Venous Pathophysiology PDF

ECHO/SONO/VASC 112 – Vascular Fundamentals Venous Pathophysiology Hemostasis  Themechanism involved in the arrest of blood from a damaged blood vessel Vasoconstriction  When a blood vessel is injured, the smooth muscle cells in the traumatized blood vessel contract, reducing the volume o...

ECHO/SONO/VASC 112 – Vascular Fundamentals Venous Pathophysiology Hemostasis  Themechanism involved in the arrest of blood from a damaged blood vessel Vasoconstriction  When a blood vessel is injured, the smooth muscle cells in the traumatized blood vessel contract, reducing the volume of blood flowing through the blood vessel  Nerve reflex  Myogenic spasm  Local humoral factors ▪ Thromboxane A2 ▪ Serotonin Formation of Platelet Plug  Normal platelet  Cell fragments derived from megakaryoblasts  Formed in bone marrow  Surface membranes contains glycoproteins that make them slippery  Cytoplasm contains numerous granules that play role in clotting process Formation of Platelet Plug  Platelet Reaction  Viscous metamorphosis ▪ Platelet comes into contact with damaged endothelium or collagen fibers ▪ Undergo complex biochemical transformation in which they swell and form irregular shapes  Adhesion ▪ Platelets become sticky and adhere to rough surfaces and fibers ▪ They secrete chemicals, ADP and Thromboxane A2 Formation of Platelet Plug  Aggregation ▪ ADP and Thromboxane A2 activate other nearby platelets to undergo adhesion reaction ▪ These platelets adhere to original platelets and repeat the cycle ▪ A plug of platelets is formed that blocks the wound ▪ Platelets also release factors that are involved in clotting reaction Coagulation  The activation or conversion of soluble factors present in the blood into an insoluble network of fiber strands that close the wound in blood vessel 1. Prothrombin activator (PTA) is a complex of substances formed to begin the coagulation process. It is formed by the intrinsic or extrinsic pathway in response to tissue or endothelial Coagulation 2. PTA catalyzes the formation of thrombin from prothrombin 3. Thrombin catalyzes the conversion of soluble fibrinogen to solid fibrin polymer threads. The fibrin threads form a mesh upon which the plasma, blood cells and platelets aggregate to make the clot. Clotting Factors  There are a number of substances that are normally present in the blood that play an integral role in the clotting process. These substances are mainly synthesized in the liver.  Factors are present in the blood as inactive agents **See handout for list of factors** Clotting Cascade Intrinsic Pathway  Initiated by trauma to blood (platelets)  Activated when the blood comes into contact with damaged endothelial cells or collagen fibers 1. Activation of Factor XII 2. Activation of Factor XI 3. Activation of Factor IX Clotting Cascade Intrinsic Pathway 4. Formation of Active Factor X This step involves the interaction of platelet factors, calcium ions, active factor IX, and factor VIII to activate Factor X 5. Formation of Prothrombin Activator A complex is formed including active Factor X, Factor V, Platelet Factors, and calcium ions. This is Prothrombin Activator. 6. Formation of Thrombin PTA converts prothrombin (inactive Factor II) into its active form, thrombin Clotting Cascade Extrinsic Pathway  Initiated by trauma to the vessel or to external tissues 1. Release of Tissue Thromboplastin Thromboplastin (Factor III) is a substance contained within many tissues and is released by them when they are damaged 2. Activation of Factor X Tissue thromboplastin activates and combines with Factor VII which activates Factor X 3. Formation of Prothrombin Activator Formation of the Clot  Resultof the conversion of a soluble plasma protein, fibrinogen (Factor I), into an insoluble meshwork of fibrin  Fibrinogen is converted to fibrin monomers by the action of the catalyst, thrombin  Fibrin monomers polymerize, are linked end to end, into a long insoluble molecule, fibrin  The fibrin strands are cross-linked to Formation of the Clot  The fibrin strands stretch across the opening in the blood vessel and the fibrin meshwork traps blood cells that try to pass through it.  This forms a barrier that prevents blood loss from the blood vessel.  