Pathology - Lab 3.

02
School of Medicine
Pathology of the Blood Vessels Batch 2023
October 22, 2020

PART 1 (CASE STUDY) Hemodynamic and electrical effects of the lesion on heart function
Case no. 1  With that thick ventricle the electrical impulse will be disorganized
This case is based on an actual autopsy case, and the images are representative because of the hypertrophied cells. The impulse will split and will be in
of what has actually been seen in the gross and microscopic. different ways.
This is a 64 year old male carpenter who is biking on his way to work one early  Cardiac hypertrophy is associated with heightened metabolic demands
morning. The man is know to the community as a hard working regular guy. due to increases in mass, heart rate, and contractility (inotropic state, or
While biking people who are walking along the sidewalk in the same street force of contraction), all of which increase cardiac oxygen consumption.
notice that the bike starts to wobble for about 50 feet until he is crosses the Because of these changes, the hypertrophied heart is vulnerable to
path of a slow moving car and is sidewiped. The bike slides along the edge of ischemia-related decompensation (as a result of diminished
the gutter and the man falls and is noticed to be unconscious. He is picked up microcirculatory perfusion, often complicated by coronary
by the neighbors and is rushed to a nearby hospital. He is declared “dead on atherosclerosis), which can evolve to cardiac failure and eventually lead
arrival” (DOA). to death.
An autopsy is performed.  Heart failure is recognized as resulting from an inability of the heart
During autopsy the medical examiner notices no significant external physical chamber to expand and fill sufficiently during diastole (diastolic
injuries. The following images represent the significant autopsy findings. dysfunction), for example, due to left ventricular hypertrophy.
The only significant history that could be obtained from his brother is that he  Delayed cardiac impulse → cardiac dysrhythmia
has been taking anti-hypertensive drugs.

Why do we need to do autopsy?

 The patient’s death was thought to be caused by being side swept by the
car.
 Even if the patient’s condition is known, the cause of death is still to be
identified

Figure 2. The left image is representative of most areas of the left ventricle. The
right image is representative of the intramyocardial arterioles.

Left picture Increased size nucleus and fibers

HYPERTROPHY
There is increase size of the myocardial cells because of the increase synthesis
of proteins. The cell undergoes cell cycle but it is arrested at g2 phase that
results in increase DNA and RNA synthesis.
Right picture Enlarged arteriole, narrowed lumen thickened arterial wall.
Fibers are atrophied.
An intramyocardial arteriole that is observed to be having a
thickened tunica intima (Hyaline Arteriosclerosis).
 The thickening of the tunica intima may have been
mediated by a previous injury. The vascular injury
stimulates smooth muscle recruitment, proliferation
and associated matrix synthesis giving rise to the
Figure 1. A transverse view of the heart which weighs 550 gm. thickened intima as a result for an attempt for the blood
vessel to heal. Presence of infarct around the vessel.
Criteria to classify the LV size FIBROSIS
normal men: 42 to 59 mm; women: 39 to 53 mm It is intiated by accumulation of lipid plaques that builds up in the arterial wall
mildly dilated men: 60 to 63 mm; women: 54 to 57 mm these can evolve into fibrous plaques. These fibrous plaques could rupture. And
moderately dilated men: 64 to 68 mm; women: 58 to 61 mm it allows activation of platelets.
severely dilated men: ≥69 mm; women: ≥62 mm

Pathophysiologic mechanism for the lesion

Pressure overload (hypertension) → inc cardiac work → inc LV wall stress →
cell stretch → hypertrophy
 Increase vascular resistance and increase stiffness of vasculature.
 Sustained increase in cardiac work due to pressure overload as in
hypertension causes an increase in LV wall stress leading to cell stretch,
and thus stimulates the myocytes to increase in size (concentric
hypertrophy); cumulatively, this increases the size and weight of the
heart.
 New sarcomeres are predominantly assembled in parallel to the long
axes of cells, expanding the crosssectional area of myocytes in ventricles
and causing a concentric increase in wall thickness

Figure 2a

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 Cardiomyocytes are hypertrophied with abundant eosinophilic
cytoplasm and box shaped nuclei
 Myocytes display bizarre forms with Y shaped branching, frequent side
to side junctions or a characteristic whorled appearance, usually around
a central fibrous core
 Hypertrophied and disorganized myocytes

*NORMAL HISTOLOGY OF HEART: With gap junctions and intercalated disc.

Box-shaped not normal (Dra. Noh)
Figure 3. In the apical region of the left ventricle the above lesion is seen. The
right image is a trichrome stain of a similar area in the left image.

Trichrome staining - assessment of cardiovascular fibrosis

 To establish collagen fiber accumulation and not tissue necrosis

Myocardial fibrosis. Fibrosis results from inflammation.

