Thromboembolism

Objectives:

(1) Understand the basic pathology of thrombogenesis and the risk factors for development of deep vein thrombosis. Editing file (2) Know the types of embolus than can occur and the

pathology of pulmonary embolism.

Black: original content. Green: Boy‘s doctor notes . Red: Important. Dark orange: Girl’s Doctor notes. Light Purple:From Robbin’s. Grey: Explanation. Blue:only found in boys slides. Pink: Only found in girls slides. Thrombosis

Definition Definition: It is a process by which a thrombus is formed. ● It represents hemostasis in the intact vascular system. ● It is considered as an intravascular coagulation of blood that often causes significant interruption to blood flow. What is a thrombus? A thrombus is a solid mass (blood clot) made up of blood constituents which develops in an artery or vein.

thrombus results from interaction of platelets, damaged endothelial cells and the coagulation cascade. All 3 are component of the hemostatic process. A thrombus results from interaction of platelets, damaged endothelial cells platelets Platelets and the coagulation cascade. maintain the integrity of the vascular endothelium and participate in They maintain the integrity of the vascular endothelium and Coagulation endothelial repair. They form platelet plugs and promote the coagulation participate in endothelial Cascade(1) cascade. repair. They form platelet plugs 1 and promote the coagulation It is a major contributor to cascade. thrombosis. It is a series of Endothelial cells

Components enzymatic conversions, that of the end in the formation of are resistant to the thrombogenic influence of platelets and coagulation Endothelial cells thrombin. Thrombin then hemostatic converts the soluble plasma proteins. Intact endothelial cells are thromboresistant. They are resistant to the 2 process 3 protein fibrinogen into the thrombogenic influence of insoluble protein fibrin. And platelets and coagulation fibrin is a constituent of the Coagulation Cascade proteins. Intact endothelial thrombus. cells are thromboresistant. is a major contributor to thrombosis. It is a series of enzymatic conversions, that end in the formation of thrombin. Thrombin then converts the soluble Three primary influences called as Virchow triad predispose plasma protein fibrinogen into the insoluble protein fibrin. And fibrin is a constituent of the thrombus to thrombus formation (2) Three primary influences called as Virchow triad predispose to thrombus formation (2) stasis or turbulence of endothelial blood blood flow injury hypercoagulability (abnormal blood flow) stasis or turbulence of endothelial blood blood flow injury hypercoagulability (abnormal blood flow)

(1)under normal conditions, fibrinolytic cascade is activated once coagulation cascade is, in order to balance one another. (2) We don’t need all factors to exist, one is enough. Only found in Thrombosis girls slides

The Virchow triad - Pathogenesis of thrombus formation A- Endothelial injury A- Endothelial Injury It is a major cause of thrombosis in the heart or arteries. It may lead to: Endothelial Injury is a major cause of thrombosis in the heart or arteries. It may lead to: ● Exposure of subendothelial ECM (the basement membrane) Definition ➢Exposure of subendothelial ECM (the basement membrane) ● Adhesion of platelets ➢Adhesion of platelets ● Release of tissue factor and ultimately thrombosis ➢Release of tissue factor and ultimately thrombosis

what clinical ➢Endocardial injury due to myocardial infarction settings does EJ ➢Ulcerated plaques in atherosclerotic arteries contribute to ➢ thrombosis in? Traumatic or inflammatory vascular injury

Endocardial injury conditions lead 1. Hypertension 4. Radiation due to myocardial to chronic subtle 2. Scarred valves 5. Hypercholesterolemia infarction Hypercholesterolemia Scarred valves endothelial 3. Bacterial endotoxins 6. Cigarette smoking dysfunction(injury)

conditions that leads Clinical settings in B- Abnormal Blood Flow to chronic subtle which endothelial Hypertension Radiation injury contribute endothelial to thrombosis in Ulcerated dysfunction(injury) Disruption of laminar blood flow can bring platelets into contact with the endothelium Traumatic plaques in and promote endothelial cell activation. or inflammatory atherosclerot Definition 1. Stasis plays a major role in the development of venous thrombi vascular injury Cigarette ic arteries Bacterial 2. Turbulence contributes to arterial and cardiac thrombosis by causing endothelial smoking endotoxins injury or dysfunction

