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BLOOD VESSELS
Dr. Dexter MD FRC Path
Undercover Professor
DEPARTMENT OF PATHOLOGY
SGUSOM GRENADA (W.I.)
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Anatomy & Histology
• Three layers of
arteries –
– Intima –
endothelial cells
– Media – smooth
muscle cells
– Adventitia –
connective
tissue
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ENDOTHELIAL CELL FUNCTIONS
• Maintenance of Permeability Barrier
• Elaboration of Antithrombotic & Prothrombotic
Molecules
• Modulation of Blood Flow and Vascular
Reactivity
– Endothelin/NO
• Regulation of Inflammation and Immunity
– IL-1, IL-6
• Regulation of Cell Growth
– PDGF/TGF-β
• Oxidation of Low-Density Lipoprotein
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Endothelial Dysfunction
• Endothelial stimulation – rapid, re-
versible; independent of new protein
synthesis.
• Endothelial activation - alteration in
gene expression and protein synthesis
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Characteristics of an “activated” endothelial cell
A normal arterial wall has anticoagulant properties and low leukocyte adhesivity
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Complement products
Hypoxia
MHC molecules Viruses
Coagulation proteins Advanced glycosylation
end products
Vasoactive mediators Lipid products
Growth factors Hemodynamic forces
Cytokines / chemokines Bacterial products
Adhesion molecules Cytokines
Induced genes Activators
Endothelial activation
2
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Vascular Smooth Muscle Cells
• Functions
–Vasoconstriction and dilation in
response to normal or pharmacological
stimuli
–Elaboration of growth factors and
cytokines
–Migration to the intima and proliferation
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Diseases of Blood Vessels
Two principal mechanisms
1. Narrowing or complete obstruction of
the lumen either
– progressively (atherosclerosis) or
– suddenly (thrombosis)
2. Weakening of the wall of the vessel -
leading to dilatation or rupture.
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Other Categories
• Hypertension
• Inflammatory disorders -vasculitis
• Congenital Malformations
• Neoplasms
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ARTERIOSCLEROSIS
ATHEROSCLEROSIS
LARGE BV
INTIMA
MEDIAL CALCIFIC
SCLEROSIS
MEDIA
ARTERIOLOSCLEROSIS
SMALL VESSEL
FULL THICKNESS
HYPERPLASTIC
HYALINE
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Atherosclerosis
• Derived from Greek word – ‘ATHEROS’ –
soft gruel or porridge like
• Chronic inflammatory disorder of
intima of large arteries characterized
by formation of fibro fatty plaques
called atheroma.
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EPIDEMIOLOGY
Five Leading Causes of Death for Males and Females – U.S.
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Atherosclerosis – Major Risk
Factors
• NONMODIFIABLE
–Age
–Gender
–Genetic
predisposition
• MODIFIABLE
–Hyperlipidemia
–Hypertension
–Cigarette
smoking
–Diabetes mellitus
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Atherosclerosis –
Uncertain, Unquantifiable or Possibly Lesser
Risk Factors
• Hyperhomocystinemia
• Lipoprotein (a)
• Inhibitors of fibrinolysis
• Low PA-1 Inhibitor
• C-reactive protein
• Lack of exercise
• Type “A” personality
• Obesity
• “Trans”-unsaturated fat
intake
• Postmenopausal
estrogen deficiency
• High carbohydrate diet
• Chlamydia pneumoniae
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NON-MODIFIABLE RISK FACTORS
• AGE - begins in childhood and progresses with
age
– 40 -60 yrs – five fold increase in incidence of MI
• SEX - Males > females
– Uncommon in premenopausal women
– Postmenopausal Increased incidence
– Favorable response to HRT
• GENETICS –
– Familial clustering of other risk factors
– Familial hypercholesterolemia
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MODIFIABLE RISK FACTORS
• HYPERLIPIDEMIA –
– ↑ cholesterol most important
– Major component associated with ↑ risk
LDL – “bad cholesterol”.
– inverse relationship between HDL levels –
“good cholesterol”.
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Evidences linking ↑ cholesterol with
Atherosclerosis
• Genetic defects in lipoprotein metabolism
– Familial hypercholesteremia defect in LDL
receptor↓ hepatic uptake of LDL↑ levels
of LDL
– ↑ LDL because of abnormal apo E it fails to
bind to LDL receptor
• Genetic or acquired diseases like DM &
hypothyroidism premature & severe
A.S.
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Evidences linking ↑ cholesterol with
Atherosclerosis
• Atheromas contain cholesterol & cholesterol esters
• ↑ levels of cholesterol & LDL↑ severity of A.S.
• High cholesterol diets produce experimental A.S.
• levels of cholesterol ↓by diet/drugs↓ progression
of A.S.
4
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RISK FACTORS
HYPERTENSION
• More importance after age of 45
• 169/95- 5 fold ↑ risk of developing IHD as
compared to 140/90
• Anti hypertensive therapy reduces
incidence of A.S. associated diseases
stroke, IHD
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RISK FACTORS
CIGARETTE SMOKING
• Smoking & A.S. Made For Each Other
• 1/> packs/day for several yearsdeath rate
increases up to 200%
DIABETES MELLITUS
• ↑ Cholesterol predisposition to AS
• 100x increased risk of AS induced gangrene
of the lower extremities.
• ↑ risk of strokes and M.I.
• AS in young patients Suspect DM
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RISK FACTORS
PLASMA HOMOCYSTEINE
• Hyper-
Homocystinuria -
Patients have
premature vascular
disease
• Can be caused by
low folate & vitamin
B intake
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RISK FACTORS
LIPOPROTEIN (a)
• Altered form of LDL
• Potentially atherogenic effects
– Lipid accumulation
– Endothelial cell modulation
– Smooth muscle cell proliferation
– Control of neo-vascularization
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LESSER FACTORS
• Stress
• Type A personality
• Obesity
MULTIPLE RISK FACTORS MAY
HAVE A MULTIPLICATIVE & NOT
ADDITIVE EFFECT
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LOWER THE BETTER
Blood sugar
Blood pressure
Body weight
LDL
Stress levels
No. of cigarettes
5
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PATHOGENESIS
• RESPONSE TO INJURY HYPOTHESIS
• Chronic inflammatory response of the
arterial wall initiated by some form of the
injury to the endothelium.
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RESPONSE TO INJURY HYPOTHESIS
• Role of endothelial cells – endothelial injury
– Endothelial activation
• Increased permeability
• Increased adhesion of leukocytes
• Increased expression of adhesion molecules
• Growth factors
– Determinants of endothelial alterations
• Hemodynamic factors – increased frequency of
lesions at branch points, ostia of vessels
• Hypercholesterolemia
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RESPONSE TO INJURY HYPOTHESIS
• Role of lipids
– Cytotoxic to endothelium
– Oxidized (modified) lipids have atherogenic
properties
• readily ingested by macrophages – foam cells
• chemotactic for circulating monocytes
• inhibits the motility of macrophages already in the
lesion
• stimulates release of growth factors and cytokines
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RESPONSE TO INJURY HYPOTHESIS
• Role of macrophages
– Cytokines like IL-1, TN (procoagulant
endothelium)F
– Growth factors
• Role of smooth muscle proliferation
– Conversion of fatty streak into fibrofatty
atheroma
• Role of T-cells
– Recruitment and activation of monocytes
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Atherosclerotic plaque
• Three principal components
• Cells – smooth muscle cells,
macrophages, and other leukocytes
• Extracellular matrix – including collagen,
elastic fibers, and proteoglycans
• Intracellular and extracellular lipid
deposits
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Complicated lesion of
atherosclerosis
• Calcification – may be patchy or massive.
