neoplasm

• Terms
Atypia, Differentiation of tumor, Cochexia
Dysplasia, Carcinoma in situ, CIN, R-S cell
Precancerous lesion

• The spread way of malignant tumor

• The growth pattern of tumor

• The difference between benign and malignant tumor

• The nomenclature of tumor

Disease Of Cardiovascular
System
 Systemic hypertension (P164)

Definition:
a persistent elevation of blood pressure to
greater than 140 mmHg systolic, and/or
greater than 90 mmHg diastolic.

Most common disease

 Definitions and Classification of blood Pressure
Levels （ WHO/ISH ）

Category Systolic （ mmHg ） Diastolic (mmHg ）

Optimal ﹤120 ﹤80
Normal ﹤130 ﹤85
High-normal 130~139 85~89
Grade 1 Hypertention （ Mild ） 140~159 90~99
Grade 2 Hypertention （ Moderat 160~179 100~109
e）
Grade 3 Hypertention （ Severe ） ≥180 ≥110
When a patients’ systolic and diastolic blood pressures fall into different
categories, the higher category should apply.
Etiology and Pathogenesis
Essential hypertension:
Elevation of blood pressure without known cause.
90% of hypertension
Usually occurring after age 40 yrs

Secondary hypertension:
Elevation of blood pressure due to a preceding
defined disease process cause
< 10% of hypertension
The pathogenesis:

BP = cardiac output + peripheral resistance

Cardiac output: blood volume, cardiac factors (heart rate,
contractility).
Peripheral resistance: major factor: arteriole constrictor (e.g.
angiotensin Ⅱ)
Inhibitors of angiotensin-converting enzyme are effective
 Primary(essential) hypertension:
polygenic inheritance + environmental factors
(Figure 6-17)

1. Genetic susceptibility
familial incidence
2. Sodium homeostasis
high dietary intake of sodium sodium
retention ﹝-﹞Na+-K+ ATPase
intracellular Ca2+↑
3. Cytosol Ca2+ ↑→vascular smooth muscle
constriction ( inhibited by calcium
channel-blocking drugs)
4. Abnormalities of renin, angiotensin and
aldosterone
5. Sympathetic nervous over activation stress
– catecholamines
6. Abnormality in the NO system
NO vasodilation
• (NO donor are effective)
Secondary hypertension :
Many factors →increase cardiac output or peripheral
resistance.
Accentuation of some factors:
renin, aldosterone, renalsodium reabsorption,
catecholamines, sympathetic stimulation
e.g.
• Renal disease: renal artery stenosis (renin)
• Endocrine causes: adrenal tumors( aldosterone )
Clinical features

Benign Hypertension:
A. Early hypertension
no clinical symptom, detecting elevation of BP
(vasoconstriction)
after a long course of sustained hypertension
Vasculature injury

B. Hypertension Heart disease, Renal disease,

cerebral disease, retinal disease
Often die in cerebral hemorrhage or congestive
heart failure.
Pathologic changes of benign hypertension
(90%-95% of cases)

• Functional disturbance

• Vasculature injury

• Organ injury
（ 1 ） Functional disturbance

intermittent spasm of systemic arterioles

accompanied with disturbance of high-grade
neural function;
---fluctuation of blood pressure
（ 2 ） Vasculature injury
Arteriolosclerosis
Arterioles are the smallest branches of the arteries
with only 1 or 2 smooth muscle cell layers in
media, generally 20 to 100 m in diameter.
e.g. afferent arteriole of the glomerulus, retinal artery,
splenic central artery.
Leakage of plasma components across vascular
endothelium
Increasing ECM production by smooth muscle cells
(SMCs)
Apoptosis of SMCs

Hyaline degeneration of the wall

Loss of underlying structural detail

Wall thickening and lumen narrowing

 Renal arteriolosclerosis
homogenous, pink and hyaline deposition within the wall
Arteriolosclerosis

arteriolar wall is
hyalinized, and the
lumen is markedly
narrowed.
Thickening of muscular arteries