1. Mitral valve stenosis 4.Ulcerated atherosclerotic plaques 2. Sickle cell anemia 5.Abnormal aortic and arterial dilations ABF B- Abnormal Blood Flow 3. Hyperviscosity syndromes 6.Acute myocardial infarction what clinical contribute to settings does thrombosis in Disruption of laminar blood flow can bring platelets into contact with the endothelium and promote endothelial cell activation. C- Hypercoagulable States 1. Stasis plays a major role in the development of venous thrombi(A thrombus within a vein). 2. Turbulence contributes to arterial and cardiac thrombosis by causing endothelial injury or dysfunction. Definition Any change of the coagulation pathways that predisposes to thrombosis

Primary/Genetic/inherited:

Mitral valve stenosis Ulcerated atherosclerotic plaques ➢mutation in factor V,prothrombin gene ➢ anti-thrombin III, protein C or S deficiencies ➢ fibrinolysis defects

Clinical settings Secondary/acquired in which Sickle cell anemia Abnormal aortic and arterial dilations abnormal blood Types A) HIGH risk for thrombosis B) LOW risk for thrombosis flow contributes ➢ Prolonged bed rest or immobilization ➢Cardiomyopathy ➢ Myocardial infarction ➢Nephrotic syndrome to thrombosis in ➢ Atrial fibrillation ➢Hyperestrogenic states (pregnancy) ➢ Tissue damage (surgery, fracture, burns) ➢Oral contraceptive use ➢Sickle cell anemia Hyperviscosity syndromes Acute myocardial infarction ➢ Cancer ➢ Prosthetic cardiac valves ➢Smoking ➢ Disseminated intravascular coagulation ➢ Heparin-induced thrombocytopenia ➢ Antiphospholipid antibody syndrome (lupus

anticoagulant syndrome)

Editing file Editing The Virchow triad - Pathogenesis of thrombus formation Thrombosis The Virchow triad - Pathogenesis of thrombus formation

C- Hypercoagulable States Mitral valve stenosis Ulcerated atherosclerotic plaques Refers to an abnormally high tendency of the blood to clot, and is typically caused by alterations in coagulation factors. Clinical settings in which abnormal Sickle cell anemia A- Primary/Genetic/inherited: blood flow Abnormal aortic and arterial dilations contributes to ● Mutation in factor V or Prothrombin gene (common) thrombosis in ● Antithrombin III, Proteins C or S deficiencies(1)(Rare) Hyperviscosity syndromes Acute myocardial infarction ● Fibrinolysis defects (Very rare)

C- Hypercoagulable States B- Secondary/acquired Refers to an abnormally high tendency of the blood to clot, and is typically caused by High risk for thrombosis Lower risk for thrombosis alterations in coagulation factors. Types ● Prolonged bed rest or immobilization ● Cardiomyopathy ● Myocardial infarction ● Nephrotic syndrome A- Primary/Genetic/inherited: ● Atrial fibrillation ● Hyperestrogenic states (pregnancy ● Tissue damage (surgery, fracture, burns) and postpartum) ● Mutation in factor V or Prothrombin gene (common) ● Cancer (Release of procoagulant tumor products) ● Oral contraceptive use ● Prosthetic cardiac valves ● Sickle cell anemia ● Antithrombin III, Proteins C or S deficiencies(1)(Rare) ● Disseminated intravascular coagulation ● Smoking ● Fibrinolysis defects (Very rare) (Thrombin generation) ● Heparin-induced thrombocytopenia B- Secondary/acquired ● Antiphospholipid antibody syndrome (lupus anticoagulant syndrome)(Autoantibodies)

High risk for thrombosis Lower risk for thrombosis Types Endothelial integrity is the single most ● Prolonged bed rest or immobilization ● Cardiomyopathy ● Myocardial infarction ● Nephrotic syndrome important factor. Note that injury to ● Atrial fibrillation ● Hyperestrogenic states (pregnancy endothelial cells can affect local blood ● Tissue damage (surgery, fracture, burns) and postpartum) flow and/or coagulability; abnormal blood ● Cancer(Release of procoagulant tumor products) ● Oral contraceptive use ● Prosthetic cardiac valves ● Sickle cell anemia flow (stasis or turbulence) can, in turn, ● Disseminated intravascular ● Smoking cause endothelial injury. The elements of coagulation(Thrombin generation) ● Heparin-induced thrombocytopenia the triad may act independently or may ● Antiphospholipid antibody syndrome (lupus combine to cause thrombus formation anticoagulant syndrome)(Autoantibodies) Virchow triad in thrombosis. Endothelial integrity is the single most important factor. Note that injury to Fibrinolysis (thrombus dissolution) endothelial cells can affect local blood flow and/or coagulability; abnormal blood Activation of the clotting Fibrinolytic cascade In the fibrinolytic flow (stasis or turbulence) can, in turn, cascade induces helps dissolve the cascade the inactive cause endothelial injury. The elements of coagulation. It also triggers thrombus and therefore proenzyme plasminogen the triad may act independently or may the fibrinolytic cascade that restores blood flow in is converted to active limits the size of the final clot. It vessels occluded by the plasmin. Plasmin then combine to cause thrombus formation runs concurrently with thrombus. The thrombus splits the fibrin in the thrombogenesis. is dissolved by plasmin. thrombus. Virchow triad in thrombosis.

