PATHO-PHYSIOLOGY

OF
CHRONIC VENOUS
INSUFFICIENCY
DR G MARK MALOUF
SURGEON
SYDNEY AUSTRALIA
Four requirements for adequate
venous flow
Cardiac pump vis a tergo
Pressure difference between the legs and
the right heart , assisted by negative
thoracic pressure
Venous pumps Calf muscle pump
Foot pump
Competent venous valves
CHRONIC VENOUS DISEASE
THE CLINICAL APPEARANCE we see in
patients with CHRONIC VENOUS
DISEASE represents CHRONIC VENOUS
INSUFFICIENCY - CVI

These clinical changes are the result of
PROLONGED HIGH VENOUS PRESSURE
ie CHRONIC VENOUS HYPERTENSION
CHRONIC VENOUS INSUFFICIENCY
The damage to the MICROCIRCULATION
in patients with CHRONIC VENOUS
HYPERTENSION
IS CALLED

VENOUS HYPERTENSIVE
MICROANGIOPATHY
CHRONIC VENOUS INSUFFICIENCY
Persistently high venous pressure FROM
WHATEVER CAUSE MAY result in the
SIGNS OF CVI

OEDEMA
PIGMENTATION
VARICOSE ECZEMA
LIPODERMATOSCLEROSIS
ATROPIE BLANCHE
LEG ULCERATION
+/- VISIBLE VARICOSITIES

CEAP CLASSIFICATION OF VARICOSE
VEINS AND VENOUS DISEASE
CLINICAL C0 C1 C2 C3 C4 C5 C6
ETIOLOGICAL CONGENITAL PRIMARY SECONDARY
ANATOMICAL WHICH VEINS AFFECTED S D P
PATHOPHYSIOLOGICAL REFLUX OBSTRUCTION BOTH
Grade Description

C 0 No evidence of venous disease
C 1 Superficial spider veins or reticular veins
C 2 Varicose veins
C 3 Ankle / calf oedema of venous origin ( ? not foot
oedema)
C 4a Skin pigmentation in the gaiter area Varicose eczema
4b Atrophie blanche Lipodermatosclerosis

C 5 A healed venous ulcer
C 6 An open venous ulcer
EACH CLASS IS DESIGNATED SYMPTOMATIC S OR
ASYMPTOMATIC A

Clinical Etiological Anatomical
Pathophysiological CEAP
CAUSES OF PROLONGED HIGH
VENOUSPRESSURE
VENOUS PATHOLOGY

VENOUS REFLUX in SUPERFICIAL or DEEP or
PERFORATING VEINS from Valvular incompetence
VENOUS OBSTRUCTION of DEEP VEINS
COMBINED REFLUX AND OBSTRUCTION

FUNCTIONAL PATHOLOGY

OBESITY
IMMOBILITY
GRAVITY
VENOUS PATHOLOGY PRODUCING
PROLONGED HIGH VENOUS PRESSURE
VARICOSE VEINS
SFI SPI
VENOUS REFLUX IN SAPHENOUS TRUNKS
AND MAJOR TRIBUTARIES
DEEP VEIN THROMBOSIS
OUTFLOW OBSTRUCTION
DEEP VEIN REFLUX PRIMARY
SECONDARY
DEEP VEIN PARTIAL OBSTRUCTION AND REFLUX
PERFORATING VEIN INCOMPETENCE
THIGH CALF

Valvular Function in V Vs
Healthy Diseased
FUNCTIONAL PATHOLOGY PRODUCING
PROLONGED HIGH VENOUS PRESSURE
OBESITY

IMMOBILITY POOR MOBILITY REDUCES CALF
MUSCLE PUMP AND FOOT PUMP.
IT REDUCES LYMPHATIC TRANSPORT

GRAVITY PROLONGED STANDING
PROLONGED SITTING
HEIGHT
CVI PATIENTS OFTEN SPEND PROLONGED PERIODS
SITTING IN A CHAIR AND MANY SLEEP PERMANENTLY
IN A CHAIR AND NEVER GO TO BED


THEORIES TO EXPLAIN HOW HIGH VENOUS
PRESSURE PRODUCES MICROANGIOPATHY
AND THE CLINICAL FINDINGS OF CVI
VENOUS STASIS THEORY

ARTERIO-VENOUS FISTULAE THEORY

DIFFUSION BLOCK THEORY

LEUCOCYTE TRAPPING AND
ACTIVATION THEORY

More modern cellular theories
CHRONIC VENOUS INSUFFICIENCY
VENOUS STASIS THEORY

1917 HOMANS
BLOOD STASIS
POOR NUTRITION
HYPOXIA
TISSUE BREAKDOWN
CHRONIC VENOUS INSUFFICIENCY
ARTERIO-VENOUS FISTUALE THEORY

1949 PRATT

SHUNT VIA ARTERIOLES

TISSUE HYPOXIA AND BREAKDOWN
CHRONIC VENOUS INSUFFICIENCY
DIFFUSION BLOCK THEORY

1981-82 BURNAND & BROWSE
WIDENED ENDOTHELIAL GAP JUNCTION
EXTRAVASATION OF FIBRINOGEN
FIBRIN CUFFS DEVELOP
BARRIER TO OXYGEN DIFFUSION AND
NUTRIENT BLOOD FLOW
EPIDERMAL CELL DEATH
CHRONIC VENOUS INSUFFICIENCY
LEUCOCYTE TRAPPING AND
ACTIVATION THEORY

