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*MOD Exam 1 > Hematopoiesis > Flashcards

Hematopoiesis Flashcards

1
Q

Before birth, what are the primary locations of Hematopoiesis and during what stage/weeks prenatally?

A

3-8 wks: yolk sac

6-30: liver

9-28: spleen (minor)

28 wks to life: bone marrow

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2
Q

Where is hematopoietically active marrow before and after puberty?

A

before: throughout skeleton

after: axillary locations (vertebrae/pelvis, sternum, ribs, tib/fib)

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3
Q

Where are hematopoietic GF produced?

A

Marrow stromal compartment

endothelial cells

marrow fibroblasts

stromal cells

adiopocytes

Developing lymphocytes and macrophages

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4
Q

What are the hematopoietic growth factors?

A

Colony-stimulating factor (CSF)

Cytokines (interleukins)

EPO

TPO

Stem cell factor (SCF)- fetal tissue and BM, makes stem cells reponsive to other cytokines

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5
Q

What is the general cytokine in myeloid stem cell differentiation?

A

IL-3

IL-6 for megakaryocytes and neutrophils

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6
Q

What is the general cytokine in lymphoid stem cell differentiation

A

IL-2

IL-6 for B-lymphocytes

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7
Q

What are the growth factors for T-cells?

A

IL-2

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8
Q

What are the growth factors for B-cells?

A

IL-2 and IL-6

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9
Q

What are the growth factors for pluripotentent stem cell differentiation into lymphoid stem cells?

A

IL-1

IL-4

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10
Q

granulocyte-macrophage colony stimulating factor

(GM-CSF)

Produced by?

Stimulated formation of?

Clinical correlation?

A

Produced: endothelial cells, T cells, fibroblasts, monocytes

Stimulates: formation of all leukocytes and reticulocytes

Clinical: increasing neutrophils during neutrocytopenia (however, G-CSF more used) - after chemo or BM transplant

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11
Q

granulocyte colony stimulating factor (G-CSF)

Produced by?

Stimulated formation of?

Clinical correlation?

A

Produced: endothelial, fibroblasts, macrophages

Stimulates: increase neutrophils

Clinical: Neutropenia tx after chemo or BM transplant

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12
Q

What does M-CSF do?

A

stimulates increase in monocytes and macrophages

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13
Q

Erythropoietin (EPO)

Produced by?

Stimulates?

Clinical?

A

Produced primarily in kidney

Stimulates formation of RBC

Clinical: tx for anemia

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14
Q

Thrombopoietin (TPO)

Produced by?

Stimulates?

Clinical?

A

Produced in liver

Stimulates increase in megakaryocytes –> PLTs

Clinical: TPO rec antagonists used therapeutically

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15
Q

What are the 5 cell types in hematopoiesis or erythrocytes?

A
  1. Pro-erythroblasts: large, round, mild basophilia
  2. Basophilic Erythroblast: smaller, deep basophilic cyto
  3. Polychromatophilic Erythroblast: basophilic ribo, eosinophilic cyto
  4. Normoblasts: eosinophilic cyto
  5. Nucleated RBC
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16
Q

What are reticulocytes?

A

enlarged, immature erythrocytes which show a residual reticular netrwork of ribosomal material (RER)

~2% of RBC and circulate 2-3 days before nucleus is extruded

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17
Q

What would be the reticulocyte vs RBC count be in hemolytic anemias?

A

Reticulocyte = elevated (high RDW), because they’re larger

Mature Erythrocytes: low, increase destruction

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18
Q

How are plasma cells produced?

A

from activated B-cells in spleen and LN w/ help of T cells

Once differentiated, plasma cells go back to BM

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19
Q

What do monocytes differentiate into in the tissues? What are they further differentiated into (give specific location)?

A

Macrophages in tissue

Microglia (CNS)

Kupffer (liver)

Alveolar Macrophages (lung)

Osteoclasts (bone)

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20
Q

What elements are in plasma?

A

dissolved proteins

glucose

ions (electrolytes)

hormones

Clotting factors

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21
Q

RDW

A

Red cell distribution width- measures range of RBC volume

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22
Q

HCT?

A

hematocrit- volume % of RBC in blood

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23
Q

What is MCV?

How is it calculated?

A

Mean corpuscular volume- avg RBC volume

*important in anemia classification*

MCV= hct/RBC

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24
Q

What is MCH?

