Hemodynamic Disorders, Thromboembolism, & Shock PDF 2024

HEMODYNAMIC DISORDERS, THROMBOEMBOLISM, & SHOCK DR. J. KUM PATHOLOGY AND LABORATORY MEDICINE, WESTERN UNIVERSITY OBJECTIVES: 1. Explain hyperemia and congestion and outline the differences in the underlying mechanisms. 2. Define edema, effusion, and anasarca. Explain the various cause...

HEMODYNAMIC DISORDERS, THROMBOEMBOLISM, & SHOCK DR. J. KUM PATHOLOGY AND LABORATORY MEDICINE, WESTERN UNIVERSITY OBJECTIVES: 1. Explain hyperemia and congestion and outline the differences in the underlying mechanisms. 2. Define edema, effusion, and anasarca. Explain the various causes of edema and its classification. 3. Define hemorrhage and describe various types of bleeds seen in tissues. 4. Explain hemostasis and the key molecules involved in the process. 5. Explain thrombosis and its cause, prognosis, and complications. 6. Differentiate between thrombus and embolus. 7. Become familiar with the types of embolism and know the effects. 8. Summarize the causes and effects of ischemia. 9. Define infarction, classify the types of infarcts, and explain the factors that influence infarct development. 10. Explain the causes, types, and stages of shock. Recommended readings: "Robbins Basic Pathology" 11th Edition, 2023. Chapter 3 - Hemodynamic Disorders, Thromboembolism and Shock (pages 57-78). Read relevant sections. HYPEREMIA & CONGESTION Hyperemia and congestion refer to an increase in blood volume within a tissue. However, these have different underlying mechanisms. Hyperemia Congestion *This table will be discussed and may be completed during class. PATHOLOGY 3500/PATHOLOGY 9535 1 HEMODYNAMIC DISORDERS, THROMBOEMBOLISM, & SHOCK EDEMA Edema is the accumulation of interstitial fluid within tissues. This results in the net movement of water into extravascular spaces. Extravascular fluid can also collect in body cavities, where it is referred to as an effusion (examples include hydrothorax; and hydroperitoneum, or ascites). CAUSES OF EDEMA 1. Increased hydrostatic pressure (Figure 1B) Increases in hydrostatic pressure are mainly caused by disorders that impair venous return or increase arteriolar dilation. Clinical examples: o Deep venous thrombosis of the lower extremity o Congestive heart failure: i. Right side failure → peripheral edema ii. Left side failure → lung edema o Neurohumoral dysregulation 2. Reduced plasma osmotic pressure (Figure 1C) Reduced plasma albumin is a common feature of disorders in which edema is caused by decreases in colloid osmotic pressure. Clinical examples: o Liver disease (e.g., cirrhosis): decrease synthesis of albumin o Damage to glomeruli allows albumin to pass into the urine 3. Lymphatic obstruction (Figure 1E) Lymphatic obstruction that compromises resorption of fluid from interstitial spaces. Clinical examples: o Cancer o Inflammation o Post-surgical lymphedema 4. Sodium and water retention Excessive salt and associated water retention can increase hydrostatic pressure and reduce plasma osmotic pressure. Clinical examples: o Renal failure o Poststreptococcal glomerulonephritis 5. Inflammation (Figure 1D) Increased vascular permeability in inflammation can result in edema. Clinical examples: o Acute inflammation o Chronic inflammation PATHOLOGY 3500/PATHOLOGY 9535 2 HEMODYNAMIC DISORDERS, THROMBOEMBOLISM, & SHOCK \ FIGURE 1: The capillary system and mechanisms of edema formation. (A) Normal. The differential between the hydrostatic and oncotic pressures at the arterial end of the capillary system is responsible for the filtration into the interstitial space of approximately 14mL of fluid per minute. This fluid is reabsorbed at the venous end at the rate of 12 mL/min. It is also drained through the lymphatic capillaries at a rate of 2 mL/min. Proteins are removed by the lymphatics from the interstitial space. (B) Hydrostatic Edema. If the hydrostatic pressure at the venous end of the capillary system is elevated, reabsorption is decreased. If the lymphatics are able to drain the surplus fluid, no edema results. If their capacity is exceeded, however, edema fluid accumulates. (C) Oncotic Edema. Edema fluid also accumulates if reabsorption is diminished by a decrease in the oncotic pressure of the vascular bed, owing to a loss of albumin. (D) Inflammatory and Traumatic Edema. Edema, either local or systemic, results if the vascular bed becomes leaky following injury to the endothelium. (E) Lymphedema. Lymphatic obstruction causes the accumulation of interstitial fluid because of insufficient reabsorption and deficient removal of proteins, the latter increasing the