Pathology - Lab 3.

03
School of Medicine
Pathology of the Heart Batch 2023
November 6, 2020

CASE 1 (MYOCARDITIS)
One week prior to the death of this 22-year-old man, he experienced
continuous low-grade fever ranging from 37.5°C to 38.2°C for which he took
Paracetamol. This was accompanied by easy fatigability, head and body
aches. He also noticed, as he described it to his father (who is a doctor), that
his heart appeared to be “skipping beats.” The low-grade fever persisted until
2 days prior to his death when his temperature became normal, and he
generally felt better. On the day of his death and against his father’s advice, he
decided to join a scheduled 10 km marathon run since he was feeling
“okay.” After running 2 kilometers, he collapsed with loss of consciousness and
was rushed to a nearby hospital.

DOC ERF:
 The cardinal sign of inflammation that affects the heart is the LOSS OF
FUNCTION. Inflammation is the main problem of the case. The heart is
not HYPERTROPHIED but SWELLED.
 The histologic section : The infiltration is by the T-lymphocytes. This is an
ACUTE HEART FAILURE because in chronic heart failure there is a
congestion of other organs.

GROSS IMAGE 1

Slide 1_40a (Presence of Congestion)

Slide 1_40b (Presence of inflammatory infiltrate in between cells)

Gross Image 1 Viral infection

 The heart was enlarged. The right and left atria as well as the right and [low-grade fever ranging from 37.5°C to 38.2°C, easy fatigability, head and body
left ventricles were all moderately to severely dilated. The myocardium aches]
was red to brown color. The mitral valve showed small vegetations. ↓
 Blue arrow- subendocardial fibrosis damage heart muscle due to infection and inflammatory cells
 Dilated ventricles and increased luminal diameter [viral infection self-limited temperature became normal, and he generally felt
 These gross lesions are characteristic of dilated cardiomyopath better; some cells may die]
 Results in systolic dysfunction- contractile power is affected, difficult ↓
ventricular contraction wasting of myocardium
↓
SLIDE 1_40 dilation of the heart
↓
increased left ventricular filling
(increase functional demand → hypertrophy of RV)
decreased myocardial contractility and electrical dysfunction
[heart “skipping beats.”]
↓
decreased cardiac output falls
↓
imbalance between perfusion and O2 demand
(cell death → fibrosis and atrophy)
↓
further injury by stimulus
[running 2 kilometers]
↓
Slide 1_40 (Right: Increase intercellular spaces → Atrophy) sudden death
[collapsed with loss of consciousness]

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 Slide 1_40c (Ventricular wall)
Yellow Arrow myocardium with increased distance between myocytes
Red Arrow Trabeculae
Hypertrophic and atrophic myocardial fibers and inflammatory cells surround
the myocytes

