Altered Cellular Proliferation and Differentiation PDF

Altered cellular proliferation and differentiation Rayan Al Dabbah RN, MScN NSG 0159  Introduction The cell is the smallest independent unit of the body Cells are often referred to as the building blocks of the body Cellular adaptation...

Altered cellular proliferation and differentiation Rayan Al Dabbah RN, MScN NSG 0159  Introduction The cell is the smallest independent unit of the body Cells are often referred to as the building blocks of the body Cellular adaptation to stress, injury or disease can directly impact an individual’s health The Impact of Cancer on the Cell Proliferation Generation of new daughter cells divided from progenitor (parent cells) Differentiation Orderly process of cellular maturation to achieve a specific function Stem cells Highly undifferentiated units  Cellular replication Review Mitosis – is the division and proliferation of all non germ cells Makes identical cells to replace what is being lost (skin, mucosa, muscle extra) Mitosis: The Amazing Cell Process that Uses Divisio n to Multiply! (Updated) – YouTube (8.5 min)  Cellular replication Review Meiosis – the process of dividing germ cells, which result in an ovum or sperm a type of cell division that results in four daughter cells each with half the number of chromosomes of the parent cell, the production of gametes Meiosis (Updated) – YouTube (7.5min) Mitosis vs Meiosis  Altered Cellular Proliferation and Differentiation Cellular proliferation and differentiation is under the control of genes. Neoplastic cells ignore genetic controls resulting in: Over - proliferation of cells Example: a tumor in tissues and or organs Lack of differentiation of cells Example: Acute myelogenous leukemia (AML) is a cancer that starts in blood stem cells which do not differentiate, resulting in blast cells (blasts), which are immature blood cells.  The impact of cancer on the cell This unit will focus on the over-proliferation (excessive production) of cells and or the loss differentiation (specialization) of cells Which results in the crowding of cellular spaces within the body Example: leukemia – immature WBCs The impact of cancer on the cell Genes are responsible for cellular proliferation and differentiation – carry’s the cells code If the gene malfunctions due to change in nutrients, from stimuli in the external environment or improper coding sequence – can cause over proliferation (excessive growth) Neoplasm – any abnormal growth resulting in new tissue  Benign vs Malignant Benign – a growth that remains localized and closely resembles the tissue of origin Malignant – growths that are invasive, destructive, can spread to other site and do not resemble the tissue of origin The impact of cancer on the cell Cancer – term used to describe highly invasive and destructive neoplasm Ignores genetic controls – do not turn off and die (apoptosis) Results in: Uncontrolled growth of cells Lack of differentiation Rapidly growing cells are at increased risk of developing into neoplasms Example: epithelial, gastric and blood cells  Carcinogenesis Mutations of DNA and therefore genes are heavily implicated in carcinogenesis Carcinogenesis – the development of cancerous neoplasms Two types of gene mutations that impact cell growth and division: 1. Inherited 1. 5% of cancers 2. Acquired 1. 95% of cancers Inherited Cancer 1. Inherited – gene mutations that are present within the egg or sperm cell Copy of a cancerous gene from one of the parents Activated by cellular changes which can occur due to environmental stimuli  Acquired Cancer 2. Acquired – gene mutation that occurs after conception NOT present in the egg or sperm cells 1. Environment exposure (smoking) 2. Carcinogenic chemicals exposure 3. Ionizing radiation 4. Ultra violet rays 5. Viruses (Human papillomavirus (HPV) – cervical cancer) Carcinogens and cancer development  Genetic mutations DNA is constantly being damaged by the environment Everyone has mutator genes which work to repair and maintain the DNA sequence If the mutator genes cannot repair the DNA – genes can become altered Two categories of genes that when altered can lead to development of neoplasms 1. Oncogenes 2. Tumor suppressor genes  Genetic mutations Oncogenes – are genes that promote unregulated cellular growth and development Can also inhibit cell death (apoptosis) Activation of these genes can occur spontaneously NOT in reproductive cells (ova or sperm) Results in: Over-proliferation Lack of differentiation  Gene Mutations Oncogenes come from proto-oncogenes which play a vital role in regulating cellular function Three ways to “mutate” proto-oncogenes into oncogenes 1. Point mutation 2. Translocation 3. Gene amplification  Genetic mutation 1. Point mutation 1. Damage to a single base pair in the DNA strand that results in altered unregulated proteins in body cells – new excessive