PATHOLOGY OBJECTIVES Cellular Adaptations and Injury 1. Appreciate the structure (at light and electron microscope levels) and function of the cells and cellular organelles and understand the changes they undergo during cell injury and death 2. Be familiar with the meaning and pronunciation of the terms and be able to use them properly 3. Be familiar with the concepts of reversible and irreversible cell injury 4. Be familiar with the mechanism that leads to the development of each of the following a. Cellular swelling b. Fatty change c. Fatty infiltration d. Caseous necrosis e. Fat necrosis f. Liquefaction necrosis g. Coagulative necrosis h. Hyaline change i. Fibrinoid necrosis j. Dystrophic calcification k. Metastatic calcification 5. Be familiar with the specific cells or tissues most commonly affected by the following (where applicable): a. Cellular swelling b. Fatty change c. Fatty infiltration d. Caseous necrosis e. Fat necrosis f. Liquefaction necrosis g. Coagulative necrosis h. Hyaline change i. Fibrinoid necrosis j. Dystrophic calcification k. Metastatic calcification
Hemodynamics I: Edema, Congestion & Hemorrhage 1. Define edema 2. List and understand the pathophysiologic mechanisms (or categories) of edema 3. Compare and contrast transudate and exudates, with reference to composition and pathogenesis 4. List important clinical settings in which edema is caused (solely or principally) by: a. Increased hydrostatic pressure b. Reduced plasma oncotic pressure c. Lymphatic obstruction d. Sodium retention 5. Understand why edema occurs in acute inflammation 6. Define nephritic syndrome 7. With respect to clinical settings of edema, know whether distribution is localized, dependent or systemic 8. Know the gross and microscopic morphologic features of pulmonary edema, and understand their pathogenesis 9. What is the clinical significance of pulmonary and cerebral edema? 10.Define, compare and contrast hyperemia and congestion 11.Compare and contrast the gross microscopic morphologic features of acute and chronic pulmonary congestion and understand their pathogenesis 12.What is the most frequent cause of pulmonary congestion? 13.What is the significance of ‘heart failure cells’ in pulmonary congestion? 14.Know the gross and microscopic features of congestion in the liver and understand their pathogenesis 15.What is the most frequent cause of hepatic congestion? 16.What is the most frequent cause of chronic congestion of the spleen? 17.Define hemorrhage 18.What is the basic cause of hemorrhage? 19.What determines the clinical significance of hemorrhage? (Name 3 determining factors) 20.Define hematoma, hemothorax, hemopericardium, hemoperitoneum, petechia, purpura and ecchymosis 21.Give examples of hemorrhage, which may lead to exsanguinations
Hemodynamics II: Thrombosis, Embolism & Infarction 1. Define thrombus and thrombosis
A. THROMBUS: AGGREGATE OF COAGULATED BLOOD CONTAINING i. PLATELETS ii. FIBIRN iii. ENTRAPPED CELLULAR ELEMENTS B. THROMBOSIS- HEMOSTASTIS IN THE WRONG PLACE OR INAPPROPRIATE ACTIVATION OF NORMAL HEMOSTATIC PROCESSES
2. Know the 3 primary factors that predispose to thrombosis
A.K.A.- VIRCHOW’S TRIAD A. CHANGES IN VESSEL WALL-ESPECIALLY ENDOTHELIUM INJURY B. CHANGES IN NORMAL BLOOD FLOW- STASIS AND/OR TURBULENCE C. ABNORMALITIES OF BLOOD- HYPERCOAGULABILITY
3. Given a major clinical setting in which thrombosis occurs, name the predisposing factor or factors involved
CLINICAL SETTING-LOCAL VASCULAR OBSTRUCTION OF BLOOD VESSELS AND HEART PRE-DISPOSING FACTOR-ATHERSCLEROSIS OTHER FACTORS- INFLAMMATION AND TRAUMA
4. Compare and contrast venous and arterial thrombi with reference to morphologic features and most common sites of origin
A. VENOUS THROMBIi. ORIGIN- VEINS OF THE LEGS (DVT ABOVE THE KNEE) ii. MORPHOLOGY- VIRTUALLY ALWAYS OCCLUSIVE AND AT SITES OF STASIS B. ARTERIAL THOMBIi. ORIGIN-SITES OF ENDOTHELIA INJURY OR TURBULENCE ii. MORPHOLOGY- USUALLY OCCLUSIVE, ADHERENT TO THE INJURED WALL, GRAY WHITE AND FRIABLE, TANGLED MESH OF CELLS, AND EXHIBIT LINES OF ZAHN.