How is it calculated?

A

Mean Corpuscular HGB- avg mass of hgb in RBCs

MCH = (Hb x 10)/RBC

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25
Q

What is MCHC?

How is it calculated?

A

Mean Corpuscular HGB Concentration- conc of hgb in given volume

*Important in determining palor of RBC*

MCHC = hb/hct

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26
Q

What are the anemia size classifications?

What are the based on and the given values of each?

A
  1. Microcytic: MCV < 80
  2. Normocytic: MCV 80-100
  3. Macrocytic: MCV >100
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27
Q

What are the anemia palor classifications?

What are the based on and the given values of each?

A
  1. Hypochromic
  2. Normochromic
  3. Hyperchromic

*Based on MCHC*

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28
Q

Anisocytosis?

A

description of peripheral blood

patient’s red blood cells are of unequal size

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29
Q

Poikilocytosis?

A

description of peripheral blood

RBC vary in shape

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30
Q

What do the words mean:

  • cytosis
  • cythemia
  • penia
  • pan
A
  • -cytosis and -cythemia: increase
  • -penia: decrease
  • -pan: all
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31
Q

Terminology: Anemia

A

↓ RBC volume or HGB

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32
Q

Terminology: Polycythemia

A

↑ amount of RBCs or HGB

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33
Q

Terminology: Thrombopenia

A

↓ platelets

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34
Q

Term: Thrombocythemia

A

↑ platelet count

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35
Q

What word describes increase and decreased WBC count?

A

Leukocytosis: increase WBC

Leukopenia: decrease WBC

36
Q

What word describes increased and decreased lymphocytes?

A

lymphocytosis: ↑ lymphocytes

Lymphopenia: ↓ lymphocytes

37
Q

What word describes increased and decreased neutrophils?

A

Neutrophilia: ↑

Neutropenia: ↓

38
Q

What word describes increased eosinophils?

A

eosinophilia

39
Q

What does pancytopenia mean?

A

↓ number of all cell lines (RBC, WBC, PLT)

40
Q

In terms of peripheral blood values, what does “Absolute” mean?

A

actual number, NOT A PERCENT

41
Q

What are rough normal values for:

HGB

HCT

MCV (fl)

A

HGB: 13.5-17.5 (M), 12.3-15.3 (F)

HCT: 40-52 (M), 36-48 (F)

MCV: 80-95 (M and F)

42
Q

Signs and Symptoms of Iron Def Anemia

A

fatigue, HA, menstrual irregularity (long), weakness, pale skin, arrhythmia, SOB, CP, cold extremities

Lab: ↓ HGB, HCT, MCV, MCHC, RBC cwt

retculocyte cwt ↓ as rate of erythropoesis ↓

43
Q

Causes of Iron Def Anemia

A
  1. Low dietary iron or malabsorption (cow’s milk to infants)
  2. impaired absorption (sprue, partial gastrect9omy- acid ↑ solubility and uptake)
  3. chronic blood or iron loss (tumor, ulcer, menometrorrhagia, extreme distance running)
44
Q

What type of anemia does iron deficiency present as?

A

hypochromic , microcytic (MCV <80)

anisocytosis (size)- no consistent shape change

↑ RDW

45
Q

What is Anemia?

Common Causes?

A

↓ RBC volume or HGB

Causes:

  • Lack of iron: Iron def Anemia (MOST COMMON), anemia of chronic disease, siberoblastic
  • megaloblastic (esp B12, folate def)
  • Aplastic anemia and pure red cell aplasia
  • Hemoglobinopathies (sickle cell, B-thalassemia, hereditary spherocytosis)
  • G6PD Def
  • Autoimmune hemolytic anemia
  • Congenital (fanconi, black-diamond)
46
Q

What type of anemias result as a lack of iron?

A
  1. Iron Def
  2. Anemia of Chronic Disease
  3. Sideroblastic anemia

*absolute lack, ↓ availability, difficulty utilizing iron in RBC

47
Q

What causes megaloblastic anemia? Result?

A

B12 or Folate Def

Deficient DNA synthesis

enlarged erythroid precursors and RBC

48
Q

What type of anemia is Aplastic? What causes it?

A

Pancytopenia: ↓ in all cell lines

direct toxin or drug effect

49
Q

What is the problem in Hemoglobinopathies? Effect?

