pathology 210

HYPERTENSION

• Persistent elevation of resting blood pressure above 140/90 mmHg.

Types of Hypertension

• Etiological classification:

  • Primary essential HTN (95%): without obvious cause.

  • Secondary HTN

• Clinico-pathological classification:

  • Benign hypertension: gradual rise and moderate BP.

  • Malignant hypertension (5%):

    • Rapidly rising blood pressure (systolic > 200 mm Hg or diastolic > 120 mm Hg).

    • De novo or sudden in person with benign hypertension (Accelerated hypertension)

    • Renal failure and retinal hemorrhages if untreated → death

Etiology and Pathogenesis

Primary Essential HTN (95%)

• BP: factor of total peripheral resistance and cardiac output.

  • (--) renal sodium excretion → (++) blood volume and COP

  • Hypersensitivity to catecholamines → (++) vascular resistance

• Genetic factors: familial hypertension due to variation in angiotensinogen or ANG I receptors

• Environmental factors: (++) sodium intake, stress, obesity, cigarette smoking

Secondary HTN

• Renal causes:

  • Renal artery stenosis (renovascular hypertension)

  • Renal disease (acute glomerulonephritis, chronic renal disease)

  • Polycystic kidney

  • Chronic pyelonephritis

• Endocrine causes:

  • Adrenocortical hyperfunction (primary aldosteronism, Cushing syndrome)

  • Exogenous corticosteroids

  • Pheochromocytoma (tumor at adrenal medulla secrete catechol amines)

  • Renin-producing tumors

  • Hyperthyroidism

• Others:

  • Coarctation of the aorta (upper half of the body)

Mechanism of Renal Hypertension

• (++) renin from juxtaglomerular cells of kidney → convert plasma angiotensinogen to Ang I → Ang II (VC → (++) peripheral resistance + salt and water retention → (++) blood volume

BENIGN HYPERTENSION

Blood Vessels

• Hyaline arteriolosclerosis:

  • Arteriolar and small arteries walls

  • Hemodynamic stress → leakage of plasma proteins into intima

  • homogeneous, pink hyaline thickening of intima and media → narrowing of lumen

• Fibroelastic hyperplasia (elastosis):

  • Larger arteries

  • duplication of internal elastic lamina → thickening of the media

Heart

• Concentric hypertrophy of left ventricle

• Atherosclerosis + (++) $O_2$ demands → ischemic heart disease and angina pectoris

Benign Nephrosclerosis: Primary Contracted Kidney

Kidney

• Both kidneys: symmetrically atrophic

• Renal surface: diffuse, fine granularity "grain leather"

Microscopically

• Hyaline arteriolosclerosis of afferent arterioles

• Glomerular tufts: sclerosed.

• Diffuse tubular atrophy and interstitial fibrosis.

• The larger blood vessels fibroelastic hyperplasia

• (--) GFR and mild proteinuria

Complications of Benign HTN (Causes of Death)

1. Heart failure

2. Cerebral hemorrhage

3. Chronic renal failure (rare)

MALIGNANT HYPERTENSION

Blood Vessels

• Fibrinoid necrosis:

  • Small arteries and arterioles

  • Granular eosinophilic material in arteriolar wall

• Hyperplastic arteriolosclerosis:

  • Hyperplasia of smooth muscles and connective tissue concentric, laminated, onionskin appearance

Heart

• Not marked hypertrophied (short duration)

Kidney

Gross

• The kidney normal in size or slightly shrunken (at accelerated hypertension)

• Small, pinpoint petechial hemorrhages on the cortical surface flea-bitten appearance.

Microscopic

• Fibrinoid necrosis of the arterioles

• Larger arteries: hyperplastic arteriolosclerosis

• Necrosis of glomeruli with microthrombi

Retina (Hypertensive Retinopathy)

• Retinal hemorrhages, exudates

• Papilledema: edema of optic disc with blurring of vision

Complications of Malignant HTN

1. Acute renal failure

2. Cerebral hemorrhage

3. Heart failure (rare)

ARTERIOSCLEROSIS

• Hardening of arteries

Types of Arteriosclerosis

1. ARTERIOLOSCLEROSIS: small arteries and arterioles (hyaline or hyperplastic)

2. MONCKEBERG CALCIFIC MEDIAL SCLEROSIS:

   • Calcium deposition at media of medium sized muscular arteries

   • Older than 50 years of age.

