The Cardiovascular System Anatomy of the Heart

▪ Coverings of the heart

▪ A closed system of the heart and blood vessels
▪ The heart pumps blood
▪ Blood vessels allow blood to circulate to all parts
of the body
▪ Functions of the cardiovascular system
▪ Transport oxygen, nutrients, cell wastes,
hormones to and from cells
Anatomy of the Heart
▪ Size of a human fist, weighing less than a pound
▪ Located in the thoracic cavity, between the lungs in
the inferior mediastinum
▪ Orientation
▪ Apex is directed toward left hip and rests on the
diaphragm
▪ Base points toward right shoulder
▪ Pericardium—a double-walled sac
▪ Fibrous pericardium is loose and
superficial
▪ Serous membrane is deep to the
fibrous pericardium and composed of two
layers
1. Parietal pericardium: outside
layer that lines the inner surface of the
fibrous pericardium
2. Visceral pericardium: next to
heart; also known as the epicardium
▪ Serous fluid fills the space between
the layers of pericardium, called the
pericardial cavity

▪ Walls of the heart

1. Epicardium
▪ Outside layer; the visceral pericardium
2. Myocardium
▪ Middle layer
▪ Mostly cardiac muscle
3. Endocardium
▪ Inner layer known as endothelium

Chambers and Associated Great Vessels

▪ Four chambers of the heart
▪ Atria (right and left)
▪ Receiving chambers
▪ Assist with filling the ventricles
▪ Blood enters under low pressure

▪ Ventricles (right and left)

▪ Discharging chambers
▪ Thick-walled pumps of the heart
▪ During contraction, blood is propelled
into circulation
Chambers and Associated Great Vessels
▪ Interatrial septum
▪ Separates the two atria longitudinally

▪ Interventricular septum
▪ Separates the two ventricles longitudinally
Chambers and Associated Great Vessels
▪ Heart functions as a double pump
▪ Arteries carry blood away from the heart
▪ Veins carry blood toward the heart
▪ Double pump
▪ Right side works as the pulmonary circuit pump
▪ Left side works as the systemic circuit pump
▪ Pulmonary circulation
▪ Blood flows from the right side of the heart to the
lungs and back to the left side of the heart
▪ Blood is pumped out of right side through the
pulmonary trunk, which splits into pulmonary arteries
and takes oxygen-poor blood to lungs
▪ Oxygen-rich blood returns to the heart from the
lungs via pulmonary veins
▪ Systemic circulation
▪ Oxygen-rich blood returned to the left side of the
heart is pumped out into the aorta
▪ Blood circulates to systemic arteries and to all
body tissues
▪ Left ventricle has thicker walls because it
pumps blood to the body through the systemic circuit
▪ Oxygen-poor blood returns to the right atrium via
systemic veins, which empty blood into the superior
or inferior vena cava
Heart Valves
▪ Allow blood to flow in only one direction, to
prevent backflow
▪ Atrioventricular (AV) valves—between
atria and ventricles
▪ Left AV valve: bicuspid (mitral) valve
▪ Right AV valve: tricuspid valve
▪ Semilunar valves—between ventricle and
artery
▪ Pulmonary semilunar valve
▪ Aortic semilunar valve
▪ AV valves
▪ Anchored the cusps in place by chordae
tendineae to the walls of the ventricles
▪ Open during heart relaxation, when
blood passively fills the chambers
▪ Closed during ventricular contraction
▪ Semilunar valves
▪ Closed during heart relaxation
▪ Open during ventricular contraction
▪ Valves open and close in response to
pressure changes in the heart
Cardiac Circulation

▪ Blood in the heart chambers does not nourish the myocardium

▪ The heart has its own nourishing circulatory system consisting of:
▪ Coronary arteries—branch from the aorta to supply the heart muscle with
oxygenated blood
▪ Cardiac veins—drain the myocardium of blood
▪ Coronary sinus—a large vein on the posterior of the heart; receives blood from
cardiac veins

