Pathology

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HuskerDevil
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87077
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Pathology
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2011-05-21 21:23:17
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DPAP2012 Pathology
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Pathology cards made by previous students
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  1. 8 major pathologic categories/processes into which diseases can be placed
    • Inflammation;
    • Neoplasia;
    • Hemodynamic/vascular;
    • Environmental/nutritional;
    • Genetic/developmental;
    • Endocrine/metabolic;
    • 2 sometimes considered subset of Inflammation: Infectious; Immunologic
  2. 3 main mechanisms of cell injury
    • Deficiency (Lack of necessary substance);
    • Intoxication (Presence of substance that interferes with cell function);
    • Trauma (Loss of structural integrity)
  3. 6 morphologically recognizable ways that cells may respond to non-lethal injury
    • Atrophy;
    • Hypertrophy;
    • Hyperplasia;
    • Metaplasia;
    • Dysplasia;
    • Intracellular Storage
  4. Examples of Deficiency (leading to cell injury)
    Lack of vitamin B12 (in vegans) or Pernicious anemia
  5. Examples of intoxication (leading to cell injury)
    May be Endogenous (Genetic defect or Accumulation of metabolite due to poor circulation) or Exogenous (Infectious agents, Chemicals, or Drugs)
  6. Examples of trauma (leading to cell injury)
    • Hypothermia (causing formation of ice crystals);
    • Hyperthermia (causing denaturation or oxidation of proteins);
    • Mechanical pressure;
    • Infections (causing cell rupture or lysis)
  7. Definition of Atrophy
    Decrease in size, and often function, of cells, generally associated with a decrease in size and/or function of a tissue or organ
  8. Definition of Hypertrophy
    Increase in size of cells, due to an increase in the amount of protein and organelles, which results in an increase in the size of the tissue or organ
  9. Causes of hypertrophy
    • Mechanical stimulus (e.g., cardiac and skeletal muscle hypertrophy);
    • Growth factor stimulation (e.g., endocrine stimulation at puberty, pregnancy);
    • Increased functional demand (e.g., unilateral nephrectomy)
  10. Definition of Hyperplasia
    Increase in the number of cells in an organ or tissue, often resulting in an increase in size of the tissue or organ
  11. Causes of hyperplasia
    • Growth factor stimulation: endocrine or stress-induced;
    • callus formation during bone healing;
    • erythroid hyperplasia under chronic hypoxic conditions
  12. Warts (viral-induced) are an example of which cellular response to injury?
    Hyperplasia
  13. Definition of Metaplasia
    Replacement of one differentiated cell type with another
  14. Main cause of metaplasia
    Irritation
  15. Common sites of metaplasia
    • Respiratory tract of smokers;
    • Cervix of sexually active females;
    • Esophagus in response to gastric acid
  16. Definition of Dysplasia
    • Abnormal or disorderly growth, recognized by a change in size, shape, and/or organization of cells within a tissue;
    • can be a precursor to cancer
  17. Examples of Intracellular Storage
    • Lipid accumulation (fatty change) in hepatocytes;
    • Anthracotic pigment in alveolar macrophages;
    • Lipofuscin
  18. Definition of necrosis
    • A morphologic expression of cell death;
    • progressive disintegration of cellular structure;
    • generally initiated by overwhelming stress;
    • generally elicits acute inflammatory cell response
  19. Definition of apoptosis
    An alternate pathway of cell death, called "programmed cell death" or "physiologic cell death"
  20. Characteristics of apoptosis
    • Controlled by specific genes;
    • Fragmentation of DNA, fragmentation of nucleus;
    • Blebs form and "apoptotic bodies" are released;
    • "Apoptotic bodies" phagocytized, no neutrophils
  21. Consequences of Necrosis
    • Loss of functional tissue;
    • Impaired organ function, transient or permanent
  22. Consequences of Apoptosis
    Removal of damaged or unnecessary cells
  23. PHYSIOLOGIC States Where Apoptosis May Be Important
    • Embryogenesis;
    • development;
    • Withdrawal of trophic hormones, growth factors
  24. Examples of trophic hormone/growth factor withdrawal
    • Prostate glandular epithelium after castration;
    • Regression of lactating breast after weaning;
    • Withdrawal of interleukin-2 results in apoptosis of stimulated T lymphocytes)
  25. Pathologic states where apoptosis may be important
    • Ionizing radiation;
    • Conditions assoc. with free radical generation;
    • MILD thermal injury;
    • Steroids (GCs induce lymphocyte apoptosis);
    • viral infection;
    • cell-mediated immunity;
    • autoimmune diseases;
    • degenerative diseases of the CNS;
    • neoplasia
  26. Viruses that encode proteins that can block apoptosis
    • Adenoviruses;
    • human papilloma virus (HPV)
  27. How is apoptosis important in HIV?
    Loss of CD4+ T lymphocytes may be mediated in part by apoptosis
  28. _______ can kill target cells by inducing apoptosis
    Cytotoxic T lymphocytes
  29. Study of disease, focusing on physiologic, gross, and microscopic morphologic changes in cells reacting to injury
    Pathology
  30. Definition of etiology
    The cause of diseases
  31. Definition of Iatrogenic
    Provider induced
  32. Definition of Idiopathic
    Unknown etiology
  33. Description of the mechanisms by which diseases develop
    Pathogenesis
  34. Objective evidence (a perceptible change) that signals disease
    Sign
  35. A patient’s subjective experience or interpretation of the disease
    Symptom
  36. A patient’s subjective experience or interpretation of the disease
    Syndrome
  37. A sign, symptom or characteristic of a disease that leads to its accurate diagnosis
    Pathognomonic
  38. Reasonable predictions about the course of a disease or process taking into account the natural history, the expected effects of therapy and particular factors specific for the individual case
    Prognosis
  39. The functional elements of an organ, e.g., myocardial cell (myocyte) of the heart; neuron of the brain
    Parenchyma
  40. The framework or support elements of an organ, e.g., the connective tissue (interstitium) of the heart surrounding the myocyte
    Stroma
  41. Any pathological abnormality of tissue structure or function
    Lesion
  42. Necrosis or Apoptosis? Usually affects large areas (contiguous cells)
    Necrosis
  43. Necrosis or Apoptosis? Control of intracellular environment lost early
    Necrosis
  44. Necrosis or Apoptosis? Cells swell and organelles swell
    Necrosis
  45. Necrosis or Apoptosis? Nuclear chromatin marginates early, while injury is still reversible
    Necrosis
  46. Necrosis or Apoptosis? When DNA is cleaved (usually a late event) fragments are random in size
    Necrosis
  47. Necrosis or Apoptosis? Cell membrane ruptures as terminal event and cell contents are released, which are chemotactic
    Necrosis
  48. Necrosis or Apoptosis? Chemotactic factors lead to neutrophil infiltration to degrade dead cells
    Necrosis
  49. A smear pattern is seen in gels in Necrosis or Apoptosis?
    Necrosis
  50. Necrosis or Apoptosis? Usually affects scattered individual cells
    Apoptosis
  51. Necrosis or Apoptosis? Control of intracellular environment maintained in early stages
    Apoptosis
  52. Necrosis or Apoptosis? Cells contract (“implode”)
    Apoptosis
  53. Necrosis or Apoptosis? Nuclear chromatin marginates and chromatin condenses, becoming very compact
    Apoptosis
  54. Necrosis or Apoptosis? Chromatin condensation and DNA fragmentation occur together; DNA cleaved into multiples of 200 base pair units
