Intro Anemia Flashcards

1
Q

What is anemia? (i.e. what leads to the final physiologic consequence)

A
  1. Decreased circulating red cell mass
  2. Decreased hemoglobin concentration of blood ⇒
  3. Decreased O2-carrying capacity of blood ⇒
  4. Decreased O2 delivery to tissues (final physiologic consequence)
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2
Q

What are the physiologic compensatory mechanisms for anemia?

A
  • Increased red cell production
  • Increased 2,3-DPG
  • Shunting of blood from non-vital to vital areas
  • Increased cardiac output
  • Increased pulmonary function
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3
Q

What are signs/symptoms of anemia? What mechanisms lead to these?

A
  • Weakness, malaise, easy fatigability ⇒ Tissue hypoxia
  • Marrow expansion with potential bony abnormalities ⇒ Increased red cell production
  • Pallor ⇒ Shunting of blood from non-vital to vital areas
  • Tachycardia; cardiac ischemia in severe cases ⇒ Increased cardiac output
  • Dyspnea on exertion ⇒ Increased pulmonary function
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4
Q

What kind of disease is anemia?

A

Anemia is NOT a disease

  • it is a symptom of other diseases and must be explained!
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5
Q

What is the functional classification of anemia?

A
  • Blood Loss
  • Decreased Production
  • Accelerated Destruction
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6
Q

What are the morphologic categories of anemia?

A
  • microcytic
    • normochromic
    • hypochromic
  • normochromocytic/normocytic
  • macrocytic
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7
Q

What causes microcytic anemias?

A
  1. Normochromic
    • Iron deficiency–early
    • Thalassemia trait
    • (Anemia of chronic disease)*
      • Most commonly normochromic/normocytic
    • Some hemoglobinopathies (e.g., hemoglobin E)
  2. Hypochromic
    • Iron deficiency
    • Thalassemia trait
    • Sideroblastic anemia
    • Anemia of chronic disease*
      • Most commonly normochromic/normocytic
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8
Q

What causes normochromic/normocytic anemias?

A
  1. Anemia of chronic disease
  2. Anemia of renal failure
  3. Marrow infiltration
  4. Aplastic anemia
  5. Blood loss**
    • normocytic or macrocytic, depending on degree of blood loss
  6. Hemolysis**
    • normocytic or macrocytic, depending on degree of blood loss
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9
Q

What causes **macrocytic **anemias?

A
  1. B12 and folate deficiency
  2. Liver disease
  3. Myelodysplastic syndromes
  4. Blood loss**
    • normocytic or macrocytic, depending on degree of blood loss
  5. Hemolysis**
    • normocytic or macrocytic, depending on degree of blood loss
  6. Some drugs
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10
Q

Investigation of anemia:

A
  • Clinical history
  • Physical exam
  • Complete blood count (CBC)
  • Reticulocyte count
  • Examination of peripheral blood smear
  • Specific diagnostic tests (guided by above)
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11
Q

What can be assessed on a peripheral blood smear?

A
  • Red cell shapes (poikilocytosis)
  • Red cell size variability (anisocytosis)
  • Average red cell size (microcytosis, macrocytosis)
  • Hemoglobinization (hypochromia, normochromia)
  • Polychromasia (reticulocytes)
  • Red cell inclusions
  • Red cell arrangement
  • White cell and platelet morphology
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12
Q

What CBC parameters are used to evaluate anemia?

this is a really long card, sorry :/

A
  1. Hemoglobin concentration (Hb; g/dL or g/L)
    • Most important parameter for assessment of O2-carrying capacity of blood
  2. Hematocrit (Hct; %)
    • Packed cell volume (percentage of blood volume comprised by RBCs)
    • Usually 3 times hemoglobin–does not add independent information in vast majority of cases
  3. Red blood cell count (RBC; # x 109/L)
    • Direct measure of # of RBCs per unit volume
    • Generally correlates well with Hb and hematocrit, adds little independent information
  4. Mean cellular (corpuscular) volume (MCV; fL)
    • Very useful in the differential diagnosis of anemia (e.g., microcytic, normocytic, and macrocytic anemias)
  5. Mean corpuscular hemoglobin (MCH; pg)
    • Calculated as Hb/RBC
    • Measure of average amount of hemoglobin per RBC
    • High correlation with MCV
  6. Mean corpuscular hemoglobin concentration (MCHC; g/dL)
    • Measure of “chromicity” of RBCs
    • Calculated as Hb/(MCVxRBC)
    • Decreased in hypochromic anemias
    • Increased in a few “hyperchromic” states (e.g., hereditary spherocytosis, hemoglobin CC disease)
  7. Red cell distribution width (RDW)
    • Measure of variability of red cell volume
    • Coefficient of variation of red cell volumes = svolume/MCV)
    • Useful for the separation of anisocytotic anemias (e.g., Fe deficiency) from non-anisocytotic anemias (e.g., anemia of chronic disease)
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13
Q

What is the differential diagnosis for a microcytic anemia?