Smooth muscle
proliferation of the media
collagen and elastic
fibrous proliferation of
the Intima

thicken arteriolar wall,

narrowing lumen
 (3) Organ injury
--Hypertensive heart disease
the heart is enlarged
early stage: compensatory hypertrophy
(concentric hypertrophy)
symmetric thickened of left ventricle wall

heart failure: dilation of left ventricle

• Gross: enlarged heart
the weight ↑, > 375g in men (N,<350) and >350g in women
(N,<300). the free wall of left ventricle >1.2 cm
The left ventricle is markedly thickened in this patient with severe
hypertension that was untreated for many years. The myocardial
fibers have undergone hypertrophy.
This left ventricle is very thickened (slightly over 2 cm in thickness), but the
rest of the heart is not greatly enlarged. This is typical for hypertensive heart
disease.(concentric hypertrophy)
Eccentric
hypertension
left ventricular
wall is thickened,
the ventricular
cavity is dilated
LM: the hypertrophic myocardial cells have an increased
diameter with enlarged , hyperchromatic nucleus
• Hypertensive renal disease
(Primary granular atrophy of the kidney)

The kidney is reduced in

size, and the cortical surface
exhibits fine granularity.
LM:
Hyaline arteriolosclerosis
Thickening of muscular arteries

Foci of tubular atrophy and interstitial fibrosis,

Glomerular hyalinization and periglomerular fibrosis,
Hypertrophy of the remaining compensated nephrons
The afferent arteriolar wall is hyalinized and the lumens narrowed,
Some glomeruli atrophied and fibrosed and the tubule atrophied.
Other glomeruli are hypertrophed.
small arteries wall show fibrous tissue proliferation
Some glomeruli are atrophy and fibrosis, and the tubules are atrophy.
The interstitial tissue is proliferated and some lymphocytes infiltrated.
• Hypertensive cerebral disease
Cerebral thrombosis and Cerebral
hemorrhage (strokes) —result from
rupture of microaneurysms in small
intracerebral perforating arteries.

severe hemorrhage frequently cause

death of the HP patients
①cerebral edema
hypertensive encephalopathy
hypertensive crisis

②cerebral softening
microinfarct (lacunar infarct)

③cerebral hemorrhage
large fatal
microaneurysm
slit hemorrhages
Blood supply of the brain
Hypertensive hemorrhage of the brain
massive hemorrhage and extended into the lateral ventricle.
• Hypertensive encephalopathy
very high BP→ spasm of small arteries in
the brain – cerebral edema--- sever
headache and transient cerebral dysfunction
• Hypertensive Retinal Disease

• Funduscopic examination
--Increased in the arteriolar light reflex
--Arteriolar-venular crossing defects (arteriovenous
nicking)
--Retinal hemorrhages, exudates and papilledema.
There is arteriolar narrowing and "cotton wool" spots.
Papilledema is shown here. Note that the margins of the optic disk are
indistinct with blurring, because there is swelling with elevation of the
optic nerve head.
Malignant Hypertension

1. Dramatic elevation of BP over a short

period of time with a progressive renal disease.

2. Often in young and middle age.

3. Diastolic BP usually over 130mmHg.

4. Clinical course is short (months to 1-2years).

Histologic alterations:

Fibrinoid necrosis
of arterioles
(necrotizing
arteriolitis)

Eosinophilic
granular change in
the wall
fibrinoid necrosis of a small artery
Hyperplastic arteriolosclerosis The wall of arteriole
show onionskin thickening.
consequences
• Hematuria and renal failure due to fibrinoid
necrosis of glomeruli and arteries.

• Cardiac failure

• Blurred vision due to papilledema and retinal

hemorrhage.

• Severe headache and cerebral hemorrhage

Diagnosis, treatment, and prognosis

• Measure several times over a period of

weeks--- sustained high blood pressure
• Essential HP --- lifelong treatment of anti-
HP drugs, progress is good
• Surgery--- adrenal tumor
 Rheumatism (P171)
Definition
a multisystem inflammatory disease that
follows an episode of group A
streptococcal infection after an interval of
a few weeks.
immunologically mediated
• Acute phase characterized by fever, carditis,
polyarthritis, high level of antistreptolysin O
Rheumatic fever

• Occurs in children between 5 and 15 yrs of age

• Recurrence

• May cause heart disease during acute phase,

chronic valvular deformities until many years
after the acute disease
Etiology and Pathogenesis

Rheumatic fever is a hypersensitivity reaction induced by Group A

streptococcal

Group A streptococcal infection ( 3%pharyngitis)

Serum antibodies Streptococci

(against M protein)
cross reaction

Host antigens
(normal protein present in the heart, joint and other tissues)
Type II hypersensitivity mediated by cross-reacting Ab
Type III hypersensitivity to Streptococal mediated by immune complexs
 Pathology
A. Early Phase (exudative, degenerative) 1-4 weeks
multisystem– heart, synovium, joints, skin.
focal fibrinoid necrosis
diffuse cellular infiltration or localized aggregation of cells