 There is migration of connective tissue cells and extracellular matrix is
deposited within a granulation tissue framework. This occurs first
through fibroblast migration and proliferation.
 New blood vessels in granulation tissue are permeable leading to the
deposition of plasma proteins, thus providing a provisional stroma for
ingrowth of fibroblasts. This increases the deposition of plasma proteins,
fibronectin, and fibrinogen into the extracellular matrix.
 Furthermore, there is also increased collagen type I deposited into the
Figure 2b ECM. This then provides a framework into which new connective tissues
Enlarged Arterioles - narrowed lumen, thickened arterial wall, have very small can be developed
portion of smooth muscles to none.
Surrounding area Collagen formation. Accumulation of lipids leaving formation of fatty streak >
 Right side: cardiac myocytes plaque progression > growth of lipid core > rapture plaque > endothelial
 Left side: atrophied (light pink) with areas of fibrosis → Infarct dysfunction > infalm > adhesion ng macrophage > platelet congregation > start
clot > hemorrhage > thrombus formation > embolus formation> blocked vessel
> dec 02 > Necrosis > remodel = (COLLAGENOUS SCAR TISSUE)
Collagen = thickened arterial wall > decrease contractility > poor perfusion of
blood > increase resistance > decrease blood flow > heart attack > cardiac
failure

PATHOGENESIS
a. Accumulation of lipids in the intima leading to formation of fatty streak
b. Clogging of vessels resulting to plaque progression
c. Once the lipid core grows, plaque ruptures.
d. Rupture will cause injury to endothelial cell in the lining of the artery then
inflammation and immune reaction occurs
e. Adhesion and migration of macrophages
f. Resulting for platelets congregate at the site in which it exposes plaque in the
blood. This will start the clotting process leading to hemorrhage into the
plaque allowing thrombus to develop.
g. Then, Embolus which blocks off downstream vessel
h. Heart muscle will decrease in oxygen
i. Necrosis of cardiac myocytes
Figure 3c. Pathophysiology of cardiac hypertrophy
j. The heart attempts to heal itself by remodeling or fibrosis
 A healed myocardial infarct showing dense collagenous scar tissue between viable
Hypertrophy, thickening, narrow blood vessel = compromised blood flow =
myocytes.
myocardial ischemia (Dr. Dela Fuente)
 The affected area of healed infarct shows old granulation tissue seen by infiltrate of
some pigmented macrophages, lymphocytes and plasma cells and few capillary
 Increased myocardial contractility, decreased ventricular volume or decreased
sized blood vessels.
afterload
 Diastolic dysfunction in HCM occurs due to abnormal dissociation of
active and myosin filaments in diastole and increase in chamber stiffness
due to hypertrophy
 Myocardial ischemia occurs due to supply demand mismatch
 Compromised coronary blood blood flow may be present as a result of
medial hypertrophy and thickening of arterial walls, associated with
luminal narrowing
 Mitral regurgitation may be present due to distortion of the mitral valve
apparatus

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  The result is a "block" of impulse conduction between the atria and the ventricles
known as "right/left bundle branch block."

Figure 6. Gross kidney

The gross kidney is atrophic due to lack of a proper blood supply brought about
by ischemia. Cortical surface shows grayish patch areas of inflammation.
FLEABITTEN KIDNEY ---> MALIGNANT HYPERTENSION

Gross appearance:
 The kidney is slightly shrunken. (Ischemia = tissue death= loss of tissue
mass) (increase RAAS= vasoconstriction = inc sodium retention =
increase blood volume)
 There is patchy ischemic atrophy with focal loss of renal parenchyma
 The surface was granular with minimal scarring (subcapsular fibrosis)
 Some parts of the kidney have pinpoint hemorrhages in the fresh state
may be due to ruptured arterioles
 Some arterioles have become thickened

Figure 4. This the left posterior circumflex coronary artery.

 INITIATION STAGE = FORMATION OF PLAQUE

 Endothelial dysfunction > increase permeability > ldl enter intima >
monocyte adhesion in adhesion protein na nag cacapture sa mono>
morphologic change > diapedisis> monocyte radical > radical +ldl =
oxidation occurs and modified ldl> this attract monocyte> more free ldl
 Turbulent flow instead of laminar
 Plaque, inc blood flow= turbulent

Figure 5. This is the serial sections of the left anterior descending branch of
Figure 7. Microscopic appearance of the arterioles.
the coronary.
 Stenosis= narrowing or lumen
Microscopic lesions
 Stenosis, repetitive deposition of ldl= fibrosis
 Top picture shows arteriolar  wall  is  thickened  with  the 
 Less blood flow, DECREASE o2 supply = ischema deposition  of  amorphous  proteinaceous material 
(hyalinized),  and  the  lumen  is  markedly  narrowed
Refer to Figure 4 & 5: Accusation of protein, smooth muscle and white blood cells —> Benign