 Diffuse infiltrates composed mostly of lymphocytes which is

characteristic of myocarditis
 In response to viral infection, fever occurs
 Presence of focal myocyte necrosis
 Young to middle-aged adults are typical patients with viral myocarditis
develop progressive dyspnea, and weakness accompanied by fever and
myalgias. This is often associated with Coxsackie b virus
 Results in chest pain, arrhythmia, heart failure, or sudden death
 Scar formation= congestive heart failure
 Decreased cardiac output= hypoxia= ischemia= Lactic acid (Lactic acid
causes chest pain)
 Arrhythmia - electrical impulses are affected (SA node, purkinje fibers,
bundle of hiss)
 Arrhythmia in myocarditis
 due to damage/injury in the heart muscles the contraction
 Complete blood count
of the heart is affected.
 Troponin test- specific to heart
 when SA node is unable to release an electrical impulse the
 CKMB blood test- specific to heart
AV node will compensate, but in arrhythmia the SA node
 C-reactive protein (CRP)- non specific marker of infection in heart.
may release an impulse as well as the AV node. (no rhythm).
Maybe caused by other organs
 Problem: contractile power of myocardial fibers and abnormal rhythm of
the heart > Congestive heart failure > Death
CASE 2
A 16-year-old female consulted her pediatrician with the complaint of pain and
PATHOPHYSIOLOGY
swelling in her lower extremities more on the left of 1-week duration. She
 Viral infection - direct viral cytotoxicity and/or immune reaction against
denied any history trauma in that region. This was accompanied by occasional
infected myocytes causing progressive inflammation and consequently
bearable chest pains. She did not seek any medical help at the time and her
heart failure.
symptoms subsided with an over-the-counter non-steroidal anti-inflammatory
 Why T-cells attacked the myocytes?
drug (NSAID).
 Due to the viral infection (prevalent cause of myocarditis)
On physical examination, the patient was afebrile with normal blood pressure,
 May be clinically asymptomatic and have subtle functional impairment
pulse rate and respiratory rate. The right lower extremity was normal. The left
that may persist for years and progress to cardiomyopathy.
extremity showed signs of tenderness in both the medial and lateral aspects of
 The hallmark pathophysiologic feature of DCM is systolic dysfunction of
her left knee. She was prescribed pain-killers and sent home.
the left or both ventricles. Reduced sarcomere contractility increases
The patient presented again 10 days later with more severe pain in different
ventricular volumes to maintain cardiac output through the Frank-
joints, mostly her ankles, wrists and knees. She reported that the symptoms
Starling mechanism, producing the thin-walled dilated LV appearance
had not improved since her last visit. The pediatrician on physical examination
that is observed in overt DCM.
noticed the following: 1) blanching erythematous plaques over her body, most
 Frank and Starling demonstrated that increased ventricular preload
noticeably over the trunk and back 2) subcutaneous nodules on both arms 3)
augments contractility, but excessive pressure and volume induces a
on auscultation a grade 2 soft pan-systolic murmur over the mitral valve area.
plateau and then a reduction in myocardial contraction. Abnormal
She was immediately admitted for further work-ups. With the appropriate
hemodynamics leads further to left ventricular (LV) remodeling.
management she eventually improved and was sent home with the appropriate
 Cardiac remodeling in response to an inciting myocardial insult or an
antibiotics and other medications.
underlying genetic abnormality has been classically considered the
Unfortunately, due to financial concerns she was not compliant to her
pathognomonic aspect of DCM.
medications. Two weeks after her discharge from the hospital she developed
 Alteration in ventricular architecture, with associated increased volume
fever and chills and noticed blood in her urine. A few days later she began
and altered chamber configuration, driven on a histologic level by a
experiencing headaches for which she sought consultation and was
combination of pathologic myocyte hypertrophy, myocyte apoptosis,
subsequently hospitalized again. Her pediatrician on physical examination
myofibroblast proliferation, and interstitial fibrosis.
noticed a change in the character of the murmur.
 CD8 cells attack viruses but can also attract myocardial cells causing
myocardial damage • Over stretched =dec contractile power •
Remodeling = CO dec

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 GROSS IMAGE 2

Gross Image 2a. Acute Rheumatic Fever

Gross Image 2c.. Liquefactive necrosis
Description
 Cerebral/Intracranial abscess- Left hemisphere is deformed, the right
 This image shows the line of the mitral valve with various uniformly sized
hemisphere shows a focal lesion with liquefactive centre containing pus,
rheumatic vegetations seen. The valves also appear to be vascularized
and thin wall.
and edematous.
 Manifested as chills, fever, and headaches.
 Presence of small, firm and friable warty lesions along the lines of
 Due to vegetations > Emboli > Abscess
closure associated with acute rheumatic fever.
 Vegetations tend to detach and can cause emboli formation that can
 Shortened and thickened chordae tendinae - Mitral valve fails to close
travel to the brain and can lead to brain infarction
during systole > Regurgitation
 Septic emboli: the bacteria from the heart might travel to the blood
 Presence of verucae→ characteristic in rheumatic heart disease
stream going to the brain
 Infective endocarditis can involve almost any systems in the body
Clinical manifestation:
including the CNS.
 Erythema marginatum- These are the blanching erythematous plaques
 Histologic features of this image present necrotic areas in the upper
seen during the PE of the patient.
portion and normal cerebral cortex in the lower portion.
 Migratory polyarthritis- She had left extremity tenderness,specifically on
the medial and lateral aspects of her knee. After 10 days, the patient
SLIDE 1053
noted to have increased severity of pain in multiple joints, mostly on her
wrist, ankles, and knees.

Slide 1053a. Aschoff bodies

 Hallmark of Rheumatic heart disease
Gross Image 2b  Myocardial interstitium has a circumscribed collection of mononuclear
inflammatory cells, including some large macrophages with prominent
Description nucleoli and a binuclear macrophage
 Friable vegetation with ulceration and perforation of the cusps (acute
bacterial endocarditis)
 Increased vascularisation are observed throughout the organ.
 The closure of valve will not function well
 Vegetations tend to detach and can cause emboli formation that can
travel to the brain and can lead to brain infarction
 This is an image of the chorda tendinae that are fused leading to
shortening of the chorda tendinae or even tearing

Clinical Manifestation
 Bacterial endocarditis- Irregular reddish vegetations overlie the valve
cusps
 Characterized by heart murmurs, and fever.
 Murmur- Patient was noted to have grade 2 soft pansystolic
murmur over the mitral area. Grade 2 murmurs are easily heard
Slide 1053b. Anitschkow cells
but are not particularly loud.
 Here, the wavy band of fibrinoid necrosis is more evident. Also, the
 Pansystolic murmur is due to mitral regurgitation, which is caused
infiltration of T-lymphocytes and anitschkow cells is much appreciated.
by chronic rheumatic scarring of the leaflets.