• Focal rupture or gross ulceration, or both,
leading to
– thrombus formation
– cholesterol emboli or atheroemboli
• Hemorrhage .
• Superimposed thrombus
• Aneurysmal dilatation – atrophy of underlying
media
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Sites of severe
atherosclerosis in
order of frequency
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Atherosclerosis-Clinical
Manifestations
– Coronary heart disease
(CHD)
• Acute myocardial
infarction (AMI)
• Angina – Stable or
Unstable
• Chronic ischemic heart
disease leading to
congestive heart
failure(CHF)
• Sudden cardiac death
– Abdominal aortic
aneurysm (AAA)
– Cerebral vascular
disease
• Stroke
• Transient ischemic
attack (TIA)
• Chronic ischemic
encephalopathy
– Peripheral vascular
disease
• Claudication
• Ischemic bowel disease
(mesenteric occlusion)
• Gangrene
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PRECLINICAL
PHASE
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Hypertension
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Hypertension
• Normal < 130 mm Hg systolic & < 85 mm Hg
diastolic)
• Hypertension - Sustained increase in blood
pressure
– Systolic > 140 mm Hg
– Diastolic > 90 mm Hg
• Mild + 20; Moderate +40; Severe +80 mm Hg
(systolic)
• Malignant hypertension - > 210/120
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Hypertension
• 25% of persons in general population are
hypertensive
• Leading risk factor – MI, DM, Stroke
• Silent Killer – painless complications
• Complications bring to diagnosis but late
• Chronic, end organ & vascular damage
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Regulation of BP:
BP = Cardiac Output x Peripheral Resistance
• Endocrine Factors
– Renin, Angiotensin, ANP, ADH, Aldosterone.
• Neural Factors
– Sympathetic & Parasympathetic
• Blood Volume
– Sodium, Mineralocorticoids, ANP
• Cardiac Factors
– Heart rate & Contractility.
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Etiologic Classification:
• Primary/Essential Hypertension (95%)
• Secondary Hypertension (5-10%)
– Renal – GN, RAS, Renin tumors
– Endocrine – Cushing, OCP, Thyrotoxicosis
Myxdema, Pheochromocytoma, Acromegaly.
– Vascular – Coarctation of Aorta, PAN, Aortic
insufficiency.
– Neurogenic – Psychogenic, Intracranial
pressure, polyneuritis etc.
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Pathogenesis
• Essential - multifactorial.
– Increased peripheral resistance (sympathetic tone)
– stress, hormonal, neural.
– Genetic, familial, life style.
• Secondary - Known abnormal control.
– Increased blood volume - Sodium retention ADH,
Aldosterone.
– Increased sympathetic tone - Adrenal tumors,
sympathetic stimulation.
– Increased vasoactive hormones - Cushing's,
Pheochromocytoma,
8
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GENETIC FACTORS
INCREASED
SYMPATHETIC
ACTIVITY
INCREASED
COP
INCREASED PERIPHERAL
RESISTANCE
HYPERTENSION
INCREASED RENAL
SODIUM RETENTION
INCREASED
BLOOD VOLUME
INCREASED RENIN
ALDOSTERONE ACTIVITY
AUTOREGULATION
ARTERIOLAR NARROWING
EXCESS DIETARY SODIUM
CHRONIC RENAL DISEASE
CUSHING SYNDROME
HYPERALDOSTERONISM
PHEOCHROMOCYTOMA
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Malignant Hypertension:
• Greater than 210/120 BP
• May complicate any type of HTN.
• Necrotizing arteriolitis.
• Rapidly progressive end organ damage.
– Renal failure
– Left ventricular failure
– Hypertensive encephalopathy
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Hypertension - complications:
• Large Blood Vessels –
– Atherosclerosis and its complications.
• Small Blood Vessels –
– Arteriolosclerosis – Hyaline & Hyperplastic
• Heart
– Left ventricular hypertrophy, Hypertensive
cardiomyopathy IHD, MI.
• Kidney
– Nephrosclerosis – Benign & Malignant.
• Eyes:
– Hypertensive retinopathy, hemorrhage
• Brain:
– Haemorrhage, infarction (stroke),
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Hyaline arteriosclerosis
• Homogenous, pink, hyaline thickening of the
walls of the arterioles with loss of underlying
structural details and with narrowing of the
lumen.
• Leakage of plasma components across vascular
endothelium and increasing extracellular matrix
production by smooth muscle cells
• Chronic hemodynamic stress in hypertension or
metabolic stress in diabetes accentuates en-
dothelial injury
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Hyperplastic arteriosclerosis
• Related to more acute or severe
elevations of blood pressure
• Onion-skin, concentric, laminated
thickening of the walls of arterioles with
progressive narrowing of the lumens.
• Necrotizing Arteriolitis - deposits of
fibrinoid and acute necrosis of the vessel
wall.
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VASCULITIS
• Inflammation and necrosis of the blood
vessels, including arteries, veins, and
capillaries.
• can be classified based on
– Type of vessel involved
– Etiology
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Type of vessel involved
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Etiology
– Direct infection- Bacterial, Rickettsial, Spirochetal, Fungal
– Immunological
• Immune complex mediated
– (hepatitis B or C virus mediated)
– SLE and rheumatoid arthritis
– Drug induced
• Antineutrophil cytoplasmic antibody (ANCA) mediated
– Wegener’s granulomatosis
– Churg-Strauss syndrome
• Direct antibody attack mediated
– Goodpasture syndrome (anti-GBM antibodies)
– Kawasaki disease (antiendothelial antibodies)
• Cell mediated
– Allograft organ rejection
– Unknown
• Giant cell (temporal) arteritis
• Takayasu arteritis
• Polyarteritis nodosa
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Anti- Neutrophil Cytoplasmic Antibodies
(ANCA)
• Heterogeneous group of auto-antibodies
against enzymes mainly found within the
primary granules in neutrophils and in
lysosomes of monocytes and in endothelial
cells
• P- ANCA: microscopic polyangiitis &
Churg-Strauss
• C-ANCA: Wegner’s granulomatosis
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c-ANCA
c-ANCA – Proteinase-3
p-ANCA - Myeloperoxidase
IMMUNOFLUORESCENT STAINING
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Giant Cell (Temporal) Arteritis
• Most common vasculitis
• Affects mainly the arteries in the head
– Temporal
– Vertebral
– Ophthalmic – can lead to blindness
• Pathogenesis – unknown
• T-cell mediated immunologic reaction
against elastin?
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Clinical features
• Age: 50 and above
• Gender: M:F: 1-1
• Symptoms, Vague: fever, weight loss,
fatigue, facial pain, headache
• Ocular symptoms: diplopia, progressive
hazy vision, loss of vision
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Giant cell arteritis
• Diagnosis: Temporal Artery Biopsy
– 2-3 cm segment
– multiple sections
– elastic trichrome stain
• Treatment: Steroids, Analgesics
• Prognosis: Good
• Elevated ESR (sed-rate)
• Association with polymyalgia rheumatica
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Takayasu arteritis
• Granulomatous vasculitis of
medium and large arteries
with obliteration of lumen
• Most commonly affects arch
of aorta with narrowing or
virtual obliteration of the
origins of great vessels
arising in the arch
• Can also involve pulmonary,
coronary, and renal arteries.
• Etiopathogenesis –
Unknown
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Clinical features
• Most common in females < 40 years
• Ocular changes: visual disturbances, retinal
hemorrhages, blindness
• Progressive diminution of upper limb pulses with
coldness or numbness of fingers - Pulseless
Disease”
• Low BP in upper limb
• Neurologic defects – dizziness, focal weakness
or complete hemiparesis
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Polyarteritis Nodosa (PAN)
• Systemic vasculitis
• Transmural necrotizing inflammation of
small or medium sized muscular arteries
• Typically involves renal and visceral
arteries and spares the pulmonary
circulation.