   • Do not encroach the lumen → not obstruct arterial flow because the intima is not involved.

   • No clinical significance

3. ATHEROSCLEROSIS:

   • Hardening of vessels due to lipid deposition in sub intimal CT

ATHEROSCLEROSIS

• Definition: Patchy intimal thickening due to lipid deposition covered by fibrous cap.

Risk Factors

Major Factors

1. Hypercholesterolemia, hyperlipidemia:

   • (Cholesterol)

     • ++LDL (bad cholesterol) (distribute cholesterol to peripheral tissues)

     • --HDL (good cholesterol) (mobilize cholesterol from plaques to liver to be excreted in bile)

     • (++) LDL:

       • Hereditary

       • with diet (++ animal fat or trans fats from artificial hydrogenated oils)

       • Exercise and omega 3 acid in fish oil → (++) HDL

2. Hypertension: ++ systolic and diastolic pr. → endothelial injury

3. Cigarette smoking

4. Diabetes mellitus, hypercholesterolemia

Constitutional Factors

1. (++) age: 40-60 years

2. Men, postmenopausal women. (female at child bearing period are protected by estrogen)

3. Obesity, lack of exercise

4. Type A personality + competitive life style

5. Genetic familial history:

   • hereditary hypercholesterolemia (small % of patients)

   • familial risk is due to that major risk factors HTN, DM are (poly genetic): controlled by multiple genes

Pathogenesis: RESPONSE TO INJURY HYPOTHESIS

Endothelial Injury and Inflammation

• Primary:

  • Hypercholesterolemia

  • Mechanical injury (hemodynamic forces) hypertension

  • Immune mechanisms

  • Smoking, Toxins, infectious agents.

  • injury to arterial endothelium (Occur at ostia and branching points of vessels "with high turbulence")

• Endothelial injury → (++) permeability to LDL that accumulates in the intima

• Platelet adhesion and aggregation

• Monocytes adhere to endothelium → migrate to intima → macrophages

• Endothelial cells and monocytes release ROS → oxidation of LDL to insoluble oxidized LDL and cholesterol crystals that are taken by macrophages mediated by B-VLDL receptor and scavenger receptor lipid laden foam cells

• PDGF, FGF, EGF, TGF ẞ from platelets and from monocytes proliferation and migration of smooth muscle cells into intima

• Production of connective tissue matrix proteins ECM (collagen, elastin, aminoglycans).

• T cells recruitment to intima activated and produce inflammatory cytokines stimulate macrophages, endothelial cells and smooth muscles

  • (The exact antigen and cause of T cell activation is not clear)

• Unstable plaques → fatal ischemic complications due to acute plaque rupture, thrombosis, or embolization

• Stable plaques → chronic ischemia by narrowing vessels

Sites

• Intima

• Descending order the most extensively involved are:

  • Infra renal abdominal aorta

  • Coronary arteries

  • Popliteal arteries

  • Internal carotid

  • Circle of Willis

• Upper extremities vessels, mesenteric and renal arteries are spared except their ostia

• Severity in one artery does not predict severity of other

Morphology

Fatty Streak (Cholesterol Clefts)

• The earliest lesion

• At age of 10 focal accumulations of lipid-laden foam cells appear from first year of life in the aorta

• Gross: Multiple flat yellow spots coalesce into elongated streaks 1 cm or longer

• Not raised so not cause any flow disturbance

Atheromatous Plaques "Atheromas": (Eccentric)

• Within intima of arteries

• White to yellow raised lesion 0.3 -1.5 cm in diameter → coalesce to form large mass

• Superadded thrombus red brown color

• Affects only part of the circumference (eccentric)

Microscopic

• Atheromatous plaque

  • Central Core:

    • Cholesterol and cholesterol esters

    • Lipid-laden macrophages (foam cells)

    • Calcium and necrotic debris, fibrin and other plasma proteins

    • Cholesterol clefts: needle shaped clefts

  • Shoulder:

    • The most cellular area (macrophages, T cells, smooth muscles)

    • Where fibrous cap meets the vessel wall

  • Fibrous Cap:

