CARDIOVASCULAR PATHOLOGY: Marian Michelle M.

Marquez, PTRP, MD

BLOOD VESSELS AND THE HEART

College of Dentistry
National University-MOA
BLOOD VESSELS

ü Structure and Function

ü Hypertensive Vascular
Disease
ü Response to Injury
ü Arteriosclerosis
ü Atherosclerosis
ü Aneurysms and Dissections
ü Vasculitis
ü Veins and Lymphatics
VASCULAR DISEASES
• Arterial lesions > Venous pathologies

• 2 Principal Mechanisms:
1. Narrowing or Complete obstruction
2. Weakening of vessel walls à Dilation or rupture
REVIEW: BLOOD VESSEL
PHYSIOLOGY
1. Aorta A. Large arteries
2. Arterioles B. Medium-sized arteries
3. Has valves C. Small arteries
4. Muscular arteries D. Capillaries
5. For nutrient exchange E. Veins
REVIEW: BLOOD VESSEL
PHYSIOLOGY
A. Large arteries: elastic fibers + SMCs (e.g. aorta, arch vessels, iliac and
pulmonary arteries)
B. Medium-sized arteries: muscular arteries, media primarily SMCs (e.g.
coronary and renal arteries)
C. Small arteries (<2mm), arterioles (20 to 100 um): media primarily SMCs
D. Capillaries: has SMC-like cells (pericytes); very large total cross-sectional
area. Where exchange of substances between blood and tissue happen
E. Veins: larger diameter, larger lumina, thinner walls, with valves

SMCs = smooth muscle cells

BLOOD PRESSURE
• Cardiac output (CO) x Peripheral vascular
resistance (PVR)
• CO: Stroke volume x heart rate
• PVR: regulated predominantly at the level of
the arterioles by neural and humoral input
Ø Vasoconstrictors: angiotensin II, catecholamines, and
endothelin
Ø Vasodilators: kinins, prostaglandins, and NO
 Low blood pressure
• Renin: from kidneys
targets
• Angiotensinogen: from liver
becomes
• Angiotensin I: inactive

activated by
• ACE (angiotensin-converting
enzyme): from lungs and kidneys.
converts Angiotensin I to
Angiotensin II
becomes
• Angiotensin II: active, potent
vasoconstrictor

High blood pressure

• Aldosterone: from adrenals,

sodium and water retention
HYPERTENSION
May be:
• Primary/ Essential – idiopathic (95%
of cases)
• Secondary - due to an identifiable
underlying condition (e.g. primary
renal disease, renal artery narrowing
or adrenal disorders)
HYPERTENSIVE VASCULAR DISEASE
Mechanisms of Essential Hypertension:
1. Reduced renal sodium excretion
2. Increased vascular resistance may stem from vasoconstriction or
structural changes in vessel walls
3. Genetic factors
4. Environmental factors
ENDOTHELIAL CELLS
• Continuous sheet of cells lining the entire vascular tree
• Main functions:
1. Maintains a non-thrombogenic blood-tissue interface
2. Modulates inflammation
3. Influences the growth and behavior of other cell types

• Endothelial dysfunction:
1. Initiates thrombosis
2. Promotes atherosclerosis
3. Contributes to the formation of vascular lesions of hypertension and diabetes
VASCULAR WALL RESPONSE TO
INJURY
• Vessel wall injury (endothelial cell injury)- the fundamental basis for the vast majority of
vascular disorders.
• Intimal thickening- stereotypical response to vascular injury
ARTERIOSCLEROSIS
• hardening of arteries
• pathology: arterial wall thickening and loss of elasticity
• 4 types:
1. Arteriolosclerosis – small arteries and arterioles affected
2. Monckeberg medial sclerosis – calcific deposits in muscular arteries
3. Fibromuscular interstitial hyperplasia – intimal hyperplasia with SMC rich
lesion
4. Atherosclerosis
ATHEROSCLEROSIS
• characterized by Atheromas (atheromatous or atherosclerotic plaques)
Ø impinge on the vascular lumen and can rupture to cause sudden occlusion
Ø raised lesions composed of soft friable (grumous) lipid cores (mainly cholesterol and
cholesterol esters, with necrotic debris) covered by fibrous caps
ATHEROSCLEROSIS: RISK FACTORS
Non-modifiable (Constitutional) Modifiable
• Genetics: e.g. Familial • Hypercholesterolemia: major risk
hypercholesterolemia factor
• Family history: most important • Hypertension
independent risk factor
• Cigarette smoking
• Age: increases 5x between 40-60 years
old • Diabetes mellitus