    Apoptosis
  55. Necrosis or Apoptosis? Blebs form and apoptotic bodies containing nuclear fragments are shed
    Apoptosis
  56. Necrosis or Apoptosis? Phagocytosis of intact apoptotic bodies, no chemotactic factors are generated
    Apoptosis
  57. A ladder pattern is seen in gels in Necrosis or Apoptosis?
    Apoptosis
  58. Morphologic Patterns of Lethal Cell Injury (5 types of necrosis)
    Coagulative Necrosis; Liquefactive Necrosis; Fat Necrosis; Caseous Necrosis; Fibrinoid Necrosis
  59. Similar to autolysis
    Coagulative Necrosis
  60. Pattern of cell death characterized by progressive loss of cell structure
    Coagulative necrosis
  61. In ______ necrosis, cytoplasm becomes more eosinophilic
    Coagulative necrosis
  62. Nucleus shrinks and chromatin condenses; nucleus becomes deeply basophilic (very dark blue with H&E stain)
    Pyknosis
  63. Nucleus breaks up into small pieces
    Karyorrhexis
  64. Nucleus becomes progressively paler staining and eventually disappears
    Karyolysis
  65. Pattern of cell death characterized by dissolution of necrotic cells
    Liquefactive Necrosis
  66. Pattern of cell death typically seen in an abscess, with pus formation
    Liquefactive Necrosis
  67. Pattern of cell death that results from release of lipases into adipose tissue
    Fat Necrosis
  68. Pattern of cell death in which fatty acids binds and precipitate calcium ions, forming insoluble salts; chalky white on gross examination
    Fat Necrosis
  69. Pattern of cell injury that occurs with granulomatous inflammation in response to certain microorganisms (e.g. tuberculosis)
    Caseous necrosis
  70. Pattern of cell injury that evokes a chronic inflammatory response
    Caseous necrosis
  71. Forms with a center of cellular debris that grossly has the appearance and consistency of cottage cheese
    Caseating granuloma
  72. Pattern of cell injury occurs in the wall of arteries in cases of vasculitis
    Fibrinoid Necrosis
  73. Pattern of cell injury in which plasma proteins, primarily fibrin, are deposited in the area of medial necrosis
    Fibrinoid Necrosis
  74. Definition of Infarction
    Cell death and coagulative necrosis due to prolonged ischemia
  75. These infarcts are typically wedge-shaped
    Renal and splenic
  76. Histologic Changes in Infarcts
    Cytoplasmic hyper-eosinophilia; Karyolysis is complete at 2 days; Acute inflammatory cell infiltration begins at 12 hours after coronary occlusion and peaks at 2-3 days
  77. Late Histologic Changes in Infarcts (Permanent Occlusion)
    • Karyorrhectic debris from neutrophils becomes prominent at 3-4 days;
    • neutrophil infiltrate abates by day 5;
    • around day 5, sprouting of new capillaries and phagocytosis of dead myocytes begin at periphery of infarct
  78. Healing Phase of Infarction
    • Sprouting of new capillaries;
    • Fibroblast proliferation;
    • Collagen synthesis;
    • Highly vascularized cellular connective tissue termed “granulation tissue”;
    • Replacement of dead myocytes by mature scar tissue
  79. Other Manifestations of Ischemic Injury
    • Enzyme release;
    • Cardiac specific protein release;
    • Arrhythmias;
    • Permanent ECG changes;
    • Heart failure;
    • Tissue rupture, aneurysm, mural thrombi
  80. Indicators of functional loss in cell injury
    Decreased oxygenation, decreased mobility, increased bilirubin
  81. Cell constitutents released in cell injury
    K+ from RBC, troponin or CPK from heart
  82. Change in electrical activity in cell injury
    EKG, EEG, EMG
  83. Define inflammation
    Response to injury (including infection)
  84. Inflammatory reaction of blood vessels leads to:
    Accumulation of fluid and leukocytes in extravascular tissues
  85. 5 cardinal signs of inflammation
    Rubor (erythema [redness]); Tumor (swelling); Calor (heat); Dolor (pain); functio laesa (loss of function)
  86. 2 signs of inflammation characterized by vasodilatation & increased blood flow
    Rubor (erythema [redness]); Calor (heat)
  87. Under what circumstances is inflammation potentially harmful?
    • Hypersensitivity reactions to insect bites, drugs, contrast media in radiology;
    • chronic diseases (arthritis, atherosclerosis);
    • disfiguring scars,
    • visceral adhesions
  88. Components of inflammatory response
    • Vascular reaction;
    • Cellular (exudative) reaction
  89. Types of Inflammation
    • Acute inflammation;
    • Chronic inflammation;
    • Granulomatous inflammation
  90. Characteristics of acute inflammation
    Short duration, edema, and mainly neutrophils
  91. Characteristics of chronic inflammation
    • Longer duration,
    • lymphocytes & macrophages predominate,
    • fibrosis,
    • new blood vessels (angiogenesis)
  92. Characteristics of granulomatous inflammation
    Distinctive pattern of chronic inflammation; activated macrophages (epithelioid cells) predominate
  93. Three major components of acute inflammation
    • Increase in blood flow (redness & warmth);
    • Edema results from increased hydrostatic pressure (vasodilation) and lowered intravascular osmotic pressure (protein leakage);
    • Leukocytes emigrate from microcirculation and accumulate in the focus of injury
  94. Transudate vs. exudate
    • Transudate, SpGr <1.012;
    • Exudate (cell- and protein-rich), SpGr >1.020
  95. Benefits of Fluid Accumulation at Injury Site
    • Dilution of toxins;
    • Pains decreases use and prevents additional injury;
    • Antibodies in blood can kill microbes;
    • Blood plasma proteins can amplify responses against the injurious agent
  96. Definition of Extravasation
    Delivery of leukocytes from the vessel lumen to the interstitium
  97. Types/Examples of Extravasation
    • In the lumen: margination, rolling, and adhesion;
    • Migration across the endothelium (diapedesis);
    • Migration in the interstitial tissue (chemotaxis)
  98. Diapedesis
    Migration across the endothelium
  99. Chemotaxis
    Migration in the interstitial tissue
  100. Role of Leukocytes
    • Ingest offending agents (phagocytosis);
    • kill microbes;
    • degrade necrotic tissue and foreign antigens
  101. Leukocyte adhesion and migration across vessel wall are determined largely by ______
    Binding of complementary adhesion molecules on the leukocyte and endothelial surfaces
  102. Morphologic Patterns of Acute Inflammation
    • Serous inflammation;
    • Fibrinous inflammation;
    • Suppurative (purulent) inflammation;
    • Ulcers
  103. Serous inflammation
    Outpouring of thin fluid (serous effusion, blisters)
  104. Fibrinous inflammation
    • In body cavities;
    • leakage of fibrin;
    • may lead to scar tissue (adhesions)
  105. Suppurative (purulent) inflammation
    • Pus or purulent exudate (neutrophils, debris, edema fluid);
    • abscess: localized collections of pus
  106. Ulcers
    Local defect of the surface of an organ or tissue produced by the sloughing (shedding) of inflammatory necrotic tissue
  107. Chronic Inflammation
    Inflammation of prolonged duration (weeks or months)
  108. What is occurring during chronic inflammation?
    Active inflammation, tissue destruction, and attempts at repair are proceeding simultaneously
  109. Examples of chronic inflammation
    • Persistent infections (Treponema pallidum [syphilis], viruses, fungi, parasites);
    • Exposure to toxic agents;
    • Autoimmunity (Rheumatoid arthritis, systemic lupus erythematosus)
  110. Exposure to toxic agents (leading to chronic inflammation)
    • Exogenous: silica (silicosis);
    • Endogenous: toxic plasma lipid components (atherosclerosis)
  111. Histological features of chronic inflammation
    • Infiltration with mononuclear cells (macrophages, lymphocytes, and plasma cells);
    • Tissue destruction (induced by the inflammatory cells);
    • Healing by replacement of damaged tissue by connective tissue (fibrosis) and new blood vessels (angiogenesis)
  112. Macrophages predominate by _____ hours
    48 hours
  113. Role of Lymphocytes in Chronic Inflammation
    • Produce inflammatory mediators;
    • Participate in cell-mediated immune reactions;
    • Plasma cells produce antibody;
    • Lymphocytes and macrophages interact in a bi-directional fashion
  114. Eosinophils in Chronic Inflammation
    • Immune reactions mediated by IgE;
    • Parasitic infections (Eosinophil granules contain a protein that is toxic to parasites)
