Vascular System Pathology.

The vascular system is a network of vessels responsible for transporting blood and lymph
fluid throughout the body, forming the core components of the circulatory system. This
system is essential for delivering oxygen and nutrients to tissues while removing waste
products to maintain cellular health and support the body’s function.

Core Components
 Heart: Acts as the central pump, propelling blood through the vessels.
 Arteries: Carry oxygen-rich blood away from the heart to body tissues; their
branching networks allow nutrients to reach all cells.
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 Veins: Return deoxygenated blood from the tissues back to the heart.
 Capillaries: Tiny vessels where exchange of gases, nutrients, and waste occurs
between blood and body tissues.

Circulation and Function

The heart pumps blood through arteries, which become smaller arterioles and then
capillaries. Here, oxygen and nutrients exit the blood and enter cells, while waste
leaves cells to enter the blood. Blood then collects into veins, bringing it back to
the heart for recirculation.

 Improtance
 Maintains homeostasis by controlling the movement of blood so each cell receives
necessary nutrients and oxygen.
 Supports immune defense via the lymphatic system.
 Regulates temperature and pH balance in the body.

Atherosclerosis

Atherosclerosis is a chronic disease involving the buildup of plaque (fat,

cholesterol, calcium, and other substances) along the walls of arteries, causing them
to narrow and harden, which restricts blood flow to various organs and tissues.

Causes
 Damage to artery walls from factors such as high cholesterol, high blood pressure,
diabetes, smoking, obesity, poor diet, and genetic predisposition initiates plaque
formation.
 The condition slowly progresses from childhood and often worsens with age.

Symptoms
 Early atherosclerosis often has no symptoms; issues arise when arteries become
significantly blocked.
 Symptoms depend on which arteries are affected:
 Chest pain or angina if heart arteries are involved.
 Numbness, weakness, trouble speaking, or vision loss if arteries to the brain are
blocked (stroke or TIA).
 Leg pain with walking (claudication) if leg arteries are blocked (peripheral artery
disease).
 High blood pressure or kidney failure if kidney arteries are affected
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The process of atherosclerosis is a multi-stage development of arterial

plaques, driven by lipid accumulation, inflammation, and cellular changes that lead
to narrowed and stiff arteries.

Stages of Atherosclerosis

1. Endothelial Injury and Activation

 Triggered by factors like high blood pressure, smoking, high cholesterol, and
diabetes, the inner lining of arteries (endothelium) gets damaged and activated.
 This increases permeability to lipids (especially LDL), and attracts immune cells.

2. Lipid Infiltration and Foam Cell Formation

 LDL cholesterol enters the vessel wall and becomes oxidized (oxLDL), amplifying
local inflammation.
 Monocytes migrate into the vessel wall, transform into macrophages, and ingest
oxLDL to form “foam cells,” resulting in fatty streaks.

3. Formation of Fibrous Plaque

 Foam cells die and release intracellular content, worsening inflammation.
 Smooth muscle cells migrate from the media to the intima, proliferate, and deposit
collagen, forming a fibrous cap over the soft, lipid-rich necrotic core.
 The plaque grows, restricting blood flow and making the artery less flexible.

4. Plaque Progression and Complications

 Advanced plaques accumulate necrotic material, cholesterol crystals, and more
inflammatory cells.
 The fibrous cap may become weak due to enzymes (metalloproteinases) released
by immune cells, increasing the risk of rupture.
 Plaque rupture exposes the lipid core, triggering clot (thrombus) formation, which
can abruptly block blood flow and cause heart attack, stroke, or other
complications.

Atherosclerosis is a dynamic cycle of injury, inflammation, lipid deposition, and

healing, resulting in progressive vessel blockage and risk of sudden events
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Types of Arteriosclerosis

Arteriosclerosis refers broadly to the hardening and loss of elasticity in arterial

walls. It encompasses three main types:

1. Atherosclerosis
Characterized by lipid-rich plaques (atheromas) forming in medium and large
arteries. Plaque buildup narrows the vessel lumen, impedes blood flow, and can
rupture, causing heart attack or stroke.

2. Arteriolosclerosis
Affects small arteries (arterioles) and has two subtypes:

 Hyaline arteriolosclerosis: Deposition of proteinaceous (“hyaline”) material in

arteriolar walls, common in hypertension and diabetes.
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 Hyperplastic arteriolosclerosis: “Onion-skin” thickening of arteriolar walls due to

smooth muscle proliferation, seen in malignant hypertension.