▪ Blood empties into the right atrium via the coronary sinus
Physiology of the Heart
▪ Intrinsic conduction system of the heart
▪ Cardiac muscle contracts spontaneously and
independently of nerve impulses
▪ Spontaneous contractions occur in a regular and
continuous way
▪ Atrial cells beat 60 times per minute
▪ Ventricular cells beat 20−40 times per minute
▪ Need a unifying control system—the intrinsic
conduction system (nodal system)
▪ Two systems regulate heart activity
▪ Autonomic nervous system
▪ Intrinsic conduction system, or the nodal
system
▪ Sets the heart rhythm
▪ Composed of special nervous tissue
▪ Ensures heart muscle depolarization in one
direction only (atria to ventricles)
▪ Enforces a heart rate of 75 beats per minute
▪ Components include:
▪ Sinoatrial (SA) node
▪ Located in the right atrium
▪ Serves as the heart’s pacemaker
▪ Atrioventricular (AV) node is at the junction
of the atria and ventricles
▪ Atrioventricular (AV) bundle (bundle of His)
and bundle branches are in the interventricular
septum
▪ Purkinje fibers spread within the ventricle
wall muscles
▪ The sinoatrial node (SA node) starts each
heartbeat
▪ Impulse spreads through the atria to the AV
node
▪ Atria contract
▪ At the AV node, the impulse is delayed briefly
▪ Impulse travels through the AV bundle, bundle
branches, and Purkinje fibers
▪ Ventricles contract; blood is ejected from the
heart
▪ Tachycardia—rapid heart rate, over 100 beats per
minute
▪ Bradycardia—slow heart rate, less than 60 beats per
minutes
▪ Cardiac cycle and heart sounds
▪ The cardiac cycle refers to one complete
heartbeat, in which both atria and ventricles contract
and then relax
▪ Systole = contraction
▪ Diastole = relaxation
▪ Average heart rate is approximately 75 beats per
minute
▪ Cardiac cycle length is normally 0.8 second
▪ Atrial diastole (ventricular filling)
▪ Heart is relaxed
▪ Pressure in heart is low
▪ Atrioventricular valves are open
▪ Blood flows passively into the atria and into
ventricles
▪ Semilunar valves are closed
▪ Atrial systole
▪ Ventricles remain in diastole
▪ Atria contract
▪ Blood is forced into the ventricles to complete
ventricular filling
▪ Isovolumetric contraction
▪ Atrial systole ends; ventricular systole begins
▪ Intraventricular pressure rises
▪ AV valves close
▪ For a moment, the ventricles are completely
closed chambers
▪ Ventricular systole (ejection phase)
▪ Ventricles continue to contract
▪ Intraventricular pressure now surpasses the
pressure in the major arteries leaving the heart
▪ Semilunar valves open
▪ Blood is ejected from the ventricles
▪ Atria are relaxed and filling with blood
▪ Isovolumetric relaxation
▪ Ventricular diastole begins
▪ Pressure falls below that in the major
arteries
▪ Semilunar valves close
▪ For another moment, the ventricles are
completely closed chambers
▪ When atrial pressure increases above
intraventricular pressure, the AV valves open
▪ Heart sounds
▪ Lub—longer, louder heart sound caused by
the closing of the AV valves
▪ Dup—short, sharp heart sound caused by the
closing of the semilunar valves at the end of
ventricular systole
▪ Cardiac output (CO) 2. Hormones and ions
▪ Amount of blood pumped by each side (ventricle) ▪ Epinephrine and thyroxine speed heart rate
of the heart in 1 minute ▪ Excess or lack of calcium, sodium, and
potassium ions also modify heart activity
▪ Stroke volume (SV)
▪ Volume of blood pumped by each ventricle in one 3. Physical factors
contraction (each heartbeat) ▪ Age, gender, exercise, body temperature
▪ About 70 ml of blood is pumped out of the left influence heart rate
ventricle with each heartbeat

▪ Heart rate (HR)

▪ Typically 75 beats per minute

▪ Cardiac output is the product of the heart rate (HR)

and the stroke volume (SV)
▪ CO = HR × SV
▪ CO = HR (75 beats/min) × SV (70 ml/beat)
▪ CO = 5250 ml/min = 5.25 L/min

▪ Regulation of stroke volume

▪ 60 percent of blood in ventricles (about 70 ml) is
pumped with each heartbeat
▪ Starling’s law of the heart
▪ The critical factor controlling SV is how much
cardiac muscle is stretched
▪ The more the cardiac muscle is stretched, the Blood Vessels
stronger the contraction ▪ Blood vessels form a closed vascular system
that transports blood to the tissues and back to
▪ Venous return is the important factor influencing the the heart
stretch of heart muscle ▪ Vessels that carry blood away from the
heart
▪ Factors modifying basic heart rate ▪ Arteries and arterioles
1. Neural (ANS) controls ▪ Vessels that play a role in exchanges
▪ Sympathetic nervous system speeds heart rate between tissues and blood
▪ Parasympathetic nervous system, primarily vagus ▪ Capillary beds
nerve fibers, slow and steady the heart rate ▪ Vessels that return blood toward the heart
▪ Venules and veins
Microscopic Anatomy of Blood Vessels
▪ Three layers (tunics) in blood vessels (except the capillaries)
▪ Tunica intima forms a friction-reducing lining
▪ Endothelium
▪ Tunica media
▪ Smooth muscle and elastic tissue
▪ Controlled by sympathetic nervous system
▪ Tunica externa forms protective outermost covering
▪ Mostly fibrous connective tissue
▪ Supports and protects the vessel