• Gender: Male > female

ATHEROSCLEROSIS: PATHOLOGY
• Endothelial cell injury: cornerstone of
the response to injury hypothesis.
• Foam cells: oxidized LDL +
macrophages
• Fatty Streaks: begin as minute yellow,
flat macules that coalesce into elongated
lesions, 1cm or more in length
• Atherosclerotic Plaque
ü key features: intimal thickening and lipid
accumulation
ü 0.3 to 1.5cm in diameter
ATHEROSCLEROSIS:
CHANGES AND CONSEQUENCES
• Rupture, ulceration, or erosion of the luminal
surface of atheromatous plaques exposes highly
thrombogenic substances à thrombus formation
• Hemorrhage into a plaque: results from rupture
of fibrous cap
• Atheroembolism: ruptured plaque can discharge
debris
• Aneurysm formation
 Vulnerable plaques Stable plaque
• high risk for rupturing • stable, but may evolve to unstable type
1. Plaques with large number of foam 1. Lesser foam cells
cells 2. Less lipid pool
2. Abundant extracellular lipid 3. Thicker fibrous cap
3. Thin fibrous cap 4. Less inflammatory cells
4. With clusters of inflammatory cells
ANEURYSMS AND DISSECTIONS
• important causes of stasis and subsequent
thrombosis; they also have a propensity to rupture—
often with catastrophic results.

• Aneurysm: congenital or acquired dilations of blood

vessels of the heart
• Arterial dissection: pressurized blood gains entry to
the arterial wall through a surface defect and then
pushes apart the underlying layer
ANEURYSM: TYPES
• “True” aneurysms: involve all three layers of the artery (intima, media, and adventitia)
or the attenuated wall of the heart. e.g. atherosclerotic and congenital vascular aneurysms.
• “False” aneurysms: wall defect leads to the formation of an extravascular hematoma
that communicates with the intravascular space (“pulsating hematoma”).
• e.g. ventricular ruptures contained by pericardial adhesions and leaks at the junction of a vascular graft
with a natural artery

• Classification according to shape:

• Saccular aneurysms - discrete outpouchings ranging from 5 to 20cm in diameter, often with a
contained thrombus.
• Fusiform aneurysms - circumferential dilations up to 20cm in diameter
 A. B. C. D. E.
1. Normal vessel
2. True aneurysm (saccular)
3. True aneurysm (fusiform)
4. False aneurysm
5. Dissection
ANEURYSMS AND DISSECTIONS:
PATHOGENESIS
Implicated factors in aneurysm formation:
• Inadequate or abnormal connective tissue synthesis
• Excessive connective tissue degradation
• Loss of SMCs or change in the SMC synthetic phenotype

• The two most important predisposing conditions for aortic aneurysms are:
atherosclerosis and hypertension.
ABDOMINAL AORTIC ANEURYSM
• Aneurysms most commonly occur in the
abdominal aorta and common iliac arteries.

• Abdominal aortic aneurysm (AAA):

Ø common in men, smoker, >50 years old
Ø results from extracellular matrix degradation, mediated by
proteolytic enzymes released from inflammatory infiltrates
in atherosclerotic lesions.
Ø typically occur between the renal arteries and the aortic
bifurcation
CLINICAL CONSEQUENCES
Risk for rupture:
1. Obstruction of a vessel • <4cm: almost never burst
branching off the aorta • between 4-5cm: rate of burst- 1%
2. Embolism per year
3. Impingement on adjacent • 5-6cm: 11% per year
structures • > 6cm: 25% risk of bursting per
4. Rupture into peritoneal cavity year
AORTIC DISSECTION
• when blood splays apart the laminar planes of
the media to form a blood-filled channel
within the aortic wall
Ø Men, 40-60 years old, hypertensive
Ø If younger patients, commonly with connective tissue
diseases (Marfan syndrome)

• Hypertension: major risk factor

AORTIC DISSECTION
• Clinical features:
Ø sudden onset of excruciating tearing or stabbing
pain à beginning in the anterior chest à radiating
to the back between the scapulae à moving
downward

Ø Most common cause of death: rupture of the

dissection into the pericardial, pleural, or
peritoneal cavity.
 • Vessel wall inflammation

VASCULITIS • The two most common pathogenic mechanisms:

1. immune-mediated inflammation
2. direct vascular invasion by infectious pathogens
IMMUNE COMPLEX-ASSOCIATED
VASCULITIS
• REVIEW: Type of Hypersensitivity?

