Anemia Flashcards
1
Q
What is anemia?
A
decrease in the number of RBCs or less than normal quantity of hemoglobin in the blood
-results in decreased O2 carrying capacity in blood
-an objective sign of disease
-several etiologies
2
Q
Where are RBCs formed?
A
in the bone marrow (termed erythropoiesis)
adults: spine, ribs, sternum, clavicle, pelvic crest, ends of long bones
children: most bone marrow space
3
Q
Describe the composition of hemoglobin.
A
protein component (2 alpha/2 beta chains)
-fetus: 2 alpha/2 gamma (higher O2 affinity)
heme (porphyrin ring + iron)
4
Q
How long does RBC maturation take?
A
~1 week
5
Q
Describe erythropoiesis.
A
erythropoetin:
-stimulates stem cells to differentiate
-increased release of reticulocytes from bone marrow
-induces Hb formation
works on a feedback loop
-decreased tissue O2 signals kidneys to increase production of EPO
normally this system is in balance
-EPO matching new erythrocyte production to the rate loss of RBCs
6
Q
What is anemia associated with?
A
nutritional deficiencies
acute or chronic disease
drug induced
7
Q
How is the pathophysiology of anemia classified?
A
by pathophysiology or morphology
8
Q
What are the classifications of anemia by pathophysiology?
A
- blood loss (trauma, ulcer, hemorhoids, etc)
- inadequate RBC production
-nutritional deficiency: B12, folic acid, iron
-erythroblast deficiency: bone marrow failure or infiltration
-endocrine disorders
-chronic disease (renal, liver, infection) - excessive RBC destruction (autoimmune, drug, infection)
9
Q
What are the classifications of anemia by morphology?
A
size:
1. microcytic
2. normocytic
3. macrocytic (megaloblastic, non-megaloblastic)
colour:
1. hypochromic
2. normochromic
3. hyperchromic
10
Q
How is size of RBC reflected?
A
by the mean corpuscular volume
-microcytic: <80fL
-normocytic: 80-100fL
-macrocytic: >100fL
11
Q
How is colour of RBC reflected?
A
by the mean corpuscular concentration (MCHC)
-hypochromic: pale
-normochromic: normally coloured
-hyperchromic: darker
12
Q
Describe microcytic RBCs.
A
primarily a result of Hb synthesis or Hb insufficiency
can be due to issues with the heme portion of the globin portion
13
Q
Describe normocytic RBCs.
A
anemia with normocytic cells means the RBC are normal-sized but there is a low a low # of them
decreased production or increased destruction or loss
14
Q
Describe macrocytic RBCs.
A
megaloblastic
-impaired DNA synthesis
-ex: B12, folate deficiency
non-megaloblastic
-not caused by impaired DNA synthesis
-ex: liver disease
15
Q
What is the general presentation of anemia?
A
onset: may be acute or develop slowly
signs & symptoms vary with degree of RBC reduction & how long it has been present
end result is a decrease in O2 carrying capacity of the blood
-perfusion to nonvital tissue is compromised to sustain perfusion of vital organs
-initially patients may be asymptomatic
16
Q
What are the common symptoms of anemia?
A
fatigue, dizziness, weakness, SOB, tachycardia
decreased mental acuity
pallor, cold extremities
17
Q
What are the components involved in the diagnosis of anemia?
A
medical history
physical examination
laboratory evaluation
18
Q
What kind of stuff should be collected in a medical history if anemia is suspected?
A
past & current Hb & bloodwork if available
comorbid conditions
occupational, environmental & social history
transfusion
family history
medications
19
Q
What are some things to look for during a physical examination if anemia is suspected?
A
pallor
postural hypotension, tachycardia
neurologic findings (B12 deficiency)
jaundice (hemolysis)
bleeding gums, blood in stool, urine, epistaxis
20
Q
What kind of laboratory evaluations should be conducted if anemia is suspected?
A
complete blood count (CBC)
-Hb
-hematocrit (packed cell volume)
-RBC count
-RBC indices (MCV, MCH, MCHC)
RBC morphology
reticulocyte count
iron studies (ferritin, serum iron, TIBC)
peripheral blood smear
stool for occult blood
bone marrow aspiration and biopsy
21
Q
What are the RBC indices?