  115. Mast cells in Chronic Inflammation
    Release mediators (histamine) and cytokines
  116. What characterizes Granulomatous Inflammation?
    • Predominant cell type is an activated macrophage with a modified epithelial-like (epithelioid) appearance;
    • Giant cells may or may not be present
  117. Foreign body granulomas form when ______
    Foreign material is too large to be engulfed by a single macrophage
  118. Immune granulomas
    Insoluble or poorly soluble particles elicit a cell-mediated immune response
  119. Endocrine and Metabolic Manifestations of Inflammation
    • Secretion of acute phase proteins by the liver;
    • Increased production of GCs (stress response);
    • Decreased secretion of vasopressin leads to reduced volume of body fluid to be warmed
  120. Role of Fever in Inflammation
    • Improves efficiency of leukocyte killing;
    • Impairs replication of many offending organisms
  121. Autonomic Nervous System Manifestations of Inflammation
    • Redirection of blood flow from skin to deep vascular beds minimizes heat loss;
    • Increased pulse and blood pressure;
    • Decreased sweating
  122. Behavioral Manifestations of Inflammation
    • Shivering (rigors),
    • chills (search for warmth),
    • anorexia (loss of appetite),
    • somnolence,
    • malaise
  123. Leukocytosis
    Increased leukocyte count in the blood
  124. Neutrophilia seen in inflammatory response to ______
    Bacterial infections
  125. Lymphocytosis seen in inflammatory response to ______
    Infectious mononucleosis, mumps, measles
  126. Eosinophilia seen in inflammatory response to ______
    Parasites, asthma, hay fever
  127. Leukopenia seen in inflammatory response to ______
    Typhoid fever, some viruses, rickettsiae, protozoa
  128. Predisposing factors to orbital mucormycosis
    Diabetic ketoacidosis; Leukemia
  129. Vasoactive mediators
    • Histamine;
    • Bradykinin;
    • Complement (C3a, C5a);
    • Prostaglandins/leukotrienes;
    • Platelet activating factor;
    • Nitric oxide;
    • Neuropeptides
  130. Chemotactic factors
    • Complement (C5a);
    • Leukotriene (B4);
    • Platelet activating factor;
    • Cytokines (IL-1, TNF);
    • Chemokines;
    • Nitric oxide
  131. Action of histamine
    Dilates arterioles and increases permeability of venules (wheal and flare reaction)
  132. Release mechanisms of histamine
    • Binding of antigen (allergen) to IgE on mast cells releases histamine containing granules;
    • Release by nonimmune mechanisms such as cold, trauma, or other chemical mediators;
    • Release by other mediators
  133. Bradykinin
    • Small peptide released from plasma precursors;
    • Increases vascular permeability;
    • Dilates blood vessels;
    • Causes pain;
    • Rapid inactivation
  134. Arachidonic Acid Metabolites
    • Prostaglandins;
    • Leukotrienes
  135. Actions of Prostaglandins
    • Vasodilatators (prostacyclin);
    • Vasoconstrictors (thromboxane A2);
    • produce pain (PGE2 makes tissue hypersensitive to bradykinin) and fever
  136. Actions of Leukotrienes
    • Increase vascular permeability;
    • Vasoconstriction;
    • Leukocyte adhesion & chemotaxis
  137. Platelet Activating Factor is synthesized by ______
    Stimulated platelets, leukocytes, endothelium
  138. Cytokines
    • Proteins produced by many cell types (principally by activated lymphocytes and macrophages);
    • Modulate the function of other cell types
  139. _____ and ______ are the major cytokines that mediate inflammation
    Interleukin-1 (IL-1) and tumor necrosis factor (TNF)
  140. Inflammatory effects of Platelet Activating Factor
    • Stim plt aggregatn;
    • Vasoconstrictn & bronchoconstrictn;
    • Vasodilatn & inc’d ven. permeability;
    • Inc’d leukocyte adhesion to endothel., chemotaxis, degranulatn, & oxidative burst;
    • Inc. synthesis of arachid. acid metabolites by leukocytes etc
  141. Chemokines
    Small proteins that act primarily as chemoattractants for specific types of leukocytes
  142. Actions of Chemokines
    Stimulate leukocyte recruitment in inflammation; Control the normal migration of cells through tissues (organogenesis and maintenance of tissue organization)
  143. Substance P and neurokinin A are _______
    Neuropeptides
  144. Substance P nerve fibers are prominent in the _______
    Lung and gastrointestinal tract
  145. Neuropeptides are produced in the __________ nervous system
    Central and peripheral nervous systems
  146. Effects of neuropeptides
    • Vasodilation (direct and through mast cell degranulation);
    • Increased vascular permeability
  147. Other chemical mediators of inflammation
    Neutrophil granules; Oxygen-Derived Free Radicals
  148. Steps in Wound Healing
    • Injury induces acute inflamn;
    • Parenchymal cells regenerate;
    • parenchymal & conn. tissue cells migrate and proliferate;
    • Extracellular matrix produced;
    • parenchymal & conn. tissue matrix remodel;
    • Increase in wound strength due to collagen deposition
  149. The hallmark of healing is ______
    Granulation tissue
  150. Histology of granulation tissue
    • Proliferation of small blood vessels and fibroblasts;
    • tissue often edematous
  151. Neutrophils are pathognomonic for _______
    Acute Inflammation
  152. Plasma cells are pathognomonic for ________
    Chronic inflammation
  153. Granulomatous inflammation for _______
    Epithelioid macrophages are pathognomonic
  154. Pathology
    Study of disease, focusing on physiologic, gross and microscopic morpholic changes in cells reacting to injury
  155. Disease
    "an impairment of the normal state of the living animal or plant body that affects the performance of the vital functions"
  156. Etiology
    cause of diseases
  157. Idiopathic
    unknown etiology
  158. iatrogenic
    "provider induced"
  159. pathogenesis
    is a description of the mechanisms by which disease develop
  160. sign
    objective evidence (a perceptible change) that signals disease
  161. symptom
    a patient's subjective experience or interpretation of the disease
  162. syndrome
    a group of signs and or symptoms that characteristically occur together as a part of a single disease process
  163. pathognomonic
    a sign, symptom of characteristic of a disease that leads to its accurate diagnosis
  164. prognosis
    reasonable predictions about the course of a disease or process taking into account the natural history, the expected effects of therapy and particular factors specific for the individual case
  165. parenchyma
    functional elements of an organ e.g., myocardial cell of the heart, neuron of the brain
  166. stroma
    framework or support elements of an organ e.g., connective tissue
  167. lesion
    any pathological abnormality of tissue structure or function
  168. What does disease result from?
    cumulative effects of injury to individual cells
  169. How do different cell types respond to stress?
    differently
  170. How do consequences of cell injury differ?
    depends on cell type
  171. How do cells interact with their environment?
    they are not static, must be able to adapt
  172. What do cells need to perform functions and maintain viability?
    energy
  173. Deficiency
    lack of necessary substance
  174. Types of deficiency
    nutritional deficiency, inability to absorb or utilize nutrients, genetic defect leading to inadequate production or regulation
  175. Intoxication
    presence of a substance that interferes with cell function
  176. Examples of endogenous intoxication
    genetic defect, accumulation of metabolite
  177. Examples of exogenous intoxication
    infectious agents, chemicals, drugs (illegal and prescription)
  178. Trauma
    loss of structural integrity
  179. Examples of trauma
    hypothermia, hyperthermia, mechanical pressure, infections
  180. Hypothermia
    formation of ice crystals
  181. hyperthermia
    denaturation or oxidation of proteins
  182. infections in trauma
    cell rupture or lysis
  183. hypoxia
    state of tissue or cell oxygen deficiency
  184. ischemia
    oxygen deprivation due to lack of blood flow
  185. What do cells need oxygen?
    anaerobic glycolysis = 2 ATP vs. oxidative phosphorylation = 36 ATP
  186. What happens to cellular metabolism in state of hypoxia?
    switches to anaerobic glycolysis as the primary source of energy
  187. What happens if O2 is lacking because of ischemia?
    inflow of substrate decreases and efflux of metabolic end-products slows - no incoming glucose, no taking out of waste products - toxic to cell