• Vasculitides:
1. SLE (Systemic Lupus Erythematosus)
2. Drug sensitivity vasculitis:
ü Penicillin, can be mild and self-limiting, or severe and fatal
ü most common feature- skin lesions

3. Polyarteritis nodosa
GIANT CELL (TEMPORAL) ARTERITIS
• chronic inflammatory condition affecting large- to
small-sized vessels in the head
• T-cell– mediated immune response with
granulomatous inflammation
• Other sites affected: Vertebral and ophthalmic arteries,
aorta (giant cell aortitis)

• Occurs in >50 years old and above

• Features: Facial pain or headache (most painful in
superficial temporal artery area)
TAKAYASU ARTERITIS
• “ Pulseless disease” - weakening of the pulses in the upper extremities
• Granulomatous vasculitis of medium- and large-sized arteries
• Manifests with transmural scarring and thickening of the aorta à severe luminal
narrowing of the major branch vessels
• Features:
Ø Initial symptoms: non-specific (fever, fatigue, weight loss)
Ø Progressive vascular symptoms: reduced upper-extremity BP and pulse, neurologic
deficits, and ocular disturbances (visual field defects, retinal hemorrhages, and total
blindness)
POLYARTERITIS NODOSA (PAN)
• systemic vasculitis of small- or medium-sized
muscular arteries; it typically involves the renal
and visceral vessels and spares the pulmonary
circulation.
• fibrinoid necrosis à segmental transmural
necrotizing inflammation
• 1/3 of patients have chronic hepatitis B
infection à formation of immune complexes
containing hepatitis B antigens that deposit in
affected vessels
fibrinoid necrosis
KAWASAKI DISEASE
• acute, febrile, usually self-limited illness of infancy and
childhood associated with an arteritis of mainly large- to
medium-sized vessels. (à Coronary arteritis)
• 80% of patients are < 4 years old
• Features:
Ø conjunctival and oral erythema and blistering
Ø edema of the hands and feet
Ø erythema of the palms and soles
Ø desquamative rash
Ø cervical lymph node enlargement (hence its other name,
mucocutaneous lymph node syndrome)
THROMBOANGIITIS OBLITERANS
(BUERGER DISEASE)
• segmental, thrombosing, acute and chronic inflammation of
medium- and small-sized arteries
• principally the tibial and radial arteries, with occasional
secondary extension into the veins and nerves of the
extremities.
• occurs almost exclusively in heavy tobacco smokers and
usually develops < 35 years of age.
• Clinical Features:
Ø cold-induced Raynaud phenomenon
Ø instep foot pain induced by exercise (instep claudication)
Ø superficial nodular phlebitis (venous inflammation)
INFECTIOUS VASCULITIS
• usually bacteria and fungi (Aspergillus and
Mucor spp.)
• Microbial invasion may be from:
1. nearby local tissue infection (e.g., bacterial
pneumonia or an adjacent abscesses),
2. less commonly— may arise from hematogenous
spread of bacteria or embolization from infective
endocarditis.

• Can cause thrombosis or infarction

RAYNAUD PHENOMENON
• vasoconstriction of arteries and
arterioles in the extremities (fingers
and toes, but also sometimes the nose,
earlobes, or lips)
• “red-white-and-blue” color changes
from most proximal to most distal
(proximal vasodilation-central
vasoconstriction-more distal cyanosis)
VEINS AND LYMPHATICS
1. Varicose veins
90% of clinically relevant venous diseases
2. Deep venous thrombosis
3. Esophageal varices
4. Lymphedema
VARICOSE VEINS
• abnormally dilated tortuous veins produced
by chronically increased intraluminal
pressures and weakened vessel wall support
• 1/5 of men and 1/3 of women
• Risk factors: obesity, pregnancy, familial
• Varicose dilation renders the venous valves
incompetent à lower-extremity stasis,
congestion, edema, pain, and thrombosis
ESOPHAGEAL VARICES
Liver cirrhosis