    • Smooth muscle cells

    • Collagen

    • Foam cells

    • Neovascularization

  • Media opposite to plaques are thin due to smooth muscles atrophy and loss

Secondary Changes: Acute Plaque Changes

• Erosion, Ulceration, hemorrhage into the plaque (intra plaque hematoma) (due to metalloprotease action), calcification

• Thrombus formation → obstructive disease

• Embolization

• Aneurysm

Effects and Complications of Atherosclerosis

In Medium Sized Arteries

1. Artery stenosis → ischemia:

   • Angina pectoris, cardiac ischemia

   • Intermittent claudication: femoral, popliteal artery stenosis → lower limb ischemia

2. Complete artery occlusion:

   • complicated plaque: rupture, hemorrhage of neovascularization, superadded thrombosis

In Large Sized Arteries

1. Atheroembolism: plaque rupture atherosclerotic debris to blood stream → microemboli

2. Thromboembolism: thrombosis on top of atheromatous plaque → embolization

3. Aneurysm formation: pressure atrophy of media → dilatation that may rupture

VASCULITIS

• Vessel wall inflammation

Types

1. Infectious:

   • Bacterial or fungal infection → mycotic aneurysm

   • Syphilitic aortitis

2. Noninfectious:

   • Hypersensitivity:

     • Immune complex deposition in vessel wall

     • Multisystemic affect mainly highly vascular tissue: skin, glomerulus, lung, GIT (Henoch-Schoenlein purpura, PAN, SLE)

   • Buerger disease (thromboangiitis obliterans) related to smoking

POLYARTERITIS NODOSA (PAN)

• Immune mediated systemic disease

• Males more than females

• Small, medium sized arteries

• 1/3 of patients have HBV: formation of immune complex depositions (contain B antigen in vessel wall)

Morphology

• Segmental transmural fibrinoid necrosis of arterial wall

• Surrounded with acute inflammatory reaction.

• Affect only part of vessel circumference

Complications

• Thrombosis with vascular occlusion or emboli → infarction

• Aneurysm due to segmental inflammatory weakness of arterial wall (coronary, cerebral, mesenteric arteries)

• Rupture hemorrhage (melena)

THROMBOANGIITIS OBLITERANS (BUERGER'S DISEASE)

• Segmental inflammatory disease

• Tibial, radial arteries + adjacent veins and nerves (neurovascular bundles)

• Exclusively in heavy smokers

Morphology

• Segmental acute transmural inflammation

• Microabscess formation

• Inflammation extend to adjacent veins and nerves

• Thrombosis, organization, recanalization

Clinical Picture

• Legs may be hands

• Sever pain, ischemic changes → gangrene

ANEURYSM

• Localized permanent arterial wall dilatation

Causes

1. Congenital absence of muscular wall and replacement by fibrous tissue

2. Loss of smooth muscles:

   • Atherosclerosis:

     • Thick intima → (--) diffusion of nutrients + thick vasa vasorum by hypertension → ischemia of media.

     • Common site: abdominal aorta

   • Syphilitic aortitis: 3ry syphilis → EAO of vasa vasorum → ischemia of media loss of muscle cells

     • Common site: ascending aorta

3. Weak arterial wall: infection → mycotic aneurysm:

   • Infective endocarditis → Embolization of infection emboli

   • Common site: cerebral arteries

   • Extension from adjacent suppurative inflammation

4. Vasculitis: immune mediated inflammation → weak arteries → small dilatations (PAN) Micro aneurysm

Classification

By Shape

1. SACCULAR: outpouching 5- 20 cm from one side of arterial wall may contain thrombus

2. FUSIFORM: circumferential dilatation up to 20 cm. common at aortic arch, abdominal aorta, iliac arteries

3. FALSE (PSEUDO) ANEURYSM: penetrating injury of arterial wall → extravascular hematoma surrounded by adventitia and fibrosis → pulsating hematoma (sac communicating with vascular lumen. Ex.: bullets, sharpnles, femoral artery puncture during arteriography, percutaneous angioplasty

