Patho unit 2 ch 9

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jnikrap
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Patho unit 2 ch 9
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2013-09-18 17:23:33
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Patho unit 2ch 9
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  1. Neoplasm (Tumor)
    New and abnormal development of cells that are unresponsive to normal growth control mechanisms
  2. What are the two types of neoplasms?
    • Benign tumor: Cells do not invade the surrounding tissue
    • Malignant tumor: They invade the surrounding tissues and they have the ability to travel to, and proliferate at distant sites (metastasis)
  3. Benign Neoplasms
    • Slow growth
    • Encapsulated
    • Non-invasive
    • Well differentiated
    • Low mitotic rate
    • Do not metastasize
  4. Malignant Neoplasms
    • Rapid Growth
    • Non-encapsulated 
    • Invade local structures and tissues
    • Poorly differentiated
    • High mitotic rate
    • Metastasize
  5. Examples of Malignant neoplasms
    • Carcinomas: Epithelial tissue-Adenocarcinoma, squamous cell carcinoma
    • Sarcomas: Connective tissue-Chondrosarcoma, osteosarcoma
    • Lymphosarcomas: Lymphatic tissue
    • Retinoblastoma and neuroblastoma
  6. Carcinoma in situ (CIS):
    Stage 0
    • Pre-invasive epithelial malignant tumors
    • The neoplasm is localized in the epithelium and has not broken through the basement membrane and invaded surrounding tissue
  7. Transformation
    • Process by which a normal cell becomes a cancer cell (malignant growth)
    • Not a single event
  8. Anaplasia
    • Loss of differentiation (de-differentiation) immature cells 
    • Loss of organization
  9. Histological  Features of Cancer Cells
    • Bizarre Nuclei: Cells don't go through normal cell division, or are rapidly dividing
    • Bizarre cell shape and size
    • Invasion of the basement membrane
    • De-differentiation: i.e. more like embryonic cells
    • Cellular or extracellular accumulations: e.g. "mucus lakes" in lung cancer
    • Necrotic debris
  10. Abnormal Gene Expression in Cancer Cells
    • Turn in genes which :
    • guide the cell through the cell cycle/cell division (violate checkpoints)
    • Bring blood vessels to the cell (angiogenesis)
    • Helps the cancer cell move to places it doesn't belong 
    •   -dissolve connective tissue barriers
    •   -move into and out of blood vessels
    • Collectively, these are called oncogenes ("cancer genes")
  11. Tumor cell Markers (TCM)
    • Biological markers produced by cancer cells:
    •   -Any kind of cellular product could be a tumor marker- Hormones, antibodies, enzymes
    •   An antigen found on a cancer cell membrane-Tumor specific antigen
    • An alteration of the genes or chromosomes in the nucleus
  12. Tumor marker examples:
    Hormones
    • "Ectopic" hormone production is the production of hormones by tumors of non-endocrine origin
    • ACTH, HCG, HGH, thyroid-stimulating hormone, epinephrine and norepinephrine from the adrenal medulla
  13. Tumor Marker Examples:
    Enzymes
    • Cancers do not produce new or unique enzymes; instead we find the abnormal levels of normal enzymes
    • Usually only detected in the blood when the tumor is very large or metastasis has occurred
  14. Tumor Marker Examples:
    Antibodies
    produced by some cancers (e.g. multiple myoloma)
  15. Tumor Marker Examples:
    Tumor-specific antigens (TSA's)
    • cancer cells express "non-self" antigens
    • These TSA's "fly" like a flag
    •   -Markers from the surface of their cell membranes
  16. Tumor Marker Examples:
    Viral Tumor-specific antigens
    produced and expressed by virally-transformed cells
  17. Tumor Marker Examples:
    Oncofetal Tumor-Specific antigens
    Expressed by cells during embryonic development but are absent or low in normal adult cells
  18. Tumor Marker Examples:
    Protein Tumor-specific Antigens
    • Function in proliferation, enzymatic processes, as receptors, and cellular structures 
    •   -Prostate-specific antigen (PSA)
    •   -PSA is a glycoprotein produced by the prostate whose values are related to prostate mass
    •   -it is therefore a tumor cell marker ( TCM) used as a screening test for prostate cancer.
  19. Paraneoplastic Syndromes
    • Signs and symptoms unrelated to the local effects/presence of the neoplasm
    • Caused by substances released from the tumor or an immune response to the tumor
    • Examples:
    •   -Hypercalcemia in breast and renal carcinomas from PTH-related protein
    •   -
  20. Anchorage-independence
    • Ability to mitotically divide without being bound to other cells 
    • continued growth even when unattached from orriginal tissue
  21. Autonomy
    • The cancer cells independence from normal cellular controls 
    • Cell cycle control, repair, cell growth, differentiation factors, and growth factor receptors
  22. Proto-oncogenes
    Unaltered, normal healthy alleles of genes that control/regulate cellular growth and differentiation
  23. Oncogene
    is a proto-oncogene that has been altered (mutated) by carcinogenic agent
  24. Tumor-suppressor genes (anti-oncogenes)
    • Encode for proteins that inhibit cell division
    • Cancer can occur due to the activation of oncogenes or the inactivation of tumor-suppressor genes.
