Hemodynamic Disorders, Thromboembolic Disease, and Shock PDF Spring 2025

HEMODYNAMIC DISORDERS,THROMBOEMBOLIC DISEASE AND SHOCK Dr. Danny Mora Oral and Maxillofacial Pathologist  OBJECTIVES The student will learn to recognize the different types of hemodynamic disorder...

HEMODYNAMIC DISORDERS,THROMBOEMBOLIC DISEASE AND SHOCK Dr. Danny Mora Oral and Maxillofacial Pathologist  OBJECTIVES The student will learn to recognize the different types of hemodynamic disorders. Will identify in general thromboembolism and its complications. Also will know the difference between types of shock. Disclosure: Most photos are from Copyright © 2017, by Elsevier Inc. All rights reserved. EDEMA AND EFFUSIONS  EDEMA AND EFFUSIONS Disorders that affect cardiovascular, renal, or hepatic function are often marked by the accumulation of fluid in tissues (edema) or body cavities (effusions). Normally the vascular hydrostatic pressure pushes water and salts out of capillaries into the interstitial space and the plasma colloid osmotic pressure pulls water and salts back into vessels. Elevated hydrostatic pressure or diminished colloid osmotic pressure disrupts this balance and results in increased movement of fluid out of vessels If the net rate of fluid movement exceeds the rate of lymphatic drainage, fluid accumulates Edema if within tissues Effusion is the fluid that accumulates within a body cavity  EDEMA 60% of lean body weight is water Two thirds of this water is intracellular The remainder is found in the extracellular space, mostly as interstitial fluid About 5% of total body water is in blood plasma.  EDEMA Is increased fluid in the interstitial tissue spaces. Depending on the area that has edema the fluid collection in body cavities are designated: Hydrothorax, Hydropericardium, Hydroperitoneum or ascites. Anasarca is a severe and generalized edema with profound subcutaneous tissue swelling. Edema and effusions may be inflammatory or non inflammatory.  TYPES OF EDEMA Increased Hydrostatic Pressure Reduced Plasma Osmotic Pressure (Hypoproteinemia) Impaired Venous Return Sodium Retention ✓ Congestive heart failure ✓ Excessive salt intake ✓ Constrictive pericarditis Protein-losing glomerulopathies with renal insufficiency ✓ Ascites (liver cirrhosis) (nephrotic syndrome) ✓ Increased tubular ✓ Venous obstruction or Liver cirrhosis (ascites) compression reabsorption of sodium Malnutrition ✓ Thrombosis ✓ Renal hypoperfusion Protein-losing gastroenteropathy ✓ External pressure ✓ Increased renin- Lymphatic Obstruction (e.g.,mass) angiotensin- ✓ Inflammatory ✓ Lower extremity aldosterone secretion inactivity with prolonged ✓ Neoplastic Inflammation dependency ✓ Postsurgical ✓ Acute inflammation Arteriolar Dilation ✓ Postirradiation ✓ Chronic inflammation ✓ Heat ✓ Neurohumoral ✓ Angiogenesis dysregulation  MORPHOLOGY Edema fluid generally manifests only as subtle cell swelling, with clearing and separation of the extracellular matrix elements.  MORPHOLOGY Subcutaneous edema ✓ Its distribution depends on the cause. ✓ Diffuse or conspicuous at the sites of highest hydrostatic pressures is called dependent. ✓ Edema of the dependent parts of the body (e.g., the legs when standing, the sacrum when recumbent) is a prominent feature of congestive heart failure, particularly of the right ventricle. ✓ Edema as a result of renal dysfunction or nephrotic syndrome is generally more severe than cardiac edema and affects all parts of the body equally.  MORPHOLOGY Pulmonary edema Typically seen in the setting of left ventricular failure and in renal failure, acute respiratory distress syndrome, pulmonary infections, and hypersensitivity reactions. The lungs are two to three times their normal weight, and sectioning reveals frothy, blood-tinged fluid representing a mixture of air, edema fluid, and extravasated red blood cells.  