3. Monckeberg (Medial) Calcific Sclerosis

Involves calcium deposition in the tunica media of medium-sized arteries
without significant lumen narrowing. Often seen in older adults and patients with
diabetes or chronic kidney disease; usually asymptomatic but visible on imaging.

Other Vascular Diseases

An aneurysm is an abnormal bulge or ballooning in the wall of an artery caused by

weakening of the vessel wall. It can occur in various parts of the body and may
remain asymptomatic until it enlarges or ruptures, posing serious health risks.

Types of Aneurysms
 Saccular (Berry) Aneurysm: A round-shaped bulge typically occurring in cerebral
arteries at the base of the brain.
 Fusiform Aneurysm: Bulging occurring on all sides of the artery, causing a spindle
shape.
 Mycotic Aneurysm: Caused by an infection weakening the artery wall.
 Common locations include the aorta (abdominal or thoracic), brain, carotid
arteries, popliteal artery (behind the knee), and more

Hypertension (high blood pressure) is a condition where the force of blood pushing
against the walls of arteries is consistently too high, leading to damage of blood vessels
and increased risk for cardiovascular diseases
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Type of hypertention
1. Primary Hypertension: This is high blood pressure with no clear cause. It happens
slowly over time because of things like eating unhealthy, not exercising, being
stressed, or older age.

 The most common type.

 Has no specific known cause.
 Develops gradually due to genetics, lifestyle, and aging.
 Influenced by factors like diet, exercise, weight, and stress.

2. Secondary Hypertension: This type happens because of another health problem,

like kidney disease or hormone issues. Fixing that problem can sometimes fix the
high blood pressure.

 caused by an underlying medical condition.

 Examples include kidney disease, hormonal disorders, or certain medications.
 More common in younger people and may be reversible if the cause is treated.

3. Resistant Hypertension: This means blood pressure stays high even when a
person takes several medicines. It might mean there’s another cause or treatment
issue.
4. Isolated Systolic Hypertension: This happens when the top blood pressure
number is high but the bottom number is normal. It mostly happens in older
people because their arteries get stiff.
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5. Malignant Hypertension: This is a very serious type where blood pressure goes
very high quickly, risking damage to the heart or brain and needing emergency
care.

 Blood pressure gradually increases with age

 The ideal target for all adults is less than 120/80 mm Hg
 Children's blood pressure is much lower than adults
 Small increases with age are normal, but high blood pressure at any age needs
attention

Morphological Responses of the Cardiovascular System

The cardiovascular system undergoes morphological responses as adaptive

changes to various physiological and pathological stimuli. These structural
adaptations involve alterations in size, shape, cellular composition, and function of
the heart and blood vessels.

Cardiac Morphological Responses

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Cardiac Hypertrophy
Cardiac hypertrophy means thickening (increase in size) of
the heart muscle, especially the walls of the ventricles.
Types of Cardiac Hypertrophy:

 Concentric Hypertrophy: Increased wall thickness with minimal change in cavity

size, typically resulting from pressure overload (hypertension, aortic stenosis).
 Eccentric Hypertrophy: Increased cavity size with proportional wall thickening,
commonly caused by volume overload (endurance exercise, valve regurgitation).

Physiological vs. Pathological Hypertrophy:

 Physiological (e.g., athlete's heart): Adaptive response to exercise with maintained

cardiac function and proportional vascularization.
 Pathological: Maladaptive response to disease states leading to dysfunction,
fibrosis, and reduced capillary density.

Cellular Changes in Cardiac Remodeling

Myocyte Changes:

 Increased cell size (hypertrophy) rather than number (hyperplasia).

 Altered contractile protein expression and calcium handling.
 Enhanced energy demands and metabolic stress.

Non-myocyte Changes:

 Fibroblast proliferation: Increased collagen deposition leading to interstitial

fibrosis.
 Endothelial cell alterations: Changes in angiogenesis and microvascular density.
 Inflammatory cell infiltration: Macrophages and lymphocytes contributing to
remodeling processes.

