3. Learning Objectives
Define atherosclerosis, arteriosclerosis, fatty
streaks, and fibrous atheromatous plaques, and
identify the most common sites of
atherosclerosis.
List the vessels most commonly affected by
atherosclerosis, and describe the vessel
changes that occur with atherosclerosis and
possible complication.
Describe possible mechanisms involved in the
development of atherosclerosis.
4. Atherosclerosis (ATH)
Hardening of arteries (Thickening and loss of elasticity of
arterial walls).
Systemic disease at multiple sites affects vital organs, in
which ATH is revealed at:
Elastic arteries, Large arteries, Medium sized arteries.
It is common worldwide, almost everyone in U.S is subject to
ATH if they live long enough. Accounting for about 50% of
all deaths in West.
The characteristic lesion of ATH is called atheroma
5. ATH: Atheroma (fibrofatty plaques)
Atheroma is focal lesion of intima, that is characterized by
intimal deposition of lipids, intruding into the lumen (0.3 to
1.5 cm in diameter),
Atheroma leads to intimal thickening, scarring, and
reducing the lumen size causing stenosis, which ends with
ischemia and infarction.
Grossly: Atheroma consist of lipid core covered by a firm
white fibrous cap, and have three main components:
Cells: including SMCs, macrophages, leukocytes
Extracellular matrix, including collagen, elastic fibers,
and proteoglycans
Intracellular and extracellular lipid.
Around the lesions, there is neovascularization.
6. Foam cells are large lipid-laden cells that derive predominantly
from blood monocytes (tissue macrophages), but SMCs can
also absorb lipid to become foam cells.
Two type of atheromatous plaques
Soft plaques (abundant lipid).
Solid or fibrous plaques (SMCs and fibrous tissue).
7. Atheroma
Plaques change and progressively enlarge through
Cell death and degeneration,
Synthesis and degradation of extracellular matrix,
Organization of thrombus.
Atheroma often undergo calcification.
Complication: rupture (ulceration or erosion), hemorrhage,
thrombosis, aneurysmal dilation
8. Large BV :
Abdominal aorta
Iliac
In descending order
Coronary
Popliteal
Carotid
Circle of Willis.
Vessels of the upper
extremities are usually
spared,
The severity of AS in one
artery does not predict its
severity in another
9. Atherosclerosis: Complications
Major consequences
Coronary arteries: IHD (myocardial infarction)
Cerebrovascular system: Cerebral infarction (stroke)
Aorta: Hypertension and aneurysm formation
Peripheral vascular system
Decreased perfusion to extremities causing
gangrene of the legs (coagulative necrosis)
More consequences (diminished arterial perfusion)
Mesenteric occlusion, Sudden cardiac death, Chronic
IHD, Ischemic encephalopathy
10.
11. Atherosclerosis: Fatty streaks
Fatty streaks, (composed of foam cells), are not
significantly raised and thus do not cause any disturbance
in blood flow.
They begin as multiple yellow, flat spots (fatty dots) less
than 1 mm, then combine into elongated streaks.
Fatty streaks appear in the aortas of children regardless of
geography, race, sex, or environment.
Coronary fatty streaks begin to form in adolescence.
The relationship of fatty streaks to atherosclerotic plaques
is uncertain.
12. Gross views of atherosclerosis in the aorta.
A. Mild atherosclerosis composed of fibrous plaques,
one of which is denoted by the arrow.
B. Severe disease with diffuse, complicated lesions.
15. Histologic features of
atheromatous plaque in the
coronary artery.
The plaque shown in A, stained
for elastin (black) demonstrating
that the internal and external
elastic membranes are
destroyed and the media of the
artery is thinned under the most
advanced plaque (arrow).
16. Histologic features of
atheromatous plaque in the
coronary artery.
The junction of the fibrous cap and
core showing scattered
inflammatory cells, calcification
(broad arrow), and
neovascularization (small arrows)
18. Atherosclerosis
Constitutional Risk Factors
Age: it is clinically evident after middle age, between ages
40-60 increases the incidence of MI 5 fold.
Sex: men > premenopausal women, but men = women by
7th-8th decades (↓ postmenopausal estrogen).
Genetics: familial predisposition (polygenic)
Well-defined hereditary genetic derangement in
lipoprotein metabolism (familial hypercholesterolemia)
Familial clustering of other risk factors: hypertension or
diabetes
19. Atherosclerosis: Major Risk Factors
Hyperlipidemia (Hypercholesterolemia)
LDL increases the risk of ATH.
HDL has a protective effect (negative risk factor).
It mobilizes the cholesterol from tissues to liver,
It is increased by exercise and ethanol use
High dietary intake
Bad fats: cholesterol and saturated fats (egg yolk, animal
fats, and butter)
Good fats such as omega-3 fatty acids (fish oils),
unsaturated fats)
Low ratio of saturated to polyunsaturated fats lowers risk.