By Etiology

1. CONGENITAL: berry (saccular) aneurysm of cerebral arteries at circle of Willis. If rupture subarachnoid hemorrhage

2. ATHEROSCLEROTIC ANEURYSM: abdominal aorta, iliac arteries (saccular or fusiform)

3. SYPHILITIC ANEURYSM: saccular at ascending part of arch of aorta

4. MYCOTIC: cerebral, coronary, mesenteric

5. POLYARTERITIS NODOSA

Complications

1. Rupture Hemorrhage

2. Mural thrombus occlusion of ostia of branches (renal, mesenteric embolism)

3. Pressure atrophy of surrounding (vertebra in aortic aneurysm)

ACUTE AORTIC DISSECTION (DISSECTING AORTIC ANEURYSM)

• Blood is forced through tear in intima of aorta → track down the aorta → splitting the media in two forming blood filled channel within aortic wall

Causes

• Hypertension: mainly at age 40 - 60 years

• Marfan syndrome: congenital absence of fibrillin (glycoprotein associated with elastic fibers): at young age

Morphology

• Tear starts within 10 cm of aortic valve. Dissection spreads distally or toward the heart

• Microscopic: at Marfan syndrome: cystic medial necrosis (mucoid degeneration and elastic fiber fragmentation)

• External rupture → hemorrhage or cardiac tamponade

Clinical Picture

• Sudden sever chest pain radiating to back between the scapulae

Treatment

• Surgical with high mortality rate

VARICOSE VEINS

• Abnormal dilated tortuous veins produced by prolonged increased intraluminal pressure → dilation of vessels and incompetence of valves

Etiology

• Risk factors: obesity, pregnancy, occupations with prolonged standing

• Familial

• Chronic venous ulcer with poor wound healing and superadded infections

Complications

• Pain, edema, stasis dermatitis

ESOPHAGEAL VARICES

• Cirrhosis or bilharzial periportal fibrosis opening of porto systemic shunts ++ blood flow at lower esophagus → hematemesis

HEMORRHOIDS

• Prolonged pelvis venous congestion (pregnancy, straining at defecation) → varicose dilatation of veins at ano rectal junction

Complications

• Bleeding per rectum

• Thrombosis

• Painful ulceration

THE HEART

CONGENITAL HEART

• Faulty embryogenesis during weeks 3-8 of gestation

• Most severe anomalies: incompatible with intrauterine survival

• Significant heart malformations: common at premature infants and stillborn

Etiology

• Sporadic genetic abnormalities (single gene mutations, small chromosomal losses, additions) in association with trisomy 21 (Down syndrome)

• Hereditary: Rare

• Environmental: (alone or in combination with genetic factors)

  • congenital rubella infection (German measles during pregnancy)

  • gestation diabetes

  • teratogen exposure: thalidomide, alcohol, unknown teratogens

• Nutritional factors: folate supplementation during early pregnancy reduces risk of congenital heart disease

Types

• Malformations causing a left-to-right shunt

• Malformations causing a right-to-left shunt

• Malformations causing obstruction: e.g. Aortic or pulmonary valve stenosis

CONGENITAL HEART DISEASE WITH LEFT TO RIGHT SHUNT (NON-CYANOTIC)

• The most common type

Ventricular Septal Defect

• Membranous VSD: large & in the membranous part of the septum

• Muscular VSD: small less than 0.5 cm (Rogers disease)

• Isolated or associated with Fallot's tetralogy

Effects & Complications

• Small lesions: well tolerated for years may not be recognized until later in life

• Large defects: significant left-to-right shunting early right ventricular hypertrophy

• Shunt reversal, cyanosis, death

• Pulmonary hypertension

• Infective endocarditis

Atrial Septal Defect

• Left-to-right shunt

• Excessive flow through the pulmonary valve and through ASD → murmur

• Well tolerated and do not become symptomatic before age 30

• Unusual to produce irreversible pulmonary hypertension

• ASD closure (surgical or catheter) prevents the complications

Complications

• Heart failure

• Paradoxical embolization

• Irreversible pulmonary hypertension

CONGENITAL HEART DISEASE WITH RIGHT-TO-LEFT SHUNTS (CYANOTIC CONGENTIAL HEART DISEASE)

Fallot's Tetralogy

1. Pulmonary stenosis.

2. RV hypertrophy

3. VSD

4. Overriding of aorta (aorta opening in both RT. & LT. Ventricles)

Effects and Complications

• Cyanosis

• Secondary polycythemia

• Clubbing of fingers

• Infective endocarditis.

