14- Intro to Anemia Flashcards

1
Q

What is anemia?

A
  • Anemia is decreased RBC mass. but we can’t measure that so we use hemoglobin concentration of blood as a surrogate
  • Decreased O2 carring capacity of blood
  • decreased O2 delivery to tissues (final physiologic consequence)
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2
Q

What are the 4 compensatory mechanisms of Anemia?

A

Increased RBC production

Increased 2,3-DPG (causes right shift)

Shunting of blood from non-vital to vital areas

increased cardic output

Increased pulmonary function

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3
Q

What 3 things cause right shift what 3 things cause left shift?

A

Right: increased temp, low DPG, low pH

Left: decreased temp, low DPG, high pH

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4
Q

A lot of the symptoms of anemai are caused by the compensatory mechanisms. What mechanisms lead to the following signs/symptoms:

weakness, malaise, easy fatigability

marrow expansion with potnetial bony abnormalities

pallor

tachycardia; cardiac ischemia in severe cases

dyspnea on exertion: increased pulmmonary function

A

weakness, malaise, easy fatigability: tissue hypoxia

marrow expansion with potnetial bony abnormalities: increased RBC 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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5
Q

Explain the disease process of anemia.

A

TRICK QUESTION!

Anemia is NOT a disease. It is a symptom of other diseases, and all anemias need to be explained

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6
Q

What are the 3 funcitonal classifications of anemai?

A

Blood loss

Decreased production

Accelerated destruction

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7
Q

What are the 3 morpholigc classifications of anemia?

A

Microcytic (MCV<80)

Normocytic (MCV=80-100)

Macrocytic (MCV>100)

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8
Q

What arer the two types of microcytic anemia? What are some things that can cause these!

A
  • Normochromatic
    • iron-deficiency-early
    • thalassemis trait
    • (anemia of chronic disease)
    • some hemoglobinopathies eg Hemoglobin E
  • Hypochromic
    • iron deficiency
    • thalassemis trait
    • siderblastic anemia
    • anemia of chronic disease
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9
Q

What are some things that case normochromic/normocytic anemia?

A
  • anemia of chronic disease
  • anemia renal failure
  • marrow infiltration
  • aplastic anemia
  • blood loss***
  • hemolysis**
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10
Q

What are some things that cause macrocytic anemia?

A

B12 and folate deficiency

liver disease

myelodysplastic syndromes

blood loss

hemolysis

some drugs

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11
Q

What are the 6 ways that we investigate 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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12
Q

What things are shown on a CBC?

A

Hemoglobin concentration

Hematocrit

RBC count

Mean cellular corpuscular volume (MCV)

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13
Q

What does the measure of hemoglobin concentration tell us?

A

Hemoglobin in lysed sample reactedwith proprietary reagents

resulting complexes measured spectraphometrically

Most important parameter for assesment of O2 carrying capacity

(Hb; g/dL or g/L)

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14
Q

What is the most important parameter for assesment of O2 carrying capacity of blood?

A
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15
Q

Hemoglobin concentration!

A
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16
Q

What is the hematocrit?

A

(Hct; %)

  • Packed cell colume (percentage of blood volume comprised by RBCs
    • old method was centrifugation
    • currentyl calculated as MCV* RBC
  • usually 3X hemoglobin- does not add independent information in vast majority of cases (ie we do it for no reason)
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17
Q

What is Red blood cell count?

A

Direct measure of number of RBCs per unit volume

generally correlated well with Hb and hematocrit, adds little independent information

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18
Q

What is Mean cellular (corpuscular) volume (MCV; fL)

A

measured directly based on either electrical impedence or light scatter

very useful in the differential diagnosis of anemia (eg microcytic, normocytic, and macrocytic anemias)

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19
Q

What four things lead to a microcytic anemia?

A

iron deficiency

thalassemis

anemia of chronic disease

other (rare)

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20
Q

What 2 things lead to macrocytic anemia?

A

Megaloblastic

non-megaloblastic

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21
Q

What is megaloblastic anemia

A

imparied DNA synthesis

B12 and folate deficiency

some drugs

myelodysplastic syndromes

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22
Q

What is non megaloblastic anemia? What things cause it?

A

macrocytic anemia not caused by impaired DNA synthesis (Megaloblastic= impaired DNA synthesis)

reticulocytosis

liver disease

hypothyroidism

some drugs

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23
Q

What is mean corspuscular hemoglobin?

