Pathmorphology

1. DISEASES OF THEDISEASES OF THE
CARDIAC-VASCULARCARDIAC-VASCULAR
SYSTEMSYSTEM
Lecture on pathomorphology forLecture on pathomorphology for
the 3-rd year studentsthe 3-rd year students
by V. Vasylykby V. Vasylyk

2. ATHEROSCLEROSISATHEROSCLEROSIS
 ATHEROSCLEROSIS IS A CHROnICATHEROSCLEROSIS IS A CHROnIC
DISEASE AFFECTIng pRIMARILYDISEASE AFFECTIng pRIMARILY
THE InTIMA OF LARgE AnDTHE InTIMA OF LARgE AnD
MEDIUM-SIzED MUSCULARMEDIUM-SIzED MUSCULAR
ARTERIES AnD CHARACTERIzEDARTERIES AnD CHARACTERIzED
bY FIbRO-FATTY pLAqUES ORbY FIbRO-FATTY pLAqUES OR
ATHEROMASATHEROMAS

3. THE MAjOR bACkgROUnDTHE MAjOR bACkgROUnD
FACTORSFACTORS
 AgeAge
 SexSex
 Genetic factors (familial hypercholesteronemia)Genetic factors (familial hypercholesteronemia)
 Geographic factorsGeographic factors
 DietDiet
 HypertensionHypertension
 Metabolic diseases:Metabolic diseases: diabetes mellitus,diabetes mellitus, myxedema,myxedema,
nephrosis, xanthomatosisnephrosis, xanthomatosis
 Cigarette smokingCigarette smoking
 Lack of physical exercise.Lack of physical exercise.
 Other risk factors (such asOther risk factors (such as obesity, hyperglycemia,obesity, hyperglycemia,
stress, coffee consumption)stress, coffee consumption)

4. A. Endothelial injury is
accompanied by the
attachment of monocytes,
platelets, and thrombus
formation.
B. Macrophages in the intima
phagocytise lipid and
transform into foam cells.
Macrophages also secrete
growth factors that
stimulate the proliferation
of smooth muscle cells.
C. Ruptured atheromas
release thrombogenic
material into the
circulation, causing
thrombus for intimal
ulceration.
pATHOgEnESIS OF
ATHEROSCLEROSIS

5. MICROSCOpICAL STAgES OFMICROSCOpICAL STAgES OF
ATHEROSCLEROSISATHEROSCLEROSIS
 Pre-lipid stagePre-lipid stage
 Stage of fatty stripesStage of fatty stripes
 Stage of liposclerosisStage of liposclerosis
 Stage of atheromatosisStage of atheromatosis
 Stage of ulcerationStage of ulceration
 Stage of atherocalcinosisStage of atherocalcinosis

7. The pale yellow lipid
streaks in the aorta are
the earliest lesion of
atherosclerosis.
EARLY LESIOnS OF ATHEROSCLEROSIS
Accumulations of fat in
intima. Intimal plaque
composed of foamy cells and
proliferated smooth muscle
cells

9. Many foam cells (macrophages and
proliferated smooth muscle cells full
of lipid material) and a cholesterol
cleft are recognized by their typical
needle-shaped appearance.
pROgRESSIng pHASE

10. This is severe atherosclerosis of
the aorta in which the
atheromatous plaques have
undergone ulceration along with
formation of overlying mural
thrombus.
LATE ULCERATIVE STAgE
There is a severe degree of
narrowing in this coronary artery. It
is "complex" in that there is a large
area of calcification. Complex
atheroma have calcification,
thrombosis, or hemorrhage. Such
calcification would make coronary
angioplasty difficult.

