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disorder of cell proliferation and differentiation
Cancer is the _____ leading cause of death.
Leading cause of death?
What does neoplasia mean?
3 char. of neoplasia?
- 1. proliferate to form new tissue
- 2. often do not differentiate to do the "job" of the tissue where they originate
- 3. they do not undergo apoptosis to control # of cells
4 most common cancers in order?
- 1. lung
- 2. colon
- 3. breast
- 4. prostrate
What is the goal of apoptosis?
How is this r/t cancer cells?
to get rid of cells not needed
cancer cells grow faster than normal cells and are not subject to stim to apoptosis so they have huge numbers of cells growing
What happens to cells once they are fully differentiated?
they are no longer capable of cell division/mitosis
lack of or loss of cell differentiation
means without form
Autonomy of cancer cells?
cancer cells are independent from normal cellular controls - do what they want
What are undifferentiated cells?
immature stem cells
If a cell does not differentiate properly what will occur?
a mutation has taken place and can cause a cancer
type of cancer depends on the mutation that occurred
When is the mutation most risk?
the less differentiated the cell is when the mutation occurs = the more damage will be done and more diff the cell will be from the parent cell and surrounding tissues
more mature cell will be better able to deal with the mutation
What does malignancy of cancer cells relate to?
the more differentiated a cell is when mutation occurs the less malignant it will be
Rapid proliferation occurs in what cells of the body
epithelial lining of the GI tract
Proliferation rate AKA?
cellular degeneration rate
What cells of the body have no cellular proliferation?
Why do cancer pt have hair loss and GI probs?
b/c the Tx for cancer attack rapid proliferating cells & the cells of hair follicles and GI rapidly proliferate
Benign V/S malignant?
benign - well-differentiated, slow growing, and doesn't spread - not cancer
malignant - anaplastic or undifferentiated, rapid growth due to doubling time, metastasis
Benign tumor cells?
1. look like normal tissue cells and may perform the normal function of the tissue
2. can secrete hormones - may lead to oversecretion
3. usually have a capsule around them
4. usually do not invade neighboring tissues
2 ways benign tumors can cause problems?
1. can oversecrete hormones
2. can damage nearby organs by compressing them - can be life-threatening
Char of benign tumor?
defined & clearly delineated
Char. of malignant tumors?
1. cells don't look like parent cells - not like tissue where they came from - less differentiated
2. can divide rapidly - tumors can grow rapidly
3. tumor has no clear boundaries and sends legs out into surr. tissue
4. do not perform the normal functions of the organ - may secrete hormones ass. with other tissues
5. can compress and/or destroy the surrounding tissues
A 1 cm malignant tumor contains ______ cancer cells.
Hormone secretion of malignant tumor?
may secrete hormones from other tissues not closeby
Causes/risk factors of cancer?
- 1. smoking and drinking
- 2. genetics
- 3. sun exposure (UVA/UVB)
- 4. diet
- 5. exposure to toxins/chemicals: agent orange
What causes cancer to occur?
a change occurs and multifactors effect it- checkpoints in cell cycle do not catch it and it gets out of control
What is required for cell division?
duplicating the DNA to daughter cells
Why do they shorten over time?
DNA sequences at the ends of the chromosomes where enzymes that duplicate DNA attach
ends do not get duplicated - cut off each time
G1 of cell cycle?
will show if DNA in chrom is damaged by radiation or chem
G2 to M of cell cycle?
will prevent entry into mitosis if the DNA is not complete/correct - proteins cyclins control cell cycle
If a man has a mutation that causes some of his cells to rebuild their telomeres after q division what will occur?
this is bad b/c the cell will never die
2 broad groups of improtant cancer-related genes?
2. tumor suppressor genes
What occurs with over activity of this gene?
genes that normally code for parts of cell growth activiation
When does cancer develop?
when proto-oncogenes are inapp. stim. or tumor-suppressor genes are lost or inactive
overactive or mutant form of proto-oncogene
genes that normally inhibit cell proliferation
What do mutant oncogenes do?
will interrupt normal intracellular communication pathways that normally regulate the growth activiation of cells
When do cancers arise in relation to tumor suppressor genes?
when TSG are lost or inhibited
4 categories of proto-oncogene cell proliferation?