20. Atherosclerosis: Major Risk Factors
Hypertension
Hypertension: Men ages 45-62 with (BP 169/95) →↑ X 5
of IHD than men with (BP 140/90).
Cigarette smoking increases the incidence and severity of
ATH in M &F and decreases HDL
1 pack +/day for years→↑ X2-3 of death rate from IHD
Diabetes mellitus
Induces hypercholesterolemia
MI (X 2)
stroke
gangrene (X100- 150)
21. Atherosclerosis: Other Risk Factors
Decrease physical activity (lack of regular exercise)
Life style (competitive, stressful with type A personality)
Obesity (decrease HDL)
Multiple risk factors have multiplicative effect.
ATH may develop in absence of known risk factor.
22. Atherosclerosis: Other Risk Factors
(Cont…)
Hyperhomocystenemia: homocysteine increases platelet
adhesion and coagulation abnormalities, resulting in
increased arterial and venous clots, leading to strokes and
heart attacks
Can be caused by low intake of Folic acid, vitamin B
23. Atherosclerosis – Pathogenesis
The Response to Endothelium Injury Hypothesis
1. ATH is considered to be a chronic inflammatory response
of the arterial wall initiated by injury to the endothelium
(focal areas of chronic endothelial injury (slight), because of
derivatives of cigarette smoke,
homocysteine,
viruses and other infectious agents,
hyperlipidemia
24. Atherosclerosis – Pathogenesis
The Response to Endothelium Injury Hypothesis
2. Result in endothelial dysfunction that causes
↑endothelial permeability,
enhanced leukocyte adhesion
alteration in expression of EC gene products (ICAM-1) &
(VCAM-1) that mediate adhesion of circulating
monocytes, lymphocytes and platelets. (thrombotic
potential)
25. Atherosclerosis – Pathogenesis
The Response to Endothelium Injury Hypothesis
3.Depositions of lipoproteins in the vessel wall, mainly LDL
with its high cholesterol content. Then modification of
lesional lipoproteins by oxidation.
4.Adhesion of blood monocytes (and other leukocytes) to the
endothelium, followed by their migration into the intima and
their transformation into macrophages and foam cells.
5.Adhesion of platelets.
26. Atherosclerosis – Pathogenesis
The Response to Endothelium Injury Hypothesis
6. Release of factors from activated platelets and
macrophages that cause migration of SMCs from media into
the intima.
7. Proliferation of SMCs in the intima, and elaboration of
extracellular matrix, leading to accumulation of collagen and
proteoglycans.
8. Enhanced accumulation of lipids both within cells
(macrophages and SMCs) and extracellularly.
27. Atherosclerosis - Pathogenesis
The Role of Endothelial Injury
Determinants of endothelial alterations
Homodynamic disturbances
Effects of hypercholesterolemia
Tendency for plaques to occur at ostia of exiting vessels,
branch points and along the posterior wall of the
abdominal aorta (where there are disturbed flow
patterns).
28. Atherosclerosis - Pathogenesis
The Role of Lipids
Evidence linking hypercholestrolemia & ATH
Increased LDL cholesterol levels, decreased HDL
cholesterol levels, and increased levels of the abnormal
Lp(a)
Lipids in atheromas (plaques) are plasma-derived
cholesterol and cholesterol esters.
Relationship between increased LDL level and the
severity of ATH
29. Atherosclerosis - Pathogenesis
The Role of Lipids ( Cont…)
Genetic or acquired conditions result in
hypercholesterolemia.
familial hypercholesterolemia
diabetes mellitus
hypothyroidism
nephrotic syndrome
alcoholism
Lowering levels of serum cholesterol by diet or drug
slows the rate of progression of ATH, and causes
regression of plaques.
30. Atherosclerosis - Pathogenesis
The Role of Lipids (mechanisms)
Hyperlipidemia, may directly impair EC function through
increased production of oxygen free radicals (in
macrophages or EC) that deactivate nitric oxide (the major
endothelial-relaxing factor).
Free radicals induce chemical changes of lipid in the
arterial wall by oxidizing LDL, leading to:
Accumulation of lipoproteins (mainly LDL or oxidized
LDL) in intima at sites of increased endothelial
permeability.
31. Atherosclerosis - Pathogenesis
The Role of Lipids (mechanisms)
Role of oxidized LDL in atherogenesis
Oxidized LDL is ingested through scavenger receptor of
macrophages thus forming foam cells.
Increases monocytes accumulation in lesion (adhesion)
Stimulates release of GF & cytokines
Oxidized LDL is cytotoxic to ECs and SMCs
Oxidized LDL can induce endothelial cell dysfunction
32. The Role of
Monocytes, Macrophages and Platelets
Adhesion of monocytes to ECs, then migration into the
intima, followed by transformation into macrophages which
engulf lipoproteins largely oxidized LDL to become foam
cells.
Macrophages produce IL-1 & TNF which increase
adhesion of leukocytes
Macrophages produce toxic O2 species
Macrophages elaborate GF that contribute in SMC
proliferation.