A

Problem in HGB synthesis

Causes RBC destruction

50
Q

What causes a G6PD Def? Effects?

A

Inability to deal with oxidative stress

Hemolysis

51
Q

What causes autoimmune hemolytic anemia?

A

autoantibodies destroying own RBC

52
Q

What causes congenital anemias?

A

instrinsic dysfunction in RBC line

53
Q

How do myelodysplastic neoplasms or metastatic tumors cause anemias?

A

cause direct dysfunction of hematopoietic cells or replacement/crowding of bone marrow elements

54
Q

5 steps in Lab Eval of Anemia?

A
  1. CBC and reticulocyte index (H= destruction of RBC, L=problem w/ RBC destruction)
  2. MCV- micro, normo, or macrocytic
  3. Peripheral smear examine- confirm
  4. serum Fe, total Fe binding capacity, serum ferritin- separate microcytic anemias
  5. RDW- distinguish iron def vs thalassemia
55
Q

What lab could you use to evaluate iron def anemia vs thalassemia?

56
Q

What are potential causes of Normocytic anemia w/ low reticulocyte count?

A

Problem w/ production or RBC destruction

  1. Marrow failure
  2. apastic anemia (drug/toxin)- esp chemo drugs
  3. Myelofibrosis, leukemia/metastasis
  4. Renal Failure (RBC produced in kidneys)
  5. Anemia of chronic disease
57
Q

What are potential causes of Normocytic anemia w/ high reticulocyte count?

A

Increased RBC Destruction

*Marked Erythroid Hyperplasia (BM):↓ myeloid:RBC

  1. Sickle cell anemia
  2. G6PD Def
  3. Hereditary Spherocytosis
  4. Autoimmune Hemolytic Anemia
  5. Paroxysmal Nocturnal Hemoglobinuria
58
Q

What are potential causes of Macrocytic anemias?

A
  1. Megaloblastic anemia (B12, folate def)
  2. Alcoholic Liver Disease (toxicity of ETOH to BM)
59
Q

What are potential causes of Microcytic anemias?

A
  1. Iron Def
  2. Thalassemia (also ↑ reticulocytes due to ↑ prod of RBC while ↓ in HGB, MCV = HCT/RBC)
  3. Anemia of chronic disease
  4. Sideroblastic anemia
60
Q

What conditions would you find nucleated RBC?

A
  1. Compensatory Erythropoesis: severe anemia, chromic hypoxemia
  2. Hyposplenism, asplenia: sickle cell, traumatic splenectomy
61
Q

What cancers commonly metastasize to bone?

A

breast, prostate, kidney cancers

cause fibrosis in marrow

62
Q

What is Extramedullary Hematopoiesis?

Presentation?

A
  • hematopoiesis occuring outside of bone marrow- frequently in spleen, liver, LN
    • occurs normally in fetal development
  • multiple megakaryocytes, erythroid and myeloid precursors in liver, spleen, LN
  • Often presents as mass like lesion w/ local issues or discretely
63
Q

When is Extramedullary Hematopoiesis a compensatory response?

A
  1. severe chronic anemia of thalassemia or sickle cell
  2. stem cell fail (toxic aplastic anemia)
  3. infection
  4. severe chronic anemia (B12, folate def)
  5. Malignant transformation and replacement (lymphoma, mets)
64
Q

What anemias have associated buzzword of “teardrop RBC”?

A

thalassemia

65
Q

Causes of Neutrophilia

A
  • acute bacterial infection (high fever, strep, pyrogen)
  • meds (glucocort, catecholamines)
  • Cig smoking
  • physical stress
  • myeloproliferative neopasms/leukemia
66
Q

What is a “left shift” on peripheral blood smear?

A

increase immature leukocytes, especially band forms (horseshoe nucleus)

67
Q

Toxic granulation?

A

dark course granules within neutrophils- esp present in inflammatory conditions

68
Q

What is associated w/ left shift neutrophilia?

A

actute bacterial infections

69
Q

HIGH YIELD RBC MORPHOLOGY

Schistocytes: appearance? meaning?

