Intro to Anemia Flashcards
What is anemia?
Decreased circulating RBC mass–>
decreased hemoglobin concentration of blood–>
decreaed O2 carrying capacity of blood–>
decreaesd O2 delivery to tissues
Compensatory mechanism in anemia
- Increased red cell production
- Increased 2,3-DPG
- Shunting of blood from non-vital to vital areas
- Increased cardiac output
- Increased pulmonary function
What causes a right shift or for O2 to offload faster?
Decreased pH, increaed H+
increased BPG
increased temp
Weakness, malaise, easy fatigability are dt:
Marrow expansion with potential bony abnormalities dt:
Pallor:
Tachycardia; cardiac ischemia:
Dysnpea on exertion:
Tissue hypoxia
Increased RBC production
Shunting of blood
Increased CO
increaed pulmon fnx
• Anemia is not a disease, it is a symptom ofother diseases thus:
• All anemias need to be explained
Three functional classes of anemia
Functional Classification of Anemia
• Blood Loss
• Decreased Production
• Accelerated Destruction
- Iron deficiency–early
- Thalassemia trait
- (Anemia of chronic disease)*
- Some hemoglobinopathies
examples of
Microcytic , normochormic anemia
- Iron deficiency
- Thalassemia trait
- Sideroblastic anemia
- (Anemia of chronic disease)*
examples of:
Microcytic, hypochromic anemia
– B12 and folate deficiency
– Liver disease
– Myelodysplastic syndromes
– Blood loss**
– Hemolysis**
– Some drugs
all cause:
MACROcytic anemia
– Anemia of chronic disease
– Anemia of renal failure
– Marrow infiltration
– Aplastic anemia
– Blood loss**
– Hemolysis**
examples of:
Normochromic/Normocytic
Key considerations when investigating anemia:
- Clinical history
- Physical exam
- Complete blood count (CBC)
- Reticulocyte count
- Examination of peripheral blood smear
- Specific diagnostic tests
– Most important parameter for assessment of O2
-carrying capacity of blood
• Hemoglobin concentration (Hb; g/dL or g/L)
– Hemoglobin in lysed sample reacted with proprietaryreagents
– Resulting complexes measured spectraphotometrically
What does Hematocrit (Hct; %) measure?
– Packed cell volume (percentage of blood volume
comprised by RBCs)
• Centrifugation (old method)
• Currently calculated as MCV x RBC
Hematocrit is usually ____ hemoglobin–does not add
independent information in vast majority of cases
3 times
– Direct measure of # of RBCs per unit volume
– Generally correlates well with Hb and hematocrit,
adds little independent information
Red blood cell count (RBC; # x 109/L)
– Measured directly based on either electrical
impedence or light scatter
– Very useful in the differential diagnosis of anemia
(e.g., microcytic, normocytic, and macrocytic anemias)
• Mean cellular (corpuscular) volume (MCV; fL)
Pt comes in with Microcytic anemia, what is on your DDx?
- Iron deficiency
- Thalassemia
- Anemia of chronic disease
Patient comes in with Macrocytic anemia, what is on your DDx?
• Megaloblastic (impaired DNA synthesis)
– B12 and folate deficiency
– Some drugs
– Myelodysplastic syndromes
• Non-megaloblastic (other mechanisms)
– Reticulocytosis
– Liver disease
– Hypothyroidism
– Some drugs
Causes of Megaloblastic anemia
type of MACROcytic anemia:
(impaired DNA synthesis)
– B12 and folate deficiency
– Some drugs
– Myelodysplastic syndromes
Causes of non-megaloblastic Macrocytic anemia:
– Reticulocytosis
– Liver disease
– Hypothyroidism
– Some drugs
– Measure of average amount of hemoglobin per RBC
– Calculated as Hb/RBC
– High correlation with MCV
Mean corpuscular hemoglobin (MCH; pg)
– Measure of “chromicity” of RBCs
– Calculated as Hb/(MCVxRBC)
Mean corpuscular hemoglobin concentration (MCHC; g/dL)
MCHC is:
–____ in hypochromic anemias
–______ in a few “hyperchromic” states (e.g., hereditary
spherocytosis, hemoglobin CC disease
Decreased
Increased
– Measure of variability of red cell volume
Useful for the separation of anisocytotic anemias
(e.g., Fe deficiency) from non-anisocytotic
anemias (e.g., anemia of chronic disease
Red cell distribution width (RDW)
Poikilocytosis refers to:
reb blood cell shape
Descirbe the abnormal RBC and when we see it in pts
Spherocytes
Round, Smaller Diameter, More densely staining, Lack of central palllor
hereditary spherocytosis, autoimmune hemolytic anemia
Describe cell and when we see it:
Target cells
Examples: Liver dz, splenectomy,
hemoglobinopathies
Describe cell and when we see it:
Elliptocytes (ovalocytes)
Examples: Hereditary elliptocytosis, megaloblastic anemia,
iron deficiency, myelofibrosis
Describe the cell and when we see it:
Teardrop cells
Examples: Megaloblastic anemia, myelofibrosis,
extramedullary hematopoiesis
Describe cell and when we see it
Fragments (schistocytes)
Examples: TTP, DIC, HUS
malignant hypertension
Describe Cell and when we see it
“Bite” cells
Example: Oxidant hemolysis
(e.g., G6PD deficiency)
- Red cell size variability =
- Average red cell size =
(anisocytosis)
(microcytosis, macrocytosis)
Hemoglobinization can be normal or too little
(below is normal)
(hypochromia,
normochromia)
What’s with these weird cells in the PB smear?