MORPHOLOGY Edema of the brain Localized: abscess or neoplasm Generalized as in encephalitis, hypertensive crisis, or obstruction to the brain's venous outflow. Trauma may result in local or generalized edema depending on the nature and extent of the injury. The brain is grossly swollen, with narrowed sulci and distended gyri, showing signs of flattening against the unyielding skull. HYPEREMIA AND CONGESTION The terms hyperemia and congestion both indicate a local increased volume of blood in a particular tissue. Hyperemia is an active process resulting from augmented tissue inflow because of arteriolar dilation, as in skeletal muscle during exercise or at sites of inflammation. The affected tissue is red because of the engorgement of vessels with oxygenated blood. HYPEREMIA AND CONGESTION Congestion is a passive process resulting from impaired outflow from a tissue. It may occur systemically, as in cardiac failure, or it may be local, resulting from an isolated venous obstruction. The tissue has a blue-red color (cyanosis), particularly as worsening congestion leads to accumulation of deoxygenated hemoglobin in the affected tissues. HYPEREMIA AND CONGESTION Congestion and edema commonly occur together, primarily since capillary bed congestion can result in edema due to increased fluid transudation. Chronic passive congestion is chronic state of congestion and edema. ✓ Capillary rupture at these sites of chronic congestion may cause small foci of hemorrhage; breakdown and phagocytosis of the red cell debris can eventually result in small clusters of hemosiderin- laden macrophages  HEMORRHAGE Hemorrhage generally indicates extravasation of blood due to vessel rupture. Capillary bleeding can occur under conditions of chronic congestion, and an increased tendency to hemorrhage from usually insignificant injury is seen in a wide variety of clinical disorders collectively called hemorrhagic diatheses. Rupture of a large artery or vein is almost always due to vascular injury, including trauma, atherosclerosis, or inflammatory or neoplastic erosion of the vessel wall.  HEMORRHAGE Hemorrhage may be manifested in a variety of patterns, depending on the size, extent, and location of bleeding. Hematoma: enclosed within a tissue ✓ Hematomas may be relatively insignificant (a bruise) or may be sufficiently large as to be fatal as in a massive retroperitoneal hematoma resulting from rupture of a dissecting aortic aneurysm. Petechiae: Minute 1 to 2 mm hemorrhages into skin, mucous membranes or serosal surfaces and are typically associated with locally increased intravascular pressure, low platelet counts (thrombocytopenia), defective platelet function (as in uremia), or clotting factor deficits.  HEMORRHAGE Purpura: Slightly larger (>3 mm) hemorrhages. These may be associated with many of the same disorders that cause petechiae and may also occur secondary to trauma, vascular inflammation (vasculitis), or increased vascular fragility as seen in amyloidosis. Ecchymoses: Larger (> 1 to 2 cm) subcutaneous hematomas and are characteristically seen after trauma and many other conditions.  HEMORRHAGE The erythrocytes in these local hemorrhages are degraded and phagocytosed by macrophages; Hemoglobin (red-blue color) is then enzymatically converted into bilirubin (blue-green color) and eventually into hemosiderin (gold-brown color), accounting for the characteristic color changes in a hematoma. Large accumulations of blood in one or another of the body cavities are called hemothorax, hemopericardium, hemoperitoneum, or hemarthrosis (in joints). Patients with extensive hemorrhage occasionally develop jaundice from the massive breakdown of red cells and systemic release of bilirubin. Hemothorax Hemopericardium HEMOSTASIS AND THROMBOSIS Normal hemostasis is the result of a set of well- regulated processes that accomplish two important functions: ✓ They maintain blood in a fluid, clot-free state in normal vessels; ✓ They are poised to induce a rapid and localized hemostatic plug at a site of vascular injury. The pathologic opposite to hemostasis is thrombosis HEMOSTASIS AND THROMBOSIS Normal hemostasis is the result of a set of well- regulated processes that accomplish two important functions: ✓ They maintain blood in a fluid, clot-free state in normal vessels; ✓ They are poised to induce a rapid and localized hemostatic plug at a site of vascular injury. The pathologic opposite to hemostasis is thrombosis  HEMOSTASIS AND THROMBOSIS Both hemostasis and thrombosis are regulated by three general components: ✓ The vascular wall ✓ Platelets ✓ The coagulation cascade  NORMAL HEMOSTASIS Primary hemostasis Arteriolar vasoconstriction by reflex neurogenic mechanisms Transient effect Adhesion of platelets and become activated, that is, undergo a shape change and release secretory granules. The secreted products have recruited