(1) Antithrombin 3: inhibits coagulation by neutralizing the enzymatic activity of thrombin. (1) Antithrombin 3: inhibits coagulation by neutralizing the enzymatic activity of thrombin. Protein C: inactivate coagulation factors Va and VIIIa. Protein C: inactivate coagulation factors Va and VIIIa. Protein S: enhances the catalytic activity of Protein C. Protein S: enhances the catalytic activity of Protein C.

Fibrinolysis (thrombus dissolution) Disseminated intravascular coagulation

Is both prothrombotic and antithrombotic disorder characterized by widespread thrombosis and Only found in hemorrhage resulting from the consumption of platelets and coagulation factors. Thrombotic disorders girls slides Anti-Thrombotic (Hemorrhagic)

Thrombotic disorders can be: leading to pathologic bleeding states such as Anti-Thrombotic (Hemorrhagic) ● Hemophilia. ● Christmas disease leading to pathologic bleeding states such as ● Von Willebrand disease. Anti-Thrombotic Disseminated Prothrombotic ● Hemophilia. (Hemorrhagic) intravascular coagulation ● Christmas disease Prothrombotic ● Von Willebrand disease. Hypercoagulability with pathologic thrombosis, for example: Hypercoagulability with leading to pathologic Is both prothrombotic and pathologic thrombosis e.g. bleeding states such as antithrombotic disorder

Prothrombotic 1. Hereditary ● hemophilia. characterized by widespread 1-Hereditary Thrombophilia 2- Antiphospholipid antibody syndrome (previously called the lupus anti-coagulant syndrome) thrombophilia ● Christmas disease thrombosis and hemorrhage Hypercoagulability with pathologic thrombosis, for example: resulting from the 2. Antiphospholipid ● von Willebrand disease. consumption of platelets and 2- Antiphospholipid antibody syndrome Clinical effects of thrombosis● Is a prothrombotic familial ● Is a prothrombotic antibody syndrome. coagulation factors. 1-Hereditary Thrombophilia (previously called the lupus anti-coagulant syndrome) syndrome. hypercoagulable autoimmune ● It depends on the site of thrombosis ● Characterized by recurrent venous multisystemic disorder caused by ● Is a prothrombotic familial ● Is a prothrombotic ● Thrombi are significant because: thrombosis and thromboembolism the presence of a type of Pro-Thrombotic Conditions syndrome. hypercoagulable autoimmune ○ They cause obstruction of arteries and ●veins.Can be caused by deficiency of antiphospholipid antibodies. ● Characterized by recurrent venous multisystemic disorder caused by ○ They are potential sources of emboli. antithrombotic proteins e,g. ● Is characterized by recurrent 1-Hereditary Thrombophilia 2- Antiphospholipid antibody thrombosis and thromboembolism the presence of a type of ● Venous thrombi have capacity to embolize to theantithrombin lungs and III,can protein cause C, and thrombosis and embolism and fetal ● Is a prothrombotic syndrome: ● Can be caused by deficiency of antiphospholipid antibodies. death. protein S. loss in pregnancy. hypercoagulable autoimmune antithrombotic proteins e,g. ● Is characterized by recurrent ● Is a prothrombotic familial ● Arterial thrombi can cause vascular obstruction● atFactor critical V Leiden sites and thrombophilia cause is a ● Patients have prolonged partial multisystemic disorder caused syndrome antithrombin III, protein C, and thrombosis and embolism and fetal serious consequence e.g. ischemia and necrosis.genetically inherited prothrombotic thromboplastin time (PTT) by the presence of a type of ● Characterized by recurrent protein S. loss in pregnancy. antiphospholipid antibodies. disorder of blood. Factor V Leiden is ● It is sometimes associated Systemic venous thrombosis and ● Factor V Leiden thrombophilia is a ● Patients have prolonged partial ● Is characterized by recurrent a mutated form of human factor V Lupus Erythematosus and so this thromboembolism genetically inherited prothrombotic thromboplastin time (PTT) thrombosis and embolism and ● Can be caused by deficiency of that causes an increase in blood antibody is also known as lupus fetal loss in pregnancy. antithrombotic proteins e,g. disorder of blood. Factor V Leiden is ● It is sometimes associated Systemic clotting (hypercoagulability). anticoagulant. Thrombotic disorders ● Patients have prolonged partial antithrombin3, protein C, and a mutated form of human factor V Lupus Erythematosus and so this thromboplastin time (PTT) protein S. that causes an increase in blood antibody is also known as lupus ● It is sometimes associated ● Factor V Leiden thrombophilia is clotting (hypercoagulability). anticoagulant. Systemic Lupus Erythematosus a genetically inherited and so this antibody is also prothrombotic disorder of blood. known as lupus anticoagulant. Factor V Leiden is a mutated Disseminated intravascular coagulation form of human factor V that It depends on causes an increase in blood the site of clotting (hypercoagulability). Is both prothrombotic and antithrombotic disorder characterized by widespread thrombosis and thrombosis hemorrhage resulting from the consumption of platelets and coagulation factors. Clinical effects of thrombus Thrombi are significant It depends on the site Arterial thrombi can because: of thrombosis cause vascular ● They cause obstruction at critical sites and obstruction of arteries cause serious and veins. consequence e.g. ● They are potential Clinical ischemia and sources of emboli. necrosis.