- 1. growth factor
- 2. growth factor receptor
- 3. cytoplasmic signaling
- 4. transcription factors
What usually is the cause of changes in proto-oncogenes an tumor suppressor genes?
mutation due to risk factors
What types of things can cause mutations that convert proto-oncogenes to oncogenes?
1. retroviral invasion into the host
2. mutagenic event
3. regulatory sequence mutation of DNA
4. error in chromosome replication
What are retroviruses?
RNA virus that replicates in a host cell & incorporates its DNA into the host
3 EX of retroviruses and the cancer that they can cause?
1. HIV - kaposi sarcoma
2. Epstein-Barr virus - Burkitt lymphoma
3. human T-lymphocyte - leukemia
form of lung cancer
Main cause of cancer?
some event leads to inapp. or inaccurate genetic info being passed on
Normal function of tumor suppressor genes?
inhibit cell division
What occurs when tumor suppressor genes are not functioning normally?
cell division is not inhibited and cells will divide continuously
EX of tumor suppressor genes?
- 1. Rb gene
- 2. P53 gene
- 3. BRCA 1 & BRCA 2
What is the Rb gene?
codes for the master break of the cell cycle - blocks cell division by binding transcription factors needed for division
quality control gene - transcription factor that binds to genes and fixes errors
Common tumor suppressor gene that is ass. with cancers?
BRCA 1 & 2 genes are ass. with what cancer?
ppl with BRCA 1 & 2 are more predisposed to breast cancer
How do chemo and radiation work?
they induce cell death by mediating P53 to catch probs
cause enough damage to the cell to trigger P53 mediated apoptosis
change from proto-oncogenes to oncogenes
Initiation -normal cell -> carcinogen (virus, sun, toxin, etc) -> DNA damage and cell mutation
Promotion - activation of oncogenes by a promoter agent
Progression - malignant tumor has formed
3 stages of cancer development?
What occurs during the initiation stage of cancer?
Etiologic agents or carcinogens that can cause initiation stage?
- 1. tabacco
- 2. radiation
- 3. certain viruses
- 4. asbestos
- 5. chemicals
- 6. chemotherapeutic and immunosppressive agents
- 7. alcohol
What occurs during promotion stage of cancer?
mutant cell is induced to replicate and divide
What occurs during the progression stage of cancer?
mutant cell receives properties that allow it to be malignant
Cancers r/t tobacco?
- 1. pancreas
- 2. bladder
- 3. kidney
- 4. mouth
- 5. esophagus
- 6. cervical
- 7. lung
Radiation can cause ____ or ____.
certain kinds can cause cancer and can also be used to Tx it
Tobacco is a _____ carcinogen which means?
complete - affects initiation and promotion
Leading cause of cancer death in men and women with survival rate of only ____%?
What increases risk of cancer r/t tobacco and alcohol?
if use tobacco and alcohol together
Risk factors for promotion of cancer?
- 1. increased dietary fat
- 2. obesity
- 3. cigarette smoking
- 4. alcohol consumption
- 5. prolonged severe stress
- 6. hormones- estrogen and testosterone
- 7. infection
What occurs during the progression stage of cancer?
mutant cells begin to exhibit malignant behavior
5 characteristics of a malignant tumor?
1. anaplastic with abnormal cell size and shape and/or undifferentiated
2. doubling time
3. infiltrates and spreads distantly through blood stream and lymphatic system (metastasis)
4. tumor necrosis
Key concept about promotion?
it is reversible
2 characteristics of malignant cells?
1. produce telomerase
2. insufficient P53
3. tumor necrosis
Telomerase produced by malignant cells?
enzyme that allows malignant cells to survive and thrive - telomeres are not shortened and the cell does not die
Effect of insufficient P53 in malignant cells?
prevents apoptosis of cells b/c P53 is what will recognize that the cell is abnormal
How does metastasis occur?
malignant cells produce special enzymes and receptors to help them escape the original tissue and go through endothelial tissue of vessels -> bloodstream or lymph -> metastasize & enter new tissues
Primary means of metastasis?
through the bloodstream or lymphatic system
What are tumor markers?
substances found in body fluids or tissue that can help Dx tissue type effected
- 1. ID tissue type
- 2. det Tx
- 3. eval pt progress
Purpose of grading and staging of metastasis?
help guide selection of Tx according to behavior of malignant tumor
TNM staging system?