B. Proliferation Phase (granulomatous phase) 4-13

weeks
multiple foci of granuloma (Aschoff bodies) characteristic
lesion
Aschoff body
central focus of fibrinoid necrosis surrounded by
mononuclear inflammatory cells and large
macrophages (Aschoff cells)
Aschoff cell:
Abundant basophilic cytoplasm and vesicular nuclei in
which the chromatin is disposed in central nuclei,
resembling an owl-eyed appearance in cross section
and a caterpillar shape longitudinal.
 Aschoff
body

Aschoff body Oval or elongated nodule of microscopic size, situated

interstitially between muscle fibers and often adjacent to a small vessel.
 Aschoff cell

Aschoff cells are large, abundant cytoplasm and central round to ovoid
nuclei in which the chromatin is disposed in a central, resembling an owl-
eyed appearance in cross section
C. Fibrosis phase (healed phase) 3-4 month
Aschoff bodies are replaced by fibrous scar
the cytoplasm of the component cell become
spindle shaped and collagenous fibers fuse to
small scars.
Common in cardiac tissue
Fibrosis---The Aschoff body is replaced by a nodule of scar.
Rheumatic Fever
an acute, immune-mediated, multisystem inflammatory
disease

Affects:
Heart: pericarditis, myocarditis and endocarditis --

pancarditis
Joints: polyarthritis
Skin: subcutaneous nodules and skin rashes
Arteries: arteritis
 Rheumatic pathologic changes in the organs
--Arthritis
• Affecting large joint (ankle, knees, wrist) , the inflammation
tends to move from joint to joint --- migratory polyarthritis

• The synovial membranes are swollen and hyperemic.

increased fluid in the joint

• Joint: red, swollen, warm, painful.

• Recover without any sequelae.
 --Skin lesion
Erythema marginatum
nodular, red, tender rash, specific for RF

• subcutaneous nodules :
small subcutaneous palpable nodules.
in the over bony prominence
indicate concurrent cardiac involvement
--Chorea
Random involuntary movement.
involvement of basal ganglia of the brain
has a excellent progress
--Carditis
Most serious manifestation
35% of patients with a first attack of RF

endocarditis: in all patient

Pancarditis myocarditis: sever cases
pericarditis: sever cases
Myocarditis
Aschoff bodies are located interstitially in the myocardium.
 Pericarditis
• Pericardial effusion --- exudate of serous fluid.
Deposits of fibrin are on both the visceral and parietal
surfaces of the pericardium (Cor villosum).

• Chest pain and a pericardial rub

• a lot of fibrin exudate constrictive pericarditis

 Endocarditis
• Involves mainly the mitral and aortic valves.
• Edema
• Denudation of the lining endocardium
--at the line of apposition of the free edge valve.
• Rheumatic vegetations
Platelets and fibrin thrombi (multiple, small, firm,
usually 1mm to 5mm in diameter), do not become
detached
• Valve edema and vegitations →turbulence of blood
--- various transient murmurs
Vegetation at line of contact of the valve multiple, small
Usually 1mm to 5mm in diameter.
Vegetations: small, warty, along the line of closure
platelet – fibrin thrombus
Precipitation of fibrin

Organization, fibrosis

thickening, shortening,
commissural fusion of
leaflets and tendinous
cord
 Chronic rheumatic heart disease
• Characterized by organization of the acute endocardial
inflammation and subsequent deforming fibrosis.

• The valvular leaflets become thickened and retracted,

causing permanent deformity.

• The mitral valve is the most commonly and severely

affected valve. The aortic valve is the second affected.
• The mitral valve:
thickening, commissural fusion and shortening.
Thickening and fusion of chordae tendineae.
• Fish mouth stenosis.

Stenosis is the failure of a valve to open completely,

thereby impeding forward flow.

Insufficiency results from failure of a valve to close

completely, thereby allowing reversed flow.
Normal valve （ thin delicate ） and chordae tendineae
Mitral valve:
Leaflet thickening, commissural fusion and shortening. Thickening and
fusion of chordae tendineae.
Leaflet thickening, commissural fusion and shortening.
Fish mouth stenosis.
 Pulmonnary
venous
congestion

Left atrial dilation

and hypertrophy

Right Left ventricular normal

ventricular or mild atrophy
hypertrophy

Pathophysiology of mitral stenosis.