A
MCV=mean corpuscular volume
-avg RBC volume
MCH=mean corpuscular hemoglobin
-avg mass of Hb divided by RBCs
MCHC=mean corpuscular hemoglobin concentration
-avg Hb conc within volume of RBC
RDW=red blood cell distribution width
-higher RDW common in mixed anemias
-marker of variation in RBC width/size
22
Q
What is the Hb level that can diagnose a man or woman with anemia?
A
men: <130g/L
women: <120g/L
23
Q
What are the specific types of anemia?
A
deficiency-related anemias
-iron, vit B12, folate
hemolytic anemia
sickle cell anemia
anemia related to other diseases/conditions
aplastic anemia
24
Q
What is the most common nutritional deficiency worldwide?
A
iron deficiency
25
What are the symptoms associated with iron deficiency anemia?
symptoms of pallor
cardiovascular
respiratory
cognitive complications
decreased QoL
26
What is iron deficiency anemia?
a negative state of iron balance in which daily iron intake are unable to meet RBC and other body tissue needs
-accounts for 50% of anemia cases
27
What are the causes of iron deficiency anemia?
lack of dietary intake
-vegetarians/vegans, poor diet
blood loss
-menstruation, GI (peptic ulcer), trauma
decreased absorption
-celiac disease, medication, gastrectomy, regional enteritis
increased requirement
-infancy, pregnant/lactating women
impaired utilization
-hereditary, iron use
28
What is the pneumonic to remember the causes of iron-deficiency anemia?
NIMBLE
need (increased need in pregnancy, children, etc)
intake is low (malnutrition)
malabsorption
blood
loss
excessive donation
29
Why do we treat iron deficiency anemia?
mortality:
-rarely a direct cause of death
-moderate-severe iron deficiency anemia can cause hypoxia (aggravate underlying pulmonary/CV disorders)
morbidity:
-symptoms can be disruptive, impair daily functioning, etc
-slowed growth rate in children, decreased ability to learn, lower IQ
-splenomegaly may occur with severe, persistent, untreated iron deficiency anemia
elderly:
-anemia associated with: risk of hospitalization and mortality, decreased QoL, decreased physical functioning
pregnancy:
-anemia during pregnancy increases risk for: LBW, preterm delivery, perinatal mortality
30
Describe iron distribution in the body.
body contains ~3-5g, of which 2g are found in Hb
significant amount is stored as ferritin or aggregated ferritin in the liver, spleen, bone marrow
small fraction in plasma, of which most is bound to transferrin
*iron stores are usually well preserved*
31
How is iron metabolism regulated?
hepciding
32
Describe iron absorption.
Fe 3+ ionized in stomach and reduction to Fe 2+
Fe 2+ absorbed from duodenum & upper jejunum by active transport
binding to transferrin
incorporation into Hb or storage as ferritin
33
What are the different iron studies?
serum iron
ferritin
TIBC
Tsat
34
What is serum iron?
concentration of iron bound to transferrin
-best interpreted in context with TIBC
-subject to individual diurnal variation
-may remain in normal range when iron stores are dropping
35
What is ferritin?
storage iron
most sensitive but non-specific and is elevated in inflammatory conditions, liver disorders, etc
36
What is TIBC?
indirect measurement of iron-binding capacity of transferrin, performed by adding and excess of iron to plasma to saturate and then removing the excess
serum transferrin receptor levels, which reflect the amount of RBC precursors available for active proliferation are increased in iron deficiency anemia
37
What is Tsat?
% transferrin saturation
a measure of how much serum iron is actually bound
serum iron/TIBC x 100
38
Describe the labwork we would expect to see with iron deficiency anemia.
decreases in:
-ferritin
-serum iron
-transferrin saturation
-Hb and Hct
increases in:
-TIBC
RBC morphology:
-microcytic (decreased MCV)
-hypochromic (decreased MCHC)
39
What are the types of iron sources?
heme iron
-derived from animal proteins
-better absorbed, more consistent absorption
-less affected by dietary factors
non-heme iron
-plant sources
-fruits and vegetables, nuts, grains, iron-fortified food
-requires acidic GI pH for absorption
40
What can decrease the absorption of iron?
phytates (grains, brans)
polyphenols/tannins (coffee/tea)
calcium
H2RAs, PPIs
gastrectomy/bariatric surgery/achlorhydria
41
What can increase the absorption of iron?
increased stomach acidity
eating heme and non-heme sources at the same time
cook with cast-iron or stainless steel pots/pans
42
What is the RDA of iron during pregnancy?
