Transcript By Dr. Sufia Hussein

Cardiovascular System
Dr. Sufia Husain
Ischemic Heart Disease
(Coronary Heart Disease)
• A group of closely related syndromes caused by
an imbalance between the myocardial oxygen
demand and blood supply.
– Angina pectoris (chest pain).
– Acute myocardial infarction.
– Sudden cardiac death.
– Chronic ischemic heart disease with congestive heart
failure.
Ischemic Heart Disease: Epidemiology(coronary atherosclerosis)
 Peak incidence: 60y for males and 70y for females.
 Men are more affected than women until the ninth
decade.
 Contributing factors:
◦ Hypertension.
◦ Diabetes mellitus.
◦ Smoking.
◦ High levels of LDL.
◦ Genetic factors (direct or indirect).
◦ Lack of exercise.
Pathogenesis of Ischemic Heart Disease
• 1) Role of Critical stenosis or obstruction:
(>=75% of the lumen of one or more coronary
arteries by atherosclerotic plaque).
Pathogenesis of Ischemic Heart Disease
2) Role of Acute Plaque Change:
• In most patients the myocardial ischemia
underlying unstable angina, acute MI, and (in
many cases) sudden cardiac death is
precipitated by abrupt plaque change
followed by thrombosis .
Pathogenesis of Ischemic Heart Disease
• Most often, the initiating event is disruption of
previously only partially stenosing plaques with any
of the following:
• Rupture/fissuring, exposing the highly thrombogenic
plaque constituents
• Erosion/ulceration, exposing the thrombogenic
subendothelial basement membrane to blood
• Hemorrhage into the atheroma, expanding its
volume.
Pathogenesis of Ischemic Heart Disease
3) Role of Coronary Thrombus:
 In acute transmural MI thrombus superimposed on a
disrupted but previously only partially stenotic
plaque converts it to a total occlusion. In unstable
angina, acute subendocardial infarction, or sudden
cardiac death, the extent of luminal obstruction by
thrombosis is usually incomplete .
 Thrombus in coronary artery can also embolize.
Pathogenesis of Ischemic Heart Disease
4) Role of Vasoconstriction:
• Vasoconstriction compromises lumen size,
and, by increasing the local mechanical forces,
can potentiate plaque disruption.
Pathogenesis of Ischemic Heart Disease
5) Role of Inflammation:
 Inflammatory processes play important roles at all
stages of atherosclerosis. Entry of leukocytes into the
wall is a consequence of the release of chemokines
by endothelial cells, and the increased expression of
adhesion proteins in these cells. At later stages of
atherosclerosis, destabilization and rupture of the
plaque may involve the secretion of
metalloproteinases by macrophages. These enzymes
weaken the plaque by digesting collagen at the
fibrous cap.
A. Plaque rupture without superimposed thrombus in a patient who
died suddenly.
B. Acute coronary thrombosis superimposed on an atherosclerotic
plaque with focal disruption of the fibrous cap, triggering fatal
myocardial infarction.
C. Massive plaque rupture with superimposed thrombus, also
triggering a fatal myocardial infarction (special stain highlighting
fibrin in red). In both
Ischemic Heart Disease: Pathogenesis
Vascular Diseases
Slide 12.1
ENDOTHELIAL CELLS
• ECs comprise the single cell-thick, continuous
lining of the entire cardiovascular system,
collectively called the endothelium.
Endothelial structural and functional integrity
is fundamental to the maintenance of vessel
wall homeostasis and normal circulatory
function.
Slide 12.3
Smooth muscle cells
• SMCs are predominant cellular element of the vascular media
• SMCs are responsible for vasoconstriction and dilation in
response to normal or pharmacologic stimuli.
• They also synthesize collagen, elastin, and proteoglycans; and
elaborate growth factors and cytokines. They migrate to the
intima and proliferate following vascular injury.
• Thus, SMCs are important elements of both normal vascular
repair and pathologic processes such as atherosclerosis.
Smooth muscle cells
• Vascular injury ( endothelial
injury/dysfunction) stimulates SMC growth.
