck or into the coronary, renal, mesenteric, or iliac arteries, causing critical vascular obstruction. iliac arteries, causing critical vascular obstruction.

Varicose VeinsVaricose Veins

Varicose VeinsVaricose Veins Varicose Veins are abnormally dilated, tortuous Varicose Veins are abnormally dilated, tortuous

veins produced by prolonged, increased pressure veins produced by prolonged, increased pressure and loss of wall support. Most common in lower and loss of wall support. Most common in lower limbs.limbs.

The condition is common in (age >50, obese and The condition is common in (age >50, obese and women).women).

Clinically: lead to venous stasis, congestion, Clinically: lead to venous stasis, congestion, edema, pain, and thrombosis. Embolism is rareedema, pain, and thrombosis. Embolism is rare

Pathogenesis: damage to valves Pathogenesis: damage to valves Stagnation Stagnation Increased pressure Increased pressure dilatation. dilatation.

Varicose Veins- MorphologyVaricose Veins- Morphology

GrossGross Veins with varicosities are dilated, tortuous, Veins with varicosities are dilated, tortuous,

elongated and scarred, with thinning at the elongated and scarred, with thinning at the points of dilatation.points of dilatation.

Thrombosis and valve deformities (thickening Thrombosis and valve deformities (thickening and shortening of the cusps).and shortening of the cusps).

Microscopically: Microscopically: variations in the thickness of the wall caused by variations in the thickness of the wall caused by

dilatation in areas and compensatory dilatation in areas and compensatory hypertrophy and subintimal fibrosis in others.hypertrophy and subintimal fibrosis in others.

Varicose veinsVaricose veinsof the leg. of the leg.

Thrombophlebitis & Thrombophlebitis & PhlebothrombosisPhlebothrombosis

Two designations for venous thrombosis and Two designations for venous thrombosis and inflammation.inflammation.

The deep leg veins account for about 90% of cases The deep leg veins account for about 90% of cases of venous thrombosis.of venous thrombosis.

The most important clinical causes.The most important clinical causes. Cardiac failure,Cardiac failure, Neoplasia,Neoplasia, Pregnancy,Pregnancy, Obesity,Obesity, Postoperative state, andPostoperative state, and Prolonged bed rest or immobilizationProlonged bed rest or immobilization

Vascular TumorsVascular Tumors

Benign Neoplasms, Developmental and Acquired Conditions

Hemangioma

Capillary hemangioma

Cavernous hemangioma

Pyogenic granuloma (lobular capillary hemangioma)

Lymphangioma

Simple (capillary) lymphangioma

Cavernous lymphangioma (cystic hygroma)

Glomus tumor

Intermediate-Grade Neoplasms

Kaposi sarcoma

Hemangioendothelioma

Malignant Neoplasms

Angiosarcoma

Hemangiopericytoma

Classification of Vascular Tumors

Benign tumors: Benign tumors: HemangiomasHemangiomas

Characterized by increased numbers of normal or Characterized by increased numbers of normal or abnormal vessels filled with blood. abnormal vessels filled with blood.

Mostly localized but may involve large segments Mostly localized but may involve large segments of the body (entire extremity) and called of the body (entire extremity) and called angiomatosis.angiomatosis.

The majority are superficial lesions often of the The majority are superficial lesions often of the head and neck, possible in liver.head and neck, possible in liver.

Benign tumors: Benign tumors: Hemangiomas (Cont...)Hemangiomas (Cont...)

Common in childhood and constitutes 7% of all Common in childhood and constitutes 7% of all benign tumors. May present at birth. benign tumors. May present at birth.

Capillary Hemangiomas are the most common Capillary Hemangiomas are the most common type. Mostly in the skin, subcutaneous tissues, and type. Mostly in the skin, subcutaneous tissues, and mucous membranes of the oral cavity and lips. mucous membranes of the oral cavity and lips. Many regress spontaneouslyMany regress spontaneously

The strawberry type of the skin of the newborn is The strawberry type of the skin of the newborn is common (juvenile hemangioma). common (juvenile hemangioma).

Capillary HemangiomasCapillary Hemangiomas

Color (bright red to blue), size varies (mm to Color (bright red to blue), size varies (mm to centimeters), flat or slightly elevated centimeters), flat or slightly elevated

Lobulated but unencapsulated aggregates of Lobulated but unencapsulated aggregates of closely packed thin walled capillaries which are closely packed thin walled capillaries which are filled with blood and lined by flat benign filled with blood and lined by flat benign endotheliumendothelium

The Lumina may contain thrombiThe Lumina may contain thrombi

Hemangioma of the tongueHemangioma of the tongue

Cavernous HemangiomasCavernous Hemangiomas Less common, and characterized by large vascular Less common, and characterized by large vascular

spaces.spaces. Are soft, red-blue measuring 1-2 cm. Sharply Are soft, red-blue measuring 1-2 cm. Sharply

defined but not encapsulated. Composed of large defined but not encapsulated. Composed of large cavernous vascular spaces filled with blood.cavernous vascular spaces filled with blood.

Cavernous Hemangiomas are less circumscribed Cavernous Hemangiomas are less circumscribed and more frequently involve deep structures.and more frequently involve deep structures.