▪ Structural differences in arteries, veins, and capillaries

▪ Arteries have a heavier, stronger, stretchier tunica media than veins to withstand
changes in pressure
▪ Veins have a thinner tunica media than arteries and operate under low pressure
▪ Veins also have valves to prevent backflow of blood
▪ Lumen of veins is larger than that of arteries
▪ Skeletal muscle “milks” blood in veins toward the heart
▪ Capillaries
▪ Only one cell layer thick (tunica intima)
▪ Allow for exchanges between blood and tissue
▪ Form networks called capillary beds that consist of:
▪ A vascular shunt
▪ True capillaries

▪ Blood flow through a capillary bed is known as microcirculation

▪ True capillaries
▪ Branch off a terminal arteriole
▪ Empty directly into a postcapillary venule
▪ Entrances to capillary beds are guarded by precapillary sphincters
Gross Anatomy of Blood Vessels
▪ Major arteries of systemic circulation
▪ Aorta
▪ Largest artery in the body
▪ Leaves from the left ventricle of the heart
▪ Regions
▪ Ascending aorta—leaves the left ventricle
▪ Aortic arch—arches to the left
▪ Thoracic aorta—travels downward through the thorax
▪ Abdominal aorta—passes through the diaphragm into the abdominopelvic
cavity
▪ Major arteries of systemic circulation (continued)
▪ Arterial branches of the ascending aorta
▪ Right and left coronary arteries serve the heart
▪ Major arteries of systemic circulation (continued)
▪ Arterial branches of the aortic arch
▪ Brachiocephalic trunk splits into the:
▪ Right common carotid artery
▪ Right subclavian artery
▪ Left common carotid artery splits into the:
▪ Left internal and external carotid arteries
▪ Left subclavian artery branches into the:
▪ Vertebral artery
▪ In the axilla, the subclavian artery becomes
the axillary artery → brachial artery → radial and ulnar
arteries
▪ Arterial branches of the thoracic aorta
▪ Intercostal arteries supply the muscles of the
thorax wall
▪ Other branches of the thoracic aorta (not
illustrated) supply the:
▪ Lungs (bronchial arteries)
▪ Esophagus (esophageal arteries)
▪ Diaphragm (phrenic arteries)
▪ Arterial branches of the abdominal aorta
▪ Celiac trunk is the first branch of the abdominal
aorta. Three branches are:
1. Left gastric artery (stomach)
2. Splenic artery (spleen)
3. Common hepatic artery (liver)
▪ Superior mesenteric artery supplies most of the
small intestine and first half of the large intestine
▪ Arterial branches of the abdominal aorta
(continued) ▪ Left and right renal arteries (kidney)
▪ Left and right gonadal arteries
▪ Ovarian arteries in females serve the ovaries
▪ Testicular arteries in males serve the testes
▪ Lumbar arteries serve muscles of the abdomen
and trunk
▪ Inferior mesenteric artery serves the second half of
the large intestine
▪ Left and right common iliac arteries are the final
branches of the aorta
▪ Internal iliac arteries serve the pelvic organs
▪ External iliac arteries enter the thigh →
femoral artery → popliteal artery → anterior and
posterior tibial arteries
Major veins of systemic circulation
▪ Superior vena cava and inferior vena cava
enter the right atrium of the heart
▪ Superior vena cava drains the head and
arms
▪ Inferior vena cava drains the lower body
▪ Major veins of systemic circulation (continued)
▪ Veins draining into the superior vena cava
▪ Radial and ulnar veins → brachial vein →
axillary vein
▪ Cephalic vein drains the lateral aspect of
the arm and empties into the axillary vein
▪ Basilic vein drains the medial aspect of the
arm and empties into the brachial vein
▪ Basilic and cephalic veins are joined at the
median cubital vein (elbow area)
▪ Veins draining into the superior vena cava
(continued)
▪ Subclavian vein receives:
▪ Venous blood from the arm via the
axillary vein
▪ Venous blood from skin and muscles
via external jugular vein
▪ Vertebral vein drains the posterior part of
the head
▪ Internal jugular vein drains the dural sinuses
of the brain
▪ Left and right brachiocephalic veins receive
venous blood from the:
▪ Subclavian veins
▪ Vertebral veins
▪ Internal jugular veins
▪ Brachiocephalic veins join to form the
superior vena cava → right atrium of heart
▪ Azygos vein drains the thorax
▪ Anterior and posterior tibial veins and fibial veins drain the legs
▪ Posterior tibial vein → popliteal vein → femoral vein → external iliac vein
▪ Great saphenous veins (longest veins of the body) receive superficial drainage of the legs
▪ Each common iliac vein (left and right) is formed by the union of the internal and external iliac
vein on its own side
▪ Right gonadal vein drains the right ovary in females and right testicle in males
▪ Left gonadal vein empties into the left renal vein
▪ Left and right renal veins drain the kidneys
▪ Hepatic portal vein drains the digestive organs and travels through the liver before it enters
systemic circulation
▪ Left and right hepatic veins drain the liver
Gross Anatomy of Blood Vessels ▪ Hepatic portal circulation is formed by veins
▪ Arterial supply of the brain and the circle of Willis draining the digestive organs, which empty into
▪ Internal carotid arteries divide into: the hepatic portal vein
▪ Anterior and middle cerebral arteries ▪ Digestive organs
▪ These arteries supply most of the cerebrum ▪ Spleen
▪ Pancreas
▪ Vertebral arteries join once within the skull to
form the basilar artery ▪ Hepatic portal vein carries this blood to the
▪ Basilar artery serves the brain stem and liver, where it is processed before returning to
cerebellum systemic circulation

