1. What are the four aspects of the disease process?
    • 1. Etiology or cause- genetic or acquired
    • 2. Pathogenesis- sequence of events in the response of cells or tissues to the etiologic event
    • 3. Morphologic change - structural alteration in cells or tissues that are either characteristic of the disease or diagnostic of the etiologic event.
    • 4. Clinical manifestation - The nature of the morphologic changes and their distribution in different organs or tissues influence normal function and determine the clinical features, course, and prognosis of the disease.
  2. The increase in the number of cells?
  3. An increase in the size of individual cells?
  4. A decrease in cell size and function?
  5. The normal stages of cellular response to stress and injury
    During times of stress and increased demand the cell adapts, if there is an inability to adapt the cell will die. If the stimulus is injurious the cell will die. Cell injury is reversible up to a certain point but if the stimulus persists the cell reaches the point of no return and suffers irreversible cell injury and death.
  6. What are the two principle patterns of cell death?
    • 1. Necrosis - Response to abnormal stresses such as ischemia and chemical injury. Always pathologic.
    • 2. Apoptosis - Cell dies through activation of an internally controlled suicide program. Eliminates unwanted cells in embryogenisis and also occurs in some pathologic events.
  7. What is deposited at the site of cell death?
  8. Metabolic derangements cause what?
    The intercellular accumulation of a number of substances.
  9. Increased physiologic demand or increased tropic stimulus?
    Hyperplasia, hypertrophy
  10. Decreased nutrients or stimulation?
  11. Chronic irritation (chemical or physical)
  12. Reduced oxygen supply, chemical injury, or microbial infection? Acute
    Acute reversible injury
  13. Reduced oxygen supply, chemical injury, or microbial infection? Progressive and severe
    Irreversible injury leading to cell death- necrosis or apoptosis
  14. Reduced oxygen supply, chemical injury, or microbial infection? Mild chronic injury
    Subcellular alterations in various organelles
  15. Induction of adaptation?
    • factors produced by the cell or surrounding cells
    • activation of cell surface receptors and downstream signaling molecules
  16. Requirement for cells to undergo hyperplasia?
    Capable of DNA synthesis and cell division
  17. Two divisions of physiologic hyperplasia?
    • hormonal - increase of the female breast at puberty and uterus during pregnancy
    • compensatory - increase tissue mass after damage or resection. The liver can regenerate. After nephrectomy the other kidney enlarges and makes up for the lose.
  18. Mechanism of hyperplasia?
    • Increase in local production of growth factors, increase in the number of growth factor receptors, or activation of intercellular signaling pathways.
    • -All lead to in increase production of transcription factors leading to cellular proliferation.
  19. Liver stem cells only proliferate if hepatocytes proliferation is compromised.
  20. Pathologic hyperplasia constitutes a fertile soil in which cancerous proliferation may occur.
  21. Causes of Pathologic hyperplasia?
    excessive hormonal stimulation or growth factors acting on a target.
  22. Increased size of cells is due to what?
    Synthesis of more structural components.
  23. Increase or decrease in cellular DNA during hypertrophy?
    Increase do to the arrest of the cell cycle without undergoing mitosis
  24. Cause of hypertrophy?
    Increased functional demand or by specific hormonal stimulation.
  25. Genes induced during CARDIAC hypertrophy?
    • Induction of embryonic genes - Beta myosin in place of alpha myosin.
    • Transcription factors -
    • Growth factors - TGF-B, IGF-1, FGF
    • Vasoactive agents- alpha adrenergic agonists, endothelin-1, angiotensin II.
  26. Atrial natriuretic factor ANF?
    • Secreted by the fetal atrium and ventricle and then by the adult atrium, response to pressure and volume change by regulating salt excretion to regulate volume and pressure.
    • ex. increased atrial pressure due to excess venous return leads to higher levels of ANF excretion and an increase in urine production by the kidneys.
  27. Two types of hypertrophic triggers for the heart.
    • 1. mechanical - stretch
    • 2. trophic- growth factors and vasoactive agents secreted by non myocytes.
  28. When does cardiac failure happen?
    when the muscle reaches it limit for enlargement and is no longer able to compensate.
  29. Common causes of atrophy? physiological and pathological
    • 1. Decreased workload
    • 2. Loss of innervation
    • 3. Diminished blood supply
    • 4. Inadequate nutrition- use of muscle for energy after fat stores are used up.
