DISEASE OF THE CARDIOVASCULAR SYSTEM

Prof: Tian Dong Ping 田东萍

Department of Pathology ,Shantou University Medical College

Section 1 Arteriosclerosis

Introduction:Arteriosclerosis encompasses any condition of

arterial vessels that result in a thickening or hardening of the walls,It generally includes three condition:

1. Arteriolosclerosis

2. Athrosclerosis

3. Monckeberg`s Sclerosis(medial calcification)

AtherosclerosisDefinition: Atherosclerosis is a disease which affects large and medium-size arteries,Characterized by intimal fatty deposits followed by proliferation of smooth muscle cells, ultimately with collagenization.

Causes : Not Clear

Clinical Significance

• Cause 50% or more deaths. Involved arteries supply brain, heart, kidneys, lower extremities and small bowel.

• Myocardial infarct (heart attack).• Cerebral infarction (stroke), and• Aneurysm are major consequences.• Gangrene of lower legs, ischemic heart d/s

and ischemic encepholopathy and others

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Morphology in Pathology

Three stage and then complicated lesion1. Fatty streaks

Location: include the abdominal aorta and large arteries of the lower limb, the coronary arteries e and the circle of Willis.

Grossly :Pale yellow lines running parallel to one another downward for several centimeters, Eath Streak is only 1to 2mm wide.

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LM: The lipid is found

1) on endothlial cells overlying the streaks 2) within foam cell

The foam cells arise from

1 )lipid-containing smooth muscle cells2) Macrophages

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2 Fibrous plaque

1) The fatty material accumulates to form a fatty pool at the center of the developing plaque.

2) Overgrowth of fibrous tissue around the fatty pool –fibrous plaque.

Grossly: Pale yellow--- palest, slightly alevated plaque

LM: a great deal foamy cells under the fibrous tissue .

3 Atheromatous plaque ( atheroma)

Groosly: different size and number lesion on the surface of the endothelial . It including thick yellow porridge –like material, Sudan III staining the fat shows up.

LM: the lumen is lined by fibrous tissue , below which is pink amorphous material.(necrosis)---cholesterol clefts, foamy cell can been see around the edge of lesion. The deposits of calcium which stain blue.

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1. Calcification 2. Plague ulceration 3. Intimal hemorrhage 4. Thrombosis and embolism 5. Aneurysm

D. Complication of atheromatous plagueD. Complication of atheromatous plague

Risk Factors

• Age: 4-6th decades; but, the disease begins much younger age, slowly progressive.

• Sex: Men are more prone to have the d/s.• After menopause, female increase and by 60-70

yrs equal to male.• Genetic: hyperlipidemia, hypertension, diabetes,

smoking and familial risk factor.

Hyperlipidemia• Hyperclosterolemia-more responsible than

hypertriglyceridemia for atherosclerosis.• High LDL cause higher risk; HDL acts in

reverse, helps prevent atherosclerosis and ischemic heart disease (HDL move choles-terol

to liver for excretion in bile).• Genetic defects(familial hyperchlosterole- mia)-inadequate hepatic uptake of LDL.

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Pathogenesis

• Two major hypotheses:• 1. Response to injury- chronic endothelial

injury; insudation of lipoprotein-LDL; adhesion of blood monocytes & platelets; porliferation/migration of smooth muscle cells; lipids accumulation within cells.

• 2. Chronic inflammatory response.

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Aneurysms and Dissection

• Localized abnormal dilatation of a blood vessel, most commonly-aorta & heart.

• Blood enters the wall of the artery, dissect- ing between its layers. Marfan• Two major causes for aneurysm-atheroscl- erosis and cystic medial degeneration.• Mycotic aneurysm-infection

Syphilitic (Luetic) Aneurysms

• Tertiary stage of syphilis-cardiovascular and nervous systems; obliterative endar-teritis-involved small vessels(vasa vasorum)

of the aorta-weaken the wall-aneurysmal formation and scarring of the intima-tree-barking.

• Luetic aortitis-aortic valve ring dilatation.

Clinical Course

• Rupture-abdominal cavity/retroperitoneal.• Occlusion of a branch vessel at the origin.• Embolism from the atheroma or thrombus.• Impingement on adjacent structure.• Presentation as an abdominal mass.* Rupture is the most feared consequence. The

bigger the higher the risk of rupture.