T - size of the original tumor & whether it has invaded nearby tissue
N - nearby lymph nodes that are involved
M - metastasis to distant tissues
4 types of tumor markers?
- 1. antigen
- 2. hormones
- 3. isoenzyme
- 4. immunoglobulins
5 types of antigen markers and cancer they are ass. with?
- 1. carcinoembryonic origin (CEA): lots of areas
- 2. CA 125: ovaries
- 3. CA 15-3: breast
- 4. CA 27-29
- 5. prostate-specific antigen (PSA) for prostate cancer
If a man has s/s of BPH what may be checked?
PSA checked - if elevated could be s/s of prostate cancer
Why is it imp in cancer?
formation of new blood vessels
tumor cannot grow to more than 2cm without angiogenesis b/c need nutrients and O2
What is tumor grading?
What does it determine?
histologic characterization of tumor cells
determines degree of anaplasia (nondifferentiated) & form of the tumor
will get a score
When does angiogenesis usually occur?
late stages of cancer
Staging of a tumor?
describes the location and pattern of spread of the tumor
benign tumors -oma
- malignant tumors:
- carcinoma - epithelial tissue
- sarcoma - mesenchymal tissue
forms linings of the body
nerve cell benign
nerve cell malignant
7 wrning signs of cancer in adults?
- C - change in bowel or bladder
- A - a sore that does not heal
- U - unusual bleeding or discharge: vomiting blood, bleeding after menapause
- T - thickening or lump: SBE, mammogram
- I - indigestion/difficulty swallowing:
- O - obvious change in mole or wart
- N- nagging cough or hoarsness
Warning signs of cancer in children?
- C - continued, unexplained weight loss
- H - HA with vomiting in the am
- I - increased swelling or persistent pain in bones or joints
- L - lump or mass in abd, neck, or elsewhere
- D - dev of whitish appearance of pupils
- R - recurrent fevers not caused by infections
- E - excessive bleeding or bruising
- N- noticeable paleness or prolonged tiredness
Cancer risk factor in diabetics?
if they have a sore that doesn't heal they will be less likely to report it
Concern if pt says they constantly have a lump in their throat?
may be esophageal or other cancer
5 manifestations of cancer?
- 1. metastasis
- 2. pain
- 3. fatigue
- 4. cachexia
- 5. altered carbohydrate metabolism = diabetes-like syndrome
- 6. anemia
- 7. leukopenia/neutropenia
- 8. thrombocytopenia
How will nagging cough or hoarseness be evaluated?
will rule out other causes before cancer is considered
4 effects of cancer on the body?
- 1. pain
- 2. cachexia - wasting/atrophy of body tissues
- 3. myelosuppression
- 4. alopecia & mucositis
What causes pain in cancer?
effects pain receptors - will have diff need for pain meds than others
need more pain meds
Cause of cachexia in cancer?
most severe form of malnutrition/anorexia of cancer r/t toxin release by cancer cells
this is r/t to the cancer not the Tx's
What causes it in cancer?
bone marrow suppression that causes decrease in blood cells - RBC, WBC, & platelets
disease process or secondary to treatment
What causes alopecia and mucositis in cancer?
What is mucositis?
chemo and/or radiation
inflammation/ulceration of MM of digestive tract
If person has cancer and H&H, WBC, and platelets are low what are the risks?
risk for bleeding and infection
5 S/S of cancer cachexia syndrome?
- 1. weight loss
- 2. muscle wasting
- 3. weakness
- 4. anorexia
- 5. anemia
Cachexia nursing consideration?
poor quality of life
Altered carb met. in cancer?
causes a syndrome similar to diabetes where insulin resistance causes hyperglycemia
Cancer pt at risk for ___ & ____.
- risk for bleeding and infections
- 1. soft toothbrushes
- 2. not using razors to shave
- 3. hand washing
- 4. reverse isolation- protect the pt from what others have
Changes in organ function in cancer?
can cause organ failure or overproduction of normal organ secretions
benign usually cause increased secretions and malignant will usually decrease secretions r/t interruption of function
5 local effects of tumor growth?
- 1. bleeding
- 2. compression of BV, lymph vessels, hollow organs, or nerves
What happens if BV are compressed?
ischemia and clots
What happens if lymph vessels are compressed?
lymph nodes enlarge and edema
What happens if nerves are compressed?
pain & movement may be affected
manifestations in sites other than where tumor is - cancer cells produce hormones or hormone-like proteins that affect body in diff ways and areas
What will occur if a tumor secretes PTH -related hormone?