effects of Arterial thrombi can thrombosis cause vascular Venous thrombi have obstruction at critical capacity to embolize to sites and cause serious ● Is a prothrombotic the lungs and can cause consequence e.g. familial syndrome. death. ischemia and necrosis. ● Characterized by recurrent venous thrombosis and thromboembolism ● Can be caused by deficiency of antithrombotic proteins e,g. antithrombin3, protein C, and protein S. ● Factor V Leiden thrombophilia is a genetically inherited prothrombotic disorder of blood. Factor V Leiden is a mutated form of human factor V that causes an increase in blood clotting (hypercoagulability ). Thrombosis ● Usually begin at a site of endothelial injury (e.g., Morphology of Thrombus Arterial atherosclerotic plaque) or turbulence (vessel bifurcation) Thrombi ● Thrombi may develop anywhere in the ● They grow in a retrograde direction from the point cardiovascular system, the cardiac chambers, of attachment (i.e. toward the heart). valve cusps, arteries, veins, or capillaries. They vary Characteristics ● Venous thrombi characteristically occur in sites of in size and shape, depending on the site of origin. Venous stasis. Of Thrombus ● The propagating tail of either thrombi may not be ● Venous thrombi extend in the direction of blood well attached (particularly in veins) is prone to Thrombi flow (i.e. toward the heart). fragmentation, creating an embolus.

A thrombus is made up of: Components ● Fibrin ● platelets Of Thrombus ● Red blood cell ● Few inflammatory cells.

