Circulatory Disturbances 5: Thrombosis, Embolism, Infarction, Shock Shannon Martinson, Feb 2016 http://people.upei.ca/smartinson/ VPM 152 General Pathology
Thrombosis, Embolism, Infarction, Shock Learning Objectives Discuss the mechanisms that lead to thrombosis (Virchow s triad). List the possible outcomes of thrombosis. Identify and classify thrombi (arterial vs venous, etc) based on location and gross/microscopic features. Describe the causes and consequences of embolism. What materials may form emboli? Which is most common? Describe the pathogenesis of ischemia and infarction. What does the term shock mean and what are the 3 main categories?
THROMBOSIS Thrombosis Inappropriate activation of hemostasis resulting in formation of a solid mass (thrombus) within the blood vessels or heart Thrombus (pl. Thrombi) Aggregate of platelets, fibrin, RBCs/WBCs within the blood vessels or heart Can lead to vascular obstruction and embolism
THROMBOSIS Pathogenesis of Thrombosis Virchow s Triad Endothelial injury THROMBOSIS Abnormal blood flow Hypercoagulability
THROMBOSIS Pathogenesis of Thrombosis Virchow s Triad Endothelial injury Dominant influence Causes thrombosis on own Alterations in blood flow Turbulence Endothelial injury / activation Stasis no dilution of clotting factors build-up of thrombi Hypercoagulability prothrombotic factors inhibitory factors
THROMBOSIS Location of thrombi in Cardiovascular System: Cardiac chambers Left ventricular thrombus Left atrial thrombus
THROMBOSIS Location of thrombi in Cardiovascular System: Cardiac valves Valvular endocarditis
THROMBOSIS Location of thrombi in Cardiovascular System: In blood vessels Caudal abdominal aortic thrombus
THROMBOSIS Location of thrombi in Cardiovascular System: Arterial thrombi Usually form at sites of turbulence and/or endothelial injury Images: Zachary and McGavin PBVD
THROMBOSIS Location of thrombi in Cardiovascular System: Arterial thrombi Grow away from the heart Often pale and meatier than venous thrombi Image: Zachary and McGavin PBVD
THROMBOSIS Location of thrombi in Cardiovascular System: Arterial thrombi May have lines of Zahn alternating lines of RBCs and fibrin Image: Zachary and McGavin PBVD
THROMBOSIS Location of thrombi in Cardiovascular System: Venous thrombi Grow towards the heart
THROMBOSIS Location of thrombi in Cardiovascular System: Venous thrombi Usually form in slow flow regions (stasis) Contain numerous RBCs gelatinous and red in colour Can be difficult to differentiate from a postmortem blood clot Image: Zachary and McGavin PBVD
THROMBOSIS Blood clot Can refer to a thrombus or a post-mortem blood clot Unlike a thrombus, PM blood clots are not associated with pathologic change and are not attached to the wall Image: Zachary and McGavin PBVD
THROMBOSIS Chicken fat clot Gelatinous yellow post-mortem clot Due to sedimentation of RBCs
Image: Zachary and McGavin PBVD THROMBOSIS Outcome of Thrombi Lysis (resolution)
Image: Zachary and McGavin PBVD THROMBOSIS Outcome of Thrombi Lysis (resolution) Organization / Recanalization
THROMBOSIS Outcome of Thrombi Organization / Recanalization Images: Zachary and McGavin PBVD
THROMBOSIS Outcome of Thrombi Lysis (resolution) Propagation Organization / Recanalization Image: Zachary and McGavin PBVD
THROMBOSIS Outcome of Thrombi Lysis (resolution) Propagation Organization / Recanalization Embolization Image: Zachary and McGavin PBVD
EMBOLISM Embolism Passage through the circulation of any material capable of lodging in a blood vessel thereby obstructing the lumen Embolus (Pl. Emboli) Detached intravascular material carried via blood to a distant site from its origin Can be solid, liquid or gaseous Thromboembolism Occlusion of a blood vessel by an embolus that has broken away from a thrombus Travels until it gets stuck Thromboembolus (Pl. Thromboemboli) The piece(s) of thrombotic material transported in the bloodstream to another site
EMBOLISM Thromboembolism Image: Zachary and McGavin PBVD
EMBOLISM Thromboembolism Image: Zachary and McGavin PBVD
EMBOLISM Thromboembolism Image: Zachary and McGavin PBVD
Other forms of Embolism EMBOLISM Parasites - nematodes Dirofilaria immitis Image: Zachary and McGavin PBVD
Other forms of Embolism EMBOLISM Parasites nematode larvae Ascarid sp Strongylus vulgaris
EMBOLISM Other forms of Embolism Fibrocartilagenous emboli Traumatic implantation of intervertebral disk material into spinal vessels Causes necrotizing myelopathy (spinal cord infarcts) IV discs
EMBOLISM Other forms of Embolism Fat (bone marrow) emboli Can occur with bone fractures, prolonged surgery, and osteomyelitis www.pathologystudent.com/wp-content/uploads/2012/12/800px-bone_marrow_embolus.jpg
Other forms of Embolism EMBOLISM Foreign material emboli Hair Tumor cells Amniotic fluid
INFECTIOUS CAUSES OF THROMBOSIS / THROMBOEMBOLISM Some bacteria and viruses can cause localized or widespread endothelial damage, thrombosis, +/- thromboembolism
INFECTIOUS CAUSES OF THROMBOSIS / THROMBOEMBOLISM Images: Zachary and McGavin PBVD Some bacteria and viruses can cause localized or widespread endothelial damage, thrombosis, +/- thromboembolism