Rarely giant forms occur, that affects large Rarely giant forms occur, that affects large subcutaneous areas of the face or extremities.subcutaneous areas of the face or extremities.

Are mostly of little clinical significance. Are mostly of little clinical significance.

Cavernous hemangioma

Pyogenic GranulomaPyogenic Granuloma(Lobular capillary hemangioma)(Lobular capillary hemangioma)

Polypoid form of capillary hemangiomas.Polypoid form of capillary hemangiomas. Occurs as rapidly growing red nodule attached by a Occurs as rapidly growing red nodule attached by a

stalk to the skin and oral mucosa , which bleeds stalk to the skin and oral mucosa , which bleeds easily and is ulcerated.easily and is ulcerated.

One third of the lesions develop after trauma.One third of the lesions develop after trauma. The proliferating capillaries are accompanied by The proliferating capillaries are accompanied by

edema and inflammatory cellsedema and inflammatory cells The appearance resembles granulation tissue.The appearance resembles granulation tissue. Pregnancy tumor ( granuloma gravidarum) is a Pregnancy tumor ( granuloma gravidarum) is a

pyogenic granuloma that occurs in the gingival of pyogenic granuloma that occurs in the gingival of pregnant ladies and regresses after deliverypregnant ladies and regresses after delivery

Pyogenic granuloma of the lipPyogenic granuloma of the lip

Pyogenic granuloma Pyogenic granuloma Lobular capillary hemangiomaLobular capillary hemangioma

Borderline Malignancies:Borderline Malignancies:HemangioendotheliomasHemangioendotheliomas

A wide spectrum of vascular neoplasms showing A wide spectrum of vascular neoplasms showing histologic features and clinical behavior histologic features and clinical behavior intermediate between benign hemangiomas and intermediate between benign hemangiomas and angiosarcomas.angiosarcomas.

The most common is epithelioid hemangio-The most common is epithelioid hemangio-endotheliomas which occurs around medium sized endotheliomas which occurs around medium sized and large veins in the soft tissues of adults.and large veins in the soft tissues of adults.

Most are cured by excision but up to 40% recur Most are cured by excision but up to 40% recur and 30% metastasize.and 30% metastasize.

Epithelioid Epithelioid hemangioendothelioma. hemangioendothelioma.

Epithelioid hemangioendothelioma. Epithelioid hemangioendothelioma. Prominent intracytoplasmic lumen Prominent intracytoplasmic lumen

formationformation

Kaposi SarcomaKaposi Sarcoma

A. Chronic type:A. Chronic type: Called classic or European mainly occurs in Called classic or European mainly occurs in

elderly elderly Red to purple nodules in the distal lower Red to purple nodules in the distal lower

extremities, increasing in size slowly and locally extremities, increasing in size slowly and locally persistent.persistent.

B. Lymphadenopathic:B. Lymphadenopathic: Called African or endemic mainly among children Called African or endemic mainly among children

of south Africaof south Africa Localized or generalized lymphadenopathy. It is Localized or generalized lymphadenopathy. It is

an aggressive tumoran aggressive tumor

Kaposi SarcomaKaposi Sarcoma C- Transplant Associated:C- Transplant Associated:

Occurs several months to a few years Occurs several months to a few years postoperatively in solid organ transplant recipient postoperatively in solid organ transplant recipient who receive high doses of immunosuppressive who receive high doses of immunosuppressive therapy.therapy.

Lesions are localized or generalizedLesions are localized or generalized Skin lesions may regress.Skin lesions may regress.

D. AIDS associated:D. AIDS associated: In one fourth of AIDS patients especially In one fourth of AIDS patients especially

homosexualshomosexuals Common to involve lymph nodes and the gut.Common to involve lymph nodes and the gut.

Kaposi sarcomaKaposi sarcomaA. Gross photograph illustrating coalescent red-purple A. Gross photograph illustrating coalescent red-purple macules and plaques of the skin.macules and plaques of the skin.

B. Histologic view of the nodular form demonstrating B. Histologic view of the nodular form demonstrating sheets of plump, proliferating spindle cells and sheets of plump, proliferating spindle cells and vascular spaces.vascular spaces.

Malignant tumors:Malignant tumors:AngiosarcomasAngiosarcomas

Occur in both sexes ant tend to affect adultsOccur in both sexes ant tend to affect adults Mostly affects skin, soft tissues, breast and liver.Mostly affects skin, soft tissues, breast and liver. Hepatic angiosarcomas are associated with Hepatic angiosarcomas are associated with

carcinogens like arsenic. carcinogens like arsenic. Shows local invasion and metastatic spread.Shows local invasion and metastatic spread. Has poor outcome.Has poor outcome.

AngiosarcomaAngiosarcomaA. Gross photograph of angiosarcoma of the heart (right ventricle).A. Gross photograph of angiosarcoma of the heart (right ventricle).

B. Moderately well differentiated angiosarcoma with dense clumps of B. Moderately well differentiated angiosarcoma with dense clumps of irregular, moderate anaplastic cells and distinct vascular lumens.irregular, moderate anaplastic cells and distinct vascular lumens.

C. Immunohistochemical staining of angiosarcoma for the endothelial cell C. Immunohistochemical staining of angiosarcoma for the endothelial cell marker CD31, proving the endothelial nature of the tumor cells.marker CD31, proving the endothelial nature of the tumor cells.