ENDOCARDITIS & VALVULAR DISEASES

• Def.: inflammation of valvular or mural endocardium.

• Infective or non-infective

• Valvular endocarditis: vegetations (small platelet (pale) thrombi valve cusps)

Etiology & Types

Non Infective Endocarditis

1. Rheumatic endocarditis. Immune mediated

2. Systemic lupus erythematosus (SLE) (Libmann sacks endocarditis)

3. Non-bacterial thrombotic endocarditis:

   • prolonged debilitating diseases as chronic sepsis

   • uremia

   • malignancy → hypercoagulable sta → source of systemic emboli

Infective Endocarditis

• Inflammatory, immune mediated multisystem disease

• Complication of streptococcal pharyngitis, tonsillitis

RHEUMATIC FEVER AND RHEUMATIC DISEASE

• Heart: pancarditis (inflammation of all layers of heart) (most important affection)

Etiology

• Endemic in Egypt and low socio-economic developing countries

• Overcrowding, (--) resistance, (++) airborne respiratory tract infections

• In children & adolescent 5-15 years

• 2-3 weeks after sore throat or streptococcal upper respiratory tract infection by group A B hemolytic streptococcus.

• Acute rheumatic carditis is a common manifestation of active rheumatic fever

• Chronic rheumatic heart disease (RHD) → valvular abnormalities → significant valve deformity appear years after the first attack or after repeated attacks

Pathogenesis

• Genetic mediated Abnormal host immune responses to group A streptococcal antigens that cross-react with host proteins

• Antibodies and CD4+Tcells against streptococcal M proteins recognize cardiac self-antigens

• Antibody binds activate complement → recruit Fc-receptor bearing cells (neutrophils, macrophages)

• Stimulated T cells cytokine production → macrophages activation (Aschoff bodies)

• Combination of antibody-and t cell-mediated reactions → damage to heart tissue

ACUTE RHEUMATIC FEVER

Cardiac (Rheumatic Pancarditis)

Pericardium

• Fibrinous pericarditis: bread and butter Fibrin between visceral

Myocardium

• Aschoff bodies

• Gross: 1-2 mm grey nodules

• Microscopic:

  • Aschoff bodies: at myocardium interstitium at paravascular location

    • Foci of fibrinoid degeneration

    • Surrounded by T lymphocytes, occasional plasma cells, plump activated macrophages (antischkow or caterpillar cells may be multinucleated)

Endocardium (Endocarditis)

• Mural endocardium: Aschoff bodies (AB) at posterior wall of left atrium

• Valvular endocardium:

  • Mitral valve (most common) (the only cause of acquired mitral stenosis is rheumatic fever)

  • Mitral and aortic then mitral, aortic, tricuspid rare Pulmonary valve

Gross:

*   Swollen cusps +

VEGETATIONS
* In face of direction of blood flow (atrial surface of mitral valve, ventricular surface of aortic valve) in face of direction of blood flow (most friction due to closure of valve and trauma of blood passage)
* Small 1-2 mm pale brown arranged linear regular at line of closure of cusps
* Firmly fixed, adherent

Microscopic

*   Fibrinoid necrosis of cusps, chorda tendinae
*   Inflammation
*   Vegetations (platelet thrombi)

Extra Cardiac Manifestations

• Fleeting arthritis:

  • Large joint (knee, elbow)

  • Red, painful, swollen

  • Resolve completely from the joint by resolution then another joint becomes affected (no residual effect)

  • No residual effect on joints

• Skin rash:

  • Erythema annulare or marginatum: reddish macules with pale center, seen on trunk

• Subcutaneous nodules:

  • Over bony prominence (knuckles of hand) 2-20 mm nodules (Aschoff bodies (AB))

• Rheumatic chorea:

  • Involuntary, Spontaneous, uncoordinated purposeless movements (due basal ganglia inflammation)

• Fibrinous pleurisy or peritonitis

• Rheumatic pneumonitis

• Rheumatic arteritis or hypersensitivity angiitis type III hypersensitivity reaction

Clinical Picture of Rheumatic Fever

• Fever, fleeting arthritis of large joints

• Pancarditis (tachycardia, murmurs, pericardial rub)

