Pathology exam 1

  1. Pathology
    Study of disease, focusing on physiologic, gross, and microscopic morphologic changes in cells reacting to injury.
  2. 8 Major Pathologic Categories/Processes of Diseases
    • Inflammation
    • Infectious
    • Immunologic
    • Neoplasia
    • Hemodynamic/Vascular
    • Environmental/Nutritional
    • Genetic/Developmental
    • Endocrine/Metabolic
  3. Etiology
    Cause of disease
  4. Idiopathic
    Unknown etiology
  5. Iatrogenic
    Provider induced
  6. Pathogenesis
    Description of the mechanisms by which diseases develop
  7. Syndrome
    Group of signs and/or symptoms that characteristically occur together as part of a single disease process.
  8. Pathognomonic
    A sign, symptom or characteristic of a disease that leads to its accurate diagnosis.
  9. 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.
  10. Parenchyma
    The functional elements of an organ, e.g., myocardial cell (myocyte) of the heart; neuron of the brain.
  11. Stroma
    The framework or support elements of an organ, e.g., the connective tissue (interstitium) of the heart surrounding the myocyte.
  12. Lesion
    Any pathological abnormality of tissue structure or function.
  13. Basic Principles That Govern Cell Injury
    • Disease results from cumulative effects of injury to individual cells.
    • Different cell types respond differently to stress.
    • Consequences of cell injury differ depending on cell type.
    • Cells are not static; they must be able to adapt to their environment.
    • Cells need energy to perform functions and to maintain viability.
  14. Causes of Cell Injury
    • Nutritional deficiency
    • Lack of vitamin B12 (vegans)

    • Inability to absorb or utilize nutrients
    • Pernicious anemia (lack of intrinsic factor; cannot absorb Vit B12)

    Genetic defect leading to inadequate production or regulation
  15. Causes of Cell Injury
    Presence of substance that interferes with cell function

    • Endogenous
    • Genetic defect (ex: inability to metabolize carbohydrates)
    • Accumulation of metabolite (poor circ.)

    • Exogenous
    • Infectious agents
    • Chemicals
    • Drugs: illegal and prescription
  16. Causes of Cell Injury
    Loss of structural integrity

    Mechanical pressure

    • Hypothermia
    • Formation of ice crystals
    • Hyperthermia
    • Denaturation or oxidation of proteins

    • Infections
    • Cell rupture or lysis
  17. Example of Deficiency
    Oxygen Deprivation
    • Hypoxia
    • state of tissue or cell oxygen deficiency
    • Ischemia
    • oxygen deprivation due to lack of blood flow
  18. Why Do Cells Need O2?
    • Anaerobic Glycolysis:
    • Glucose + 2 ADP ---> 2 Lactate + 2 ATP

    • Glycolysis + Oxidative Phosphorylation:
    • Glucose + 6 O2 + 36 ADP ---> 6 CO2 + 6H2O + 36 ATP
  19. What happens if there is not enough O2?
    Cellular metabolism switches to anaerobic glycolysis as the primary source of energy with accumulation of lactic acid and inorganic phosphate.

    If O2 is lacking because of ischemia, inflow of substrate decreases and efflux of metabolic wastes slows.

    Energy reserves are consumed. Myocytes in muscle (heart) try to use creatine phosphate for energy. Adenine nucleotides break down.
  20. What cellular processes require energy continuously and consume energy at the highest rate?
    Most cellular energy is used for ion transport.
  21. Why Cells Swell During Ischemia
    • Na+/K+ ATPase is needed to keep intracellular [Na+] from rising.
    • When pump is off, Na+ comes in (which increases # of particles within the cell) & water follows.
    • Tissue osmolality increases due to catabolism within ischemic cells.
    • Water flows in passively.
  22. Fatty Change
    Lipid accumulation (especially in hepatocytes).

    Impaired lipoprotein synthesis (ethanol, protein malnutrition).