The fibrin strands eventually contract and form an impermeable barrier. Prevention of Blood Clotting  Endothelial Surface Factors  Smoothness of endothelium  Layer of glycocalyx  Thrombomodulin  Antithrombin Agents  Fibrin – once fibrin is formed it inhibits thrombin  Antithrombin III – binds thrombin Prevention of Blood Clotting  Heparin  Secreted by mast cells  Increases effectiveness of antithrombin III  Decreases effectiveness of Factors XII, XI, IX and X  Alpha 2 Macroglobulin  Combines with coagulation factors and inactivates them Fibrinolysis  Plasmin  Plasminogen is a normal constituent of plasma but is not active  Plasminogen is trapped among the fibrin strands in clot  Tissue plasminogen activator is released from damaged tissues and converts plasminogen to plasmin  Plasmin digests the fibrin strands as well as other clotting factors such as fibrinogen, prothrombin and some factors ECHO/SONO/VASC 112 - Vascular Fundamentals Venous Pathophysiology Part II DVT Annual Estimates 1 - 10 million cases of DVT  600,000 cases of PE  200,000 deaths from PE Incidence of DVT  Major GYN Surgery 30%  Average Surgical Patient 20 – 30%  Older Surgical Patient 40 – 59%  Hip Fracture 40 – 50%  Hip or Knee Replacement 50%  Myocardial Infarction 20 – 50%  Stroke 30 – 60% *PE is a major cause of post-op death *Post phlebitic syndrome is common and one of the most intractable problems in medicine Definitions  Thrombus  The presence of a blood clot within a blood vessel  Thrombophlebitis  The formation of a blood clot followed by an inflammatory reaction in the vessel wall and in perivascular structures  Deep Vein Thrombosis (DVT)  Presence of thrombus within the peripheral deep venous system  Superficial Venous Thrombosis/Superficial Thrombophlebitis  Presence of thrombus within the peripheral superficial venous system  Stasis Hypercoagulability Vein wall injury Vessel Damage  Causes  Direct trauma  Previous thrombosis  Inflammation  Infection  Mechanisms of thrombus  Activation of clotting factors  Inhibition of natural fibrinolysis  Exposing blood to collagen fibers Stasis of Blood Flow  Causes  Bed rest  Immobility  Spinal cord injury  Venous obstruction  Pregnancy  Mechanism of thrombosis  Inactivity of calf muscle pump  Allows clotting factors to accumulate locally Hypercoagulability of Blood  Causes  Pregnancy  Neoplastic disease/cancer  Oral Contraceptives/estrogen replacement  Mechanism of thrombosis  Presence of excessive amounts of clotting factors  Absence of normal amounts of fibrinolytic factors Formation of Venous Thrombus Location  90% of DVT occurs in legs  Acute DVT usually begins by platelet and fibrin deposits accumulating behind the venous valve cusps  Usual site in in the muscular veins of the calf Formation of Venous Thrombus Propagation of Thrombus  Clot begins to grow  It may produce a long, free flowing clot, loosely attached to point on the venous wall  Clot may fill the vein and occlude it. This may or may not obstruct venous return from the area.  Clot may undergo spontaneous lysis Formation of Venous Thrombus Fate of Thrombus  Clot eventually undergoes organization  Clot contracts, pulling vein walls together  New channels for blood flow are formed within the vessel lumen  The vein valves are destroyed Clinical Manifestations  Silent DVT  Venous obstruction  Intraluminal thrombosis  Extramural compression  Pathophysiology  Increased venous resistance  Increased venous pressure  Edema  Extravasation of blood Symptoms of DVT Persistent leg pain with acute onset Persistent leg swelling Calf pain/tenderness Leg discoloration If patients have above symptoms, 50% chance of DVT Clinical Diagnosis of DVT  Low sensitivity  Many DVTs are clinically asymptomatic  Incomplete patient history/vague complaints  Low specificity  Non-thrombotic disorders can cause the same clinical symptoms as DVT Complications  Embolization  Phlegmasia  Unnecessary treatment  Post phlebitic syndrome  Chronic venous insufficiency  Venous stasis ulcer Symptom with high positive predictive value for DVT: Phlegmasia cerulea dolens  Massive thigh and calf swelling  Limb cyanosis  Ilio - femoral outflow obstruction Phlegmasia cerulea dolens CFV Thrombosed