Pathophysiology of Varicose Vein - Chronic Venous Insufficiency

8/12/2019 Pathophysiology of Varicose Vein - Chronic Venous Insufficiency

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PATHO-PHYSIOLOGYOF

CHRONIC VENOUSINSUFFICIENCY

DR G MARK MALOUF

SURGEON

SYDNEY AUSTRALIA







Four requirements for adequate

venous flowCardiac pump “vis a tergo”

Pressure difference between the legs and

the right heart , assisted by negative

thoracic pressure

Venous pumps Calf muscle pump

Foot pumpCompetent venous valves



CHRONIC VENOUS DISEASE

THE CLINICAL APPEARANCE we see in

patients with CHRONIC VENOUS

DISEASE represents CHRONIC VENOUSINSUFFICIENCY - CVI

These clinical changes are the result ofPROLONGED HIGH VENOUS PRESSURE

ie CHRONIC VENOUS HYPERTENSION





CHRONIC VENOUS INSUFFICIENCY

The damage to the MICROCIRCULATION

in patients with CHRONIC VENOUS

HYPERTENSIONIS CALLED

VENOUS HYPERTENSIVE

MICROANGIOPATHY




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

SECONDARYDEEP VEIN PARTIAL OBSTRUCTION AND REFLUX

PERFORATING VEIN INCOMPETENCE

THIGH CALF



Valvular Function in V V’s

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 SITTINGHEIGHT

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




VENOUS STASIS THEORY

1917 HOMANS

BLOOD STASISPOOR NUTRITION

HYPOXIA

TISSUE BREAKDOWN




ARTERIO-VENOUS FISTUALE THEORY

1949 PRATT

SHUNT VIA ARTERIOLES

TISSUE HYPOXIA AND BREAKDOWN




DIFFUSION BLOCK THEORY

1981-82 BURNAND & BROWSE

WIDENED ENDOTHELIAL GAP JUNCTIONEXTRAVASATION OF FIBRINOGEN

FIBRIN CUFFS DEVELOP

BARRIER TO OXYGEN DIFFUSION ANDNUTRIENT BLOOD FLOW

EPIDERMAL CELL DEATH




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





CVI Pathophysiology Sequence of Events

High venous pressure

Extravasation RBCs and 2 macroglobulins &fibrinogen

Degradation & chemotaxis beginning the inflammatoryprocess

Leukocytes attracted especially mast cells and monocytesRelease 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

fibroblastsExpression of intracellular adhesion

molecules ICAM 1 used for diapedesis of

white cellsCascade of inflammatory events

Expression of PDGF & VEGF

Leukocyte recruitment



Tissue Matrix Changes

Matrix deposition is controlled bymatrix metalloproteinases (MMPs)

Their inhibitors are tissue inhibitors of MMPs= TIMPs

TGF 1 controls matrix deposition and remodelingTGF 1 binds to dermal fibroblasts resulting in

intense dermal fibrosis collagen synthesis

Diminished fibroblast proliferation: senescence

and poor ulcer healingOther matrix proteins Fibronectin

- Galactosidase

Extracellular Matrix Contraction




VENOUS MICROCIRCULATION PATHOLOGY

ENDOTHELIAL CELLS THICKER

INTER-ENDOTHELIAL JUNCTIONS WIDER

EXTRACELLULAR MATRIX ALTERED

LEUCOCYTES ARE PARTICIPATINGINTERCELLULAR ADHESION MOLECULES COHESINS

TRANSFORMING GROWTH FACTORS

TGFB1 PDGF VEGF

DERMAL FIBROBLASTS BECOME SENESCENTMATRIX METALLO PROTEINASES

MMPs TIMPS

CYTOKINES VENOUS ULCER WOUND FLUID



SUMMARY OF CVI PATHO-PHYSIOLOGY

1. VARICOSE VEINS AND VENOUS THROMBOSIS OCCURCOMMONLY AND HAVE A GENETIC COMPONENT MODIFIED BYENVIRONMENTAL AND LIFESTYLE FACTORS

2. THEY PRODUCE CHRONIC VENOUS HYPERTENSION WHICH INSUSCEPTIBLE PATIENTS PRODUCES MICROVASCULAR

PATHOLOGY

3. IN DERMAL CIRCULATION A CASCADE OF INFLAMMATORY

EVENTS OCCURS4. MACROMOLECULES AND RBCs EXTRAVASATE STIMULATING

ONGOING INFLAMMATION CYTOKINES AND GROWTHFACTORS RELEASED LEUCOCYTE MIGRATION INTO

TISSUES

5. INTENSE DERMAL FIBROSIS RESULTS FIBROBLASTPROLIFERATION DIMINISHES – SENESCENCE

MMP-2 SYNTHESIS IMPEDES ULCER HEALING

COMPLEX MULTI-FACTORIAL INTERACTION IN SUSCEPTIBLE PTS

PRODUCING THE CLINICAL FINDINGS OF CVI

Ai f T t t i CVI



Aims of Treatment in CVI

Patients

Reduce the persistently high venous pressureTreat and eliminate venous reflux

Relieve venous obstruction

Elevate the foot of the bed

Graduated compression stockingsWeight reduction and increased walking

Modify the inflammatory process occurring in the gaiter

area of these legs DAFLON 500Block 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

Pathophysiology of Varicose Vein - Chronic Venous Insufficiency

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