Pathophysiology Of Varicose Vein - Chronic Venous Insufficiency 1i3g4y

PATHO-PHYSIOLOGY OF CHRONIC VENOUS INSUFFICIENCY DR G MARK MALOUF SURGEON SYDNEY AUSTRALIA

Four requirements for adequate venous flow 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  Cardiac

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

Clinical Etiological Anatomical Pathophysiological CEAP Grade

C0 C1 C2 C3 C 4a 4b

Description

No evidence of venous disease Superficial spider veins or reticular veins Varicose veins Ankle / calf oedema of venous origin ( ? not foot oedema) Skin pigmentation in the gaiter area Varicose eczema Atrophie blanche Lipodermatosclerosis

C5 A healed venous ulcer C6 An open venous ulcer EACH CLASS IS DESIGNATED SYMPTOMATIC S ASYMPTOMATIC A

OR

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 V’s Healthy

Diseased

FUNCTIONAL PATHOLOGY PRODUCING PROLONGED HIGH VENOUS PRESSURE OBESITY IMMOBILITY

GRAVITY

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

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.

2.

3. 4.

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VARICOSE VEINS AND VENOUS THROMBOSIS OCCUR COMMONLY AND HAVE A GENETIC COMPONENT MODIFIED BY ENVIRONMENTAL AND LIFESTYLE FACTORS THEY PRODUCE CHRONIC VENOUS HYPERTENSION WHICH IN SUSCEPTIBLE PATIENTS PRODUCES MICROVASCULAR PATHOLOGY IN DERMAL CIRCULATION A CASCADE OF INFLAMMATORY EVENTS OCCURS MACROMOLECULES AND RBCs EXTRAVASATE STIMULATING ONGOING INFLAMMATION CYTOKINES AND GROWTH FACTORS RELEASED LEUCOCYTE MIGRATION INTO TISSUES 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