Reconstitution of the damaged vascular wall is
a physiologic healing response that includes
the formation of a neointima, in which SMCs
(1) migrate from the media to the intima, (2)
multiply as intimal SMCs, and (3) synthesize
and deposit ECM
Smooth muscle cells
• During the healing response, SMCs undergo changes
that resemble dedifferentiation. In the intima they
lose the capacity to contract and gain the capacity to
divide.
• Intimal SMCs may return to a nonproliferative state
when either the overlying endothelial layer is reestablished following acute injury or the chronic
stimulation ceases.
Arteriosclerosis
Arteriosclerosis (literally, "hardening of the
arteries") is a generic term for thickening and
loss of elasticity of arterial walls. Three
patterns of arteriosclerosis are recognized;
they vary in pathophysiology and clinical and
pathological consequences.
1)Atherosclerosis, the most frequent and
important pattern
Arteriosclerosis
2)Mönckeberg medial calcific sclerosis is characterized
by calcific deposits in muscular arteries in persons
older than age 50. They do not encroach on the
vessel lumen.
3)Arteriolosclerosis affects small arteries and
arterioles. There are two anatomic variants, hyaline
and hyperplastic, both associated with thickening of
vessel walls with luminal narrowing that may cause
ischemic injury. Most often associated with
hypertension and diabetes mellitus.
Atherosclerosis
• Atherosclerosis is characterized by intimal
lesions called atheromas, or atheromatous or
fibrofatty plaques, which protrude into and
obstruct vascular lumens and weaken the
underlying media. They may lead to serious
complications
Atherosclerosis: Morphology
 Fatty streaks are the earliest lesion of
atherosclerosis. They are composed of lipid-filled
foam cells. They are not significantly raised and thus
do not cause any disturbance in blood flow. Fatty
streaks begin as multiple yellow, flat spots less than 1
mm in diameter that coalesce into elongated streaks,
1 cm long or longer. They contain T lymphocytes and
extracellular lipid in smaller amounts than in
plaques.
Fatty streak—a collection of foam cells in the intima.
A. Aorta with fatty streaks ( arrows), associated largely with the ostia of branch vessels.
B. Close-up photograph of fatty streaks from the aorta of an experimental hypercholesterolemic rabbit
shown after staining with Sudan red, a lipid-soluble dye, again illustrating the relationship of the lesions to
the two-branch vessel ostia.
C. Photomicrograph of fatty streak in an experimental hypercholesterolemic rabbit, demonstrating intimal
macrophage-derived foam cells ( arrow).
Slide 12.9
Morphology
• The key processes in atherosclerosis are
intimal thickening and lipid accumulation. An
atheroma or atheromatous plaque consists of
a raised focal lesion initiating within the
intima, having a soft, yellow, grumous core of
lipid (mainly cholesterol and cholesterol
esters), covered by a firm, white fibrous cap.
Morphology
• The atheromatous plaques appear white to
whitish yellow and impinge on the lumen of
the artery. They vary in size from
approximately 0.3 to 1.5 cm in diameter but
sometimes coalesce to form larger masses.
Atherosclerotic lesions usually involve only a
partial circumference of the arterial wall
("eccentric" lesions) and are patchy and
variable along the vessel length.
Atherosclerosis: Morphology
• The most heavily involved vessels are the
abdominal aorta then coronary arteries, the
popliteal arteries, the internal carotid arteries,
and the vessels of the circle of Willis.
Atherosclerosis: Morphology
Atherosclerotic plaques have three principal
components:
• (1) cells, including SMCs, macrophages, and other
leukocytes
• (2) ECM, including collagen, elastic fibers, and
proteoglycans
• (3) intracellular and extracellular lipid . These
components occur in varying proportions.
Atherosclerosis: Morphology
• Typically, the superficial fibrous cap is composed of
SMCs and relatively dense ECM. Beneath and to the
side of the cap (the "shoulder") is a cellular area
consisting of macrophages, SMCs, and T
lymphocytes.
• Deep to the fibrous cap is a necrotic core, containing
a disorganized mass of lipid (primarily cholesterol
and cholesterol esters), cholesterol clefts, debris
from dead cells, foam cells, fibrin, variably organized
thrombus, and other plasma proteins.
