Cellular Regulation Flashcards
What is cellular regulation
Cells function within cells to maintain homeostasis including response to extra cellular signals and the way each cell produces intracellular response
Cells contain natural functions that help them respond to stress to keep them in the intact state
Want to look at ways cells respond to normal stressors
Proliferation
Normal cells reproduce new cells through cell division
Hyperplasia: increased number of cells in response to stress, increased metabolic demands, or increased hormones
Neoplasia: abnormal and progressive multiplication of cells; multiplying without a purpose and can lead to cancer
Neoplasm: new and abnormal tissue growth; uncontrolled and progressive
Neoplasia is a little controlled; neoplasm is uncontrolled
Differentiation
Acquisition of a specific cell function; new cells acquire structural, microscopic, and functional characteristics of cells they replace
Differentiation refers to how close the cells are to the parent cells they came from; the less differentiated, the more problems because they are less like the parent cells and more neoplastic
Metaplasia: change in normal differentiation- normal for type of cell but wrong location; protective response to adverse conditions; under normal control of DNA
Dysplasia: loss of DNA control over differentiation in response to adverse conditions
Anaplasia: regression to immature or undifferentiated state; no DNA control; looking at cancer that is out of control
Benign
Continues inappropriate cell growth
Retains parent morphology
Small nuclear to cytoplasmic ratio
Specific differentiated function continues; well differentiated: close to parent cell
Tight adherence to each other
No migration- does not spread to anywhere else in the body
Orderly cell growth even though cell growth is out of control
Normal chromosomes
Loss of apoptosis (orderly cell death where old cells die and we create new ones): there is no cell death resulting in the tumor
Less division than a malignant tumor
Malignant
Rapid proliferation; rapid cell division requires a lot of energy and need to increase caloric intake; may become cachectic or malnourished and thin because of energy the tumor is taking
Anaplasia- decreased cell death; no signal for apoptosis
Large nuclear to cytoplasmic ratio
Poor differentiation; no homeostatic control because DNA is different from parent cell
Lose adherence and migration
No contact inhibition
Abnormal chromosomes
Step 1: initiation
Irreversible mutation of gene but still able to carry out original function; there is an oncogene (e.g., BRCA1), there is some irreversible agent (e.g., exposed to something like benzene) that changes the cell, or some carcinogen
Something changes on initiation that changes the genetic or purpose of the cell; simply the process of changing the cell and what it does
Oncogene over expression
Irreversible event
Carcinogens change cells genes
Step 2: promotion
Enhancement of growth of initiated cell
Hormones like insulin or estrogen are big promoting agents that stimulate the growth of the cell that has mutated. Some of the cells have a threshold- there is a certain amount of promotion that needs to occur to stimulate the process
Threshold dose is required to stimulate
In obesity, there is insulin resistance which can create inflammation and other problems like hyperglycemia or anaerobic oxidation. Fat cells produce estrogen; increased estrogen leads to hyperplasia which can all lead to uterine cancers
Looking at cytokines production as an initiator; estrogen and insulin as a promoter; all which leads to progression
Step 3: promotion
The cell changes lead to an undifferentiated cell state
Increased growth rate
Increased invasive ability
Metastasis
Angiogenesis
Start with a normal cell with a mutation, end up with some hyperplasia, have some dysplasia (some change in the cell for a purpose), an in situ cancer (something that is in place and hasn’t invaded anything yet), the the invasive malignant cells
With progression, we have promoting that leads to an undifferentiated cell that starts growing faster that increases our invasive ability and have metastasis
Metastasis spread
Lymphatic system: WBCs will attack and clear the lymphatic system. With a cancer cell, it will enter the system where it will die, spread through the lymphatic system and remain dormant, or start growing a mass. Mass can break off into thoracic duct into the vasculature. Sentinel node is the first node after original tumor
Hematogenous system: invaded capillaries and venules; GI & pancreas feed into portal vein where thee liver mets; vena cava where the lung mets ; breakdown ECM (extra cellular membranes) with enzymes and goes into the venous system
Cancer risk: age
Long-term exposure to promotional agents
Decreased immune response especially with advanced ages of 70s and 80s
Hormonal changes with estrogen
Free radical production as we age and have more oxidative stress
76% of cancer occurs in people over the age of 55; children account for about 1% of all cancers
Cancer risk: hereditary
Inherited predisposition- about 5-10% of cancers are genetically linked; BRCA1 causes breast, prostate, ovarian cancers
Familial clustering- familial polyposis where there are polyps in the colon; may remove the colon when they are little because risk for dying of colon cancer is very high; more cancers in the family and looking at their genes to determine why they have so many cancers in their family
Other autosomal dominant things: retinal blastoma which is a tumor of the retina, BRCA1, familial polyposis, etc.