    Decreased fatty acid oxidation (hypoxia).

    Increased liberation of fat from peripheral stores (starvation).
  23. Manifestations of Cell Injury
    • Acute cessation of specialized functions.
    • Persistent impairment of function after cessation of noxious stimulus.
    • Loss of ability to replicate.
  24. Sensitivity to Ischemia
    Brain > Heart > Kidney >> Skin
  25. Reversible Cellular Injury
    • Blebs form.
    • Generalized swelling.
    • Clumping of nuclear chromatin.
    • Autophagy of mitochondria by lysosomes.
    • Aggregation of intramembranous particles.
    • ER swelling.
    • Ribosomes fall of ER.
    • Mitochondrial swelling.
    • Small densities form within mitochondria.
  26. Responses to Radiation Injury
    Radiation generates free radicalls that damage cell membranes and DNA.

    • Dose: 300rad
    • Latency: 2wks
    • Death: 3wks
    • Affects bone.

    • Dose: 1000rad
    • Latency: 3days
    • Death: 2wks
    • Affects GI tract.

    • Dose: 2000rad
    • Latency: 1hr
    • Death: 1day
    • Death of neurons.
  27. 6 Morphologic Responses to Non-Lethal Injury
    • Atrophy
    • Hypertrophy
    • Hyperplasia
    • Metaplasia
    • Dysplasia
    • Intracellular Storage
  28. Atrophy
    Decrease in size, and often function, of cells, generally associated with a decrease in size and/or function of a tissue or organ.

    • Causes:
    • Disuse atrophy of muscle; voluntary or denervation-induced
    • Decreased blood supply
    • Inadequate nutrition
    • Loss of endocrine stimulation
    • Loss of growth factors
  29. 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.

    • Causes:
    • Mechanical stimulus; cardiac and skeletal muscle hypertrophy
    • Growth factor stimulation; endocrine stimulation at puberty, pregnancy
    • Increased functional demand; unilateral nephrectomy
  30. Hyperplasia
    Increase in the number of cells in an organ or tissue, often resulting in an increase in size of the tissue or organ.

    • Causes:
    • Growth factor stimulation; endocrine or stress-induced (endometrial proliferation with each menstrual cycle, callus formation during bone healing, erythroid hyperplasia under chronic hypotoxic conditions)
    • Viral induced; warts
  31. Metaplasia
    Replacement of one differentiated cell type with another.

    Main cause is chronic irritation: ex; respiratory tract of smokers, cervix of sexually active females, esophagus in response to gastric acid
  32. 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.
  33. Intracellular storage
    Lipid accumulation (fatty change) in hepatocytes.

    Anthracotic pigment in alveolar macrophages.

    Lipofuscin (waste product of metabolism as cells age)
  34. 2 Types of Cell Death
    • Necrosis
    • - a morphologic expression of cell death
    • - progressive disintegration of cellular structure
    • - generally initiated by overwhelming stress
    • - generally elicits acute inflammatory cell response

    • Apoptosis
    • An alternate pathway of cell death, called "programmed cell death" or "physiologic cell death"
    • - controlled by specific genes
    • - fragmentation of DNA, fragmentation of nucleus
    • - blebs form and "apoptotic bodies" are released
    • - "apoptotic bodies" phagocytized, no neutrophils

    • Consequences:
    • Necrosis: Loss of functional tissue, impaired organ function, transient or permanent
    • Apoptosis: Removal of damaged or unnecessary cells
  35. Physiologic States Where Apoptosis May Be Important
    • Embryogenesis; development
    • Withdrawal of trophic hormones, growth factors
    • Prostate glandular epithelium after castration
    • Regression of lactating breast after weaning
    • Withdrawal of interleukin-2 results in apoptosis of stimulated T lymphocytes, presumably to remove unnecessary T cells after antigen clearance
    • Ionizing radations
    • Conditions associated with free radical generation
    • Mild theramal injury
    • Steroids (glucocorticoids induce apoptosis in lymphocytes)

    • Viral infection
    • 1. Apoptosis can be a potent defense mechanism against virus infection, and some viruses such as adenoviruses and human papilloma virus, encode proteins that can block apoptosis.
    • 2. In AIDS, loss of CD4+ T lymphocytes may be mediated in part by apoptosis.