5 EX of paraneoplastic syndrome?
1. PTH - hormone secreted = hypercalcemia
2. ACTH released = cushing syndrome
3. ADH = hyponatremia and water overload
4. cancer cells may produce proteins that affect clotting
5. may cause neurologic disorders
Pt with paraneoplastic syndrome may be predisposed to ___ and ___.
clotting and bleeding
What may be the earliest indicator of a cancer prob?
paraneoplastic syndrome s/s
What is usually the first s/s of cancer?
What will occur with Tx?
Dx measures for cancer?
- depends on type of cancer suspected
- 1. pap smear
- 2. biopsy - gold standard
- 3. tumor markers
- 4. staging and grading
3 goals of cancer treatment?
Reed sternberg cell?
cell found in Hodgkins lymphoma that can be Dx of this cancer
9 Cancer Tx?
- 1. surgery
- 2. radiation
- 3. chemo
- 4. immunotherapy
- 5. interferon
- 6. interleukins
- 7. monoclonal antibodies
- 8. gene and molecular therapy
- 9. stem cell transplantation
6 SE of cancer Tx?
- 1. N/V, abd pain
- 2. alopecia
- 3. anemia
- 4. leukopenia/neutropenia
- 5. thrombocytopenia
- 6. infection
3 things surgery used for in cancer?
- 1. Dx
- 2. staging
- 3. palliative
- 4. curative
Relationship of radiation, chemo, and surgery?
may use radiation to decrease tumor size so can operate, may be used in conjunction
Radiation and chemo local or systemic?
radiation - local
chemo - systemic
______ is primary Tx for most hematologic cancers and some solid tumors
Disadvantage of chemo?
does not distinguish b/t cancer cells and normal body cells esp. MM & hair follicles
S/S that most pt report r/t chemo?
fatigue is primary s/s
will also have nausea
What lab needs to be monitored for pt undergoing radiation or chemo?
must monitor WBC - if get too low cannot do the Tx
Hormone therapy in cancer?
use hormones necessary for the cancer to grow to kill it
What V/S being abnormal would be most concerning in cancer pt?
fever - infection risk
Stem cell transplantation - where do the stem cells come from?
harvest from bone marrow or peripheral blood
bone marrow is richer source
may have stem cell donars
How is N/V Tx in cancer?
zofran/ondansetron is primary
Nursing considerations about alopecia?
- teaching and therapeutic comm are imp
- 1. teach about SE and provide emotional and physical issues
2. wig info
3. therapeutic teaching is imp
4. when might expect to lose their hair
5 can be rapid and occur in clumps
6. can grow back and may look diff than when they lost it: diff color or texture
Nursing consideration about risk for infection regarding teaching?
teach pt risk and to report fever even if low-grade and taking temp is important
any temp increase in cancer is bad
3 different sources of stem cells and where do they come from?
- 1. autologous - from pt
- 2. allogenic - tissue matched person
- 3. syngeneic - identical twin
6 common solid tumors of childhood?
- 1. brain and NS tumors
- 2. neuroblastoma
- 3. Wilms' tumor
- 4. retinoblastoma
- 5. osteosarcoma
- 6. Ewing's sarcoma
3 tendencies of heritable forms of cancer?
- 1. an earlier age of onset
- 2. higher frequency of multifocal lesions
- 3. bilateral involvement of paired organs or multiple primary tumors
Dx of childhood cancers?
- 1. prolonged/recurrent fever not ass. with infection
- 2. unexplained weight loss
- 3. growing masses
nephroblastoma - cancer of kidneys that usually occurs in children
cancer that dev in the cells of the retina
aggressive malignant neoplasm that starts in the bone
rare bone cancer
Risk of cancer in siblings?
double that of normal population
malignant neoplasm of blood-forming tissues of the bone marrow, spleen, and lymph system that causes abnormal proliferation and accumulation of immature WBC
Patho of leukemia?
abnormal or immature WBC form and do not function properly -> massive proliferation of abnormal immature cells -> fewer normal WBCs are produced -> normal bone marrow becomes diffusely replaced with abnormal or immature WBC -> interferes with bone marrow ability to produce cells -> bone marrow does not function
How is leukemia categorized?
by type of WBC affected and the course and duration of the disease
2 char of acute lymphocytic/lymphoblastic leukemia? (ALL)?