Adhesion of platelets
Release of factors from activated platelets and
macrophages that cause migration of SMCs from media
into the intima.
33. Atherosclerosis - Pathogenesis
The Role of Smooth Muscle Cell Proliferation
Proliferation of SMCs in the intima and elaboration of ECM,
leading to accumulation of collagen and proteoglycans.
Convert fatty streak into a mature fibrofatty atheroma and
contribute to the progression of ATH.
Enhanced accumulation of lipids both within cells
(macrophages and SMCs) and extracellularly.
35. Aneurysms
Abnormal dilations of blood vessel or the heart.
Develop where there is marked weakening of the wall
(congenital, infections, trauma, systemic diseases).
True aneurysms (Atherosclerotic, syphilitic, congenital
vascular aneurysms and the left ventricular aneurysm)
are of two shapes: Fusiform and Saccular.
False aneurysm is a tear in the vascular wall leading to
an extravascular hematoma that freely communicates
with the intravascular space (pulsating hematoma).
Aortic dissection (dissecting hematoma), patients
with hypertension or with abnormality of connective
tissue that affects the aorta (Marfan syndrome).
Complications: Thrombosis, Embolism, Rupture
36. Proximal aortic dissection
demonstrating a small, oblique
intimal tear (demarcated by the
probe), allowing blood to enter
the media, creating an
intramural hematoma (narrow
arrows).
Note that the intimal tear has
occurred in a region largely
free from atherosclerotic
plaque, and that propagation of
the intramural hematoma is
arrested at a site more distally
where atherosclerosis begins
(broad arrow).
37. Abdominal Aortic Aneurysm (AAA)
Causes
Atherosclerosis causes arterial wall thinning through medial
destruction.
Cystic medial degeneration of the arterial media
Focal loss of elastic and muscle fibers in the aortic media
and replacement by cystic spaces filled with myxoid
material (hypertension, Marfan’s syndrome)
Common site is abdominal aorta below the renal arteries
and above the bifurcation of the aorta. But the common iliac
arteries, the arch, and descending parts of the thoracic aorta
can be involved.
AAAs are saccular or fusiform, and thrombus frequently fills
at least part of the dilated segment .
38. Abdominal Aortic Aneurysm (AAA)
Two variants: Inflammatory AAAs and Mycotic AAAs
Males > 50 years old, (50% of patients are hypertensive).
Complications: depend primarily on location and size:
Rupture into the peritoneal cavity or retroperitoneal
tissues with massive hemorrhage.
Obstruction of a vessel, particularly of the iliac,
mesenteric, renal, or vertebral branches.
Embolism from atheroma or mural thrombus.
Pressure on an adjacent structure (ureter or vertebrae).
40. A. Cross-section of aortic media with marked elastin
fragmentation and formation of areas devoid of elastin that
resemble cystic spaces, from a patient with Marfan syndrome.
<cystic medial necrosis>
B. Normal aortic media, showing the regular layered pattern of
elastic tissue.
In both A and B the tissue section is stained to highlight elastin
as black.
41. Aortic Dissection (Dissecting
Hematoma)
Entry of blood into the arterial wall, through an intimal tear,
usually in the aortic arch, dissecting the media between the
middle and outer third, causing massive hemorrhage.
Aortic dissection (dissecting hematoma), occurs in
patients with hypertension (90%) or with abnormality of
connective tissue that affects the aorta (Marfan
syndrome).
Dissection of the aorta or other branches (coronary) may
occur during or after pregnancy (rare).
42. Histologic view of the dissection demonstrating
an aortic intramural hematoma (asterisk). Aortic
elastic layers black and blood red in this section,
stained with Movat stain.
43. Aortic Dissection (Dissecting
Hematoma)
Sudden onset of severe pain, beginning in the anterior
chest, radiating to the back, and moving downward as the
dissection progresses. (Not MI).
Aortic dissections are classified into two types:
Proximal lesions: more common (dangerous), involving
the ascending aorta or both the ascending and the
descending aorta (called type A).
Distal lesions begin distal to the subclavian artery (called
type B)
45. Aortic Dissection (Dissecting Hematoma)
Complication
The most common cause of death is rupture of the
dissection outward into any of the three body cavities
(pericardial, pleural, or peritoneal).
Retrograde dissection into the aortic root can cause
disruption of the aortic valve causing cardiac tamponade,
aortic insufficiency, and myocardial infarction.
Extension of the dissection into the great arteries of the
neck or into the coronary, renal, mesenteric, or iliac arteries,
causing critical vascular obstruction.
47. Ischemic Heart Diseases (IHD)
A group of closely related syndromes caused by an
imbalance between the myocardial oxygen demands and
blood supply.
It accounts for 80% of cardiac death and nearly 1/3 of all
deaths in developed countries .
The most common cause of IHD is luminal narrowing of
the C.A. by atherosclerosis and the following contributing
factors:
Acute plaque changes
Coronary artery thrombosis
Coronary artery vasospasm
50. Angina Pectoris (AP)
Characterized by episodic attacks of crushing or squeezing
substernal pain, radiating to precordium and left arm.