Atherosclerosis: Morphology
• Foam cells are large, lipid-laden cells that derive
predominantly from blood monocytes (tissue
macrophages), but SMCs can also imbibe lipid to
become foam cells.
• Around the periphery of the lesions, there is usually
evidence of neovascularization (proliferating small
blood vessels). Typical atheromas contain relatively
abundant lipid.
• Atheromas often undergo calcification.
Major components of well-developed atheromatous plaque:
fibrous cap composed of proliferating smooth muscle cells, macrophages,
lymphocytes, foam cells, and extracellular matrix. The necrotic core consists
of cellular debris, extracellular lipid with cholesterol crystals, and foamy
macrophages.
Slide 12.6
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 and complicated lesions.
Slide 12.7
Histologic features of atheromatous plaque in the coronary artery.
A. Overall architecture demonstrating a fibrous cap (F) and a central lipid core (C) with typical cholesterol clefts. The
lumen (L) has been moderately narrowed. Note the plaque-free segment of the wall ( arrow). In this section, collagen
has been stained blue (Masson trichrome stain).
B. Higher-power photograph of a section of 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).
C. Higher-magnification photomicrograph at the junction of the fibrous cap and core showing scattered inflammatory
cells, calcification ( broad arrow), and neovascularization ( small arrows).
Slide 12.8
American Heart Association classification of human atherosclerotic lesions from the fatty dot (type I) to the
complicated type VI lesion. The diagram also includes growth mechanisms and clinical correlations.
Slide 12.11
COMPLICATIONS
The advanced lesion of atherosclerosis is at risk for
the following pathological changes that have clinical
significance:
1) Focal rupture, ulceration, or erosion of the luminal
surface of atheromatous plaques may result in
exposure of highly thrombogenic substances that
induce thrombus formation or discharge of debris
into the bloodstream, producing microemboli
composed of lesion contents (cholesterol emboli or
atheroemboli).
COMPLICATIONS
2) Hemorrhage into a plaque, especially in the
coronary arteries, may be initiated by
rupture of either the overlying fibrous cap or
the thin-walled capillaries that vascularize
the plaque. A contained hematoma may
expand the plaque or induce plaque rupture.
COMPLICATIONS
3)Superimposed thrombosis, the most feared
complication, usually occurs on disrupted
lesions (those with rupture, ulceration,
erosion, or hemorrhage) and may partially or
completely occlude the lumen. Thrombi may
heal and become incorporated into and
thereby enlarge the intimal plaque.
4)Aneurysmal dilation may result from ATHinduced atrophy of the underlying media, with
loss of elastic tissue, causing weakness and
potential rupture
5) Calcifications.
Natural history of atherosclerosis
Slide 12.5
Risk Factors for Atherosclerosis
Major
Nonmodifiable
• Increasing age
• Male gender
• Family history
• Genetic abnormalities
PotentiallyControllable
• Hyperlipidemia
• Hypertension
• Cigarette smoking
• Diabetes
Risk Factors for Atherosclerosis
Lesser, Uncertain, or Nonquantitated
• Obesity
• Physical inactivity
• Stress ("type A" personality)
• Postmenopausal estrogen deficiency
• High carbohydrate intake
• Alcohol
• Lipoprotein Lp(a)
• Hardened (trans)unsaturated fat intake
• Chlamydia pneumoniae
PATHOGENESIS: response to injury
hypothesis
• This concept, called the response to injury
hypothesis, considers atherosclerosis to be a
chronic inflammatory response of the arterial
wall initiated by injury to the endothelium.
Moreover, lesion progression is sustained by
interaction between modified lipoproteins,
monocyte-derived macrophages, T
lymphocytes, and the normal cellular
constituents of the arterial wall.
Processes in the response to injury hypothesis.
1, Normal.
Slide 12.13
2, Endothelial injury with adhesion of monocytes and platelets (the
latter to denuded endothelium).
Slide 12.14
3, Migration of monocytes (from the lumen) and smooth muscle
cells (from the media) into the intima.