• Arterioles, capillaries, and venules are not
affected
• Associated with Hepatitis B antigen (30%)
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r
e
Remember
No glomerulonephritis
Pathguy..com
• Disease of
young adults
•Course may be
acute,
subacute, or
chronic and is
frequently
remittent.
•30% of
patients have
HBV antigen in
serum
Clinical features
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Morphology
• Gross - Distribution of lesions in descending order of
frequency
– Kidney, Heart, Liver, GIT
• Lesions have a predilection for branching points and
bifurcations
• Histologically
– Acute stage - Transmural inflammation, fibrinoid necrosis of the
inner half of the vessel wall.
– Later stages - inflammation is replaced by fibrous thickening
of the vessel wall. Risks of thrombus or infarction.
• All stages of activity may coexist in different vessels
or even within the same vessel – characteristic
feature
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Complications - PAN
• Weakening of arterial wall owing to
inflammatory process may cause
aneurysmal dilatation or localized rupture.
• Impairment of perfusion causing
ulcerations, infarcts, ischemic atrophy, or
hemorrhages in the areas supplied by
these vessels.
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Kawasaki syndrome
• Arteritis involving the large, medium, and
small arteries (often coronary arteries)
• Associated with mucocutaneous lymph
node syndrome
• Usually in young children and infants (80%
cases < 4 years)
• Epidemic in Japan
• Leading cause of acquired heart disease
in children in US (can lead to MI)
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Kawasaki disease
• Pathogenesis – Unknown
• Autoantibodies against endothelium, smooth
muscle cells, leading to acute vasculitis
• Clinical features –
– Fever
– Conjunctival and oral erythema
– Edema of the hands and feet
– Skin rash often with desquamation
– Enlargement of cervical lymph nodes
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Buerger disease
(Thromboangitis obliterans)
• Characterized by segmental, thrombosing, acute
and chronic inflammation of medium sized and
small arteries, characterized by microabcesses
• Mainly the tibial and radial arteries and sometimes
secondarily extending to veins and nerves of the
extremities (painful)
• Predisposing factors
– Cigarette smoking
– Hypersensitivity reaction to tobacco – direct endothelial
injury
– Genetic influence
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Wegener Granulomatosis
• Classic triad
1. Acute necrotizing granulomas of upper and lower respiratory
tract
2. Focal necrotizing or granulomatous vasculitis affecting small to
medium sized vessels, most prominent in lungs, and upper
airways but affecting other sites as well
3. Renal disease in the form of focal or necrotizing, often
crescentic glomerulitis
• Limited WG
– No renal involvement
• Males > females
• Average age of onset = 40 years
• 95% of the patients have c-ANCA
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Clinical features
• Persistent pneumonitis with bilateral
nodular and cavitary infiltrates
• Chronic sinusitis
• Mucosal ulceration of the nasopharynx
• Evidence of renal disease
• Untreated patients die within 1 year.
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Morphology
• Gross – ulcerative
lesions of the nose,
pharynx, palate
• Lungs - dispersed
focal necrotizing
granulomas
coalesce to
produce nodules
that may undergo
cavitations.
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Aneurysms
• Localized abnormal dilatation of a blood
vessel caused by a congenital or
acquired weakness in the media.
• Aneurysms can be classified based on
– Composition of wall
– Gross morphology
– Etiology
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Composition of the aneurysmal sac
True –
• Complete but attenuated vessel wall. The blood
remains within the confines of the circulatory
system.
• Atherosclerotic, syphilitic, and congenital
vascular aneurysm
False (pseudoaneurysm)
• is an extravascular hematoma that
communicates with the intravascular space.
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Etiology
• Atherosclerosis
• Syphilis
• Mycotic – infective.
• Vasculitis (PAN, Kawasaki’s disease)
• Congenital defect in media – Marfan’s
syndrome, Berry aneurysm
• Iatrogenic – Arteriovenous aneurysms for
chronic renal failure patients for dialysis
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Atherosclerotic aneurysms
• Most common site – abdominal aorta
• Abdominal aortic aneurysm - diameter is
increased at least 50%.
• Most frequent aneurysms, usually
developing after the age of 50 years.
• 6% after the age of 80 years
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Clinical course
• Many aneurysms are asymptomatic.
• Abdominal mass
• Occlusion of a branch vessel- renal, mesenteric
vertebral vessels.
• Embolism from atheroma or mural thrombus.
• Impingement on an adjacent structure
– compression of ureter or erosion of vertebrae.
• Rupture with massive or fatal hemorrhage.
• The risk of rupture - about 2% for a small
abdominal aortic aneurysm (<4 cm) to 25-40%
for aneurysms larger than 5 cm.
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Treatment
• Large aneurysms- surgically replaced by
prosthetic grafts.
• Timely surgery is critical; operative
mortality is about 5% for unruptured
aneurysms whereas emergency surgery
after rupture carries a mortality rate of
>50%.
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Syphilitic aneurysms
• Seen in the tertiary stage of the syphilis.
• Due to obliterative endarteritis of the vasa
vasorum of the aorta - Destruction of the
tunica media
• Leading to narrowing of the lumen of these
vessels which causes ischemic injury of
the aortic media followed by inflammation
and scarring.
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Clinical course
• Encroachment on the mediastinal structures by
enlarged heart (Cor bovinum)
– Respiratory difficulties.
– Difficulty in swallowing.
– Persistent cough due to pressure on recurrent laryngeal nerve
• Pain caused by erosion of the ribs or vertebrae.
• Valvular incompetence (aortic regurgitation) leading to
left ventricular hypertrophy, cardiac ischemia due to
obstruction to coronary ostia.
• Rupture of the aneurysm.
• Most common cause of death - heart failure due to
aortic regurgitation.
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Aortic dissection (dissecting
hematoma)
• Entry of blood in between and along the
laminar planes of media and its extension
along the length of the vessel.
• Often ruptures causing massive
hemorrhage
• Not usually associated with marked
dilatation of aorta
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Etiopathogenesis
• Most commonly men 40-60 years of age, in
whom hypertension is almost always present
(>90% of cases of dissection).
• Younger patients with abnormality of connective
tissue (Marfan’s syndrome).
• As a complication of
– arterial cannulation (e.g. during diagnostic
catheterization or cardiopulmonary bypass)
• During pregnancy - unknown reason.
• Can result from cystic medial necrosis (loss of
elastic tissue)
14
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Morphology
• Intimal tear - starting point
• Occurs most commonly in the ascending aorta,
1 or 2 cm above the aortic ring.
• The dissection separates the inner two thirds of
the aorta from the outer third.
• The dissection can extend proximally toward the
heart as well as distally along the aorta to
variable distances.
• Re-rupture into the lumen of the aorta - ‘double-
barreled’ aorta.
80
Double-barreled’ aorta.
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2 Types
• Type A - the more
common (and dangerous)
proximal lesions,
involving either the
ascending portion only or
both ascending and
descending aorta.
• Type B – distal lesions
not involving the
ascending part and
usually beginning distal to
subclavian artery
Type A Type B
82
Clinical features
• Sudden onset of excruciating (tearing)
pain, usually beginning in the anterior
chest, radiating to the back, and moving
downwards as the dissection progresses.
• Loss of one or more arterial pulses is
common
83
Complications
• Most common cause of death - rupture of the
dissection into any of the three major body
cavities (i.e., pericardial. Pleural, and peritoneal)
• Retrograde dissection into the aortic root leading
to disruption of aortic valvular apparatus.
• Compression of spinal arteries - Transverse
myelitis.
• Cardiac tamponade, aortic insufficiency, and
myocardial infarction can also occur.