▪ Posterior cerebral arteries form from the division

of the basilar artery
▪ These arteries supply the posterior cerebrum

▪ Anterior and posterior blood supplies are united

by small communicating arterial branches
▪ Result—complete circle of connecting blood
vessels called cerebral arterial circle, or circle of Willis

Physiology of Circulation
▪ Vital signs
▪ Measurements of arterial pulse, blood
pressure, respiratory rate, and body temperature

▪ Arterial pulse
▪ Alternate expansion and recoil of a blood
vessel wall (the pressure wave) that occurs as the
heart beats
▪ Monitored at pressure points in superficial
arteries, where pulse is easily palpated
▪ Pulse averages 70 to 76 beats per minute at rest, in a
healthy person
Blood Pressure
▪ Blood pressure
▪ The pressure the blood exerts against the inner
walls of the blood vessels
▪ The force that causes blood to continue to flow in
the blood vessels
▪ Blood pressure gradient
▪ When the ventricles contract:
▪ Blood is forced into elastic arteries close to the
heart
▪ Blood flows along a descending pressure gradient
▪ Pressure decreases in blood vessels as distance from
the heart increases
▪ Pressure is high in the arteries, lower in the
capillaries, and lowest in the veins
▪ Effects of various factors on blood pressure
▪ Arterial blood pressure (BP) is directly related
to cardiac output and peripheral resistance
▪ Cardiac output (CO; the amount of blood
pumped out of the left ventricle per minute)
▪ Peripheral resistance (PR; the amount of
friction blood encounters as it flows through
vessels)
BP = CO × PR
▪ Neural factors: the autonomic nervous system
▪ Parasympathetic nervous system has little to
no effect on blood pressure
▪ Sympathetic nervous system promotes
vasoconstriction (narrowing of vessels), which
increases blood pressure
▪ Renal factors: the kidneys
▪ Kidneys regulate blood pressure by altering
blood volume
▪ If blood pressure is too high, the kidneys
release water in the urine
▪ If blood pressure is too low, the kidneys
release renin to trigger formation of angiotensin
II, a vasoconstrictor
▪ Angiotensin II stimulates release of
aldosterone, which enhances sodium (and water)
reabsorption by kidneys
▪ Temperature
▪ Heat has a vasodilating effect
▪ Cold has a vasoconstricting effect
▪ Chemicals
▪ Various substances can cause increases or
decreases in blood pressure
▪ Epinephrine increases heart rate and blood
pressure
▪ Diet
▪ Commonly believed that a diet low in salt,
saturated fats, and cholesterol prevents
hypertension (high blood pressure)
▪ Variations in blood pressure
▪ Normal human range is variable
▪ Systolic pressure ranges from 110 to 140 mm Hg
▪ Diastolic pressure ranges from 70 to 80 mm Hg
▪ Hypotension (low blood pressure)
▪ Low systolic (below 100 mm Hg)
▪ Often associated with illness
▪ Acute hypotension is a warning sign for
circulatory shock
▪ Substances take various routes entering or
leaving the blood
1. Direct diffusion through membranes
2. Diffusion through intercellular clefts (gaps
between cells in the capillary wall)
3. Diffusion through pores of fenestrated
capillaries
4. Transport via vesicles

▪ Hypertension (high blood pressure)

▪ Sustained elevated arterial pressure of 140/90
mm Hg
▪ Warns of increased peripheral resistance