Polychromasia: presence of reticulocytes = larger cells that look purple, sign of increased reticulocytes
What the fudge are those things?
Howell-Jolly Bodies (nuclear
fragments)
Examples: Splenectomy,
megaloblastic anemia
What are those little nugglets? why are they in there?
Pappenheimer bodies (iron
granules)
Examples: Splenectomy, iron
overload
It looks like that poor cell has the chicken pox, whaaaaa?
Basophilic stippling (coarse)~ defect of hemoglobin synthesis
Examples: Thalassemias,
MDS, lead poisoning
What is that? Why? Why is it there, WHY?
what is it called when RBC stack like coins and why does this occur?
Rouleaux
Decreased repulsive forces between RBCs
Examples: Increased serum proteins (Ig,
fibrinogen)
Why do RBC clump up in this image?
Agglutination
Examples: IgM RBC
antibodies (cold agglutinins) that are xlinking
Anemia of Blood Loss–Acute
What happens initially?
When do we see signs of anemia?
- Initially no anemia by CBC parameters despite decrease in blood volume
- Anemia develops as tissue fluid enters vascular space to restore blood volume, producing dilution of cellular elements
In anemia of acute blood loss: Reticulocyte count increases after ____days and peaks after _____
2-3
7-10 days
Anemia of Blood Loss–Chronic
• No anemia initially because:
• Slight reticulocytosis
marrow is able to compensate
In anemia of chronic blood loss, what occurs eventually?
• Eventual development of iron deficiency with
resultant iron deficiency anemia
Sites of RBC production
– Embryo: ____
– Fetus (3 months gestation until birth):
– Shortly after birth through adult life:
Yolk sac
Liver
BM
How is RBC production regulated in terms of oxygen delivery and EPO?
– Decreased oxygen delivery induces the production of
erythropoietin by kidney
– Erythropoietin causes proliferation and differentiation
of committed progenitor cells
(EPO–>CFU-E to inducte Erythroblasts to become RBC)
Normoblastic Maturation
• Normoblasts (nucleated RBC precursors) obtain
iron from _______ for hemoglobin
synthesis
plasma transferrin
Up to _____ produced from each pronormoblast (earliest morphologically recognizable erythroid precursor)
16 reticulocytes
**• Roughly equal numbers of reticulocytes and
normoblasts in marrow
As we go vrom Stemcell to RBC in the normoblastic maturation, what happens to Hemoglobin and RNA?
Hemoglobin INCREASES
RNA DECREAES
*cells shrink and will lose nucleus
What is pictured below?
pronormoblast (earliest morphologically
recognizable erythroid precursor)
very roud regular nuclei with concentric ring of cytoplasm
***basophilic normoblasts are more basophilc and look simular
Admix of RNA and proteins, just note polychromatophilcl and basophilic thing
look at picture before
Earliest anucleate erythroid form
• Larger than mature RBCs
• Contain residual RNA which gives cytoplasm a
blue tinge on routinely stained blood smears
(polychromasia)
Reticulocytes
How long to reticulocytes reside in marrow and what do they do there?
Stay in marrow for 1 to 2 days synthesizing
hemoglobin before being released into
circulation
Reticulocytes:
• Normally circulate for approximately ____before
losing residual ribosomes, mitochondria, and other
organelles to becoming _______
• Normally __% of peripheral erythrocytes
one day , mature erythrocytes
1%
How can we detect reticulocytes?