5. Define the lines of Zahn
THESE LINES ARE SEEN IN ATERIAL THROMBI AND ARE USUALLY HARDER TO SEE IN SMALLER ARTERIES AND VEINS. ON GROSS, MICROSCOPIC EXAMINATIONS, THERE ARE ALTERNATING PALE AND DARK AREAS. SIGNIFICANCE IS THAT THEU IMPLY THROMBOSIS AT THE SITE. THE DARK AREAS REPRESENT MORE BLOOD/RBC, WHILE THE PALE AREAS ARE REPRESENTIVE OF PLATELETS MIXED WITH FIBIRN
6. Define vegetations:
THROMBI ON HEART VALVES. THEY CAN BE DUE TO BACTERIAL OR BLOOD BORNE INFECTIONS. THEY CAN ALSO BE DUE TO HYPERCOAGULABLE STATES. MITRAL AND ARTERIAL VALVES ARE DAMAGED EXTENSIVEY BY THE FORMER
7. What is the fate of a thrombus? List 5 possibilities
A. B. C. D. E. PROPAGATION-MAY GROW DISSOLUTION-THROMBOLYSIS OF RECENTLY FORMED THROMBUS DISSOLUTION WITH t-PA ORGANIZATION-FIBROSIS OF THE THROMBUS DUE TO MACROPHAGES AND FIBROBLASTS RECANILIZATION- THROMBUS BECOMES INCOPORATED INTO WALL WITH BLOOD VESSELS FLOWING THROUGH IT F. MYCOTIC ANEURYSM G. EMBOLIZATION
8. How can one distinguish a thrombus from a postmortem blood clot?
SOMETIMES IT IS DIFFICULT TO DISTINGUISH BETWEEN POSTMORTEM CLOTS AND THROMBI, ESPECIALLY VENOUS THROMBI. SOME OF THE DIFFERENCES ARE AS FOLLOWS: A. THE PM CLOT IS NOT ATTACHED TO THE UNDERLYING WALL B. TWO LAYERS DUE TO THE SETTLIGN OF BLOOD; ONE IS MORE YELLOW, WHILE THE BOTTOM LAYER IS DARKER AND GELATINOUS C. THE THROMBI ARE FIRMER AND EXHIBIT THE LINES OS ZAHN
9. Define embolus and embolism
EMBOLI ARE/REPRESENT (FOR THE MOST PART) REPRESENT DISLODGED THROMBI. EMBOLISM IS THE PROCESS WHERE THE TAIL OF THE THROMBUS IS NOT FIRMLY ATTACHED, THEREFORE DISLODGES AND MAY FLOW TO OTHER SITES IN THE CIRCULATION
10.Define thromboembolus
AN EMBOLUS DERIVED FROM A THROMBUS
11.List six less common forms of emboli
A. B. C. D. E. F. DROPLETS OF FAT BUBBLES OF AIR ATHEROSCELROTIC DEBRIS TUMOR FRAGMENTS FRAGMENTS OF BONE MARROW FOREIGN BODY (I.E. BULLET)
12.Compare and contrast venous and arterial embolism with reference to major (i.e. most frequent) sites of origin and destination of emboli, morphologic features, and clinical significance (i.e. consequences)
A. VENOUS EMBOLISMa. ORIGIN: USUALLY DVT ABOVE THE KNEE b. DESTINATION: DEPOSIT IN THE PULMONAR VASCULATURE c. MORPHOLOGIC FEATURES: WILL OBSTRUCT THE PULMOANRY CIRCULATION d. CLINICAL- LEADS TO PE AND DEATH B. ATERIAL EMBOLISMa. ORIGIN: MAJORITY ARE FROM CARDIAC MURAL THOMBI b. DESTINATION: LEGS, BRAIN, INTESTINES, KIDNEYS, SPLEEN, ARMS TO A LESSER EXTENT c. MORPHOLOGICAL FEATURES-OCCLUSION OF THE VESSEL WALL d. CLINICAL-INFARCTION IN DISTRIBUTION OF BLOCKED VESSEL
13.Define paradoxical embolism
THIS REFERS TO AN EMBOLISM THAT HAS ARISEN IN THE VENOUS CIRCULATION, TRAVELS TO THE RIGHT HEART, BYPASSES THE LUNGS B/C OF DEFECT, AND ENDS UP IN THE SYSTEMIC CIRCULATION.