Types of Angina
Typical stable AP
Prinzmetal or variant angina
Unstable Angina (preinfarction angina or crescendo
angina)
51. Angina Pectoris (AP)
Typical stable AP
Chest pain associated with exertion, stress and emotion.
Usually there is fixed atherosclerotic narrowing (75%) of
C.A (stenosis).
Relieved by rest and nitroglycerine.
Prinzmetal or variant angina
Occurs at rest, less frequently related to effort
Caused by C.A. spasm usually near atherosclerotic
plaque.
Respond to nitroglycerine
52. Angina Pectoris (AP)
Unstable Angina (preinfarction angina or crescendo angina)
More frequent, more intense and provoked by less effort
or emotion
Increased frequency of anginal pain and Lasts longer
Caused by acute plaque change with superimposed
partial thrombosis or vasospasm
Nitroglycerine is required more but it is less effective
53. What is your diagnosis
Severe, crushing substernal chest pain, which may radiate
to the neck, jaw, epigastrium, shoulder, or left arm.
This pain lasts several hours to days and is not significantly
relieved by nitroglycerin.
The pulse is generally rapid and weak
Patient is diaphoretic (sweating) with short breathing
(dyspnea).
56. Myocardial Infarction (MI)
An area of myocardial necrosis caused by local ischemia.
Acute MI is the most common cause of death in the west.
1.5 million MI/ year in USA, with 1/2 million deaths, 50% do
not reach hospital.
Ages 45-54, M>F (Risk factors same as of atherosclerosis).
Pathogenesis: Most acute MIs are caused by coronary
artery thrombosis.
Important contributing factors are:
Acute plaque changes followed by thrombosis.
Vasospasm and platelet aggregation may contribute
to coronary artery occlusion.
57. Acute myocardial infarction (MI)
MI typically begins in the subendocardial region and
extends over the next (3-6) hours to involve the mid- and
subepicardial areas of the myocardium
Two types of M I
Transmural: full thickness infarction > 2.5 cm in diameter
caused by sever atheroma with acute plaque changes
leading to complete occlusion.
Subendocardial: limited to inner 1/3 of wall thickness,
caused by ischemia due to diffuse coronary
atherosclerosis (stenosis).
58. Morphology of MI
Size of MI depends on segment of C.A. blocked and
collateral circulation
The location of MI depends on site of occlusion and type of
coronary circulation
Left anterior descending coronary artery (LAD) (40%-
50%)
Anterior and apical LV+ ant 2/3 of IVS
Right coronary artery (RCA) (30% - 40%)
Posterior LV + post 1/3 of IVS( in right dominance)
Left circumflex coronary artery LCA (15% - 20%)
Lateral LV + post wall ( in left dominance)
59. There are no morphological changes yet.
0-12 hours
Coagulation necrosis begins, the cytoplasm of the necrotic myocytes becomes
eosinophilic, loss of cross striations, pyknosis and karyorrhexis. Wavy fiber
change at the periphery of the infarct.
12-18 hours
The area shows a slight pallor. Neutrophils begin to show up and peak about 3
days and subsequently diminish. Hemmhorage is rare because MIs are
ischemic by definition. contraction bands at the periphery of the infarct
produced by hypercontraction of myofibrils in dying cells.
18-72 hours
The infarct will appear pale firm with a hyperemic boarder. Macrophages,
fibroblasts and capillaries first appear at the margins then begin to migrate
into center. Macrophages begin to phagocytize the necrotic myocytes.
4-7 days
The necrotic area is yellow, soft; the granulation tissue is visible grossly at the
edge of the infarct as a red-purple zone. Collagen fibers are seen and many
macrophages with remnants of myocytes.
10 days
Vascularity diminishes and most infarcts have been replaced by dense scar
tissue. The ventricular wall is thinned, firm, and gray at the site of the
healed infarct
4-8 weeks
60. Myocardial Infarct, early changes (1-2 days)
myocardial fibers have dark red contraction bands
extending across them. The myocardial cell nuclei
have almost all disappeared. There is beginning
acute inflammation.
67. Complications of MI
After infarction about 25% of patients experience sudden
death due to fatal arrhythmia.
If patients survive the acute event, 80% to 90% develop
complications.
Arrhythmias (75% - 95%)
Left ventricular failure with mild to severe pulmonary
edema (60%)
Cardiogenic shock (10%) if infarct > 40% of LV mass.
Thromboembolic phenomena (15%-49%).
68. Complications of MI
Infarcted papillary muscle rupture is most common at third
day. It causes acute left ventricular failure and is associated
with a high mortality rate.
External rupture usually towards the end of the week 1 as
blood dissects through the myocardium. It causes
hemopericardium and cardiac tamponade. It can also dissect
through the IV septum.
Mural thrombi are potential sources for systemic emboli.
Acute pericarditis occurs in (15%) of patients with MI within 2
to 4 days.