Slide 12.15
4, Smooth muscle cell proliferation in the intima.
Slide 12.16
5, Well-developed plaque.
Slide 12.17
Slide 12.18
PATHOGENESIS: response to injury
hypothesis
Central to this thesis are the following:
• Accumulation of lipoproteins, mainly LDL, with
its high cholesterol content, in the vessel wall
• Chronic endothelial injury, usually subtle,
yielding increased permeability, leukocyte
adhesion, and thrombotic potential.
PATHOGENESIS: response to injury
hypothesis
• 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
• Adhesion of platelets
• Release of factors from activated platelets,
macrophages, or vascular cells that cause migration
of SMCs from media into the intima
PATHOGENESIS: response to injury
hypothesis
• Proliferation of smooth muscle cells in the
intima, and elaboration of extracellular matrix,
leading to the accumulation of collagen and
proteoglycans
• Enhanced accumulation of lipids both within
cells (macrophages and SMCs) and
extracellularly.
PREVENTION
• primary prevention programs, aimed at either
delaying atheroma formation or causing regression
of established lesions in persons who have never
suffered a serious complication of atherosclerotic
coronary artery disease
• secondary prevention programs, intended to prevent
recurrence of events such as myocardial infarction in
patients with symptomatic disease.
PREVENTION
• based on risk factor modification: abstention
from or cessation of cigarette smoking, control
of hypertension, weight reduction and
increased exercise, moderation of alcohol
consumption, and, most importantly, lowering
total and LDL blood cholesterol levels while
increasing HDL. on
Angina pectoris
• Angina pectoris is a symptom complex of IHD
characterized by paroxysmal and usually
recurrent attacks of substernal or precordial
chest discomfort (variously described as
constricting, squeezing, choking, or knifelike)
caused by transient (15 seconds to 15
minutes) myocardial ischemia that falls short
of inducing the cellular necrosis that defines
infarction.
Angina pectoris
• There are three overlapping patterns of
angina pectoris: (1) stable or typical angina,
(2) Prinzmetal or variant angina, and (3)
unstable or crescendo angina
Angina pectoris
 Stable angina, the most common form and therefore
called typical angina pectoris, appears to be caused
by the reduction of coronary perfusion to a critical
level by chronic stenosing coronary atherosclerosis;
this renders the heart vulnerable to further ischemia
whenever there is increased demand, such as that
produced by physical activity, emotional excitement,
or any other cause of increased cardiac workload.
Episodic chest pain associated with exertion or some
other form of stress.
Angina pectoris
• The pain is described as a crushing or
squeezing substernal sensation, which may
radiate down the left arm. Typical angina
pectoris is usually relieved by rest (thereby
decreasing demand) or nitroglycerin, a strong
vasodilator.
Angina Pectoris
• Prinzmetal variant angina is an uncommon
pattern of episodic angina that occurs at rest
and is due to coronary artery spasm.
Prinzmetal angina generally responds
promptly to vasodilators, such as nitroglycerin
and calcium channel blockers.
Angina Pectoris
 Unstable or crescendo angina refers to a pattern of
pain that occurs with progressively increasing
frequency, is precipitated with progressively less
effort, often occurs at rest, and tends to be of more
prolonged duration. It is induced by disruption of an
atherosclerotic plaque with superimposed partia)
thrombosis and possibly embolization or vasospasm
(or both). Unstable angina is often the precursor of
subsequent acute MI. Thus this referred to as
preinfarction angina.
Myocardial Infarction
• Definition: MI, also known as "heart attack," is
the death of cardiac muscle resulting from
ischemia.
• Risks are the same as those of coronary
atherosclerosis.
Pathogenesis of MI
• Any form of coronary artery disease.
• In the typical case of MI, the following
sequence of events can be proposed:
• The initial event is a sudden change in the
morphology of an atheromatous plaque, that
is, disruption-manifest as intraplaque
hemorrhage, erosion or ulceration, or rupture
or fissuring.
