Chapter 15
Alterations of Blood Flow
Organization of Circulatory and lymphatic systems
Circulatory circuit
o Absorption and delivery of nutrients
o Oxygen uptake and delivery
o Removal of waste products
Lymphatic circulation
o Specialized system of channels and tissues (nodes)
o Collect the excess fluid (2-4 liters/day) that leaks from
vascular network into the interstitium and returns it to the
general circulation.
Interaction of the capillary
And lymphatic networks
The complete process moving ~5 liters
of blood through the entire circuit takes
only ~1 minute
Anatomy of Arteries and Veins
Three microscopically distinct layers
(tunicae)
Lumen
o Intima: endothelial cells in direct
contact with the blood as it flows
through the vessel
• Peridically, the intima layer protrudes into
the lumen, creating valves that prevent
the backflow of blood
o Media: smooth muscle tissue (thickest
section in arteries)
o Adventitia: collagenous connective
tissue (thickest section in veins)
Contains elastic tissue
Elastic tissue only in
large veins
Anatomy of Capillaries
Single thickness of endothelial
cells attached to a basement
membrane
Diameter decreases as capillaries
move from end of arteriole to the
beginning of venule
Spaces (pores) between
endothelial cells determine the
capillary permeability
o Blood-brain barrier (very tight)
o Kidney capillary beds (more porous)
Smooth Muscle
Principles of flow
Known as hemodynamics of the circulatory system
• Govern the quantity of blood passing by a given point in a
specific period
• Measured as a given number of liters, milliliters, per second,
minute, or hour
• Includes the concepts of
• Pressure
• Resistance
• Velocity
• Turbulent flow
• Wall tension
Blood flow, pressure and resistance
Blood flow—movement along a
pressure gradient within the vascular
bed
Pressure—blood moves from areas
of higher pressure (arteries) to an
area of lower pressure (veins); the
greater the pressure difference, the
greater the blood flow
Resistance—opposing forces that
deter blood flow; as resistance
increases, blood flow decreases
A significant decrease in pressure occurs
as blood flows through the arterioles into
The capillaries
Question 1
Which of the following is the major site of resistance
in the vascular system and requires a greater
pressure to maintain blood flow?
A.
B.
C.
D.
Vena cava
Venules
Arterioles
Capillaries
Blood Flow, Pressure and Resistance
Physical laws govern the flow of blood though vessels
Determinants of Resistance
1. Vessel length
2. Vessel radius
3. Blood viscosity
Important Laws:
oFlow = Pressure/Resistance
oBlood pressure = flow (cardiac output) x Resistance
oResistance = Pressure/Flow
Blood Flow, Pressure and Resistance
At a constant pressure gradient:
The longer the blood vessel,
the higher the resistance and
the lower the flow
The narrower the blood
vessel, the higher the
resistance, the lower the flow
Velocity and turbulence
Velocity and Laminar and Turbulent Flow
o Laminar flow: Fastest blood flow in the center of
stream
Laminar blood flow
o Turbulent flow is an interruption in the forward
current of blood flow by crosswise flow.
Turbulent flow may manifest as
o Bruit (audible vascular sound)
o Thrill (vibratory sensation on the skin over a
turbulent flow)
o Thrombus formation (blood clot affecting flow)
• Example of pathologic cause of turbulence
Turbulent flow generated
at a vessel bifurcation
Wall tension and compliance
Distending pressure (P) is the difference
between the pressures on either side of the
vessel
An increase in radius or distending pressure
results in increased wall tension.
o If pressure reaches 20 mm Hg, called the critical
closing pressure, blood flow ceases entirely.
Compliance reflects the distensibility of a blood
vessel: veins are highly distendible and are
referred to as capacitance vessels.
Wall tension (T) = Distending pressure (P) x radius (r)
Dynamics in the Microcirculation (Capillaries)
Essence of the entire circulatory system
Exchange of nutrients and gases takes place
Clinically, The capillary fluid pressure and plasma
colloid osmotic pressure are most important
Capillary fluid pressure is the blood pressure inside
the capillary (force that pushes fluid out of vessel)
Pathologic conditions resulting in increases in BP or
resistance to flow, can alter this force, increasing it
and propelling more fluid into the interstitial space,
resulting in the formation of edema
Question
A patient has edema caused by heart failure and hypertension. In this
situation, the edema has developed because of
A.