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Section 2 Section 2

Coronary Atherosclerosis Coronary Atherosclerosis

And Coronary Heart Diseas(CHD)And Coronary Heart Diseas(CHD)

1.1. Coronary Atherosclerosis (CA)Coronary Atherosclerosis (CA)

Location:Location:

left coronary artery----the most frequent site left coronary artery----the most frequent site of CAof CA

And thenAnd then the right coronary artery the right coronary artery

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2.Coronary Heart Diseas(CHD)2.Coronary Heart Diseas(CHD)

Definition:Cardiac disease resulting from coronary Atherosclerosis and its complications is referred to as Atherosclerotic Atherosclerotic coronary heart diseasecoronary heart disease

•More than 90% is due to atherosclerotic coronary arterial obstruction (Coronary heart disease

Types:

*angina pectoris angina pectoris

*myocardial infarction*myocardial infarction

*myocardial fibrosis*myocardial fibrosis

(chronic ischemic heart disease)(chronic ischemic heart disease)

*Sudden coronary death*Sudden coronary death

1. angina pectoris Clinical feature: is paroxysmal pain in the chest,

occasionally radiating down the medial aspect of the left arm.

Cause : coronary atherosclerosis, with narrowing or occlusion of the coronary arteries---- oxygen deficiency of the myocardium.

Classically, angina is precipitated by activities increasing myocardial oxygen demand, such as exercise, and is relieved with in minutes by rest or nitroglycerin

2. Myocardial Infarction

Cause: Coronary atherosclerosis→ Prolonged ischemia of over 30 to 45 minutes→ muscle death.

Location: almost occur in the left ventricle.

The most frequent site is the anterior region of the left ventricle, including the anterior two thirds of the interventricular septum.

Grossly: (1) during the first few hours: is not striking

(2) 48 to 72 h: paler and drier than normal——“ Coagulation ncrosis”.

(3) about 8 to 10 days: a reddish purple zone is noticed at the periphery of the infarct as a result of the granulation tissue, and the infracted area shrinks somewhat because of the resortion of necrotic muscle.

(4) about 2 to 3 months: a gray- white or white fibrous shrunken scar replaces he resorbed dead muscle.

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LM:

(1) 6-12 h- fibres show degenerative changes

① Increased eosinophilia

② Swelling and inflammatory response

(2) 48 to 72h: Tissue degradation and removal of necrotic fibers begins.

(3) about the third week: scar formation begins

(4) By the sixth week: the scar well established

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Outcomes:

Myocardial infarction depresses ventricular function as a result of the loss of contractility in the necrotic muscle.

Complications and causes of death

(1) papillary muscle dysfunction

(2) Mural thrombosis and embolism.

(3) Rupture of heart.

(4) Cardiac Aneurysm.

(5)Immediate mortality

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3. Myocardial fibrosis

Focal fibrosis of the myocardium is the lesion with a chronic, progressive type of myocardial ischemia. The myocardial lesion is observed in the heart of patients who have had a history of attacks of angina pectoris.

Section 3 Hypertension

•Most important risk factor in coronary heart disease and cerebrovascular accidents. Also lead to cardiac hypertrophy-heart failure; aortic dissection; renal failure. 90-95% are idiopathic and apparently primary (essential), 5-10% secondary to renal disease and others. 5% of patients-malignant hypertensive and die within 2 yrs if untreated (diastolic-120mm Hg+)

Definition: Hypertension is the persistent elevation of systemic arterial pressure above normal level.

1. Normal blood pressure: B. P.≤18.6/12 kPa (140/90mmHg)

2. Hypertension: B. P. ≥ 21.3/12.6 kPa (160/95mmHg)

3. Borderline: between normal and hypertension.

Types of Hypertension

• Essential hypertension: 90-95%.• Secondary hypertension: 5-10%• Renal.• Endocrine.• Cardiovascular.• Neurologic.• Arterial pressure depends on two variables-cardiac

output and total peripheral resistance.

Types of Essential Hypertension (EH)

1. Benign hypertension: In 95% of EH

2. Malignant Hypertension: In 1~5% of EH

1. Benign hypertension: In 95% of EH

Pathological Changes: (1) In early stage, arterioles and small arteries constrict intermittently. The symptoms are headaches or dizzy spells. The B. P. level is labile and decreases significantly with bed rest.

(2) Changes of Blood vessels ① Hyaline arteriolosclerosis:

occurs in arterioles and is characterized by thickening and hyalinization of the vessel walls and narrowing of their lumens. The hyaline material is deposited in the arteriolar intima and media, which become thickened, poorly cellular, and more or less homogeneous.

② Small and medium-sized arteries A. Medial mucular hypertrophy, proliferation and later fibrosis

B. Duplication of the elastic lamina

C. Intimal proliferation

Clinical features:

The symptoms include headaches, fatigability, insomnia, dizzy spells, and palpitation. The diagnosis is established by measurement of the blood pressure. The BP is higher and more fixed.