    • Cell-mediated immunity
    • 1. Cytotoxic T lymphocytes can kill target cells by inducing apoptosis.

    • Autoimmune diseases
    • Removal of autoreactive immature lymphocytes is by apoptosis.
    • Degenerative diseases of the central nervous system, possibly including Alzheimer's disease and Parkinson’s disease.

    • Neoplasia
    • 1. Apoptosis may be an important mechanism for eliminating cells with genetic defects.
    • 2. Inhibition of apoptosis may contribute to prolonged life span of malignant cells
  36. 5 Common Types of Necrosis
    • Coagulative Necrosis
    • Liquefactive Necrosis
    • Caseous Necrosis
    • Fat Necrosis
    • Fibrinoid Necrosis
  37. Coagulative Necrosis
    Pattern of cell death characterized by progressive loss of cell structure, with coagulation of cellular constituents and persistence of cellular outlines for a period of time, often until inflammatory cells arrive and degrade the remnants.

    Similar in many respects to autolysis - which can be defined as self digestion - which is what happens to tissue that is incubated for a period of time in the absence of blood flow or oxygen, i.e. does not require the participation of inflammatory cells.

    Characterized by changes in cytoplasmic staining in routine histology sections and changes in nuclear morphology and/or staining characteristics

    Cytoplasm becomes more eosinophilic

    Several different patterns of nuclear change
  38. Patterns of Nuclear Change in Coagulative Necrosis
    Pyknosis - nucleus shrinks and chromatin condenses; nucleus becomes deeply basophilic (very dark blue with H&E stain)

    Karyorrhexis - nucleus breaks up into small pieces

    Karyolysis - nucleus becomes progressively paler staining and eventually disappears
  39. Liquefactive Necrosis
    Pattern of cell death characterized by dissolution of necrotic cells.

    Typically seen in abscess where there are large numbers of neutrophils that release hydrolytic enzymes and break down dead cells.

    Pus forms (liquified remnants of dead cells, including neutrophils).
  40. Fat Necrosis
    The result of release of lipases into adipose tissue.

    Triglycerides are cleaved into fatty acids.

    Fatty acids binds and precipitate calcium ions, forming insoluble salts (chalky white on gross examination, basophilic when stained with H&E).
  41. Caseous Necrosis
    This pattern of cell injury occurs with granulomatous inflammation in response to certain microorganisms (tuberculosis).

    The host response to the organisms is a chronic inflammatory response.

    A caseating granuloma forms with a center of cellular debris that grossly has the appearance and consistency of cottage cheese.
  42. Fibrinoud Necrosis
    This pattern of cell injury occurs in the wall of arteries in cases of vasculitis.

    Endothelial damage and necrosis of smooth muscle cells of the media.

    This allows plasma proteins, primarily fibrin, to be deposited in the area of medial necrosis.
  43. Infarction
    Cell death and coagulative necrosis due to prolonged ischemia.

    Renal and splenic infarcts are typically wedge-shaped.
  44. 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.
  45. Other Manifestations of Ischemic Injury
    • Enzyme release: CK, LDH, transaminases
    • Cardiac specific protein release: CK-MB, cardiac troponin isoforms
    • Arrhythmias - heart block, PVCs, V Tach, VF
    • Permanent ECG changes
    • Heart failure - related to cumulative infarct size
    • Tissue rupture, aneurysm, mural thrombi
  46. Identifying and Monitoring Cell Injury
    • Functional loss: ↓oxygenation, ↓mobility, ↑ bilirubin
    • Release of cell constituents: K+ from RBC, troponin or CPK from heart
    • Change in electrical activity: EKG, EEG, EMG
    • Direct examination of tissue
  47. What is Inflammation?
    • Response to injury (including infection).
    • Reaction of blood vessels leads to accumulation of fluid and leukocytes in extravascular tissues.
    • Destroys, dilutes, or walls off the injurious agent.
    • Initiates the repair process.
    • Fundamentally a protective response.

