Download BHS 116.3 –Physiology III Date: 4/19/2013, 2nd hour Notetaker

BHS 116.3 –Physiology III
Notetaker: Shruti Patel
Date: 4/19/2013, 2nd hour
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Nomenclature
 Neoplasia = new growth
o Tumor (2 types)
 Benign tumor
o Localized and does not spread
o Will be removed and patient will survive without any issues
o Most benign tumors end in –oma (ie. fibroma)
 Malignant (cancerous) tumor
o Lesion can spread to local or distant tissues (metastatic tissue—spreading through the
blood or lymphatic tissue to another tissue)
o 2 main types
 Sarcomas (mesenchymal origin)
 Carcinoma (epithelial origin)
Cancer Incidence
 Prostate cancer found most frequently in males
 Breast cancer found most frequently in females
 2nd most common incidence: lung cancer in both male and female
Cancer Deaths
 Lung cancer is the biggest cause of deaths in both males and females
o Usually by the time lung cancer is detected, it is a big tumor and has spread to other
tissues
 Even though prostate cancer and breast cancer is much more prevalent in males and females,
respectively, it is not the leading cause of death because we have much better and earlier
detection systems for prostate and breast cancer.
Changes in Female Cancer Rates
 Purple line- incidence of lung cancer rate (it has been increasing since the mid 60s---this
coincides when women started getting into the workforce—they had more rights and they
started smoking more, so more incidence of lung cancer)
 Elevation of lung cancer and decline in breast and uterine cancers
Changes in Male Cancer Rates
 Started well before—men were the major players in the industrial age. They were working in the
coal mines and the major industrial plants with the toxic pollutants in the air. They were
smoking much earlier than women.
 Deaths from lung cancer AND prostate cancer have started to decline—because of early
detection, early screening, and better treatment options.
Genetics vs. Environment
 Many cancers have both genetic and environmental influences.
 Chart compares death rates of different types of cancers and normalize it to California whites
o Compare to Japanese males
 Their death rate from stomach and liver cancer is much higher.
 Death rate from colon and prostate cancer is much lower.
o Compare to Male Japanese immigrants that moved to California (new environment)
BHS 116.3 –Physiology III
Notetaker: Shruti Patel
o
Date: 4/19/2013, 2nd hour
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o New environment is altering death rate from certain cancers.
o Stomach and prostate are still well above California white male but it is decline
o Colon and prostate cancer is going up, however.
Compare to Sons of Japanese immigrants
o Elevated stomach and liver cancer death rates
o Environmental influence on prostate and colon cancer—much more similar to
the death rates of California whites
Diagnostic Methods for Neoplasia
 History and physical examination
o Many times, people with cancer will suffer from sudden weight loss, fatigue, and pain
 Weight loss from tumor is because tumor tissue is very metabolic, so tumors will
use up much of your body’s energy stores (break down fat and even protein
stores)
 Radiographic techniques
o X-rays, CT (Computed Tomagraphy) scans, MRIs ( Magnetic Resonance Imaging),
Mammography, and ultrasonagraphy (ultrasound)
 Laboratory Analyses
o Blood exams—Anemia, enzyme abnormalities, hematuria, or positive stool occult blood
o Testing for specific genes may indicate increased risk for certain cancers (gene specific
tumors). For example, BRCA-1 for breast cancer.
 Cytology
o Sample cells (Pap smear, fine needle aspiration)
 Tissue Biopsy and Surgery
o Endoscopic techniques (colonoscopy)
 Autopsy
o Many people have tumors growing and they never show any symptoms.
** We constantly have cancer floating around in our body, but our immune system is very good at
keeping it under control so it never manifested as cancer.
Benign vs. Malignant
 Benign tumors
o Well-differentiated
o Slow growing (slow, steady, progressive)
o No local invasion (usually a well demarcated tumor)
o Do not spread to local or distant tissue ( not metastatic)
 Malignant tumors
o Lack complete differentiation ( in muscle tissue, the cells will look completely different
from muscle cells already present)
o Growth is erratic (not a continuous and progressive type of growth as with benign
tumor)
o Lot of local invasion
o Metastasis (will get into blood and lymph, migrate to distant tissues, and start growing
into tumor tissues)
Tumors of the Myometrium
 Same organ- two completely different tumors
BHS 116.3 –Physiology III
Notetaker: Shruti Patel
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Date: 4/19/2013, 2nd hour
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Benign (Leiomyoma—“smooth muscle tumor”)
o Smaller
o Well demarcated (borders)
o Slow growing, progressive
o Not invading any neighboring tissue
o Not metastatic
o Histologically: look like smooth muscle cell (well differentiated)
Malignant (leiomyosarcoma)
o Larger
o Poorly demarcated
o Metastatic
o Centers become necrotic because blood supply is only going to be able to get nutrients
to the outer cells of the tumor
o Locally invading
o Histologically: do not look like smooth muscle cells (poorly differentiated)
Classification of Neoplasms
1.) Connective tissue derived tumors
 General Rule
o Malignant—“sarcoma”
o Benign—“-oma”
 Sarcomas account for 5% of cancers found in the body.