Pathogenesis of MI
• Exposed to subendothelial collagen and
necrotic plaque contents, platelets undergo
adhesion, aggregation, activation, and release
of potent aggregators including thromboxane
A2, serotonin, and platelet factors 3 and 4.
• Vasospasm is stimulated by platelet
aggregation and the release of mediators.
Pathogenesis of MI
• Other mediators activate the extrinsic
pathway of coagulation, adding to the bulk of
the thrombus.
• Frequently within minutes, the thrombus
evolves to completely occlude the lumen of
the coronary vessel
Pathogenesis of MI
• Most common cause is thrombosis on a
preexisting disrupted atherosclerotic plaque.
• Platelet aggregate and vasospasm may
participate but are rarely the sole cause of
occlusion.
• Hypoperfusion + atherosclerosis may lead to
subendocerdial infarct without thrombosis.
Pathogenesis of MI
• Myocardial necrosis begins within 20-30
minutes, mostly starting at the subendocardial
region (less perfused, high intramural
pressure).
• Infarct reaches its full size within 3-6 hrs.,
during this period, lysis of the thrombus by
streptokinase or tpa, may limit the size of the
infarct.
Pathogenesis of MI
• Table 12-4. Approximate Time of Onset of Key
Events in Ischemic Cardiac Myocytes
• FeatureTimeOnset of ATP
depletionSecondsLoss of contractility<2
minATP reducedto 50% of normal10 minto
10% of normal40 minIrreversible cell injury2040 minMicrovascular injury>1 hr
Pathogenesis of MI
 Location of the MI is determined by the site of the
occlusion and by the anatomy of coronary circulation.
 Left anterior descending(40-50%): anterior and apical
left ventricle and anterior two thirds of interventricular
septum.
 Right coronary artery(30-40%): posterior wall of the left
ventricle, posterior one third of interventricular septum
(rt. Dominant coronary circulation).
 Left circumflex: lateral wall of lt. Ventricle (posterior
wall in persons with left-dominant coronary
circulation).
Pathogenesis of MI
• The precise location, size, and specific
morphologic features of an acute myocardial
infarct depend on:
• The location, severity, and rate of
development of coronary atherosclerotic
obstructions
• The size of the vascular bed perfused by the
obstructed vessels
• The duration of the occlusion
Pathogenesis of MI
• The metabolic/oxygen needs of the
myocardium at risk
• The extent of collateral blood vessels
• The presence, site, and severity of coronary
arterial spasm
• Other factors, such as alterations in blood
pressure, heart rate, and cardiac rhythm.
Pathogenesis of MI
 Myocardial necrosis begins within 20-30 minutes, mostly
starting at the subendocardial region (less perfused, high
intramural pressure).
 Infarct reaches its full size within 3-6 hrs., during this
period, lysis of the thrombus by streptokinase or tpa, may
limit the size of the infarct.
Myocardial Infarction: Morphology
• Coagulation necrosis and inflammation.
• Formation of granulation tissue.
• Organization of the necrotic tissue to form a
fibrous scar.
• Morphology is dependent on age of the
infarct, its size, recurrence, reperfusion.
Myocardial Infarction: Morphology
Time
Gross
Microscopy
0-30 min
No change
No change
1-2 hr
No change
Few wavy fibers at margin of infarct
4-12 hr
No change
Early coagulation necrosis, edema, occasional
neutrophils, minimal hemorrhage
18-24 hr
Slight pallor
Continuing coagulation necrosis(nuclear pyknosis,
and disintegration, cytoplasmic eosinphilia),
contraction band, necrosis at periphery of infarct,
neutrophilic infiltrate
24-72 hr
Pallor
Complete coagulation necrosisof myofibers, heavy
neutrophilic infiltrate with early fragmentation of
neutrophil nuclei
4-7 days
Central pallor with
hyperemic border
Macrophages appear, early disintegration and
phagocytosis of necrotic fibers, granulation tissue
visible at edge of infarct
10 days
Maximally yellow,
shrunken; purple
border
Well-developed phagocytosis, prominent
granulation tissue in peripheral areas of infarct
7-8 wks
Firm gray
Fibrosis
13.16Figure 13–8 (p. 560) Microscopic features of myocardial
infarction.