Portal vein obstruction/ portal hypertension

Opening of portosytemic shunts

Increased blood flow into veins at

gastroesophageal junction
DEEP VENOUS THROMBOSIS
• Accounts for more than 90% of cases of
thrombophlebitis and phlebothrombosis.
• Deep venous thrombosis (DVT) of the
legs: prolonged immobilization resulting in
venous stasis is the most important risk
factor.
• Complication:
Ø Pulmonary embolism - common and serious
clinical complication of DVT, resulting from
fragmentation or detachment of the venous
thrombus.
LYMPHEDEMA
• Primary lymphedema
• Secondary lymphedema: stems from the
accumulation of interstitial fluid behind
an obstructed, previously normal
lymphatic

1. Tumors involving lymphatic channels or lymph nodes

2. Surgical procedures that sever lymphatic connections
3. Post-radiation fibrosis
4. Filariasis
5. Post-inflammatory thrombosis and scarring
HEMANGIOMA
• very common tumors composed of blood-
filled vessels
• benign tumor of infancy and childhood
• present from birth à initially increase in size
à many eventually regress spontaneously

1. Capillary hemangioma: most common (in skin, subcutaneous tissue, mucous membranes)
2. Juvenile hemangioma: “strawberry hemangioma” ; seen in newborn skin
3. Pyogenic granulomas: rapidly growing, red, pedunculated lesions on the skin, gingival, or oral
mucosa
4. Cavernous hemangioma: composed of large dilated vascular channels
KAPOSI SARCOMA
• vascular neoplasm caused by Kaposi
sarcoma herpesvirus (KSHV, also known
as human herpesvirus-8, or HHV-8)
• it is most common in patients with
AIDS
• It is transmitted both through sexual
contact and potentially via oral
secretions and cutaneous exposures
ANGIOSARCOMA
• malignant endothelial neoplasms ranging from highly differentiated tumors resembling
hemangiomas to wildly anaplastic lesions
• in older adults, without gender predilection
• lesions can occur at any site, but most often involve the skin, soft tissue, breast, and liver.
• aggressive tumor that invade locally and metastasize
 HEART

ü Review of Heart Anatomy

and Physiology
ü Heart Failure
ü Congenital Heart Disease
ü Ischemic Heart Disease
ü Hypertensive Heart Disease
ü Valvular Heart Disease
ü Cardiomyopathies
REVIEW: HEART ANATOMY
CONGENITAL HEART DISEASE
• most commonly due to faulty embryogenesis at 3-8 weeks of gestation, when major
cardiovascular structures develop.
• Shunts: abnormal communication between chambers or blood vessels.

Left-to-right shunt Right-to-left shunt

• (+) right-ventricular hypertrophy and • (+) cyanosis because pulmonary circulation is

right-sided failure bypassed
Ø Atrial septal defect (ASD) Ø Tetralogy of Fallot: (1) VSD, (2) R ventricular
outflow obstruction, (3) overriding of the
Ø Ventricular septal defects (VSD) aorta, (4) R ventricular hypertrophy
Ø Patent ductus arteriosus (PDA) Ø Transposition of great arteries
SIX PRINCIPAL MECHANISMS OF
HEART DISEASE
1. Failure of the pump
2. Obstruction to flow
3. Regurgitant flow
4. Shunted flow
5. Disorders of cardiac conduction
6. Rupture of the heart or major vessels
RELATIONSHIP OF
CARDIAC
DISEASES
REVIEW: CARDIAC CYCLE
• Chambers of the
Heart
• Systole
• Diastole
• Venous return
• End systolic
volume (ESV)
• End diastolic
volume (EDV)
• Cardiac output
(CO) = HR x SV
HEART FAILURE
• Congestive heart failure (CHF)
Ø common end point of many cardiac conditions
Ø progressive, with poor prognosis

• Systolic dysfunction:
- results from inadequate myocardial contractile function
- usually a consequence of ischemic heart disease or hypertension

