Fate of Thrombi Propagation: growth and spread with maintenance of physical continuity Embolization: detachment and dislocation to other sites Dissolution: by fibrinolysis Organization: fibrosis and recanalization

Complications of Thrombi Occlusion of blood vessels Veins: Congestion and edema Arteries: Ischemia and infarcts in areas supplies by the vessel Embolization. The most serious is pulmonary embolism

Venous Thrombosis Mostly in superficial or deep veins of the legs Superficial vein thrombosis lead to local edema, tenderness and infections of overlying skin Deep vein thrombosis is more serious; it may lead to pulmonary emboli, causes edema, pain and tenderness

Deep Vein Thrombosis (DVT) Stasis due to heart failure Sedentary life style and inactivity Conditions associated with DVT include Cancers, pregnancy, advanced age, prolonged bed rest, post-operative, late pregnancy, and postpartum Congenital conditions such as Factor V mutation, antithrombin III deficiency, protein C and S deficiency and defects in fibrinolysis

EMBOLISM Intravascular passage of detached material distant to the site of origin leading to obstruction of the vascular lumen. Types of emboli Thrombi (99%) Atherosclerotic fragments (lipid, cholesterol, calcific tissue) Air Fat droplets Liquid Tumor fragments

Pulmonary Thromboembolism Etiology: Deep vein thrombosis (95%) Small thrombi are silent (majority) Large thrombi cause saddle emboli and lead to death or cor pulmonale Medium size thrombi lead to pulmonary hemorrhage, but not infarcts Recurrent emboli may cause pulmonary hypertension

Systemic Thromboembolism Etiology: Intracardiac thrombi. Less commonly, aterial origin, valvular vegetations. Affected Sites depend on the site of origin Lower limbs (75%) and brain (10%) are affected most Manifestations and complications depend on collateral circulation

Infarction An area of ischemic necrosis caused by occlusion of either arterial supply or the venous drainage of a particular tissue 99% are caused by arterial occlusion due to thromboembolic events Less common causes include: Vasopasm hemorrhage within atheroma Twisted artery External pressure

TYPES OF INFARCTS Red infarcts (hemorrhagic). White infarcts (anemic). Septic infarcts.

TYPES OF INFARCTS Red infarcts occur in: White infarcts occur: venous occlusion (eg. ovarian torsion). loose tissue, eg. lung. tissues with dual circulation, eg. intestine. tissues previously congested. reestablished flow to a site with previous arterial occlusion. White infarcts occur: with arterial occlusions. in solid organs.

Factors influencing the development of an infarct Nature of vascular supply. Rate of the development of arterial occlusion. Vulnerability of tissue to hypoxia. Blood oxygen content.

Shock Definition: Systemic hypoperfusion and reduced oxygen delivery due to either reduced cardiac output, or ineffective circulatory blood volume. Results of shock: hypotension. impaired tissue perfusion. cellular hypoxia.

Major types of shock Cardiogenic shock. Hypovolemic shock. Septic shock.

Septic shock High mortality rate (25-75%). Gram positive bacteria: most common cause Gram negative bacteria produce endotoxins Endotoxins are lipopolysaccharides (LPS). LPS is composed of fatty acid core (lipid A) and a polysaccharide coat. LPS binds as a complex with circulating protein to CD14 on monocytes and macrophages.

LPS TNF IL-6/IL-8 NO, PAF Low doses Medium doses High doses other mediators Low doses Monocyte activation Enothelial activation Complement activation Medium doses Fever Acute phase reactants High doses Systemic vasodilatation Deacreased myocardial contractility Endothelial injury ARDS, thrombosis. DIC Local inflammation Systemic effects Septic shock

Stages of Shock Non-progressive stage: Progressive stage: Compensatory mechanisms maintains perfusion of vital organs. Progressive stage: Tissue hypoperfusion with metabolic and circulatory worsening. Irreversible stage: Severe irreversible tissue and cellular injury.