27mg
43
What are the symptoms of iron deficiency anemia?
typical anemia symptoms
other symptoms:
-brittle, spoon-shaped nails
-pica (appetite for non-nutritive substances)
-pagophagia (consumption of icy drinks)
-smooth tongue
44
What is the first-line dosage form of iron for the treatment of iron deficiency anemia?
oral (tablets or liquid)
-safe, convenient, cheap
*parenteral only to be used if needed*
45
What is the adult dosing of iron for iron deficiency anemia?
~105-200mg elemental Fe/day
46
Why do we avoid SR or EC iron tablets?
dont dissolve much until they reach the small intestine
significantly decreased iron absorption, esp for patients with decreased gastric acidity
47
What are the available salts of iron?
ferrous fumarate
-33% elemental
ferrous sulfate
-20% elemental
ferrous gluconate
-11% elemental
polysaccharide iron complex
-100% elemental
heme iron polypeptide supplement
-100% elemental
48
Which type of iron do most supplements come as?
non-heme
49
What are the side effects of iron?
NV, constipation (sometimes diarrhea)
dark stools
50
How is iron best taken?
on an empty stomach
make patients aware of other meds
avoid interactions with foods/drinks/minerals
51
What is the pediatric dosing of iron?
weight based-->depending on severity of anemia, 3-6mg/kg/d TID
52
True or false: iron overdose in children is toxic
true
53
What is the possible effect that iron can have on teeth?
may stain teeth
-mix liquid forms with juice or water to prevent staining
-use a straw, rinse with water after
54
Describe the onset and symptoms of iron poisoning.
symptoms usually appear within 6 hours
-severe vomiting
-diarrhea
-abdominal pain
-dehydration and lethargy if not treated
-childs vomit or stool may be bloody
55
What can be used to bind up excess iron with iron poisoning?
deferoxamine
56
What are some ways to make oral iron supplementation easier for patients?
lower the dose
-will take longer to correct anemia but still works
-EOD could be considered
use small initial dose and gradually increase
alternate day dosing
take it with food
-may affect absorption, but better than nothing
-consider vit C to increase absorption
take it before bed
57
What are some instances where iron would be given parenterally?
evidence of iron malabsorption
intolerance to oral iron
long-term non-adherence to oral therapy
excessive iron loss
58
What are the formulations available for parenteral iron?
iron dextran
iron sucrose
iron sodium ferric gluconate
iron isomaltoside
59
What is the risk with parenteral iron?
anaphylaxis
other side effects:
-systemic reactions
-headache
-NV
-flushing
-itching
-fever
-injection site reactions
*can be diluted in NaCl to decrease risk of reactions*
60
How long does it take to correct anemia?
6 weeks
61
How long should iron therapy be continued after anemia is resolved?
at least 3 months
-allow for repletion of iron stores and to prevent relapse
-monitor via ferritin
62
What is the rate at which Hb concentrations increase from iron therapy?
~10g/L per week
63
Describe vitamin B12.
aka cobalamin
required for proper RBC formation, neurological function, and DNA synthesis
the body cant make it; must be consumed
large stores in the liver & low daily requirements
-deficiency develops over many years
64
What are some sources of B12?
fish, meat, poultry, eggs, milk and milk products
fortified foods (breakfast cereals)
nutritional yeast products
supplements (as cyanocobalamin)
65
Describe absorption of B12.
HCl acid & gastric protease in stomach releases B12 bound to protein in food
-synthetic vitamin B12 is already in "free form"
free B12 combines with intrinsic factor (IF)
-IF: a glycoprotein secreted by parietal cells of the stomach
the IF is discarded and the B12 is bound to a transport protein (transcobalmin II) for secretion into the blood
*absorption is generally poor*
66
What is a secondary method of B12 absorption?
passive diffusion
-important only when large amounts of B12 are ingested
-provides only small amounts of B12
*absorption of B12 is significantly decreased when the capacity of IF is exceeded*
67
What are common causes of B12 deficiency?
inadequate intake
-vegans, low SES, elderly
malabsorption
-age
-pernicious anemia
-gastrectomy, bariatric surgery, achlorhydria, small bowel disorders, drugs
inadequate utilization
68
What is pernicious anemia?