84
Mycotic (infectious) aneurysms
• result from the weakening of the vessel
wall by a microbial infection.
• Common sites of involvement include the
aorta, cerebral vessels, and mesenteric,
renal, and splenic arteries.
15
85
Mycotic (infectious) aneurysms
• Mycotic aneurysms may originate –
– At the site of sticking of a dislodged septic
embolus within a vessel, usually as a
complication of infective endocarditis
– As an extension of adjacent suppurative
process like tuberculosis infection or a
bacterial abscess.
– By circulating organisms directly infecting the
arterial wall.
86
HEART
SGUSOM GRENADA (W.I.)
87
Weights & Measurements of an
adult heart
- Weight Weight Weight Weight
- 250-300g – males
- 200-250g - females)
- Wall thickness
- Right ventricle : 3-5 mm
- Left ventricle : 10-15 mm
- Cardiomegaly Cardiomegaly Cardiomegaly Cardiomegaly – increase in cardiac weight or size
- Cardiac hypertrophy – increased weight and ventricular
thickness
- Dilation – enlarged chamber size
88
Normal Histology
• The wall of the heart is composed of three layers
– Epicardium
– Myocardium
– Endocardium
• Heart is surrounded and enclosed by visceral and
parietal pericardium, separated by the pericardial
cavity.
• Pericardial cavity – contains 30-50 ml of fluid
- Acts as a shock absorber
89
VALVES
• 4 cardiac valves ( Mitral, Tricuspid, Aortic, and
Pulmonary valves)
• Maintain unidirectional blood flow
- Scanty blood supply – thin enough to be
nourished by diffusion from the heart’s blood
• Atrioventricular valves
– Mitral and Tricuspid
– The leaflets of these valves are held in place by the
chordae tendineae, which are contiguous with the
underlying ventricular wall.
• Semilunar valves
– Aortic and pulmonary valves – guard the aorta and
pulmonary arteries respectively.
– Three leaflets or cusps
90
BLOOD
SUPPLY
•Left Coronary A.
•L.A.Descending
•Left Circumflex
•Right Coronary A.
LCx
LAD
16
91
Blood supply
Functionally
- Right & left coronary arteries are end arteries
- Numerous interconnections – collateral
circulation – contains little blood in normal hearts
- Collaterals open up when one artery is severely
narrowed
• Most blood flow to the myocardium is during
diastole
92
Heart failure
(congestive heart failure)
• Is the inability of the heart, working at
normal or elevated filling pressure, to
pump enough blood to meet the metabolic
demands of the body.
93
Etiology
Systolic dysfunction – inability to contract properly
• MI
• Hypertension
• Volume overload – valvular regurgitation
• Cardiomyopathy
Diastolic dysfunction - Inability of the heart chamber
to relax/expand and fill sufficiently during diastole
• Massive ventricular hypertrophy
• Amyloidosis
• Constrictive pericarditis
94
CHF can also be categorized as
• Left-sided failure – left ventricle is the failing
chamber
– Systemic hypertension
– Mitral or aortic valve disease
– Ischemic heart disease
– Cardiomyopathy
• Right-sided failure
• Left heart failure
• Intrinsic disease of lung parenchyma/vasculature –
COPD, Pulmonary hypertension
95
Compensatory Mechanisms
- Adrenergic stimulation by endogenous
catecholamines
- Myocardial hypertrophy
- Concentric hypertrophy - hypertension
- Eccentric hypertrophy – valvular regurgitation
- Myocardial dilation - Frank Starlings law –
increased force of contraction with dilation
96
• Compensated heart failure – dilated
ventricle is able to maintain cardiac output
to meet the needs of the body
• Decompensated heart failure – failing
myocardium is no longer able to propel
sufficient blood to meet the needs of the
body, even at rest.
17
97
HEART
FAILURE
DECREASED DECREASED DECREASED DECREASED
CARDIAC OUTPUT CARDIAC OUTPUT CARDIAC OUTPUT CARDIAC OUTPUT
RENAL RENAL RENAL RENAL
HYPOPERFUSION HYPOPERFUSION HYPOPERFUSION HYPOPERFUSION
SODIUM & SODIUM & SODIUM & SODIUM &
WATER RETENTION WATER RETENTION WATER RETENTION WATER RETENTION
RENIN RENIN RENIN RENIN- -- -ANGIOTENSIN SYSTEM ANGIOTENSIN SYSTEM ANGIOTENSIN SYSTEM ANGIOTENSIN SYSTEM
EDEMA
PASSIVE CONGESTION PASSIVE CONGESTION PASSIVE CONGESTION PASSIVE CONGESTION
OF PULMONARY CIRCULATION OF PULMONARY CIRCULATION OF PULMONARY CIRCULATION OF PULMONARY CIRCULATION
PULMONARY ARTERIAL PULMONARY ARTERIAL PULMONARY ARTERIAL PULMONARY ARTERIAL
HYPERTENSION HYPERTENSION HYPERTENSION HYPERTENSION
RIGHT HEART FAILURE
SEVERE & SEVERE & SEVERE & SEVERE &
SUSTAINED SUSTAINED SUSTAINED SUSTAINED
SYSTEMIC VENOUS
CONGESTION
PULMONARY EDEMA PULMONARY EDEMA PULMONARY EDEMA PULMONARY EDEMA
FORWARD FAILURE FORWARD FAILURE FORWARD FAILURE FORWARD FAILURE BACKWARD FAILURE BACKWARD FAILURE BACKWARD FAILURE BACKWARD FAILURE
98
Pathological consequences
of congestive heart failure
99
Clinical features
• Left ventricular failure
– Dyspnea
– Orthopnea
– Paroxysmal nocturnal dyspnea
• Right ventricular failure
– Systemic venous congestion
• Distended neck veins
• Enlarged tender liver
– Soft tissue edema
100
Types of heart disease
• Five categories of disease account for
nearly all cardiac mortality
1. Ischemic heart disease (IHD)
2. Hypertensive heart disease (systemic and
pulmonary)
3. Valvular heart disease
4. Non-ischemic (primary) myocardial disease
5. Congenital heart disease
101
ISCHEMIC HEART DISEASE (IHD)
• Definition
–Generic term for imbalance
between myocardial need for and
supply of oxygenated blood
102
Epidemiology
• Leading cause of death for both men and
women in the US and other industrialized
nations
• Each year nearly half a million Americans
die of IHD.
• May affect any age, but most common in
older individuals
• Males > females until the ninth decade
18
103
IHD - syndromes
1. Various forms of angina pectoris (chest pain)
2. Acute myocardial infarction (MI)
3. Sudden cardiac death
4. Chronic ischemic heart disease with congestive
heart failure
• Acute coronary syndromes
– MI
– Unstable angina
– Sudden cardiac death
104
ETIOLOGY
• Atherosclerosis – 90% of cases
• Other causes of ischemia
– Anemia - hypoxemia
– Lowered systemic blood pressure - Shock
– Increased cardiac demand – hypertrophy,
exercise
– Vasculitis (Kawasaki, PAN)
– Aortic dissection
105
ETIOPATHOGENESIS
• Complex dynamic interaction between
the following factors
1. Fixed coronary obstruction
2. Acute plaque changes
3. Coronary intraluminal thrombosis
4. vasoconstriction
106
Role of Acute Plaque Changes
• Disruption of plaque – an inability of
plaque to with stand imposed mechanical
stresses
• Most often the initiating event
• Changes in plaque morphology include
– Hemorrhage
– Rupture or fissuring
– Erosion or ulceration
107
Vulnerable or Unstable Plaque
• Characterized by
– Moderately stenotic
plaque (50-75%)
– Thinner fibrous cap
– A core rich in lipid,
macrophages and T-
cells
– less evidence of
smooth muscle
proliferation
– Markedly eccentric
(not uniform around
the vessel
circumference)
METALLOPROTEINASES
T-cells activate
108
Role of Coronary Artery Thrombosis
• Plaque rupture, erosion or ulceration – exposure
of thrombogenic lipid and subendothelial
collagen
• Platelet aggregation, thrombin generation and
thrombus formation.
