Topic 6: Introduction Thrombosis Formation of Thrombi Causes of Thrombosis Events Occurring in Thrombosis The Gross and Microscopic Appearance of Thrombi Embolism Composition of Emboli Thrombotic Emboli Venous Thrombotic Emboli Arterial Thrombotic Emboli The Significance of Embolism Infarction Origin of Infarcts Appearance of Infarcts Gross Appearance Microscopic Appearance Factors Favoring Infarction References Learning Guide Objectives Definitions Workbook Web Site Images Study Questions Definitions Flash Cards Terms Flash Cards Web Reader with Images Reader/Learning Guides PDF 2008 William H. Crawford, Jr., D.D.S., M.S. All rights reserved. Copying for commercial purposes is prohibited. 95
Introduction Diseases of the heart and blood vessels (cardiovascular disease) are responsible for 1,000,000 deaths in the United States each year. In order to put this number in perspective, you will remember that cancers claim about 400,000 each year only 40% of deaths that succumb to cardiovascular diseases. If 1,000,000 die each year there is a much larger number many million who are being treated for cardiovascular disorders. Many of these wish to continue their regular dental care. It is, therefore, necessary for those who provide for their dental needs dentists and dental hygienists to know the basic features of cardiovascular diseases. The formation of a blood clot within a blood vessel or a heart chamber is a fairly common occurrence. A blood clot can impede blood flow to the tissues supplied by the vessel it blocks. These blood clots are known as thrombi. Pieces of thrombi can travel down stream blocking blood flow at some distant site. Such detached fragments are known as emboli. Blood flow blockage (ischemia) caused by thrombi or emboli can result in death of tissues supplied by the blocked vessel. An area of tissue necrosis caused by ischemia is known as an infarct. Thus, thrombosis, embolism, and infarction are three interrelated disease processes that have in common the formation of an intravascular blood clot. Thrombosis The act of formation of a blood clot in a living patient is known as thrombosis. This term refers to a process, not a thing. The actual blood clot that is formed by the process of thrombosis is known as a thrombus ; more than one of them are thrombi. In order to qualify as a thrombus a blood clot must occur in a living patient (antemortem) and be found within a blood vessel or heart chamber. Put succinctly, a thrombus is an intravascular antemortem blood clot (intravascular = within a vessel; antemortem = before death). By this definition, blood clots found outside a blood vessel or with a vessel after death are not thrombi; the names given these other clots will be presented later. The Formation of Thrombi Common Clotting Pathway Thrombosis is the initiation of the blood clotting mechanism in response to abnormalities within blood or within blood vessels. The clotting mechanism is usually initiated and sustained by blood platelets in conjunction with chemicals carried in blood plasma. A series of interdependent reactions lead to the activation of a plasma protein named prothrombin which in the presence of an activator forms thrombin. Thrombin, in turn, catalyzes the transformation of another plasma protein, fibrinogen, into an insoluble fibrillar protein end product known as fibrin. It is fibrin that becomes the main ingredient in thrombi. Because these reactions are common to all blood clotting pathways, the pathway is known as the common pathway. Intrinsic Clotting Pathway There are two ways the common pathway can be activated. The first is initiated by exposure of collagen surrounding damaged blood vessels followed by clumping of platelets at that site. A series of reactions on platelet surfaces lead to formation of fibrin by activation of the common pathway. Because all the elements required for blood clotting are present, this chain of events is known as the intrinsic pathway. Thrombi form by activation of the intrinsic and common pathways. Extrinsic Clotting Pathway The second method of activating the common pathway is initiated by damage of tissue cells (as in trauma or surgery) resulting in the release from damaged cells of tissue thromboplastin. With only a few intervening steps, this material is capable of triggering the common pathway and the formation of a fibrin clot. Because this abbreviated pathway is related to outside injury, it is known as the extrinsic pathway. 96