    • 5. Loss of endocrine stimulation- loss of estrogen after menopause results in atrophy of the endometrium, breast, and vaginal epithelium.
    • 6. aging
    • 7. pressure - enlarged benign tumor can compress and cause atrophy of surrounding tissue.
  30. Atrophied cells may have a diminished function but are not dead.
    can die if blood supply is inadequate for even the atrophied cell.
  31. Function of the ubiquin-proteasome pathway?
    • degradation of cytosolic and nuclear proteins.
    • Proteins are first conjugated to ubiquin then degraded within protease's.
    • Stimulated by glucocorticoids and thyroid hormones
    • Inhibited by insulin.
    • Cytokines such ad TNF are capable of increasing muscle proteolysis in this way.
  32. Metaplasia?
    • reversible change from one cell type to another. May represent an adaptive substitution where one cell type is better suited to withstand an adverse environment.
    • -most common is columnar to squamous, in the respiratory tract in response to chronic irritation. The new cells can survive but the special feature of mucus secretion is lost.
  33. Barret esophogus?
    Esophageal squamous cells are changed to columnar under the influence of refluxed gastric acid.
  34. Myositis ossification?
    Bone formation in muscle after bone fracture
  35. Mechanism of metaplasia?
    • Not a change in the phenotype but reprogramming of the stem cells in the tissue or of undifferentiated mesenchymal cells in connective tissue.
    • BMP's induce chondrogenic or osteogenic expression of stem cells while repressing differentiation to muscle of fat.
  36. effect of influx of calcium into the cell?
    • activates phospholipases that degrade membrane phospholipids
    • activates proteases that breakdown the membrane and cytoskeleton
    • activates ATPase
    • Activates endonucleases
  37. Free radical propigation
    Once induced free radicals cause an autocatalytic chain reaction producing more free radicals
  38. Five processes that will form free radicals
    • Absorption of radiation
    • Enymatic metabolism of chemicals or drugs, CCL4
    • Normal reduction oxidation reactions
    • Transition metals
  39. Three anti-oxidents
    • Vit E
    • Ascorbic acid
    • Glutathione
  40. Free radical scavengers
    • catalase
    • glutathiione
    • peroxidase
    • superoxide dismutase
  41. Increased serum count of AST, ALT, CK, AAlaline phosphate?
    Irreverible cell injury
  42. Necrotic cells stain?
    More Pink
  43. Pyknosis
    Small dense nucleus
  44. karyolysis
    faint, dissolved nucleus
  45. karyorrhexis
    fragmented nucleus
  46. Nucleus of a necrotic cell, Stages?
    • pyknosis
    • karyorrhexis
    • kayyolysis
  47. Coagulative necrosis
    • protein denaturation
    • preservation of cell and framework
    • hypoxic death except brain
    • undergo heterolysis or autolysis
  48. Liquifaction necrosis
    • when heterolysis or autolysis predominates over protein denaturation
    • soft and fluid filled
    • frequently seen in bacterial infection (abscess) and in the brain
  49. Caseous necrosis
    appears soft, friable, and cheesy
  50. Fat necrosis
    • lipase activation in adipose tissue
    • released fatty acids react with calcium to create soaps
    • white chalky areas
  51. hypoxia vs ischemia
    • hypoxia still delivers nutrients for glycolysis
    • ischemia injures faster
  52. Loss of ATP
    • Loss of Na/K pump, influx of Ca water and Na, cell swells
    • Increased glycolysis, decreased pH and glycogen, clumping of chromatin, intracellular release of lysosomal enzymes
    • detachment of ribosomes, loss of protein synthesis
  53. Irreversible injury
    • Pore formation in mitochondrial membrane and diffusion out of calcium and cytochrome C
    • Cytochrome c drives apoptosis
    • increases calcium activates enzymes and proteasses
    • free fatty acids and lysophosphilipids accumulate in the ischemic cell, toxic to membranes
  54. Ischemic re-perfusion injury
    • increased generation of free radicals , incomplete reduction of oxygen by damaged mitochondria or normal anti-oxidase activity is disrupted
    • Blood flow increases local inflammation
    • activation of compliment, bind to IgM in the tissue
  55. Characteristics of apoptosis
    • membrane is not damaged
    • smaller number of cells
    • does not cause inflammation
  56. Physiologic Causes of apoptosis
    • programmed cell death
    • hormone dependent, endometrium
    • maintain a constant cell number
    • harmful self reactive lymphocyte
    • eliminate virus
  57. Pathologic causes of apoptosis
    • Damaged DNA, cell kills itself rather then risk mutation
    • viral infection, hepititis
    • duct abstruction , pancrease
    • Tumor cell death
  58. Apoptotic cell size
    it shrinks, and chromatin condenses
  59. What proteases break down cell proteins in apoptosis
  60. Presentation of what lipophosphate on cell membrane signals for apoptosis by phagocytosis
  61. Two pathways for initiation phase of apoptosis
    extrinsic and intrinsic
  62. extrinsic apoptosis pathway
    • TNF receptor family
    • TNF-1 or FAS ligand
    • enzymtically cleave caspase 8 which starts a caspase cascade
  63. Intrinsic apoptosis pathway
    • mitochondrial permeability is increased
    • death receptors are not involved
    • BCL-2 and BCL-x are anti-apoptotic
    • When cells are deprived of survival signal bcl2 is lost and replaced by back, bax, and bim; pro-apoptotic
    • cytochrom c is released into the cytoplasm and binds to Apaf-1 and trigers caspase 9.