A. One-day-old infarct showing coagulative necrosis, wavy fibers
with elongation, and narrowing, compared with adjacent normal
fibers (lower right). Widened spaces between the dead fibers
contain edema fluid and scattered neutrophils.
B. Dense polymorphonuclear leukocytic infiltrate in an area of
acute myocardial infarction of 3 to 4 days' duration.
C. Nearly complete removal of necrotic myocytes by phagocytosis
(approximately 7 to 10 days).
D. Granulation tissue with a rich
vascular network and early collagen
deposition, approximately 3 weeks
after infarction.
E. Well-healed myocardial infarct
with replacement of the necrotic
fibers by dense collagenous scar. A
few residual cardiac muscle cells
are present. (In D and E, collagen is
highlighted as blue in this Masson
trichrome stain.)
Complications of MI
• Myocardial rupture
• Arrhythmias. Many patients have conduction
disturbances and myocardial irritability
following MI, which undoubtedly are
responsible for many of the sudden deaths
• Pericarditis
Complications of MI
• Infarct extension. New necrosis may occur adjacent
to an existing infarct.
• Infarct expansion
• Mural thrombus. With any infarct, the combination
of a local myocardial abnormality in contractility
(causing stasis) with endocardial damage (causing a
thrombogenic surface) can foster mural thrombosis
and, potentially, thromboembolism
Complications of MI
• Ventricular aneurysm. In contrast to false
aneurysms mentioned above, true aneurysms
of the ventricular wall are bounded by
myocardium that has become scarred.
• Papillary muscle dysfunction.
Complications of MI
•
•
•
•
•
External rupture of the infarct.
Mural thrombi.
Acute pericarditis.
Ventricular aneurysms.
Progressive late heart failure is discussed as
chronic IHD below.
Myocardial Infarction: Clinical Features
 Pain:
◦ Severe crushing substernal chest pain, which may radiate
to the neck, jaw, epigastrum, shoulder or left arm.
◦ Pain lasts for hours to days and is not relieved by
nitroglycerin.
◦ Absent in 20-30% of patients (diabetics, hypertensive,
elderly).
 Pulse is rapid and weak.
 Diaphoresis.
 Dyspnea.
 Cardiogenic shock in massive MI(>40%of lt. ventricle).
Myocardial Infarction:Electrocardiographic
Abnormalities
•
•
•
•
Changes of Q waves.
ST-segment abnormalities.
T-wave inversion.
Arrhythmias.
Myocardial Infarction:Outcomes
 Sudden coronary death due to ventricular
arrhythmia (25%).
 No complications in 10-20%.
 80-90% experience one or more of the followings:
◦ Cardiac arrhythmia (75-90%).
◦ Left ventricular failure with mild to severe
pulmonary edema (60%).
◦ Cardiogenic shock (10%).
◦ Rupture of free wall, septum, papillary muscle
(4-8%).
◦ Thromboembolism (15-49%).
Myocardial Infarction: Laboratory Evaluation
• Creatine kinase (CK) … CK-MB.
– Rise 2-4 hrs, peaks 18 hrs, persists 48 hrs.
• Lactate dehydrogenase (LD)… LD1.
– Rise 24 hrs, peaks 72 hrs, persists 72 hrs.
• Troponins: cTnT, cTnI (more specific).
– Persists for 4-7 days.
Sudden Cardiac Death
• Morphology:
– Marked degree of coronary atherosclerosis.
– ?acute rupture of plaque, thrombosis, vasospasm,
fatal ventricular arrhythmia.
– Acute or remote myocardial infarction.
Sudden Cardiac Death
• This catastrophe strikes down about 300,000
to 400,000 individuals annually in the United
States. Sudden cardiac death (SCD) is most
commonly defined as unexpected death from
cardiac causes early after symptom onset
(usually within 1 hour) or without the onset of
symptoms.
Sudden Cardiac Death
• Atherosclerosis is the most commom cause.