Procoagulants and Anticoagulants The factors and pathways leading to formation of a fibrin clot are sometimes known as procoagulants. If there were no safeguards that prevent procoagulant events from occurring, thrombi would be far more common than they are. Happily, there are a number of processes, structures, and substances that act as anticoagulants. Foremost among these is the character of blood flow. Rapid blood flow prevents blood cells from contacting and sticking to endothelial lining cells. Because normal rapid blood flow prevents platelets from sticking to endothelial cells, it prevents the activation of the intrinsic pathway and the formation of a thrombus. While normal blood flow is important, endothelial cells also act to prevent thrombus formation. By their very presence, these cells prevent exposure of underlying collagen which powerfully attracts platelets. Endothelial cells also secrete a number of anticoagulant substances. The most well known of these is heparin, a substance that inhibits the intrinsic pathway. In addition to the anticoagulant effects of endothelial cells, there are a number of chemicals that circulate in blood plasma that can prevent the formation of thrombin (antithrombins) and destroy fibrin if it should appear (fibrinolysins). From this discussion of procoagulants and anticoagulants, it should be apparent that thrombus formation can occur only when procoagulant forces overwhelm anticoagulant forces. Causes of Thrombosis Table 1: Comparison of the Intrinsic and Extrinsic Blood Clotting Pathways Characteristic Intrinsic Pathway Extrinsic Pathway Triggering Event Damage to endothelial lining with exposure of underlying collagen Damage to tissue cells Cell Involved Platelets Tissue cells Factors Involved XII, XI, IX, VIII Tissue thromboplastin, VII Ca ++ Needed? Yes Yes Endothelial Cell Damage The intrinsic pathway is triggered when collagen is exposed to blood. Since endothelial cells separate blood from underlying collagen, damage to these cells is a prerequisite to thrombosis. There are many ways endothelial cells can be damaged. Increased blood pressure (hypertension) is one common cause of endothelial damage. Diseases of blood vessel walls (e.g., atherosclerosis) can damage endothelial cells directly or roughen the endothelial lining producing turbulent blood flow that, in turn, damages endothelial cells. Damage to endothelial cells by these processes (i.e., hypertension and atherosclerosis) is, by far, the most common cause of thrombosis. Stasis If blood flow becomes abnormally slow, platelets have the opportunity to contact the endothelial lining. Once in contact, platelets may stick and initiate the intrinsic blood coagulation pathway forming a thrombus. Because blood flow is considerably slower in veins than in arteries, veins are where most thrombi occur. Blood returning to the heart from the lower extremities is assisted by valves in leg veins. It is common for these veins to become abnormally wide and for the valves consequently to become ineffective. The resulting abnormality is called varicose veins ; it is accompanied by stagnation, or stasis, of blood flow and the subsequent development of thrombi. Stagnation of blood flow in veins venous stasis is another important cause of thrombosis. Sluggish Blood Flow Other conditions indirectly can produce sluggish blood flow and, therefore, thrombosis. For example, certain alterations in red blood cells (e.g., some anemias) can make them stickier than normal resulting in clumping of erythrocytes and slowing of blood flow. Similarly, overproduction of red blood cells (polycythemia) can cause slowing of blood flow. 97
Blood Diseases While endothelial damage and venous stasis are the most common causes of thrombosis, changes in the composition of blood may account for the formation of some thrombi. For example, if the numbers of platelets rise in the blood stream, there is more chance for the formation of thrombi. This condition is known as thrombocytosis (thrombocyte = platelet). In some other uncommon circumstances, patients may have deficiencies in anticoagulation factors (e.g., antithrombins, fibrinolysins) in their plasma. If these deficiencies appear, the balance of procoagulation-anticoagulation is tipped in favor of procoagulation forces leading to thrombosis. Table 2: Precipitating Factors and Underlying Causes of Thrombosis Precipitating Factor Underlying Cause Endothelial cell damage Hypertension Atherosclerosis Stasis Changes in blood composition Slower blood flow in veins Varicose veins Increased numbers of rbcs Changes in rbc shape and surface features (anemias) Increase numbers of platelets (thrombocytosis) Decrease in anticoagulants (antithrombins, fibrinolysin) Events Occurring in Thrombosis Once thrombosis gets started and anticoagulant strategies are outwitted, a thrombus develops. The resultant thrombus undergoes a series of changes that ensures its permanency. If a patient survives the immediate effects of a thrombus and most do reparative mechanisms already presented will come into play reducing the threat a thrombus poses. Some events occur before repair starts ( early events ) while occur along with repair ( late events ). Figure 1: Diagrammatic representation of early events in thrombosis In the early stages of thrombosis, endothelial cell damage exposes collagen attracting a platelet plug (left). Soon fibrin appears (center) forming a meshwork that traps blood formed elements (right). Early Events Thrombosis usually starts with damage to the endothelial cells lining a blood vessel. Such damage exposes the collagen of the underlying basement membrane and/or surrounding tissues. Platelets are attracted and stick to the exposed collagen; more attracted platelets stick to other platelets. This aggregation of platelets acts as a plug sealing the damaged area preventing escape of blood into surrounding tissues. The surfaces of platelets provide a work table upon which the activation of the clotting factors along the intrinsic pathway can proceed. In a matter of minutes, strands of fibrin appear on the platelet plug. Over the next several hours, more and more fibrin is produced forming a meshwork that, in turn, traps passing blood formed elements. In short order, then, the developing thrombus is composed of platelets, fibrin, erythrocytes, leukocytes, and more platelets. With additional time, the new thrombus increases in size by producing more fibrin and entrapping more formed elements. 98
Figure 2: Late Stages in the Development of a Thrombus. In the later stages in the development of a thrombus, granulation tissue enters from the underlying c.t. (left) attaching the thrombus and recanalizing it (right). Later Events If the patient doesn t die from blood vessel blockage, reparative connective tissue will transform it. In order to understand what will happen next, it is important to recall that one of the earliest events in thrombosis is the exposure of the connective tissue surrounding a damaged blood vessel. This exposure makes it possible, as demonstrated in Figure 2, for the surrounding connective tissue to gain access to the interior of the thrombus. The granulation tissue (fibroblasts and endothelial cells) entering the thrombus has two important effects: (1) the entrance of endothelial cells will form new capillaries and (2) collagen fibers formed by fibroblasts will stitch the thrombus to the blood vessel wall preventing its detachment. Further, if the thrombus completely blocks the vessel, new blood vessels within the thrombus may join with one another in such a way that blood flow through the thrombus is re-established. Formation of continuous channels of this kind is known as recanalization of a thrombus. As months pass, a scar (cicatrix) will form within the thrombus increasing the amount of collagen and decreasing the new blood vessels. Contraction of the cicatrix may pull the thrombus away from the far wall reopening the vessel to blood flow once again. Table 3: Steps in Thrombus Formation Early Steps Endothelial cell damage Exposure of collagen Formation of platelet plug Initiation of clotting sequence Formation of fibrin Entrapment of blood cells Later Steps Granulation Recanalization Cicatrization Contraction The Gross and Microscopic Appearance of Thrombi Types of Thrombi Virtually all thrombi start at a site of endothelial cell damage on a blood vessel wall. As the thrombus enlarges, it extends into the lumen for a distance but does not, at least at first, close (occlude) it. Such thrombi are known as mural thrombi (mural = wall). In time, if the blood vessel has a narrow enough lumen, the thrombus will block the vessel stopping blood flow through it. Such thrombi are known as occlusive thrombi (occlude = to close). Sometimes an occlusive thrombus will elongate causing it to extend (propagate) up the vessel for a distance. Such enlarging thrombi are called propagative thrombi. Thrombi of this type are commonly encountered in varicose veins of the leg and, more ominously, in the coronary arteries of heart attack patients. Texture and Color of Thrombi In its earliest stages a thrombus may appear to be soft and bright red due to the predominance of rbcs in them; sometimes, these are called red thrombi. At later stages most thrombi acquire a pinkish-grey color due to the increased proportions of wbcs, fibrin, and collagen; these are mixed thrombi. As might be expected, the texture of thrombi changes with time. As mentioned, early thrombi are soft and become firmer as collagen is deposited. In fact older thrombi become increasingly crumbly (friable) as fibrin and collagen accumulate. Since thrombi originate within a blood vessel, large ones will conform to the shape of the blood vessel wall. When the cross-section of a thrombus is viewed with the unaided eye, it is seen to be composed 99
