what is anemia?
low RBCs
what are 4 common causes of anemia?
impaired erythrocyte production
blood loss (acute or chronic)
increase erythrocyte destruction
combination of these 3
what are Sx of anemia?
paler of skin, hyper dynamic state, fatigue
what are characteristics of B12 deficiency anemia (mechanism, RBC characteristics + primary cause)?
abnormal DNA/RNA synthesis
macrocytic + normochromic
1- congenital
2- intrinsic factor deficiency
what are characteristics of folate (B9) deficiency anemia (mechanism, RBC characteristics + primary cause)?
abnormal DNA/RNA synthesis
macrocytic + normochromic
1- dietary folate deficiency
what are characteristics of iron deficiency anemia (mechanism, RBC characteristics + primary cause)?
insufficient Hb synthesis
microcytic + hypochromic
1- chronic blood loss
2- dietary iron deficiency
what are characteristics of aplastic anemia (mechanism, RBC characteristics + primary cause)?
insufficient erythropoiesis
normocytic + normochromic
1- bone marrow suppression
what are characteristics of posthemmorhagic anemia (mechanism, RBC characteristics + primary cause)?
significant blood loss
normocytic + normochromic
1- bleeding
what are characteristics of hemolytic anemia (mechanism, RBC characteristics + primary cause)?
premature destruction of RBC
normocytic + normochromic
1- increased fragility of RBCs
what are characteristics of sickle cell anemia (mechanism, RBC characteristics + primary cause)?
abnormal hemoglobin synthesis
normocytic + normochromic
1- congenital
what is the pathophysiology of B12-deficiency anemia?
pernicious = highly injurious/destructive
absence of intrinsic factor
- parietal cell destructions (congenital; autoimmune)
- stomach or distal ileum surgical removal
- malnutrition
b12 binds to intrinsic factor
what are the manifestations of B12-deficiency anemia?
common anemia Sx (slow onset of 20-30 years)
specific Sx: demyelination -> neuronal death (not reversible)
what is the pathophysiology of folate deficiency anemia?
more common than B12
folate = essential for DNA/RNA synthesis
most common causes:
1- malnutrition -> often related to alcholism
2- folate malabsorption -> ex: IBS
what are the manifestations of folate-deficiency anemia?
ulcerations + inflammation of bucco-oral area
no neurological manifestations
what is the pathophysiology of iron deficiency anemia?
most common 20% of all cases -> females higher risk cuz of pregnancy + menses
common cause in developed countries -> pregnancy + chronic blood loss
2 main ethologies:
1- inadequate dietary intake
2- excessive blood loss
what are the causes + manifestations of aplastic anemia?
bone marrow suppression
stem cell environment issues
classic anemia Sx
thrombocytopenia
leukopenia
what are the causes + manifestations of posthemorrhagic anemia?
any significant bleeding
initial Sx masked by cardiovascular adaptations to hemorrhage
severe shock if blood loss > 2000 mL
fatal lactic acidosis
can lead to IDA
what are the causes + manifestations of hemolytic anemia?
autoimmune
sepsis
sickle cell anemia
classic anemia Sx
elevated erythropoietin (EPO)
jaundice
what is polycythemia vera? pathophysiology? manifestations?
excessive RBC production
JAK2 mutation increases EPO receptor sensitivity -> increased proliferation for RBC precursors regardless of EPO levels
increased viscosity + thrombocythemia -> hypercoagulable state + elevated BP = increased thrombosis risk
intense painful itching caused by water (aquagenic pruritus)
survival: 10-15 yrs possible but less than 18 months if untreated
what are 5 things necessary for proper RBC development?
healthy bone marrow
erythropoietin -> stimulate RBC maturation
iron -> hemoglobin synthesis
vitamin B12 -> DNA synthesis
folic acid -> DNA synthesis
what is the iron RDA for male, female and pregnant?
11mg/day
18mg/day
27mg/day
what is iron necessary for?