12. CLInICAL-MORpHOLOgICALCLInICAL-MORpHOLOgICAL
AppEAREnCESAppEAREnCES
 Atherosclerosis of aortaAtherosclerosis of aorta
 Atherosclerosis of coronary arteriesAtherosclerosis of coronary arteries
of heartof heart
 Atherosclerosis of cerebral arteriesAtherosclerosis of cerebral arteries
 Atherosclerosis of renal arteriesAtherosclerosis of renal arteries
 Atherosclerosis of mesentericAtherosclerosis of mesenteric
arteriesarteries
 Atherosclerosis of femoral arteriesAtherosclerosis of femoral arteries

13. ATHEROSCLEROSIS OF AORTAATHEROSCLEROSIS OF AORTA
Here, the dissection went into the
muscular wall.
Atherosclerosis may weaken the wall of the
aorta such that it bulges out to form an
aneurysm. An atherosclerotic aortic aneurysm
typically occurs in the abdominal portion below
the renal arteries. Aortic aneurysms that get
bigger than 6 or 7 cm are likely to rupture.

14. This is the gross appearance of
severe coronary atherosclerosis,
which involves virtually 100% of the
surface of the coronary. There is
extensive calcification, especially at
the right where the lumen is
narrowed.
Atherosclerosis of coronAryAtherosclerosis of coronAry
ArteriesArteries
Here is a coronary artery with
atherosclerotic plaques. There is
hemorrhage into the plaque. This is
one of the complications of
atherosclerosis. Such hemorrhage
could acutely narrow the lumen.

15. An acute cerebral infarct
is seen here. Such
infarcts are typically the
result of arterial
thrombosis.
AtherosclerosisAtherosclerosis
of cerebrAl Arteriesof cerebrAl Arteries
Atherosclerosis with
thrombus of the internal
carotid artery is seen
here.

16. Atherosclerosis
of renAl Arteries
Atherosclerosis of renal artery
can lead to renal infarction or to
development of scars or
atrophy of kidney

17. therosclerosis of mesenteric Arterietherosclerosis of mesenteric Arterie
Hemorrhagic infarct and
gangrene
of small intestine

18. This is gangrene of the
lower extremity ( "dry"
and "wet" gangrene)
due to loss of blood
supply. Gangrenous
necrosis involves the
tissues of a body part.
Because multiple
tissues are non-viable,
amputation of such
areas is necessary.
Atherosclerosis of femorAl ArteriesAtherosclerosis of femorAl Arteries

19. clinicAl effectsclinicAl effects
((AtherosclerosisAtherosclerosis))
 Slow luminal narrowing causing ischemiaSlow luminal narrowing causing ischemia
and atrophyand atrophy
 Sudden luminal occlusion causing infarctionSudden luminal occlusion causing infarction
 Propagation of plaque by formation ofPropagation of plaque by formation of
thrombi and embolithrombi and emboli
 Formation of aneurism and eventual ruptureFormation of aneurism and eventual rupture

20. hypertensionhypertension
 Arterial hypertension isArterial hypertension is
defined clinically asdefined clinically as
borderline when it richesborderline when it riches
140/90 mm Hg and140/90 mm Hg and
hypertensive whenhypertensive when
165/95 mm Hg.165/95 mm Hg.

21. hypertension is clAssifiedhypertension is clAssified
into two typesinto two types
 1) Primary or essential hypertension in which the cause of1) Primary or essential hypertension in which the cause of
increase in blood pressure in unknown. This hypertensionincrease in blood pressure in unknown. This hypertension
constitutes aboutconstitutes about 90-95%90-95% patients of hypertension.patients of hypertension.
 2) Secondary hypertension, in which the increase in blood2) Secondary hypertension, in which the increase in blood
pressure is caused by diseases of the, kidneys, endocrinepressure is caused by diseases of the, kidneys, endocrine
or some other organs.or some other organs.
According to the clinical course, both typesAccording to the clinical course, both types
of hypertension may be benign or malignant.of hypertension may be benign or malignant.
 Benign hypertension is moderate elevation of bloodBenign hypertension is moderate elevation of blood
pressure and the rise is slow as the years pass. About 90%pressure and the rise is slow as the years pass. About 90%
patients of hypertension have benign disease.patients of hypertension have benign disease.
 Malignant hypertension, is marked and rapid increase ofMalignant hypertension, is marked and rapid increase of
blood pressure to 200/140 mm Hg or more and the patientsblood pressure to 200/140 mm Hg or more and the patients
have hemorrhages and hypertensive encephalopathy.have hemorrhages and hypertensive encephalopathy.