• If the vessel is completely occluded – MI
• Incomplete obstruction –
– Unstable angina or arrhythmias – sudden cardiac
death
– Embolization to distal branches - micro infarcts
19
109
Role of vasoconstriction
• Increases mechanical forces that can contrib-
ute to plaque rupture
• Stimulated by
– Locally released platelet contents – Thromboxane A2
– Impaired secretion of EDRF – Nitric oxide (NO)
relative to contracting factors (Endothelin)
– Increased adrenergic activity
– Smoking
110
• Four syndromes
– Angina pectoris (AP)
– Myocardial infarction (MI)
– Chronic ischemic heart disease
– Sudden cardiac death (SCD)
Consequences
111 112
ANGINA PECTORIS
• Intermittent chest pain or discomfort
due to transient, reversible myocar-
dial ischemia, not quite infarction
• No elevation in cardiac enzymes
• Three types
– Typical (stable) angina pectoris
– Prinzmetal (variant) angina
– Unstable angina pectoris
113
Responds to vasodilators Responds to vasodilators Relieved by rest, vasodilators
Harbinger of subsequent MI –
pre-infarction angina
Pain - crushing or squeezing
substernal, may radiate down
the left arm
Induced by disruption of
plaque with superimposed
thrombosis and possibly
vasospasm
Cause and mechanism not
clear
May be due to coronary artery
spasm
Due to critical stenosis -
reduction of coronary
perfusion due to fixed
stenosis
Associated with ST segment
elevation, indicative of
transmural ischemia
Associated with increased
demand -physical activity,
emotional excitement
Pain that occurs with
progressively increasing
frequency and is precipitated
with progressively less effort,
often occurs at rest, and
tends to be of more prolonged
duration.
Occurs at rest, awakens the
patient from sleep
Most common form
UNSTABLE (CRESCENDO) PRINZMETAL VARIANT
ANGINA
(~50-75% occlusion)
ANGINA
STABLE (TYPICAL) ANGINA
(~75% occlusion)
114
MYOCARDIAL INFARCTION
(HEART ATTACK)
• Indicates the development of an area of
myocardial necrosis caused by local ischemia
• About 1.5 million individuals in the US suffer an
acute MI annually, and approximately one third
of them die.
• At least half of them die before they reach the
hospital.
• Decreasing incidence since the early 1970’s
20
115
• Age
– Occurs at any age
– Incidence increases with increasing
age
• Gender
– Males 4 – 5 : 1 ages 45 – 54
– Males 2 : 1 up to age 80
– No difference > age 80
Epidemiology
116
MAJOR CONTRIBUTING FACTORS
• Hypercholesterolemia
• Smoking
• Hypertension
• Diabetes mellitus
CRP: Good marker for risk of MI
117
Pathogenesis
• Coronary artery occlusion – 90% of cases
– Disruption of plaque – 2/3
rd
are < 50% stenotic & 85%
have < 70% stenosis.
• Remaining 10% of cases
– Vasospasm – isolated, intense and relatively
prolonged with or without coronary atherosclerosis
– Emboli – from the left sided mural thrombus
– Unexplained –
• ? Disease of small intramural coronary vessels
• ? Hematological abnormalities like hemoglobinopathies
118
Myocardial response
• Coronary artery
obstruction – loss of
critical blood supply to
the myocardium
• Induces profound
functional,
biochemical, and
morphological
consequences
> 1 hr Microvascular
injury
20-40 min Irreversible cell
injury
ATP reduced
- To 50% of normal 10 min
- To 10% of normal 40 min
< 2 min Loss of
contractility
Seconds Onset of ATP
depletion
Time Feature
119
C CCO OOR RRO OON NNA AAR RRY YY C CCI IIR RRC CCU UUL LLA AAT TTI IIO OON NN A AAN NND DD T TTH HHE EE L LLO OOC CCA AAT TTI IIO OON NN O OOF FF I IIN NNF FF S SS A AAR RRC CCT TT
120
• Progression of
myocardial
necrosis after coronary
artery occlusion
• Begins in
subendocardial region
21
121
Morphology
• The essential sequence of events in MI is
– Coagulation necrosis followed by
– Inflammation, resorption of necrotic
myocardium followed by
– Formation of granulation tissue and finally
– Organization of granulation tissue to form a
collagen rich scar tissue
122
collagen cellularity Firm, grey; scarring complete 2-8 weeks
Active granulation tissue Red-gray depressed border 10-14 days
Early coagulation necrosis Dark Mottling (Occasional) 4-12 hr
LM FEATURES GROSS FEATURES TIME
Dense collagenous scar Scarring complete 2 months +
Well developed phagocytosis
Extensive macrophages
Maximum softening
(no myocytes/no collagen)
7-10 days
Macrophages appear
Breakdown of myofibers
Central softening (Yellow/tan)
Hyperemic border
3-7 days
Heavy neutrophilic infiltrate Mottling (Yellow/tan center) 1-3 days
Early neutrophil infiltrate
Coagulation necrosis,
Contraction bands
Dark Mottling 12-24 hr
Wavy fibers No change 1/2-4 hr
No change No change 0-30 min
123
• Contractile dysfunction – cardiogenic shock
• Arrhythmias
• Papillary muscle dysfunction
• External rupture of the infarct (3-7 days)
– Ventricular free wall
– Ventricular septum
• Mural thrombi
• Ventricular aneurysms (after fibrosis, 2+ months)
• Pericarditis
– Acute fibrinous or fibro hemorrhagic
– Autoimmune – Dresslers’ syndrome
COMPLICATIONS
124
Clinical features
• Severe, crushing, substernal chest pain,
which may radiate to neck, jaw, epigastrium,
shoulder, or left arm
• Levine’s sign (clenched fist over chest)
• Pain lasts several hours to days and not
significantly relieved by vasodilators
• Diaphoresis, dyspnea, rapid weake pulse
• Silent MI
– elderly patients
– underlying Diabetes mellitus/ Hypertension
125
Clinical course
• 25% sudden death (SCD) – vast majority of
deaths occurring before hospitalization
• Patients reaching hospital alive
– 10 – 20% uncomplicated course
– 80 – 90% complicated but not necessarily
fatal course
– Complicated course
• Cardiac arrhythmias 75 – 95%
• LVF with pulmonary edema 60%
• Cardiogenic shock 10%
• Rupture of myocardium 4 – 8 %
126
Diagnosis of MI
• “Myocardial infarction is diagnosed when
blood levels of sensitive and specific
biomarkers, such as cardiac troponin and
the MB fraction of creatine kinase (CK-
MB), are increased in the clinical setting of
acute ischemia”
JACC, vol 36, No. 3, 2000:959-69
22
127
Electrocardiographic abnormalities
ST segment
elevation
Q wave
Inversion of
T wave
128
Cardiac Injury Markers
• Creatine Kinase isoenzymes (CK-MB)
• Troponins (I and T)
• LD (lactate dehydrogenase, LDH)
• Myoglobin
129
Troponin I and T
• Troponins are most sensitive and specific
• Regulate calcium-mediated muscle contraction
• Normally not detectable in circulation
• Troponin I (TnI) commonly measured clinically
• Rise in 2-4 hours
• Peak at 48 hours
• Persists for 7-10 days
130
Creatine Kinase
• CK is a dimer composed of M and B
subunits: MM, MB, BB
• CK-MB: most specific for heart, trace
amount in skeletal muscle
• Rises within 2-4 hours of MI
• Peaks at 24 hours
• Disappears by 72 hours
131
Cardiac Injury Markers
• Early MI, TnI and CK-MB with similar sensitivity
• Troponin is most specific for cardiac injury