DISSEMINATED INTRAVASCULAR COAGULATION (DIC) DIC Sudden onset of widespread fibrin thrombi in microcirculation Potential causes of DIC: Severe burns Heat stroke Systemic Viral Disease Shock (toxemia/septicemia) Widespread metastatic tumours Heartworm Pancreatitis Anything that leads to the generation of excess thrombin Often consumptive coagulopathy hemorrhage
INFARCTION Infarct An area of ischemic necrosis resulting from occlusion of either arterial supply or venous drainage Most often due to: thrombosis, embolism, or vascular occlusion from twisting of a vessel Pulmonary, intestinal and renal infarction are most common in animals
INFARCTION Factors that influence the development / characteristics of an infarct 1. Nature of the vascular supply 2. Rate of development of occlusion 3. Vulnerability of the affected tissue to hypoxia 4. Oxygen content of blood at time of infarction
INFARCTION Infarct - Gross appearance Often wedge-shaped Early ill defined & hyperemic Later may become more pale Image: Zachary and McGavin PBVD
INFARCTION Infarct - Gross appearance Red Infarct Contain blood Acute infarcts with damaged vessels and hemorrhage
INFARCTION Image: Zachary and McGavin PBVD Infarct - Gross appearance Red Infarct Venous infarcts (no drainage of blood)
INFARCTION Infarct - Gross appearance Red Infarct Organs with dual blood supply (eg lung)
INFARCTION Infarct - Gross appearance Pale Infarct Lack of blood mostly arterial occlusions in solid organs (heart, kidney) Often have a red zone at the periphery
INFARCTION Infarct - Histology Ischemic necrosis of affected tissue
INFARCTION Infarct Repair Scar tissue replaces the parenchyma Parenchymal loss + Fibrous tissue contraction = Depression / Indentation of the surface
INFARCTION Septic Infarct Mostly from a septic (bacterial infected) thromboembolus Occasionally a necrotic tissue seeded by opportunistic bacteria
INFARCTION Venous Obstruction/Infarction Severe obstructions cause venous infarction Often due to twisting of vessels (eg intestinal volvulus) shock / death Occasionally obstruction of portal vein or vena cava (eg thrombosis or tumour)
INFARCTION Acute blockage of portal venous system
INFARCTION Blockage of the caudal vena cava Etiology in dogs: Severe heartworm infection Tumour invasion
Blockage of the caudal vena cava INFARCTION Etiology in ruminants: Rupture of hepatic abscesses into the caudal vena cava Image: Dr C Legge
Blockage of the caudal vena cava INFARCTION Outcome Acute sudden death Chronic possible collateral circulation from azygous vein
INFARCTION Pulmonary Artery Thrombosis / Thromboembolism
INFARCTION Pulmonary Artery Thrombosis / Thromboembolism Many possible causes: Pneumonia Parasites (eg. Heartworm) Hypercoagulability Nephrotic syndrome Hyperadrenocorticism Exogenous steroids Liver abscess rupture into the vena cava Deep vein thromboembolism Downer cows
INFARCTION Pulmonary Artery Thrombosis / Thromboembolism Result depends on the size of the artery blocked Large artery death Small artery pulmonary infarction (usually red)
SHOCK Shock Systemic hypotension due to reduced cardiac output or reduced blood volume Final common pathway for: Microbial sepsis Severe hemorrhage Trauma or burns Myocardial damage Severe pulmonary embolism Results in impaired tissue perfusion Brain and heart especially 3 Categories of Shock 1. Cardiogenic Shock 2. Hypovolemic Shock 3. Vasogenic Shock (blood maldistribution)
SHOCK 1. Cardiogenic shock Failure of the heart to adequately pump the blood Can result from: Myocardial infarction Arrhythmias Cardiomyopathy Obstruction of blood flow Valvular disease
SHOCK 2. Hypovolemic shock Decreased circulating blood volume May result from Blood loss from hemorrhage (internally or externally) Fluid loss Vomiting Diarrhea Burns
SHOCK 3. Vasogenic shock Maldistribution of blood Due to decreased peripheral vascular resistance pooling of blood in peripheral tissues Results from vasodilation Anaphylactic shock Release of vasoactive amines Neurogenic shock Occurs with severe CNS damage Loss or ANS signals to arteriolar smooth muscle Septic shock* Release of chemical mediators associated with inflammation
SHOCK 3. Vasogenic shock Septic shock - Pathogenesis Microbial substances are released from bacteria (LPS) Activation / endothelial cells and stimulation of WBCs to release cytokines Vasodilation, coagulation activation (DIC), complement activation
SHOCK Three stages of shock: Compensated Reflex compensation HR, peripheral vasoconstriction Perfusion of vital organs Progressive Tissue hypoperfusion Worsening circulatory and metabolic imbalances Irreversible Severe cell/tissue injury Survival is not possible 1 2 3
SHOCK LESIONS OF SHOCK Pulmonary congestion & edema (cattle and horses) Hepatic congestion (dog) Heart - hemorrhage and necrosis Brain - neuronal cell death Kidneys - acute tubular necrosis Blood vessels - endothelial damage (thrombosis / DIC) Adrenal glands - hemorrhage GI Tract congestion and hemorrhage Skeletal muscle - pallor
Questions?