IF deficiency
autoimmune disease that affects the gastric mucosa
results in gastric atrophy
-destruction of parietal cells
-achlorhydria
-failure to produce IF
malabsorption of B12, even with appropriate dietary intake
associated with increased risk of gastric cancer
69
What are the symptoms of B12 deficiency?
typical anemia sx
often neurological
-numbness/tingling in the hands and feet
-difficulty maintaining balance
-depression, confusion, dementia, poor memory
also: soreness of the mouth or tongue
*neurological sx of B12 deficiency can occur without anemia*
*neurological sx are often progressive and can be irreversible*
70
What are some important pieces of information regarding a persons history when suspecting a B12 deficiency?
diet
age
any GI surgery, intestinal disease, etc
med use
-H2RAs, PPIs
-colchicine
-metformin
71
What are the expected labs for a B12 deficiency anemia?
decrease in:
-serum or plasma vitamin B12 levels
increase in:
-serum homocysteine level (early)
-methylmalonic acid (MMA) levels
to check for pernicious anemia:
-Schilling test, antibodies to IF/parietal cells
RBC:
-macrocytic (increased MVC)
-normochromic (normal MCHC)
72
Why do we treat B12 deficiency?
infants:
-failure to thrive, movement disorders, developmental delays
irreversible neurological damage
increase homocysteine levels are a risk factor for CV disease, some links to Alzheimers
73
What is the treatment for B12 deficiency?
correct underlying cause (if possible)
replenish stores
reverse symptoms
*B12 supplementation*
-most common form cyanocobalamin
-oral or IM
74
Describe oral B12 supplementation.
for treatment in pts with deficiency not related to pernicious anemia
-100ug daily po has been shown to normalize B12 levels within one month
now sometimes used in pts with impaired absorption
-~1% of an oral dose of B12 can be absorbed by non-IF process
75
When is IM B12 supplementation more commonly used?
pernicious anemia
severe malabsorption issues
non-adherence with oral therapy
neurologic symptoms (until resolution)
76
What are the disadvantages of IM B12 supplementation?
more expensive
inconvenient
injection related AE
77
Describe folate.
water-soluble B vitamin
-easily destroyed by cooking or processing
the body cant make enough to meet daily needs
-consume in foods/supplements
-~4-6 months supply stored in liver (may deplete in 6wks if diet is severely deficient)
absorbed in small intestine
THF is a cofactor in DNA synthesis, metabolism of homocysteine
folate important to prevent neural-tube defects
78
What are good dietary sources of folate?
leafy green vegetables (spinach)
fruits (citrus fruits and juices)
dried beans and peas
beef liver
fortified cereals (contain folic acid instead of folate)
*supplements come as folic acid*
79
What is the recommended dietary intake of folate during pregnancy and lactation?
pregnancy: 600ug/day
lactation: 500ug/day
80
What are causes of folate deficiency?
inadequate intake (common)
increased requirements (pregnancy)
malabsorption
certain drugs (may reduce absorption or alter metabolism)
81
What are drug causes of folate deficiency?
anticonvulsants
metformin
methotrexate
sulfasalazine
triamterene
trimethoprim
82
What are the symptoms of folate deficiency anemia?
similar to those seen with B12 deficiency but without neurological sx
83
What are the expected labs of folate deficiency anemia?
decreased serum folate
increased homocysteine levels
*always check B12 levels*
RBCs:
-macrocytic, normochromic (indistinguishable from B12 deficiency)
84
Why do we treat folate deficiency?
pregnancy
-LBW, prematurity, neural tube defects
children
-slow overall growth rate
general morbidity related to anemia
85
What is the treatment for folate deficiency?
oral supplementation (even in pts with absorption problems)
dose:
-1mg/d folic acid usually sufficient
-5mg/d (Rx) if absorption compromised or drug-induced
duration:
-4 months to allow all folate-deficient RBCs to be cleared from the circulation
-correct diet
86
True or false: someone being treated for folate deficiency with concurrent B12 deficiency will see their neurologic issues related to B12 deficiency reversed by folate
false
87
Describe response rate & monitoring for both B12 and folic acid.
reticulocyte response within 3-4 days
Hb improving by ~ day 10
full resolution of the anemia ~ 2 months
neurologic deficits with B12 may take 6 months or longer
production of new hematopoietic cells leads to a shift from K from extracellular to intracellular compartments
-may cause profound hypokalemia
88
What is hemolytic anemia?
decreased survival time of RBCs secondary to destruction in the spleen or circulation
-RBC lifespan be as short as 5 days
-can be acute event or chronic, mild to severe
89
How do RBCs appear in hemolytic anemia?