Chromosomes: people with a known chromosomal disorder have a much higher risk of leukemias (e.g., Down syndrome have 25% higher risk; Klinefelters syndrome have a high risk for breast cancer because males with XXY chromosomes grow breast tissue; Turners syndrome is a woman with one X chromosome and higher risk of leukemia)
Genetic testing does not detect cancer but shows if there is an increased risk
Cancer risk: obesity
Insulin resistance and increased insulin production
Increased androgen and estrogens which are proliferated in fat cells
Chronic inflammation state which puts cells in contact with cytokines which are cancerous promoting agents
Cytokines respond to these things that promote growth
Cancer risk: chemical
Form highly reactive species- looking at free radical production which are some of those promoting agents that put us at risk for cancer such as smoking, benzoprene (foods that are fried and reused fat like McDonald’s), polycystic aeromatic hydrocarbons (animal fat in charcoal in smoked meats), ethanol (metabolism interferes with DNA synthesis and repair), asbestos, benzene (bladder cancer r/t benzene in paper)
Bunds to DNA and RNA cause cell mutation
Change cell proteins and enzymes
Cancer risks: radiation
Ionizing
Ultraviolet- causes additional damage added to the initiation stage
Radon- most common; test houses for this
Medical: x-rays are 11% of our radiation risks, nuclear medicine testing like CAT or PET scans are 4%- don’t order undue tests
Increased brain tumors in kids who’ve had a head CT; want to reduce: for concussions, monitoring is better than a CT
Radiation mutates the genes by chromosome breakage; it’s the initiation stage that increases the risk
Cancer risks: viral
Viral insertion of genetic material into DNA can activate oncogene and damage suppressor genes
HPV- can cause cervical, penile, and oral cancer
EBV
HBV- can cause liver cancer
HHV-8- human herpes virus can cause throat and mouth cancer
Helicobacter pylori- bacteria that causes ulcers can put you at risk for gastric cancer
Cancer risk: other
Immune function: protect from foreign and non-self cells where T cells destroy abnormal cells so we can’t proliferate it and cause cancer
Decreased immune function= high risk for cancer; organ transplant on immunosuppressants are high risk for lymphomas
Gender: male- higher risk for prostrate and bladder (esp. in men who smoke)
Female- higher risk for breast and thyroid
Socioeconomic status- poor access to healthcare screening and counseling; poorer diet and more stress (increases cytokine hormones)
Assessment: history
Discovery of lump, mass, or lesion
Unexplained bleeding, bruising, cough, or fatigue
Change in appearance: skin and moles (ABCDE), loss of appetite, weight loss, mental status changes, bowel changes, swallow changes, pallor, unexplained bruising, persistent fevers, unexplained vomiting (may be a brain tumor from vomiting centers being pushed on by tumor), bone pain, headaches, changes in gait or personality, fatigue, new diagnosis of SIADH could be indicative of a brain tumor, new diagnosis of Cushings, hypercalcemia, new blood clot
Signs of altered body function
Family history
Risk history
ABCDE for skin cancer
A-asymmetry
B-border that is uneven, crusty, or notched
C- color that is various esp. white and or blue tends to be bad
D-diameter that is larger than a pencil eraser tends to be a melanoma
E- evolving or changing in size, shape, or color or begins to bleed or scab is often bad
7 warning signs of cancer
CAUTION
- Change in bowel or bladder habits
- A sore that does not heal
- Unusual bleeding or discharge
- Thickening or lump in breast or elsewhere
- Indigestion (persistent) or difficulty with swallowing
- Obvious change in wart or mole
- Nagging cough or hoarseness of voice