2.) Epithelial tissue derived tumors
 General Rule
o Malignant—“carcinoma”
o Benign—“-oma”
o Glandular epithelial tissue derived tumors—“adenoma”
 Carcinomas account for about 85% of cancers found in the body.
3.) Hematopoietic and immune system tissue
 Do not follow the normal rule of thumb
 Leukemias and lymphomas account for about 0.5% of cancers found in the body.
4.) Nervous system tissue
 Different names: “blastoma”
 Nervous system neoplasms account for about 5% of cancers found in the body.
**Do NOT have to memorize these lists but KNOW the general nomenclature.
Adenoma of Thyroid Gland & Squamous Cell Carcinoma
 Benign
o Cuboidal thyroid follicular cells (they look like normal thyroid cells)
o Well differentiated
 Malignant
BHS 116.3 –Physiology III
Notetaker: Shruti Patel
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Date: 4/19/2013, 2nd hour
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Lacks differentiation (atypical dysplastic cells)
Glands are irregular
Pleomorphic cells (many different shapes and sizes) and nuclei with mitotic figures
Anaplastic Tumor Cells
 Pleomorphic cells
 Undifferentiated
 Hyperchromatic and polymorphic nuclei
 Giant cells
 Advanced cancer cells
 Some tumors will have tripolar mitotic, so DNA has three poles, which is pulling it in
three different directions.
Rate of Growth
 Fibroadenoma of the Breast
o Encapsulated by fibrous capsule
 Due to slow growing
 Invasive Ductal Carcinoma of the Breast
o No capsule
Metastases to the lungs and liver
 Liver and the lungs are the most common site for metastases, especially those that spread via
the blood.
 Liver is a highly vascularized tissue and all the blood in the body goes through the liver and gets
processed.
Metastases
 Carcinomas are more proliferative through the lymphatic system.
 Sarcomas are more likely to spread through the blood (hematogenous spread).
 Both tumor types can spread through either route, however.
Angiogenesis
 Once most tumors get beyond a diameter of 2 mm, they are going to require more blood supply
because they will not have sufficient nutrients—so they undergo vascularization.
 Tumors will secrete VEGF and bFGF, which will stimulate new blood vessel growth.
 Tumor vessels are very leaky (so not a very efficient delivery of nutrients, but it is still better
than not having ANY blood delivered to them)
What makes a tumor cell metastatic?
 Subclones within a benign tumor possess a combination of gene products.
 Abnormalities occur in 1 or many of the benign tumor cells giving the tumor a presdisposition
for metastasis (metastatic signature).
Metastatic Cascade
 Two phases:
o Invasion of extracellular matrix
BHS 116.3 –Physiology III
Notetaker: Shruti Patel
Date: 4/19/2013, 2nd hour
Page5
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Break through the basement membrane of the tissue of origin, invade the ECM,
get through interstitial tissue, and get to the blood vessel
o Vascular dissemination
 travel through the blood, evade detection of the immune system, bind to
endothelial cell at a distant site, migrate out of the blood vessel, and set up in a
new tissue
Most metastatic cells do not survive.
Invasion
 Detachment
o Detachment of adjacent cells, so we lose E-cadherin function and expression so the cells
are no longer attached to each other.
 Attachment to matrix
o They start expressing fibronectin and laminin receptors so they can start bind those
extracellular matrix proteins.
 Degrade matrix
o Increased expression and secretion of metalloproteases—break up extracellular matrix
proteins so this is helping to now clear the path for those malignant cells to migrate
through.
 Migrate
o The breakdown peptides serve as chemoattractants—so the degraded ECM proteins can
act as autocrine motility factors.
Vascular Dissemination
 Once it gets into the circulation, its going to be vulnerable to our immune system.
 Those that make it through, they will start binding to endothelial wall and start forming masses
there.
 They will go through extravasation through the basement membrane
 They will undergo angiogenesis
 They will continue to proliferate and growing into larger masses at a distant site
Tumor Progression
 Look at a lung carcinoma:
o Start out with normal cell
o Something happens to convert it to single cancer cell
o It has to go through about 30 doublings, which would leave us with 100 million cell mass
before we can even detect it.
o Each of these cells will have different characteristics but they all make up one mass.
Different characteristics give the tumor of variety of capabilities. Some cells are going to
non-antigenic (will protect from immune system), some cells will be invasive and go
through the connective tissue, some will require fewer growth factors.
o If we let it go another 10 doublings, it reaches its maximum mass.
Clicker Question:
Which of the following is a malignant tumor? Fibroma, Chondrosarcoma, lipoma, rhabdomyoma