    • May be potentially harmful:
    • Hypersensitivity reactions to insect bites, drugs, contrast media in radiology
    • Chronic diseases: arthritis, atherosclerosis
    • Disfiguring scars, visceral adhesions

    • How: Chemical mediators
    • Derived from plasma proteins
    • Derived from cells inside and outside of blood vessels

    • Components of inflammatory response:
    • Vascular reaction
    • Cellular (exudative) reaction
  48. Types of Inflammation
    Acute inflammation: short duration, edema, and mainly neutrophils.

    Chronic inflammation: longer duration, lymphocytes & macrophages predominate, fibrosis, new blood vessels (angiogenesis).

    Granulomatous inflammation: distinctive pattern of chronic inflammation; activated macrophages (epithelioid cells) predominate.
  49. Acute Inflammation
    • Three major components:
    • 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
    • Stimuli: infections, trauma, physical or chemical agents, foreign bodies, immune reactions
  50. Benefits of Fluid Accumulation at Injury Site
    • Dilution of toxins
    • Pain decreases use and prevents additional injury
    • Antibodies in blood can kill microbes
    • Blood plasma proteins can amplify responses against the injurious agent
  51. Leukocyte Extravasation
    • Extravasation: delivery of leukocytes from the vessel lumen to the interstitium
    • In the lumen: margination, rolling, and adhesion
    • Migration across the endothelium (diapedesis)
    • Migration in the interstitial tissue (chemotaxis)

    Leukocytes ingest offending agents (phagocytosis), kill microbes, and degrade necrotic tissue and foreign antigens

    There is a balance between the helpful and harmful effects of extravasated leukocytes
  52. Leukocyte Adhesion
    • Leukocyte adhesion and migration across vessel wall determined largely by binding of complementary adhesion molecules on the leukocyte and endothelial surfaces.
    • Chemical mediators affect these processes by modulating the expression or avidity of the adhesion molecule
  53. Sequence of Leukocyte Emigration
    • Neutrophils predominate during the first 6 to 24 hours.
    • Monocytes in 24 to 48 hours.
    • Induction/activation of different adhesion molecule pairs and specific chemotactic factors in different phases of inflammation.
  54. Morphologic Patterns of Acute Inflammation
    • Serous inflammation: Outpouring of thin fluid (serous effusion, blisters).
    • Fibrinous inflammation: Body cavities; leakage of fibrin; may lead to scar tissue (adhesions).
    • Suppurative (purulent) inflammation: Pus or purulent exudate (neutrophils, debris, edema fluid); Abscess: localized collections of pus.
    • Ulcers: Local defect of the surface of an organ or tissue produced by the sloughing (shedding) of inflammatory necrotic tissue.
  55. Chronic Inflammation
    Inflammation of prolonged duration (weeks or months).

    • Active inflammation: tissue destruction, and attempts at repair are proceeding simultaneously
    • May follow acute inflammation or begin insidiously and often asymptomatically.

    • Persistent infections
    • Treponema pallidum [syphilis], viruses, fungi, parasites

    • Exposure to toxic agents
    • Exogenous: silica (silicosis)
    • Endogenous: toxic plasma lipid components (atherosclerosis)

    • Autoimmunity
    • Rheumatoid arthritis, systemic lupus erythematosus

    • Histological features
    • 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)
  56. Macrophages
    • Monocytes begin to emigrate into tissues early in inflammation where they transform into the larger phagocytic cell known as the macrophage.
    • Macrophages predominate by 48 hours
    • Recruitment (circulating monocytes); division; immobilization
    • Activation results in secretion of biologically active products.
  57. 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.
  58. Eosinophils in Chronic Inflammation
    • Immune reactions mediated by IgE
    • Parasitic infections: eosinophil granules contain a protein that is toxic to parasites.
  59. Mast Cells in Chronic Inflammation
    Release mediators (histamine) and cytokines that trigger inflammation.
  60. Granulomatous Imflammation
    • Distinctive pattern of chronic inflammation.
    • Predominant cell type is an activated macrophage with a modified epithelial-like (epithelioid) appearance.
    • Giant cells may or may not be present.