14.Know the factors that determine the outcome of pulmonary embolism
AS IN ANY OTHER SITE, THE CONSEQUENCES DEPEND ON: A. SIZE OF EMBOLUS B. SIZE OF OCCLUDED VESSEL C. EXENT TO WHICH BLOOD FLOW IS OCCLUDED/OBSTRUCTED D. AVAILABILTY OF ALTERNATIVE BLOOD SOURCE E. OVERALL CVS FUNCTON OF THE PERSON INVOLVED
15.Define infarct and infarction
INFARCT-NECROTIC TISSUE INFARCTION- NECROSIS OF TISSUE DUE TO THE UPSTREAM BLOCKAGE OF ITS ARTERIAL SUPPLY.
16.What are the two most common causes (or mechanisms) of infarction?
THE TWO MOST COMMON CAOUSES ARE THROMBOSIS OR EMBOLISM. MAJOR CAUSE OF DEATH
17.What are the occasional causes (or mechanisms) of infarction? (List at least two)
OTHER CAUSES OF INFARCTION INCLUDE: LOCAL VASOSPASM, COMPRESSION OF BLOOD SUPPLY, TWISTING OF BLOOD SUPPLY, HEMORRHAGE INTO AN ATHEROSCLEROTIC PLAQUE, AND HEMORRHAGE ITSELF.
18.Compare and contrast anemic and hemorrhagic infarcts with reference to gross and microscopic morphologic features, affected organs, etiology and pathogenesis
A) WHITE, ANEMIC INFARCTS- THESE USUALLY OCCUR WITH ARTERIAL OCCLUSIONS. THE ORGANS THAT ARE AFFECTED ARE SOLID (HEART, KIDNEY, SPLEEN) WHICH LIMITS THE AMOUNT OF BLEEDING. ALSO, THE TISSUES DO NOT HAVE A DUAL ARTERIAL BLOOD SUPPLY. GROSSLY, THE WHITE INFARCTS BECOME PROGRESSIVELY MORE SHARPELY DEFINED AND PALER B) RED, HEMORRHAGIC INFARCTS-THESE USUALLY OCCUR WITH VENOUS OCCLUSIONS; TISSUE PREVIOUSLY CONGESTED WITH VENOUS OUTFLOW. TISSUES AFFECTED ARE USUALLY LOOSE TISSUE, I.E. THE LUNG, AND HAVE DUAL CIRCUALTION/SUPPLY. GROSSLY, AS TIME PROGRESSES, THE TISSUE BECOMES FIRMER AND MORE BROWN C) COMPARABLE ASPECTS- BOTH OF THE INFARCTS HAVE HISTOLOGICAL CHANGES THAT LEADS TO ISCHEMIC COAGULATIVE NECROSIS. AT THE EDGES OF THE INFARCTS, HYPERMIA AND INFLAMMATION START. THIS IS FOLLOWED BY GRADUAL DEGRADATION OF THE NECROTIC TISSUE AND PHAGOCYTOSIS OF THE CELLULAR DEBRIS. MOST IS REPLACED BY FIBROUS SCAR
19.What type of ischemic necrosis occurs in an infarct of the brain?
LIQUEFACTIVE NECROSIS
20.What determines whether occlusion of a vessel wall will cause an infarct? Name four determining factors.
MAJOR DETERMINANTS INCLUDE: A) NATURE OF VASCULAR SUPPLY; ARE THERE ALTERNATIVE SOURCES B) RATE OF DEVELOPMENT C) VULNERABILITY OF TISSUE TO HYPOXIA, WHERE NEURONS ARE THE MOST VULNERABLE D) BLOOD OXYGEN CONTENT-IS THE PERSON ANEMIC OR HAVE A REDUCED OXYGEN-CARRYING CAPACITY