  64. Execution pathway of apooptosis
    • caspase 6 and 3
    • cleave all types of protein
  65. what does caspase stand for
    • c= cysteine for the active site
    • aspase = cleaves after aspartic acid
  66. Four examples of apoptosis
    • growth factor deprivation, intrinsic path
    • DNA damage, radiation or chemo, p53 accumulates, arrests cell in G1 phase, p53 will act as a transcription factor for bax and bak and Apaf-1, p53 can be mutated in some cancers
    • TNF; Fas(cd95)
    • cytotoxic T lymphocyte; recognize forign material in host cell and secrete perforin, allows entrance to ganzyme B, activates caspase, can also ecpless FasL
  67. Lipofusion
    undigested product
  68. What leads to hypertrophy of the ER
    chronic ingestion of some drugs, leads to increased tolerance
  69. Size of mitochondria in alcoholic liver
  70. Oncocytomas
    benign tumor consisting of cells with large mitochondria
  71. A1-antitypsin disease
    • antitrypsin accumulates in the hepatocytes that produce it
    • mutations slow folding , partly folded enzymes accumulate in the ER
  72. Six causes of fatty liver
    • excessive entry of free fatty acids; starvation, corticosteroid therapy
    • enhanced fatty acid synthesis
    • increases esterfication of fatty acids to triglycerides
    • decreased apoprotein synthesis; starvation
    • impaired lipoprotein secretion; alcohol
  73. Disease that is due to a mutation of a cholesterol catabolism enzyme
    Niemann-pick type C
  74. Amyloidosis
    accumulation of protein in the extracellular spaces
  75. aggregated intermediate filaments
    mallory bodies
  76. Protein droplets
    Russell bodies
  77. Anthracosis
    exogenous pigment in pulmonary macrophages
  78. causes of hemosiderin
    • increased dietary iron intake; primary hemochromotosis
    • impaired utilization; thalassemia
    • chronic transfusions
  79. Four main sources of calcium in metastatic calcification
    • increased secretion of parathyroid hormone; parathyroid tumor or ectopic parathyroid hormone secreting tumor
    • Destruction of bone tissue; cancer, immobilization
    • Vit D disorder; intoxication
    • Renal failure; causes secondary hyperparathyroidism due to phosphate retention.
  80. Diminished metabolic functions in cell aging, 6
    • reduced ATP generation
    • diminished protein synthesis
    • decreased capacity for nutrient uptake
    • increased DNA damage, reduced repair
    • accumulation of oxidative damage
    • accumulation of glyation end products causing cross linking
  81. Three mechanisms for cellular aging.
    • replicative senescence; limited number of replications, telomere shortening-lose a little piece with every replication. telemerease activation in cancer causes cell to keep dividing ( inactivates internal clock)
    • genes that influence aging; decreased IGF-1 signaling can lead to prolonged life span
    • progressive accumulation of metabolic and genetic damage from exogenous influence,
  82. Disease that shows premature aging
    Werner syndrom, defect in DNA helicase causes rapid accumulation of DNA damage
Card Set
Robins chapter 1