• Subcutaneous nodules, erythema marginatum

• Sydneham chorea

Fate

• Blood tests: (++) ESR, CRP, ASOT

• Most of cases → recovery

• 1% die from fulminant myocarditis

• Recurrent acute attacks → fibrosis, deformity of cardiac valves

CHRONIC RHEUMATIC HEART DISEASE

• Healing phase of rheumatic fever → fibrosis

Morphology

Pericardium

• Common healing by resolution (without squelae)

• Or fibrosis: (milk spots) white patches on visceral pericardium

• Rare: adhesion - constrictive pericarditis

Myocardium

• Healing of Aschoff bodies (AB) by fibrosis → fine white streaks of fibrosis within muscle

Endocardium

• Mural: MacCallum patches: white patch of fibrosis of Aschoff bodies (AB) of posterior wall of left atrium also by jets of regurgitating blood

• Valvular endocardium:

  • Most common Mitral valve followed by aortic then tricuspid but pulmonary valve is spared (one or more valves)

  • Valve become thick, opaque, white, deformed

    • Mitral stenosis:

      • fibrosis, fusion of commissures → narrow valve (button hole, fish mouth)

      • thick chorda tendinea

      • hypertrophy of papillary muscles

      • valve become funnel shape when we look from the atrium

    • Mitral incompetence:

      • shrinkage of valve cusps improper closure → blood leak

    • Double valve lesion (double mitral or double deformity produce stenosis and incompetence:

      • fibrosis affects commissures and leaflets → narrow valve + does not close properly

Complications

• Subacute infective endocarditis on top of deformed fibrotic valves

• Heart failure 2ry to valvular lesions

INFECTIVE ENDOCARDITIS

Acute Infective Endocarditis

• Necrotizing Destructive infections

• High virulent organism (Staph. Aureus) That reach blood from cutaneous infection, lung infection, UTI

• On normal valve

• Rapidly fatal High morbidity and mortality even with treatment: septicemia, perforation of cusps, acute heart failure

Subacute Infective Endocarditis

• Low virulent non pyogenic organism (Streptococci viridans) at bacteremia

• Attack only abnormal valve

• Abnormal heart (scarred or deformed valves)

• (chronic rheumatic valve, congenital heart disease, prosthetic valve)

• Reach blood from minor surgery (tooth extraction, tonsillectomy)

• Treatable: Recover after antibiotic therapy, but healing by fibrosis may cause Valves deformity (stenosis or incompetence)

Acute vs. Subacute Infective Endocarditis

MITRAL STENOSIS

Causes

1. Chronic rheumatic heart disease (commonest cause in Egypt)

2. Healed subacute infective endocarditis

Effects

• Dilatation and hypertrophy of left atrium

• Arrhythmia (atrial fibrillation)

• Left atrial thrombosis → embolism

• Chronic venous congestion of the lungs pulmonary hypertension → right ventricular hypertrophy dilatation and failure

• Left ventricular is unaffected in isolated mitral stenosis

MITRAL INCOMPETENCE

Causes

1. Chronic rheumatic heart disease

2. Healing of subacute infective endocarditis

3. Dilatation of mitral ring 2ry to left ventricular dilatation

4. Rupture of papillary muscle in recent infarction

5. Mitral valve prolapse (myxomatous degeneration of mitral valve)

Effects

• Dilated left atrium, dilated hypertrophied left ventricle

• Chronic venous congestion of lung → pulmonary hypertension → right ventricular hypertrophy and dilatation

• Heart failure

AORTIC STENOSIS

Causes

1. Rheumatic heart disease

2. Healed subacute infective endocarditis

3. Congenital aortic stenosis

4. Senile calcific aortic stenosis

5. Calcification of congenital bicuspid valve

Effects

• Pressure overload → concentric hypertrophy of left ventricle diminished microcirculatory perfusion ischemia (complicated by coronary atherosclerosis), angina pectoris.