Ventricular aneurysm is a late complication
69. MI - Laboratory diagnosis
Creatine kinase (MB fraction) rises within 4-6 hours, peaks
early and is normal within 4 days.
LDH rises in about 24 hours, peaks in 3-6 days and may
be abnormal for 14 days. The most sensitive is the ratio of
LDH1 to LDH2 (normally < 1.0 ; ratio "flipped" in
infarction).
Troponin I & T, troponin levels remain elevated for 4 to 7
days after the acute event
70. Sudden cardiac death
Unexpected death from cardiac causes within one hour of
the onset of symptoms.
Majority are complication of IHD.
75 - 95 % have marked coronary atherosclerosis.
Ultimate cause of death is fatal arrhythmias.
71. Sudden cardiac death
Coronary Artery Diseases
Coronary atherosclerosis
Developmental abnormalities (anomalous origin, hypoplasia)
Coronary artery embolism
Other (vasculitis, dissection)
Myocardial Diseases
Cardiomyopathies
Myocarditis and other infiltrative processes
Right ventricular dysplasia
Valvular Diseases
Mitral valve prolapse
Aortic stenosis and other forms of left ventricular outflow obstruction
Endocarditis
Conduction System Abnormalities
74. Myocarditis
Inflammatory condition of the myocardium result in
myocardium injury.
The heart may be of normal size, but more commonly it is
dilated.
The myocardium is flabby, pale and often contains small
areas of hemorrhage.
In most cases, myocarditis appears to be self-limited
Clinical features range from an asymptomatic state to
severe congestive heart failure at late stage
Arrhythmia: lethal ventricular arrhythmias accounting for
most sudden cardiac deaths.
Major Causes : infections, Immune-mediated reactions
75. Myocarditis: Major Causes
Infections
Viruses: the most common cause in USA (e.g.,
coxsackievirus, echovirus).
Chlamydia (e.g., C. psittaci)
Rickettsia (e.g., R. typhi [typhus fever])
Bacteria (e.g., Corynebacterium [diphtheria], Neisseria
[meningococcus], Borrelia [Lyme disease])
Fungi (e.g., Candida)
Protozoa (e.g., Trypanosoma [Chagas disease], the most
common cause in South America)
Helminths (e.g., trichinosis)
76. Myocarditis: Major Causes
Immune-Mediated Reactions
Postviral and Poststreptococcal (rheumatic fever)
Systemic lupus erythematosus
Drug hypersensitivity (e.g., methyldopa, sulfonamides)
Transplant rejection
Unknown : Sarcoidosis, and Giant cell myocarditis
77. Myocarditis: Microscopically
Viruses: edema and inflammatory infiltrate dominated by
lymphocytes, myocyte degeneration and necrosis.
Chronic cases: ventricular dilation, inflammation is less
obvious, myocardial fibrosis becomes more prominent
Parasites: the organism is demonstrable histologically,
(Chagas disease, trypanosomes directly infect cardiac
muscle fibers).
Bacteria: neutrophilic infiltrate, and sometimes abscess.
Cardiac transplant rejection: interstitial lymphocytes and
myocyte degeneration.
Giant cell myocarditis is characterized by an inflammatory
infiltrate in which multinucleated giant cells are prominent.
80. Giant Cell Myocarditis:
Mononuclear inflammatory infiltrate
(lymphocytes and macrophages), with
extensive loss of muscle, and multinucleated
giant cells, apparently derived from muscle.
83. Pericarditis
Inflammation of Pericardium
Primary: uncommon, mostly viral and sometimes by other
organisms (pyogenic bacteria, mycobacteria and fungi).
Secondary to:
Acute myocardial infarction, cardiac surgery, or
radiation to the mediastinum.
Associated with systemic disorders, mostly with
uremia, rheumatic fever, systemic lupus
erythematosus (SLE), and metastatic malignancies
(bloody effusions).
84. Pericarditis Outcomes
Pericarditis may
Cause immediate hemodynamic complications if a
significant effusion is present
Resolve without significant sequelae
Progress to a chronic fibrosing process.
85. Acute Pericarditis: Morphology
In uremia, and acute rheumatic fever: the exudate is
fibrinous and impart a shaggy irregular pericardial surface
(bread and butter pericarditis).
Viral pericarditis fibrinous exudate.
Acute bacterial pericarditis fibrinopurulent exudate.
Tuberculosis caseous materials and hemorrhagic
pericarditis
Pericardial metastases: irregular nodules with a shaggy
fibrinous exudate and a bloody effusion .
87. The pericardial surface shows strands
of pink fibrin extending outward.
There is underlying inflammation.
88. Chronic Pericarditis:
Morphology
Ranges from delicate adhesions to dense fibrotic scars.
In extreme cases the heart cannot expand normally during
diastole, a condition called constrictive pericarditis.
89. Pericarditis: Clinical
Atypical chest pain (worse on reclining),
Friction rub.