Hb, myoglobin, some enzymes
what are causes of iron deficiency?
blood volume expansion -> ex: pregnant, puberty
chronic blood loss (GI bleed, menses)
mostly increase in demand related
what are consequences of iron deficiency?
iron deficiency anemia (severe -> tachycardia + angina
impaired myoglobin synthesis
impaired enzyme synthesis
impaired child development
impaired cognition
what are diagnosis of iron deficiency?
hallmarks:
1- microcytic/hypochromic RBCs
2- absence of aggregated ferritin
lab tests to confirm:
decreased RBC + reticulocyte count
decreased Hb + hematocrit values
decreased serum iron content
increased serum iron-binding capacity
what are indications of ferrous iron salts?
Tx + prevention of iron deficiency anemia
all formulations have equivalent efficacy + toxicity
ferrous sulfate = preferred choice because cheaper
what are adverse effects of ferrous iron salts?
GI disturbances (dose dependant) -> nausea, diarrhea, heartburn
teeth staining
iron poisoning in children = leading poisoning fatality -> acidosis + shock, antidotes = gastric lavage or iron chelating agents
what are drug interactions of ferrous iron salts?
antacids decrease absorption/ vitamin C increases absorption
what are indications of iron dextran?
Px for whom oral iron is inefficient/impossible (GI disease)
what is optimal dosage of oral iron salts? parenteral iron dextran?
65mg 3x/day for 200mg, best between meals to max absorption
depends on BW + severity of anemia
safety: fatal anaphylactic reactions -> test dose before full blown administration, IV has lower risk than IM, have epinephrine + reanimation equipment ready
what are nursing assessments for iron deficiency?
determine cause
monitor reticulocyte + Hb for success/failure
avoid therapeutic combinations w/other iron, folic acid or B12 meds
duration: until Hb normal, usually 1-2 months
what is main utility of B12?
folic acid activation
what are causes of B12 deficiency?
impaired absorption
insufficient diet (very rare)
what are diagnosis of B12 deficiency?
megaloblast detection
plasma B12 levels
B12 absorption test
what are consequences of B12 deficiency?
megaloblastic (pernicious) anemia -> severe Sx = systemic hypoxia, heart failure + dysrhythmias
nervous system injuries -> demyelination of neurons, long term deficiency (permanent damage), unrelated to folic acid or DNA
GI disturbances
decreased WBC + platelets
what is cyanocobalamin?
drug of choice for all B12 deficiencies
may produce hypokalemia -> RBC synthesis requires K+
oral: mild/moderate deficiency pt, even if lack of intrinsic factor as around 1% is still absorbed
parenteral (NEVER IV): best for pt w/severe deficiency
intranasal: good alternative to parenteral
what are nursing guidelines for moderate B12 deficiency?
only manifestation = megaloblasts
no neuronal damage or WBC decrease
manage via B12 supplements
what are nursing guidelines for severe B12 deficiency?
Sx: disruptions of all blood cells + GI + neuronal injuries
treatment: IM B12 + folic acid injection + blood replacement + platelet transfusion
monitor success: megaloblast disappear + reticulocyte count increases
potential neurologic recovery is inversely proportional to duration of deficiency
what are nursing guidelines for long term therapy for B12 deficiency?
pt with B12 malabsorption -> intrinsic factor deficiency
monthly injections or very large oral doses
what is folic acid necessary for?
DNA synthesis
can folic acid deficiency develop rapidly?
yes due to daily loss
what are causes of folic acid deficiency?
alcoholism: poor diet, enterohepatic folate recycling decreases
sprue: malabsorption syndrome
very rare: drug induced
what are consequences of folic acid deficiency?
similar to B12 except NO neuronal injuries
potential increase of colorectal cancer + atherosclerosis
neural tube defect
what are diagnosis of folic acid deficiency?
megaloblastic anemia with high B12 levels
what is folic acid supplement? indications? adverse effects?