• Troponin STAYS elevated long after CK is gone
• Both elevate sooner in reperfused patients
• 2 days of unchanged TnI and CK-MB r/o AMI
132
Intervention
• Primary prevention
• Thrombolysis
• Angioplasty
• Coronary bypass graft (CABG)
23
133
Chronic ischemic heart disease
• Insidious onset of congestive heart failure
in patients who have past episodes of MI
or anginal attacks
• Cardiac decompensation owing to
exhaustion of the compensatory
hypertrophy of non- infarcted viable
myocardium or severe coronary
obstructive disease leading to diffuse
myocardial dysfunction
• Dilation of all 4 heart chambers (may
be difficult to distinguish from dilated
cardiomyopathy
134
Sudden Cardiac Death
• Unexpected death from cardiac causes
early (usually within 1 hour) after or
without the onset of symptoms
• Causes
– IHD – most common cause
– Mitral valve prolapse
– Aortic valve stenosis
– Dilated or hypertrophic cardiomyopathy
– Myocarditis
135
• Ultimate mechanism of SCD is a lethal
arrhythmia
• Morphology
– 80-90% of cases – critical stenosis of one or
more coronary arteries, high grade stenosis
associated with acute plaque disruption
– 10-20% - non atherosclerotic in origin
136
Hypertensive heart disease
• Presence of left ventricular hypertrophy in
an individual with a history of hypertension
and in whom other causes of hypertrophy
have been excluded
137
Pathogenesis
• Stimulus – sustained pressure overload
Growth factors
Local mechanical effects
Changes in genes controlling expression of actin, myosin
Hypertrophy
138
Morphology
• Concentric hypertrophy of left ventricle –
symmetric, circumferential pattern
• Long standing cases – right ventricular
hypertrophy and dilation
• Histologically – enlarged myocytes
containing large, hyperchromatic,
rectangular “box-car shaped nuclei
24
139
Clinical features
• Early stages – asymptomatic
• Angina pectoris
• Signs and symptoms of heart failure with
progression
• Cerebrovascular accidents (stroke)
• Sudden cardiac death
140
Pulmonary heart Disease
(Cor Pulmonale)
• Disease of right sided cardiac chambers
secondary to pulmonary parenchymal or
pulmonary vascular diseases
• Excluded from this definition are
– Pulmonary hypertension due to left heart
failure
– Pulmonary hypertension due to congenital
heart disease
141
Acute cor pulmonale
• Pulmonary embolism causing sudden
increase in burden on the right heart
• Right ventricle is dilated but no
hypertrophy
• Possible cause - Saddle embolus
142
Valvular Heart Disease
• Congenital
• Acquired
• Valvular involvement by disease causes
– Stenosis – failure of a valve to open completely,
thereby impeding forward flow
– Incompetence, regurgitation, or insufficiency – failure
of a valve to close completely, thereby allowing
reversed flow
• Abnormalities of flow often produce abnormal
heart sounds known as murmurs
143 Myocarditis
Marfan syndrome Dilated cardiomyopathy
Syphilitic aortitis Infective endocarditis
Degenerative aortic dilation –
hypertension
Rheumatic heart disease
Rheumatic heart disease Myxomatous degeneration (mitral
valve prolapse
AORTIC REGURGITATION MITRAL REGURGITATION
Calcification of congenitally deformed
valve
Senile calcific aortic stenosis
Rheumatic heart disease Rheumatic heart disease
AORTIC STENOSIS MITRAL STENOSIS
Aortic valve disease Mitral valve disease
144
Rheumatic fever
• Acute, immunologically mediated, multisystem
inflammatory disease that follows an episode of
‘rheumatogenic’ group A streptococcal
pharyngitis after an interval of few weeks.
• Occurs in only about 3% of patients with group A
streptococcal pharyngitis
• Mainly a disease of third world countries and
crowded, economically depressed areas of
western world
25
145
Pathogenesis
• Exact pathogenesis is not known
• Hypersensitivity reaction induced by group A
streptococci
• Antibodies directed against the M proteins of
group A streptococci cross react with normal
proteins present in heart, joints, and other
tissues
• Evidence in support of this hypothesis
– Streptococci are absent from the lesions
– Symptoms do not develop until 2-3 weeks after
infection
146
T-cells activated
by streptococcal
antigens
B-cells produce anti-streptococcal
antibodies
Antibodies and T-cells cross react with
Cardiac sarcolemma and valvular glycoproteins
147
Morphology- Acute rheumatic fever
• Acute rheumatic carditis – inflammatory changes
in all three layers of the heart – Pancarditis
• Myocarditis - Hallmark is the presence of Aschoff
bodies within connective tissue of the heart.
• Endocarditis – edematous and thickened valves
with foci of fibrinoid necrosis
• Pericarditis – fibrinous pericarditis
148
• Arthritis – chronic inflammatory infiltrate
and edema in the joints and periarticular
soft tissues.
– arthritis is self limited and does not cause
chronic deformities
• Erythema marginatum – maculopapular
rash
• Skin nodules – contain focal lesions that
are essentially large Aschoff bodies
149
Chronic rheumatic heart disease
• Chronic Mitral valvulitis
– Conspicuous irregular thickening and calcification of
the leaflets, often with fusion of the commissures
and the chordae tendineae
• Chronic aortic valvulitis – cusps are thickened, firm,
and adherent to each other – valve orifice is reduced to
rigid, triangular channel
150
Clinical features
• Acute rheumatic fever
– Occurs anywhere from 10 days to 6 weeks
after an episode of group A streptococcal
pharyngitis
– Peak incidence – 5-15 years
– Arthritis – migratory, large joints
– Carditis – pericardial friction rub, weak heart
sounds, congestive heart failure
– Stenosis of mitral valve, most common and
characteristic complication
26
151
Clinical features
• Chronic rheumatic carditis
– Valvulitis - murmurs
– Cardiac hypertrophy and dilation
– Congestive heart failure
– Arrhythmias
– Infective endocarditis
152
Diagnosis
• Jones criteria
– Major manifestations (ACCNE)
• Migratory polyarthritis of large joints
• Pancarditis
• Sydenham chorea – involuntary, purposeless, rapid movements
• Subcutaneous nodules
• Erythema marginatum of skin
– Minor manifestations – Fever, Arthralgia, and elevated ESR
• Presence of either of the 2 major manifestations or 1
major and 2 minor manifestations
+
Evidence of preceding streptococcal infection in the form
of elevated serum ASO titers or positive streptococcal
throat culture
153
Calcific aortic stenosis
• Narrowing of the aortic valve lumen as a
result of deposition of calcium in the cusps
and the valve ring.
• It can occur in
– Elderly patients as a degenerative process.
90% of the patients are > 65 years of age
– Congenital bicuspid aortic valve (40-65 years)
– Aortic valve scarred as a result of rheumatic
fever (5-15 years)
154
Mitral valve prolapse
• One of the most common cardiac disorder
occurring in 3-5% of the general adult
population.