cellular growth 2. Can occur due to exposure from the environmental cause (smoking) or spontaneously  Genetic mutations 2. Translocation 1. When the chromosome breaks, relocated and unites with another chromosome – changing the sequencing – excessive protein production  Genetic mutations 3. Gene amplification – the rapid replication of genes due to changes in a chromosome 1. Overproduction of gene products – excessive protein production Gene BRCA 1 – presence linked to development of breast cancer A woman with this gene has an 80% chance of developing breast cancer by 65 years of age Genetic testing can allow for early detection through increased screening processes  Genetic mutations Tumor suppression Tumor suppressor genes regulate the rate at which cells divide and die Apoptosis – cells are programed to die at a specific time by the genes, so the optimal number of cells is maintain for homeostasis Example red blood cells – life span 120 days When “mutated” tumor suppression genes do not turn off – cells continue to live Lead to unrestricted proliferation and neoplastic transformations can take place Example: BCL 2 – first found in leukocytes – a gene that signals apoptosis is turned off and leukocytes continue to multiple (proliferate) – leads to leukemia Review  carcinogens Carcinogen – a substance or agent that causes the development or increases the incidence of cancer Carcinogen agents can: Directly causes modification of the cell’s DNA, which leads to alterations in cellular function Indirect changes – cause immune suppression or chronic inflammation which leads to DNA damage and then changes in cellular function  Carcinogens Radiation – high levels of radiation are capable of damaging genetic material in the cell and or the cell itself Ultraviolet rays – from the sun – skin cancer Radiation – x – rays (monitor doses) Hormones – influence cellular growth Estrogen sensitive tissues (breast) are impacted by hormone levels Tamoxifen (medication)– lowers estrogen levels to reduce tumor growth  Carcinogens Chemicals – asbestos, benzene, insecticides, and formaldehyde Tobacco – contains multiple substances which are carcinogenic More exposure the greater the risk for cancer development Microbes Human papillomavirus (HPV) – contributes to cervical cancer Helicobacter pylori (bacteria) contributes to gastric cancer Hepatitis B and C (viruses) – contributes to liver cancer  Carcinogenesis Theory Initiation, Promotion and Progression Theory 1. Initiation – a exposure to a stimuli causes a mutation in a cell 2. Promotion – the mutated cell begins to growth and replicate – sharing the mutative trait 3. The mutated cell is exposed to a promotor – results in the activation of oncongenes 4. New excessive cellular growth 5. Progression – continued growth – not dependent on promotor – growth becomes autonomous Carcinogenesis Theory  The impact of Cancer on Tissues and Organs Neoplasm – any abnormal growth of new tissue Neoplasms exhibit autonomy and anaplasia Autonomy – unregulated proliferation (growth) of the neoplasm Anaplasia – loss of cell differentiation The greater the anaplasia – the more aggressive or malignant the tumor growth will be  Characteristics of neoplasms Characteristics of neoplasms: A. Loss of cell to cell communication – allows unrestricted growth of tumor cells B. Uses more energy resources (nutrients) – starves other cells of nutrients C. Increased motility and loss of adhesion – allows cells to break free and move to other locations  Characteristics of neoplasms Characteristics of neoplasms (cont’d): D. Rapid angiogenesis – creation of new blood vessels which increases blood flow to tumor cells E. Substance secretion – alters the metabolism and degrades neighboring cells F. Presence of foreign antigens on cancer cells surface, triggering an immune response  Benign vs. Malignant Neoplasms Benign – a growth that remains localized and closely resembles the Malignant – growths tissue of origin that are invasive, May over-proliferate but does not destructive, can spread demonstrate a significant loss of to other site and do not differentiation resemble the tissue of Can impinge on nearby structures origin (organs) Promote ischemia of necrosis of other tissue Uses a lot of energy (nutrients) Angiogenesis  Cancer spread Local spread – the term used to describe proliferation of a neoplasm within the tissue of origin Example: tumor cells growing within the epidermis and dermis layers of the skin Direct extension – the process of tumor cells moving into adjacent tissue and organs Moving beyond the local tissue is defining characteristic of malignancy Example: tumor cells growing thru the basement membrane of the skin into adjacent tissue (ECF) Cancer spread Seeding – form of direct extension in which neoplastic proliferation occurs within the affected tissue or organ Stage 2 – within the pleural cavity  Cancer