pteroylglutamic acid: inactive folic acid -> rapidly activated upon absorption
already active form are no more effective + more expensive
folic acid deficiency Tx + prophylaxis
initial severe B12 megaloblastic anemia therapy
non short term
increased colorectal cancer + atherosclerosis risks long term
what are nursing guidelines for folic acid deficiency?
intervention should match cause: poor diet -> not supplements
malabsorption -> folate supplements
prophylactic supplements: only for soon to be pregnant, pregnant, lactating
severe deficiency management:
initially IM injection of B12 + folic acid -> combination fastens recovery
continue w/oral folate only
monitor success same as B12
what is leukocytosis?
increased leukocyte count -> normal protective response
however abnormal when count doesn't go back down or rises for no reason -> pathologic condition or myeloproliferative disorders
what is leukopenia?
decreased leukocyte count < 4000 cells/mm3
decrease in neutrophils
caused by bone marrow suppression
what is neutropenia? what are causes?
neutrophils < 2000/ uL
inversely proportional to infection risk
bone marrow suppression (ex: chemo, anemia, anorexia)
increased destruction
severe prolonged infection
what is agranulocytosis?
neutrophil count is 0
complete bone marrow destruction or drug induced
leads to recurrent and persistent life-threatening infection
what is infectious mononucleosis? what are manifestations?
acute viral/bacterial infection of B cells
85% of cases -> Epstein Barr virus (HSV-4)
more than 90% of adults have indications of subclinical EBV infections
called kissing disease
self limiting, recovery within weeks
sore throat + fever
complications in immunocompromised (HIV!!)
splenic rupture is rare (0.1-0.5%)
what are leukemias?
uncontrolled proliferation of malignant leukocytes -> overcrowding of bone marrow -> decreased production + function of normal hematopoietic cells
what are leukemias classified based on?
1- progenitor cells -> myeloid or lymphoid
2- rate of proliferation -> acute vs chronic
ALL - acute lymphoid leukaemia
AML -acute myeloid leukaemia
CLL - chronic lymphoid leukemia
CML - chronic myeloid leukemia
what is pathophysiology of acute leukemias? manifestations?
characterized by undifferentiated or immature cells, usually a blast cell
onset of disease is abrupt and rapid
strong genetic ethology w/chromosomal abnormalities
similar across variety of acute leukemias
fatigue (anemia), bleeding (thrombocytopenia), fever (infection)
splenomegaly + hepatomegaly
pain in bones + joints
CNS - leukaemia infiltration or cerebral bleeding
what is pathophysiology of chronic leukemias? manifestations?
cells are more differentiated but do not function normally
relatively slow progression
CLL involved mostly B cells/ CML chimeric BRC-ABL fusion
CLL: 70% asymptomatic at time of dx, lymphadenopathy + suppression of humoral immunity
CML: splenomegaly + hyperuricemia (gout arthritis), terminal blast phase (rapid progressive leukocytosis survival 3-6 months)
what are malignant lymphomas?
diverse group of neoplasms (cancer) that develop from proliferation of malignant lymphocytes in lymphoid system
often originates from lymph nodes/lymphoid tissue of stomach or intestines
result of genetic mutations or viral infection
produce tumor masses
what is pathophysiology of Hodgkin lymphoma (HL)?
unknown malignant transformation trigger
Reed-Sternberg (RS) cells: large binucleate malignant transformed lymphocytes -> hallmark of HL
hypothesis: abnormal B cell survives thanks to EBV infection -> leads to first few RS cells -> RS cells release cytokines -> inflammatory response
what are manifestations of Hodgkin lymphoma (HL)?
progression from lymph nodes to lymph nodes
pressure + obstruction of local lymph nodes
development of systemic symptoms of infection (fever, fatigue...)
what is pathophysiology of Non-Hodgkin lymphoma (NHL)?
acquired mutation -> cell immortalization + proliferation -> progressive expansion of B cells (80-90%), T cells or NK cells
NO RS cells
what are manifestations of Non-Hodgkin lymphoma (NHL)?