▪ Capillary exchange of gases and nutrients

▪ Interstitial fluid (tissue fluid) is found between
cells
▪ Substances move to and from the blood and
tissue cells through capillary walls
▪ Exchange is due to concentration gradients
▪ Oxygen and nutrients leave the blood and
move into tissue cells
▪ Carbon dioxide and other wastes exit tissue
cells and enter the blood
▪ Fluid movements at capillary beds
▪ Fluid movement out of or into a capillary depends
on the difference between the two pressures
1. Blood pressure forces fluid and solutes out of
capillaries
2. Osmotic pressure draws fluid into capillaries
▪ Blood pressure is higher than osmotic pressure at
the arterial end of the capillary bed
▪ Blood pressure is lower than osmotic pressure at
the venous end of the capillary bed
▪ Thus, fluid moves out of the capillary at the
beginning of the bed and is reclaimed at the opposite
(venule) end
Developmental Aspects of the Cardiovascular
System
▪ In an embryo
▪ The heart develops as a simple tube and
pumps blood by week 4 of pregnancy
▪ The heart becomes a four-chambered
organ capable of acting as a double pump over
the next 3 weeks
▪ Umbilical cord
▪ Carries nutrients and oxygen from
maternal blood to fetal blood
▪ Fetal wastes move from fetal blood to
maternal blood
▪ Houses:
▪ One umbilical vein, which carries
nutrient- and oxygenrich blood to the fetus
▪ Two umbilical arteries, which carry
wastes and carbon dioxide–rich blood from the
fetus to placenta
▪ Shunts bypassing the lungs and liver are
present in a fetus
▪ Blood flow bypasses the liver through the
ductus venosus and enters the inferior vena cava
→ right atrium of heart
▪ Blood flow bypasses the lungs
▪ Blood entering right atrium is shunted
directly into left atrium through foramen ovale
(becomes fossa ovalis at or after birth)
▪ Ductus arteriosus connects aorta and
pulmonary trunk (becomes ligamentum
arteriosum at birth)
▪ Age-related problems associated with the
cardiovascular system include:
▪ Weakening of venous valves
▪ Varicose veins
▪ Progressive arteriosclerosis
▪ Hypertension resulting from loss of elasticity
of vessels
▪ Coronary artery disease resulting from fatty,
calcified deposits in the vessels
 Hypertensive Vascular Disease
Hypertension
 One of the leading cause of the global burden of
disease affecting > 1B individuals with 8.4
million deaths/year
 Often associated w/ additional cardiovascular
disease risk
 Doubles the risk of Cardiovascular diseases:
1. Coronary heart disease
2. Congestive Heart Failure
3. Ischemic and Hemorrhagic stroke
4. Renal Failure
5. Peripheral Arterial Disease
Epidemiology
 In children and adolescent, high BP is associated
with growth and maturation
 Ave high SBP in early adulthood for men
 > 60 yo, SBP of women are higher due to
decrease in estrogen levels
 Among adults, DBP increases w/ age until 55 yo:
 Causing a widening of pulse pressure
beyond age 60 due to stiffness of vessels
Mechanism of Hypertension
1. Cardiac output is determined by Stroke
volume (SV) & Heart rate (HR):
 SV – is related to the myocardial
contractility and to the size of the
vascular compartment
 Peripheral resistance – is determined by
functional and anatomic changes in
small arteries (lumen diameter 100-
400 um) and arterioles
1. Intravascular volume
 Sodium
1. predominant determinant in ECF vol
2. Increases CO during excess NaCl intake
& increased vascular vol response
3. Vascular beds autoregulate blood
flow, and to maintain blood flow in
increased arterial pressure, resistance
w/in that bed must also increase,
since:
 Pressure natriuresis
1. Increase in GFR
2. Decreased absorbing capacity of the renal
tubules
3. Hormonal factors such as atrial natriuretic
factor
4. As arterial pressure increases in response to
high NaCl intake, urinary sodium excretion
increases and Na balance is maintained at the
expense of an increase in arterial pressure
 NaCl dependent hypertension
1. Decreased capacity of the kidney to excrete
sodium due to:
• Intrinsic renal disease
• Increased mineralocorticoid resulting in
increased renal tubular reabsorption of Na
 ESRD volume dependent hypertension
1. 80% of patients, vascular volume and
hypertension can be controlled with adequate
dialysis
2. In 20%, the mechanism of HTN is related to
increased activity of the RAAS and is likely to
be responsive to pharmacologic blockade
2. Autonomic Nervous System
 Norepinephrine – mostly activates alpha
receptors (a1 & a2)
 Epinephrine – both receptors are equally
activated (a & b)
SHORT TERM – adrenergic reflexes modulate
Blood pressure
ARTERIAL BAROREFLEX
▶ Mediated by stretch-sensitive sensory nerve
endings in the carotid sinuses and the aortic arch
▶ Negative feedback loop:
• Elevated BP causes increased firing of
baroreceptors that decreases sympathetic flow,
thus HR and BP decreases
• Decreased BP causes decreased baroreflex
activation increasing HR & BP
Utilization of ANS physiology for HTN treatment:
 Baroreceptor activation via electrical
stimulation of carotid sinus afferent
nerves lowers BP in patients with
“resistant” hypertension
 Sympathetic nervous system antagonists
are potent antihypertensive agents
 Surgical excision of a tumor, a1 receptor
antagonist, or with an inhibitor of
tyrosine hydroxylase decrease
hypertension due to pheochromocytoma
(increased catecholamine production)
3.Renin-Angiotensin-Aldosterone system
LONG TERM – adrenergic function with
hormonal and volume-related factors regulating
arterial pressure
▶ Primarily via vasoconstrictor properties of
angiotensin 2 and the sodium-retaining
properties of aldosterone
▶ There are 3 primary stimuli for renin secretion:
1) Decreased NaCl transport
2) Decreased pressure or stretch w/in the renal afferent arteriole (baroreceptor)
3) Sympathetic nervous system stimulation of renin secreting cells via beta 1 adrenoreceptor
4.Vascular Mechanisms
▶ Ion transport by vascular smooth muscle cells
may contribute to HTN-associated abnormalities
of vascular tone and vascular growth
▶ Vascular radius and compliance of resistance
arteries are important determinants of arterial
pressure:
• Resistance to flow varies inversely with the
fourth power of the radius
• Small decreases in lumen size increases
resistance
Three ion transport mechanisms participate in the
regulation of pH:
1. Na dependent HCO3-Cl exchange
2. Cation independent HCO3-Cl exchange
3. Na-H exchange – increased in HTN, resulting in
increased vascular tone by 2 mechanisms
• Increased Na entry may lead to increased
vascular tone by activating Na-Ca exchange increasing
intracellular Ca
• Increased pH enhances Ca sensitivity of the
contractile apparatus, leading to an increase in
contractility
• Increased Na-H exchange stimulate growth of
vascular smooth muscle cells enhacing sensitivity of
mitogens
5.Immune Mechanisms
▶ Patients w/ primary hypertension have
increased levels of autoantibodies
▶ Inflammation, vascular stretch, Angiotensin
2, & salt have all been shown to result in the
generation of ROS, which modify T cell function
and further enhance inflammation
▶ ROS attenuate the effects of endogenous
small-molecule vasodilators
▶ Infiltration of T cells into the renal
interstitium contributes to inflammation &
oxidative stress
▶ Renal medullary oxidative stress disrupts
pressure-natriuresis & contributes to the
development of HTN in experimental models
Pathologic consequences of Hypertension
 Heart
 Brain
 Kidney
 Peripheral Arteries
HEART Cerebral blood flow remains unchanged over a
HEART DISEASE – most common cause of death in wide range of arterial pressures (MAP of 50-150
hypertensive patients mmHg) autoregulation of blood flow:
▶ Hypertensive heart disease is the result of structural
and functional adaptations: ▶ In patients with the clinical syndrome of
 Left ventricular hypertrophy malignant hypertension, encephalopathy is
 CHF related to failure of autoregulation of cerebral
 Atherosclerotic coronary artery disease blood flow at the upper pressure limit, resulting
 Microvascular disease in vasodilation and hyperperfusion
 Cardiac arrhythmias
 Atrial fibrillation