A

(MCH; pg)

calculated as Hb/RBC

measure of averae amoutn of hemoglobin per RBC

high correlation with MCV

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24
Q

What is mean corpuscular hemoglobin concentration?

A

(MCHC; g/dL)

measure of “chromicity” of RBCs

Calculated as Hb/(MCV*RBC)

decreased in hypochromic anemais

increased in a few “hyperchromic” states (eg. hereditary spherocytosis, hemoglobin CC disease)

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25
Q

What is Red cell distribution width?

A

(RDW)

Measure of variability of red cell volume

coefficient of variation of red cell volumes=standard deviation volume/MCV . Óvolume/MCV

useful for the separation of anisocytotic anemias (eg iron deficiency) from non-anisocytotic anemias (anemia of chronic disease)

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26
Q

What is poikilocytosis?

A

abnormal RBC shape

27
Q

What poikilocytosis do these RBCs have? Describe their shape. What are 2 examples of things thaat cause this?

A

Spherocytes (spheres 3D)

round, small diameter, more densely staining, lack of central pallor

ex: hereditary spherocytosis, autoimmune hemolytic anemia

28
Q

What poikilocytosis do these RBCs have? Describe their shape. What are 3 things taht cause this?

A

target cells

Ex: Liver dz, splenectomy, hemoglobinopathies

29
Q

What poikilocytosis do these RBCs have? What are 4 things that cause this?

A

Elliptocytes (ovalocytes)

Ex: hereditary elliptocytosis, megaloblastic anemia, iron deficiency, myelofibrosis

30
Q

What poikilocytosis do these RBCs have? What are 3 things that cause this?

A

Tear drop cells

megaloblastic anemia, myelofibrosis, extramedullary hematopoiesis

31
Q

What is up with these RBCs?

A

sickle cells! from sickle cell disease

32
Q

What poikilocytosis do these RBCs have? What are 3 things that cause this?

A

Fragments (schistocytes)

TTP, DIC, HUS, Malignant hypertension

33
Q

What poikilocytosis do these RBCs have? What causes these?

A
34
Q

What is anisocytosis?

A

red cell size variability- the the red cells aren’t the same size

35
Q

What is polychromasia?

A

reticulocytes

36
Q

What is in this picture?

A

Howell-Jolly Bodies (nuclear fragments)

ex: spelenectomy megaloblastic anemia

37
Q

What is in this picture?

A

Pappenheimer bodies (iron granules)

ex: splenectomy, iron overload

38
Q

What is in this picture?

A

Basophilic stippling (coarse)

thalassemias, MDS, lead poisoning

39
Q

What is in this picture?

A

Hemoglobin C crystals

ex: Hb CC disease, Hb SC disease

40
Q

What is the arangement of these RBCs called?

A

Rouleaux

decreased repulsive forced between RBCs

Ex: increased serum proteins (Ig, fibrinogen)

41
Q

WHat RBC arrangement is shown in these pictures?

A

Agglutination

ex: IgM RBC antibodies (cold agglutinins)

42
Q

What 8 things do we look at on a peripheral blood smear?

A

red cell shapes (poikilocytosis)

red cell variability (anisocytosis)

average red cell size (microcytosis, macrocytosis)

hemoglobinization (hypochromia, normochromia)

polychromasia (reticulocytes)

red cell inclusions

red cell arangements (Howell-Jolly Bodies, Pappenheimer bodies, Basophillic stippling)

White cell and platelet morphology

43
Q

What hapens during acute anemia of blood loss?

A

initially no anemia by CBC parameters despite decrease in blooc 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 and peaks after 7-10 days

44
Q

What happens during chronic anemia of blood loss?

A

no anemia initially because marrow is able to compensate

slight reticulocytosis

eventual development of iron deficicnecy with resultant iron deficiency anemia

45
Q

Where are RBCs produced for an embryo? fetus (3 months after gestation until birth)? shortly after bibrth through adult life?

A

embryo: yolk sac
fetus: liver

shortly after birth through adult life: bone marrow

46
Q

how is RBC production regulated?

A

decreased oxygen delivery induces production of erythropoietin by kidney

erythropoietin causes proliferation and differentiation of commmitted progenitor cells

47
Q

How do normoblasts mature?

A

normoblasts (nucleated RBC precurors) obtain iron from plasma transferrrin for hemoglobin synthesis

up to 16 reticulocytes are produced from each pronormblast (earliest morphologically recognizabel erythroid precursor)

roughyl equal numbers of reticuloctes and normoblasts in marrow

As they mature they have more hemoglobin (more red) and less RNA (less blue)

48
Q

Fill in the blanks

A
49
Q

What are reticulocytes? What is in their cytoplasm? How long do they stay in marrow vs circulate?