    Granuloma: focal area of granulomatous inflammation.

    Foreign Body Granulomas: Form when foreigh material is too large to be engulfed by a single macrophage.

    Immune Granulomas: Insoluble or poorly soluble particles elicit a cell-mediated immune response.
  61. Systemic Manifestations of Inflammation
    • Endocrine and Metabolic
    • Secretion of acute phase proteins by the liver.
    • Increased production of glucocorticoids (stress response).
    • Decreased secretion of vasopressin leads to reduced volume of body fluid to be warmed.

    • Fever
    • Improves efficiency of leukocyte killing.
    • Impairs replication of many offending organisms.

    • Autonomic
    • Redirection of blood flow from skin to deep vascular beds minimizes heat loss.
    • Increased pulse and blood pressure.
    • Decreased sweating.

    • Behavioral
    • Shivering (rigors), chills (search for warmth), anorexia (loss of appetite), somnolence, and malaise.

    • Leukocytosis: Increased leukocyte count in the blood
    • Neutrophilia: Bacterial infections
    • Lymphocytosis: Infectious mononucleosis, mumps, measles
    • Eosinophilia: Parasites, asthma, hay fever

    Leukopenia: Reduced leukocyte count; typhoid fever, some viruses, rickettsiae, protozoa
  62. General principles of chemical mediators
    • May be derived from plasma or cells
    • Most bind to specific receptors on target cells
    • Can stimulate release of mediators by target cells, which may amplify or ameliorate the inflammatory response
    • May act on one or a few target cells, have widespread targets, and may have differing effects depending on cell and tissue types
    • Usually short-lived Most have the potential to cause harmful effects
  63. Chemical Mediators of Inflammation
    Vasoactive Mediators
    • Vasoactive Mediators:
    • Histamine
    • Bradykinin
    • Complement (C3a, C5a)
    • Prostaglandins/leukotrienes
    • Nitric oxide
    • Neuropeptides

    • Chemotactic Factors: attract leukocytes
    • Complement (C5a)
    • Leukotriene (B4)
    • Cytokines (IL-1, TNF)
    • Chemokines (chemotactic cytokines)
    • Nitric oxide
    • Histamine
  64. Histamine (vasoactive)
    Mast cells (also basophils and platelets)

    • Release mechanisms:
    • >Binding of antigen (allergen) to IgE on mast cells releases histamine-containing granules
    • >Release by non-immune mechanisms such as cold, trauma, or other chemical mediators
    • >Release by other mediators

    Dilates arterioles and increases permeability of venules (wheal and flare reaction)
  65. Bradykinin (vasoactive)
    • Small peptide released from plasma precursors
    • Increases vascular permeability
    • Dilates blood vessels
    • Causes pain
    • Rapid inactivation
  66. Arachidonic Acid Metabolites (vasoactive)
    • Prostaglandins (NSAIDs prevent formation of prostaglandins)
    • >Vasodilatators: prostacyclin (PGI2), PGE1, PGE2, PGD2
    • >Vasoconstrictors: thromboxane A2
    • >Pain (PGE2 makes tissue hypersensitive to bradykinin)
    • >Fever (PGE2)

    • Leukotrienes
    • >Increase vascular permeability: leukotrienes C4, D4, E4
    • >Vasoconstriction: lipoxins
    • >Leukocyte adhesion & chemotaxis: leukotriene B4, HETE, lipoxins
  67. Nitric Oxide (vasoactive)
    Made by macrophage enzyme iNOS and endothelial cells eNOS.

