WHATSUNDER YOUR SKIN? WHATS UNDER YOUR SKIN? Skin Care of Breast Cancer Patients Undergoing Standard External Beam Radiation Donna M. Braunreiter RN BSN OCN MSN Student Alverno College Spring 2009, MSN 621 dmbraunreiter @ aol.com dmbraunreiter @ wi.rr.com
Objectives 1.Explain effects of external beam radiation therapy. 2.Briefly describe genetic mechanisms involved in radiation. 3.Summarize the acute physiologic mechanisms of inflammation. 4.Describe the structure and function of skin. 5.Identify breast skin changes after radiation treatment. 6.Review nursing care for breast cancer patients undergoing radiation therapy.
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RADIATION GENETICS INFLAMMATION SKIN STRUCTURE AND FUNCTION BREAST SKIN CHANGES NURSING CARE AND PATIENT EDUCATION
RADIATION Microsoft Office Clip Art 2007
Radiation Treatment Skin reaction is the most common side effect during breast cancer radiation treatments Over 90% of women receiving radiation for breast cancer will develop some skin changes during their course of treatment
Radiation Interacts with all biological materials in its path Direct and indirect damage to cells causes DNA changes Causes many molecular responses that induce cellular mechanisms for DNA repair, cell cycle arrests, and apoptosis
Radiation Major effect on dividing cells is reproductive death Leaves cells unable to reproduce Radiosensitivity of cell determines degree of injury and when it will happen
Radiation Direct Effect DNA absorbs radiation The atoms become ionized and damaged Less common than indirect damage Microsoft Office Clip Art 2007
Radiation Indirect Effect Water molecules surrounding DNA are ionized Creates highly reactive free radicals such as hydroxyl radicals, peroxide, hydrated electrons, and oxygen radicals These radicals interfere with DNA and cause damage and strand breakage Common because 80% of a cell is water
Radiation Damage Direct and indirect damage break bonds in DNA backbone Results in loss of base, nucleotide, or one or both strands of DNA Single-strand DNA breaks are repaired using the opposite strand as a template Can result in mutation if not repaired correctly
Radiation Damage Double-strand DNA breaks related to cell killing Results in mitotic death X-rays are sparsely ionizing and cause locally clustered damage Leads to clinically significant events DNA Structure United States National Library of Medicine http://ghr.nlm.nih.gov/handbook/illustrations.dnastructure.jpg
Radiation CONTROLS CANCER CELLS BY 1.Inducing apoptosis 2.Causing permanent cell cycle arrest or terminal differentiation 3.Inducing cells to die of mitotic catastrophe
Apoptosis Programmed cell death Radiation damage triggers signaling cascades which causes cell self-destruct mechanisms Characteristics are nucleus fragmentation and blebbing Tumors undergoing apoptosis have good clinical response
Cell Cycle Death/Terminal Differentiation (Denucleation) Cells can arrest in any phase of cell cycle Radiation damage mainly in G1 and G2 phases Normal cells and cancer cells retaining p53 function block in G1 Cancer cells with p53 loss or mutation block in G2 phase G2 arrest related to cellular repair of DNA radiation-induced DNA damage
Radiation Effects Radiosensitive Cells renewing rapidly with little or no differentiation Examples are skin cells, mucous membranes, and hematopoietic stem cells Radioresistant Cells that do not divide regularly or at all and are highly differentiated Examples are muscle cells and nerve cells
Radiation Effects Radiosensitive Acute effects Damage within weeks to months of exposure Temporary Normal cells affected are capable of repair Dependent upon dose-time- volume factors Radioresistant Late effects Damage months or years after first exposure Permanent Damage becomes more severe as time goes on Dependent upon dose-time- volume factors
Radiation Effects Radiosensitive Higher doses over shorter periods of time to larger volumes of tissues result in more severe acute reactions Acute damage results from depletion of actively proliferating parenchymal or stromal cells Characteristics are vascular dilation, local edema, and inflammation Radioresistant Severity of late effects more dependent upon total dose delivered and volume if tissue irradiated Damage to endothelial cells or connective tissues results in late effects occurring as a result of narrowing or occlusion of small vasculature and fibrosis
Radiation Effects Acute and late side effects from radiation therapy are LOCAL and ONLY affect tissues receiving treatment Presence and severity of acute effects can not predict late effects of radiation Late reactions such as tissue necrosis or dense tissue fibrosis can occur independently of acute reactions
SUPINE POSITION Most common position for breast cancer radiation therapy MUST be used if lymph nodes need to be treated May involve radiation exposure to heart, lungs, ribs, and contralateral breast Microsoft Office Clip Art 2007
PRONE POSITION Used for women with larger pendulous breast, cardiac and/or pulmonary comorbidities Possible improved dose homogeneity Potential reduction in lung and heart irradiation Microsoft Office Clip Art 2007
Patient-Related Considerations Normal age-related changes: thinning of the epidermis and dermis, diminished elasticity, decreased dermal turgor, which results in delayed healing. Nutritional status is also important for healing.