Lines Of Zahn Arterial Thrombi Venous Thrombi Arterial Thrombi ● Arterial or cardiac thrombi usually ● Characteristically occur in sites of begin at a site of endothelial injury stasis. Thus, they contain more ● Arterial or cardiac thrombi usually (e.g., atherosclerotic plaque) or enmeshed erythrocytes and are ● Thrombi may develop anywhere in the cardiovascularWhen a system, thrombus the is formed in the heart or Mural Thrombi begin at a site of endothelial injury aorta, thrombi may have grossly (and turbulence (vessel bifurcation). therefore known as red, or stasis (e.g., atherosclerotic plaque) or cardiac chambers, valve cusps, arteries, veins, or capillaries. They When arterial thrombi arise in microscopically) apparent laminations, called ● They grow in a retrograde direction thrombi. turbulence (vessel bifurcation). vary in size and shape, depending on the site of origin. heart chambers or in the aortic lines of Zahn; these are produced by from the point of attachment (i.e. ● Venous thrombi extend in the ● They grow in a retrograde direction lumen they are termed mural from the point of attachment (i.e. ● The propagating tail of either thrombi may not bealternating well attached pale layers of platelets admixed toward the heart). direction of blood flow (i.e. toward thrombi. Abnormal myocardial toward the heart). (particularly in veins) is prone to fragmentation, creatingwith some an fibrin embolus and darker layers containing ● Are usually occlusive. the heart). ● Most common sites in descending ● Also called phlebothrombosis, is contraction or endomyocardial ● Are usually occlusive. more red cells. ● Usually begin at a site of endothelial injury (e.g., order are: coronary, then cerebral, almost invariably occlusive injury promotes cardiac mural ● Most common sites in descending then femoral arteries. ● the thrombus often takes the shape thrombi. order are: coronary, then cerebral, atherosclerotic plaque) or turbulence (vessel then femoral arteries. Arterial ● It is usually superimposed on an of the vein. bifurcation) atherosclerotic plaque and are ● Phlebothrombosis most commonly ● It is usually superimposed on an Thrombi ● They grow in a retrograde direction from the point of firmly adherent to the injured arterial affects the veins of the lower atherosclerotic plaque and are firmly adherent to the injured arterial wall. attachment (i.e. toward the heart). wall. extremities (90% of cases). ● Arterial thrombi are gray-white and ● Venous thrombi also can occur in the upper ● Arterial thrombi are gray-white and ● Venous thrombi characteristically occur in sites of stasis. friable. extremities, periprostatic plexus, or ovarian friable. Venous and periuterine veins, and under special ● Venous thrombi extend in the direction of blood flow circumstances they may be found in the Thrombi (i.e. toward the heart). dural sinuses, portal vein, or hepatic vein. Arterial Thrombi

● Characteristically occur in sites of stasis. Thus, they contain more enmeshed erythrocytes and are therefore known as red, or stasis thrombi. ● Venous thrombi extend in the direction of blood flow (i.e. toward the heart).

● Also called phlebothrombosis, is almost invariably occlusive

● the thrombus often takes the shape of the vein.

● Phlebothrombosis most commonly affects the veins of the lower extremities (90% of cases). ● Venous thrombi also can occur in the upper extremities, periprostatic plexus, or ovarian and periuterine veins, and under special circumstances they may be found in the dural sinuses, portal vein, or hepatic vein. Arterial, venous, heart valves and deep vein thrombosis Thrombosis

Lines Of Zahn ● Usually begin at a site of endothelial injury (e.g., Lines Of Zahn Mural Thrombi Arterial atherosclerotic plaque) or turbulence (vessel bifurcation) When a thrombus is formed in the heart or Thrombi aorta, thrombi may have grossly (and When arterial thrombi arise in ● They grow in a retrograde direction from the point microscopically) apparent laminations, called heart chambers or in the aortic of attachment (i.e. toward the heart). Arterial Thrombi lines of Zahn; these are produced by lumen they are termed mural alternating pale layers of platelets admixed thrombi. Abnormal myocardial ● Venous thrombi characteristically occur in sites of with some fibrin and darker layers containing contraction or endomyocardial ● Growth: Venous stasis. more red cells. injury promotes cardiac mural - Usually begin at a site of endothelial thrombi. Thrombi ● Venous thrombi extend in the direction of blood injury (e.g., atherosclerotic plaque) or flow (i.e. toward the heart). turbulence (vessel bifurcation).

- They grow in a retrograde direction from the point of attachment (i.e. toward the heart). ● Because these thrombi form in a ● Are usually occlusive. relatively static environment, they ● Most common sites in descending order contain more enmeshed are: coronary, then cerebral, then erythrocytes and are therefore femoral arteries. Deep Vein Thrombosis & Thrombophlebitis known as red, or stasis thrombi. ● It is usually superimposed on an atherosclerotic plaque and are firmly ● Venous thrombosis often arises in the deep veins of the legs and then it is adherent to the injured arterial wall. called deep vein thrombosis (DVT). (commonly cause deep pain in the calf muscles). ● Arterial thrombi are gray-white and friable. ● They occur with stasis or in hypercoagulable states. ● Often associated with inflammation and then it is termed thrombophlebitis ● DVT may embolize to the lungs giving rise to pulmonary embolism with Venous Thrombosis resultant pulmonary infarct.(DVT → Right atrium →Right ventricle→lungs→ Pulmonary embolism) ● Growth: ● Common in deep the larger leg veins— at or above the knee (e.g., - Venous thrombi characteristically popliteal, femoral, and iliac veins) occur in sites of stasis. Thus, they contain ● can cause local pain and edema. more enmeshed erythrocytes and are ● DVTs are asymptomatic in approximately 50% of affected individuals and therefore known as red, or stasis thrombi. are recognized only in retrospect after embolization - Venous thrombi extend in the direction of blood flow (i.e. toward the heart). - The potential for amniotic fluid infusion into the circulation at the time of ● Also called phlebothrombosis, is almost delivery can cause thrombogenesis. Congestive heart failure (a invariably occlusive - Late pregnancy and the postpartum Pregnancy period are also associated with cause of impaired venous ● the thrombus often takes the shape of return) systemic hypercoagulability. the vein.