A
  1. Iron deficiency
  2. Thalassemia
  3. Anemia of chronic disease
  4. Other (rare)
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14
Q

Macrocytic Anemia: Differential Diagnosis

  • Megaloblastic:
  • Non-megaloblastic:
A
  • Megaloblastic:
    • B12 and folate deficiency
    • Some drugs
    • Myelodysplastic syndromes
  • Non-megaloblastic:
    • Reticulocytosis
    • Liver disease
    • Hypothyroidism
    • Some drugs
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15
Q

What measures ‘‘chromicity” of RBCs?

A

Mean corpuscular hemoglobin concentration (MCHC)

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16
Q

What CBC parameter would be used to differentiate between Fe deficiency anemia (anisocytosis) vs. anemia of chronic disease (non-anisocytosis)?

A

Red cell distribution width (RDW)

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17
Q

What CBC parameter is used to differentiate between microcytic, normocytic and macrocytic anemias?

A

**Mean cellular (corpuscular) volume **(MCV)

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18
Q

Type of cell and associations?

A

Spherocytes

  • Round
  • Smaller Diameter
  • More densely staining
  • Lack of central pallor
  • Associations:
    • hereditary spherocytosis
    • autoimmune hemolytic anemia
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19
Q

Type of cell and associations?

A

Bite cells

  • Oxidant hemolysis (G6PD deficiency)
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20
Q

Type of cell and associations?

A

Target cells

  • liver dz
  • splenectomy
  • hemoglobinopathies
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21
Q

Type of cell and associations?

A

Elliptocytes (ovalocytes)

  • hereditary elliptocytosis
  • megaloblastic anemia
  • iron deficiency
  • myelofibrosis
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22
Q

Type of cell and associations?

A

Schistocytes (fragments)

  • TTP
  • DIC
  • HUS
  • malignant hypertension
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23
Q

Type of cell and associations?

A

Teardrop cells

  • megaloblastic anemia
  • myelofibrosis
  • extramedullary hematopoiesis
24
Q

Type of cell and associations?

A

Sickled cells

  • Sickle cell disease
25
Q

Describe this peripheral blood smear:

A

Macrocytosis

26
Q

Describe this peripheral blood smear:

A

Microcytosis

27
Q

Describe this peripheral blood smear:

A

Normochromic

28
Q

Describe this peripheral blood smear:

A

Hypochromic

29
Q

Describe this peripheral smear:

What type of cell is this?

A

Polychromasia = Reticulocytes

30
Q

What is this?

What are the associations?

A

Howell-Jolly Bodies (nuclear fragments)

  • splenectomy
  • megaloblastic anemia
31
Q

What is this?

What are the associations?

A

Pappenheimer bodies (iron granules)

  • splenectomy
  • iron overload
32
Q

What is this?

What are the associations?

A

Basophilic stippling (coarse)

  • Thalassemias
  • MDS
  • Lead poisoning
33
Q

What is this?

What are the associations?

A

Hemoglobin C crystals

  • Hb CC disease
  • Hb SC disease
34
Q

What is this pattern? Causes?

A

Rouleaux

  • Decreased repulsive forces between RBCs
  • Examples: Increased serum proteins (Ig, fibrinogen)
35
Q

What is this pattern?

A

Agglutination

  • IgM RBC antibodies (cold agglutinins)
36
Q

What can cause anemia?

A
  • Blood Loss
  • Decreased Production
  • Accelerated Destruction
37
Q

What are the changes seen in acute blood loss?

A
  • 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
  • Reticulocyte count increases after 2-3 days
    • peaks after 7-10 days
38
Q

What are the changes seen in chronic blood loss?

A
  • No anemia initially because marrow is able to compensate
  • Slight reticulocytosis
  • Eventual development of iron deficiency ⇒ iron deficiency anemia
39
Q

RBC Production:

  • Sites of Production
  • Regulation of RBC Production
A
  • Sites of RBC production
    • Embryo ⇒ Yolk sac
    • Fetus (3 months gestation until birth) ⇒ Liver
    • Shortly after birth through adult life ⇒ Bone Marrow
  • Regulation of RBC production
    • Decreased oxygen deliveryproduction of erythropoietin by kidney
    • Erythropoietin ⇒ proliferation and differentiation of committed progenitor cells
40
Q