  188. What do hypoxic cells consume first?
    energy reserves
  189. Energy reservers
    creatine phosphates in muscle, adenine nucleotides break down
  190. What happens to anaerobic glycolysis in state of hypoxia?
    increase, with accumulation of lactic acid and inorganic phosphate
  191. What cellular processes are impacted first during hypoxia?
    ion transport
  192. What happens when there is not enough energy to man ion pumps?
    concentration gradient takes over
  193. What is Na+/K+ ATPase needed for?
    keep intracellular Na+ from rising
  194. What happens when ion pump is off?
    Na+ comes in and water follows
  195. What happens to tissue osmolality when there is not enough energy for ion pumps to function?
    increases due to catabolism within ischemic cells, water flows in passively
  196. What is one of the first signs of ischemia?
    swelling of the cell
  197. Where does lipid accumulation occur the most?
    liver
  198. How does lipid accumulation affect lipoprotein synthesis?
    impaired lipoprotein synthesis (ethanol, protein malnutrition)
  199. How does lipid accumulation affect fatty acid oxidation?
    decreased fatty acid oxidation (hypoxia)
  200. How does lipid accumulation affect liberation of fat?
    increased liberation of fat from peripheral stores (starvation)
  201. How does starvation accumulate fat in liver?
    fat stores in body are liberated and liver picks them up
  202. What are the manifestations of cell injury?
    acute cessation of specialized functions, persistent impairment of function after cessation of noxious stimulus, loss of ability to replicate
  203. What are the three main mechanisms of cell injury?
    deficiency, intoxication, trauma
  204. How can radiation affect cells?
    damage cell membranes and DNA
  205. What are the six morphologic responses to non-lethal injury?
    atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia, intracellular storage
  206. Morphology
    study of shape
  207. Atrophy
    decrease in size, and often function, of cells, generally associated with a decrease in size and/or function of a tissue or organ
  208. What are some causes of atrophy?
    disuse of muscle, decreased blood supply, inadequate nutrition, loss of endocrine stimulation, loss of growth factors
  209. What are the two types of disuse atrophy of muscle?
    voluntary or denervation-induced
  210. Hypertrophy
    increase in size of cells, due to an increase in the amount of protein and organelles, which results in an increase in the size of the tissue or organ
  211. Examples of mechanical stimulus in hypertrophy
    cardiac and skeletal muscle hypertrophy
  212. example of growth factor stimulation in hypertrophy
    endocrine stimulation at puberty, pregnancy
  213. Example of increase functional demand in hypertrophy
    unilateral nephrectomy
  214. What are the three causes of hypertrophy?
    mechanical stimulus, growth factor stimulation, increased functional demand
  215. hyperplasia
    increase in number of cells in organ or tissue
  216. Causes of hyperplasia
    growth factor stimulation: endocrine or stress-induced, viral-induced
  217. Example of growth factor stimulation in hyperplasia
    endometrial proliferation w/ menstrual cycle, callus formation during bone healing, erythroid hyperplasia under chronic hypoxic conditions
  218. Example of viral-induced hyperplasia
    warts
  219. Metaplasia
    replacement of one differentiated cell type with another
  220. What is the main cause of metaplasia?
    chronic irritation
  221. What are examples of chronic irritation in metaplasia?
    respiratory tract of smokers, cervix of sexually active females, esophagus in response to gastric acid
  222. Dysplasia
    abnormal or disorderly growth, recognized by a change in size, shape, and/or organization of cells within a tissue
  223. What can dysplasia be a precursor to?
    cancer
  224. What are examples of intracellular storage?
    lipid accumulation in hepatocytes, anthracotic pigment in alveolar macrophages, lipofuscin
  225. Lipofuscin
    aging related pigment, "stuff in the cytoplasm that can't get broken down"
  226. Anthracotic
    black particles, from smoke and other things
  227. What is the most common genetic disease in the US?
    hemochromatosis
  228. What does hemochromatosis cause?
    systemic overload of iron
  229. How do organ or tissue dysfunction occur?
    as the result of the cumulative impact of injury to individual cells
  230. What is a good way to understand disease processes?
    focus on individual cells and their response to noxious stimuli
  231. How can acute cell injury manifest itself?
    in many different ways, some of which are fully reversible and some of which are not
  232. Can cells exhibit persistent dysfunction after noxious stimulus is over and still fully recover over time?
    yes
  233. What is an example of cells being permanently injured without affecting their viability directly?
    radiation - prevent cells from dividing without killing them
  234. What does cell injury but intact viability result in?
    lag between cell injury and organ dysfunction
  235. Necrosis
    a morphologic expression of cell death
  236. What happens to the cellular structure in necrosis?
    progressive disintegration
  237. What is necrosis generally initiated by?
    overwhelming stress
  238. What does necrosis generally elicit?
    acute inflammatory cell response
  239. Apoptosis
    an alternate pathway of cell death, called "programmed cell death" or "physiologic cell death"
  240. What is apoptosis controlled by?
    specific genes
  241. What happens to DNA and nucleus in apoptosis?
    fragmentation of DNA and nucleus
  242. What is the process of apoptosis?
    • blebs form and "apoptotic bodies" are released,
    • "apoptotic bodies" phagocytized,
    • no neutrophils
  243. What are the pathologic states where apoptosis may be important?
    • embryogenesis,
    • withdrawal of trophic hormones,
    • growth factors,
    • ionizing radiation,
    • free radical generation,
    • mild thermal injury,
    • steroids
  244. How can apoptosis be important in viral infection?
    potent defense mechanism against virus - some viruses encode proteins to block apoptosis
  245. In AIDS, what may be mediating loss of CD4+ T lymphocytes?
    apoptosis
  246. How is apoptosis involved in cell-mediated immunity?
    cytotoxic T lymphocytes can kill target cells by inducing apoptosis
  247. How is apoptosis important in autoimmune disease?
    removal of autoreactive immature lymphocytes is by apoptosis
  248. What types of cell death may be involved in degenerative diseases of the central nervous system?
    apoptosis
  249. How may apoptosis be important in neoplasia?
    eliminating cells with genetic defects + inhibition of apoptosis may contribute to prolonged life span of malignant cells
  250. What size of areas does necrosis usually affect?
    large areas - contiguous cells
  251. What size of areas does apoptosis usually affect?
    scattered individual cells
  252. When is control of intracellular environment lost in necrosis?
    early
  253. When is control of intracellular environment lost in apoptosis?
    maintained in early stages
  254. What happens to cell shape in necrosis?
    cells swell and organelles swell
  255. What happens to cell shape in apoptosis?
    cells contract
  256. How can you tell when a cell is in early apoptosis?
    chromatin margination and condensation
  257. How can you tell when a cell is later in apoptosis?
    nucleus is fragmented
  258. What happens to a cell after apoptosis?
    phagocytosis of apoptotic cellular remnants by adjacent cell
  259. When does apoptosis happen in the thymus?
    stress - body releases corticosteroids causing apoptosis of t-cells
  260. How is apoptosis regulated?
    the balance between factors that stimulate apoptosis and factors that inhibit apoptosis
  261. What role does bcl-2 have in apoptosis?
    pro-survival
  262. What role does bax have in apoptosis?
    pro-apoptosis
  263. What does p53 do?
    helps cells respond to injury, if cells have too much damage, p53 up-regulates bax, tipping the scale to apoptosis
  264. What are various ways cells can be signaled to undergo apoptosis?
    injury, withdrawal of growth factors, hormones, cytotoxic T lymphocytes, receptor-ligand interactions
  265. What role do caspases play in apoptosis?
    initiator caspases signal executioner caspases which cause breakdown of cytoskeleten, forming the bleb
  266. What two things can happen when a cell is exposed to a noxious agent in necrosis?
    excess of normal cell constituents or edema
  267. At what point does a cell considered to have irreversible injury?
    when the cell becomes necrotic
  268. What happens to a necrotic cell?
    autolysis, replacement, then regeneration or fibrosis….OR calcification
  269. What are the types of necrosis?
    coagulative, liquefactive, fat, caseous, fibrinoid
  270. What changes characterize necrosis?
    changes in cytoplasmic staining, in nuclear morphology and/or staining characteristics
  271. In necrosis how does cytoplasm look?
    more eosinophilic
  272. pyknosis
    nucleus shrinks and chromatin condenses; nucleus becomes more deeply basophilic (very dark blue with H&E stain)
  273. Karyorrhexis
    nucleus breaks up into small pieces
  274. Karyolysis
    nucleus becomes progressively paler staining and eventually disappears
  275. Liquefactive necrosis
    pattern of cell death characterized by dissolution of necrotic cells
  276. Where is liquefactive necrosis typically seen?
    in an abscess - large numbers of neutrophils release hydrolytic enzymes, break down dead cells
  277. Pus
    liquified remnants of dead cells, including neutrophils
  278. fat necrosis
    result of release of lipases into adipose tissue
  279. In fat necrosis, what are triglycerides cleaved into?
    fatty acids
  280. What do fatty acids bind to?
    bind to and precipitate calcium ions, forming insoluble salts
  281. caseous necrosis
    occurs with granulomatous inflammation in response to certain microorganisms
  282. Where is fat necrosis most commonly found?
    in pancreas injury
  283. What is the most common microorganism that causes caseous necrosis?
    tuberculosis
  284. What is the host response to microorganisms that cause caseous necrosis?
    chronic inflammatory response
  285. Fibrinoid necrosis
    occurs in the wall of arteries in cases of vasculitis
  286. What does fibroid necrosis cause?
    endothelial damage and necrosis of smooth muscle cells of the media
  287. What does necrosis of smooth muscle cells and endothelial damage cause in fibrinoid necrosis?
    allows plasma proteins, primarily fibrin, to be deposited in the area of medial necrosis