    Med: Nitroglycerine
  68. Neuropeptides
    • Substance P and neurokinin A
    • Produced in central and peripheral nervous systems
    • >Substance P nerve fibers prominent in lung and gastrointestinal tract
    • Vasodilation (direct and through mast cell degranulation)
    • Increased vascular permeability
  69. Cytokines (chemotactic)
    • Proteins produced by many cell types (principally by activated lymphocytes and macrophages)
    • Modulate the function of other cell types
    • Interleukin-1 (IL-1) and tumor necrosis factor (TNF) are the major cytokines that mediate inflammation
  70. Chemokines (chemotactic)
    • Small proteins that act primarily as chemoattractants for specific types of leukocytes (approximately 40 known)
    • Stimulate leukocyte recruitment in inflammation
    • Control the normal migration of cells through tissues (organogenesis and maintenance of tissue organization)
    • Examples: IL-8, eotaxin, lymphotactin
  71. Summary of Inflammatory Mediators
    • Vasodilation
    • Prostaglandins
    • NO

    • Increased Vascular Permeability
    • Histamine, Serotonin
    • Complement (C3a, C5a)
    • Bradykinin
    • Leukotrienes (C4, D4, E4)
    • NO
    • Substance P
    • Oxygen metabolites

    • Chemotaxis, Leukocyte Activation
    • Complement (C5a)
    • Leukotriene B4
    • Chemokines
    • NO

    • Fever
    • IL-1
    • TNF
    • Prostaglandins

    • Pain
    • Prostaglandins
    • Bradykinin

    • Tissue Damage
    • Neutrophil and Macrophage lysosomal enzymes
    • Oxygen metabolites
    • NO
  72. Steps in Wound Healing
    • Injury induces acute inflammation.
    • Parenchymal cells regenerate.
    • Both parenchymal and connective tissue cells migrate and proliferate.
    • Extracellular matrix is produced.
    • Parenchyma and connective tissue matrix remodel.
    • Increase in wound strength due to collagen deposition.
  73. Granulation Tissue
    • Hallmark of healing
    • Term comes from soft, pink, granular appearance when viewed from the surface of a wound
    • Histology: Proliferation of small blood vessels and fibroblasts; tissue often edematous
  74. Neoplasia
    • Defined as:
    • “An abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissue and persists in the same excessive manner after cessation of the stimuli that evoked the change” R.A. Willis, 1952

    In current usage, neoplasm = tumor

    Oncology (Greek oncos = tumor) is the study of tumors or neoplasms
  75. Types of Neoplasms
    • Benign
    • verruca (“wart”)
    • nevus (“mole”)
    • uterine leiomyoma (“fibroids”)

    • Malignant
    • cancers
    • carcinoma, sarcoma, leukemia, lymphoma
  76. Nomenclature of Benign Tumors
    • Usually designated by addition of “oma” to cell of origin
    • Fibroma
    • Chondroma
    • Osteoma
    • Adenoma
    • (but watch for exceptions!)
    • Melanoma, hepatoma, lymphoma are all malignant tumors!
  77. Nomenclature of Malignant Tumors
    • Arising from mesenchymal tissue: (Greek “sar” = fleshy)
    • sarcoma

    • Arising from epithelial cells:
    • carcinoma

    • Arising from blood-forming cells:
    • leukemia/lymphoma
  78. Nomenclature of Carcinomas
    • Growth pattern:
    • adenocarcinoma (glandular)
    • squamous cell carcinoma (flat)
    • papillary carcinoma (finger-like)

    Organ of origin
  79. Components of Benign and Malignant Tumors
    Proliferating neoplastic cells: parenchyma

    Stroma: connective tissue, blood vessles, inflammatory cells
  80. Desmoplasia
    marked collagenous stromal response to a neoplasm
  81. Anaplasia
    Lack of differentiation.