of layers or laminations. This laminated appearance is characteristic of thrombi; they are called the lines of Zahn. Figure 3: Types of Thrombi Mural Occlusive Propagative There are three types of thrombi according to whether or not they block blood flow: mural thrombi extend into the lumen (left), occlusive thrombi block the lumen (center), and propagative thrombi extend along the blood vessel (right). More important than these color and texture changes is the fact that except at their earliest stages (first few hours) thrombi become attached to the vessel wall. Old scarred thrombi become, quite literally, part of the blood vessel wall. Such attachment, of course, assists in the prevention of detachment and entrance of thrombi into the blood stream. The microscopic appearance of thrombi changes with time. At first they are composed of platelets, fibrin, rbcs and wbcs. As time goes on, granulation tissue becomes increasingly prominent. In the latest stages of thrombus formation, collagen is the predominant component. Because of the changes in microscopic appearance with time, pathologists can estimate the age of thrombi. Often establishment of the age of a thrombus is important in determining whether a disease is recent or long-standing. Sometimes the age of thrombi even are helpful in solving murders. Comparison of Thrombi and Postmortem Clots In keeping with the forensic tone struck above, pathologists often must determine whether a blood clot found within a blood vessel occurred before or after death. Is it a thrombus (antemortem clot) or a postmortem clot? As has already been described, thrombi are dry, friable, and gray. They are attached to the vessel wall, conform to the shape of the vessel, and have display lines of Zahn. On the other hand, postmortem clots have completely different colors and textures. They are slimy and gelatinous; they are bright purple to red in color. Given the texture and color, sometimes they are known as currant jelly clots. Postmortem clots are not attached to the vessel wall and have no lines of Zahn. Table 4: Comparison of Thrombi and Postmortem Clots Thrombi (antemortem clots) Postmortem Clots Dry and friable Gelatinous Gray Dark purple-red Attached to vessel wall Free in blood vessel Conform to vessel shape Do not conform to vessel shape Lines of Zahn No lines of Zahn Embolism Formation of a thrombus is a serious event even if it stayed where it arose. If, however, if a thrombus breaks loose from its moorings or if a piece of it breaks off, blood flow will carry it to a distant location. Such an event is called embolism. More specifically, embolism is defined as the formation of an detached mass within a blood vessel that is carried along with blood flow. The actual mass produced by the process of embolism is an embolus; several of these are called emboli. 100
Composition of Emboli Most emboli are thrombi (or pieces of thrombi) that have been carried along by blood flow. Somewhere around 95% of emboli are derived from pre-existing thrombi thrombotic emboli. Because this source of emboli is such a common one and because it is common for thrombi to produce emboli, this process is frequently known as thromboembolism. Occasionally emboli are composed of other things. Once in a while, fat may enter the blood stream causing a situation known as fat embolism. This usually is the result of a bone fracture with the entrance of fatty bone marrow into venous sinusoids. Air droplets may also enter the circulation, a condition called air embolism. If enough air accumulates in blood something on the order of 100 cc. or more a foamy froth will develop that will behave as if it were a solid body. Skin divers know of the risk of the bends, a condition in which nitrogen gas forced into supersaturation during descent may bubble out of solution during a too rapid return to the surface. In this example, nitrogen produces gas embolism. Tooth picks, broken hypodermic needles, and even bullets may enter the circulation producing foreign body emboli. Finally, it was emphasized in the previous chapter that malignant tumor cells all too often enter the blood stream. Although blood-borne tumor cells rarely cause cardiovascular disease, they are known as tumor emboli. Table 5: Composition of Emboli Thrombi Fat Air Gas Foreign bodies Malignant tumor cells Thrombotic Emboli Thrombotic emboli are, as their name implies, derived from thrombi that are already present (pre-existing) in blood vessels. If the pre-existing thrombus is located in a vein, an embolus that arises from it is known as a venous embolus. If, on the other hand, an embolus arises from a thrombus located in an artery or in a heart chamber, the name arterial embolus is used. Emboli are named, then, for the side of the circulation from which they arise (veins or arteries). Venous Thrombotic Emboli Most venous emboli arise from pre-existing thrombi in leg veins (varicose veins again). Once free in a vein, blood flow carries the embolus along until it wedges into a blood vessel to narrow for it to pass. A venous embolus arising from a thrombus in a leg vein will pass through larger and larger vessels until it reaches the heart. The embolus will pass through the right atrium to the right ventricle where it is pumped into a pulmonary artery. Once there, the embolus will pass through smaller and smaller vessels until it can go no further. Since the embolus is too big to pass through lung capillaries, it