(3) Changes of organs:

① Heart Left ventricular hypertrophy——the heart is enlarged, the eall of the heart is thick and the weight exceeds 400gm→ eventually left-sided congestive heart failure develops.

② Kidneys (hypertensive nephrosclerosis) A. Gross appearances: firm, decreased in size and granular surface.

Cut surface: thin cortex, arcuate arteries prominent and thick-walled-called “primery granular atrophic of the kidney”.

B. LM:

(i) Glomeruli: Hyaline degeneration

Tubular: atrophy and interstitial fibrosis.

(ii) Some nephron compensatory hypertrophy and dilatation

Early Clinical Features: only slightly impaired; Later, nocturia, slight polyuria, decreased concentrating power, and a slight albuminuria appear→ uremia.

③ Brain.

A. Hypertensive encephalopathy—— cerebrospinal fluid pressure elevated; cerebral edema

B. Multiple small infarcts

C. Apoplexy—— cerebral hemorrhage

④ Retina

Funduscopic examination reveals retinal arteriolosclerosis——siler wire appearance; exudates, and papiledema.

Outcome:

The course of benign hypertension is protracted and covers several decades. Most patients have few symptoms and eventually die of unrelated conditions.

2. Malignant Hypertension: In 1~5% of EH

Pathological Changes:

(1) Arteriolar necrosis with fibrinoid (fibrinoid deposits).

(2) Hyperplastic arterioles due to intimal and medial smooth muscle muscle proliferation—— “onionskin” appearance.

Clinical Features:

The blood pressure exceeds 27/16 kPa (200/120 mmHg), and the diastolic pressure is usually about 17.3 kPa (130 mmHg) and over.

The major symptoms are severe headache, nausea and vomiting, failing vision, mental disturbances, and manifestations of left-sided congestive heart failure or hypertensive encephalopathy.

Outcome:

The course is rapid, and death occurs within 2 years of onset, the average duration being 8 months, Death is usually due to uremia, congestive heart failure, or both, or occasionally to cerebral hemorrhage.

Causes of EH: is unknown

The immediate cause is an increase of the total peripheral resistance. The increased peripheral resistance is due to widespread arteriolar constriction. The possible causes resulted in the constriction include vasospastic response, rennin-angiotensin system abnormality, and hereditary predisposition.

Pathogenesis of Essential Hypertension

• Genetic factor: Gene defect in enzymes involved in aldosterone metabolism-increased salt and water resorption--Hypertension.

• Mutation in protein that affect sodium reabsorption-salt sensitive hypertension

• Environmental factors: more in USA than China• Vasoconstriction & vascular hypertrophy.* Hypertension accelerates atherosclerosis.

Section 4 Rheumatic Fever (RF)

Definition:

Rheumatic fever is a hypersensitivity inflammatory disease. It affects the connective tissues in the whole body, with the damage in the heart, joints, arteries, brain et al.

Incidence: between 10 and 15 years of age.

Clinical Features:

The major criteria: 1. Carditis The major criteria: 1. Carditis

2. Poyarthritis 2. Poyarthritis

3. Chorea 3. Chorea

4. Subcutaneous nodules4. Subcutaneous nodules

5. Erythema marginatum5. Erythema marginatum

Etiology and pathogenesis: not clear Cause:

Occurs 2 to 3 weeks after an infection with Group A streptococci, but bot directly caused by organisms.

Mechanism:

The theory of immunologic reaction has been stressed

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Pathologic changes

Three phases in development:

1. Early phase (exudative, degenerative): 1 to 4 weeks

(1) Mucoid degeneration

(2) Fibrinoid degeneration or necrosis is associated with an infiltration of some neutrophils.

1. Alterative and exudative stage: (4 weeks )

2. Proliferative phase (granulomatous phase): 4 to 13 weeks

The most distinctive proliferative lesion: Aschoff body

(1) Fibrinoid necrosis

(2) Accumulation of Aschoff cells.

Large cells with abundant basophilic cytoplasm and one to four nuclei- contain a prominent central chomatin mass.

① In longitudinal section, the nucleus is serrated—— “ caterpillar-like”.

② In cross section, a halo is observed about the chromatin bar —— “owl-eye”.

3. Fibrosis phase (healed phase): In 3 to 4 months

The Aschoffbody is fusiform, the cytoplasm of the component cells is diminished in amount, and the cells become spindle shaped. The collagenous fibers fuse→ small scars.

Rheumatic Heart Disease 1. Pericarditis:

affects the serous memberane. Characterized by fibrin, mononuclear inflammation infiltrates—— “ bread- and- butter”.

Outcome: Organization may ultimately result in scarring, adhesion

2. Myocarditis

(1) Pathology:

Location: interventricular septum or poserior wall of left ventricle.

LM: Aschoff bodies are found about vessels.