- 1. immature lymphocytes proliferate in the marrow
- 2. rapid onset & progression with short clinical course
Age of onset of ALL?
acute lymphocytic/lymphoblastic leukemia
most common in children b/t 2 -10 but can occur in middle age or older
What occurs in Acute myologenous/myelocytic leukemia (AML)?
immature granulocytes proliferate and accumulate in marrow
granulocyte precursor/stem cell
bone marrow is damaged and makes dysfunctional or immature blood cells
can progress to acute myelogenous/myelocytic leukemia (AML)
Diff b/t myelodysplastic syndrome and aplastic anemia?
mayelodysplastic syndrome bone marrow makes dysfunctional or immature blood cells
in aplastic anemia blood cells are not made
3 char of acute leukemia?
- 1. rapid onse
- 2. rapid progression with short clinical course
- 3. left untreated death will result in days to months
Incidence of AML increases with ____?
age over 50
What occurs in chronic lympocytic leukemia (CLL)?
abnormal incompetnet lymphocytes proliferate and accumulate
CLL is more common in ____ & _____.
more common in men and ppl b/t age 50-70
more gradual onset with age 50-70
Chronic myelogenous leukemia (CML)?
abnormal stem cells lead to an uncontrolled proliferation of granulocyte cells resulting in a marked increase in circulating blast cells
When does CML primarily occur?
Incidence slightly higher in _____.
chromasomal abnormality ass. with CML
presence is highly Dx of CML
Chronic leukemia characteristics?
- 1. insidious onset
- 2. more prolonged clinical course
- 3. asymptomatic early in disease
- 4. life expectancy may be more than 5 years
16 S/S of acute and chronic leukemia?
- 1. anemia
- 2. leukopenia
- 3. thrombocytopenia
- 4. dyspnea
- 5. fatigue/malaise
- 6. decreased activity tolerance
- 7. anorexia and weight loss
- 8. bone or joint pain
- 9. HA
- 10. visual disturbances
- 11. fever
- 12. lymphadenopathy - enlarge lymph nodes
- 13. hyperuricemia - high uric acid
- 14. splenomegaly
- 15. increased WBC
- 16. hepatomegaly
8 nursing assessments for leukemia pt?
- 1. pain
- 2. nutrition
- 3. signs of bleeding
- 4. signs of infection
- 5. vital signs
- 6. oral mucosa
- 7. neutropenia
- 8. H&H/CBC/PLT count
Only definitive Dx test for leukemia?
bone marrow biopsy
Meds for leukemia?
- 1. pain
- 2. antiemetics
- 3. chemo - induction therapy
initial treatment - usually chemo with leukemia
Bone marrow transplant in leukemia?
can be curative
chemo to destory abnormally deviding blast cells of pt -> marrow removed from hip/long bones of donar is injected into pt blood stream -> will migrate to bone marrow and start to produce healthy cells
SE of bone marrow transplant?
- 1. flu-like s/s: fever, chills, body aches
- 2. chest pain
- 3. N/V & diarrhea
s/s may last a few weeks
Complications/ risks of bone marrow transplantation?
- 1. destroys WBC - risk for infection
- 2. transplant rejection
Tx of risk for infection in bone marrow transplant pt?
Where are bone marrow biopsy taken from?
Pre nursing consideration?
Post nursing consideration?
posterior iliac crest, anterior iliac crest, or sternum
assess coagulation before procedure
after procedure apply firm pressure for 5 minutes
3 ways to protect bone marrow transplant/biopsy pt from infection?
- 1. vital sign assessments
- 2. neutropenic precautions
- 3. monitor Nadir - lowest blood count of WBC
Nadir and chemo?
chemo will cause nadir point then will climb back up
Nursing management of leukemia?
- 1. meds
- 2. bone marrow transplant
- 3. bone marrow biopsy
- 4. protect from infection
- 5. prevent bleeding
- 6. prevent fatigue
- 7. maintain hydration & nutrition
- 8. stomatitis
- 9. discuss concerns and fears
- 9. alopecia
group of malignant neoplasms that affect the lymphatic system
2 types of lymphoma?