Extensive swelling and cyanosis of left leg Venous Stasis Ulcers  Venous vs. Arterial symptoms VENOUS ARTERIAL  Acute onset SX  Progressive SX  Limb swelling  Intermittent pain  Persistent pain when walking calf/thigh  Foot/limb  Local coolness tenderness  Limb pallor  Palpable “cord”  Gangrene  Chest pain/SOB Deep Vein Thrombosis Obstructive Acute vs. Chronic DVT  Acute  Chronic  Distended vein  Vein lumen is small  New, propagating  Old, consolidated clot clot  Not tightly attached  Tightly attached to to vein wall vein wall  High risk for  Low risk for embolization embolization  Large lumen filled with thrombus Deep Vein Thrombosis Non-Obstructive Acute vs. Chronic  Acute  Chronic  Thrombus is  Thrombus adheres eccentric to vein wall  May have free-  Chronic scarring and floating tail thickening of vein  Flow is normal wall around thrombus  Flow is directed to center of vein  Damage to valves may cause flow abnormalities Deep Vein Thrombosis Fate of Thrombus  Lysis of thrombus  Size  Obstructive thrombus lasts longer  Non-obstructive thrombus in high flow channels absorbs quickly  Rate of lysis is due to exposure to lytic substances Deep Vein Thrombosis Fate of Thrombus  Neointimal Thickening  Thrombus adheres to vein wall  Fibroelastic tissue is deposited on and incorporated into thrombus  Restoration of Flow  Partially reopened native venous channels  Small channels in vaso vasorum  Development of collateral channels Deep Vein Thrombosis Fate of Thrombus  Post Thrombotic Syndrome/Post Phlebitic Syndrome  Chronic deep vein obstruction  Chronic deep valve incompetence  Clinical manifestations  Progressive leg pain and swelling  Hyperpigmentation  Ulceration Varicose Veins  Dilated, elongated and tortuous superficial veins  Most commonly found in the legs Primary Varicose Veins  Varicose veins that develop in the absence of DVT  Caused by incompetent valves in the common femoral and/or great saphenous veins  Valves may be congenitally absent in the common femoral and iliac veins  Calf muscle pump propels blood upward; however, retrograde flow is noted in superficial veins due to valvular incompetence  Results in increased venous pressure  Primary Varicose Veins (cont.) Figure 3-11. Patterns of venous flow with primary varicose veins. Secondary Varicose Veins  Valvular incompetence as a result of valve damage from DVT  Valve incompetence is typically noted in the deep, superficial, and perforating veins  Venous flow patterns are completely disrupted  Flow from deep to superficial  Bidirectional flow in perforators  Increased venous pressure is noted throughout system  Secondary Varicose Veins (cont.) Figure 3-12. Patterns of venous flow with secondary varicose veins. Pregnancy and Varicose Veins  Pregnancy does not cause varicose veins but may magnify predisposing factors  Enlarged uterus compresses IVC and iliac veins  Results in increased venous pressure  Humoral factors circulating during pregnancy cause the veins to be more compliant  Causes increased venous distention  Decrease in velocity of venous flow  These factors can lead to the development of varicose veins and DVT Risk Factors  Family History  Increasing Age  Female Gender  Pregnancy  Obesity  Standing Occupations  History of Previous DVT Clinical Manifestations of Varicose Veins  Cosmetic disturbance  Subjective symptoms  Pain, soreness, aching, burning  Throbbing, cramping  Muscle fatigue, restless legs  Chronic skin and soft tissue changes  Swelling  Discoloration  Inflammatory dermatitis  Recurrent or chronic cellulitis  Cutaneous infarction and ulcerations  Malignant degeneration Venous Stasis Ulcers  Increased venous pressure results in distention of capillaries and increased capillary pressure  Junctions between endothelial cells open and plasma proteins move into the tissue  Additional fluid follows the protein movement  As a result, tissue damage and ulceration occur  Decreased oxygen transfer at the capillary level leads to ischemia and ulceration Superficial Thrombophlebitis  Thrombosis of the superficial veins  Not as dangerous as DVT  Risk Factors  IV infusion  IV drug abuse  Symptoms  Erythema / inflammation  Local tenderness  Palpable cord or mass  Usually more painful than DVT