will block a large or small artery depending on its size. Because almost all veins lead to the right heart, almost all venous emboli will lodge in the lungs. Arterial Thrombotic Emboli Most arterial emboli arise from pre-existing thrombi in the chambers of the heart s left side (usually the left ventricle). An arterial embolus arising from a thrombus in the left ventricle will be pumped directly into the aorta. From there it will enter smaller and smaller arteries. Since it cannot pass through a capillary bed, it will lodge in the arterial side of the circulation through some organ. Because most arteries lead away from the heart, almost all arterial emboli will lodge in some important organ like the brain, kidney, or spleen. The Significance of Embolism It should be obvious that if emboli block blood vessels in the lungs, brain, kidneys, or spleen, serious damage will likely result. In fact, if the embolus is large enough to block a large blood vessel in the brain or lungs, the patient thus afflicted may die. Death, then, is one outcome of embolism. If, however, a smaller vessel is blocked, the patient may survive. Even so, there will be tissue death in the region supplied by the blocked vessel. An area of tissue death caused by an embolus is the subject of the next topic. 101
Infarction The formation of a localized area of tissue death that is caused by blockage of blood supply or drainage is known as infarction. Put more scientifically, infarction is the process of forming a localized area of ischemic necrosis. The area of tissue death is known as an infarct. Arterial and Venous Infarcts There are two ways infarcts can occur: blockage of the arterial inflow and blockage of the venous outflow from an organ. The first are arterial infarcts and the second venous infarcts. Arterial Infarcts The most common way arteries can be blocked is by arterial or venous emboli. As has already been mentioned, arterial emboli block arteries in the brain, kidney, spleen and other systemic organs; venous emboli block arteries in the lung. Blockage of these vessels cut oxygen and nutrient supplies causing tissue necrosis. Large emboli will block large arteries and cause large areas of tissue necrosis (large infarcts). Conversely, small emboli will block smaller arteries causing smaller areas of tissue necrosis (smaller infarcts). Because blood supply is interrupted, arterial infarcts will be paler than the surrounding tissues; they are known as white infarcts or anemic infarcts. Arterial infarcts are caused by emboli impacting in the arterial inflow to an organ. Venous Infarcts It is also possible for tissue death to be caused by blockage of the veins leading away from an organ. The area of tissue death caused by such blockage is known as a venous infarct. Venous infarcts are caused by a thrombus not an embolus blocking the venous outflow from an organ. If one thinks about it for a moment it should be clear that emboli cannot produce venous infarcts. In order to block a vessel, emboli must be carried toward an organ; since blood flows away from an organ through veins, blockage of veins by emboli cannot occur. The most logical explanation of venous infarcts, then, is thrombi arising in veins leading away from an organ. Such blockage prevents blood from leaving the organ; since blood cannot leave it, new blood cannot enter either. It is the resultant stagnation and absence of new blood that causes tissue death. Because blood backs up behind the thrombus throughout the organ, venous infarcts often appear red. They are known, therefore, as red infarcts or hemorrhagic infarcts. Venous infarcts are caused by thrombi arising in the venous outflow from an organ. Other Causes There is no doubt that emboli and thrombi cause most infarcts. However, on occasion other events can cause them. Expanding tumors, for example sometimes compress nearby arteries or veins causing arterial or venous infarcts. Similarly, the intestines sometimes get tied in a knot or extend through a body passage (hernia) compressing arteries or veins supplying them. Appearance of Infarcts Gross Appearance It has already been mentioned that infarcts may be white or red depending on their origin (white = arterial; red = venous). In organs with a tree-like circulation (e.g., kidney) infarcts are cone-shaped with the small end of the cone pointing toward the obstruction. When the cone-shaped infarct is cut longitudinally, it appears as a wedge or triangle. Infarcts occurring in organs with other circulation patterns may not demonstrate the classic conical appearance. Infarcts of the heart may, for example, have very irregular outlines. Microscopic Appearance If an infarct causes immediate death (like a cardiac infarct), there will be little time for it to develop. You may remember that necrosis takes several hours to become manifest under the LM. If the patient does not succumb, the infarct will progress through a series of changes usually classified as early and later events. 102