What is the effect of radiation on cells? A. Reproductive death of cells throughout the body C. Radiation skin reactions cause internal injuries. D. Radiation helps repair DNA damage. B. Reproductive death of cells in the treated area only
Wrong answer, try again. Radiation only affects the area being treated and causes damage to DNA. Click here to return to question
Correct! Radiation causes the reproductive death of cells in the treated area only.
GENETICS Microsoft Office Clip Art 2007
Chromosome: rod-shaped molecule of DNA threaded around proteins containing specific genes that carry hereditary information Histones are proteins that act as spools around which DNA winds, as compaction is necessary to large genes inside cell nuclei; histones also function as gene regulators United States National Library of Medicine http://ghr.nlm.nih.gov/handbook/illustrations/chromosomestructure.jpg
GENE: biological unit of hereditary; segment of DNA needed to contribute to a function and specifies a trait United States Library of Medicine http://ghr.nlm.nih.gov/handbook/illustrations/geneinchromosome.jpg
Radiation effect on genes 1.Ionizing radiation causes phosphorylation of histone H2AX (forming gamma-H2AX) 2.Reaction dependent on ataxia telangiectesia mutated (ATM) molecule 3.Followed by accumulation of 53BP1, a protein acting as central mediator for critical pathways, including phosphorylating (which conveys the DNA damage signal to) tumor suppressor protein p53
Genetics in Radiation 4.Next, phosphorylating the ATM protein amplifies the damage signal 5.And recruits proteins critical for repair, such as the BRCA1 and HDAC4 6.Which allows a G2 cycle checkpoint 7.53BP1 important in double-strand DNA damage sensing, repair, and tumor suppression
Genetics in Radiation HR (homologous repair) efficient in late S or G2 phase when sister chromatids have replicated but not separated Repair is cell cycle dependent Undamaged homologous chromosome or sister chromatid or replicated chromosome is used as a template to fill in missing DNA sequences in damaged chromosome
Genetics in Radiation Human tumor cells block in G2 after DNA double-strand damage, when repairs are detectible, and irradiation induced G2 checkpoint allows more time for cells to undergo HR (homologous repair) and survive radiation
Genetics in Radiation NHEJ (nonhomologous endjoining) is where blunt ends of chromosomes severed by radiation are directly rejoined Less cell cycle dependent Highly mutagenic due to template-free rejoining lacks specificity of HR Ends of different chromosomes can be rejoined, leading to chromosomal aberrations or expression of dangerous fusion proteins
p53 Tumor Suppressor Gene p53 stops activity of tumors Loss or mutation of p53 predisposes to cancer (e.g. inheriting only one functional copy of p53 gene from parents) p53 protein binds DNA and stimulates another gene to produce protein p21 and blocks next stage of cell division Mutant p53 no longer binds DNA and does not interact with p21 Results in p21 unable to act as a stop signal Cells divide uncontrollably
Genetics in Radiation Ras, Raf, and EGFR alter cellular sensitivity to radiation, but exact mechanisms unknown Ras is a proto-oncogogene (portion of DNA that regulates normal cell proliferation and repair) Raf is a gene coding for protein kinase EGFR (epidermal growth factor receptor) found on surface of some cells and where epidermal growth factor binds, causing the cells to divide
What is a common gene that can lead to many cancers it is mutated or lost? A. EGFR B. p 21 D. Ras C. p 53
Wrong answer, try again. EGFR is epidermal growth factor, Ras is a proto- oncogene, and p21 is a protein influenced by p53 and acts as a stop signal in the cell cycle. Click here to return to question
Correct! p 53
INFLAMMATION Microsoft Office Clip Art 2007
Inflammation Reaction of vascularized tissue to local injury. Causes are many and varied. Commonly it results from an immune response to infection organisms. Other causes are trauma, surgery, caustic chemicals, extremes of heat and cold, and ischemic damage to body tissues. (Porth, 2005).