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 SLIDE B106 CASE 3
This 54-year-old widower, a top executive in the banking industry and living
alone in a high scale condominium has not been reporting for work for the past
3 days. Concerned co-office workers after getting no response from their
texting and calls through his smartphone called his son to inquire about his
whereabouts. His son decided to go to his condominium. Since there was no
response to the doorbell, he had the door opened. He saw his father dead in
the bathroom floor.

GROSS IMAGE 3

Slide b106.
 Thickening of mitral valve
 Narrowing of the valve or mitral valve stenosis blocks blood flow to the
left ventricle
 RHF- dilation of left atrium
 Can lead to pulmonary congestion and right sided heart failure (right
ventricle hypertrophy ) due to regurgitation of blood flow
Gross image 3a-1. The heart hypertrophied.
There was severe atherosclerosis of all the major coronary arteries with a
recent thrombotic occlusion of the proximal left anterior descending coronary
artery. A recent transmural infarct was present in the left ventricle that
involved the interventricular septum and the papillary muscle

Slide b106a
 Necrosis with possible valvular calcification
 Inflammation starting to infiltrate Gross image 3a-2. Old infarct on the anterior wall of the left ventricle
 The valve is thickened due to fibrosis, and there is disruption of the  The infarcted region appears dark red because of trapping of the red
normal layers of the valve cells and hemorrhage from ruptured necrotic capillaries
 The snapshot shows a different segment of the mitral valve which is  Fresh MI> Old infarct = Massive
characterized by the infiltration of the inflammatory cells along with the
amorphous fibrin deposits in the endocardium. The thickened mitral
valve is also evident here, the fibrin deposits are very noticeable.
 It is more of thrombosis rather than calcification

Gross image 3b-1.The heart was markedly hypertrophied and dilated.

 There was a marked coronary atherosclerosis with an old occlusion of
the left anterior descending vessel.

Slide b106b. Bacterial colonies

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 Slide 16a-1.
Gross image 3b-2. A healed infarct  Presence of thrombus (presence of lines of Zahn)
 Involved the anteroseptal and apical region of the left ventricle. A mural  Muscle below the big artery show many fibrosis possibly because of
thrombus covered much of the infarct within the heart cavity. infarctions that have occured.
 The central area is has yellow discoloration surrounded by a thin rim of  Presence of ATHEROSCLEROTIC PLAQUE (80% occluded)
highly vascularized hyperemia

Slide 16a-2. Thrombus formation

SLIDE 4134

SLIDE 16A

Slide 4134a. Upper right hemorrhage

Slide 16a. Plaque formation on the inner layer of the artery.

 Rupture of atheromatous plaque in the tunica intima.
 Marked narrowing or stenosis or the vessel associated with plaque
formation.
 Fatty infiltration observed in the adjacent myocardium. Slide 4134b. Hypertrophied cardiac myocytes
 Disorganized pattern of the myocardium is suggestive of an infarct.

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Slide 4134c. Widened spaces between the dead fibers containing edema fluid
and scattered neutrophils

Slide 4239b. Variable waviness: Seen in patients with current infarct

Slide 4134d. Coagulative Necrosis & Lymphocytic infiltration

Slide 4239c. Myocardial fiber hypertrophy

Slide 4134e. Dense polymorphonuclear leukocytic infiltrate

SLIDE 4239
Slide 4239d. Congested blood vessel with hemorrhage

Slide 4239e
Slide 4239a. Fibrosis (+); Dilated veins: passive congestion

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 SLIDE 3687 SLIDE 4009

Slide 4009a
Blood Vessels With Atherosclerosis
Constricted lumen which could lead to disturbance of laminar flow and
increased pressure in the blood vessels

Slide 3687a
Hypertrophied nucleus on myocytes
Hypertrophied myocytes
Interstitial fibrosis - suggestive of chronic infarct Slide 4009b. Presence of cholesterol clefts
Note: There is obligatory fibrosis when there is hypertrophy

Slide 3687b
Pyknosis of nuclei, myocyte hypereosinophilia, marginal contraction band
necrosis Slide 4009c. Hyperemia with macrophage infiltraion

Slide 4009d. Early calcium deposition

Slide 3687c. Necrotic myocardial fibers (w/out nuclei)

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 SEQUENCING 6. CBC with platelet count, Na, K, Ca. RBS, BUN
GROSS Obtain a complete blood cell (CBC) count if myocardial infarction (MI) is
suspected in order to rule out anemia as a cause of decreased oxygen
supply and prior to giving thrombolytic agents.