The non-atherosclerotic causes include the following:
• Congenital structural or coronary arterial
abnormalities
• Aortic valve stenosis
• Mitral valve prolapse
• Myocarditis
• Dilated or hypertrophic cardiomyopathy
• Pulmonary hypertension
Sudden Cardiac Death
• Hereditary or acquired abnormalities of the
cardiac conduction system
• Isolated hypertrophy, hypertensive or
unknown cause. Increased cardiac mass is an
independent risk factor for cardiac death;
thus, some young patients who die suddenly,
including athletes, have hypertensive
hypertrophy or unexplained increased cardiac
mass as the only finding
Sudden Cardiac Death
• The ultimate mechanism of SCD is most often
a lethal arrhythmia (e.g., asystole, ventricular
fibrillation
Hypertension and Hypertensive
Vascular Disease
• Hypertension: Definition: a sustained diastolic
pressure more than 90 mm hg or a sustained systolic
pressure in excess of 140 mm hg.
• Hypertension is an important risk factor in:
– Coronary heart disease.
– Cerebrovascular accidents.
– May lead to:
• Congestive heart failure.
• Aortic dissection.
• Renal failure.
Hypertension: Types/ Cause
• Primary or essential hypertension(90-95%).
• Secondary hypertension(5-10%):
– Renal:
•
•
•
•
•
Acute glomerulonephritis.
Chronic renal disease.
Renal artery stenosis.
Renal vasculitis.
Renin-producing tumors.
Hypertension: Types/ Cause
• Secondary hypertension:
– Endocrine:
•
•
•
•
•
•
Adrenocortical hyperfunction (Cushing’s syndrome)
Oral contraceptives.
Pheochromocytoma.
Acromegaly.
Myxedema.
Thyrotoxicosis (systolic).
Hypertension: Types/ Cause
• Secondary hypertension:
– Vascular:
• Coarctation of aorta.
• Polyarteritis nodosa.
• Aortic insufficiency (systolic)
– Neurogenic:
• Psychogenic.
• Increased intracranial pressure.
• Polyneuritis, bulbar poliomyelitis, others.
Hypertension: Types/ Clinical
• Benign:
– Modest level.
– Fairly stable over years to decades.
– Compatible with long life.
• Malignant(5%):
– Rapidly rising blood pressure.
– Severe hypertension (diastolic>120)
– Renal failure.
– Retinal hemorrhages and exudates (w/wo
papilledema).
– Leads to death in 1 or 2 years if untreated.
Hypertension: Pathogenesis
• Blood pressure:
BP = Cardiac Output x Peripheral Resistance
Atriopeptin: peptides secreted by heart
atria in response to volume
expansion:inhibit Na reabsorption
in distal tubules and cause
vasodilation
Glomerular
filtration
rate
Hypertension: Possible Factors
• Genetic:
– Twin studies.
– Familial clustering.
– Gene linkage studies (red in previous slide)
• Environmental:
– Low incidence in native Chinese as compared to
immigrants to US.
– May include: stress, obesity, inactivity, and heavy
consumption of salt.
1.
Behavioural or neurogenic factors
2.
release of vasoconstrictors
(endothelin., angiotensin II)
3.
1ry  sensitivity of vascular smooth
muscle
Hypertrophy, remodeling and
hyperplasia of SMCs.
Vascular pathology in hypertension.
A. Hyaline arteriolosclerosis. The arteriolar wall is hyalinized and the lumen is markedly
narrowed.
B. Hyperplastic arteriolosclerosis (onionskinning) causing luminal obliteration ( arrow),
with secondary ischemic changes, manifested by wrinkling of the glomerular capillary vessels
at the upper left (periodic acid–Schiff [PAS] stain).
Vascular pathology in hypertension.
• Hyaline arteriolosclerosis:
– Can also be seen in elderly without
hypertension and in diabetic patients.
– Leads to benign nephrosclerosis due to diffuse
renal ischemia.
• Hyperplastic arteriolosclerosis:
– Characteristic of malignant hypertension.
– May be associated with necrotizing arteriolitis.
Heart in Hypertension
• Clinically:
• Early: no symptoms (chest x-ray, echo-, electrocardiography).
• Late: heart failure, symptoms and signs of ischemic
heart disease.