metastases Metastases – neoplasms are spread to distance sites by the lymph and blood vessels Stage 3 and 4 of previous image – lung cancer  Cancer classifications Staging is the process of classifying the extent to which the neoplasm has spread Also references tumor size, location, lymph node involvement and spread (TNM) T – tumor size N – lymph node involvement M – metastases  Cancer classifications Tumor grading – differentiating the level of anaplasia Stage I – well differentiated – similar to the tissue of origin Stage II - differentiated – some resemblance the tissue of origin Stage III – undifferentiated – poor resemblance to the tissue of origin Stage IV – highly undifferentiated – does not resemble the tissue of origin  Cancer Local signs and General signs and symptoms symptoms: depends on Inflammatory and immune tumor location responses Lymphadenopathy - enlargement of Lung cancer more than two non-contiguous Persistent cough lymph node groups. Hemoptysis (bloody sputum) Fever Chest pain Anorexia and weight loss Shortness of breath Cachexia – unexplained weight loss and tissue wasting related to stimulation of inflammatory mediators along with excessive energy use  Diagnostic tests Imaging studies Computerized tomography (CT) scan Magnetic Resonance Imaging (MRI) Ultrasounds and x-ray Biopsy and cytology studies Sample of tumor cells to lab for analysis Tumor markers Substances from tumors found in cells and fluids Examine blood, urine, sputum and tissues  Cancer treatment Surgery Nursing – pre and post surgical care for tumor removal Prevent and monitor for complications Bleeding – monitor incision, monitor Hgb. and Hct. Infection – monitor for fever, increasing WBCs, redness and warmth at incisions site DVTs – Homan’s sign, compression socks and devices Post-op pneumonia – deep breathing and coughing, incentive spirometer, early ambulation  Cancer treatment Chemotherapy Is an aggressive form of drug therapy meant to destroy rapidly growing cells in the body Cancer cells grow and divide faster than other cells Monitor for nausea, vomiting – antiemetic's, maintain hydration Monitor for hair loss (disturbed body image) therapeutic communication, support groups Monitor for infection and bleeding – good hand hygiene, avoid crowds, limit raw foods  Cancer treatment Radiation Using focused ionizing radiation to damage cell DNA and stop replication Skin care – can cause redness, itching – tepid water, fragrances free lotions Poor wound healing – proper dressing changes, vitamin C and E  Cancer treatment Hormones Tumors that are sensitive to hormones (estrogen – breast tumors) Administer medication that suppress or enhance hormone production Tamoxifen – suppresses estrogen – deprives estrogen sensitive tumors – reduces growth  Cancer treatment Biologic Response Modifiers (BMRs) are substances that modify immune responses They can be both endogenous (produced naturally within the body) and exogenous (as pharmaceutical drugs), and they can either enhance an immune response or suppress it. Immunomodulators can be helpful in treating cancer (where targeted therapy often relies on the immune system being used to attack cancer cells) Cancer treatment Nursing interventions Preventative care: 1.Avoid known carcinogens 2.Stop smoking 3.Exercise moderately 4.Consume a balanced diet 5.Use sun screen 6.Limit alcohol intake 7.Vaccinations – HPV and Hepatitis General Manifestations of Cancer Lymphadenopathy Fever Anorexia Cachexia Palpable mass Loss of tissue function–variable depending on site Cachexia Application of the Concepts of Altered Cell Proliferation and Differentiation Lung cancer Colon cancer Brain cancer Leukemia Lymphoma  Learning Objectives What are the two types of genetic mutations? (Be able to define them) How do oncogenes get activated? (Be able to describe the three processes) How does the tumor suppressor gene contribute to increased cellular proliferation? Give an example of a tumor suppressor gene contributing to the development of neoplasm?  Learning Objectives What is a carcinogen? What is an example of carcinogens? As the nurse, what actions can you teach patients to reduce their risk of developing cancer? What are the characteristics of neoplasms? What are the differences between benign and malignant?  Learning Objectives What is meant by local vs systemic manifestations of cancer (neoplasms)? Could you give an example? What kinds are treatments are being used to treat cancer? What is involved in preventative cancer care?  Review Videos Review cellular replication – 6.5 min Mitosis vs. Meiosis: Side by Side Comparison – YouTube Review cell cycle and cancer – 9 min The Cell Cycle (and cancer) [Updated] - YouTube  Questions Chapter 7 Applied pathophysiology Review questions – page 195 - 196 Chapter Medical – Surgical Nursing in Canada Chapter 18 p. 316 - 327 Contact me with questions [email protected]