additional platelets (aggregation) to form a hemostatic plug;  NORMAL HEMOSTASIS Secondary hemostasis Tissue factor, a membrane bound pro coagulant factor synthesized by endothelium, is also exposed at the site of injury. Thrombin converts circulating soluble fibrinogen to insoluble fibrin Thrombin also induces further platelet recruitment and granule release. Takes longer to happen than the initial platelet plug. Polymerized fibrin and platelet aggregates form a solid, permanent plug to prevent any further hemorrhage  NORMAL HEMOSTASIS Clot stabilization and resorption Polymerized fibrin and platelet aggregates undergo contraction to form a solid, permanent plug that prevents further hemorrhage Also, counterregulatory mechanisms (e.g., tissue plasminogen activator, t-PA) are set into motion that limit clotting to the site of injury and eventually lead to clot resorption and tissue repair.  PLATELETS Platelets play a central role in normal hemostasis. Platelets contain two specific types of granules. Alpha granules: ✓ Express the adhesion molecule P-selectin on their membranes ✓ Contain fibrinogen, fibronectin, factors V and VIII, platelet factor 4 (a heparin binding chemokine), platelet-derived growth factor, and transforming growth factor-beta. Dense bodies or granules Contain adenine nucleotides (ADP and adenosine triphosphate [ATP]), ionized calcium, histamine, serotonin, and epinephrine.  PLATELETS After vascular injury, platelets encounter ECM constituents that are normally sequestered beneath an intact endothelium ✓ collagen ✓ Proteoglycans ✓ Fibronectin ✓ adhesive glycoproteins On contact with ECM, platelets undergo three general reactions: ✓ adhesion and shape change ✓ secretion (release reaction) ✓ aggregation  PLATELETS Platelet adhesion To extracellular matrix is mediated largely via interactions with vWF, which acts as a bridge between platelet surface Receptors (e.g., glycoprotein Ib, complexed with serum factors V and IX) and exposed collagen. Platelets can also adhere to other components of the ECM like fibronectin vWF -glycoprotein Ib associations are the only interactions sufficiently strong to overcome the high shear forces of flowing blood. Genetic deficiencies of vWF or of its glycoprotein Ib (GpIb) receptor result in defective platelet adhesion and bleeding disorders.  PLATELETS Secretion (release reaction) Occurs soon after adhesion. The process starts by binding of agonists to platelet surface receptors followed by an intracellular protein phosphorilation cascade. Calcium is required in the coagulation cascade  PLATELETS Platelet aggregation Follows adhesion and secretion. ADP and Thromboxane A2 stimulate platelet aggregation This is the primary hemostatic plug and it is reversible With the activation of the coagulation cascade, thrombin is generated. Thrombin binds to platelets and causes more aggregation. Contraction of the platelets creates an irreversible mass of platelets producing a secondary hemostatic plug. Fibrinogen is also important in the platelet aggregation connecting multiple platelets together.  COAGULATION CASCADE Constitute the third component of the hemostatic process. The end result is the formation of thrombin. Thrombin converts fibrinogen into fibrin. It also exerts a wide variety of effects on the local vasculature and inflammation. The blood coagulation scheme has been divided into extrinsic and intrinsic pathways, converging where factor X is activated. The intrinsic pathway may be initiated in vitro by the activation of Hageman factor (factor XII), while the extrinsic pathway is activated by tissue factor, a cellular lipoprotein exposed at sites of tissue injury. Once activated, the coagulation cascade must be restricted to the local site of vascular injury to prevent clotting of the entire vascular tree.  THE COAGULATION CASCADE CAN BE DIVIDED INTOTHE EXTRINSIC AND INTRINSIC PATHWAYS. The prothrombin time (PT) assay assesses the function of the proteins in the extrinsic pathway (factors VII, X, V, II [prothrombin], and fibrinogen). Tissue factor, phospholipids, and calcium are added to plasma, and the time for a fibrin clot to form is recorded. Normal value is 10 to 12 seconds. The partial thromboplastin time (PTT) assay screens the function of the proteins in the intrinsic pathway (factors XII, XI, IX, VIII, X, V, II, and fibrinogen). Clotting of plasma is initiated by the addition of negatively charged particles (e.g., ground glass) that activate factor XII (Hageman factor) together with phospholipids and calcium, and the time to fibrin clot formation is recorded. Normal value is 30 to 45 seconds.  