- 1. Hodgkin's disease
- 2. Non-Hodkin's Lymphoma
Hodgkins's disease and nonhodgkin's lymphoma?
hodgkins- char by the presence of Reed-Sternberg cell
nonhodgkins - include all lymphomas except hodgkin
giant cells from B lymphocytes that are ass. with/Dx of Hodgkin's lymphoma
Cause of lymphomas?
Patho of Hodgkin's lymphoma?
Reed-Sternberg cells replace normal cells in 1 lymph node -> spreads to adjacent structures through lymph system-> infiltrates other tissues
Age of Hodgkin's disease occurrence?
Who does occur more in?
peaks in 2 age groups: 15 to 35 and 55-75
occurs more often in men
Non-Hodgkin's lymphoma patho?
cells that make up lymphoid tissue become a bnormal and eventually crowd out normal cells
originates outside lymph nodes and disseminates rapidly
What cells are present in Hodgkin's lymphoma but not non-Hodgkin's?
Reed sternberg cells
Incidence of non-hodgkin's lymphoma?
incidence increases b/t 50-70
more often in men
4 risk factors/etiologic factors for non-hodgkin's lymphoma?
- 1. viral infections - Epstein Barr
- 2. env factors
- 3. exposure to chem/radiation
- 4. H. pylori
Tx of non-hodgkin's lymphoma?
will have AGGRESSIVE TX
3 char of lymphoma?
9 manifestations with advanced disease?
- 1. insidious onset
- 2. painless unilateral or bilateral lymph node enlargement
- 3. enlarged lymph nodes - cervical first then to axillary to inguinal
- 1. weight loss
- 2. night sweats
- 3. malaise
- 4. chills
- 5. pruritis
- 6. anorexia
- 7. non-productive cough
- 8. dyspnea
- 9. renal failure
Nursing assessments of lymphoma?
- 1. lymph nodes
- 2. pain
- 3. nutrition
- 4. weight
- 5. activity level
- 6. respiratory status
- 7. kidney function
- 8. Dx tests
Dx tests to monitor in lymphoma?
- 1. CBC
- 2. BUN/creatinine
- 3. lymph node biopsises
2 systems that can be affected by lymphoma?
kidneys and lungs
8 nursing considerations for lymphoma?
- 1. meds
- 2. raidation
- 3. post-procedure lymphangiogram
- 4. protect from infection
- 5. maintain normal body temp
- 6. pain
- 7. adequate nutrition
- 8. aggressive treatment
plasma cell neoplasms
WBC that are normally in lymph nodes and act as antigen presenting/immune response cells
Incidence of multiple myeloma?
mostly men 50-69
more prominent in Aa
Cause of mult myeloma?
Patho of multiple myeloma?
malignant plasma cells arise form 1 clone of B cells & proliferate withing the hematopoietic tissue -> infiltrate bone to produce osteolytic lesions -> bone destruction leads to hypercalcemia and pathologic fractures -> proliferation of plasma cells crowds marrow space -> plasma cells synth and secrete abnormal small number of immunoglobulins & large # of proteins -> marked increase in IgG or IgA & increased blood viscosity r/t proteins ->
Bence jones protein?
proteins that are a part of regular antibodies & will spill into the urine with mult myeloma
11 manifestations of mult myeloma?
- 1. gradual insidious onset
- 2. pain
- 3. infection
- 4. cord compression
- 5. osteoporosis
- 6. renal stones
- 7. hypercalcemia
- 8. GI distress
- 9. altered musculoskeletal status
- 10. F&E imbalance
- 11. altered cardiopulmonary function
6 nursing assessments for mult myeloma?
- 1. pain
- 2. fractures
- 3. pneumonia
- 4. kidney probs
- 5. MS problems
- 6. CV probs
Dx tests for mult myeloma?
- 1. electrolytes
- 2. CXR
- 3. labs
- 4. CT
- 5. UA for bence jones proteins
Meds for mult myeloma?
- 1. antimicrobials
- 2. chemo
- 3. management of hypercalcemia
Tx of mult myeloma?
palliative only - no cure
meds and radiation
Nursing considerations for mult myeloma?
adequate hydration & ROM
Supportive care for mult myeloma?
- 1. manage pain
- 2. blood products
- 3. when occurs: rest joint, apply ice, admin hemophilia factors