Assessment: diagnostic
Radiographic/X-ray- show size and location
Visualization: colonoscopy, esophoduodenaloscopy, MRI, CT, mammograms, ultrasounds
Labs: tumor markers (antigen on surface of tumor cells), CBC which shows bone marrow function
Cytologic- taking a sample of cells like a Pap smear where you look at cancer cells that exfoliate and change secretions
Tissue biopsy to look at tissue under microscope
Immunohistochemistry is looking at type of tumor markers
Microarray technology detects and quantifies the expression of large numbers of oncogenes
Grading a tumor
Dependent on the degree of differentiation
G1- well differentiated
G4- not differentiated where cells are far away from parent; difficult to determine origin of cell because so far away
Staging tumor size
Tx- not measured
T0- no evidence of tumor; may have peripheral evidence but no tumor seen
Tis- malignant cells only in superficial layer; not invaded anywhere
T1-T4 is based on size and invasion
Staging- regional lymph node
Nx- not assessed
N0- no metastasis; sentinel node is clear
N1-N3 is based on size, location, and number of lymph nodes involved
Look at sentinel node- the first lymph node past the tumor
Staging- metastasis
Mx- presence not assessed
M0- none
M1-M4- distant
Looking at nearby tissue, if it’s spread into the vascular system, and where it might have gone into after the vascular system
Terminology
Oma: benign tumor for parenchymal tissue (organ tissue) type
Carcinoma: malignant epithelial origin
Adenocarcinoma- gland-like structures (thyroid, parathyroid, adrenal)
Sarcoma- mesemchymal tissue (looking at non organs)
Blastoma- embryonic tissue
Primary prevention- prevents!
Regular physical activity- decreasing obesity and inflammation rates
Balanced diet
Avoid known or potential carcinogens- smoking, protective gear, sunscreen
Modify associated factors
Remove at risk tissues
Chemoprevention- vitamins, minerals, antioxidants, etc.
Vaccination- HPV
Secondary prevention- screen!
Mammography should begin at age 40 unless familial history, then want to start earlier or BRCA1 testing
PSA- prostate specific antigens with family history of prostate cancer; is it inflamed or cancer
PAP for cervical cancer
Colonoscopy starting at age 50 or sooner with family history
Childhood cancers
Hematopoietic, nervous, soft tissue, bone, and kidney
Embryonic origin and some are mesenchymal
Lymphoblastic leukemia- look to see if they have other disorders in their genes that will focus treatment
Puberty- bone cancer (osteosarcoma is high in the teenage population), lymphoma, gonadal (boys may get testicular cancer as teenagers; girls can get ovarian cancer as teenagers but not commonly) (look at stages of growth)
Cancer impact on function: GI
Cachexia- extreme body waiting and malnutrition
Increased catabolism as tumor is using a lot of energy
Treat- smaller frequent meals; nutritional supplements; enteral feeding; parenteral nutrition
Decreased appetite from N/V, mucosal changes, feeling of fullness
Cancer impact on function, neuro, motor, and sensory
Invasion of bone: risk for fractures, pain, spinal cord compression, hypercalcemia
Invasion of brain: impact dependent on location; can have cognitive, sensory, personality disorders, hormonal changes
Nerve compression: pain, motor and sensation issues
Cancer impact on function: pain
Tumor compression
Metastasis
Treatment
Pain is often what causes the person to be evaluated; want to relieve so they have good QOL and make sure they are comfortable but can function
Cancer consequences- psychological
Fear, stress, anxiety
Familial dynamics
Financial
Self-image and identity
Cancer treatment: surgical
Prophylactic- removes potential source of cancer
Diagnostic- excisional biopsy, remove all or part of the tumor
Staging- size, metastasis, etc.