22. bAckground fActors to essentiAlbAckground fActors to essentiAl
hypertensionhypertension
 genetic factorsgenetic factors
 environmental factors including salt intake, obesity, skilledenvironmental factors including salt intake, obesity, skilled
occupation, higher living standards and patients in high stressoccupation, higher living standards and patients in high stress
 ageage
 sexsex
 atherosclerosisatherosclerosis
The pathogenetic mechanisms are:The pathogenetic mechanisms are:
 1) high plasma level of catecholamines;1) high plasma level of catecholamines;
 2) increase in blood volume, i.e. arterial overfilling (volume2) increase in blood volume, i.e. arterial overfilling (volume
hypertension) and arteriolar constriction (vasoconstrictorhypertension) and arteriolar constriction (vasoconstrictor
hypertension);hypertension);
 3) increased cardiac output;3) increased cardiac output;
 4) low-renin essential hypertension found in approximately 20%4) low-renin essential hypertension found in approximately 20%
patients due to decreased responsiveness to renin release;patients due to decreased responsiveness to renin release;
 5) high renin essential hypertension due to decreased adrenal5) high renin essential hypertension due to decreased adrenal
responsiveness to angiotensin 2responsiveness to angiotensin 2

23. clAssificAtion depending on stAge ofclAssificAtion depending on stAge of
hypertensive diseAse.hypertensive diseAse.
 Subclinical stage occurs by hypertrophy ofSubclinical stage occurs by hypertrophy of
muscular layer and elastic structures ofmuscular layer and elastic structures of
arterioles and small-sized arteries, spasm ofarterioles and small-sized arteries, spasm of
arterioles.arterioles.
 The stage of general changes of arteriesThe stage of general changes of arteries
begins as arterial pressure increases.begins as arterial pressure increases.
 The stage of secondary changes of organs.The stage of secondary changes of organs.

24. morphologicAl chAngesmorphologicAl chAnges
– Hypertrophy of muscular layer and elasticHypertrophy of muscular layer and elastic
structures of arterioles and small-sized arteries,structures of arterioles and small-sized arteries,
spasm of arterioles.spasm of arterioles.
– Small muscular arteries show segmentalSmall muscular arteries show segmental
dilatation as a result of necrosis of smoothdilatation as a result of necrosis of smooth
muscle cells.muscle cells.
– Fibrinoid necrosis.It is the combination of cellFibrinoid necrosis.It is the combination of cell
necrosis and deposition of plasma proteins in thenecrosis and deposition of plasma proteins in the
vessel wall.vessel wall.
– Proliferation and a striking increase in theProliferation and a striking increase in the
number of layers of smooth muscle cells, so-number of layers of smooth muscle cells, so-
calledcalled onion-skinonion-skin appearance.appearance.
– Arteriosclerosis, elastofibrosis and hylinosis.Arteriosclerosis, elastofibrosis and hylinosis.
– Circular atherosclerosis.Circular atherosclerosis.

25. the mAin clinicAl-morphologicAlthe mAin clinicAl-morphologicAl
types of essentiAl hypertensiontypes of essentiAl hypertension
 Cardiac typeCardiac type
 Cerebral typeCerebral type
 Renal typeRenal type

26. Hypertrophy of the myocardium
occurs. Weight of heart reaches
1 kg, thickness of left ventricle
walls is up to 3 cm. Heart is
called “cor bovinum”. Ischemic
heart disease (IHD).
cArdiAc type
In eccentric hypertrophy
(hypertrophy and
dilation), the heart is
decompensated

27. The large hemorrhage in this adult brain
arose in the basal ganglia region of a
patient with hypertension. This is one cause
for a "stroke".
Cerebral type

28. In malignant nephrosclerosis,
the kidney demonstrates
focal small hemorrhages.
This is due to an accelerated
phase of hypertension in
which blood pressures are
very high (such as 300/150
mm Hg).
renal typerenal type
Sometimes the small arteries and
arterioles can be damaged so
severely in malignant hypertension
that they demonstrate necrosis with
a pink fibrin-like quality that gives
this process its name--fibrinoid
necrosis.

