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Neoplasia

Pathophysiology of tumors and cancer

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The following pictures and descriptions were found at:

www-medlib.med.utah.edu/WebPath/NEOHTML

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Cells normally differentiate, grow, mature and divide.

These are regulated processes, balanced in a healthy system such that cell birth is nearly equal to cell death

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Regulation of cell division includes:

1. Signaling by biochemicals released from one cell that interact with other cells

growth factors or cytokines

2. Other external factors , such as contact inhibition

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3. Genes and internal factors that promote and regulate cell division

genes and chromosomal factors - telomeres

braking proteins – Rb proteins

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A tumor cell’s growth is autonomous – independent of controls

Neoplasm – a type of tumor – group of neoplasic cells

Study of tumors is oncology from Greek for tumor

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Two major types: Benign and Malignant (table 6.2)

Benign: grow slowly

low mitotic rate

well differentiated

not invasive; well-defined borders

remain localized; do not metastasize

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Malignant – cancer – from Latin for crab

autonomy and anaplasia

Grow rapidly ; high mitotic index, poorly differentiated; do not have a capsule; invade surrounding structures; can metastasize from the primary to a secondary site (metastasis).

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Malignant tumors – use embryonic origin of tissue

Carcinomas come from ectoderm and

Endoderm - epithelial and glandular tissue

Sarcomas arise from mesoderm

connective tissue, muscle, nerve and endothelial tissues

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Genetic Basis of cancer

• Older theory : Initiation-promotion-progression

• “Multi-hit” hypothesis

• Cancer is a disease of aging

• Clonal proliferation

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Viral causes of cancer:

viruses assoc. with about 15 % of cancers world wide – us. Cervix or liver

hepatitis B or C in chronic form

Human papilloma virus

spread through sexual contact

HPV integrates into DNA and uses viral oncogenes

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Epstein-Barr and Kaposi sarcoma

both herpes viruses

Human T cell leukemia-lymphoma virus

blood transfusions, needles, sex and breast feeding

infections may be asymptomatic

may have high incidence, but low #’s of cancer

cofactors increase the risk of cancer

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Bacterial causes of Cancer

Helicobacter pylori infects >1/2 world’s population

assoc. with B cell lymphomas of the stomach

treatment with antibiotics can cause regression of lymphoma

Tumors arise in MALT -MALTomas

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Environmental factors

• Tobacco use

• Diet

• Alcohol use

• Sexual and reproductive behavior

• Air pollution

• Occupation hazards – asbestos

• UV radiation and other radiation

• hormones

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Gene-Environment Interactions:

Exposure to environmental agents can cause increased risk of cancer

cancer in lab animals – carcinogens

Comparisons of populations

genetics vs. lifestyle

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Diagnosis:

screening procedures and blood tests:

Tumor markers

substances on plasma membranes

in blood, spinal fluid or urine

hormones, genes antigens or antibodies

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Tumor spread

• Local spread– Cellular multiplication

• Function of generation time• Growth if cell reproduction > cell death

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Stages of cancer spread:

Stage 1 – confined to site of origin

Stage 2- cancer is locally invasive

Stage 3 – cancer has spread to regional structures

Stage 4- cancer has spread to distant sites

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Patterns of spread: Metastasis

• Direct or continuous extension

• By lymphatics or blood stream– As clumps or as single cells– Lymphatics most common

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Clinical manifestations of Cancer

• Pain– Usually not in early stages– 60 – 80 % of terminally ill– Psychogenic, cultural and physiologic

components– Due to pressure, obstruction, stretching,

tissue damage or inflammation

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Clinical manifestations of Cancer

Fatiguesleep disturbancesbiochemical changesloss of muscle function

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Clinical manifestations of Cancer

Cachexia – wastinganorexiaearly satietyweight lossanemiamarked weakness taste alterationsaltered metabolism

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Clinical manifestations of Cancer

Anemia

chronic bleeding

malnutrition

medical therapies

malignancy in blood forming organs

Administer erythropoietin

Clinical manifestations of Cancer

• Infection

• most significant cause of complications and death

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Cancer Treatment• Chemotherapy

– Cytotoxic drugs + body defenses

• Combination chemotherapy

• Radiation

• Surgery

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Side effects of treatment• Gastrointestinal tract:

– Oral ulcers– Malabsorption– Diarrhea– Vomiting – caused by effects on CNS

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Side effects of treatmentBone marrow:

chemo and radiation suppress bone marrow

decrease in red blood cells, white blood cells and platelets

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Side effects of treatmentHair and skin:

alopeciaskin breakdown and dryness

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Side effects of treatmentReproductive tract:

affects gametespremature menopausealso due to damage of hypothalamus

and/or pituitarysperm or embryo bank