Vascular Morphological Responses

Vascular Remodeling
Structural Changes:

 Arterial wall thickening: Smooth muscle cell proliferation and matrix deposition.
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 Lumen diameter changes: Narrowing (inward remodeling) or dilation (outward

remodeling).
 Endothelial dysfunction: Altered vasodilator and vasoconstrictor responses.

Adaptive Mechanisms:

 Flow-mediated remodeling: Vessels adapt to changes in blood flow patterns.

 Pressure-induced changes: Arterial stiffening and resistance vessel modifications.
 Angiogenesis: Formation of new blood vessels to meet metabolic demands.

Microvascular Changes
Capillary Density Alterations:

 Physiological adaptation: Maintained or increased capillary-to-fiber ratio during

exercise training.
 Pathological rarefaction: Reduced capillary density relative to increased myocyte
size.
 Angiogenic imbalance: Insufficient new vessel formation despite increased oxygen
demands.

Molecular Mechanisms
Growth Factors and Signaling:

 VEGF (Vascular Endothelial Growth Factor): Critical for cardiac angiogenesis and
vascular adaptation.
 Angiotensin II: Promotes myocyte hypertrophy and fibrosis.
 TGF-β: Mediates fibrotic responses and extracellular matrix remodeling.

Temporal Sequence:

 Early phase (0-7 days): Inflammatory response, myocyte hypertrophy, vascular

regression.
 Later phase (7-28 days): Fibroblast proliferation, collagen deposition,
angiogenesis recovery

Ischemic Heart Diseases

Ischemic heart diseases (IHD), also known as coronary artery disease

(CAD) or coronary heart disease, arise when the heart muscle (myocardium) does
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not receive sufficient blood flow and oxygen due to narrowed or blocked coronary
arteries. IHD is the leading cause of death globally.

Types of Ischemic Heart Disease

 Stable Angina: Predictable chest pain or discomfort triggered by exertion or stress,
relieved by rest or nitroglycerin.
 Unstable Angina: Chest pain at rest or of increasing frequency and severity;
heralds a high risk of myocardial infarction.
 Myocardial Infarction (Heart Attack): Prolonged ischemia causes death of heart
muscle cells (necrosis), often presenting as severe, crushing chest pain lasting >20
minutes, sweating, nausea, and shortness of breath.
 Silent Ischemia: Myocardial ischemia without noticeable symptoms; common in
diabetics and the elderly, often detected only on testing.
 Chronic Ischemic Cardiomyopathy: Long-term reduction in blood flow leads to
weakened heart muscle, heart failure, and arrhythmias.

Causes and Risk Factors

The primary cause of IHD is atherosclerosis, where lipid-rich plaques build up in
coronary arteries, narrowing the lumen and stiffening the vessel walls. Key risk
factors include high blood pressure, high LDL cholesterol, smoking, diabetes,
obesity, physical inactivity, and family history.

Bacterial Pneumonia
 “Pneu” = air / lungs
 “-monia” = condition/disease

So, pneumonia = disease of the lungs (due to infection)

Bacterial pneumonia is an acute infection of the lung parenchyma and airspaces

caused by pathogenic bacteria. It triggers an intense inflammatory response,
leading to alveolar filling with exudate, impaired gas exchange, and systemic
symptoms.

Etiology and Risk Factors

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The most common pathogens include

 Streptococcus pneumoniae
 Haemophilus influenzae
 Staphylococcus aureus
 Gram-negative bacilli (e.g., Klebsiella pneumoniae).
Risk factors are advanced age, smoking, alcoholism, chronic lung disease,
immunosuppression, and aspiration risk (e.g., neurologic impairment).

Pathogenesis of Bacterial Pneumonia

The pathogenesis of bacterial pneumonia involves a complex interplay between

bacterial virulence factors, host defense mechanisms, and inflammatory responses
that lead to infection and inflammation of the lung parenchyma.

Routes of Bacterial Entry

1. Microaspiration (Most Common)

 Small aspirations of organisms residing in the throat or nose occur in about 50%
of normal people during sleep
 Oropharyngeal colonization by pathogenic bacteria followed by aspiration into
lower airways
 Normal throat flora provides protection, but pathogenic bacteria can colonize
under certain conditions

2. Inhalation of Contaminated Droplets

 Airborne transmission of bacteria like Mycobacterium tuberculosis and Legionella

pneumophila
 Respiratory droplets from infected individuals containing pathogenic organisms

3. Hematogenous Spread