• Most cases are discovered between the
ages of 20 and 40 years
• More common in females (7x)
• May arise as a complication of Marfan
syndrome
155
Morphology
• Soft and enlarged mitral valve cusps
– ballooning of the valve leaflets into the left
atrium during systole
• The chordae tendineae which are often
elongated and fragile, may rupture in
severe cases
• The mitral annulus may be dilated
156
Clinical features
• Most patients are asymptomatic
• Palpitations
• Fatigue or atypical chest pain
• Mid-systolic click (when valve prolapses)
• Severe complications in about 3 % of cases
– Mitral regurgitation and congestive heart
failure
– Infective endocarditis
– Ventricular arrhythmias
27
157
Infective endocarditis
• Infection of the cardiac valves or mural
surface of the endocardium resulting in the
formation of adherent, bulky mass of
thrombotic debris and organisms – termed
vegetations
158
Classification
• Clinical
– Acute endocarditis – destructive fulminant infection,
frequently of a previously normal heart valve with a
highly virulent organism, that leads to death within
days to weeks of more than 50% of patients despite
antibiotics and surgery.
– Sub acute endocarditis – organisms of low virulence
cause infection in a previously abnormal heart,
particularly on deformed valves. Most patients
recover with appropriate therapy.
• Etiological – Bacterial, Fungal, Rickettsial
159
Predisposing factors
• Preexisting cardiac abnormality
– Mitral valve prolapse – most common factor
– Chronic rheumatic valvulitis
– Degenerative calcific aortic stenosis
• Prosthetic heart valves – 10-20% of cases
• Intravenous drug abuse (Tricuspid valve!)
• Transient bacteremia – dental procedures,
urinary catheterization, endoscopy.
160
Pathogenesis
• Hemodynamic factors
– Abnormal blood flow across a damaged valve
– Endothelial injury
– Focal deposition of platelets and fibrin
• Adherence properties of microorganisms
– Fibronectin
– Adhesion factors - polysaccharides
161
Causative organisms
• Native valve
– Most common (50-60%) – Streptococcus viridans ; deformed
valves
– Staph. aureus (10-20%) – previously healthy or deformed valves
– HACEK GROUP – Haemophilus, Actinobacillus,
Cardiobacterium, Eikenella, Kingella
• Prosthetic valve
– Staph. Epidermidis
– Gram negative bacilli
– fungi
• Intravenous drug abuse
– Staph. Aureus – most common
– Streptococci
– Gram negative bacilli
– Fungi
162
Morphology
• Mitral and aortic most commonly involved
• Tricuspid valve – I.V. drug abuse
• Acute bacterial endocarditis
• Gross
– Bulky, friable vegetations that may obstruct the valve
orifice
– Rapid destruction of the valves – rupture of the
leaflets, chordae tendineae, papillary muscles
– Ring abscess – abscesses in perivalvular
myocardium
• Microscopy
– Large number of organisms mixed with fibrin and
blood cells
– Minimal inflammatory response
28
163
Subacute endocarditis
• Gross
– Vegetations are less friable
– Associated with less valve destruction
– Ring abscesses uncommon
• Microscopy
– Presence of granulation tissue
– Fibrosis, calcification
– Chronic inflammatory infiltrate
164
Clinical features
• Acute bacterial endocarditis
– High grade fever with chills
– Features of septicemia
• Subacute bacterial endocarditis
– Low grade fever; malaise
– Weight loss
• Changing cardiac murmurs
• Splenomegaly
• Clubbing of fingers
165
Glomerulonephritis
Immune complex formation Release of bacterial
antigen
CNS emboli and stroke,
myocardial infarction, splenic or
kidney infarcts, mycotic aneurysm
Splinter hemorrhages→nails
Janeway lesions (palms/soles)
Roth spots→retinal hemorrhage
Osler nodes→subQ nodules in
pulp of digits
Peripheral emboli
Fragmentation
Congestive heart failure
Heart blocks (1°, 2°or 3°)
Valvular insufficiency
AV conduction
abnormalities
Tissue destruction
Joint, bone, organ disease Seeding of distant sites
Constitutional symptoms Cytokine release
Persistent bacteremia
Host Consequence Complication
Consequence of
Vegetation
166
Diagnosis
• Repeated blood cultures for both aerobic
and anaerobic organisms
• Treatment
– Difficult infection to eradicate – avascular
nature of the valves
– Antibacterial therapy
167
Nonbacterial thrombotic
Endocarditis
• Characterized by the presence of sterile
vegetations
• Pathogenesis – incompletely understood
– Endothelial abnormalities
– Hypercoagulable states
– Adenocarcinomas (pancreatic & other abdominal)
• Usually asymptomatic
• Embolization and infective endocarditis –
possible complications
168
Libman- Sacks endocarditis
• Characterized by presence of sterile
vegetations on the cardiac valves in
patients of SLE
• No special predilection for the lines of valve
closure (vegetations on both sides)
• Vegetations comprised of fibrin & WBC’s
29
169
Myocarditis
• Generalized inflammation of the myocar-
dium associated with necrosis and
degeneration of myocytes.
• The inflammatory process plays a primary
role in the development of myocardial
injury.
170
Major causes of Myocarditis
Transplant rejection Bacteria – c. diphtheriae
Helminthes – trichinosis
Protozoa – chagas
disease, toxoplasmosis
Drugs – sulfonamides Fungi – aspergillus,
candida
SLE Rickettsia – typhus fever
Giant cell myocarditis Post streptococcal –
rheumatic fever
Chlamydia- c. psittaci
Sarcoidosis Post viral Viral – coxsackievirus,
CMV, ECHO, HIV
Unknown Immune-
mediated
Infections
171
Viral Myocarditis
• Most common cause of myocarditis in US
• Coxsackie A and B and other enter-
oviruses account for most cases
• Pathogenesis –
– Direct viral cytotoxicity
– Cell mediated immune reactions against
infected myocytes
– Diffuse lymphocyte infiltrate with patchy
necrosis
infected myocyte
172
Clinical features
• Most cases – self limiting disease
• Flu like symptoms – viral myocarditis
• Complications
– Acute heart failure – giant cell myocarditis
– Chronic congestive heart failure – viral myocarditis
– Arrhythmias – ventricular arrhythmias most
dangerous
173
Cardiomyopathy
• Primary disease of the myocardium ex-
cluding myocardial diseases caused by
ischemia, hypertension, valvular lesions,
congenital anomalies, or inflammatory
disorders.
• Three categories
– Dilated cardiomyopathy
– Hypertrophic cardiomyopathy
– Restrictive cardiomyopathy
174
Dilated Cardiomyopathy
• Most common type of cardiomyopathy
(90%)
• Characterized by
– Progressive cardiac hypertrophy
– Dilation (of all 4 chambers)
– Contractile (systolic) dysfunction
30
175
Etiopathogenesis
• Idiopathic – unknown, majority of cases
• Genetic mutations – 20-30% of cases
– Dystrophin gene on X- chromosome
– Mitochondrial genes – abnormal oxidative phosphorylation
• Alcohol – direct cytotoxicity
• Viral myocarditis
• Nutritional disturbances – thiamine deficiency,
chronic anemia,
• Pregnancy associated - peripartum cardiomyopathy
– pregnancy associated hypertension (reversible)
– Nutritional disturbances
176
Clinical features
• Fundamental defect is ineffective
contraction
• Ejection fraction is < 25% (normal 50-
65%)
• 20-60 year – most common
• Progressive congestive heart failure
refractory to therapy
• Death usually occurs due to progressive
cardiac failure or arrhythmias
177
Hypertrophic cardiomyopathy
• Characterized by
– Myocardial hypertrophy
– Abnormal diastolic filling
– Intermittent left ventricular outflow obstruction
in one third of cases
• Primarily a diastolic rather than systolic
dysfunction
178
Pathogenesis
• Familial autosomal dominant condition –
50% of cases.