• Diastolic dysfunction:
- inability of the heart to adequately relax and fill
- consequence of: massive left ventricular hypertrophy, myocardial fibrosis, amyloid deposition,
or constrictive pericarditis
HEART FAILURE: MECHANISMS
• Failing heart is no longer efficient in pumping blood à increased end diastolic
volume and pressures, elevated venous pressure
• Forward failure = inadequate cardiac output
• Backward failure = increased venous congestion
• Compensated heart failure:
Ø via the Frank-Starling mechanism, the dilated heart (due to increased EDV) causes cardiac
myofiber stretching, increasing force of contraction

• Decompensated heart failure:

Ø the failing muscle is no longer able to propel sufficient blood to meet the needs of the body
LEFT-SIDED HEART FAILURE
• The morphologic and clinical effects stem from
diminished systemic perfusion and elevated
back-pressures within the pulmonary circulation.
• Causes: ischemic heart disease, systemic
hypertension, mitral or aortic valve disease
RIGHT-SIDED HEART FAILURE
• Usually a consequence of left-sided failure.
• Morphologic and clinical effects of pure
right-sided heart failure are due to
engorgement of the systemic and portal
venous systems > pulmonary congestion.
REVIEW: BLOOD
SUPPLY TO THE HEART
• Coronary circulation
ISCHEMIC HEART DISEASE (IHD)
• Myocardial ischemia
• In more than 90% of cases, IHD is due to reduced coronary
blood flow from atherosclerosis (Coronary artery disease)

• Cardiac syndromes:
Ø Angina pectoris (“chest pain”)
Ø Myocardial infarction (MI)
Ø Chronic IHD with CHF.
Ø Sudden cardiac death (SCD)
IHD: PATHOGENESIS
• Consequence of inadequate coronary
perfusion relative to myocardial demand
(commonly due to a preexisting (“fixed”)
atherosclerotic occlusion of the coronary
arteries, and superimposed thrombosis
and/ or vasospasm).
• Coronary arteries:
Ø left anterior descending (LAD): most
commonly affected
Ø left circumflex (LCX)
Ø right coronary artery (RCA)
MYOCARDIAL INFARCTION (MI)
• “Heart attack”
• Necrosis of the heart muscle resulting
from ischemia (Coagulation necrosis)
• Majority occur in < 65 years old, Men >
Women, Blacks = whites
• Pathogenesis: vast majority is caused by
acute thrombosis within coronary arteries
MYOCARDIAL RESPONSE TO
ISCHEMIA
• Myocardial injury results as a consequence of decrease/ loss of blood supply:
ü early changes are reversible
ü prolonged ischemia lasting for 20-40 minutes causes irreversible damage and
coagulative necrosis
• Patterns of myocardial infarct:
Ø Transmural: involves full thickness of the ventricle (in ECG, called ST-elevation MI or
STEMI)
Ø Subendocardial: limited to inner 1/3 of myocardium (in ECG, called Non-ST-elevation
MI or NSTEMI)
Ø Microscopic infarcts: small-vessel occlusions, no ECG changes
MYOCARDIAL INFARCTION
• Features:
ü Severe, crushing substernal chest pain (or
pressure) that can radiate to the neck, jaw,
epigastrium, or left arm.
ü Pulse generally is rapid and weak
ü Patients are often diaphoretic (sweating)
and nauseous (particularly with posterior
wall MIs)
ü ECG abnormalities: Q waves, ST segment, T
wave inversions
ü Abnormal blood levels of: CK-MB,
Troponin-I and Troponin-T
REVIEW: CONDUCTION SYSTEM OF
THE HEART
• Pacemaker of the heart?
• Location?
• Normal heart rate?
 ARRHYTHMIAS
• aberrant rhythm of the heart
• IHD: most common cause of rhythm disorders
(due to direct damage or dilation of the heart)
• can be: Supraventricular (from atrium), or
ventricular
1. Tachycardia (fast)
2. Bradycardia (slow)
3. Ventricular fibrillation (chaotic depolarization
without functional ventricular contraction)
4. Asystole (no electrical activity)
SUDDEN CARDIAC
DEATH
• defined as unexpected death due to a lethal
arrhythmia such as asystole or sustained
ventricular fibrillation.
• autopsy typically shows severe
atherosclerotic disease without evidence of
acute plaque disruption.
REVIEW: CONTRACTILITY OF
THE HEART
• Cardiac output
(CO) = HR x SV
• Preload
• Afterload
HYPERTENSIVE HEART DISEASE
• Consequence of the increased demands
placed on the heart by hypertension,
causing pressure overload and
ventricular hypertrophy