Debulking- entire tumor cannot be removed r/t damage to vital organ but large amounts are removed so radiation can work better
Cure- remove all cancerous tissue; usually for skin cancers or benign tumors that are encapsulated
Palliative- not curing, may be end stage, can remove parts for improved QOL
Reconstructive/ rehabilitative- increasing function or appearance
Side effects: loss of organ function- change in appearance from loss of body part
Care-post-surgical: psychological and acceptance
Cancer treatment: radiation therapy external
Gamma ray, radionuclides, or ionizing beams: effects in path or field of radiation- not always full body except leukemia; exposure- what is delivered into the tissue; radiation dose- fractionation (to decrease damage to good tissue), what is absorbed into the tissue
External beam: patient not radioactive because particles dissipate quickly
Gamma knife targets one area from different angles to decrease damage to good tissue; seen often with brain tumors
Cancer treatment: radiation side effects
Acute: alopecia (possibly permanent if damage to hair follicle), cerebral edema, N/V, somnolence (very sleepy), mucositis, xerostomia (dry mouth), esophagitis, pharyngitis, anorexia, diarrhea, cystitis, vaginitis, fatigue, taste changes, bone marrow suppression
Late: cognitive, pituitary/hypothalamus (SIADH, temp regulation issues), dental caries, hypothyroid, xerostomia, cardiomyopathy, lung fibrosis (hard lung tissue, decreased respiratory function), lymphedema, bowel injury
Radiation therapy: patient skin care
Wash daily with water or mild soap
Do not scrub
Do not remove ink markings
Pat dry
Use only prescribed lotions
Avoid sun exposure
Oils on skin need to be washed off with radiation therapy because oils on the skin will make it burn more
Radiation: brachytherapy
Small radioactive rods placed near the tumor in the body
Internal contact with tumor; implanted- patient is radioactive, degrade or need removal; ingested- body fluids radioactive
Patient care: private room and bath, caution sign and lead shield, wear dosimeter badge (detects amount of radiation exposure) and lead apron (don’t turn back, increases exposure), do not try to conceive, limit visitor time to 30 minutes a day
No exposure to pregnant women or children if radioactive
Cancer treatment: chemotherapy
Chemicals to prevent multiplication
Effect during cell division
Selection: tumor cell cycle, growth factors and size
Effect ALL body cells
Nadir- time of greatest effect on bone marrow- time of lowest WBCs, RBCs to see when they are at greatest risk for infection, anemia’s, etc.
Timed mixture
High-dose causes bone marrow depression: growth factors;m to increase WBC production; HST/BMT (hematopoietic stem cell/bone marrow transplant) may be required
Cancer treatment: chemotherapy continued
IV admin requires chemo-certification; but anyone can monitor the patient once it’s up and running
PPE with chemo or patient bodily fluids: double glove or chemo glove, gown for 48 hours after administering; eye protection of risk for splashing
Vesicants- drugs damage tissue on contact: extravasation prevention; call provider for antidote if suspected
Oral- handle with gloves: do NOT split, crush, break, or chew
Cancer treatment: chemo side effects
Mucositis (erosion of mouth tissue)- use soft bristled tooth brush; salt and soda swish and spit; avoid spicy, acidic, hard foods
Alopecia- whole body hair loss; avoid direct sunlight; body image
Cognitive alterations (“chemo brain”)- decreased concentration, memory loss
Peripheral neuropathy- decreased sensation; poor gait and balance, orthostatic hypotension, pain; patient education on shoes, inspecting feet, fall risk
Cancer treatment: chemo bone marrow suppression- neutropenia
Cause for dose limiting and mortality; risk of infection and sepsis
ANC <500: severe infection risk
ANC= [(seg% + band%) x WBC] /100
Patient report fever >100, cough, cloudy urine, wound
