the impact of nanoparticles on cellular functions

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SCBM342-Cardiovascular Pathology

Associate Professor Dr. Wannee Jiraungkoorskul

Department of Pathobiology, Faculty of Science, Mahidol University

Tel: 02-201-5563, E-mail: [email protected]

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• Mr. A is 55 years old, high 158 cm and weight 82 kg. He

works as the personal officer more than 30 years, smokes

cigarette 1 pack/day and drinks 2-3 times/week. What are

the risk factors of his disease or illness?

Problem

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Cardiovascular Pathology

• Cardiac Failure

• Cardiac Adaptation

• Myocardial Infarction

• Endocarditis

• Myocarditis

• Pericarditis

• Cardiac tumor

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• Heart failure is a clinical syndrome not a disease.

• The heart is unable to pump sufficient blood to the body

tissues to meet ordinary metabolic demands.

• HF is defined as “a complex clinical syndrome that an result

from any structural of functional cardiac disorder that

impairs the ability of the ventricle to eject blood (systolic

heart failure) or to fill with blood (diastolic heart failure) .”

(American Heart Association Guidelines 2013)

CARDIAC FAILURE: Definition

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• Ischemic heart disease ~ 40 percent

• Dilated cardiomyopathy ~ 30 percent

• Primary valvular heart disease ~ 15 percent

• Hypertensive heart disease ~ 10 percent

• Other ~ 5 percent

CARDIAC FAILURE: Causes

6http://saypeople.com/wp-content/uploads/2011/05/Heart-failure-Symptoms.gif

Clinical Manifestations of CHF

7http://image.slidesharecdn.com/chf-140124151550-phpapp02/95/congestive-heart-failure-6-638.jpg?cb=1390576817

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• Left heart failure

• Increase diastolic volume causes

– pulmonary congestion, edema, hemoptysis

• Decreased output causes

– renal ischemia, acute tubular necrosis, oliguria

– CNS ischemia, confusion

– bowel ischemia, GI bleeding, sepsis

– skeletal muscle ischemia, weakness, fatigue

CARDIAC FAILURE

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Pulmonary edema and congestion

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Pulmonary edema and congestion

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Heart failure cells (Hemosiderin-laden macrophages)

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“Heart failure cells” in lung

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• Right heart failure

• Increase diastolic volume causes

– visceral congestion, edema and effusions

– pitting edema

• Usually caused by left heart failure

CARDIAC FAILURE

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Nutmeg (ลกูจันทนเ์ทศ)Liver (passive congestion)

Myristica fragans

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Liver, passive congestion

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Pitting edema of leg in right heart failure

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• What is not one of the main symptoms of heart failure?

A. Edema

B. Cool hands

C. Reduced urinary output

D. Shortness of breath

E. Stomach pain

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• What is not a primary cause of heart failure?

A. Cardiomyopathy

B. Coronary artery disease

C. High blood pressure

D. Valvular disease

E. Polio

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• What is the name for shortness of breath when lying

down?

A. Apnea

B. Orthopnea

C. Narcolepsy

D. Paroxysmal nocturnal dyspnea

E. Sleep apnea

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• Right heart failure causes each of the following except:

A. Splenomegaly

B. Pulmonary edema

C. Ankle edema

D.Distended neck veins

E. Liver congestion

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CARDIAC ADAPTATION

• CO = HR x SV (Male 5.6 L/min, Female 4.9 L/min)

• HR 60-180 beats per minute, SV 70-120 ml

Major cardiac adaptive changes to increased workload

• 1. Heart rate increases

• 2. Stroke volume increases

• 3. Hypertrophy

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• Each of the following result in left ventricular hypertrophy

except:

A. Aortic stenosis

B. Coarctation of the aorta

C. Mitral stenosis

D.Severe prolonged anemia

E. Systemic hypertension

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MYOCARDIAL INFARCTION

Etiology and pathogenesis

- Atherosclerosis of coronary arteries

- Decreased supply (atherosclerotic stenosis, coronary

thrombosis, vasospasm)

- Increased O2 demand (e.g., LVH due to hypertension or

aortic stenosis)

- Decreased pO2 with fixed stenosis (e.g., pulmonary

disease, anemia, high altitude, CO poisoning)

- M : F = 2-6 : 1

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48-hour-myocardial infarct

4 to 7 days MI

2 months MI

MYOCARDIAL INFARCTION

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One-day-old infarct 3 to 4 days' duration

7 to 10 days’ duration Granulation tissues

35Well-healed myocardial infarct

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Atherosclerotic plaque rupture.

A, Plaque rupture without superimposed thrombus, in patient who died suddenly.

B, Acute coronary thrombosis superimposed on an atherosclerotic plaque with focal disruption of the fibrous cap, triggering fatal myocardial infarction.

C, Massive plaque rupture with superimposed thrombus, also triggering a fatal myocardial infarction (special stain highlighting fibrin in red).

In both A and B, an arrow points to the site of plaque rupture.

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Schematic representation of

sequential progression of

coronary artery lesion

morphology, beginning with

stable chronic plaque

responsible for typical

angina and leading to the

various acute coronary

syndromes.

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Acute myocardial infarct, predominantly of the posterolateral left ventricle,

demonstrated histochemically by a lack of staining by the

triphenyltetrazolium chloride (TTC) stain in areas of necrosis (arrow). The

staining defect is due to the enzyme leakage that follows cell death. Note

the myocardial hemorrhage at one edge of the infarct that was associated

with cardiac rupture, and the anterior scar (arrowhead), indicative of old

infarct. (Specimen the oriented with the posterior wall at the top.)

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• What term refers to damage of the heart muscle due to

inadequate blood flow?