29. Here is an example of renal vascular disease
known as benign nephrosclerosis. The
smaller arteries in the kidney have become
thickened and narrowed. Hyaline
arteriolosclerosis with hypertension is
present. It can lead to patchy ischemic
atrophy with focal loss of parenchyma that
gives the surface of the kidney the
characteristic granular appearance as seen
here. It is called “primary shrunken kidney”.
Thickening of the arterial
wall with malignant
hypertension also produces
a hyperplastic arteriolitis.
The arteriole has an "onion
skin" appearance.

30. The end result of many renal diseases--whether
they are renal vascular diseases,
glomerulonephritis, or chronic pyelonephritis--is
end stage renal disease. In end stage renal
disease, the kidneys are small bilaterally, as
shown here. This condition is associated with
chronic renal failure, and the patient's creatinine
are elevated. Chronic renal failure can be treated
by dialysis or by transplantation, as shown here.
The microscopic appearance of the
"end stage kidney“. The cortex is
fibrotic, the glomeruli are sclerotic, there
are scattered chronic inflammatory cell
infiltrates, and the arteries are
thickened.

32. What is isChemiC heart Disease?
Ischemic heart disease is caused by an
imbalance between the myocardial blood flow
and the metabolic demand of the myocardium.
Reduction in coronary blood flow is related to
progressive atherosclerosis with increasing
occlusion of coronary arteries. Blood flow can be
further decreased by superimposed events such
as vasospasm, thrombosis, or circulatory
changes leading to hypoperfusion.

33. •Decreased aortic diastolic pressure
•Increased intraventricular pressure and
myocardial contraction
•Coronary artery stenosis, which can be further
subdivided into the following etiologies:
•Fixed coronary stenosis
•Acute plaque change (rupture, hemorrhage)
•Coronary artery thrombosis
•Vasoconstriction
•Aortic valve stenosis and regurgitation
•Increased right atrial pressure
FaCtors reDuCing Coronary blooD FloW

34. 1. Angina pectoris - a symptom complex of IHD
characterized by paroxysmal attacks of chest pain,
usually substernal or precordial, caused by myocardial
ischemia that falls short of inducing infarction. There
are several patterns:
•Stable angina (typical)
•Variant or Prinzmetal's angina
•Unstable angina
•Sudden cardiac death
2. Myocardial Infarction (MI)
3. Ischemic Cardiomyopathy
patterns
oF isChemiC heart Disease (ihD)

35. suDDen CarDiaC Death is defined as
death occurring within an hour of onset of
symptoms. Such an occurrence often
complicates ischemic heart disease. Such
patients tend to have severe coronary
atherosclerosis (>75% lumenal narrowing).
Often, a complication such as coronary
thrombosis or plaque hemorrhage or rupture
has occurred. The mechanism of death is
usually an arrhythmia.

36. •Occlusive intracoronary thrombus - a thrombus
overlying an ulcerated or fissured stenotic
plaque causes 90% of transmural acute
myocardial infarctions.
•Vasospasm - with or without coronary
atherosclerosis and possible association with
platelet aggregation.
•Emboli - from left sided mural thrombosis,
vegetative endocarditis, or paradoxic emboli
from the right side of heart through a patent
foramen ovale.
the pathogenesis
oF myoCarDial inFarCtion (mi)

37. Patterns include:
•Transmural infarct - involving the entire thickness of
the left ventricular wall from endocardium to
epicardium, usually the anterior free wall and
posterior free wall and septum with extension into the
RV wall in 15-30%.
•Isolated infarcts of RV and right atrium are
extremely rare.
•Subendocardial infarct - multifocal areas of necrosis
confined to the inner 1/3-1/2 of the left ventricular
wall. These do not show the same evolution of
changes seen in a transmural MI.
the gross appearanCe
oF a myoCarDial inFarCtion Can vary.