oncotic pressure of the fluid in the interstitial space. “Essential Pathology”, Rubin & Farber, 2nd Edition 1995, J.B. Lippincott Company, p173. PATHOLOGY 3500/PATHOLOGY 9535 3 HEMODYNAMIC DISORDERS, THROMBOEMBOLISM, & SHOCK Edema is classified into two types: o Localized edema: occurs due to increased hydrostatic pressure due to vascular obstruction (local) Lymphatic obstruction: compression by tumour or inflammation (local) o Generalized edema: occurs due to increased hydrostatic pressure (e.g., heart failure) decreased oncotic pressure (colloid osmotic pressure) due to: - loss of albumin in renal failure - decreased synthesis of albumin (liver failure) Sodium retention → kidney disease Other terminologies to be familiar with: o Transudate Edema fluid due to high hydrostatic pressure or low colloid pressure is a protein-poor transudate. o Exudate Edema fluid due to increased vascular permeability, inflammatory edema fluid is a protein-rich exudate. HEMORRHAGE Hemorrhage (bleeding) is the extravasation (discharge or escape) of blood from the blood vessels into the surrounding tissues or to the exterior of the body or into a body cavity. CAUSES OF HEMORRHAGE Damage to the blood vessels and may be exacerbated by defects in blood clotting. o Trauma to large blood vessels due to surgical procedures or fracture o Weakened artery (from atherosclerosis, congenital weakness) o Infections (e.g., pulmonary tuberculosis) o Invasive tumours (erosion of vessel wall) o Hypertension (increase intraluminal blood pressure) o Hemorrhagic diatheses (spontaneous hemorrhage) affecting capillaries (small blood vessels) including: Thrombocytopenia Severe decrease in the number of platelets Deficiency of coagulation/clotting factors Other terminologies to be familiar with: o Hematoma: blood accumulation within a tissue. Large bleeds into body cavities are described according to their location. - Hemothorax: Collection of blood in the pleural cavities due to trauma or rupture of the aorta. - Hemopericardium: Collection of blood in the pericardial cavity around the heart due to rupture of the heart or the aorta. - Hemoperitoneum: Collection of blood in the abdominal cavity due to rupture of an aortic aneurysm or trauma to the liver, spleen, or aorta. - Hemarthrosis: Collection of blood in the joint cavity. PATHOLOGY 3500/PATHOLOGY 9535 4 HEMODYNAMIC DISORDERS, THROMBOEMBOLISM, & SHOCK  o Petechia: a pinpoint hemorrhage (1-2 mm); represents the rupture of capillaries and mainly involves the skin, mucous membranes, and serosal surfaces. Causes include thrombocytopenia, defective platelet function, and vitamin C deficiency (scurvy). o Purpura: slightly larger hemorrhages (3-5 mm). Causes include those that cause petechiae, as well as trauma, vasculitis, and increased vascular fragility. o Ecchymosis: a larger, subcutaneous hematomas (e.g., bruises) (1-2 cm). Skin discoloration reflects products of heme degradation from hemoglobin in the extravasated red cells. HEMOSTASIS & THROMBOSIS HEMOSTASIS Hemostasis is a precisely orchestrated process initiated by a traumatic vascular injury that leads to the formation of a blood clot to prevent or limit the extent of bleeding. This process involves platelets, clotting factors, and endothelium, and is broken down into four steps: o Transient arteriolar vasoconstriction o Primary hemostasis: formation of the platelet plug o Secondary hemostasis: deposition of fibrin o Clot stabilization THROMBOSIS Thrombosis is the pathological counterpart to hemostasis. It is the formation of a clot (a thrombus) in the blood vessels that have been damaged by a disease process. A thrombus consists of: o Red blood cells o White blood cells o Platelets o Fibrin CAUSES OF THROMBOSIS: “Virchow triad” o Endothelial injury injury → tear inflammation o Abnormal blood flow stasis (slow circulation) - lack of activity - decreased cardiac output - increased blood viscosity o Hypercoagulability Changes in blood composition: ↑ platelets PROGNOSIS (outcome) OF THROMBOSIS PATHOLOGY 3500/PATHOLOGY 9535 5 HEMODYNAMIC DISORDERS, THROMBOEMBOLISM, & SHOCK  o Propagation o Embolization o Dissolution o Organization and recanalization COMPLICATIONS OF THROMBI o Fragments of thrombus may break off and result in thromboembolization/emboli. o Reduced blood flow to a tissue/organ resulting in ischemic injury or infarction. EMBOLISM An embolus is a detached intravascular mass transported from its point of origin to a distant site through the bloodstream, where it can cause tissue dysfunction or infarction. TYPES OF EMBOLI o Thrombi The most common type of emboli