Normoblastic Maturation

  • What is their function?
  • How many reticulocytes are produced from 1 pronormoblast?
  • What is the normal reticulocytes:normoblasts?
A
  • Normoblasts (nucleated RBC precursors) obtain iron from plasma transferrin for hemoglobin synthesis
  • Up to 16 reticulocytes produced from each pronormoblast
  • Roughly equal numbers of reticulocytes and normoblasts in marrow
41
Q
  • What are reticulocytes?
  • How do they appear morphologically?
  • How long are they normally in the marrow?
A
  • Earliest anucleate erythroid form
    • Larger than mature RBCs
  • Contain residual RNA which gives cytoplasm a blue tinge on routinely stained blood smears (polychromasia)
  • Stay in marrow for 1 to 2 days synthesizing hemoglobin before being released into circulation
42
Q
  • How long are reticulocytes normally in the peripheral blood?
  • What is the normal % of reticulocytes in the peripheral blood?
A
  • Normally circulate for approximately one day before losing residual ribosomes, mitochondria, and other organelles to becoming mature erythrocytes
  • Normally 1% of peripheral erythrocytes
43
Q
  • What is the reitculocyte count?
  • Why do we use this?
  • How can anemias be classified based on the reticulocyte count?
A
  • 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:
    • decreased red cell production
    • adequate marrow response to blood loss
    • increased RBC destruction
44
Q
  • What are the potential drawbacks of the reticulocyte count?
  • How is this overcome?
A
  • Problem: Reticulocyte % varies depending on total RBC count
  • Solution: Corrected reticulocyte percentage
    • Retic% x (patient HCT/45)
  • Better Solution: Absolute reticulocyte count
45
Q

What can cause decreased RBC production?

A
  • Ineffective erythropoieis
  • Decreased RBC precursors (marrow failure)
  • Anemia of chronic disease (anemia of inflammation)
46
Q
  • Define ineffective erythropoeisis:
  • Give examples of ineffective erythropoeisis
A
  • Definition: Decreased red cell production despite increased RBC precursors in marrow
    • Characterized by defects in maturation
  • Examples:
    • Iron deficiency (cytoplasmic maturation defect)
    • Megaloblastic anemia (nuclear maturation defect)
    • Myelodysplastic disorders
47
Q

Ineffective Erythropoiesis:

General Features

A
  • Prominent morphologic abnormalities of erythrocytes due to disordered maturation
  • Dysmaturation of erythroid precursors in marrow
  • Decreased reticulocyte count despite increased erythroid mass in marrow
48
Q

What can cause decreased RBC precursors?

A
  • Proliferation defect
  • Characterized by an absolute decrease in the marrow mass of erythroid precursors:
    • Decreased erythroid progenitors available for RBC production

or

  • Decreased proliferative capacity of numerically adequate erythroid progenitors
49
Q

Decreased RBC precursors:

General features

A
  • Usually normochromic/normocytic
  • Usually little anisopoikilocytosis (compared to maturation defects/ineffective erythropoiesis)
  • Decreased reticulocyte counts
50
Q

Decreased RBC precursors:

  • What is casued by stem cell defects with adequate erythropoietin?
A
  • Red cell aplasia (pure) vs. pan-aplasia (aplastic anemia)
  • Congenital
    • Diamond-Blackfan syndrome (pure red cell aplasia)
    • Fanconi’s anemia (pan-aplasia)
    • Others
  • Acquired
    • Idiopathic
    • Drugs and toxins
    • Autoimmune
    • Infections
    • Paraneoplastic
51
Q

Other causes of decreased RBC precursors:

  • Marrow replacement
  • Decreased erythropoeitin
A
  • Marrow replacement
    • Leukemias/lymphomas
    • Metastatic carcinoma
    • Fibrosis
    • Storage disease
  • Decreased erythropoietin
    • Anemia of renal failure
52
Q

What is the RBC structure?

A
  • 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
53
Q

Accelerated RBC destruction (hemolysis):

  • How does this affect the bone marrow?
  • When will anemia develop?
  • What will cause anemia not to develop?
A
  • 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, anemia develops
    • New steady state at lower hemoglobin level
  • Can have hemolysis without anemia if bone marrow is able to compensate
54
Q

How is hemolysis classified?

A
  • Intravascular
  • Extravascular
  • Combination
55
Q

Extravascular Hemolysis

  • What is it?
  • Describe the final common pathway:
A
  • Predominates in most forms of hemolytic anemia
  • Final common pathway: Decreased RBC deformability
    • 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
56
Q

Fate of Hemoglobin

A
57
Q

Hemolysis:

General Features

A
  • Reticulocytosis
  • Increased indirect bili from heme metabolism
  • Increased LDH released from destroyed RBCs
  • Decreased haptoglobin
  • Morphologic abnormalities of red cells characteristic of specific disorders
  • Splenomegaly in chronic cases
  • Bony abnormalities in severe chronic hemolytic anemias