Transcript Atherosclerosis - Shantou University

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)
Atherosclerosis
Definition:
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
Slide 12.5
Morphology in Pathology
Three stage and then complicated lesion
1. 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.
Slide 12.9
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 cells
2) Macrophages
Slide 12.10
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.
Slide 12.7
D. Complication of atheromatous plague
1. Calcification
2. Plague ulceration
3. Intimal hemorrhage
4. Thrombosis and embolism
5. Aneurysm
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 hyperchlosterolemia)-inadequate hepatic uptake of LDL.
Slide 12.12
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.
Slide 12.17
Slide 12.18
Aneurysms and Dissection
• Localized abnormal dilatation of a blood
vessel, most commonly-aorta & heart.
• Blood enters the wall of the artery, dissecting between its layers. Marfan
• Two major causes for aneurysm-atherosclerosis and cystic medial degeneration.
• Mycotic aneurysm-infection
Syphilitic (Luetic) Aneurysms
• Tertiary stage of syphilis-cardiovascular and
nervous systems; obliterative endar-teritisinvolved small vessels(vasa vasorum)
of the aorta-weaken the wall-aneurysmal
formation and scarring of the intima-treebarking.
• 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.
Slide 12.33
Slide 12.36
Section 2
Coronary Atherosclerosis
And Coronary Heart Diseas(CHD)
1. Coronary Atherosclerosis (CA)
Location:
left coronary artery----the most frequent site of CA
And then the right coronary artery
Slide 13.9
Slide 13.4
Slide 13.6
Slide 13.7
2.Coronary Heart Diseas(CHD)
Definition:
Cardiac disease resulting from coronary Atherosclerosis
and its complications is referred to as Atherosclerotic
coronary heart disease
•More than 90% is due to atherosclerotic coronary
arterial obstruction (Coronary heart disease
Types:
*angina
pectoris
*myocardial infarction
*myocardial fibrosis
(chronic ischemic heart disease)
*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
Coronary atherosclerosis→ Prolonged
ischemia of over 30 to 45 minutes→ muscle death.
Cause:
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.
Slide 13.10
Slide 13.11
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
Slide 13.14
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
Slide 13.20
Slide 13.21
Slide 13.23
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 leftsided 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-walledcalled “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
2. Poyarthritis
3. Chorea
4. Subcutaneous nodules
5. 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
Slide 13.39
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: ① Valves show edema and fibrinoid necrosis.
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
Slide 13.36
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
Slide 13.40
Slide 13.42
Noninfected Vegetations
• 1. NBTE (nonbacterial thrombotic
endocarditis)- blood components on the leaflets of the cardiac valves. In pancreatic
cancer patient or sepsis(Marantic endocarditis), clinical significant-embolism.
• 2. Libman-Sacks endocarditis: SLE patient
with mitral and tricuspid valvulitis-small
sterile vegetations. Cl significant-as above
Slide 13.44
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
Slide 13.49
Slide 13.50
Slide 13.18
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, Postviral, SLE, Drug hypersensitivity, Transplant rej;
Unknown-Sarcoidosis, Giant cell myocarditis
Morphology
• Characterized by an interstitial inflammatory infiltrates and by injury to myocytes.
• Hypersensitivity myocarditis-eosinophils,
lymphocytes and macrophages
• Giant cell myocarditis-wide spread infiltrates containing multinucleate giant cells
• Chagas disease-parasitization of myocytes
Slide 13.52
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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