Thromboemboli arise from thrombi and can range in size from microscopic to those which are large enough to occlude major arteries Thromboemboli may occur in either arteries or veins o Gas (bubbles of air or nitrogen) o Fat (often fracture of large bones) o Tumour o Others (e.g., foreign body) ISCHEMIA & INFARCTIONS ISCHEMIA Ischemia is a condition in which blood flow is restricted or reduced to an area of tissue. CAUSES OF ISCHEMIA o Decreased blood supply (inadequate cardiac output) o Obstruction of blood vessel by thrombus embolus pressure (outside pressure) damage of the vessel wall (e.g., inflammation) PROGNOSIS OF ISCHEMIA (depends on the degree of ischemia) o If there is an alternate blood supply, no effect o If severe and complete, infarction (necrosis) INFARCTION An infarct is an area of ischemic necrosis caused by occlusion of the vascular supply of the PATHOLOGY 3500/PATHOLOGY 9535 6 HEMODYNAMIC DISORDERS, THROMBOEMBOLISM, & SHOCK affected tissue. Infarction is an irreversible process, and most infarcts are ultimately replaced by fibrosis (fibrotic scar). CLASSIFICATION OF INFARCTS Based on colour: o Red (hemorrhagic) infarct Venous or arterial occlusion Tissues with dual blood supply (e.g., lung and small intestine) Previously congested tissue (sluggish venous outflow) Re-established flow after infarction has occurred (e.g., after angioplasty of an arterial obstruction) o White (anemic) infarct Arterial occlusion in solid organs (e.g., heart, spleen, kidney, brain) Wedge-shaped Presence or absence of microbial infections: o Septic infarct converted into an abscess, with correspondingly greater inflammatory response and healing by organization and fibrosis. o Bland INFLUENCING FACTORS ON INFARCT DEVELOPMENT The effects of vascular occlusion range from inconsequential to tissue necrosis leading to organ dysfunction and sometimes death. The range of outcomes is influenced by the following: Anatomy of the vascular supply Rate of occlusion Tissue vulnerability to hypoxia *This table will be discussed and may be completed during class. SHOCK Shock is a state in which diminished cardiac output and/or reduced effective circulating blood volume (failure of the circulatory system to maintain an appropriate blood supply) impairs tissue perfusion and leads to cellular hypoxia. It is a state of systemic tissue hypoperfusion. PATHOLOGY 3500/PATHOLOGY 9535 7 HEMODYNAMIC DISORDERS, THROMBOEMBOLISM, & SHOCK  Categories of shock: o Cardiogenic shock The inability of the heart to pump blood due to myocardial damage (myocardial infarction), extrinsic compression (cardiac tamponade - fluid accumulation in the pericardial sac that compresses the heart), or outflow obstruction (e.g., pulmonary embolism). o Hypovolemic shock Due to loss of blood or plasma volume, resulting in low cardiac output. - E.g., fluid loss from severe burn Cardiogenic and hypovolemic shock result in decreased perfusion. o Septic shock Triggered by microbial infections and is associated with severe systemic inflammatory response syndrome (SIRS). Mechanism: massive outpour of inflammatory mediators from innate and adaptive immune cells that produce arterial vasodilation, vascular leakage, and venous blood pooling. These abnormalities result in tissue hypoperfusion, cellular hypoxia, and metabolic derangements that lead to organ dysfunction. If severe and persistent, it will lead to organ failure and death. Less common: o Neurogenic shock Loss of vascular tone associated with anesthesia or secondary to spinal cord injury. o Anaphylactic shock Triggered by IgE-mediated hypersensitivity reaction (e.g., allergic reaction to ingested peanuts) that leads to systemic vasodilation and increased vascular permeability. Peripheral vasodilation is associated with anaphylaxis, neurogenic and septic shock (due to the release of factors (cytokines, bacterial endotoxins, etc.) that cause dilation and increased permeability of the vessels). STAGES OF SHOCK (for hypovolemic and cardiogenic shock) o Nonprogressive stage: reflex compensatory mechanisms are activated, and vital organ perfusion is maintained. o Progressive stage: tissue hypoperfusion and the onset of worsening circulatory and metabolic derangement, including acidosis (widespread tissue hypoxia; vital organs begin to fail). o Irreversible stage: cellular and tissue injury is so severe that survival is not possible even if the hemodynamic defects are corrected. PATHOLOGY 3500/PATHOLOGY 9535 8 HEMODYNAMIC DISORDERS, THROMBOEMBOLISM, & SHOCK STUDENT NOTES: PATHOLOGY 3500/PATHOLOGY 9535 9 HEMODYNAMIC DISORDERS, THROMBOEMBOLISM, & SHOCK