• Hypertensive heart disease (HHD) is the response of
the heart to the increased demands induced by
systemic hypertension.74 Pulmonary hypertension
also causes heart disease and is referred to as rightsided HHD, or cor pulmonale
SYSTEMIC (LEFT-SIDED) HYPERTENSIVE HEART
DISEASE
• In hypertension, hypertrophy of the heart is an
adaptive response to pressure overload that can
lead to myocardial dysfunction, cardiac dilation,
CHF, and sudden death.
• The minimal criteria for the diagnosis of systemic
HHD are the following: (1) left ventricular
hypertrophy (usually concentric) in the absence of
other cardiovascular pathology that might have
induced it and (2) a history or pathologic evidence
of hypertension
SYSTEMIC (LEFT-SIDED) HYPERTENSIVE HEART
DISEASE
• Morphology. Hypertension induces left
ventricular pressure overload hypertrophy
without dilation of the left ventricle. The
thickening of the left ventricular wall and
increase in the weight of the heart and
increase in the overall cardiac size. In time, the
increased thickness of the left ventricular wall
imparts a stiffness that impairs diastolic filling.
This often induces left atrial enlargement
SYSTEMIC (LEFT-SIDED) HYPERTENSIVE HEART
DISEASE
• Microscopically, the earliest change of
systemic HHD is an increase in the transverse
diameter of myocytes, which may be difficult
to appreciate on routine microscopy. At a
more advanced stage, the cellular and nuclear
enlargement becomes somewhat more
irregular, with variation in cell size among
adjacent cells, and interstitial fibrosis.
SYSTEMIC (LEFT-SIDED) HYPERTENSIVE HEART
DISEASE
Depending on the severity, duration, and underlying
basis of the hypertension, and on the adequacy of
therapeutic control, the patient may
• (1) enjoy normal longevity and die of unrelated
causes, (2) develop progressive IHD owing to the
effects of hypertension in potentiating coronary
atherosclerosis,
• (3) suffer progressive renal damage or
cerebrovascular stroke,
• (4) experience progressive heart failure.
SYSTEMIC (LEFT-SIDED) HYPERTENSIVE HEART
DISEASE
• The risk of sudden cardiac death is also
increased. Effective control of hypertension
can prevent or lead to regression of cardiac
hypertrophy and its associated risks.
PULMONARY (RIGHT-SIDED) HYPERTENSIVE HEART DISEASE
(COR PULMONALE)
• Cor pulmonale, as pulmonary HHD is
frequently called, consists of right ventricular
hypertrophy, dilation, and potentially failure
secondary to pulmonary hypertension caused
by disorders of the lungs or pulmonary
vasculature. Pulmonary HHD is the right-sided
counterpart of left-sided (systemic) HHD.
PULMONARY (RIGHT-SIDED) HYPERTENSIVE HEART DISEASE
(COR PULMONALE)
• Although right ventricular dilation and
thickening caused either by diseases of the
left side of the heart or congenital heart
diseases are generally excluded by this
definition of cor pulmonale, pulmonary
venous hypertension that follows left-sided
heart diseases of various etiologies is quite
common
PULMONARY (RIGHT-SIDED) HYPERTENSIVE HEART DISEASE
(COR PULMONALE)
 Cor pulmonale may be acute or chronic, depending
on the suddenness of development of the
pulmonary hypertension. Acute cor pulmonale can
follow massive pulmonary embolism. Chronic cor
pulmonale usually implies right ventricular
hypertrophy (and dilation) secondary to prolonged
pressure overload caused by obstruction of the
pulmonary arteries or arterioles or compression or
obliteration of septal capillaries (e.g., owing to
primary pulmonary hypertension or emphysema
PULMONARY (RIGHT-SIDED) HYPERTENSIVE HEART DISEASE
(COR PULMONALE)
• Morphology. In acute cor pulmonale, there is
marked dilation of the right ventricle without
hypertrophy. In chronic cor pulmonale, the
right ventricular wall thickens, sometimes up
to 1.0 cm or more, and may even come to
approximate that of the left ventricle.