● Phlebothrombosis most commonly Common predisposing Trauma, surgery, and affects the veins of the lower extremities factors for DVT Advanced age burns (90% of cases). (are included in the hypercoagulable status table)

Bed rest and Tumors immobilization Thrombosis

Arterial, venous, heart valves and deep vein Thrombi on Heart Valves thrombosis ● Thrombi on Heart Valves are called vegetations, and are divided into:

Infective Vegetations Sterile Vegetations

Bacterial or fungal bloodborne nonbacterial thrombotic endocarditis develop infections may result in the on non-infected valves in patients with: ● Hypercoagulable state development of large thrombotic ● Subtle endothelial abnormality masses on heart valves, called as ● Some patients with malignancy and vegetations (infective endocarditis). other debilitating disease.

● Less commonly, noninfective, verrucous (Libman-Sacks) endocarditis attributable to elevated levels of circulating immune complexes may occur in patients with systemic lupus erythematosus ● At autopsy, postmortem clots may be confused for venous thrombi. Postmortem(1) clots: ● Post-mortem clots are gelatinous with a dark red dependent portion where red cells have settled by At autopsy, postmortem clots may be confused for venous thrombi. gravity and a yellow chicken fat supernatant resembling melted and clotted chicken fat. They are Postmortem Clots Venous (Red) thrombi not attached to the underlying wall. ● Red Thrombi are firmer, almost always have a point of Gelatinous & Rubbery Firm & homogenous in color attachment, and on transection reveal vague strands of pale gray fibrin. They have a dark red dependent portion On transection reveal vague where red cells have settled by gravity and strands of pale gray fibrin. a yellow fat supernatant resembling melted (Rich admixture of RBCs that and clotted chicken fat.(Dark red in one appears red). Text side and yellow in the other).

They are not attached to the underlying Almost always have a point of wall(Vessel wall). attachment (Attached to vessel wall).

Fate of Thrombus: Same thing Resolution Propagation Embolism organization and recanalization organization and incorporation into the wall

(1): Postmortem: occurring after death. Antemortem: occurring before death (ex: thrombus)

Fate of Thrombus: ● Resolution Venous(Red) Thrombi Postmortem● Propagation Clots ● Embolism ● Organization and recanalization ● Rubbery and gelatinous● Organization and incorporation into the wall.● Firm ● Dark red in one side and yellow in the other. ● Rich admixture of RBCs and appear red ● Not attached to the vessel wall ● Attached to the vessel wall Embolism

Definition An embolus (plural: emboli): is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin.

The majority of the emboli represent some part of a dislodged thrombus, hence the commonly used term thromboembolism.

Resulting in partial The emboli get depending on site or complete lodged in a vessel of the blockage it vascular occlusion An embolus is too small to can be leading to ischemic detach permit further A- pulmonary necrosis of distal passage B- systemic tissue, (infarction).

Types of embolism

Pulmonary Systemic Air embolism thromboembolism thromboembolism

Amniotic fluid Fat embolism embolism

1- PULMONARY THROMBOEMBOLISM

Definition ● An embolus that gets lodged in the pulmonary vasculature. ● In more than 95% of cases, venous emboli originate from deep leg vein thrombi above the level of the knee

It depends upon the size of the embolus. 1. Main pulmonary artery 2. Across the bifurcation (saddle embolus) Location 3. Branching arterioles it may lead to infarction

Rarely, emboli may pass through an interatrial or interventricular septal defect to gain access to the systemic circulation. (paradoxical embolism).

- Most pulmonary emboli (60% to 80%) are clinically silent because they are small. - Sudden death, right heart failure (cor pulmonale) occurs when 60% or more of Clinical the pulmonary circulation is obstructed with emboli. complications - Embolic obstruction of small end-arteriolar pulmonary branches may result in infarction. Embolism Embolism

2- SYSTEMIC THROMBOEMBOLISM

Definition It is an embolus traveling within the arterial circulation.