1988 COLERIDGE SMITH SCURR
CIRCULATING NEUTROPHILS TRAPPED IN VENOUS
MICROCIRCULATION SECONDARY TO HIGH VENOUS
PRESSURE
SLUGGISH CAPILLARY FLOW
HYPOXIA
NEUTROPHIL ACTIVATION
DAMAGE TO ENDOTHELIAL CELLS
EVENTUAL SKIN DAMAGE
Venous Hypertensive
Microangiopathy
Early investigators looked at suspected hypoxia from
Stagnation or pooling of blood
Arteriovenous shunting
Peri-capillary fibrin cuff reducing oxygen diffusion
Recent investigators are looking at
Extravasation of RBCs and macromolecules
CYTOKINES signaling molecules cellular
communications
Leukocyte activation INFLAMMATION Release of
other cytokines and growth factors in the dermis
Fibroblast activity
Remodeling of the dermis producing fibrosis

CVI Pathophysiology Sequence of Events
High venous pressure
Extravasation RBCs and 2 macroglobulins &
fibrinogen
Degradation & chemotaxis beginning the inflammatory
process
Leukocytes attracted especially mast cells and monocytes
Release of Transforming GF 1 - TGF 1
Fibroblast activity is modified by TGF 1
Other cytokines & growth factors released (VEGF &
PDGF)
Extracellular matrix changes Soft tissue destruction
Dermal fibrosis and remodeling
Ulceration
Immunohistochemistry &
Immunoreactivity Studies
TGF 1 is the most potent modulator of
cellular dysfunction in CVI especially of
fibroblasts
Expression of intracellular adhesion
molecules ICAM 1 used for diapedesis of
white cells
Cascade of inflammatory events
Expression of PDGF & VEGF
Leukocyte recruitment

Tissue Matrix Changes
Matrix deposition is controlled by
matrix metalloproteinases (MMPs)
Their inhibitors are tissue inhibitors of MMPs
= TIMPs
TGF 1 controls matrix deposition and remodeling
TGF 1 binds to dermal fibroblasts resulting in
intense dermal fibrosis collagen synthesis
Diminished fibroblast proliferation: senescence
and poor ulcer healing
Other matrix proteins Fibronectin
- Galactosidase
Extracellular Matrix Contraction
CHRONIC VENOUS INSUFFICIENCY
VENOUS MICROCIRCULATION PATHOLOGY

ENDOTHELIAL CELLS THICKER
INTER-ENDOTHELIAL JUNCTIONS WIDER
EXTRACELLULAR MATRIX ALTERED
LEUCOCYTES ARE PARTICIPATING
INTERCELLULAR ADHESION MOLECULES COHESINS
TRANSFORMING GROWTH FACTORS
TGFB1 PDGF VEGF
DERMAL FIBROBLASTS BECOME SENESCENT
MATRIX METALLO PROTEINASES
MMPs TIMPS
CYTOKINES VENOUS ULCER WOUND FLUID
SUMMARY OF CVI PATHO-PHYSIOLOGY
1. VARICOSE VEINS AND VENOUS THROMBOSIS OCCUR
COMMONLY AND HAVE A GENETIC COMPONENT MODIFIED BY
ENVIRONMENTAL AND LIFESTYLE FACTORS
2. THEY PRODUCE CHRONIC VENOUS HYPERTENSION WHICH IN
SUSCEPTIBLE PATIENTS PRODUCES MICROVASCULAR
PATHOLOGY
3. IN DERMAL CIRCULATION A CASCADE OF INFLAMMATORY
EVENTS OCCURS
4. MACROMOLECULES AND RBCs EXTRAVASATE STIMULATING
ONGOING INFLAMMATION CYTOKINES AND GROWTH
FACTORS RELEASED LEUCOCYTE MIGRATION INTO
TISSUES
5. INTENSE DERMAL FIBROSIS RESULTS FIBROBLAST
PROLIFERATION DIMINISHES SENESCENCE
MMP-2 SYNTHESIS IMPEDES ULCER HEALING

COMPLEX MULTI-FACTORIAL INTERACTION IN SUSCEPTIBLE PTS
PRODUCING THE CLINICAL FINDINGS OF CVI
Aims of Treatment in CVI
Patients
Reduce the persistently high venous pressure
Treat and eliminate venous reflux
Relieve venous obstruction
Elevate the foot of the bed
Graduated compression stockings
Weight reduction and increased walking

Modify the inflammatory process occurring in the gaiter
area of these legs DAFLON 500
Block the release or activation of TGF 1
Modify fibroblast activity Reduce leukocyte attraction
C6 patients: Wound care dressings compression
medications to encourage wound healing


Practical Points when using stockings in CVI
Below-knee almost always
Patient often unable to apply or remove
strong stockings
Stockings may aggravate venous eczema
due to heat under stocking
Two lower compression stockings easier
to apply than a very strong one
Fitting and education VITAL Who is fitting
Thank you and Greetings from Sydney