  288. Infarction
    cell death and coagulative necrosis due to prolonged ischemia
  289. What do renal and splenic infarcts typically look like?
    wedge-shaped
  290. What do liver infarcts look like?
    central lobular necrosis - area around central vein undergoes necrosis
  291. What histologic changes occur in infarcts?
    • cytoplasmic hyper-eosinophilia,
    • karyolysis (complete at 2 days),
    • acute inflammatory cell infiltration begins at 12 hours after coronary occlusion and peaks at 2-3 days
  292. Inflammation
    response to injury
  293. Reaction of blood vessels leads to
    accumulation of fluid and leukocytes in extravascular tissues
  294. What does inflammation do to the injurious agent?
    destroys, dilutes, or walls off the injurious agent
  295. What does inflammation do in the repair process?
    initiates it
  296. Is inflammation protective or harmful?
    fundamentally protective, may be harmful
  297. Examples of harmful inflammation
    arthritis, atherosclerosis, scars, insect bites
  298. What are the components of inflammatory response?
    vascular reaction, cellular (exudative) reaction
  299. How is inflammation mediated?
    chemical mediators - derived from plasma proteins and from cells inside and outside of blood vessels
  300. acute inflammation
    short duration, edema, and mainly neutrophils
  301. chronic inflammation
    longer duration, lymphocytes & macrophage predominate fibrosis, new blood vessels (angiogenesis)
  302. granulomatous inflammation
    • distinctive pattern of chronic inflammation;
    • activated macrophages (epithelioid cells) predominate
  303. cellulitis
    inflammation of soft tissue - mononuclear cells predominate
  304. rubor
    erythema (redness) - vasodilation, increased blood flow
  305. tumor
    swelling - extravascular accumulation of fluid
  306. calor
    heat - vasodilatation, increased blood flow
  307. dolor
    pain
  308. 5th sign (Virchow)
    functio laesa - loss of function
  309. What are the three major components of acute inflammation?
    increased blood flow, edema, leukocytes
  310. What visible signs does increased blood flow cause?
    redness and warmth
  311. In acute inflammation, what does edema result from?
    increased hydrostatic pressure (vasodilation) and lowered intravascular osmotic pressure (protein leakage)
  312. What do leukocytes do in acute inflammation?
    emigrate from microcirculation and accumulate in the focus of injury
  313. acute inflammation stimuli
    infections, trauma, physical or chemical agents, foreign bodies, immune reactions
  314. During acute inflammation, increased hydrostatic pressure increases flow through lymphatics, causing what?
    increases antigen presentation and immune responses - lymph fluid enters back at thoracic duct
  315. What effect does fluid accumulation have on toxins?
    dilutes toxins
  316. How does fluid accumulation causing pain benefit the injury site?
    decrease use and prevent additional injury
  317. Fluid accumulation cause rise in antibodies in blood which provide what benefit?
    can kill microbes
  318. What can blood plasma proteins do to help in injury?
    amplify responses against the injurious agent
  319. What is the first mechanism of increased vascular permeability?
    gaps due to endothelial contraction - fast and short lived (minutes, most common, venules
  320. What is the second mechanism of increased vascular permeability?
    direct injury - toxins, burns, chemicals, fast and may be long lived - arterioles, capillaries, venules
  321. What is the third mechanisms of increased vascular permeability?
    leukocyte-dependent injury - mostly venules, pulmonary capillaries, late response, long lived
  322. What is the fourth mechanism of increased vascular permeability?
    increased transcytosis - venules, vascular endothelium-derived growth factor
  323. What is the fifth mechanism of increased vascular permability?
    new blood vessel formation - angiogenesis - persists until intercellular junctions form
  324. Extravasation
    delivery of leukocytes from the vessel lumen to the interstitium
  325. What happens in the lumen in extravasation?
    margination, rolling and adhesion
  326. diapedesis
    migration across the endothelium
  327. chemotaxis
    migration in the interstitial tissue
  328. What do leukocytes do in extravasation?
    phagocytize, kills microbes, degrade necrotic tissue and foreign antigens
  329. What determines leukocyte adhesion and migration across vessel wall?
    binding of complementary adhesion molecules on the leukocyte and endothelial surfaces
  330. What is the sequence of leukocyte emigration?
    • neutrophils (6-24 hrs),
    • monocytes in 24-48 hrs
  331. What happens after neutrophils and monocytes show up in leukocyte emigration?
    induction/activation of different adhesion molecule pairs and specific chemotactic factors in different phases of inflammation
  332. What do chemical mediators do in leukocyte adhesion?
    affect these processes by modulating the expression or avidity of the adhesion molecule
  333. serous inflammation
    outpouring of thin fluid (serous effusion, blisters)
  334. Fibrinous inflammation
    body cavities; leakage of fibrin; may lead to scar tissues
  335. suppurative (purulent) inflammation
    pus or purulent exudate (neutrophils, debris, edema fluid) abscess: localized collections of pus
  336. ulcers
    local defect of the surface of an organ or tissue produced by the sloughing of inflammatory necrotic tissue
  337. chronic inflammation
    inflammation of prolonged duration (weeks or months)
  338. What proceed simultaneously in chronic inflammation?
    active inflammation, tissue destruction, and attempts at repair
  339. How does the timing of chronic inflammation intersect with that of acute inflammation?
    may follow acute inflammation or being insidiously and often asymptomatically
  340. persistent infections
    Treponema pallidum (syphilis), viruses, fungi, parasites
  341. exposure to toxic agents - exogenous
    silica (silicosis)
  342. exposure to toxic agents - endogenous
    toxic plasma lipid components (atherosclerosis)
  343. autoimmunity
    rheumatoid arthritis, systemic lupus, erythematosus
  344. histological features of chronic inflammation
    infiltration, tissue destruction, healing
  345. infiltration with mononuclear cells in chronic inflammation
    macrophages, lymphocytes, and plasma cells
  346. tissue destruction in chronic inflammation
    induced by the inflammatory cells
  347. How does healing occur in chronic inflammation?
    fibrosis and angiogenesis
  348. Fibrosis
    replacement of damaged tissue by connective tissue
  349. Angiogenesis
    new blood vessel formation
  350. Monocytes emigrate into tissue early in inflammation and transofrm into what cell?
    macrophage - a larger phagocytic cell
  351. When do macrophages predominate in chronic inflammation?
    48 hours - recruitment, division, immobilization
  352. What does the activation of macrophages result in?
    secretion of biologically active products
  353. When do monocytes begin to emigrate into tissues?
    early in inflammation where they transform into the larger phagocytic cell known as the macrophage
  354. What do lymphocytes produce in chronic inflammation?
    inflammatory mediators
  355. What do lymphocytes participate in in chronic inflammation?
    cell-mediated immune reactions
  356. What do lymphocyte plasma cells produce in chronic inflammation?
    antibody
  357. How do lymphocytes and macrophages interact in chronic inflammation?
    a bi-directional fashion
  358. What are eosinophils involved in?
    immune reactions mediated by IgE, parasitic infections (contain protein toxic to parasites)
  359. How do eosinophils fight against parasitic infections?
    eosinophil granules contain a protein that is toxic to parasites
  360. Mast Cells
    release mediators (histamine) and cytokines
  361. granulomatous inflammation pattern of inflammation
    predominant cell type is an activated macrophage with a modified epithelial-like appearance. Giant cells may or may not be present
  362. granuloma
    focal area of granulomatous inflammation
  363. foreign body granulomas
    form when foreign material is too large to be engulfed by a single macrophage
  364. immune granulomas
    insoluble or poorly soluble particles elicit a cell-mediated immune response
  365. sarcoidosis
    poorly soluble antigen-antibody complexes
  366. How is liver involved in inflammation?
    secretion of acute phase proteins
  367. What glucocorticoid response occurs in inflammation?
    increased production (stress response)
  368. What happens to vasopressin in inflammation?
    decreased secretion leading to reduced volume of body fluid to be warmed
  369. What does fever do in inflammation?
    improves efficiency of leukocyte killing, impairs replication of many offending organisms
  370. What autonomic responses occur in inflammation?
    redirection of blood flow to minimize heat loss, increase pulse, bp, decreased sweating
  371. What behavioral responses occur in inflammation?
    shivering, chills, anorexia, somnolence, malaise
  372. leukocytosis
    increased leukocyte count in the blood
  373. neutrophilia occurs in what cases?