A. Non-ischemic cardiomyopathy

B. Dilated cardiomyopathy

C. Hypertrophic cardiomyopathy

D. Ischemic cardiomyopathy

E. Cardioplegia

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• Myocardial infarction or heart attack occurs when there is

blood clotting in_____.

A. Aorta

B. Coronary artery

C. Hepatic artery

D.Mesenteric artery

E. Renal artery

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I. Types of endocarditis

– Non-infective

• acute rheumatic fever

• systemic lupus

• Non-bacterial thrombotic

– Infective

• Mainly bacterial or fungal infections

• Destroy valve tissue (non-infective doesn't)

• Thrombus with microorganisms

ENDOCARDITIS

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• Inflammation

– Resulting in injury to cardiac myocyte

– Cardiac allograft rejection

– Collagen vascular disease

– Drug hypersensitivity

• Infection

– Virus

• Coxsackievirus A & B and other enterovirus (most common)

• Cytomegalovirus

• Human immunodeficiency virus

MYOCARDITIS

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– Parasites

• Chagas’ disease (Trypanosoma cruzi)

(most common cause in S. America)

• Toxoplasmosis

– Bacteria

• Lyme disease

• Diphtheria (injury from toxin of Corynebacterium

diphtheriae)

MYOCARDITIS

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• Morphology (Gross)

– Cardiac dilation

– Myocardium flabby,

pale, with

hemorrhage

MYOCARDITIS

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Morphology (Microscopic):-

Acute virus infection

• Edema

• Inflammatory infiltrate of lymphocyte and other

mononuclear cell

• Myocyte degeneration and/or necrosis

• Viral inclusion may be present

MYOCARDITIS

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Inflammation of the pericardium

Types and (in parentheses: causes)

- Fibrinous (MI, uremia)

- Purulent (Staphylococcus)

- Granulomatous (TB)

- Hemorrhagic (tumor, TB, uremia)

- Fibrous (constrictive)

PERICARDITIS

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• Causes

– Infection

• virus (most common)

• pyogenic bacteria

• mycobacteria

• fungi

– Secondary

• acute myocardial infarction

• cardiac surgery

• radiation to mediastinum

PERICARDITIS

• Causes

– Systemic disorder

• uremia

• acute rheumatic fever

• systemic lupus

erythematosus

• metastatic malignancy

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I. Most common are metastatic: lung, breast, melanoma

II. Primary tumor

Rare, but most common is left atrial myxoma

- arise from interatrial septum, on a stalk , mostly in LA

- can prolapse through MV into LV, cause CHF

- can embolize, cause stroke, etc.

CARDIAC TUMOR

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MYXOMA

Pedunculated mass is

attached to the left arterial

endocardium.

(left -external surface, right

- cut surface)

Vascular showing basophilic myxoid stroma and stellate cells

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Atrial myxoma

Minimal cellularity, only scattered spindle cells with scant pink cytoplasm are present in a loose myxoid stroma.

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METASTATIC TUMOR

• Metastatic cardiac

tumors are 20X more

common than primary

tumors arising in the

heart

• Commonly from lung,

breast, lymphoma.

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• What is the most common tumor of cardiac?

A. Cardiac squamous cell carcinoma

B. Cardiac metastasis

C. Cardiac adenocarcinoma

D.Cardiac small cell cancer

E. Cardiac large cell cancer

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• What is the most common primary originating site of

cardiac metastases?

A. Breast cancer

B. Pancreas cancer

C. Testes cancer

D.Uterus cancer

E. Stomach cancer

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• Atrial myxoma commonly arises from____.

A. Left atrium

B. Left ventricle

C. Right atrium

D.Right ventricle

E. Heart wall

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• Narrowing or completely obstructing the lumina

– Atherosclerosis (thrombosis, embolism)

• Weakening of the wall.

– Dilatation or rupture

DISEASES OF ARTERIES

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Degenerative arterial disease, segmental and

multifocal

• Characterized by intimal deposition of lipids,

which results in intimal thickening (atheroma)

and scarring

• Causes stenosis, predisposes to thrombosis

• Results in ischemia and infarction

ATHEROSCLEROSIS

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Three types of lesions

• 1. Atheroma (raised, lipid center, dangerous)

• 2. Fatty streak (small, intracellular fat, innocuous)

• 3. Fibrous plaque (intimal scar, innocuous)

ATHEROSCLEROSIS

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ATHEROMA LESION

Sites:

-Intimal, may involve media

- Aorta and its major branches

(coronaries, cerebrals,

peripheral, etc.)

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ATHEROMA LESION

• Three major elements

– Necrotic center of extracellular lipid

– Fibrous cap

– Proliferating cells (myofibroblasts)

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Mechanism for intimal thickening

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Major components of well-developed atheromatous plaque

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Schematic diagram of sequence of cellular events and cellular interaction in atherosclerosis

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Summary of the pathology, pathogenesis, complications and natural history of atherosclerosis

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Mild Severe

Fibrous plaque

Atherosclerosis, aorta

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Atherosclerotic plaque with needles and clot

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RISK FACTORS FOR ATHEROSCLEROSIS

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Sites of atherosclerosis

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Complication of

atherosclerosis

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References

Illustrated Textbook

of Cardiovascular

Pathology.

by

P. Chopra

R. Ray

A. Saxena

2004

Practical

Cardiovascular

Pathology.

by

Allen Burke

Fabio Tavora

2010

Braunwald's Heart

Disease. 10th ed. by

Douglas Mann

Douglas Zipes

Peter Libby

Robert Bonow

2014

Practical

Cardiovascular

Pathology.

2nd ed. By

Mary Sheppard

2011

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SCBM342

Cardiovascular Pathology

the impact of nanoparticles on cellular functions

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