1. Hemodynamic disorders 2

2. Thrombosis
Thrombosis Is the formation of blood clot inside blood vessels.
Both hemostasis and thrombosis involve three components:
Vascular wall.
Platelets.
Coagulation cascades.

3. Pathogenesis of thrombus
There are three primary abnormalities that lead to thrombus formation called Virchow’s triad.
Endothelial injury.
Stasis or turbulence of blood flow.
Blood hypercoagulability.

4. 1. Endothelial injury
Is an important cause of thrombosis, particularly in the heart and arteries.
Normally high flow rates of blood in the heart and the arterial circulation prevent clotting by preventing platelets adhesion or diluting coagulating factors.
Physical loss of endothelium lead to exposure of subendothelium ECM, adhesion of platelets, release of coagulating factors that help in thrombus formation.
Location of thrombus-within cardiac chambers after myocardial infarction, over ulcerated plaques in atherosclerotic arteries., at site of traumatic or inflammatory vascular injury ( vasculitis).

5. 2. Alteration in normal blood flow
Turbulence contribute to thrombosis by causing endothelial injury or dysfunction, as well as by forming countercurrent and local pockets of stasis.
Stasis is the major contributor to the development of venous thrombie, normal blood flow is laminar, such as platelets flow centrally in the vessel lumen, separated from endothelium by a slower moving clear zone of plasma.
Stasis and turbulence will: disrupt laminar flow, prevent dilution of activated clotting factors, retard the inflow of clotting factor inhibitors and promote endothelial cell injury leading to platelet adhesion

6. Causes of turbulence and stasis:
Ulcerated atherosclerotic plaque-.
Abnormal aortic or arterial dilatation called aneurysm.
Acute myocardial infarction lead to focally noncontractile myocardium.
Mitral valve stenosis.
Hyper viscosity syndrome ( such as polycythemia) increase resistance to flow and cause small vessels stasis.
Deformed red cells in sickle cell anemia cause vascular occlusions

7. 3. Hypercoagulability.
It is any alteration of coagulation pathway that predispose to thrombosis.
It is contribute infrequently to arterial or intracardiac thrombosis but important underlying risk factor for venous thrombosis and can be divided into:
Primary ( genetic) disorders like mutation in the factor V gene and the prothrombin gene.
Secondary (acquired) disorders, the pathogenesis frequently multifactorial and more complicated and include:- cardiac failure, oral contraceptive use and pregnancy due to increase hepatic synthesis of coagulation factors, disseminated cancer due to procoagulatory tumor products, smoking and obesity also cause hypercoagulation.

8. Morphology of thrombus
Thrombosis can have grossly and microscopically apparent laminations called lines of Zahn; these represent pale platelets and fibrin layers alternating with darker erythrocyte rich layers.
These lines distinguish antemorten thrombosis from the bland nonlaminated clots that occur in postmortem state.

11. Types of thrombus
Mural thrombus: occur in heart chamber or in the aortic lumen and caused by .
Arrhythmia and myocardial infarction causing abnormal myocardial contraction.
Myocarditis or catheter trauma causing endomyocardial injury.
Ulcerated atherosclerosis plaque and aneurysmal dilatation.
2. Arterial thrombi: frequently occlusive and produced by platelet and coagulation factor activation; they are typically friable meshwork of platelets, fibrin, erythrocytes and degenerating leukocytes, caused by vascular injury (vasculitis) or atherosclerosis plaque .

12. 3. Venous thrombosis (phlebothrombosis: almost occlusive, result of coagulation cascade activation, platelets play secondary role, vein of lower limb are most commonly affected. 4. Vegetation: thrombi on heart valves, bacterial and fungal blood borne infection can cause valve damage, subsequently leading to large thrombotic masses ( infective endocarditis)

13. Fate of thrombus
propagation: thrombi accumulate more platelets and fibrin causing vessels obstruction.
Embolization: thrombi dislodged or fragmented and are transported elsewhere in the vasculature.
Dissolution: thrombi removed by fibrinolytic activity which leads to rapid shrinkage and even total lysis of recent thrombi.
Organization and recanalization: thrombi induce inflammation and fibrosis with recanalization

14. Embolism
Detached intravascular solid, liquid or gaseous mass carried by the blood to a site distant from its point of origin.
99% of all emboli represent dislodged thrombus so called thromboembolism.
Rare emboli includes fat droplets, bubbles of air or nitrogen (chest wall injury), cholesterol emboli, tumor fragments, bits of bone marrow, or foreign bodies.
Emboli lodged in vessels too small to permit further passage, resulting in partial or complete vascular occlusion end in ischemic necrosis (infarction) ofg downstream tissue.

15. Fat embolism
Microscopic fat globules can be found in circulation after fractures of long bones (which contain fatty marrow) or after soft tissue trauma.
Although fat and marrow embolism occur in some 90% of individuals with sever skeletal injuries, fewer than 10% of such patients show any clinical finding.

16. Infarction
Area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue.
Nearly 99% of all infarcts result from thrombotic or embolic event, and almost all result from arterial occlusion.
Morphology classified on the basis of their color (reflecting amount of hemorrhage ) and presence and absence of microbial infection, therefore, infarcts may be either red (hemorrhagic) or white (anemic) and may be either septic or non septic.

17. Morphology
Dominant histological features of infarction is ischemic coagulative necrosis.
In stable or labile tissue, parenchymal regeneration can occur in periphery. However most infarct are ultimately replaced by scar.
The brain is an exception to these generalization; where liquefactive necrosis occur.

21. Factors that influence development of infarct
Nature of vascular supply: presence of alternative blood supply is the most important, lung, liver, hand, forearm have a double arterial supply; all are resistant to infarct, while kidney and spleen has end-arterial blood supply so obstruction generally cause infarct.
Rate of occlusion development: slow developing occlusions are less likely to cause infarct.
Tissue susceptibility to hypoxia: neurons undergo irreversible damage when deprived of blood supply for only 3-4 min, myocardial cells are also sensitive and die after20-30 min of ischemia, in contrast fibroblasts remain viable after many hours.
Oxygen content of blood: anemic and cyanotic patient more liable to tissue infarct.

22. Shock
Final step for a number of potentially lethal clinical events including :
Sever hemorrhage.
Extensive trauma or burn.
Large myocardial infarct.
Large pulmonary embolism.
Microbial sepsis.
Regardless underlying pathology, shock lead to systemic hypoperfusion caused either by decrease cardiac output or by reduce circulatory blood volume.

23. Types of shock
Cardiogenic shock: cardiac pump failure caused by myocardial infarction, pulmonary embolism and ventricular arrhythmia.
Hypovolemic shock: blood loss may be caused by hemorrhage, sever burn, fluid loss or trauma.
Septic shock: by microbial infection, gram positive and negative or fungal infection.
Neurogenic shock: spinal cord injury or anesthetic accident.
Anaphylactic shock: systemic vasodilatation and increase vascular permeability caused by immunoglobulin E hypersensitivity reaction.

24. Morphology
Shock will induce cellular and tissue necrosis due to hypoxia or combination of decrease blood supply and fibrin thrombi which may be identified in any tissue, mostly visualized in kidney glomeruli.