• Decompensation → congestive heart failure

• Angina, syncope, symptoms of heart failure

AORTIC INCOMPETENCE

Causes

1. Rheumatic heart disease

2. Infective endocarditis

3. Syphilitic aortitis

4. Marfan syndrome

Effects

• Dilatation of all chambers of the heart, the heart is more than 1 Kg (Cor Bovinum)

• Heart failure

PULMONARY STENOSIS

Causes

1. Congenital

2. Healed subacute infective endocarditis

3. Chronic rheumatic heart disease

4. Carcinoid syndrome

Effects

• Right ventricle hypertrophy right ventricular failure

TRICUSPID STENOSIS

Causes

1. Chronic rheumatic valvulitis

2. Healed subacute infective endocarditis

3. Carcinoid syndrome: serotonin released → valve fibrosis on the right side of the heart

ISCHEMIC (CORONARY) HEART DISEASE (IHD)

• Syndromes resulting from myocardial ischemia due to imbalance between perfusion (supply) and demand for oxygenated blood

Causes

• 90% atherosclerosis of coronary arteries

• Coronary embolism

• Coronary vessel inflammation

• Vascular spasm

• Syphilitic aortitis: narrowing of coronary ostial

• Increase oxygen demand: myocardial hypertrophy or tachycardia

• Decrease perfusion: shock

• Clinical syndromes:

  • Angina pectoris: chest pain (++) with exercise

  • Myocardial infarction (MI): frank myocardial necrosis

  • Chronic IHD with heart failure

  • Sudden cardiac death (SCD)

• Epidemiology: the leading cause of death in developed countries

ANGINA PECTORIS AND CHRONIC ISCHEMIC HEART DISEASE

Causes

• 90% atherosclerosis at one or more of coronary arteries

• Fixed lesion obstructing more than 75% of vascular cross sectional area= significant coronary artery disease → angina pectoris

• Plaque more common at first cms of (LAD) and (LCX)

Pathological Changes of Chronic Ischemic Heart Disease

• Size of heart: normal, small (atrophy), large hypertrophied (hypertension)

• Myocardium: show grey fibrous streaks

• Left ventricle: subendocardial fibrosis

• Mitral and aortic valve: thickening, calcification with normal chorda tendinae

MYOCARDIAL INFARCTION (HEART ATTACK)

• Irreversible myocardial injury → Necrosis of cardiac muscle due to prolonged sever ischemia

Pathogenesis

• CORONARY ARTERY SUDDEN COMPLETE OCCLUSION: 90% of cases

• The major cause: atherosclerosis with superimposed luminal thrombus

Sequence of Events

• Coronary artery atheromatous plaque acute changes (hemorrhage, erosion, ulceration, fissuring or rupture)

• Exposed subendothelial collagen and necrotic plaque → platelet adhere, activated, release their granules contents, aggregate to form microthrombi

• Vasospasm by mediators from platelets

• Activation of coagulation pathway by tissue factors

• Within minutes thrombus expand complete occlusion of the vessel

Other Causes

• Vasospasm with or without coronary atherosclerosis (drugs: cocaine, ephedrine) or platelet aggregation

• Emboli from left atrium:

  • Mural thrombus

  • Atrial fibrillation

  • Vegetations of infective endocarditis

• Dissecting aortic aneurysm involving coronary ostia

• Shock, hypotension, coronary vasculitis

Effects of Sudden Coronary Occlusion

• Asymptomatic: if good collaterals

• Sudden death: fatal arrythemia (VF)

• Myocardial infarction

Sites

• Anterior infarction: The most common occlusion of (LAD) 40-50% → anterior ventricular wall, anterior part of interventricular septum, apex of heart

• Lateral infarction: occlusion of (LCX) → infarction at lateral ventricular wall

• Posterior infarction: occlusion of right coronary → infarction of posterior wall and posterior part of septum

Pathological Features of Myocardial Infarction

• Ischemia is most at subendocardium. So irreversible injury (necrosis) of ischemic myocytes first at subendocardial zone (as myocardial perfusion pattern from epicardium to endocardium) Then moves through myocardium progressively transmural

Patterns of Myocardial Infarction

Transmural Infarction

• Full thickness: epicardial vessel occlusion (atherosclerosis, plaque rupture, thrombosis). Without any therapeutic intervention

Subendocardial Infarction

• Involve inner third of ventricular wall.

• Epicardial vessel occlusion when thrombus become lysed (spontaneous or therapeutic) before necrosis extends to full thickness of myocardium

• Prolonged severe reduction of blood pressure:

  • Shock

  • Superimposed on non-critical coronary stenosis. So