B.
C.
D.
increased capillary fluid (hydrostatic) pressure.
increased plasma colloid osmotic pressure.
decreased interstitial fluid colloid osmotic pressure.
decreased lymphatic fluid pressure.
Control of blood flow
By Extrinsic mechanisms
All blood vessels except small venules and capillaries contain smooth muscle cells.
Arteries have much more smooth muscle than veins
Smooth muscle cells are innervated by nerve fibers from the sympathetic nervous
system (SNS)
Smooth muscle cells have α1 adrenergic receptors that respond to the SNS
neurotransmitter, noradrenaline resulting in vasoconstriction
Skeletal muscle blood vessels contain β2 adrenergic receptors which respond to
epinephrine (adrenaline) resulting in vasodilation
Control of blood flow
By intrinsic mechanisms
Autoregulation is ability of blood vessels within organs to
maintain a relatively constant blood flow regardless of changes
in arterial pressure
o When vascular smooth muscle is stretched, it contracts in response
causing vasoconstriction
o Endothelial cells also play an important role in vessel dilation and
constriction
• Produce nitric oxide (NO) gas which causes dilation by relaxing neighboring
smooth muscle cells
General causes of altered blood flow
Obstructions of the vessels
Alterations in arterial flow
Alterations in venous flow
Blood vessel structural alterations
Blood vessel obstructions
May involve arterial or venous system
Obstruction results in reduced flow beyond the obstruction
(downstream) and increased pressure before the obstruction (upstream).
In the arterial system obstruction manifests as distal ischemia.
In the venous system obstruction manifests as edema.
Thrombus as a cause of obstruction
Thrombus is a stationary blood clot formed within a vessel or a
chamber of the heart
Etiology: Thrombosis Initiated by alterations in one or more of the
following:
o Blood flow: slow or turbulent flow
o Blood vessel wall: damage or inflammation to the intimal wall of vessel
o Blood coagulability: emergence of a hypercoagulable state
oCan occur in arteries and veins
o Oral contraceptives may increase tendency for thrombosis
Thrombus as a cause of obstruction
Pathogenesis
oArterial thrombosis
• Clot within an artery reduces flow and increases turbulence which enhances
thrombus enlargement and formation of more thrombi
• Decreased distal flow can cause ischemia which can cause
 Arterial occlusion
 Myocardial infarction (heart attack)
 Stroke
oVenous thrombosis
• Clot in a vein alters venous return impairing the removal of metabolic waste and
producing swelling
• Inflammation that occurs in a vein is called phlebitis and when it is accompanied
with a clot, it is called thrombophlebitis
Thrombus as a cause of obstruction
Clinical manifestation and treatment
oArterial thrombosis
o Usually manifested by intermittent claudication (pain with activity) in the
affected limb that improves with rest
o Limb might be cool and cyanotic (bluish discoloration)
o Painful arterial ulcer around one toe
oVenous thrombosis
o Symptoms may be absent or maybe life-threatening secondary to
pulmonary embolism (PE)
o Calf or groin tenderness
o Swelling of the affected limb
Treatment: Surgical or Medical (anticoagulant therapy)
Embolus as a cause of obstruction
Embolus is a travelling clot that is propelled forward in the
bloodstream to a distant point, where it lodges to produce a new site of
obstruction
Etiology and pathogenesis
o Clot usually originates from deep veins of the pelvis and lower extremities (legs)
o Go through the right heart and then most commonly lodge in the lung arteries to
cause pulmonary embolism (PE)
o Clots dislodged from the left side of the heart usually end up in the brain artery
and cause “ischemic stroke”.