  25. P53 (Tumor-Suppressor) Gene Mutations
    • Normally, if cells are exposed to hypoxic environment, p53 is activated to produce the p53 protein
    • The p53 protein will activate apoptosis 
    • In many cancers, the p53 gene is mutated, allowing the abnormal proliferation of cells
  26. Contributors to cancer Growth:
    Autocrine stimulation
    Cancers acquire the ability to secrete and respond to their own growth factors
  27. Contributors to cancer Growth:
    Increased expression of the growth-factor receptors
    • Gene amplification allows cancer cells to create numerous copies of genes and expression of gene products 
    •   -HER2/neu in breast cancers
    •   -bcr/abl receptor tyrosine kinase in CML
  28. Contributors to cancer Growth:
    Immortality
    • Normally, the only cells in the body that are immortal are stem cells
    • other cells can only divide a given number of times 
    • Telomeres are protective end-caps of chromosomes, maintained by telomerase
    • As the telomeres are lost, a cell loses its ability to divide
    • cancer cells can activate telomerase
  29. Contributors to cancer Growth:
    Angiogenesis
    • Physiological process contributing to the growth of new blood vessels 
    • through secretion of angiogenic factors, cancers can continue to enlarge
  30. Metastasis
    • The spread of cancer from the initial site of neoplasm development to distance tissues of the body
    • localized neoplasms are much easier to treat 
    • Metastasis, similar to the initial cancer development, is a sequence of events
  31. Metastasis:
    Detachment
    cells break loose from their original location
  32. Metastasis:
    Invation
    • Cellular proliferation
    • Barrier destruction by lytic enzymes
    •   -Secretion of protease activators
    • Down-regulation of cell adhesion molecules 
    •   -Desmosomes, hemidesmosomes, and tight junctions 
    • Increased motility
    •   -secretion of autocrine motility factors
  33. Metastasis:
    Intravasation
    • passage into vessels (blood or lymph)
    • Lymphatic spread
    • blood dessemination 
    •   -
  34. Metastasis:
    Adherence in favorable sites
    • Metastatic cancer cells can spread diffusely throughout the body, but certain types of cancerous cells have a preference for specific organs
    • This is often referred to as " organ tropism"
    •   -Factors encouraging colonization
    •     -Growth factors from target organ
    •     -Hormones
    •     -Presence of tumor receptors on the tissue
    •     -Route
  35. Metastasis:
    Extravasation
    Leaves blood vessels and invades secondary tissue
  36. Metastasis:
    Colonization
    establishment in new tissue
  37. Metastasis:
    Sequence
    • Local transformation and extension 
    • Motility
    • Angiogenesis
    • Invasion
    • Intravasation (blood/lymph penetration)
    • Adherence at a favorable site
    • Extravasation
    • Colonization
  38. Cancer Staging
    • Stage 1: Neoplastic cells in original site- Well-differentiated cells
    • Stage 2: Metastatic cell in original site and local lymphatics- Moderately-differentiated cells
    • Stage 3: Cells in original site and distant lymphatics- Poorly differentiated cells
    • Stage 4: Metastatic cells are found in many body areas- very poorly-differentiated cells
  39. Systemic Effects of Neoplasms
    • Vessel invasion- bleeding
    • Lymphatic invasion- lymphedema
    • Nerve invasion- pain, numbness, tingling
    • Bone marrow invasion- pancytopenia, infection, and bleeding
    • Liver invasion- hepatic insufficiency
  40. Clinical Manifestations:
    Pain
    • Little or no pain is associated with early malignancy
    • Pain is influenced greatly by fear, anxiety, sleep loss, and psychological responses
    • Pressure on sensitive structures, obstruction, severe stretching of tissues- all cause pain
    • Patients that have terminal cancer will usually manifest severe pain
    •   -Bone metastases (periosteal irritation, medullary pressure and/or fractures)
  41. Clinical Manifestations:
    Fatigue
    • Due to:
    •   -Sleep disturbance
    •   -Biochemical changes to treatment
    •   -Diminished activity level
    •   -Nutritional status
    • Muscle tone loss can be due to lack of activity and/or circulating necrosis factors
  42. Clinical Manifestations:
    Anemia
    • Reduction in red blood cell numbers
    • Causes
    •   -chronic bleeding
    •   -Malnutrition
    •   -therapies
    •   -Malignancy in blood-forming organs
    • Malignancy of the bone marrow can also cause leukopenia and thromboycytopenia
  43. Clinical Manifestations:
    Infection
    • This is the most common event leading to the demise of patient with malignancy
    • Reduction in immunologic functions due to treatment regimens
    • Poor wound care
    • Comprised patient care
  44. Clinical Manifestations:
    Cachexial Syndrome
    • State of ill health, wasting, emaciation and decreased quality of life
    • Symptoms
    •   -Reduced sweet, sour, and salty sensation
    •   -depression of appetite (early filling response)
    •   -Weight loss and asthenia (marked weakness)
    •   -Altered metabolism (increased BMR)
    •   -Cachexia and anorexia are present in 80% of cancer deaths
  45. Cancer Treatments
    Chemotherapy
    • intended to destroy cells that are in a stage of vulnerability 
    •   -Mitotically active cells are very vulnerable
    • The chemotherapy must eliminate enough cells to allow the immune system to destroy the others
    • Usually a cocktail of drugs
    • Molecular-era anti cancer drugs
    • "Targeted therapy"
    •   -Enzyme inhibitors
    •   -monoclonal antibodies
    •     -Directed at a specific tumor antigen
  46. Cancer Treatments:
    Radiation
    • Damages the DNA of the rapidly dividing neoplastic cells
    • General and targeted radiation therapy
  47. Cancer Treatments:
    Excisional, Debulking, Palliative
    • useful when the tumor is accessible and has not passed beyond stage 3 (regional lymph nodes) 
    • The tumor and any affected lymph nodes must both be removed
    • Surgery decreases the total number of cancer cells, giving normal immune mechanisms a fighting chance
    • Palliative surgery can relieve symptoms of malignancy

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