• Occurs due to genetic defect in any of the
following genes
– β-myosin heavy chain – most common
– Cardiac troponin T
– α-tropomyosin
– Myosin-binding protein C
179
Clinical features
• Exertional dyspnea
• Angina or MI
• Sudden death – due to arrhythmias
(especially in atheletes)
180
Restrictive Cardiomyopathy
(Decreased compliance)
• Least common type of cardiomyopathy
• Etiology
– Endomyocardial fibrosis – most common
cause
– Loffler’s syndrome
– Radiation fibrosis
– Amyloidosis
– Hemochromatosis
– Metastatic tumors
– Sarcoidosis
31
181
Congenital Heart Disease
• Abnormalities of the heart or great vessels
that are present from birth
• Most common form of heart disease
among children
• 1% of live births, higher in premature
infants and stillborns
• Incidence increased due to increased
diagnostic sensitivity
182
Etiology and pathogenesis
• Only 10% well-defined environmental or genetic
influence
• Trisomy 13,15,18,21, and Turner syndrome
– Trisomy 21 the most common known genetic cause
• Defect in sibling or parent the greatest risk factor
• Environmental factors (congenital rubella)
183
Frequency of cardiac
malformations
1% Tricuspid atresia
1% Truncus Arteriosus
4% Transposition of the Great Vessels
5% Tetralogy of Fallot
4% Aortic stenosis
5% Coarctation of the Aorta
8% Pulmonary Stenosis
10% Atrial Septal Defect
7% Patent Ductus Arteriosus
42% Ventricular Septal Defect
% of Congenital
Heart Disease
Malformation
184
Malformation categories
• Based on flow of blood
– Left-to-right shunt
– Right-to-left shunt
– Obstruction
• Based on cyanosis
– Cyanotic from birth
– Cyanotic later in life
– Not cyanotic
185
Normal
186
Fetal circulation
32
187
Right-to-left Shunt:
Cyanotic heart defects
• At birth: The T’s (Tetralogy of Fallot,
Truncus Arteriosus, Tricuspid Atresia,
Total Anomalous Pulmonary Venous
Connection, Transposition of the Great
Vessels)
• After birth, when right-sided pressures
increase: Atrial Septal Defect, Ventricular
Septal Defect, Patent Ductus Arteriosus
188
Tetralogy of Fallot
• Most common form of cyanotic congenital
heart disease
• The four features of tetralogy are
– Ventricular septal defect
– Pulmonary stenosis
– overriding aorta
– right ventricular hypertrophy
189 190
Clinical features
• Usually present by 6 months
• Dyspnea on exertion, cyanosis
• Polycythemia – cerebral thrombosis
• Infective endocarditis
• Pulmonary vasculature decreased
• Associated with Down’s Syndrome
191
Transposition of the Great Arteries
• Aorta off RV and
Pulmonary artery off
LV
• AV connections
normal
• Incompatible with
post natal life, unless
a shunt (VSD or PDA)
is present
192
Truncus Arteriosus
• Failure of partitioning of embryologic
truncus into aorta and pulmonary artery
• Single great artery gets blood from both
ventricles
• Underlying VSD
• Blood from both ventricles mixes
• Cyanotic
33
193
Truncus Arteriosus
194
Left-to right shunts: The D’s
• Atrial Septal Defect
• Ventricular Septal Defect
• Patent Ductus Arteriosus
195
Remember…
D’s are red (acyanotic, left-to-
right shunt) and T’s are blue
(cyanotic, right-to-left shunt).
196
Ostium secundum
Septum primum
Membranous
I.V. septum
Muscular I.V.
Septum
197
Ventricular Septal Defect
• Most common congenital heart lesion
• Associated with Trisomy 21 (DS), 13, 18
• Most commonly (90%) – membranous
• Most VSDs close spontaneously in childhood
• Clinical features: Pulmonary hypertension; CHF,
pansystolic murmur,
• Shunt reversal leads to cyanosis -
EISENMENGER COMPLEX
198
Atrial Septal Defect
• 10% of CHD
• Age at presentation variable, may be
asymptomatic into adult
• Most common congenital cardiac
malformation diagnosed in adults
• Pulmonary vascularity increased if significant
left-to-right shunt
34
199
Three types Three types Three types Three types – –– –
75% Ostium secundum 75% Ostium secundum 75% Ostium secundum 75% Ostium secundum
15% Ostium primum 15% Ostium primum 15% Ostium primum 15% Ostium primum
10% Sinus venosus 10% Sinus venosus 10% Sinus venosus 10% Sinus venosus
200
Patent Ductus Arteriosus
• 7% of cardiac malformations
• 90% isolated anomaly
• Females more common than males
• Continuous, “machinery-like” murmur
• May need to keep open with prostaglandin
E if associated with other malformations
• Shunt may reverse leading to cyanosis
201
PDA Pathology
• Connect left pulmonary artery to aortic
arch
• Closes with high oxygen tension
• Higher incidence in maternal rubella
infection
• Associated with polycythemia
202
Patent Ductus Arteriosus
203
Obstructive Congenital Anomalies
• Coarctation of the Aorta
• Pulmonary Stenosis and Atresia
• Aortic Stenosis and Atresia (Hypoplastic
Left Heart Syndrome)
204
Coarctation of the Aorta
• Narrowed aortic lumen
• Associated with Turner’s Syndrome
• 50% cases – isolated cardiac anomaly
• Remaining cases – associated with PDA,
VSD, ASD
• Two types
– Preductal (infantile)
– Postductal (adult)
35
205
PATHOGENESIS
206
Clinical features
• Preductal - Presents in infancy as
– Congestive heart failure
– Selective cyanosis of lower extremities
– Femoral pulses are weaker than those of the upper
extremities
• Postductal –presents in older children and adults
– no selective cyanosis is seen
– Hypertension of the upper extremities
– Blood pressure is low and pulses are weak in lower
extremities
– Notching of ribs due to collaterals
– Intermittent claudication – arterial insufficiency
207
TUMORS OF THE HEART
• Primary tumors are rare
• Most common are metastatic neoplasms
• Clinical presentation –
– Sudden onset of severe, rapidly progressive
heart failure without apparent cause and/or
arrhythmia
• Silent till impair function
208
Cardiac Myxomas
• Most common primary tumor
• Female preponderance
• Age 30 – 60 years
• Often calcify and can, at times, be
seen on X- ray
209
Morphology
• Gross – lobulated pedunculated mass
• Most common location - Left atrium
• Histologically – multinucleated
stellate cells suspended in an
edematous mucopolysaccharide rich
stroma
210
Clinical features
• Most are asymptomatic
• Some may fragment and embolize
• Ball-valve obstruction of atrioventricular
valve – syncopal episodes, sudden death
• Associated with diastolic murmur
36
211
Secondary Tumors
• Direct extension of lung cancer
• Breast
• Lymphoma
• Malignant melanoma
212
Pericardial diseases
• Effusions -
• Serous
– Congestive heart failure
– Hypoalbuminemia
• Serosanguineous
– Trauma
– malignancy
• Chylous – mediastinal lymphatic obstruction
• Hemopericardium – cardiac tamponade
– Ruptured aortic aneurysm or myocardial infarct
– Penetrating traumatic injury
213
Pericarditis
• Primary – uncommon; usually infectious in
origin; virus most commonly
• Secondary – acute MI, cardiac surgery,
radiation, rheumatic fever, SLE,
Dressler’s Syndrome
• Uremia – most common systemic disorder
associated with pericarditis
214
Clinical features
• Chest pain; worsens on reclining
• High-pitched friction rub
• Cardiac tamponade
– Faint distant heart sounds
– Distended neck veins
– Declining cardiac output
– Shock
215
Morphology
• Acute pericarditis – fibrinous pericarditis
• Chronic pericarditis
– Delicate adhesions to dense, fibrotic scars
that obliterate the pericardial space
– Extreme cases – heart is completely encased
with dense scar tissue; can not expand –
constrictive pericarditis

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