THROMBOSIS Three primary influences predispose to thrombus formation or Virchow triad: ✓ Endothelial injury ✓ Stasis or turbulence of blood flow ✓ Blood hypercoagulability  ENDOTHELIAL INJURY Endothelial injury by itself can lead to thrombosis. ✓ Physical loss of endothelium ✓ Dysfunctional endothelium o May occur due to the hemodynamic stresses of hypertension, turbulent flow over scarred valves, or bacterial endotoxins. Homocystinuria, hypercholesterolemia, radiation, or products absorbed from cigarette smoke may initiate endothelial injury.  ALTERATIONS IN NORMAL BLOOD FLOW Turbulence ✓ Arterial and cardiac thrombosis Stasis is a major factor in the development of venous thrombi. HYPERCOAGULABILITY  MORPHOLOGY OF THROMBOSIS Thrombi may develop anywhere in the cardiovascular system Arterial or cardiac thrombi usually begin at a site of endothelial injury (e.g., atherosclerotic plaque) or turbulence (vessel bifurcation) Venous thrombi characteristically occur in sites of stasis Thrombi formed in the heart or aorta have grossly (and microscopically) apparent laminations, called lines of Zahn, ✓ Produced by alternating layers of platelets admixed with some fibrin and layers containing more red cells. ✓ When arterial thrombi arise in heart chambers or in the aortic lumen, they usually adhere to the wall of the underlying structure and are called mural thrombi.  MURAL THROMBI. A. THROMBUS IN THE LEFT AND RIGHT VENTRICULAR APICES, OVERLYING WHITE FIBROUS SCAR. B. LAMINATED THROMBUS IN A DILATED ABDOMINAL AORTIC ANEURYSM. NUMEROUS FRIABLE MURAL THROMBI ARE ALSO SUPERIMPOSED ON ADVANCED ATHEROSCLEROTIC LESIONS OF THE MORE PROXIMAL AORTA (LEFT SIDE OF PICTURE). Thrombus with lines of Zahn  MORPHOLOGY OF THROMBOSIS Arterial thrombi are usually occlusive Common sites ✓ Coronary ✓ Cerebral ✓ Femoral arteries The thrombus is usually superimposed on an atherosclerotic plaque, also seen in vasculitis or trauma. The thrombi are typically firmly adherent to the injured arterial wall and are gray-white and friable  MORPHOLOGY OF THROMBOSIS Venous thrombosis or phlebothrombosis The thrombus often creates a long cast of the vein lumen. They have more erythrocytes and are called red, or stasis, thrombi. Lower extremities (90% of cases) Upper extremities Periprostatic plexus Ovarian and periuterine veins Postmortem clots at autopsy may be confused for venous thrombi. Postmortem clots are gelatinous with a dark red dependent portion where red cells have settled by gravity and a yellow chicken fat supernatant resembling melted and clotted chicken fat; they are usually not attached to the undelying wall.  FATE OF THE THROMBUS If a patient survives the immediate effects of a thrombotic vascular obstruction, thrombi undergo some combination of the following four events in the ensuing days to weeks: Propagation. ✓ The thrombus may accumulate more platelets and fibrin (propagate), eventually leading to vessel obstruction. Embolization. ✓ Thrombi may dislodge and travel to other sites in the vasculature. Dissolution. ✓ Thrombi may be removed by fibrinolytic activity. Organization and recanalization. ✓ Thrombi may induce inflammation and fibrosis (organization) and may eventually become recanalized; that is, may reestablish vascular flow, or may be incorporated into a thickened vascular wall. DISSEMINATED INTRAVASCULAR COAGULATION (DIC) DIC is the sudden or insidious onset of widespread fibrin thrombi in the microcirculation. Although these thrombi are not usually visible on gross inspection, they are readily apparent microscopically and can cause diffuse circulatory insufficiency, particularly in the brain, lungs, heart, and kidneys. With the development of the multiple thrombi, there is a rapid concurrent consumption of platelets and coagulation proteins (hence the synonym consumption coagulopathy); Fibrinolytic mechanisms are activated, and as a result an initially thrombotic disorder can evolve into a serious bleeding disorder. DIC is not a primary disease but rather a potential complication of any condition associated with widespread activation of thrombin.  