Blood flow was resisted during diastole – turbulence (murmur); left atrial
dilation and hypertrophy.
Acute left heart failure → pulmonary venous pressure↑ --- pulmonary
edema, hemorrhage
Chronic left heart failure → chronic venous congestion, pulmonary arterial
hypertention → Right ventricular hypertrophy
 Infective Endocarditis
• An infection associated with formation of vegetations
(infected thrombi---adherent, bulky mass of thrombotic
debris and organisms )
• Common on the valves of left side of the heard ( mitral >
aortic > tricuspid > pulmonary)
• Usual term bacterial endocarditis.
• Classification:
acute infective endocarditis
subacute infective endocarditis
 Acute infective endocarditis
• Organisms —highly virulent staphylococcus
aureus
• Infecting previous normal valve→ severe
destruction of valve
• Gross: irregular, friable, bulky, microbe-laden
vegetation
LM: platelets, fibrin, cell debris, neutrophil and
clusters of organisms.
• Severe bacteremia → abscesses
• A high mortality rate
irregular, friable, bulky vegetation attached the normal valve.
Subacute infective endocarditis
• Abnormal valves
• Organisms — less virulent streptococcus
• Vegetation is composed of platelets, fibrin,
cell debris, and masses of organisms.
irregular, friable, bulky vegetation attached the valve.
Vegetation---- clusters of bacteria, platelets, fibrin, and neutrophils.
clusters of bacteria, platelets, fibrin, cell debris and neutrophils
 Atherosclerosis (ATH)
Definition
a disease of large and medium-size
arteries that results in progressive
accumulation within the intima of
SMCs, lipids and connective tissue.
Etiology
Risk factors:
1. Hypertension
The most important risk factor in people > 45 yrs
IHD is 5 times more common in individual blood
pressure>160/95 mmHg than normal people
2. Cigarette Smoking:
>10 cigarettes/day, the risk increasing
carbon monoxide(CO) cause ECs injury
3. Hyperlipidemia
• Total serum cholesterol
> 240mg/dL( > 6 mmol/L), high risk
• LDL-C
> 160mg/dL( > 4.2 mmol/L), high risk
• Total plasma triglyceride
> 250mg/dL( > 2.8 mmol/L), high risk
• Low HDL-C
< 35mg/dL( > 0.9 mmol/L), high risk
• Abnormal apoproteins
familial type III hyperlipoproteinemia
abnormal HDL-associated apoproteins
increased lipoprotein
4. Diabetes :
coexistence of other risk factors: obesity, hypertension,
hyperlipidemia.
• Increase glycosylation of collagen---LDL↑
• glycosylated HDL easily degraded
5. Other factors:
Increasing Age
 Pathogenesis
• Reaction to vascular injury hypothesis
endothelium injury adherence of monocytes (imbibe LDL,
enter the intima and become macrophages).
Macrophages release free radicals --- oxidize LDL --- endothelium
loss —fibrin deposition
Macrophages or SMCs release various factors (PDGF) SMCs
migrate into intima and proliferation
Proliferating SMCs produce collagens and proteoglycans.

Macrophages, SMC and matrix accumulate LDL from the

plasma.
• Thrombus encrustation hypothesis
Thrombus plays a role in development and
enlargement of the lesion
• Monoclonal hypothesis
Monoclonal SMC proliferation—important
in the development of the lesion
• Insudation hypothesis
lipid in the lesion is derived from plasma
lipoproteins
LDL accelerate ATH
• Intimal cell mass hypothesis
Focal accumulation of SMCs in intima
• Hemodynamic hypothesis
the location of the lesions
hemodynamic factors related to turbulence,
pressure, and shear forces.
Pathology

ATH lesion:
• The Fatty streak
• The Fibrous atheromatous plaque
• The complicated lesion
 1. Fatty streak

Gross view multiple thin, flat, yellow streaks.

Common sites: around the aortic valve ring and thoracic

aorta
Histological feature
intimal thicken; many foamy cells
 2. The fibrous atheromatous plaque
•Gross:
•Yellow-white elevation
•Cut section--- center of the plaque --- semisolid
yellow material (porridge)
•Most common sites: abdominal aorta
coronary, carotid, vertebrobasilar, mesentric,
renal,
iliofemoral arteris
 Gross view

yellow-White
plaque along the
vessel length.