usually normocytic and normochromic
increased levels of reticulocytes
90
What are the causes of hemolytic anemia?
often idiopathic
can be caused by immune reactions, malignancy, drugs
-drugs: ACEi, NSAIDs, ASA, antibiotics
G6PD enzyme deficiency
-inherited defect
-normally protects RBCs against oxidative stress
91
What is the treatment of hemolytic anemia?
correcting or controlling the underlying cause
steroids and other immunosuppressive agents have been used for autoimmune hemolytic anemias
splenectomy sometimes indicated
92
What is the cause of sickle cell anemia?
autosomal recessive Hgb disorder characterized by DNA substitution at the B-globulin gene
93
What does sickle cell anemia result in?
abnormal type of Hb called hemoglobin S
HbS distorts the shape of RBC, especially when exposed to low oxygen levels
sickled RBCs are rigid and do not pass through microvasculature, prone to rupture
94
What are the symptoms of sickle cell anemia?
impaired growth and development
enlarged spleen
chronic damage to many organs
vaso-occlusive crises
-sludging of sickled cells in microvasculature
-pain in bones of the back, long bones, chest
95
How do RBCs present in sickle cell anemia?
normochromic, normocytic
presence of sickled cells
96
What is the treatment of sickle cell anemia?
acute episodes: pain meds, hydration
vaccinations & penicillin prophylaxis for children up to 6yrs
hydroxyurea
-stimulates production of fetal Hb
-HbF prevents formation of sickled cells
-concerns regarding tumors/leukemia with chronic use
partial blood transfusions
bone-marrow transplant (curative, risks involved)
97
What is anemia of inflammation?
a term used to describe both anemia of chronic disease and anemia of critical illness
reflects inflammatory process resulting in disturbances in iron homeostasis underlying both types of anemia
98
What are the causes of anemia of chronic disease?
chronic inflammation, infection, malignancy
-can occur as early as 1-2mo after onset of the above
-exact mechanisms unclear
-tx aimed at correcting underlying pathology
*a diagnosis of exclusion*
99
What are the symptoms of anemia of chronic disease?
may be mild and non-specific
100
What are the expected labs of anemia of chronic disease?
decreased Hct
decreased serum iron but normal or increased ferritin and normal or decreased TIBC
RBC:
-usually normocytic and normochromic (can be microcytic)
101
What is the main difference between iron deficiency anemia and anemia of chronic disease?
TIBC is normal or low for anemia of chronic disease
TIBC is elevated for iron deficiency anemia
102
Describe anemia due to CKD.
erythropoiesis is decreased
uremic metabolites decrease the life span of circulating RBCs
symptoms:
-general anemia sx, angina, ischemia on ECG, CHF
treatment:
-iron
-erythropoietin stimulating agents
-transfusions
103
Describe contributing factors to anemia in the critically ill.
*found almost universally in this patient population*
factors:
-sepsis
-frequent blood samples, blood loss
-immune-mediated functional iron deficiency
-decreased EPO production
-reduced RBC life span
104
Describe the expected labs for anemia in the critically ill.
decreases in:
-serum iron, TIBC, iron/TIBC ratio
serum ferritin is normal to high
105
What is the treatment of anemia in the critically ill?
address cause
exogenous EPO may/may not improve clinical outcomes
106
What is aplastic anemia?
failure of pluripotent stem cells in bone marrow
hematopoiesis is interrupted
107
What are the causes of aplastic anemia?
70% idiopathic
can be related to toxicity from drugs/chemicals, congenital defects, viruses
-allopurinol, chloramphenicol, NSAIDs, sulfonamides, chemo drugs
immune-mediated suppression of stem cell function
108
What are the symptoms of aplastic anemia?
depends on which cell line is affected the most
-anemia sx (fatigue, pallor, etc)
-bleeding
-fever, infection
109
What are the expected labs for aplastic anemia?
normochromic, normocytic RBC
very low blood counts
110
What is the treatment of aplastic anemia?
supportive care, removal of causative agent
bone-marrow transplant or immunosuppression if not possible
111
Provide a summary of anemia by RBC size.
microcytic:
-iron deficiency, thalassemia, anemia of chronic disease
normocytic:
-sickle cell, hemolytic, aplastic, chronic disease, CKD, mixed
macrocytic:
-B12/folic acid deficiency, liver disease