Significant exudate signs and symptoms of cardiac
tamponade faint distant heart sounds, distended neck
veins, declining cardiac output, and shock.
Chronic constrictive pericarditis venous distension and
low cardiac output.
90. Pericardial Effusions
Accumulation of fluid in the pericardium, fluid nature varies
with cause, major types and their causes are:
Serous: congestive heart failure, hypoalbuminemia
Serosanguineous: blunt chest trauma, malignancy
Chylous: mediastinal lymphatic obstruction
Fibrinous / Serofibrinous: RF, connective tissue
diseases, MI and post-MI, trauma & uremia
Blood (Hemopericardium): ruptured aortic aneurysms,
ruptured myocardial infarcts, penetrating traumatic
injury to the heart.
92. Infective Endocarditis (IE)
Infection of the cardiac valves and/or the endocardium,
resulting in the formation of vegetation (mass of thrombotic
debris and micro-organisms) on valve leaflets, mostly
aortic and mitral valves.
IE. is divided into two forms:
Acute Infective Endocarditis
Subacute Infective Endocarditis
93. Infective Endocarditis
Acute Subacute
Organism High virulant
staphylococcus
Low virulant hemolytic
streptococcus
Valve Normal and deformed
valves
Deformed valve
Progression Rapid Slow
Response Little local reaction,
lession is destructive
Local inflammation,
lession is less
destructive
Resolution Death (50%) Recovery (antibiotics)
94. Infective Endocarditis
Etiology and Pathogenesis
Bacteremia
Obvious hematogenous infection as with:
Intravenous drug abusers,
Elsewhere infection,
Previous dental, surgical or interventional procedure
(urinary catheterization).
Occult source of bacteremia
Small injuries to skin or mucosal surfaces such as
brushing the teeth.
95. Infective Endocarditis
Etiology and Pathogenesis
Causative Organisms
-Hemolytic (viridans) streptococci attacks deformed valves
(50-60%).
Staphylococcus aureus attacks healthy or deformed valves
(intravenous drug abusers) (10-20%) .
Coagulase-negative staphylococci (S. epidermidis) attacks
prosthetic valve.
96. Infective Endocarditis
Risk Factors
Cardiac abnormalities: such as chronic valvular diseases
and high pressure shunts within the heart (small ventricular
septal defects).
Prosthetic heart valves (10% to 20%).
Intravenous drug abusers (right side of the heart)
97. Pathology of Acute
Endocarditis
Gross: vegetations may obstruct valve orifice and cause
rupture of the leaflets, cordae tendineae, or papillary
muscles.
May cause abscess in perivalvular tissue (ring abscess).
Vegetations may become systemic emboli infarcts
(brain, kidneys, myocardium) and abscesses.
Micro: vegetations consist of large number of organisms,
fibrin and blood cells.
99. Pathology of Subacute
Endocarditis
Gross: vegetations are firmer and less destructive (ring
abscess uncommon).
Systemic emboli may develop and cause infarcts, without
abscesses.
Micro: granulation tissue is seen at the base of the
vegetations.
Later: fibrosis, calcifications and chronic inflammatory
infiltrates.
100. Infective Endocarditis
Clinical Manifestation
Onset: gradual or explosive (organisms).
Organism of low virulence cause low-grade fever,
malaise, weight loss.
Organism of high virulence cause high fever, shaking
chills.
Cardiac murmurs, enlargement of spleen, clubbing of digits
(particularly in subacute cases), and petechiae.
Blood culture is important (only minority of cases remain
negative).
101. Infective Endocarditis
Complications
Regurgitation leading to congestive heart failure.
Myocardial abscess (ring abscess).
Extension of infection to root of aorta (mycotic aneurysm).
Systemic emboli, also pulmonary emboli in right-sided
endocarditis.
Renal complications (glomerulonephritis and Infarction).
103. Endocarditis of the mitral valve
(subacute, caused by streptococcus
viridans)
104. Acute endocarditis of a congenitally
bicuspid aortic valve with severe cuspal
destruction and ring abscess (arrow).
105. Nonbacterial Thrombotic Endocarditis
(NBTE), Marantic Endocarditis
Characterized by sterile small nodules less than 5 mm, (fibrin,
platelets and other blood components) on the valve leaflets
along the line of closure.
The valve leaflets are normal, no inflammation or fibrosis.
Mitral valve is the most common site, followed by aortic valve
It has been found to be associated with endothelial
abnormalities, deep venous thrombosis, and malignancy
(adenocarcinoma).
106. Nonbacterial Thrombotic Endocarditis (NBTE).
Nearly complete row of thrombotic vegetations
along the line of closure of the mitral valve leaflets.
107. Libman-Sacks Endocarditis
(LSE)
Small sterile vegetations on ventricular or both surfaces of
mitral & tricuspid valves in some patients with Systemic
Lupus Erythematosus.
108. RHD: row of small vegetations along the lines of closure of the
valve leaflets.
IE: large, irregular masses on the valve cusps that extend onto
the cords.