Embolus as a cause of obstruction
Clinical Manifestation
Pulmonary Embolism (PE)
o
o
o
o
May be asymptomatic or present vague (non-specific) signs and symptoms
Sudden shortness of breath
Chest pain
Sudden death
Stroke: manifestation depends on the area of the brain affected
o Loss of cognitive function
o Motor changes
o Various levels of sensory loss
Treatment: Embolectomy; Filter in vena cava
Emboli produced by other causes:
o Fat aggregates
o Metastasizing tumor cells inside the bloodstream forming aggregate
o Bacterial emboli
o Air bubbles (intravenous catheters)
Other causes of vessel obstruction
Vasospasm: sudden contraction of arterial smooth muscle
Inflammation: intima of the artery and veins
Mechanical compression: Trauma, tight casts, stockings
Atherosclerosis
Means hardening of the arteries
Coronary atherosclerosis plague
Pathologic origin for the vast majority of arterial disease
Ultimately the leading cause of death in U.S and western
Europe
Develops mostly in large and medium size arteries
o Coronary (associated with most mortality; coronary artery
disease [CAD])
o Cerebral
o Carotid
o Femoral
o Aorta
o Other organs
Site of plaque
rupture
Pathogenesis of atherosclerosis
In response to irritation or
trauma to the intima,
platelets and leukocytes are
stimulated
These activated cells attach
to the endothelial cells
1
Pathogenesis of atherosclerosis
Medial smooth muscle cells
proliferate and migrate into
the intima
Cholesterol leaks into the
vessel wall
Lipids get oxidized by
leukocytes and endothelial
cells causing more damage
2
Pathogenesis of atherosclerosis
A fibrous cap forms over the
plaque
The lesion slowly grows to
decrease the vessel
diameter
3
Pathogenesis of atherosclerosis
Additional injury may cause
rupture of the plaque
resulting in thrombus
formation and manifestation
of acute occlusion
Atherosclerotic plaque composed of
Smooth muscle cells, lipoproteins
and inflammatory debris
4
Atherosclerosis Risk Factors
Modifiable Risk Factors
o Smoking
o Elevated blood pressure
o Glucose intolerance
o Elevated cholesterol
o Decreased physical activity
o Ineffective stress management
o Depression
Nonmodifiable Risk Factors
o Age
o Gender
o Heredity (Family history)
Atherosclerosis : Clinical Manifestations and Treatment
Disease manifestations vary with the tissues involved and the severity
of altered flow
Atherosclerosis is an underlying condition for much of
o Hypertension
o Renal disease
o Cardiac disease
o Peripheral arterial disease (PAD)
Treatment
Nonpharmacologic (weight loss, diet, cessation of smoking etc.)
Surgical (angioplasty, bypass surgery)
Peripheral Artery Diseaese (PAD)
Intermittent claudication
(Pain with Activity)
Less common conditions affecting blood flow
Aneurysms
Localized arterial dilations, bulge outward
Classified as true or false aneurysms
True aneurysms include
• Saccular: one-sided balloon
• Fusiform: both sides balloon out
• Berry: balloon has a stem/neck
Frequently found in cerebral circulation
and thoracic and abdominal aorta
Less common conditions affecting blood flow
Raynaud Syndrome
Extreme vasoconstriction producing cessation of flow to fingers
and toes
o Color changes: white, blue (cyanosis), red (hyperemia); pain, numbness;
cold triggers attacks
Intrinsic structural factors, extrinsic neuroregulation, and locally
produced mediators involved
Treatment: enhancing circulation through relaxation,calciumchannel blockers, sympatholytic drugs, prostaglandins
Alterations of Venous Flow
Incompetent valves (e.g. in obesity,
pregnancy, right heart failure, prolonged
standing) producing
o Varicose veins
• Superficial veins affected
o Chronic venous insufficiency
• Deep veins affected
o Deep vein thrombosis
• Could lead to life-threatening pulmonary emboli
Accompanied by edema, venous stasis,
inflammation, ulcers, and pain
Open valves
Closed valves
Incompetent
valve
Alterations in Lymphatic Flow
Lymphedema
Occurs when normal flow is obstructed or
altered in some fashion
Primary lymphedema results from
congenital anomaly or dysfunction of the
lymphatic system.
Secondary lymphedema associated with a
disease process or iatrogenic
o Most common worldwide: infection by filarial
worms (Wuchereria bancrofti)
o Most common in United States because of
lymph node removal, radiation
Lymphedema associated
with mastectomy