    bacterial infections
  374. lymphocytosis occurs in what cases?
    infections mono, mumps, measles
  375. eosinophilia occurs in what cases?
    parasites, asthma, hay fever
  376. leukopenia
    reduced leukocyte count, in typhoid fever, some viruses, rickettsiae, protozoa
  377. What are predisposing factors for orbital mucormycosis?
    diabetic ketoacidosis, leukemia
  378. Where may chemical mediators of inflammation be derived from?
    plasma or cells
  379. Where do chemical mediators of inflammation bind?
    to specific receptors on target cells
  380. What do chemical mediators of inflammation cause in target cells?
    release of mediators, which may amplify or ameliorate inflam. Response
  381. How many cells do chemical mediators of inflammation work on?
    one or a few, have widespread targets and may have differing effects depending on cell and tissue types
  382. How long is the response of chemical mediators of inflammation?
    usually short lived
  383. What do chemical mediators of inflammation have the potential to cause?
    harmful effects
  384. Review vasoactive vs. chemotactic mediators
    slide #62
  385. Histamine
    released from mast cells (also basophils and platelets)
  386. What does binding of antigen (allergen) to IgE on mast cells cause?
    release of histamine contained granules
  387. What other mechanisms cause release of histamine?
    nonimmune mechanisms (cold, trauma), release by other mediators
  388. What does histamine do?
    dilates arterioles and increases permeability of venules (wheal and flare reaction)
  389. Bradykinin
    small peptide release from plasma precursors
  390. What does bradykinin do?
    increases vascular permeability, dilates blood vessels, causes pain, rapid activation
  391. What are some arachidonic acid metabolites?
    prostaglandins & leukotrienes
  392. What do prostaglandins do?
    vasoconstrict or vasodilate, involved in pain and fever
  393. What do leukotrienes do?
    increase vascular permeability, vasoconstrict, leukocyte adhesion & chemotaxis
  394. What is platelet activating factor synthesized by?
    platelets, leukocytes, endothelium
  395. What are some inflammatory effects of platelet activating factor?
    stimulates platelet aggregation, vasoconstriction & bronchoconstriction, vasodilation and increased venular permeability
  396. What are some more inflammatory effects of platelet activating factor?
    increased leukocyte adhesion, chemotaxis, degranulation, and oxidative burst, increases synthesis of arachidonic acid metabolites
  397. Cytokines
    proteins produced by many cell types (principally by activated lymphocytes and macrophages)
  398. What do cytokines do?
    modulate the function of other cell types?
  399. What are the major cytokines that mediate inflammation?
    Interleukin-1 (IL-1) and tumor necrosis factor (TNF)
  400. Chemokines
    small proteins that act as chemoattractants for specific types of leukocytes (~40)
  401. What do chemokines do?
    stimulate leukocyte recruitment in inflammation
  402. What else do chemokines do?
    control normal migration of cells through tissues
  403. What are examples of chemokines?
    IL-8, eotaxin, lymphotactin
  404. Neuropeptides
    Substance P and neurokinin A
  405. Where are neuropeptides produced?
    central and peripheral nervous systems
  406. Where are substance P nerve fibers prominent?
    in lung and GI tract
  407. What are neuropeptides mechanisms of action?
    vasodilation and increased vascular permeability
  408. Neutrophil granules
    Cationic proteins increase vascular permeability, immobilze neutrophils, chemotactic for mononuclear phagocytes, and more
  409. How are oxygen-derived free radicals produced?
    during phagocytosis by neutrophils "respiratory burst"
  410. What do oxygen-derived free radicals cause?
    tissue damage including endothelium
  411. What inflammatory mediators are involved in vasodilation?
    prostaglandins & nitric oxide
  412. Histamine and serotonin cause what response in inflammation?
    increased vascular permeability
  413. Complement (C3a, C5a) causes what response in inflammation?
    increased vascular permeability
  414. Bradykinin and leukotrienes (C4, D4, E4) cause what response in inflammation?
    increased vascular permeability
  415. PAF, nitric oxide, substance P and oxygen metabolites cause what response in inflammation?
    increased vascular permeability
  416. Complement (C5a), leukotriene B4, chemokines and nitric oxide cause what response in inflammation?
    chemotaxis, leukocyte activation
  417. Interleukin-1, TNF, and prostaglandins cause what response in inflammation?
    fever
  418. Prostaglandins and bradykinin cause what response in inflammation?
    pain
  419. neutrophil & macrophage lysosomal enzymes, O2 metabolites and nitric oxide cause what response in inflammation?
    tissue damage
  420. Wound healing
    a complex but orderly process involving many chemical mediators and other growth facotrs, as well as cell-matrix interactions
  421. Step 1 in wound healing
    injury induces acute inflammation
  422. Step 2 in wound healing
    parenchymal cells regenerate
  423. Step 3 in wound healing
    both parenchymal and connective tissue cells migrate and proliferate
  424. Step 4 in wound healing
    extracellular matrix is produced
  425. Step 5 in wound healing
    parenchyma and connective tissue matrix remodel
  426. Step 6 in wound healing
    increase in wound strength due to collagen deposition
  427. What is the "hallmark of healing"?
    granulation tissue
  428. "Granulation tissue" term comes from what?
    soft, pink, granular appearance when viewed from the surface of a wound
  429. Histology of granulation tissue
    proliferation of small blood vessels and fibroblasts, tissue often edematous
  430. Summary - acute inflammation
    neutrophils are pathognomonic
  431. Summary - chronic inflammation
    plasma cells are pathognomonic
  432. Granulomatous inflammation
    epithelioid macrophages are pathognomonic
  433. Neoplasia
    abnormal mass of tissue with excessive growth
  434. Neoplasm
    tumor
  435. Oncology
    study of tumors neoplasms
  436. Benign neoplasms
    verruca, nevus, uterine leiomyoma
  437. Verruca
    wart
  438. Nevus
    mole
  439. uterine leiomyoma
    fibroids
  440. malignant neoplasms
    cancers
  441. Types of cancers
    carcinoma, sarcoma, leukemia, lymphoma
  442. "oma"
    added to cell of origin, but some exceptions
  443. What are the "omas" that are malignant?
    melanoma, hepatoma, lymphoma
  444. Sarcoma
    arising mesenchymal tissue - Greek - flesh
  445. Carcinoma
    arising from epithelial cells
  446. Leukemia/lymphoma
    arising from blood-forming cells
  447. growth pattern
    adenocarcinoma, squamous cell carcinoma, papillary carcinoma
  448. nomenclature of carcinoma
    growth pattern, organ of origin
  449. proliferating neoplastic cells
    parenchyma
  450. stroma
    connective, tissue, blood vessels, inflammatory cells
  451. desmoplasia
    marked collagenous stromal response to a neoplasm
  452. benign vs. malignant
    differentiation/anaplasia, rate of growth, local invasion, distant metastases
  453. differentiation
    extent to which cells in neoplasm resemble normal cells in form and function
  454. anaplasia
    lack of differentiation, lack of features that characterize mature cell
  455. How are benign neoplasms differentiated?
    generally well differentiated, but abnormal mass
  456. What degree of differentiation do malignant neoplasms?
    some degree of anaplasia - range from well-differentiated to undifferentiated
  457. What are some markers of anaplasia?
    pleomorphism, hyperchromatic nuclei, increase nuclear to cytoplasmic ratio
  458. What are more markers of anaplasia?
    prominent nucleoli, clumped chromatin, atypical mitotic figures, loss of polarity