Approximately 1/3 of patients with CHF have

normal systolic function but abnormal diastolic
function:
▶ Diastolic dysfunction – is an early consequence of
hypertension-related heart disease and is exacerbated
by left ventricular hypertrophy and ischemia
▶ Cardiac catheterization provides the most accurate
assessment of diastolic function

BRAIN
STROKE – is the second most frequent cause of
death in the world; 85% of strokes are due to
infarction, 15% due to either intracerebral or
subarachnoid hemorrhage

▶ Incidence of stroke rises w/ increasing systolic BP

levels in individuals aged >65

▶ HTN associated w/ impaired cognition in an aging

population; beta amyloid deposition (dementia)

▶ HTN related cognitive impairment may be due to

a single infarct occlusion of a “strategic” larger vessels
resulting in subcortical white matter ischemia
KIDNEY
Primary renal disease is the most common etiology of
secondary hypertension. Mechanisms include:
▶ Diminished capacity to excrete sodium
▶ Excessive renin secretion in relation to volume
status
▶ Sympathetic nervous system overactivity

Clinically, macroalbuminuria (a random urine

albumin/creatinine ratio >300 mg/g) or
microalbuminuria (a random urine albumin/creatinine
ration 30-300 mg/g) are early markers of renal injury

Conversely, hypertension is a risk factor for renal injury

and ESRD, closely related to SBP, and black men.

▶ Atherosclerotic hypertension-related vascular DEFINING HYPERTENSION

lesions in the lidney primarily affect preglomerular ▶ BP is based on an average of > 2 careful seated
arterioles, resulting in ischemic changes in the readings obtained on > 2 occasions
glomeruli and post-glomerular structures ▶ Individuals with SBP and DBP in 2 categories
should be designated to the higher BP category
▶ Glomerular injury as consequence of direct damage
to the glomerular capillaries due to glomerular
hyperperfusion

▶ Loss of autoregulation of renal blood flow at the

afferent arteriole results in transmission of elevated
pressures to an unprotected glomerulus leads
hyperfiltration, hypertrophy, & eventual focal
segmental glomerular sclerosis

