Tuesday, August 7, 2012

Pathophysiology - Neoplasia / Cancer

Neoplasia / Cancer
  • Results from a process of altered cell differentiation and growth
  • Lacks normal regulatory control over cell growth and division
Oncology – study of tumor and their treatment
Cancer in situ – localized pre-invasive lesion depending on location

Tissue renewal and repair
  • Cell proliferation
    • Or the process of cell division
    • Inherent adoptive mechanism for replacing body cells when old cells die or additional cells are needed
    • 2 Major Categories of Cells
      • Gametes (Ovum/Sperm)
      • Somatic cells
  • Cell differentiation
    • Process of specialization whereby new cells acquire the structure and function of the cells they replace
    • Fertilized ovum
      • Where all of the different cell types of the body originate
Tumor / Neoplasm
  • Swelling caused by inflammation or trauma
Classification
  • Benign
    • Contains well-differentiated cells that are clustered together in a single mass which resembles cells of tissue origin
    • Presence of well-defined fibrous capsule (facilitates easy surgical removal, no metastasis)
  • Malignant
    • Anaplasia
    • Lack of cell differentiation and characteristic (mutation occurs early in the process of differentiation)
    • Ability to break loose, enters circulatory and lymphatic system and form secondary malignant tumors on other sites (metastasis)
    • Usually causes suffering and death
    • Rapid growth and spread (outnumber normal cells), non-functional, long lived
    • Compresses blood vessels and decreases blood supply resulting to ischemia and tissue necrosis
    • Rob normal cells of essential nutrients and liberate enzymes and toxins that destroy tumor and normal cells
    • Lots of cohesiveness and adhesion, impaired cell to cell communication
    • Crablike projections in surrounding tissues making removal difficult
    • 2 categories of cancer
      • Solid tumors – confined to specific tissue or organ
      • Hematologic cancer – involves blood forming cells
3 Factors Affecting Tumor Growth
  1. Number of cells that are actively dividing or moving thru cell cycle
  2. Duration of cell cycle
  3. Number of cells lost and number of cells produced
  • Growth fraction – ratio of dividing cells to resting cells in a tissue mass
  • Doubling time – length of time it takes for fatal mass of cells in a tumor to double, continues until there is a decreased blood supply and nutrients
  • Detection – doubled 30 times, contains 1 billion cells
Oncogenesis – genetic mechanism wherein normal cells are transformed into cancer cells

2 Kinds of Genes
  • Proto-oncogenes – growth promoting regulatory gene
  • Anti – oncogenes – growth inhibiting regulatory genes; inhibits proliferation of cancer cells
Contributing Factors
  • Hereditary – family history of cancer
  • Carcinogen – agents capable of causing cancer
  • Radiation – cancer of skin and blood (leukemia)
    • Atomic bomb survivors, diagnostically exposed patients
    • Industrial workers, scientists
    • Ultra Violet Rays (UVR) – skin cancer
    • Radon – radioactive gas formed from uranium decay (uranium miners)
  • Oncogenic viruses
    • Papillomavirus, human t-cell leukemia virus, Epstein-barr virus, hepa-B virus, herpes simplex 2
  • Immunologic defects
    • Play a central role against development of tumor
Antineoplastic Agents
  • Alkylating agents
    • Non-cell cycle specific (affect cell even in resting phase)
    • Action: binds with cellular DNA, disrupting cellular mechanism
    • Indication: slow-growing Cancer
    • Drugs that protect cells from side effects of cisplastin
      • Amifestine (Ethyol)
        • Preserves healthy cells from toxic effects
        • Scavenger of free radicals
        • Given within 30 minutes after starting cisplastin therapy (timing is important)
        • Side Effects: nausea and vomiting
      • Mesna (mesnex)
        • Reduces incidence of haemorrhagic cystitis
        • Side effects: nausea and vomiting
  • Antimetabolites
    • Replace needed metabolites and prevent normal cell function
    • Used as a combination therapy to prevent development of resistance
    • Action: inhibits DNA production in cells that depend on certain natural metabolites
    • Indication: rapidly dividing cells
    • Drugs that protect cells against metabolites
      • Leocovorin (Welleovorin)
        • Active form of folic acid used to “rescue” normal cells from adverse effects of methotrexate
  • Antineoplastic antibiotics
    • Cell cycle specific
    • Action: interferes, disrupts cellular DNA synthesis
    • Cardioprotective antineoplastic drug:
    • Dexrazoxane (Zinecard)
      • Powerful intracellular chelating agent, interferes with cardiotoxic effects of doxorubicin
      • Given 30 minutes before doxorubicin
  • Mitotic inhibitors
    • Cell cycle specific
    • Action: kill cells as process of mitosis begins, inhibit DNA synthesis
    • Contraindications: allergy, pregnancy, lactation
    • Caution: bone suppression, renal/hepatic dysfunction, GI ulcerations
    • Adverse Effects: bone marrow suppression, leukopenia, thrombocytopenia, anemia, pancytopenia, nausea and vomiting, anorexia, diarrhea, hepatic/renal toxicity
  • Hormones and hormone modulators
    • Receptor-site specific / hormone specific
    • Action: block stimulation of growing cells that are sensitive to the presence of that hormone
    • Indications: breast cancer in post-menopausal women or without ovarian function
    • Contraindications: allergy, preganancy, lactation, hypercalcemia if used with toremifene
    • Adverse effects: menopausal effects (estrogen is blocked or inhibited), hot flashes, vaginal spotting and dryness, moodiness, depression, GI toxicity, hepatic dysfunction, hypercalcemia
    • Interactions: anticoagulants: increased risk of bleeding

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