Early Appearance At around 12 hours after infarction, the dead tissue will show signs of necrosis. If it is an arterial infarct, coagulation necrosis will develop. As the necrotic area develops, it will soon be surrounded by a ring of acute inflammation. Later Appearance If the patient survives, the infarct will undergo regeneration and repair. A few days after onset, granulation tissue appears at the edge and then enters the necrotic area (macrophages clean up the dead tissue). If the tissue is able to regenerate, parenchymal cells will proliferate on the delicate collagen scaffolding that the granulation tissue provides. If not, fibrous connective tissue will accumulate and ultimately replace the necrotic tissue. References: Kumar, Abbas, Fausto: Robbins and Cotran Pathologic Basis of Disease. Elsevier-Saunders, Seventh Edition, 2005. Learning Guide 1. After completion of this topic, the student should be able to diagram and identify the final blood clotting steps along the common pathway. list and identify three causes of thrombosis. list, describe, and identify the early and late events in thrombosis. differentiate and identify the differences between mural, occlusive, and propagative thrombi. identify the basic differences between thrombi and postmortem clots. trace blood flow from the femoral vein to the lungs. trace blood flow from the left ventricle to the kidneys. identify the features that differentiate venous and arterial emboli. identify the features that differentiate venous and arterial infarcts. list and identify three factors favoring infarction. 2. Associate (by identifying them) the following prefixes/suffixes and their meanings. In other words, when confronted with these prefixes/suffixess, be able to pick the correct term/definition from a list (multiple choice or matching). ante before mortem death bolus round mass post after em before thrombo platelet 3. Associate (by writing them) the following terms with their definitions or with clinical examples of them. In other words, when confronted with the definition or example of the following, be able to write, and correctly spell, the defined term. In addition, be able to recognize the context in which each exists. In addition be able to pick the correct term/definition from a list (multiple choice or matching). Embolus Infarct Thrombus A detached mass within a blood vessel that is carried along with blood flow. An area of tissue death caused by blockage of blood flow; a localized area of ischemic necrosis. A blood clot found within a blood vessel in a living person (an antemortem blood clot). 4. Associate (by identifying them) the following terms and their definitions. In other words, when 103
confronted with the term or definition of the following, be able to pick the correct term/definition from a list (multiple choice or matching). Arterial Embolus Arterial Infarcts Common Pathway Embolism Extrinsic Pathway Fibrin Fibrinogen Formed Elements Infarction Intrinsic Pathway Mural Thrombus Occlusive Thrombus Postmortem Clots Propagative Thrombus Prothrombin Stasis Thrombin Thrombocyte Thrombocytosis Thromboembolism Thrombosis Thrombotic Emboli Tissue Thromboplastin Venous Infarcts Venous Stasis An embolus that originates from a thrombus pre-existing in an artery or heart chamber. An infarct caused by blockage of arterial supply to an organ; most are caused by thrombotic emboli. The final steps in the clotting sequence; may be accessed by intrinsic and extrinsic pathways. The process of forming a detached mass within a blood vessel. A reduced number of steps initiated by damage to tissue cells and the release of tissue thromboplastin; a short cut to the common blood clotting pathway. A fibrillar protein that makes up blood clots; the end product of the clotting sequence. The precursor to fibrin; found in blood plasma. Cells and cell fragments that circulate in blood: rbcs, wbcs and platelets. The process of forming an area of tissue death caused by blockage of blood flow. A series of steps initiated by platelets and a number of factors that lead to activation of the common pathway of blood clotting. A thrombus that extends into, but does not close, the lumen of a blood vessel. A thrombus that extends into and closes the lumen of a blood vessel blocking blood flow. Clots that occur after death; caused by settling of blood in veins and in heart chambers. A thrombus that elongates and increasingly extends along a blood vessel. A precursor of an important substance in the common pathway of blood clotting; found in blood plasma. Stagnation of blood; decreased velocity of blood. The activated form of prothrombin; important in conversion of fibrinogen to fibrin. A blood platelet. Increased numbers of blood platelets. Process of forming emboli from thrombi. The process of formation of a blood clot within the blood vessel of a living person. Emboli composed of all or part of a thrombus. Substance released from damaged tissue cells that activate the extrinsic blood clotting pathway. An infarct caused by blockage of the venous drainage from an organ; most are caused by a thrombus arising in a vein. Decreased velocity of blood within veins. 104