similar to HL
begin as lymphadenopathy (enlarged lymph node)
entranodal involvement = main difference
what is pathophysiology of Burkitt lymphoma ?
fast growing B cell tumor
EBV-induced mutations in c-Myc Proto-oncogene
Boosted by immunocompromised status (HIV!!)
what are clinical features of Burkitt lymphoma ?
tumor primarily in the jaw and facial bones
extra nodal locations develop over time
highest prevalence in Africa in New Guinea
what is pathophysiology of multiple myeloma ?
masses grow slowly in + destroy bone marrow -> leads to pancytopenia (low RBC, WBC + platelets)
multiple genetic mutations + translocation
what is manifestations of multiple myeloma ?
plasma cells produce defective antibodies (M protein) -> proteinuria (90%) + hyper viscosity syndrome (20%)
secret growth factors + bone resorption-promoting factors -> bone lesions + hypercalcemia
what are hematopoietic growth factors (HGF)? what are therapeutic applications?
naturally occurring hormones regulating proliferation + differentiation of blood cells also called colony stimulating factors (CSF)
1-post chemo platelet + WBC regeneration
2- boost bone marrow transplant recovery
3- boost RBC synthesis in chronic renal failure (CRF) patients
what are characteristics of erythropoietin?
primary function -> stimulate maturation of RBCs
other functions: angiogenesis modulation, cell injury apoptosis inhibition -> maintain cellular integrity
alternative to blood transfusions
inefficient w/out B12 + folate + iron
what is purpose of Epoetin Alfa (EPO)? admin? indications? adverse effects?
decrease transfusion requirements
parenteral injections only
1- anemia in chronic renal failure (CRF) Pt: no QOL improvement
2- chemo-induced anemias: palliative purpose only
3- elevate RBC count prior to surgery: only if anticipate hemorrhage
4- AIDS pt on zidovudine
1- hypertension in CRF pt, due to increase in hematocrit
2- serious cardiovascular events: heart failure, stroke, MI, cardiac arrest
what is purpose of Darbepoetin Alfa? admin?
it is a long acting EPO (longer T1/2), same toxicity + efficacy profile as epoetin alfa
purpose: decrease # of injections
1- anemia associated w/CRF
2- anemia associate w/chemo
what are nursing EPO considerations?
safety -> minimize serious cardio events in CRF Pt
dosage should be lowest effective RBC elevation
decrease dosage if Hb increase > 1g/dl in 2wks
temporarily hold Tx if Hb > 11g/dL
warnings -> contraindicated for all cancer pt on curative/remission
must be combined w/anticoagulant for preoperative RBC elevation
monitor
- measure Hb levels at baseline + 2x/week until target
- blood them, iron, complete blood count routinely
what are leukopoietic growth factors (LGF)? what are 2 agents?
stimulate WBC (leukocytes) production
filgrastim (G-CSF, for neutrophils)
sargramostim (GM-CSF, for neutrophils + macrophages)
what is physiology of LGFs? therapeutic use? administration? adverse effects?
released in response to inflammation
increase neutrophil synthesis + macrophages
decrease neutropenia during chemo + bone marrow transplant (BMT) pt
increase pre-BMT hematopoietic stem cell (HSC) harvest
accelerate BMT recovery + increased failed BMT survival time
increase neutrophil recovery + decreased infections in acute myeloid leukaemia pt
parenteral administration only
short term: none + no interactions
bone pain: usually mild, use NSAIDs
leukocytosis/thrombocytosis: only with high dosage
what are thrombopoietic growth factors (TGF)? what is main one?
stimulate platelet (thrombocytes) production
oprelvekin = endogenous interlukin-11
what is action of TGFs? therapeutic use? administration? adverse effects?
stimulates HSC differentiation into megakaryocytes
decreased thrombocytopenia + platelet transfusion during chemo
efficacy decrease in highly myelosupressive chemo regimen
parenteral only
increase kidney sodium/water retention -> edema + increase plasma V
tachycardia + AF -> possibly related to plasma V
rare case: severe anaphylactic