A

fragmented part of a red blood cell- typically irregularly shaped, jagged, and have two pointed ends

Can be sign of Microangiopathic hemolytic anemia

  • DIC, TTP/HUS (Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome- thrombocytopenia, microangiopathic hemolytic anemia, neur abnorm, fever, renal impairment)
70
Q

HIGH YIELD RBC MORPHOLOGY

What does peripheral smear look like w/ G6PD?

A
  • “Bite cells” and Heinz bodies- looks like a legit bite was taken from the cell (like 1 bite into a cookie)
  • Denatured HGB due to oxidative stress (infection, drugs, foods)
71
Q

HIGH YIELD RBC MORPHOLOGY

Sickle Cell Anemia

A
  • Elongated, almost worm like flattened RBC
  • Due to polymerized abdnomal hgb S
  • Leads to ↑ RBC destruction
72
Q

HIGH YIELD RBC MORPHOLOGY

Spherocytes

A
  • uniform, very spherical shape
  • Hereditary spherocytosis- ↑ RBC Destruction
73
Q

HIGH YIELD RBC MORPHOLOGY

Megaloblastic Anemia: B12, Folate Def

A
  • large RBC (macrocytic)
  • hypersegmented neutrophils (6+ lobes)
  • BM is hypercellular w/ giant metamyelocytes and band forms (megaloblastic hyperplasia)
74
Q

Leukemoid Reaction

A
  • Marked increase in WBC >50,000/uL- left shift neutrophilia, Positive toxic granules
  • Myeloid hyperplasia
  • Due to infection, drugs, carcinoma (paraneoplastic IL-6)
  • Elevated leukocyte alkaline phosphatase (not typically elevated in leukemia)
75
Q

What should your top DDx for WBC > 50,000?

A
  1. leukemia
  2. lymphoproliferative process
76
Q

Chronic Myelogenous Leukemia (CML)

A
  • Median WBC >100,000
  • Few immature blasts initially (10-19%), % ↑ w/ disease progression (>20%)
  • Immature cells, basophils, eosinophils
  • Adults
77
Q

Acute Myeloid Leukemia (AML)

A
  • All ages, but peaks at age 60
  • Accumulation of immature myeloid blasts (>20%) in BM
  • Present: anemia, thrombocytopenia, neutropenia due to BM crowding
78
Q

What pathogens are pt’s w/ neutropenia at increased risk for?

A

bacterial and fungal

79
Q

2 Main pathophysiologic causes of Neutropenia

A
  1. Inadequate Granulopoiesis
    • Suppression of precursors (drugs, toxins)
    • supression of hematopoietic stem cells
    • ineffective hematopoiesis
    • Congenital neuropenia
  2. Increased Destruction/Sequestration
    1. Immue mediated neutrophil injury (lupus)
    2. splenomegaly (portal htn)
    3. increased peripheral utilization (bad fungal or bacterial infection)
80
Q

Morphological Blood Smear Patterns for

Mono (EBV)

A
  • Atypical T-lymphocytes- misshaped, nonuniform
  • large cells, enlarged hyperchromic nuclei
    • on heterophile antibody test
81
Q

What test would you use for concerns of Leukemia?

A

flow cytometry- analyzes different antibody markers

Leukemia is clonal = all cells from same precursor

82
Q

Causes of Eosinophilic Leukocytosis

A

allergies

parasites

drug rxns, malignancies (non-hodgkins)

atheroembolic disease (transient)

83
Q

Causes of Basophilic Leukocytosis

A

Rare- can be seen in leukemia

chronic myeloid leukemia (myeloproliferative neopl)

84
Q

Causes of Monocytosis

A

Atypical Bacterial Infections: endocarditis, malaria, TB

Autoimmune: SLE

IBS (ulcerative collitis)

85
Q

Physiological range for platelets?

A

150,000-450,000 PLT/uL

86
Q

What would the patient present with in Thrombocytopenia?

A
  • Mucocutaneous bleeding (low PLT) - depends on severity
  • <100 k = high risk surgery (cardiac, neuro, major ortho) should be avoided
  • <50 k = surgical bleeding
  • <20 k = severe spont intracranial bleed
87
Q

Causes of Thrombocytopenia

A
  1. ↑ PLT destruction: IDP, immune (SLE, HIV), drug induced HIT, DIC, TTP/HUS, HIV
  2. ↓ PLT production: BM transplant, liver disease (↓TPO)
  3. Sequestration -> hypersplenism

*MOD Exam 1 (15 decks)

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