Most (80%) arise from intracardiac mural thrombi. (the ventricular Origin chamber).

The major sites for arterial embolization are the lower extremities (75%) Location and the brain (10%).

The consequences of systemic emboli depend on the extent of collateral vascular supply in the affected tissue, the tissue's vulnerability to ischemia, Complications and the caliber of the vessel occluded; in general, arterial emboli cause infarction of tissues supplied by the artery.

3- FAT EMBOLISM

Definition Microscopic fat globules that are found in the circulation.

Fractures of long bones (which have fatty marrow) or, rarely, in soft and Origin adipose tissue trauma and burns which will release fat into the circulation through rupture of the blood vessels and act as an embolus.

Fat embolism It is characterized by pulmonary insufficiency, neurologic symptoms, syndrome anemia, and thrombocytopenia.

Fact Less than 10% of patients with fat emboli have any clinical findings.

4- AMNIOTIC FLUID EMBOLISM

A grave and uncommon complication of labor and the immediate postpartum period caused by infusion of amniotic fluid or fetal tissue into Definition the maternal circulation via a tear in the placental membranes or rupture of uterine veins

● Patient will suffer from sudden severe dyspnea, cyanosis, and hypotensive shock, followed by seizures and coma. characteristics ● If the patient survives the initial crisis, pulmonary edema develops, along with disseminated intravascular coagulation, owing to release of thrombogenic substances from amniotic.

● Presence in the pulmonary microcirculation of squamous cells shed from fetal skin, fetal hair, fetal fat etc. Microscopy ● Marked pulmonary edema and diffuse alveolar damage. ● Systemic fibrin thrombi indicative of DIC can also be seen. Embolism Embolism

5- AIR EMBOLISM

Gas bubbles within the circulation that can obstruct vascular flow (and cause distal ischemic injury) acting as thrombotic masses. Definition Bubbles may coalesce to form frothy masses sufficiently large to occlude major vessels.

Air may enter the circulation during obstetric procedures or as a When does it consequence of chest wall injury. happens? An excess of 100 cubic centimetres of air is required to have a clinical effect.

Occurs when individuals are exposed to sudden changes in atmospheric pressure. Definition such as: (and to whom it happens) ● SCUBA and deep sea divers ● underwater construction workers ● individuals in unpressurized aircraft in rapid ascent.

Air is breathed at high pressure (e.g. during a deep sea dive) → increased amount of gasses (especially nitrogen) in blood and tissues → diver ascend Pathogenesis (depressurizes) too rapidly → nitrogen expands in the tissues & bubbles out of solution in the blood → gas emboli.

● ’Grecian Bends’ I.e. joint/muscle pain symptoms ● ‘chokes’ i.e. respiratory distress

placing the individuals in a compression chamber where the barometric pressure may be raised, thus forcing the gas bubbles back into solution followed by Treatment subsequent slow decompression.

More chronic form of decompression sickness, in which, persistence of gas emboli in the skeletal system Caisson leads to multiple foci of ischemic necrosis; the more common sites are heads of: Air embolism: decompression sickness disease ● femurs ● tibia ● humeri. Summary

Thrombosis

● Fibrin Composed ● Platelets of ● RBCs ● Some inflammatory cells

Virchow Triade: ● Endothelial cell injury Pathogenesis ● Stasis or turbulence of blood flow ● Blood hypercoagulability

Arterial Venous (Phlebothrombosis)

Endothelial injury or turbulence Stasis

Morphology Coronary, Cerebral and Femoral Popliteal, Femoral and Iliac veins arteries (Deep Vein Thrombosis)

Occlusive Prone to fragmentation can cause ischemia and necrosis can cause pulmonary embolism

Thrombus is dissolved by plasmin Fibrinolysis ● Fibrinolytic cascade: Plasminogen → Plasmin

Embolism

Pulmonary Systemic Amniotic Fluid Fat Embolism Air Embolism Types Thromboembolism Thromboembolism Embolism

Infusion of Release of fat amniotic fluid Entry of air due from bone due to a tear in Arise Intracardiac to chest wall marrow after the placental Mural Thrombi injury or obstetric from DVT long bone membranes or procedure fracture rupture of uterine veins

Lower Pulmonary Circulation Circulation Circulation extremities and Site artery brain