PERIPHERAL ARTERIES

▶ Blood vessels are a target organ for atherosclerotic

disease secondary to long-standing elevated BP.
▶ In hypertensive patients, vascular disease is a major
contributor to stroke, heart disease, and renal failure o
 Hypertensive patients with arterial disease of the
lower extremities have increased risk of CVD

▶ The ankle brachial index (ABI) is a useful approach

for evaluating PAD and is defined as the ratio of
noninvasively assessed ankle to brachial (arm) SBP
▶ An ABI <0.90 is considered diagnostic of PAD
associated with >50% stenosis in at least one major
lower limb vessel
▶ An ABI <0.80 is associated w/ elevated
BP, particularly SBP
 How to properly take a Blood Pressure measurement

Clinical Disorders of Hypertension Clinical Disorders of Hypertension

SECONDARY HYPERTENSION
PRIMARY or ESSENTIAL HYPERTENSION ▶ 5-20% of hypertensive patients with specific
▶ 80-95% of hypertensive patients which have underlying disorder causing the elevation of
probable no known cause and are genetically related blood pressure can be identified
o Likely consequence of interaction between
environment and genetic factors
o Prevalence increases with age
o Represents spectrum of disorders with different
underlying pathophysiology
❖ Established hypertension: PR is increased & CO
is normal or decreased
❖ Younger px w/ mild or labile HTN: CO increased
& PR normal

METABOLIC SYNDROME
Clinical Criteria for cardiovascular risk pattern: > 3 is
diagnostic of metabolic syndrome
1. Renal Parenchymal Disease
Renal disease is the most common cause of
secondary hypertension.
▶ >80% hypertensive pxs are w/ chronic renal
failure
▶ More severe in glomerular diseases than in
interstitial diseases
▶ HTN may cause nephrosclerosis, & in some
instances it may be difficult to determine whether
HTN or renal disease was the initial disorder
▶ Proteinuria >1,000 mg/D & an active urine
sediment are indicative of primary renal disease
▶ Goals are to control BP & retard the rate of
progression of renal dysfunction (ACE inhibitors &
ARBs)
2. Renovascular HTN
HTN due to a stenosis or occlusive lesion of a renal
artery, is potentially curable. Two groups of patients
are at risk of this disorder:
• Older arteriosclerotic pxs who have a plaque
obstructing the renal artery like Atherosclerosis,
accounts for the majority of pxs w/ renovascular HTN
• Pxs w/ fibromuscular dysplasia has a strong
predilection for your white women w/ lesions tending
to affect more distal portions of the renal artery
50% of px w/ renovascular HTN have an abdominal or
flank bruit, and is significant if it lateralizes or extends
throughout systole into diastole:
o Contrast angiography remains the “gold standard”
for evaluation and identification if renal artery lesions
Treatment:
▶ Medical therapy (ACEi or ARBs but C/I in bilateral
lesions) or
▶ Endovascular intervention (stenting via balloon
angioplasty)
Renovascular HTN should be considered in patients
w/ other evidence of atherosclerotic vascular disease
due to:
 Severe or refractory hypertension
 Recent loss of hypertension control
 Unexplained deterioration of renal function
 Deterioration of renal function associated with a n
ACE inhibitor
3. Primary Aldosteronism
▶ Increased aldosterone production is
independent of the RAA, leading to sodium
retention, hypertension, hypokalemia.
▶ Prevalence of this disorder varies from < 2 to
~15% of hypertensive individuals
▶ Most patients are asymptomatic or
infrequently:
 Polyuria, polydipsia
 Paresthesias, or muscle weakness may be
present as a consequence of
hypokalemic alkalosis
 Rarely edema
▶ PA/PRA ratio screening test obtained in
ambulatory patients in the morning
 A ratio > 30:1 in conjunction w/ a plasma
aldosterone con’c (>20 ng/dl) has a
sensitivity of 90% and a specificity of 91%
for an aldosterone producing adenoma
 Diagnosis of primary aldosteronism can be
confirmed by demonstrating failure to
suppress plasma aldosterone to
4. Cushing’s Syndrome
▶ Excess cortisol production due either to excess
ACTH secretion (from a pituitary tumor or an
ectopic tumor) or to ACTH independent adrenal
production of cortisol
▶ HTN occurs in 75-80% of patients with
Cushing’s syndrome
• Excess cortisol stimulates mineralocorticoid
receptors causing increased secretion of other
adrenal steroids
▶ Cushing’s disease – primary cause is a pituitary
tumor secreting too much ACTH increasing
cortisol
▶ Cushing’s syndrome – peripheral ACTH
independent cause of excess cortisol
5. Catecholamine secreting tumors Approach to the patient