A

earliest anucleate erythroid form

larger than mature RBCs

contain residual RNA which gives cytoplasm a blu tinge on routinely stained blood smears (polychromasia)

stay in marrow 1-2 days then circulate for ~1 day before losing residual ribosomes, mitochondria, and other organelles to becoe mature erythrocytes

50
Q

WHat percentage of circulating RBCs are erythrocytes? How do we detect them? WHat is ti used as a measure of?

A

~1% of peripheral erythrocytes

can be detected using RNA stains to obtain a “reticulocyte count” which is expressed as % of total RBCs

used as a measure of RBC production-identifies anemias with decreased RBC production and those with adequate marrow response to blood loss or increased RBC destuction

51
Q

WHat is the problem with a reticulocyte count? what is an average solution

what is a better solution?

A

prblem: reticuloycte % varies on total RBC count
solution: corrected reticulocyte percentage retic%*(patient HCT/45)

BETTER SOLUTION: Absolute reticulocyte count

52
Q

What is the definition of ineffective erythropoiesis?

A

decreased red cell production despite increased RBC precursors in marrow

charcterized by defects in maturation

ex: iron deficiency (cytoplasmic maturation defect)m megaloblastic anemia (nuclear maturation defect), myelodysplastic disorders

53
Q

WHat are 3 general features of ineffective erythropoiesis?

A

prominent morphologic abnormalities of erythrocytes due to disordered maturation

dysmaturation of erythroid precursors in marrow

decreased reticulocyte erythroid mass in marrow

54
Q

What is the significance of RBC precursors? WHat are 3 features of the progenitors

A
  • proliferation defect
  • characterized by an absolute decrease in the marrow mass of erythroid precursors
    • decreased progenitors available or decreased proliferative capcaity of progenitors
  • features
    • normochromic/normocytic
    • little anisopoikilocytosis (comapred to matration defects/ineffective erythropoiesis)
    • decreased reticulocyte count
55
Q

What are 2 possible results of stem cell defects with adequate erythropoietin? WHat are 3 congenital causes of this and 5 acquired causes?

A

red cell aplasia (pure) and pan-aplasia (aplastic anemia)

congenital: DIamons-Blackfan syndrome (pure red cell aplasia), Fanconi’s anemia (pan-aplasia)
acquired: idiopathic. drugs and toxins, autoimmune, infections, paraneoplastic

56
Q

How do leukemias/lymphomas, metastatic carcinoma, fibrosis, storage disease impact the number of RBC precursors?

A

decrease RBC precuros! Bc they replace them in the bone marrow

57
Q

How does anemia from renal failure impact number of RBC precursors?

A

decrease! Bc decrease Erythropoietin

58
Q

How does anemia of chronic disease occur?

A

inflammatory block in erythropoiesis

mediated by IL-1, TNFa, IF gamma

probably multiple mechanisms

59
Q

What is the size of a RBC? What is the volume? What does the special membrane structure provide?

A

7.5-9.7m in diamteter (can get through a 2.8m diameter capillary)

average volume of fluid is 90fl (can swell to 150fl)

special membrane structure which provides durability, flexibility and tensile strength. it springs back into shape after distortion (same)

60
Q

How long do RBCs circulate? How does increased RBC destruction influence bone marrow production?

A

120 days!

Increased destrction results in increased marrow production (8X normal in ideal circumstances-enough iron, folate, good health)

61
Q

What happens when rate of destruction exceeds bone marrow’s ability to compensate?

A

anemia develops, new steady state at a lower hemoglobin

you can have hemolysis wihtout anemia is bone marrow is able to compensate

62
Q

What are the 3 kinds of hemolysis?

A

intravascular

extravascular

combination

63
Q

What is extravascular hemolysis? When does it happen?

A

it predominates in most forms of hemolysis

final common pathway: decreased RBC deformability

  • rigid, non-defomable cells have trouble traversing narrow slits between splenic cords and sinusoids
  • cells are damaged further with prolnged exposure to splenic environment
  • damaged cell phagocytized by cordal macrophages
64
Q

What are the 7 general features of hemolysis?

A

reticulocytosis

increased indirect bili from heme metabolism

increased lDH released from destroyed RBCs

decreased hepatoglobin

morpholig abnormalities of red cells characteristic of specific disorder

splenomegaly in chronic cases

bony abnormalities in severe chronic hemolytic anemias