• Used as measure of marrow RBC production
– Cleaves anemias broadly into those with decreased red cell
production and those with adequate marrow response to
blood loss or increased RBC destruction
Can be detected using RNA stains to obtain a
“reticulocyte count”
– Expressed as % of total RBCs
Used as measure of marrow RBC production
– Cleaves anemias broadly into those with decreased red cell
production and those with adequate marrow response to
blood loss or increased RBC destruction
Reticulocytes
The Reticulocyte Count
• Problem:
• Solution: Corrected reticulocyte percentage
– Retic% x (patient HCT/45)
• Better Solution:
Reticulocyte % varies depending on
total RBC count
Absolute reticulocyte count
Decreased RBC Production
leads to what 3 problems
• Ineffective erythropoieis
• Decreased RBC precursors (marrow failure)
• Anemia of chronic disease (anemia of
inflammation)
Decreased red cell production despite increased RBC precursors in marrow
• Characterized by defects in maturation
Ineffective Erythropoiesis
Three examples of Ineffective erythropoiesis
– Iron deficiency (cytoplasmic maturation defect)
– Megaloblastic anemia (nuclear maturation defect)
– Myelodysplastic disorders
Features of Ineffecitve Erythropoiesis:
Ineffective Erythropoiesis:
General Features
• Prominent______ abnormalities of erythrocytes due to disordered mutation
•______ of erythroid precursors in marrow
• Decreased_____ count despite increased erythroid mass in marrow
morphologic
Dysmaturation
reticulocyte
Proliferation Defect characterized by an absolute decrease in the marrow mass of erythroid precursors
Decreased RBC precursors
Cause of absolute decrease in the marrow
mass of erythroid precursors seen in Decreased RBC Precursors
– Decreased erythroid progenitors available for RBC
production or
– Decreased proliferative capacity of numerically adequate
erythroid progenitor
– Usually normochromic/normocytic
– Usually little anisopoikilocytosis (compared to maturation
defects/ineffective erythropoiesis)
– Decreased reticulocyte counts
General features of Decreased RBC precursors:
Decreased RBC Precursors
• Stem cell defects with adequate erythropoietin: 3 causes
Red cell aplasia (pure) vs. pan-aplasia (aplastic anemia)
– Congenital
– Acquired
Diamond-Blackfan syndrome (pure red cell aplasia)
• Fanconi’s anemia (pan-aplasia)
both examples of:
congenital Stem cell defects with adequte erythropoietin
(see decreased RBCs)
In Decreased RBC precursors we can see marrow replacement caused by what?
– Leukemias/lymphomas
– Metastatic carcinoma
– Fibrosis
– Storage disease
Decreased EPO could case decreased RBC precursors, when would we see that?
Anemia of renal failure
- Inflammatory block in erythropoiesis
- Thought to be mediated by IL-1, TNF-alpha, and IFN gamma
- Probably multiple mechanisms
Anemia of Chronic Disease
General properties of RBCs
• Biconcave disc
– 7.5-8.7 m in diameter
– Average volume of 90 fl
• Special membrane structure which provides
durability, flexibility, and tensile strength
– Can swell to a volume of 150 fl
– Can get through a 2.8 m diameter capillary
– Springs back to original shape after distortion
Key in RBC membrane cytoskeleton
ankyrin
Beta spectrin
Alpha spectrin
***RBC should be able to do red cell
Accelerated RBC Destruction
(Hemolysis)
• Red cells normally circulate for ~120 days
• Increased destruction results in
increased marrow production
– 8 times normal in ideal circumstances
• Enough iron
• Enough folate
• Otherwise good health
• When rate of destruction exceeds bone marrow’s ability to
compensate,_____ develops
– we see a new steady state at _____
anemia
lower hemoglobin level
Predominates in most forms of hemolytic anemia
• Final common pathway: Decreased RBC
deformability
Extravascular Hemolysis
What results from decreased RBC deformability seen in Extravascular hemolysis?
– Rigid, non-deformable cells have trouble traversing
narrow slits between splenic cords and sinusoids
– Cells are damaged further with prolonged exposure to
splenic cordal environment
– Damaged cells phagocytized by cordal macrophages
What is the fate of Hemoglobin in the Intravascular pathway?
Hemoglobin + Haptoglobin –> to the liver
1/2 = 10-30 mins
What is the fate of Hemoglobin in the extravascular pathway?
taken up by splenic macrophage and combines with lysosome–> get lipid + protein + heme breakdown
Heme –> Biliveridin how?
Biliveriden –> Bilirubin how?
via Heme oxygenase
Biliveridin Reductase
Features of Hemolysis
- _____ indirect bili from heme metabolism
- _____ LDH released from destroyed RBCs
- _____ haptoglobin
Increased
Increased
Decreased
Features of hemolysis:
• Splenomegaly in ____ cases
• Bony abnormalities in _____ hemolytic
anemias
chronic
severe chronic