38. gross morphologiC Changes
evolve over time as FolloWs:
Time from
Onset
Gross Morphologic Finding
18 - 24 Hours Pallor of myocardium
24 - 72 Hours Pallor with some hyperemia
3 - 7 Days Hyperemic border with central yellowing
10 - 21 Days
Maximally yellow and soft with vascular
margins
7 weeks White fibrosis

39. Time
from
Onset
Microscopic Morphologic Finding
1 - 3
Hours
Wavy myocardial fibers
2 - 3
Hours
Staining defect with tetrazolium or basic fuchsin dye
4 - 12
Hours
Coagulation necrosis with loss of cross striations, contraction
bands, edema, hemorrhage, and early neutrophilic infiltrate
18 - 24
Hours
Continuing coagulation necrosis, pyknosis of nuclei, and
marginal contraction bands
24 - 72
Hours
Total loss of nuclei and striations along with heavy neutrophilic
infiltrate
3 - 7
Days
Macrophage and mononuclear infiltration begin, fibrovascular
response begins
10 - 21
Days
Fibrovascular response with prominent granulation tissue
7 Weeks Fibrosis

40. •Arrhythmias and conduction defects, with possible
"sudden death"
•Extension of infarction, or re-infarction
•Congestive heart failure (pulmonary edema)
•Cardiogenic shock
•Pericarditis
•Mural thrombosis, with possible embolization
•Myocardial wall rupture, with possible tamponade
•Papillary muscle rupture, with possible valvular
insufficiency
•Ventricular aneurysm formation
CompliCations
of myoCardial infarCtion

41. The interventricular septum of the heart has
been sectioned to reveal an extensive acute
myocardial infarction. The dead muscle is
tan-yellow with a surrounding hyperemic
border.

42. The earliest change histologically
seen with acute myocardial infarction
in the first day is contraction band
necrosis. The myocardial fibers are
beginning to lose cross striations and
the nuclei are not clearly visible in
most of the cells seen here. Note the
many irregular darker pink wavy
contraction bands extending across
the fibers.
This high power microscopic view of
the myocardium demonstrates an
infarction of about 1 to 2 days in
duration. The myocardial fibers have
dark red contraction bands extending
across them. The myocardial cell
nuclei have almost all disappeared.
There is beginning acute
inflammation.

43. In this microscopic view of a recent
myocardial infarction, there is
extensive hemorrhage along with
myocardial fiber necrosis with
contraction bands and loss of nuclei.
This myocardial infarction is about 3
to 4 days old. There is an extensive
acute inflammatory cell infiltrate and
the myocardial fibers are so necrotic
that the outlines of them are only
barely visible.

44. This is an intermediate myocardial
infarction of 1 to 2 weeks in age.
Note that there are remaining
normal myocardial fibers at the top.
Below these fibers are many
macrophages along with numerous
capillaries and little collagenization.
There is pale white collagen
within the interstitium between
myocardial fibers. This
represents an area of remote
infarction.

45. One complication of a transmural
myocardial infarction is rupture of
the myocardium. This is most
likely to occur in the first week
between 3 to 5 days following the
initial event, when the myocardium
is the softest. The white arrow
marks the point of rupture in this
anterior-inferior myocardial
infarction of the left ventricular free
wall and septum. Note the dark
red blood clot forming the
hemopericardium. The
hemopericardium can lead to
tamponade.

46. The infarction was so extensive that,
after healing, the ventricular wall was
replaced by a thin band of collagen,
forming an aneurysm. Such an
aneurysm represents non-contractile
tissue that reduces stroke volume and
strains the remaining myocardium. The
stasis of blood in the aneurysm
predisposes to mural thrombosis.
A cross section through the heart
reveals a ventricular aneurysm with a
very thin wall and rupture (arrow).
Note how the aneurysm bulges out.

48. 1. There may be previous myocardial infarction (focal
cardiosclerosis)
2. Severe coronary atherosclerosis involving all major
branches (diffuse cardiosclerosis).
The result is an inadequate vascular supply which leads to myocyte loss,
fibrosis, hypertrophy, development of aneurism.
Cardiac dilation results in overload of remaining myocytes. This keeps
the process going, with compensation by continuing myocyte
hypertrophy. Eventually, the heart can no longer compensate, and
cardiac failure ensues with arrhythmias and/or ischemic events.
Thus, clinically, there is slow, progressive heart failure with or without a
history of a previous MI or anginal pain. Ischemic cardiomyopathy is
responsible for as much as 40% of the mortality in IHD.
isChemiC Cardiomyopathy

49. ТТhank you for your attentionhank you for your attention