  459. How do benign tumors grow in relation to local tissue?
    grow as cohesive, expansile masses that remain localized
  460. What are some characteristics of benign tumors?
    discrete, easily moveable, can be surgically removed, pushing, not infiltrating
  461. What are characteristics of malignant tumor invasion?
    demonstrate progressive infiltration, invasion and destruction of surrounding tissue
  462. What are characteristics of the cancers in relation to surrounding tissue?
    poorly demarcated, lack well-defined cleavage plane
  463. Carcinoma in situ
    displays all cytologic features of malignancy without invasion of the basement membrane
  464. When does carcinoma in situ occur?
    in cancers that evolve from a pre-invasive stage
  465. What are some examples of carcinoma in situ?
    carcinoma of the cervix, colon carcinoma
  466. metastasis
    defined as distant spread of tumor
  467. What does metastasis tell you about malignant vs. benign?
    marks a tumor as malignant - benign neoplasms do not metastasize
  468. Can all malignant tumors metastasize?
    most, but not all, can metastasize
  469. How can distant metastases occur?
    direct seeding, lymphatic spread, bloodstream spread
  470. What is the most common target of metastases spreading through the bloodstream?
    liver or lungs
  471. When may direct seeding of cavities and surfaces occur in metastases?
    when any malignant neoplasm penetrates into a cavity
  472. When is direct seeding of cavities in metastasis common?
    in ovarian carcinoma, spreading to the peritoneal cavity
  473. What is the most common route of spread for carcinomas and some sarcomas?
    lymphatic spread
  474. Why does hematogenous spread usually target liver or lungs?
    portal drainage to liver, vena caval drainage to lungs
  475. When is hematogenous spread common?
    sarcomas, but also occurs in carcinomas
  476. What types of cancer tend to invade veins?
    renal and hepatocellular
  477. What percentage of North American adults die from cancer every year?
    25 percent
  478. what is the 2nd leading cause of death?
    cancer
  479. What are risk factors for cancer?
    age, family history, acquired pre-neoplastic disorders, geography and environment
  480. Above what age do most cancers occur?
    55 years and above
  481. What is the leading cause of death in children under age 15?
    cancer
  482. How does family history affect cancer risk?
    reflects inheritance of cancer susceptibility genes
  483. What some examples of pre-neoplastic disorders?
    cirrhosis, HPV, UC
  484. What are some factors that affect cancer risk?
    tobacco smoke, asbestos, radiation exposure, alcohol abuse
  485. How do genetics affect cancer risk?
    cancer results from non-lethal genetic damage
  486. Genetic hypothesis of cancer
    tumor arises from clonal expansion of the damaged cell
  487. More on genetic hypothesis of cancer
    prediction that tumors have a monoclonal origin has been confirmed experimentally
  488. carcinogenesis - molecular basis of cancer
    a multistep process at both phenotypic and genetic levels
  489. tumor progression
    progressive acquisition of mutations leading to malignancy or metastasis
  490. initiators
    stimulate mutation
  491. promoters
    stimulate cell division
  492. Damage to growth-promoting proto-oncogenes can result in what?
    cancer
  493. Damage to growth-inhibiting tumor suppressor genes can cause what?
    cancer
  494. Damage to genes that regulate cell death can cause what?
    cancer
  495. Damage to genes that affect DNA repair can cause what?
    cancer
  496. What is needed for cancer to allow unlimited cell division?
    activation of telomerase
  497. oncogenes
    cancer-causing genes, derived from proto-oncogenes
  498. Proto-oncogenes
    cellular genes that control normal growth and differentiation
  499. insertional metagenesis
    retroviral promoter insertion near gene dysregulates its expression
  500. What can activates oncogenes?
    insertional mutagenesis, point mutation, amplification, chromosomal translocation
  501. mutation of ras oncogene
    mutant ras is always on
  502. Where is ras anchored?
    cytoplasmic domain of growth factor receptors via a lipid group
  503. What prevent addition of the lipid group, preventing ras localization?
    inhibitors of farnesyl transferase
  504. What does translocation do to proto-oncogenes?
    places expression of protooncogene under control of highly active promoters
  505. What is the result of translocation?
    formation of hybrid genes that encode growth-promoting chimeric proteins
  506. What gene does translocation occur in with Burkitt's lymphoma?
    c-myc
  507. Are coding regions changed in Burkitt's lymphoma?
    they are unchanged
  508. Over-expression due to translocation in mantle cell lymphoma
    cyclin D1 gene placed adjacent to IgH locus
  509. Over-expression due to translocation in follicular lymphoma
    bcl-2 gene placed adjacent to IgH locus
  510. Tumor suppressor genes
    products of these genes regulate cell growth (usually negatively)
  511. What has to happen to tumor suppressor genes for cancer to take over?
    both copies of the gene have to inactivated - "recessive" cancer gene
  512. What are the functions of tumor suppressor gene products?
    regulate the cell cycle, regulate nuclear transcription, cell surface receptors
  513. What is the purpose of cell surface receptors?
    growth inhibition, adhesion
  514. What does tumor growth depend on?
    balance between cell growth and cell death
  515. What does dysregulation of apoptosis allow?
    accumulation of mutations that would otherwise by lethal
  516. What is an example of dysregulation of apoptosis?
    bcl-2 overexpression in lymphoma
  517. genes that regulate DNA repair
    mismatch repair genes
  518. Are mutations in DNA repair genes oncogenic in and of themselves?
    no
  519. What do mutations in DNA repair genes allow?
    allow mutations to occur in other genes during normal cell division
  520. Can mutation of one gene transform cells?
    no - every human cancer has multiple genetic alterations including oncogenes and tumor suppressor genes
  521. What does the rate of tumor growth depend on?
    growth fraction and the rate of cell loss
  522. What does the growth fraction of tumors have an effect on?
    has a profound effect on susceptibility to chemotherapy
  523. Crude indication of growth rate?
    frequency of mitoses
  524. What is the first step for metastasis?
    loosening of intercellular junctions
  525. In metastasis, what happens after loosening of intercellular junctions?
    attachment
  526. In metastasis, what happens after attachment?
    degradation
  527. In metastasis, what happens after degradation?
    migration
  528. "soil and seed" theory
    different organs provide growth conditions optimized for certain cancers
  529. Homing theory
    different organs have special abilities to attract cancer cells
  530. Cartilage and skeletal muscle are rarely targets of metastasis, helping prove what theory?
    soil and seed
  531. What are three ways tumors cause disease?
    tissue destruction, organ compression, obstruction
  532. What are three more ways tumors cause disease?
    infection, anemia, soluble products
  533. Which mechanisms of disease caused by tumors cause pain?
    tissue destruction, organ compression
  534. Staging categorizes malignant tumors based on what?
    potential for invasion and metastasis
  535. Tumor grading is based on what?
    histologic examination of the tumor, provides estimated degree of malignancy
  536. TMN system
    tumor staging
  537. T in TMN system
    reflects size of tumor
  538. N in TMN system
    reflects lymph node involvement
  539. M in TMN system
    reflects the extent of metastasis
  540. In tumor staging, which number indicates a better prognosis?
    lower
  541. Who performs tumor grading?
    pathologist
  542. Is grading system the same for all tumors?
    no - differs according to tumor type
  543. Grade I tumor
    well-differentiated, low anaplasia
  544. Grade II, III tumor
    intermediate differentiation
  545. Grade IV tumor
    poorly differentiated; high anaplasia
  546. Major therapeutic modalities for cancer
    surgery, radiation, chemo, immunotherapy, molecularly-based therapy, combination therapy