5. By placing Xs in the empty cells, match the thrombus types with the printed definitions. Propagative Thrombus Mural Thrombus Occlusive Thrombus Definition Closes the lumen Increasingly extends along a blood vessel Does not close the lumen 6. By placing Xs in the empty cells, match the pathways with the printed circumstances. Intrinsic Pathway Extrinsic Pathway Common Pathway Circumstance Evoked by surgical wounds Damage to blood vessel lining Factors VIII, IX, XI, and XII involved Platelets involved Tissue cells involved Prothrombin conversion to thrombin Tissue thromboplastin involved Ca +2 needed Fibrinogen catalyzed by thrombin Exposure of collagen Damage to tissue cells Evoked by coronary artery disease Fibrinogen converted to fibrin 105
7. By placing Xs in the empty cells, match the pathways with the printed circumstances. Endothelial Cell Damage Stasis Changes in Blood Composition Circumstance Hypertension Increased numbers of platelets Varicose veins Changes in rbc shapes and surfaces Decrease in natural anticoagulants Atherosclerosis Slower blood flow in veins Thrombocytosis Increased numbers of rbcs 8. To indicate the steps in thrombosis, place the following terms in their correct order: granulation, endothelial cell damage, formation of fibrin, recanalization, exposure of collagen, entrapment of rbcs and wbcs, formation of platelet plug, cicatrization, initiation of the clotting sequence. Early Events 1. 2. 3. 4. 5. 6. Late Events 7. 8. 9. 106
9. By placing Xs in the empty cells, match thrombus and postmortem clot with the printed thrombus features. Thrombus Postmortem Clot Thrombus Features Lines of Zahn Free in blood vessel Occur in living people Soft, gelatinous May cause emboli Dry and friable Attached to vessel wall Conforms to blood vessel shape Does not cause infarcts 10. By placing Xs in the empty cells, match the embolus type with the printed features. Arterial Embolus Venous Embolus Features Arise from leg thrombi May become arrested in kidney Arise from left ventricle thrombi Become arrested in the lungs May become arrested in the brain May come arrested in the spleen 107
11. To trace the pathways followed by venous and arterial emboli, place the following terms in their correct orders: renal artery, femoral vein, left ventricle, lung, brain, splenic artery, right ventricle, aorta, cerebral artery, inferior vena cava, spleen, pulmonary artery, kidney, right atrium. Path of Venous Emboli Path of Arterial Emboli 1. 1. 2. 2. 3. 3. 4. 4. 5. Alternative pathway: 6. 3. 4. Alternative pathway: 3. 4. 12. By placing Xs in the empty cells, match the infarct type with the printed situations. Arterial Infarct Venous Infarct Situation Often pale in color Area of tissue death Often caused by in-situ thrombi Often red in color Coagulation necrosis a common feature Often caused by emboli Lung Brain, kidney, spleen 108
13. By placing Xs in the empty cells, indicate which of the following situations favor or do not favor infarction. Favors Infarction Does Not Favor Infarction Situation Double blood supply Brain, kidney, heart Inadequate blood flow Parallel blood supply End artery blood supply Anemia Transient ischemia 109
14. By placing Xs in the empty cells, match the terms with the printed fictitious histories. Sign Symptom Infarct Necrosis Thrombus Embolus Recanalization Ischemic Necrosis Venous Embolism History Mr. Brendel, a 62 year-old white male, experienced crushing chest pain while climbing a fairly steep hill on his golf course. The pain did not subside with rest so he was rushed to the nearest hospital. After several tests he and his wife was informed that he had experienced blockage of a coronary artery supplying a portion of his myocardium (heart muscle). As a result, a portion of Mr. Brendel s heart muscle had died. After several months of rehabilitation, Mr. Brendel recovered. Mrs. Mutter, a 52 year-old white female experienced pain and swelling in her right leg. A day later this pain was followed by chest pain and shortness of breath. After hospitalization, test proved that she had not suffered a heart attack but that a clot had entered her lung. At surgery, a large clot was removed from her right leg and anticoagulant therapy instituted. After a time Mrs. Mutter recovered. Mr. Solti, a 51 year-old white male had sudden partial blindness in his left eye. After some tests, his physician stated that the episode was caused by a clot in a blood vessel supplying the retina. The physician went on to say that with time and anticoagulant therapy, the clot would shrink and/or be bypassed by new blood vessels. As predicted, Mr. Solti s vision improved within six months. 110