Pulmonary Leads to Sudden death Fat embolism Decompression Infarction edema Cor pulmonale syndrome sickness

Answer key: Answers Explanation File

B 1) ; C 2) ; C 3) ; E; 4) A 5) ; A 6)

Quiz ;

1) A 67-year-old man presents with 2) A 60-year-old man with a history of emphysema sudden left leg pain, absence of pulses, returns home from the hospital after suffering a and a cold limb. His past medical history is myocardial infarction involving the apex of the left ventricle. Six months later, an echocardiogram significant for coronary artery disease and reveals the development of a ventricular bulge a small aortic aneurysm. Which of the that does not contract during systole. The patient following is most likely responsible for subsequently suffers a massive stroke and development of a cold limb in this suddenly expires. Which of the following is an patient? expected pathologic findings at autopsy?

A) Acute myocardial B) Arterial thromboembolism. A) Calcific aortic stenosis B)Dilated cardiomyopathy infarction.

C) Cardiogenic shock. D) Deep venous thrombosis. C) Mitral valve prolapse D) Mural thrombus.

E) Ruptured aortic aneurysm. E) Ventricular rupture

3) A 60-year-old man who is recovering from 4) A 69-year-old retired man is brought to the emergency department because he experienced sudden onset of surgery to correct an abdominal aneurysm left-sided chest pain, which is exacerbated upon inspiration. He suddenly develops acute chest pain and is taking no medications and has been in good health. Physical dies. A thromboembolism at the bifurcation of examination reveals dyspnea and hemoptysis. Temperature is 38°C (101°F), pulse rate is 98 per minute, respirations are 35 per the left and right pulmonary arteries is noted minute, and blood pressure is 158/100 mm Hg. A pleural friction at autopsy (shown in the image). Which of rub is present on auscultation. The left leg is markedly edematous, with a positive Homans’ sign. An ECG shows a the following is the most likely cause of this normal sinus rhythm. A chest X-ray reveals a left pleural effusion. patient’s pulmonary embolism? What is the most likely cause of this patient’s pulmonary condition?

A) Bacterial endocarditis. B) Complicated A) Congestive heart failure. B) Cor pulmonale. atherosclerotic plaque.

C) Deep venous thrombosis. D) Paradoxical embolization. C) Mitral stenosis. D) Subacute endocarditis.

E) Right ventricular mural thrombus. E) Thromboembolism.

5) A 68-year-old obese woman (BMI = 32 kg/m2 ) presents with 6) A 30-year-old woman presents with a heart murmur. substernal chest pain and a history of recurrent angina pectoris There is a history of recurrent episodes of arthritis, skin and intermittent claudication. The following day, she develops rash, and glomerulonephritis. Blood cultures are a fever of 38°C (101°F). Results of laboratory studies include an negative. Laboratory tests for antinuclear antibodies elevated WBC count (13,000/µL), CK-MB of 6.6 ng/mL, and (ANA) and anti–double-stranded DNA are positive. troponin-I of 2.5 ng/mL. ECG confirms a myocardial infarction Which of the following is the most likely cause of heart of the left ventricular wall. Which of the follow- murmur in this patient? ing mechanisms is most likely responsible for the myocardial infarction in this patient?

A) Coronary artery B) Coronary artery A) Libman-Sacks endocarditis B) Mitral valve regurgitation thrombosis vasospasm

C) Decreased collateral D) Deep venous thrombosis C) Myocardial infarct D) Mitral valve prolapse blood flow

E) Paradoxical embolism E) Rheumatic fever Team leaders ● Raghad AlKhashan ● Mashal Abaalkhail

Team Members

● Alhanouf Alhaluli ● Abdulaziz Alghamdi ● Amirah Alzahrani ● Alwaleed Alarabi ● Danah Alhalees ● Alwaleed Alsaleh ● Deana Awartani ● Faisal Almuhid ● Elaf AlMusahel ● Jehad Alorainy ● Lama Alassiri ● Khalid Alkhani ● Lama Alzamil ● Mohammed Alhumud ● Leena Alnassar ● Mohammad Aljumah ● Leen Almazroa ● Mohanad makkawi ● Njoud Alali ● Muath Aljehani ● Noura Alturki ● Nawaf AlBhijan ● Reema Alserhani ● Suhail Basuhail ● Rema Almutawa ● Abdulla Alhawamdeh ● Taibah Alzaid ● Hani Alhudhaif ● Tariq Aloqail