Blood flow

regulation of
venous system


The oldest known illustration
of a venous disease (4th
century B.C.)

The original marble panel is

exposed in the Greek National
Archeological Museum in Athens
 Development of artery and vein

Swift MR and Weinstein BM. Circ. Res. 2009;104;576-588

Development of artery and vein
 Contents

Venous structure, compliance

1 and permeability

2 Regulation of venous flow

3 Venous function in health and disease

 Differences Between Arteries and Veins

Arteries
Blood pumped into single
Delivery
systemic artery the aorta
Deep, and protected by
Location
tissue
Pathways Fair, clear, and defined
Supply/drainage Predictable supply
Veins
Blood returns via superior and
interior venae cavae and the
coronary sinus
Both deep and superficial
Convergent interconnections
Dural sinuses and hepatic portal
circulation
Generalized Structure of Blood Vessels
 Venous System: Veins

Thicker tunica interna than arteries

Poorly developed Middle layer of venous wall
thinner, less smooth muscle, less elastic tissue
Thick tunica externa consisting of collagen fibers and elastic networks
Lumens have greater diameter.
Compliance in systemic arterial and venous
systems
Systemic Blood Pressure
Velocity of Blood Flow
 Valves of Veins

Found in many veins,

especially in limbs
Project inward from the
lining
Composed of 2 leaflets
that close if blood
begins to back up in a
vein.
Aid in returning blood to
the heart (open if flow is
toward the heart)
 Veins
Veins are blood volume reservoir

Due to thinness of vessel wall less resistance to stretch = more

compliance

Veins are 30 times

more compliant
than arteries
 Dynamic regulatory portion in blood vessel

5% in the capillaries

8% in the heart

12% in the pulmonary vasculature

15% in the arterial system

60% in the venous vasculature

 Blood volume distribution and mobilization
by sympathetic nerve stimulation

In the cat, 64% of splanchnic blood volume (21% of total blood volume)
mobilized by direct electrical stimulation of sympathetic nerves
23% of blood volume from vascular beds in muscle, skin, adipose tissue,
cardiopulmonary region, heart, and kidneys mobilized by sympathetic stimulation
 Veins are primary site of permeability
during inflammation

1: untreated
vessels
2: vessels treated
with TNF-
3: endothelium in
IVC of untreated
animals
4: IVC in TNF-
treated animals
5: TNF- treated
IVCs where
primary antibody
was excluded
from staining
protocol.

Eriksson EE, et al. Arterioscler Thromb Vasc Biol 2005;25;723-728

Veins are primary site of permeability
during inflammation

Leukocyte rolling
and adhesion in
the mouse aorta,
IVC, and cremaster
muscle
venules.

Plasma leakage in mouse IVC and

aorta detected by confocal imaging
of vessel accumulation of plasma
tracer molecule FITCdextran

Eriksson EE, et al. Arterioscler Thromb Vasc Biol 2005;25;723-728

 Contents

Venous structure, compliance and

1 permeability

2 Regulation of venous flow

3 Venous function in health and disease

 Baroreflex system

Afferent pathway: Baroreceptors: Terminals of glossopharyngeal and vagus nerves Nucleus of tractus
solitarius (NTS) in medulla Nucleus ambiguus
Sympathetic efferent pathway: caudal ventrolateral medulla (excitatory pathway) and from there to the
rostral ventrolateral medulla (inhibitory pathway)
In response to a sustained BP fall in blood pressure, vasopressin release from magnocellular portion of the
paraventricular nucleus and supraoptic nucleus of hypothalamus.
 RELATIVE SENSITIVITY OF RESISTANCE (arterioles)
AND CAPICATANCE (venules) VESSELS

C apa citance
ves sels
% of Maximal Response

Resistance vessels

Frequency of sympathetic stimulation (impulses/sec)

 Determinant of venous capacitance

Compliant veins: Mainly splanchnic

Receiving approximately 25% of cardiac output and
containing approximately 20% of total blood volume
Splanchnic and cutaneous veins having high population
of 1- and 2-adrenergic Rcs, thus highly sensitive to
adrenergic stimulation
Non-compliant veins: Veins of extremities
Relatively minimal role as blood volume reservoir
skeletal muscle veins having relatively insignificant
sympathetic innervation
Cutaneous circulation mainly controlled by temperature
 Factors Aiding Venous Return

Venous BP alone is too low to

promote adequate blood
return and is aided by the:
Respiratory pump pressure
changes created during breathing
suck blood toward the heart by
squeezing local veins
Muscular pump contraction of
skeletal muscles milk blood
toward the heart
Valves prevent backflow
during venous return
 Thoracoabdominal venous pump

A: During inspiration, intrathoracic pressure and

intraabdominal pressure , speeding up blood flow from
abdominal veins toward chest.
B: During expiration, blood flow toward chest is inhibited by
thoracic pressure and abdominal pressure
 Factors influencing venous return
1- Skeletal muscle pump
and valves

2- Respiratory pump

3- Blood volume

4- Venomotor tone
 Contents

Venous structure, compliance and

1 permeability

2 Regulation of venous flow

3 Venous function in health and disease

 Normal response to standing

500-1000mL of blood pooled in lower extremities and

splanchnic circulation on upright posture
Rapid decrease in venous return to heart
Diminished cardiac output and blood pressure
Compensatory CNS reflex
Increasing sympathetic outflow -> rise in peripheral resistance
Decreasing parasympathetic outflow
Heart rate and peripheral vascular resistance
Cardiac output and blood pressure
Normal response on standing
Small fall in SBP reduction: 5 10mmHg
Increase in DBP: 5 10mmHg
Increase in pulse rates: 10 25beats per minutes
 Physical maneuver helpful in venous return

Cross legs while standing

Squat, stooping forward
Raise head of bed 10 to 20 degrees
Elastic waist high stocking

(A) Toe raise. (B) Leg cross. (C) Forward lean.