Explain possible reasons why the left anterior descending branch lesion is more
hypertension
severe than that of the posterior circumflex branch.
 Bottom picture shows fibrinoid necrosis of arterioles
 The LAD artery is the most commonly occluded of the coronary arteries. It
 Tubules are dilated and contain many red blood cells.
provides the major blood supply to the interventricular septum, and thus bundle
 Hyperplastic arteriolosclerosis  (“onion-skinning”)  causing 
branches of the conducting system.
luminal  obliteration 
 Hence, blockage of this artery due to coronary artery disease can lead to
 Proliferation of smooth muscle and Reduplication of basement
impairment or death (infarction) of the conducting system.
membrane —> Malignant hypertension

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 AUTOPSY REPORT
The autopsy report There are various ways of making an autopsy report. The
simplest autopsy report contains the following which will serve our purpose at
your level of study:
1) A chronological listing of the anatomic finding i.e., from the present
event and going backward to past event/s that have contributed to the
present event
2) A clinico-pathologic correlation i.e., hypothesizing and explaining the
sequence of clinical events past and present based on the pathologic
findings. This is best done in an algorithm form.

SUMMARY OF CLINICAL HISTORY

Figure 9.
The patient was a 64 year old male with past medical history of hypertension
 No. Image on the left shows ruptures and hemorrhage.
based on his medications. While biking people who are walking along the
 Picture on right (slide)= Fatty streak
sidewalk noticed the bike wobbled for about 50 feet until he crossed the path
 Gross: indicates an advanced type of atherosclerosis, because here
of a slow moving car and was sideswiped. The patient was picked up by the
you'll see the prominent yellow atheromatous plaques and there are
neighbors and rushed to the hospital. The patient was declared “dead on
areas of ulceration and hemorrhage.
arrival.”
 Microscopic: indicates fatty streak along the intima.
DESCRIPTION OF GROSS LESIONS
EXTERNAL EXAMINATION: No significant external physical injuries.
HEART AND CORONARY ARTERIES: The heart weighs 550 gm. The left
ventricular wall is grater than normal. Several lesions on the heart indicates MI
that may be the cause and wobbling. Accompanied by cardiomegaly and
atherosclerosis. Fatty streak on the left posterior circumflex coronary artery.
KIDNEY: Cortical surface shows grayish patch areas.

MICROSCOPIC DESCRIPTION
HEART AND CORONARY ARTERIES: Increased in size of individual muscle fibers.
Enlarged myocyte nucleus. Hypertrophied and disorganized myocytes with
abundant eosinophilic cytoplasm and box-shaped nuclei. Myocytes display
bizarre forms with Y shaped branching, whorled appearance. Figure 10.
 YES. Both slides show fibro-lipid plaque.
KIDNEY:Hyperplastic arteriolitis or onion-skin lesion was noted.  (1st slide is the aorta)
 1st image: Presence of lipid pools/core near the tunica media of the
CLINICOPATHOLOGICAL CORRELATION artery.
The patient’s bicycle wobbled, indicative of disruption of function. Considering  Vulnerable plaque- fibrous cap is thin, lipid core=thick, more
that no severe external injuries were notes MI is the cause of death. Based on inflammatory cells
pathologic algorith from gross to histological the conclusion of MI can be  Stable plaque- Thick fibrous cap, thin lipid core, less inflammatory
derived. cells
 DOC ERF: They dont match
 In the histologic picture , it shows a fibrous cap with lipid
PART 2 (ATHEROSCLEROSIS) depositions, without any ulcerations and hemmorages, that
“Do the gross and microscopic fit?” suggests that this picture is a mild atherosclerosis.
 The gross picture on the other hand, indicates an advanced
atherosclerosis.

Figure 8.
 No. The gross image is an adult aorta showing the earliest lesion of Figure 11.
atherosclerosis which are fatty lipid streaks while the microscopic image  YES. The sides has areas of ulceration
is a crosssection of the coronary artery showing a progressing phase  Dystrophic calc: Violet stain on tunica media, there is tissue death
where many foamy macrophages and a cholesterol cleft are recognized.  Metaplastic calc: Another type of calcification.
 Cholesterol left: Parang hiwa  Calcification not seen on gross anatomy.
 Bottom na super pink: Necrotic  Plaque is protruded in the lumen
 Foamy macrophages: Bilog bilog
 DOC ERF: They dont match.
 Gross: indicates the presence of fatty streaks which is pointed by the  In the gross picture, it shows a mild type of atherosclerosis, the
white arrow. black arrow is the fibrous plaque, you'll see that there are no
 Microscopic: there is an increase accumulation of foam cells, which ulcers and hemorrhages.
means plaque is now developing. The histologic picture is a fibrotic type  While in the histologic picture is the most prominent calcification
of plaque. of the plaque which is pointed by the white arrow That
calcification is one of the key features of an advanced type of
atherosclerosis.

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 Figure 12. A Summary of Atherosclerosis

TRANSCRIBER’S MESSAGE

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