Five Cardinal Signs of Inflammation 1.Redness 2.Swelling 3.Heat 4.Pain 5.Loss of function Microsoft Office Clip Art 2007
Acute Inflammation Two major components 1.VASCULAR 2.CELLULAR Inflammatory mediators, acting together or in sequence, amplify the initial response and influence its evolution by regulating the subsequent vascular and cellular responses (Porth, 2005). Microsoft Office Clip Art 2007
Vascular Stage Constriction of small blood vessels in injured area Vasoconstriction followed rapidly by vasodilation of the arterioles and venules Causes the area to becomes congested and results in redness and warmth
Vascular Stage Capillary permeability increases causes swelling, pain, and impaired function Movement of fluid from capillaries into interstitial spaces (swelling) dilutes the offending agent Extravasation of plasma proteins into extracellular spaces causes exudate Blood stagnation and clotting of blood in the capillaries around the injury site; aids in localizing the spread of infectious microorganisms
Vascular Stage 1.FIRST is immediate transient response 2.SECOND is immediate sustained response which occurs with more serious injury and continues for several days and damages vessels in the area 3.THIRD is a delayed hemodynamic response, which increases capillary permeability that occurs 4 to 24 hours after injury, seen with RADIATION types of injuries
Cellular Stage Movement of phagocytic white blood cells (leukocytes) into area of injury Two types of leukocytes involved-- granulocytes and monocytes Requires the release of chemical mediators from sentinel cells (mast cells and macrophages) already positioned in tissues
Cellular Stage: Granulocytes Granulocytes divided into three types neutrophils, eosinophils, and basophils. 1.Neutrophils are primary phagocytes; arrive within 90 minutes to injury site; contain enzymes and antibacterial substances that destroy and degrade engulfed particles.
Cellular Stage: Monocytes Mononuclear phagocytes are largest of white blood cells Last 3 to 4 times longer than granulocytes and survive longer in the tissues. Help to destroy agent, aid in signaling processes of specific immunity, and help to resolve inflammatory process. Arrive by 24 hours and at 48 hours monocytes and macrophages are predominant cells at injury site Engulf larger and greater quantities of foreign materials and migrate to lymph nodes.
Phases of Acute Inflammation Response MARGINATION Leukocytes increase adhesion molecules, slow migration, and move along periphery of blood vessels
Phases of Acute Inflammation Response EMIGRATION Leukocytes pass through capillary walls and migrate into tissue spaces
Phases of Acute Inflammation Response CHEMOTAXIS Leukocytes in tissues guided by cytokines, bacteria, and cell debris
Phases of Acute Inflammation Response PHAGOCYTOSIS Neutrophils and macrophages engulf and degrade bacteria and debris Phagocytosis http://upload.wikimedia.org/.../180px-Phagocytosis2. png
Inflammatory Mediators CYTOKINES Polypeptide products of various cell types- mostly lymphocytes and macrophages modulate functions of other cell types COLONY-STIMULATING FACTORS directs growth of immature marrow precursor cells INTERLEUKINS (Ils) INTERFERONS (Ifs) TUMOR NECROSIS FACTOR
Inflammation with Chemical Mediator INFLAMMATORY RESPONSE Swelling, redness, and tissue warmth (vasodilation and increased capillary permeability) CHEMICAL MEDIATOR Histamine (fast acting and causes dilatation and increased permeability of capillaries), Prostaglan...