• Myocyte hypertrophy: adaptive

response to pressure overload
ü commonly on the Left ventricle (due to
Systemic hypertension)
ü Right ventricle affected in Pulmonary
hypertension (Cor pulmonale)
REVIEW: VALVES OF THE HEART
• Function: The valves prevent the
backward flow of blood. They act
as one-way inlets of blood on one
side of a ventricle and one-way
outlets of blood on the other side of
a ventricle.
• Location?
• Side of the heart?
• Valve with only two leaflets?
REVIEW: VALVES AND HEART
SOUNDS
• Normal heart sounds: (“lub dub”)
❤ S1: mitral/tricuspid valve closure (AV valves)
❤ S2: aortic/pulmonic valve closure (semilunar
valves)

• Abnormal heart sounds:

❤ S3: ventricular overload
❤ S4: decreased LV compliance
❤ Heart murmurs: extra sound in the heartbeat --
such as a ''whooshing'' -- that is caused by
turbulent blood flow through the heart valves
VALVULAR HEART DISEASE
• Stenosis: failure of a valve to open
completely, obstructing forward
flow.
• Insufficiency: results from failure of
a valve to close completely, thereby
allowing regurgitation (backflow) of
blood.
• Stenosis or regurgitation may occur
alone or together in the same valve.
AORTIC STENOSIS
• a degenerative valve disease
• Calcific aortic degeneration: most common
cause
• Morphology:
ü Heaped-up calcified masses on the outflow side
of the cusps: Hallmark of calcific aortic stenosis

• Clinical features:
ü Left ventricular hypertrophy
ü Systolic and diastolic dysfunction
ü Prone to angina and ischemia
RHEUMATIC VALVULAR DISEASE
• acute, immunologically mediated, multisystem inflammatory
disease that occurs after group A β-hemolytic streptococcal
infections
• Type ___? Hypersensitivity reaction, antibodies are directed
against M proteins of the streptococcal strains.
• Inflammatory response, healing and scarring, causes
myocardium and cardiac valve injury
• Aschoff bodies: myocardial inflammatory lesions,
pathognomonic of rheumatic fever
• Anitschow cells: composes the Aschoff bodies, called
“caterpillar cells” because of slender chromatin
ORAL HEALTH
AND HEART
DISEASE
INFECTIVE ENDOCARDITIS
• Microbial infection of the heart valves or the mural endocardium that leads to the
formation of vegetations composed of thrombotic debris and organisms, often
associated with destruction of the underlying cardiac tissues.
Ø The aortic and mitral valves: most common sites of infection
Ø Tricuspid valve: frequent target in the setting of intravenous drug abuse

• Prosthetic heart valves, pacemakers, indwelling catheters, periodontitis/ dental

procedures are common sources of bacterial build-up and seeding to the heart
• Infectious agents:
ü Streptococcus viridans: a relatively banal group of normal oral flora.
ü S. aureus: 10-20% of cases; in deformed valves and intravenous drug abusers
ü Enterococci and the so-called “HACEK group” (Haemophilus, Actinobacillus, Cardiobacterium,
Eikenella, and Kingella), all commensal in the oral cavity.
REVIEW: CARDIAC ANATOMY/
HISTOLOGY
Microscopic Gross
CARDIOMYOPATHY
• “Heart muscle diseases”
• due to intrinsic myocardial dysfunction
• three time-honored, clinical, functional, and
pathologic patterns:
1. Dilated cardiomyopathy (DCM) – most common
(90%)
2. Hypertrophic cardiomyopathy (HCM)
3. Restrictive cardiomyopathy – least frequent
CARDIOMYOPATHY
• DCM:
Ø progressive cardiac dilation and
contractile (systolic) dysfunction
Ø fundamental defect: ineffective
contraction

• HCM:
• myocardial hypertrophy, defective
diastolic filling, and— in one third
of cases—ventricular outflow
obstruction.
• due to missense mutations
THANK YOU FOR Questions?

LISTENING mmmmarquez@nu-moa.edu.ph