PHEOCHROMOCYTOMA (tumor lies in adrenal History

medulla) vs PARAGANGLIOMA (tumor lies in • duration of HTN
paraganglion outside the adrenal) • Previous therapies; response & S/E
- Accounts for hypertension in 0.05% of patients • Family Hx
• Diet and psychosocial Hx
▶ Normal in between attacks but may go into • RF: weight change, dyslipidemia, smoking,
sudden severe BP elevations, headaches, sweating, DM, sedentary lifestyle
tachycardia, and other signs of Catecholamine surge. • Evidence of secondary HTN

▶ Laboratory testing: Evidence of target organ damage:

 Measuring catecholamines in either urine or • Hx of transient ischemic attack, stroke
plasma • Transient blindness
 24 h urine metanephrine excretion • Angina, MI, CHF
 Fractionated plasma free metanephrines • Sexual function

Miscellaneous Cause of Hypertension Physical Exam

▶ Obstructive Sleep Apnea • Body habitus
▶ Coarctation of the Aorta • BP in both arms
▶ Thyroid diseases and Acromegaly • Supine & standing BP
• Fundoscopic exam
Approach to the patient Complete History and • Quality of femoral and pedal pulses
Physical Exam • Vascular & abdominal bruits
▶ Screen for other cardiovascular disease risk factors • HR and rhythm
▶ Screen for secondary causes • Signs of CHF or secondary HTN
▶ Identify cardiovascular consequences of HTN &
other comorbidities
▶ Assess BP related lifestyles and determine the
potential for intervention

Treatment
LIFESTYLE INTERVENTIONS
Treatment
PHARMACOLOGIC THERAPY
▶ Lowering SBP by 10-20 mmHg and DBP by 5-6
mmHg reduces 35-40% risk of stroke and 12-16% for
CHD w/in 5 years of the initiation of treatment
▶ risk of Heart failure decreased by > 50%
▶ HTN control is the single most effective
intervention for slowing the rate of
progression of HTN related kidney diseases
▶ Most agents reduce SBP by 7-13 mmHg and
DBP by 4-8 mmHg when corrected for placebo
effect as monotherapy
▶ Combination of agents w/ complementary
anti-HTN mechanisms are required to achieve
goal BP reductions
▶ Selection of anti-HTN agents and
combination of agents should be
individualized taking into account the ff:
 Age, severity of HTN, CVD risk factors
 Comorbid conditions
 Practical considerations (cost, S/E, &
frequency of dosing)
1. Diuretics
▶ Low dose thiazide diuretics may be used
alone or in combination with other
antihypertensive drugs
2. Blockers of RAAS ACEis
▶ Decrease the production of Ang 2
▶ Increase bradykinin levels
▶ Reduce sympathetic nervous system
activity
DIRECT RENIN INHIBITORS
▶ Blockade of RAAS is more complete with
DRI
▶ Aliskiren is the 1st of a class of PO,
nonpeptide competitive inhibitors of the
enzymatic activity of renin
ARBs 7. Calcium channel blockers
▶ Provide selective blockade of AT1 receptors, & the ▶ CCBs reduce vascular resistance through L-
effect of Ang 2 on unblocked AT2 receptors may calcium channel blockade which reduces
augment their hypotensive effect intracellular calcium and blunts
▶ Used as monotherapy or in combination w/ vasoconstriction
diuretics, CCB, and alpha blocking agents ▶ Side effects include:
▶ Improve insulin action and ameliorate the A/E of • Flushing, g=headache with
diuretics on glucose metabolism dihydropyridines
• Edema is due to an increase in
3. Aldosterone Antagonists transcapillary pressure gradients, not to net
▶ May be a particularly effective agent in px with: salt and water retention
 low renin primary HTN
 Resistant HTN Common uses for Anti-hypertensive Drugs
 Primary aldosteronism
BP Goals
4. Beta blockers ▶ Maximum protection against combined
▶ Decreasing cardiac output owing to a reduction of cardiovascular endpoints are achieved with:
heart rate and contractility • SBP < 135 to 140 mmHg
▶ CNS effect and inhibition of renin release • DBP < 80 to 85 mmHg
▶ Are particularly effective in HTN px w/
Tachycardia, and their hypotensive potency is
enhance by co-administration with a diuretic

5. Alpha adrenergic blockers

▶ Postsynaptic, selective alpha-adrenoceptor
antagonists lower BP by decreasing peripheral
vascular resistance
▶ These agents are also effective:
1. Treating lower urinary tract symptoms in men
w/ BPH
2. Management of patients with
pheochromocytoma

6. Sympatholytic agents
Centrally acting alpha 2 agonists
▶ Decrease peripheral resistance by inhibiting sympa
outflow for px w/ autonomic neuropathy who have
wide variations in BP die to baroreceptor denervation

Peripheral Sympatholytics
▶ Decrease peripheral resistance and venous
constriction by depleting nerve terminal NE
▶ Limited by orthostatic hypotension, sexual
dysfunction and numerous drug to drug interactions