Fibrous cap
LM:
• fibrous cap
a layer of fibrous connective tissue
dense collagen scattered SMCs and macrophages
• Lipid zone
Foam cells (lipid-laden macrophages and SMCs)
extracellular lipid and debris
Needle-shaped cholesterol crystals
• Basal zone
Proliferated SMCs and connective tissue
Fibrous cap

Foamy cell
Raised focal lesion with a soft yellow grumous core of lipid and
covered by a firm, gray fibrous cap.
Atheromatous plaque
A thickend and
hyalined fibrous cap.
Amorphous pink
staining core with
cholesterol clefts.
Granulation tissue can
be seen by the core,
some foamy cells.The
internal elastic lamina
is destroyed and the
media of artery
becomes thinner.
a high magnification of the aortic atheroma
with foam cells and cholesterol clefts.
3.The Complicated plaque
• Thrombosis may cause complete occlusion
caused by – slowing and turbulence of blood
– ulceration of the plaque
• Ulceration
may cause thrombosis
discharge the lipid contents of the plaque
• Dystrophic calcification
in the lipid zone of the plaque, very common
• Vascularization
ingrowth of poorly supported vessels
• Hemorrhage
plaque rupture--- hemorrhage---occlusion of
small blood vessels,
ulceration and thrombosis
• Aneurysm
abdominal aorta
arteries weakened by extensive plaque
formation
Ulceration and thrombosis
ulceration of the luminal surface with rupture of the plaque

Ulcerated lesions may develop superimposed thrombosis.

There is a pink to red recent thrombosis in this narrowed coronary
artery. The open, needle-like spaces in the atheromatous plaque
are cholesterol clefts.
Hemorrhage
 Aneurysm
a permanent dilatation of an artery.
severe ATH cause the aorta wall weakened and
dilated
A large bulge appears just
above the aortic bifurcation

aneurysm
This large abdominal atherosclerotic aortic aneurysm has
been opened to reveal abundant layered mural thrombus
within the aneurysm.
 calcification

There is a large area of calcification on the lower

right, which appears bluish.
Atherosclerosis of brain arteries
Brain arteries (Willis arterial circle)
are tortuous and hardening.
Willis arterial circle---basilar artery,
internal carotid artery, anterior and
posterior cerebral artery, and
anterior and posterior
communicating artery)
 Coronary atherosclerosis
Narrowing of the lumen of the coronary artery myocardial
ischemia ischemic heart disease or coronary heart
disease.
• The location of coronary ATH
1) left anterior descending coronary artery, 40-50%
2) right coronary artery, 30-40%
3) left circumflex coronary artery, 15-20%
• The obstruction grades of coronary artery
• Grade Ⅰ: ≤25%
• Grade Ⅱ : ≤26-50%
• Grade Ⅲ : ≤51-75%
• Grade Ⅳ: ≥75%
 Coronary heart disease
• Coronary ATH narrowing of the lumen flow
of blood is inadequate for the oxygen demands of
the heart.
• Syndromes:
- angina pectoris
- acute myocardial infarction (MI)
- sudden cardiac death
- chronic IHD
 angina pectoris
• Definition:
episodic chest pain caused by transient, reversible
myocardial ischemia.
recurrent episodes of chest pain
increased by physical activity or emotional excitement.
limited duration (1~15min)

relieved by reducing physical activity or by sublingual

nitroglycerin
Myocardial Infarction

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

Distribution of infarction:
The left ventrical, interventricular septum,
and conducting system.
A—posterolateral infarct: occlusion of the left circumflex artery.
B—anterior infarct: occlusion of the anterior descending branch of the left
coronary artery.
C—posterior infarct occlusion of the right coronary artery.
Transmural infarct--- ischemic necrosis involves the full
thickness of the ventricular wall.
Subendocardial infarct--- ischemic necrosis limited to the
inner one-third of the ventricular wall.
Left ventricular infarction
ventricular infarction
Microscopic view of a recent myocardial infarction.

there is extensive hemorrhage along with myocardial fiber

necrosis with contraction bands and loss of nuclei.
COMPLICATIONS

-- Ectopic electrical foci

-- Heart block
-- Left ventricular failure – cardiogenic shock ,
acute pulmonary edema, sudden death
-- Progressive infarction
-- Pericarditis
fibrinous or hemorrhagic pericarditis
-- Systemic embolism from Mural thrombi
-- Myocardial rupture
-- Ventricular aneurysm
Rupture of the myocardium

Rupture point was narrowed in this

anterior-inferior myocardial
infarction of the left ventricular free
wall and septum. Note the dark red
blood clot forming the
hemopericardium.
The point of rupture of the myocardium is shown with the arrow. In this
case, there was a previous myocardial infarction 3 weeks before, and
another myocardial infarction occurred, rupturing through the already thin
ventricular wall 3 days later.
Mural thrombus

The opened, dilated

left atrium contains a
large thrombus
resulting from stasis
of blood in this
chamber .