  547. What is the 3rd most common cancer in incidence and mortality?
    colorectal cancer
  548. What percent of colorectal cancer has hereditary component?
    15-50 percent
  549. What percent of colorectal cancer is due to known mutations?
    roughly 15 percent - FAP, HNPCC
  550. Can tobacco cause colon cancer?
    yes
  551. The body's adaptation to restore or maintain normal function is called
    Homeostasis
  552. The best example of a cytoplasmic architecture found in a cells hyaloplasm is
    Microfilaments
  553. The definition of epidemiology is
    The study of the cause and distribution of disease
  554. The necrosis type associated with the pancreas is
    Fat
  555. The necrosis type associated with the kidney , liver & heart is
    coagulative
  556. Poor circulation that results in mummified appearing toes is called
    dry gangrene
  557. Nuclear manifestations of irreversible cell injury include
    karyolysis and pyknosis
  558. Mitochondrial swelling
    reversible cell injury
  559. Torch syndrome
    Toxoplasma Other agents Rubella Cytomegalovirus Herpesvirus
  560. Diseases of a receptors
    Myasthenia gravis
  561. Hormone related cell number increase
    Hyperplasia
  562. Cell shrinkage that can be from old age or ischemia is best called
    Atrophy
  563. Vasculoar degeneration, acidic pH and decreased protein synthesis are sings of
    Reversible cell injury
  564. Vitamin B12 deficiency can cause
    Pernicious anemia
  565. Environmental agents that permanently harm a developing fetus are called
    teratogens
  566. A male phenotype with all stature, atrophic testes, effeminate with possible gynecomastia best describes
    Klinefelter syndrome (XXY)
  567. American President Abe Lincoln has been felt by some researchers to have been likely to have this autosomal dominant disease affecting collagen that results in increased risk of dissecting aortic aneurysms and ocular lens subluxation. what is this conditi
    Marfan's disease
  568. Which autosomal recessive condition is associated with increased risk of liver disease (cirrhosis) and emphysema
    alpha-1 antitrypsin deficiency (AAT)
  569. Typical of Turner Syndrome (XO)
    Lack of ovary develometn (infertile); Increased risk of coarctation of the aorta
  570. Which of the following conditions is considered multifactorial in etiology?
    Diabetes mellitus
  571. which word below best describes the process of maintaining internal steady state or balance within a cell or living system?
    Homeostasis
  572. Patient type with greater amount of adipose tissue than normal
    elderly; women; infants
  573. The correct example below that is an insensible loss of fluids is
    sweating
  574. Transcellular fluids make up a very small % of extracellular fluids. Which of the following is an example of a transcellular fluid?
    Cerebrospinal fluid (CSF)
  575. Example of active hyperemia
    blushing
  576. Smallest manifestation of bleeding under the skin below is
    Petechiae
  577. Hormones or proteins involved in maintaining fluid balance include
    ADH, Atrial natriuretic peptide, aldosterone
  578. melena
    Tarry appearing digested blood in stool
  579. What % of total body weight is water
    60%
  580. White infarction
    arterial
  581. Red infarction
    venous (testes/gut)
  582. Causes Caisson's disease and the bends
    Gaseous
  583. Emboli type
    White infarction - Arterial (heart/kidney) red infarction (venous - testes/gut) Causes Caisson's disease and Bends - Gaseous emboli (air in vein)
  584. Arterial hemorrhage can be recognized from venous in that the arterial blood is
    Bright red and flows in a pulsating manner
  585. Histamine is released from mast cells when they are in a tissue or organ. What are mast cells called when they are circulating in the blood?
    Basophils
  586. Which arachidonic acid derivatives results from the lipoxygenase pathway, plus they are associated with asthma and anaphylaxis?
    Leukotrienes
  587. Tuberculosis infections cause caseous granulomas. What type of granulomas are seen with Sarcoid (Sarcoidosis)
    Non-Caseous granulomas
  588. Inflammation
    Elevated WBC count, body temperature, ESR
  589. Cardinal Signa of Inflammation
    Rubor, Swelling, Calor, Dolor, functio laesa
  590. Band cells are also known as
    Immature WBCs
  591. Complement system, a key component of the body’s inflammatory response, can be activated by a longer classical and a shorter alternative pathway. They both end up in a common mechanism - which pathway (endpoint)
    Membrane Attack Complex
  592. Immune System Body Sites
    Primary - bone marrow, thymus; Secondary - Tonsils, Peyer's patches
  593. Atrophic gastritis and Crohn's disease are most typically associated with
    B-12 deficiency
  594. Microcytic hypochromic anemia with low hemosiderin stores in the bone marrow will respond favorably to treatment with
    Iron
  595. Nature Killer Cell
    from Lymphoid stem cell
  596. Arachidonic acid
    precursor for cyclooxygenase and lipoxygenase pathways
  597. Immunoglobulin found in mucosa and body secretions
    IgA
  598. Immunoglobulin makes the second and largest response
    IgG
  599. Immunoglobulin associated with allergy and hypersensitivity
    IgE
  600. Immunoglobulin mounting the primary/earliest response to invasion
    IgM
  601. What are circulating basophils called when they reside in tissues
    Mast cells
  602. Loss of Cd4 helper T-cells and increased opportunistic infections are best associated with
    AIDS
  603. treatment for severe idiopathic aplastic anemia
    bone marrow transplant
  604. who tends to have secondary polycythemia
    professional mountain climber
  605. Hematopoiesis
    from flat bone and long bone
  606. RBC life
    120 days
  607. Repairing tears in the endothelium of vessels
    Platelets
  608. Rapid RBC turnover
    elevated reticulocyte count
  609. What organism causes pseudomembrane formation in antibiotic induced colitis
    C. difficile
  610. Arterial emboli
    Cerebral, kidney, spleen, intestines
  611. Arterial emboli
    white/pale infarction (heart/kidney)
  612. Arterial emboli Red Infarction
    venous-testes/gut
  613. Thrombocytopenia
    Low platelet count < 75K (Normal 150K - 300K)
  614. Etiology
    Acquired - infection, bone marrow suppression, hypersplenism
  615. Drugs effect
    heparin
  616. ITP (idiopathic thrombocytopenic purpura)
    immune disorders
  617. Spontaneous Bleeding
    When platelet count drops below 20K
  618. Thrombocythemia
    High thrombocyte count > 600K
  619. Thrombocythemia treatment
    hydroxyurea
  620. Acute Lymphoblastic Leukemia (ALL)
    Highest among children, 20% of all leukemia
  621. Acute Myelogenous Leukemia (AML)
    Most common leukemia, 40% of total leukemia, bone marrow transplant the only treatment
  622. Chronic Myelogenous (CML)
    15%, affecting adults and increases with advancing age, 90% with Philadelphia chromosomes
  623. CML Mortality
    Poor prognoses without Philadelphia chromosomes present
  624. Hodgkin's lymphoma
    1. nodular sclerosis; 2. lymphocyte predominance; 3. mixed cellularity; 4. lymphocyte depletion
  625. Hemostasis
    Vasospasm; Platelet activation (locally released factors); Platelet adhesion (von Willebrand's factor); Platelet aggregation; fibrin thrombus formation
  626. Inhibition of excessive clotting
    circulating anticoagulants; protein C, Protein S, antithrombin III; Thrombomodulin released by endothelial cells
  627. Fibrinolysis
    TPA: tissue plasminogen factor; Urokinase
  628. Hypocoagulability
    Coumadin; heparin
  629. Vitamin K utilization by liver
    inhibited by Coumadin (warfarin)
  630. Hypercoagulability Venous
    Red clots: RBC/fibrin; Stasis; Inappropriate activation of clotting factors; surgery, malignancy, CHF, obesity, OCs, estrogens, HPT, DM, polycythemia; pregnancy
  631. Hemophilia
    congenital bleeding disorder
  632. hemophilia A
    common disorder - 2/10,000; lacking factor VIII
  633. von Willebrand's Factor
    Most common generic bleeding disorder
  634. von Willebrand's Factor
    1% of population
  635. von Willebrand's Factor
    autosomal dominant; affect both platelets and factor VIII
  636. Virchow's triad
    slow venous flow; hypercoagulability; inflammation of vessel wall
  637. DVT
    25% clinically evident edema/swelling discrepancy in limb size Homan's sign
  638. 40% DVT lead to
    Pulmonary emboli
  639. 50% DVT lead to
    postphlebitic syndrome
  640. Disseminated Intravascular Coagulopathy
    Systemic disorder of thrombosis and hemorrhage with evidence of widespread pro-coagulant activity fibrinolytic activation inhibitor consumption and end organ damage from thrombosis
  641. DIC treatment
    blood, clotting factors, anticoagulation
  642. DIC Mortality
    60 - 80% of cases
  643. DVT Treatment
    Reduce risk factors prophylactic therapy anticoagulant therapy thrombolytic therapy greenfield filter
  644. Thrombotic thrombocytopenic Purpura
    Mortality - 90% Rare 1/50,000 hospital patients
  645. IgM
    Primary response
  646. IgG
    Secondary response, placenta
  647. IgA
    Secretions/mucosal
  648. IgD
    Intercellular signaling
  649. IgE
    Hypersensitivity, least amount

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