EMBOLISM An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin. Almost all emboli represent some part of a dislodged thrombus, hence the commonly used term thromboembolism. Rare forms of emboli include: Droplets of fat Bubbles of air or nitrogen Atherosclerotic debris (cholesterol emboli) Tumor fragments Bone marrow Foreign bodies An embolism should be considered to be thrombotic in origin unless specified. Inevitably, emboli lodge in vessels too small to permit further passage, resulting in partial or complete vascular occlusion. The potential consequence of such thromboembolic events is the ischemic necrosis of distal tissue, known as infarction.  PULMONARY THROMBOEMBOLISM Pulmonary embolism causes about 200,000 deaths per year. In more than 95% of instances, venous emboli originate from deep leg vein thrombi above the level of the knee. It may occlude the main pulmonary artery, impact across the bifurcation (saddle embolus), or pass out into the smaller, branching arterioles. Rarely, an embolus may pass through an interatrial or interventricular defect to gain access to the systemic circulation (paradoxical embolism). Most pulmonary emboli (60% to 80%) are clinically silent because they are small.  PULMONARY THROMBOEMBOLISM Sudden death, right heart failure (cor pulmonale), or cardiovascular collapse occurs when 60% or more of the pulmonary circulation is obstructed with emboli. Embolic obstruction of medium-sized arteries may result in pulmonary hemorrhage but usually does not cause pulmonary infarction because of the dual blood flow into the area from the bronchial circulation. Embolic obstruction of small end arteriolar pulmonary branches usually does result in associated infarction. Multiple emboli over time may cause pulmonary hypertension with right heart failure.  SYSTEMIC THROMBOEMBOLISM Systemic thromboembolism refers to emboli traveling within the arterial circulation. 80% arise from intracardiac mural thrombi, two thirds of which are associated with left ventricular wall infarcts and another quarter with dilated and fibrillating left atria The remainder originate from aortic aneurysms, thrombi on ulcerated atherosclerotic plaques, or fragmentation of a valvular vegetation, with a small fraction due to paradoxical emboli. 10% to 15% of systemic emboli are of unknown origin. The consequences of systemic emboli depend on: ✓ Extent of collateral vascular supply in the affected tissue, ✓ Tissue's vulnerability to ischemia, ✓ Caliber of the vessel occluded  FAT EMBOLISM Fat is released by marrow or adipose tissue injury and enters the circulation by rupture of the marrow vascular sinusoids or of venules. Although traumatic fat embolism occurs in some 90% of individuals with severe skeletal injuries, less than 10% of such patients have any clinical findings. Fat embolism syndrome is characterized by: ✓ pulmonary insufficiency, ✓ neurologic symptoms, ✓ anemia, ✓ thrombocytopenia. Symptoms typically begin 1 to 3 days after injury, with sudden onset of tachypnea, dyspnea, and tachycardia. Neurologic symptoms include irritability and restlessness, with progression to delirium or coma.  FAT EMBOLISM Patients may present with thrombocytopenia, anemia may result as a consequence of erythrocyte aggregation and hemolysis. A diffuse petechial rash in nondependent areas (related to rapid onset of thrombocytopenia) is seen in 20% to 50% of cases and is useful in establishing a diagnosis. In its full-blown form, the syndrome is fatal in up to 10% of cases. Micro emboli of neutral fat cause occlusion of the pulmonary and cerebral microvasculature, Causes local toxic injury to endothelium  AIR EMBOLISM It is secondary to the release of gas bubbles within the circulation that obstructs blood vessels causing distal ischemic injury. Air may enter the circulation during obstetric procedures or as a consequence of chest wall injury. An excess of 100 cc is required to have a clinical effect A particular form of gas embolism, called decompression, occurs when individuals are exposed to sudden changes in atmospheric pressure. ✓ Scuba and deep sea divers, ✓ Underwater construction workers, ✓ Individuals in unpressurized aircraft in rapid ascent. Treatment of gas embolism requires placing the individual in a compression chamber where the barometric pressure may be raised, thus forcing the gas bubbles back into solution.  