    • Markers of Anaplasia:
    • Pleomorphism, cells vary a lot in size and shape
    • Hyperchromatic nuclei
    • Increased nuclear to cytoplasmic ratio
    • Prominent nucleoli
    • Clumbed nuclear chromatin
    • Atypical mitotic figures
    • Loss of normal orientation (polarity)
  82. Differentiation
    The extent to which cells in a neoplasm resemble comparable normal cells in form and function.
  83. Differences Between Benign vs Malignant Tumors
    • Differentiation/Anaplasia
    • Benign neoplasms are generally well differentiated. Cells may be cytologically normal but abnormally mass into a nocule.
    • Malignant neoplasms have some degree of anaplasia and range from well-differentiated to undifferentiated.

    • Rate of growth
    • Benign tumors have slow growth.
    • Malignant tumors grow rapidly and often hemorrhage and have tissue necrosis.

    • Local invasion
    • Benign tumors tend to grow as cohesive, expansile masses that remain localized (discrete, easily moveable, can be surgically enucleated, push other tissue away, not infiltrating).
    • Malignant tmors demonstrate progressive infiltration, invasion, and destruction of surrounding tissue (poorly demarcated, lacks well-defined cleavage plane).

    • Distant Metastases
    • Most, but not all, malignant tumors can metastasize.
    • Benign neoplasms do not metastasize.
  84. Metastasis
    • Constant spread of tumor.
    • Unequivocally marks a tumor as malignant.
    • Benign tumors do not metastasize.
  85. Pathways of Metastasis
    • Lymphatic spread
    • Hematogenous spread
  86. Sarcoma
    • Greek “sar” = fleshy
    • Arise from mesenchymal tissue
  87. Carcinoma
    Arising from epithelial cells.
  88. Lymphoma/Leukemia
    Arising from blood-forming cells.
  89. Initiators and Promotors in Chemical Carcinogenesis
    Initiators stimulate mutation.

    Promotors stimulate cell division.
  90. 6 Hallmarks of Cancer
    • Evading apoptosis.
    • Self-sufficiency in growth signals.
    • Insensitivity to antigrowth signals.
    • Tissue invasion and metastasis.
    • Limitless replicative potential.
    • Sustained angiogenesis.
  91. Oncogenes
    • Cancer-causing genes.
    • Derived from proto-oncogenes, cellular genes that control normal growth and differentiation.

    • Activation of Oncogenes:
    • Insertional mutagenesis
    • Point mutation
    • Amplification
    • Chromosomal translocation
  92. Molecular Basis of Cancer
    • Cancer results from damage to:
    • >Growth-promoting proto-oncogenes
    • >Growth-inhibiting tumor supressor genes
    • >Genes that regulate cell death
    • >Genes that affect DNA repair

    Also need activation of telomerase to allow unlimited cell division.
  93. Steps for Metastasis
    • Loosening of intercellular junctions.
    • Attachment to basement membrane.
    • Degradation of basement membrane.
    • Migration.
  94. Tumor Grading and Staging
    • Grading is based on histologic examination of the tumor and provides and estimated degree of aggressiveness.
    • Performed by a pathologist.
    • System varies according to tumor type.

    • I = well differentiated; low anaplasia
    • II,III = intermediate differentiation
    • IV = poorly differentiated; high anaplasia

    Staging is a system of categorizing malignant tumors in terms of their potential for invasion and metastasis.

    • TNM system (lower number = better prognosis)
    • T = size of tumor
    • N = lymph node
    • M = extent of metastasis
  95. 6 Major Therapeutic Modalities
    • Surgery
    • Radiation Therapy
    • Chemotherapy
    • Immunotherapy
    • Molecularly-Based Therapy (tx affects pathways within the tumor)
    • Combination Therapy)
Card Set
Pathology exam 1
Pathology DPAP2012 cell injury inflammation neoplasia