(2) Outcome: Perivascular scarring may result.

3. Endocarditis (valvulitis)

Location: the valve leaflets —— frequently the mitral

(1) In active stage:

Grossly: thickening and loss of transparency of the valve leaflets, followed by the formation of characteristic tiny, mainly along the closure line of the cusps, wartlike nodules—— “verrucous vegetations”.

LM: Valves show edema and fibrinoid necrosis.①

② Verrucous vegetations—— composed of platelets and fibrin (white thrombus).

(2) In inactive disease:

The changes are as follows: ① Fibroblastic proliferation and collagen formation——

fibrosis

② Organization of the vegetations

③ Adhesions between the lateral portions of cusps

④ Fibrous thickening, shortening, and fusion of the chordae tendines

Outcome of valvulitis:

Healing and fibrosis may cause thickening, deformity and shortening of the cusps and chordae.

 

Section 5

Chronic Rheumatic Valvulitis

The late stage of rheumatic heart disease is characterized by chronic valvulitis with resulant valve deformities. These deformities are of two type:

1. Stenosis:

2. insufficiency

1. Stenosis: The valve leaflets are thickening, adhesions and retraction→ narrowing of the valve.

The walls of the heart chamber behind the stenotic valve will be required to work harder to force blood through the narrow orifice→ hypertrophy.

The valve leaflets cannot properly→ blood regurgitates through the valve.

The walls of the heart chamber behind the insufficient valve will undergo hypertrophy, because it is required to pump its normal stroke volume plus the additional volume of blood that regurgitates into it during its diastole.

Rheumatic Mitral valvulitis

1. Mitral stenosis:

Increased work of the left atrium will compensate for a mild mitral stenosis. An uncompensated stenosis results in increased pressure and stasis in the pulmonary circulaion and increase the work of the right ventricle→ left atrial dilatation, chronic passive congestion of the lungs→ right ventricular hypertrophy. The left ventricle is normal or small in size.

2. Mitral insufficiency

 

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Infectious Endocarditis

• Microbiologic agents-friable vegetations often associated with defect/deformed cardiac tissue, mostly valves.

• Bacterial endocarditis-bacterial origin; acute and subacute: depends the virulence of the

infecting organisms and the presence of underlying cardiac disease.

Infectious Endocarditis 1

• Acute-destructive infection leads to death within days to weeks in more than 50% of patients, despite of antibiotics and surgery.

The organism is usually Staph. Aureus.• Subacute-by low virulence organisms, weeks

to months and recover after appropriate treatment. The organisms are usually Staph. Epidermidis & Strep viridans

Complications

• Cardiac complications: Valvular insufficiency/ stenosis-heart failure. Myocardial ring abscess with perforations. Suppurative pericarditis Partial dehiscence c`leak on artificial valves• Embolic complications: Infarcts to organs.• Renal complications: Focal and difuse• Multiple abscesses: Staph endocarditis, often

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Noninfected Vegetations

• 1. NBTE (nonbacterial thrombotic endocarditis)- blood components on the leaf-lets of the cardiac valves. In pancreatic cancer patient or sepsis(Marantic endocardi-tis), clinical significant-embolism.

• 2. Libman-Sacks endocarditis: SLE patient with mitral and tricuspid valvulitis-small

sterile vegetations. Cl significant-as above

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Myocardial Disease, Cardiomyopathy

• A. Dilated cadiomyopathy (DCM), progressive dilatation-systolic dysfunction

• B. Hypertrophic cardiomyopathy (HCM), abnormal diastolic filling-diastolic dysfunction

• C. Restrictive cardiomyopathy, impaired ventricular filling-diastolic dysfunction

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Myocarditis

Inflammatory processes of the myocardium-injury to the cardiac myocytes.

Major Causes: three types Infections-Viruses, Chlamydiae, Rickettsiae, Bacteria, Fungus, Protozoa & Helminths Immune mediated reactions-Poststrept, Post- viral, SLE, Drug hypersensitivity, Transplant rej; Unknown-Sarcoidosis, Giant cell myocarditis

Morphology

• Characterized by an interstitial inflamma- tory infiltrates and by injury to myocytes.

• Hypersensitivity myocarditis-eosinophils, lymphocytes and macrophages

• Giant cell myocarditis-wide spread infil- trates containing multinucleate giant cells

• Chagas disease-parasitization of myocytes

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Clinical Features

• May be entirely asymptomatic, may be on the extreme-precipitous onset of heart failure or arrhythmias, even sudden death.

• Sometime mimic acute MI, some patients later may diagnosed as having DCM.

• Other Specific Causes:• Drugs-adriamycin, cytoxan • Others-amyloidosis, iron overload

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