AMNIOTIC FLUID EMBOLISM Grave complication of labor and the immediate postpartum period (1 in 50,000 deliveries). ❖ The underlying cause is the infusion of amniotic It has a mortality rate of 20% to 40%, that fluid or fetal tissue into the maternal circulation via has become an important cause of maternal a tear in the placental membranes or rupture of mortality. uterine veins. The onset is characterized by sudden severe ❖ Presence in the pulmonary microcirculation of dyspnea, cyanosis, and hypotensive shock, squamous cells shed from fetal skin, lanugo hair, fat followed by seizures and coma. from vernix caseosa, and mucin derived from the If the patient survives the initial crisis, fetal respiratory or gastrointestinal tract. pulmonary edema typically develops, along ❖ There is also marked pulmonary edema and with Disseminated Intravascular changes of diffuse alveolar damage as well as Coagulopathy (DIC), owing to release of systemic fibrin thrombi indicative of DIC. thrombogenic substances from amniotic fluid. Lung with amniotic fluid embolism  INFARCTION An infarct is an 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 events, and almost all result from arterial occlusion. Occasionally, infarction may also be caused by other mechanisms, such as local vasospasm, expansion of an atheroma owing to hemorrhage within a plaque, or extrinsic compression of a vessel. Other uncommon causes include twisting of the vessels (e.g., in testicular torsion or bowel volvulus), compression of the blood supply by edema or by entrapment in a hernia sac, or traumatic rupture of the blood supply  INFARCTION Morphology Infarcts are classified on the basis of their color (reflecting the amount of hemorrhage) and the presence or absence of microbial infection. Infarcts may be: ✓ red (hemorrhagic) ✓ white (anemic) ✓ septic ✓ bland  INFARCTION Red (hemorrhagic) infarcts occur: Red and white infarcts. Venous occlusions A) Hemorrhagic, roughly wedge-shaped pulmonary red infarct. ✓ Ovarian torsion, B) Sharply demarcated white infarct in the spleen. ✓ Lung, ✓ Dual circulations (e.g., lung and small intestine), permitting flow of blood from the unobstructed vessel into the necrotic zone, ✓ Tissues that were previously congested because of sluggish venous outflow, ✓ When flow is re-established to a site of previous arterial occlusion and necrosis White (anemic) infarcts occur: In arterial occlusions in solid organs with end- arterial circulation (such as heart, spleen, and kidney). Most infarcts tend to be wedge-shaped, with the occluded vessel at the apex and the periphery of the organ forming the base. Hemorrhagic Cerebral infarction White Myocardial infarction  SHOCK Neurogenic shock Cardiogenic shock Less commonly, shock may occur in the Results from myocardial pump failure. setting of anesthetic accident or spinal cord Caused by intrinsic myocardial damage (infarction), injury owing to loss of vascular tone and ventricular arrhythmias, extrinsic compression (cardiac peripheral pooling of blood. tamponade), or outflow obstruction (e.g., pulmonary Anaphylactic shock embolism). Initiated by a generalized IgE-mediated Hypovolemic shock hypersensitivity response, is associated with Results from loss of blood or plasma volume. This may systemic vasodilation and increased vascular be caused by hemorrhage, fluid loss from severe burns, permeability. or trauma. Widespread vasodilation causes a sudden Septic shock increase in the vascular bed capacitance, Caused by systemic microbial infection. which is not adequately filled by the normal Most commonly, this occurs in the setting ofgram- circulating blood volume. negative infections (endotoxic shock), but it can also Hypotension, tissue hypoperfusion, and occur with gram-positive and fungal infections. cellular anoxia result.  STAGES OF SHOCK Shock is a progressive disorder that, if not corrected, leads to death. Nonprogressive phase during which reflex compensatory mechanisms are activated and perfusion of vital organs is maintained A progressive stage characterized by tissue hypoperfusion and onset of worsening circulatory and metabolic imbalances, including acidosis. Irreversible stage that sets in after the body has incurred cellular and tissue injury so severe that even if the hemodynamic defects are corrected, survival is not possible. Questions?