NBTE: small, bland vegetations, usually attached at the line of
closure.
LSE: has small or medium-sized vegetations on either or both
sides of the valve leaflets.
110. Vasculitis
Inflammation of blood vessels of any size, affecting one
or few vessels in a limited area or it could be systemic
affecting multiple organ systems.
113. Classification of
Vasculitis
Based on
Pathogenesis
Direct Infection
Bacterial (e.g., Neisseria)
Rickettsial (e.g., Rocky Mountain spotted fever)
Spirochetal (e.g., syphilis)
Fungal (e.g., aspergillosis, mucormycosis)
Viral (e.g., herpes zoster-varicella)
Immunologic
Immune complex-mediated
Infection-induced (e.g., hepatitis B and C virus)
Henoch-Schönlein purpura
Systemic lupus erythematosus and rheumatoid arthritis
Drug-induced
Cryoglobulinemia
Serum sickness
Antineutrophil cytoplasmic autoantibody-mediated
Wegener granulomatosis
Microscopic polyangiitis (microscopic polyarteritis)
Churg-Strauss syndrome
Direct antibody attack-mediated
Goodpasture syndrome (anti-glomerular basement membrane antibodies)
Kawasaki disease (antiendothelial antibodies)
Cell-mediated
Allograft organ rejection
Inflammatory bowel disease
Paraneoplastic vasculitis
Unknown
Giant cell (temporal) arteritis
Takayasu arteritis
Polyarteritis nodosa (classic polyarteritis nodosa)
114. Classification of vasculitis
The systemic vasculitides are classified on the basis of
the
Size and
Anatomic site of the involved blood vessels,
Histologic characteristics of the lesion, and
Clinical manifestations.
There is considerable clinical and pathologic overlap
among these disorders,
115. Classification of vasculitis
Polyarteritis nodosa:
Medium - sized & small arteries.
Wegener’s granulomatosis:
Arterioles,venules,capillaries and small blood vesseles.
Microscopic polyarteritis (hypersensitivity vasculitis):
Venules, capillaries & arterioles.
Temporal (giant cell,cranial) arteritis:
Mainly affects large blood vesseles.
116.
117. Giant Cell (Temporal) Arteritis
The most common of the vasculitis, is an acute and
chronic, often granulomatous inflammation of arteries of
large to small size (mainly in the head-especially the
temporal arteries but also the vertebral and ophthalmic
arteries (Blindness).
Lesions have also been found in other arteries throughout
the body, including the aorta (giant cell aortitis).
118. Giant Cell (Temporal) Arteritis:
Morphology
Characteristically, segments of affected arteries develop
nodular thickenings with reduction of the lumen and may
become thrombosed.
Common variant:
granulomatous inflammation of the inner half of the media
centered on the internal elastic membrane marked by
a lymphocytic infiltrate,
multinucleate giant cells,
fragmentation of the internal elastic lamina,
macrophages are seen close to the damaged elastic
lamina.
119. Giant Cell (Temporal) Arteritis
(Morphology Cont..)
Less common pattern, a nonspecific panarteritis with a
mixed inflammatory infiltrate (lymphocytes, macrophages,
neutrophils and eosinophils).
Healed stage of both of these patterns reveals collagenous
thickening of the vessel wall; organization of the luminal
thrombus sometimes transforms the artery into a fibrous
cord.
120. Giant Cell (Temporal) Arteritis:
Pathogenesis
Evidence points to a T-cell-mediated immune response to
an unknown, possibly vessel wall, antigen.
Supporting this hypothesis are a granulomatous
inflammatory response with the presence of CD4+ T cells.
121. Giant Cell (Temporal) Arteritis:
Clinical Features
Rare before the age of 50 (F:M = 2:1) .
Symptoms are constitutional fever, fatigue, weight loss-
without localizing signs or symptoms
The diagnosis depends on biopsy and histologic
confirmation.
Treatment with anti-inflammatory agents is remarkably
effective.
122. Temporal (giant cell) arteritis.
Giant cells at the degenerated internal elastic
membrane in active arteritis and intimal
thickening.
123. Temporal (giant cell) arteritis.
Elastic tissue stain demonstrating focal
destruction of internal elastic membrane (arrow)
and intimal thickening (IT) characteristic of long-
standing or healed arteritis.
125. Cardiac Tumors
Heart tumor are rare
Metastatic Neoplasms: metastases may reach the heart via
lymphatic, venous, or arterial channels.
seen in up to 10% of patients dying of disseminated
cancer, mostly involving pericardium.
The most common primary neoplasms that metastasize
to the heart are:
carcinomas of the lung and breast,
malignant melanomas,
lymphomas & leukemias.
126. Cardiac tumors
Primary tumors include:
Myxoma: is commonest heart tumor in adults, benign, 90%
in Lt atrium.
They appear as sessile or pedunculated gelatinous mass
covered by endothelium
Microscopically: multinucleated stellate (Star-shaped)
cells, edema and mucoid stroma.