(D) Step up. (E) Genuflectioncontraction. (F) Squat.
Phillip A Low, Wolfgang Singer, Lancet Neurol 2008; 7: 45158
 Meal and Water Drinking effect
in orthostatic BP change

Postprandial hypotension aggravated by large meals especially

high in carbohydrate and alcohol
Experiment below in 7 patients of autonomic OH, who drank
480 mL of tap water at room temperature in less than 5 minutes

Shannon JR, et al. Am J Med. 2002;112:355360

 Causes of peripheral neuropathy
resulting in orthostatic hypotension
Diabetes mellitus: Most common cause of autonomic dysfunction
Wernicke-Korsakoff syndrome
Uremia
Amyloidosis
Porphyria
Paraneoplastic syndromes
Nutritional deficiencies (vitamin B12, folate)
Guillain-Barre syndrome
Syringomyelia
Tabes dorsalis
Systemic collagen vascular diseases
Pernicious anemia
Spinal cord injury
 Diabetic autonomic dysfunction

Autonomic insufficiency may result in reduced

noradrenaline release in response to postural changes
Venous compliance reduced relative to that of healthy controls
Response to noradrenaline increased due to defective neuronal
uptake mechanism (Denervation supersensitivity?)
No difference in response to Endothelin-1.
Usually but not always associated with generalized
polyneuropathy
Orthostatic hypotension may occur early in clinical course
Other autonomic manifestations may include
Gastroparesis
Diarrhea, Constipation, Urinary retention
Erectile dysfunction
 Hemodialysis

Dizziness, malaise, nausea, abdominal cramps, and

hypotension occurred in 25% of HD patients
Despite autonomic neuropathy in most HD patients
Intact efferent sympathetic nerves: reduced venous compliance and
increased MAP and noradrenaline in response to the cold pressor test
Autonomic defect either in afferent baroreflex arc, efferent
parasympathetic nerves, or heart: Impaired response to Valsalva
maneuver
HD patients with hypotension associated with increased
venous compliance and reduced venous return, stroke
volume, CO, as well as calf blood flow
Vasoconstriction and venoconstriction impaired during
ultrafiltration plus HD, contributing to hypotension
 Hypertension
Hypertensive subjects have
Higher central venous pressure
Lower total blood and venous blood volumes
Similar arterial blood volume due to arterial compliance
Decreased venous compliance (-25%) in
Several forms of experimental hypertension in experimental animals
Human subjects with established or borderline hypertension
Normotensive subjects with a family history of hypertension
Reduced compliance in peripheral veins leads to
centralization of blood volume, thereby
increasing diastolic pressure and cardiac output
Might be compensatory mechanism against increased peripheral
vascular resistance that decreases CO
Distribution of the vein valves in the hind limb
 Leg Vein Anatomy

Perforating veins
connect the deep system
with the superficial
system
They pass through the
deep fascia at mid-thigh,
knee and ankle
60-80% drop of pressure
during perforating veins
from superficial to deep
vein due to orthostatic
muscle work
 Venous Reflux Disease

1. Vein valves become

damaged or
diseased, resulting
Normal Vein Dilated Vein
in vein valve failure
Heart
2. Reflux or backward
flow in the veins
occurs
3. Pooling of blood
causes pressure in
Foot
leg veins
Valve Valve Leaky
Open Closed Valve 4. Increased pressure
may cause surface
veins to become
varicose
Venous Reflux Disease

In America, 72% of women and

42% of men will experience
varicose veins by the time they
are in their 60s.
High prevalence among the
aged and females

Clinical manifestations of
chronic venous desease

A: teleangiectases
B: varicose veins
C: pigmentation
D: active ulceration

N. Engl. J. Med. 355: 488-98, 2006

 Summary

Venous system contains ~ 70% of the blood volume with buffering

capacity against volume shift.
Maintenance of venous circulation through
Sympathetic nervous system
Respiratory and Muscular pump with valves
Most common consequence of impaired venous function is
orthostatic hypotension and syncope due to
Interference of autonomic function through the intake of nitrovasodilators or
sympathetic blockers
Autonomic failure or baroreflex dysfunction (e.g., dysautonomia, DM,
vasovagal syncope, and hypertension)
Increased venous compliance (e.g.,hemodialysis, hypertension, and bed rest)
Reduced blood volume (as with microgravity)
Increased venous pressure and valve damage resulting in venous
reflux disease in lower extremity
Determinants of venous pressure

Alterations in venous return

alter end-diastolic volume
(EDV);
increased EDV directly
increases stroke volume and
cardiac output.