7. Creatinine, Urinalysis, Baseline PT, PTT

In the general population, moderately elevated plasma creatinine was
associated with increased risk of myocardial infarction
 urinary proteome analysis – (a non-invasive test) could not only
assist in the diagnosis of coronary artery disease but also in
monitoring its progress and the efficacy of treatment.

8. 2D-Echo with Doppler (once stable)

A 2-D (or two-dimensional) echocardiogram is capable of displaying a
cross-sectional “slice” of the beating heart, including the chambers,
valves and the major blood vessels that exit from the left and right
ventricle. A Doppler echocardiogram measures the speed and direction
of the blood flow within the heart

TROPONIN
Sensitivity and Approximate Description
Specificity peak
The most sensitive 12 hours Troponin is released during MI from
and specific test the cytosolic pool of the myocytes. Its
for myocardial dam subsequent release is prolonged with
age. Because it has degradation of actin and myosin
increased filaments. Isoforms of the protein, T
specificity and I, are specific to myocardium.
compared with CK- Differential diagnosis of troponin
MB, troponin is elevation includes acute infarction,
MICROSCOPIC composed of 3 severe pulmonary embolism causing
Case sequence: slide 4009 (atherosclerosis) =>slide 3687 (cardiac hypertrophy) proteins- Troponin acute right heart overload, heart
prev MI=> slide 4239 (neovascularization) => slide 16a (fibrosis) => slide 4134 C, Cardic troponin I, failure, myocarditis. Troponins can
(coagulative necrosis)=>DEATH and Cardiac also calculate infarct size but the peak
IF patient survived/alive: slide 4009 (atherosclerosis) =>slide 3687 (cardiac troponin T. must be measured in the 3rd day.
hypertrophy) => slide 4134 (coagulative necrosis)=>slide 4239 Troponin I After myocyte injury, troponin is
(neovascularization) =>slide 16a (fibrosis)=>survived especially has a released in 2–4 hours and persists for
high affinity for up to 7 days. Normal value are-
According to Doc Abiba (from Doc Erf daw): 3687 (Hypertrophy, interstitial myocardial injury. Troponin I <0.3 ng/ml and Troponin T
fibrosis) → 4009 (Atherosclerotic plaque) → 4239 (Fibrosis) → 4134 (Ischemia, <0.2 ng/ml
necrosis) → 16a (Organized thrombus, infiltration of fats) CK-MB
Sensitivity and Approximate Description
LABORATORY TESTS Specificity peak
1. CK-MB
It is relatively 10–24 hours The CK-MB isoform of creatine
More specific and sensitive for myocardial cell injury (M.I.)
specific when kinase is expressed in heart muscle. It
Higher than normal CK-MB enzymes indicate inflammation of the heart
skeletal muscle resides in the cytosol and facilitates
muscle or are having or recently had a heart attack.
damage is not movement of high energy phosphates
2. Troponin T
present. into and out of mitochondria. Since it
Raised troponin levels indicate cardiac muscle cell death as the enzyme
has a short duration, it cannot be
is released into the blood upon injury to the heart.
used for late diagnosis of acute MI
3. ECG Stat then repeat after 12-24 hours
but can be used to suggest infarct
ST elevation indicating injury extension if levels rise again. This is
Q waves indicating necrosis usually back to normal within 2–3
T-wave inversion indicating ischemia and evolution of the days. Normal range- 2-6ng/ml
infarction
These changes are called the indicative changes of infarction and occur TRANSCRIBER’S MESSAGE
in leads facing the damaged tissue.
4. Lipid profile
Biomarker potential of using various lipids fractions for predicting risk in
M.I.
Increased Triglyceride, Total cholesterol, LDL
Decreased HDL
 To monitor treatment of unhealthy lipid levels.
5. Portable Chest X-ray
It is suggested that the chest x-ray film is a useful additional index of the
severity of heart failure in myocardial infarction.
 The radiographic picture of post-MI syndrome is that of a heart that
is enlarged because of pericardial effusion. Unilateral pleural
effusions are common, though bilateral effusions may also occur;
lower-lobe consolidation, particularly on the left side, occurs in less
than 20% of patients. These findings generally appear 2-6 weeks
after MI and are analogous to postpericardiotomy syndrome.

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