127. Cardiac tumors
Rhabdomyoma
Common (infancy and children)
Associated with tuberous sclerosis
Grossly: myocardial masses project into the ventricular
lumen, solitary or multifocal.
Microscopically: eosinophilic, polygonal cells (contain
large, glycogen-rich cytoplasmic granules).
Lipoma, and Papillary Elastofibromas,
Sarcomas: Angiosarcomas, and Rhabdomyosarcomas.
130. Benign tumors: Hemangiomas
Characterized by increased numbers of normal or
abnormal vessels filled with blood.
Mostly localized but may involve large segments of the
body (entire extremity) and called angiomatosis.
The majority are superficial lesions often of the head and
neck, possible in liver.
Common in childhood and constitutes 7% of all benign
tumors. May present at birth.
The strawberry type of the skin of the newborn is common
(juvenile hemangioma).
131. Capillary Hemangiomas
Capillary Hemangiomas are the most common type. Mostly
in the skin, subcutaneous tissues, and mucous membranes
of the oral cavity and lips. Many regress spontaneously
Color (bright red to blue), size varies (mm to centimeters),
flat or slightly elevated
Lobulated but unencapsulated aggregates of closely
packed thin walled capillaries which are filled with blood
and lined by flat benign endothelium
The Lumina may contain thrombi
133. Cavernous Hemangiomas
Less common, and characterized by large vascular spaces.
Cavernous Hemangiomas are less circumscribed and
more frequently involve deep structures.
Rarely giant forms occur, that affects large subcutaneous
areas of the face or extremities.
Are soft, red-blue measuring 1-2 cm.
Histologically, sharply defined but not encapsulated.
Composed of large cavernous vascular spaces filled with
blood.
Are mostly of little clinical significance.
135. Pyogenic Granuloma
(Lobular capillary hemangioma)
Polypoid form of capillary hemangiomas.
Occurs as rapidly growing red nodule attached by a stalk to
the skin and oral mucosa , which bleeds easily and is
ulcerated.
One third of the lesions develop after trauma.
The proliferating capillaries are accompanied by edema and
inflammatory cells
The appearance resembles granulation tissue.
Pregnancy tumor ( granuloma gravidarum) is a pyogenic
granuloma that occurs in the gingival of pregnant ladies and
regresses after delivery
138. Glomus Tumor (Glomangioma)
Benign but often painful tumors arising from modified
SMCs of the glomus body, a specialized arteriovenous
structure involved in thermoregulation.
They are most commonly found in the distal portion of the
digits, especially under the fingernails. Excision is curative.
Morphology: Glomus tumors are round, slightly elevated,
red-blue, firm nodules (generally much less than 1 cm in
diameter) that can initially resemble a minute focus of
hemorrhage under the nail.
Histologically, these are aggregates, nests, and masses of
specialized glomus cells, all within a connective tissue
stroma.
Individual tumor cells are small, uniform, and round or cuboidal,
with scant cytoplasm and ultrastructural features similar to SMCs
139. Borderline Malignancies:
Hemangioendotheliomas
A wide spectrum of vascular neoplasms showing histologic
features and clinical behavior intermediate between benign
hemangiomas and angiosarcomas.
The most common is epithelioid hemangio-endotheliomas
which occurs around medium sized and large veins in the
soft tissues of adults.
Most are cured by excision but up to 40% recur and 30%
metastasize.
142. Kaposi Sarcoma
A. Chronic type:
Called classic or European mainly occurs in elderly
Red to purple nodules in the distal lower extremities,
increasing in size slowly and locally persistent.
B. Lymphadenopathic:
Called African or endemic mainly among children of
south Africa
Localized or generalized lymphadenopathy. It is an
aggressive tumor
143. Kaposi Sarcoma
C- Transplant Associated:
Occurs several months to a few years postoperatively in
solid organ transplant in recipient who receive high doses
of immunosuppressive therapy.
Lesions are localized or generalized
Skin lesions may regress.
D. AIDS associated:
In one fourth of AIDS patients especially homosexuals
Common to involve lymph nodes and the gut.
144. Kaposi sarcoma
A. Gross photograph illustrating coalescent red-purple macules
and plaques of the skin.
B. Histologic view of the nodular form demonstrating sheets of
plump, proliferating spindle cells and vascular spaces.
145. Malignant tumors:
Angiosarcomas
Occur in both sexes ant tend to affect adults
Mostly affects skin, soft tissues, breast and liver.
Hepatic angiosarcomas are associated with carcinogens
like arsenic.
Shows local invasion and metastatic spread.
Has poor outcome.
146. Angiosarcoma
A. Gross photograph of angiosarcoma of the heart (right ventricle).
B. Moderately well differentiated angiosarcoma with dense clumps of
irregular, moderate anaplastic cells and distinct vascular lumens.
C. Immunohistochemical staining of angiosarcoma for the endothelial cell
marker CD31, proving the endothelial nature of the tumor cells.