Decrease purulence and pus because decreased WBCs, decreased fever response because decreased WBCs
Nursing interventions: hand washing; antibiotics with fever- blood and wound culture before; WBC daily; colony stimulating factors
Cancer treatment: chemo bone marrow suppression
Anemia & consequences: blood transfusions; erythropoiesis stimulating agents (darbepoetin and epoetin alpha- both increase clot risk)
Thrombocytopenia-
Bleeding precautions: platelet transfusions; eltrombopag or romiplastin- risk of fluid retention
Cancer treatment: chemotherapy N/V
Anticipatory (before going in), acute (first 24 hours, persists 1-2 days), delayed (after 24 hours of stopping chemo)
Breakthrough, emetogenic
Serotonin antagonist- block in brain and intestine (ondansetron; give before chemo starts)
Corticosteroids (dexamethasone) to decrease brain swelling
Neurokinin receptor antagonist (aprepitant) to block warfarin and oral contraceptives effectiveness
Prokinetic- increase gastric emptying (metoclopramide)
Benzodiazepines (lorazepam, Ativan)
Cancer treatment: humoral
Target or block receptor and feedback loops
Direct anti tumor activity
Interleukins regulate inflammation: macrophage and NK cells to target the tumor; side effects: capillary leak syndrome (neuro- confusion, fatigue, agitation, hallucinations, depression)
Interferons slow cell division: block oncogene expression; cancer cells to normal function
Cancer treatment: target
Antibody and small molecule inhibitors
Prevent growth signaling: block angiogenesis; block oncogene expression (can block cells from dividing); stimulate immune destruction
Tyrosine kinase inhibitors: side effects include N/V, fluid retention, bone marrow suppression
Herceptin will block HER-2 cancer cells
Cancer treatment: hormonal manipulation
Androgen and antiestrogen: Hair and acne Amenorrhea- stop periods Fluid retention Hypercalcemia
Estrogen/ progestins:
Osteoporosis
Gynecomastia
Loss of facial hair
Cancer treatment: HSCT/ BMT
Allogeneic (someone else; typically used for leukemia) and autologous (my own)
Donor identification- HLA matching
High dose chemo destroys BM (bone marrow)
GVHD- graft versus host disease: skin, gut, liver
Oncology emergencies
Sepsis: neutropenia, temp >100
DIC- caused by sepsis and chemotherapy
SIADH- pituitary and small cell lung cancers
Hypercalcemia- cancers secrete PTH and bone metastasis: bone pain and renal calculi
Oncologist emergencies: spinal cord compression
Tumor invaded spine
Vertebrae collapse, spinal cord damage
Sx: back pain, weakness, decreased sensation, urinary retention, constipation, decreased DTRs, vibratory sense, paralysis if not treated quickly
Treat: high dose steroids, XRT (radiation and debulking), surgery
Oncologist emergencies: superior vena cava syndrome
Compression blocking venous return
Sx: pain, periorbital edema, neck and chest tightness, airway compression, worse when flat, signs of decreased venous return
Death if not treated
Treat: XRT and chemo to shrink tumors
Oncologic emergencies: tumor lysis syndrome
Chemo destroys large number of cells
Hyperkalemia risk
Hyperuricemia- acute renal failure
Hyperphosphatemia
Liver occlusion
Treat: hydration; alkaline body fluids- NaHCO3, check urine pH; allopurinol for Uric acid piece
Cancer signs in children
General- mass, purpura, pallor, weight loss, fatigue
Overt- white eye reflection , vomiting in morning, recurrent/persistent fever
Covert- bone pain, headache, persistent lymphadenopathy, change in gait, balance, personality
Leukemia
ALL/ANLL
Overproduction of immature WBCs
Competition for metabolic elements
Dx: CBC- blasts and decreased RBC/platelet count; bone marrow flow cytometry; LP for CNS involvement
Leukemia therapy: ALL
- Induction chemo
- CNS prophy
- Intensification
- Maintenance
Leukemia therapy: ANLL
- Chemo 2-4 courses with CNS prophy
2. BMT or consolidation
Leukemia nursing management
Emotional support Pain Infection Hemorrhage Anemia Chemotherapy N/V Anorexia Mucosal ulceration Neuropathy Hemorrhagic cystitis Alopecia Mood changes
