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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
What is MCHC? How is it calculated?
Mean Corpuscular HGB Concentration- conc of hgb in given volume \*Important in determining palor of RBC\* MCHC = hb/hct
26
What are the anemia size classifications? What are the based on and the given values of each?
1. Microcytic: MCV \< 80 2. Normocytic: MCV 80-100 3. Macrocytic: MCV \>100
27
What are the anemia palor classifications? What are the based on and the given values of each?
1. Hypochromic 2. Normochromic 3. Hyperchromic \*Based on MCHC\*
28
Anisocytosis?
description of peripheral blood patient's red blood cells are of unequal **size**
29
Poikilocytosis?
description of peripheral blood RBC vary in **shape**
30
What do the words mean: - cytosis - cythemia - penia - pan
* -cytosis and -cythemia: increase * -penia: decrease * -pan: all
31
Terminology: Anemia
↓ RBC volume or HGB
32
Terminology: Polycythemia
↑ amount of RBCs or HGB
33
Terminology: Thrombopenia
↓ platelets
34
Term: Thrombocythemia
↑ platelet count
35
What word describes increase and decreased WBC count?
Leukocytosis: increase WBC Leukopenia: decrease WBC
36
What word describes increased and decreased lymphocytes?
lymphocytosis: ↑ lymphocytes Lymphopenia: ↓ lymphocytes
37
What word describes increased and decreased neutrophils?
Neutrophilia: ↑ Neutropenia: ↓
38
What word describes increased eosinophils?
eosinophilia
39
What does pancytopenia mean?
↓ number of all cell lines (RBC, WBC, PLT)
40
In terms of peripheral blood values, what does "Absolute" mean?
**actual number**, NOT A PERCENT
41
What are rough normal values for: HGB HCT MCV (fl)
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
Signs and Symptoms of Iron Def Anemia
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
Causes of Iron Def Anemia
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
What type of anemia does iron deficiency present as?
hypochromic , microcytic (MCV \<80) anisocytosis (size)- no consistent shape change ↑ RDW
45
What is Anemia? Common Causes?
↓ 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
What type of anemias result as a lack of iron?
1. Iron Def 2. Anemia of Chronic Disease 3. Sideroblastic anemia \*absolute lack, ↓ availability, difficulty utilizing iron in RBC
47
What causes megaloblastic anemia? Result?
B12 or Folate Def **Deficient DNA synthesis** enlarged erythroid precursors and RBC
48
What type of anemia is Aplastic? What causes it?
Pancytopenia: ↓ in all cell lines direct toxin or drug effect
49
What is the problem in **Hemoglobinopathies**? Effect?
Problem in HGB synthesis Causes RBC destruction
50
What causes a **G6PD Def**? Effects?
Inability to deal with oxidative stress Hemolysis
51
What causes autoimmune hemolytic anemia?
autoantibodies destroying own RBC
52
What causes congenital anemias?
instrinsic dysfunction in RBC line
53
How do myelodysplastic neoplasms or metastatic tumors cause anemias?
cause direct dysfunction of hematopoietic cells or replacement/crowding of bone marrow elements
54
**5 steps in Lab Eval of Anemia?**
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
What lab could you use to evaluate iron def anemia vs thalassemia?
RDW
56
What are potential causes of Normocytic anemia w/ low reticulocyte count?
**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
What are potential causes of **Normocytic** anemia w/ **high reticulocyte** count?
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
What are potential causes of **Macrocytic** anemias?
1. Megaloblastic anemia (B12, folate def) 2. Alcoholic Liver Disease (toxicity of ETOH to BM)
59
What are potential causes of Microcytic anemias?
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
What conditions would you find nucleated RBC?
1. _Compensatory Erythropoesis_: severe anemia, chromic hypoxemia 2. _Hyposplenism, asplenia_: sickle cell, traumatic splenectomy
61
What cancers commonly metastasize to bone?
breast, prostate, kidney cancers cause fibrosis in marrow
62
What is Extramedullary Hematopoiesis? Presentation?
* 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
When is Extramedullary Hematopoiesis a compensatory response?
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
What anemias have associated buzzword of "teardrop RBC"?
thalassemia
65
Causes of Neutrophilia
* acute bacterial infection (high fever, strep, pyrogen) * meds (glucocort, catecholamines) * Cig smoking * physical stress * myeloproliferative neopasms/leukemia
66
What is a "left shift" on peripheral blood smear?
increase immature leukocytes, especially band forms (horseshoe nucleus)
67
Toxic granulation?
dark course granules within neutrophils- esp present in inflammatory conditions
68
What is associated w/ left shift neutrophilia?
actute bacterial infections
69
HIGH YIELD RBC MORPHOLOGY **Schistocytes:** appearance? meaning?
**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
HIGH YIELD RBC MORPHOLOGY What does peripheral smear look like w/ **G6PD**?
* **"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
HIGH YIELD RBC MORPHOLOGY ## Footnote **Sickle Cell Anemia**
* Elongated, almost worm like flattened RBC * Due to polymerized abdnomal hgb S * Leads to ↑ RBC destruction
72
HIGH YIELD RBC MORPHOLOGY ## Footnote **Spherocytes**
* uniform, very spherical shape * Hereditary spherocytosis- ↑ RBC Destruction
73
HIGH YIELD RBC MORPHOLOGY **Megaloblastic Anemia**: B12, Folate Def
* large RBC (macrocytic) * hypersegmented neutrophils (6+ lobes) * BM is hypercellular w/ giant metamyelocytes and band forms (megaloblastic hyperplasia)
74
Leukemoid Reaction
* 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
What should your top DDx for WBC \> 50,000?
1. leukemia 2. lymphoproliferative process
76
Chronic Myelogenous Leukemia (CML)
* Median WBC \>100,000 * Few immature blasts initially (10-19%), % ↑ w/ disease progression (\>20%) * Immature cells, basophils, eosinophils * **Adults**
77
Acute Myeloid Leukemia (AML)
* All ages, but peaks at age 60 * Accumulation of immature myeloid blasts (\>20%) in BM * Present: anemia, thrombocytopenia, neutropenia due to BM crowding
78
What pathogens are pt's w/ neutropenia at increased risk for?
bacterial and fungal
79
2 Main pathophysiologic causes of Neutropenia
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
Morphological Blood Smear Patterns for ## Footnote **Mono (EBV)**
* Atypical T-lymphocytes- misshaped, nonuniform * large cells, enlarged hyperchromic nuclei * + on heterophile antibody test
81
What test would you use for concerns of Leukemia?
flow cytometry- analyzes different antibody markers Leukemia is clonal = all cells from same precursor
82
Causes of **Eosinophilic** Leukocytosis
**allergies** **parasites** drug rxns, malignancies (non-hodgkins) atheroembolic disease (transient)
83
Causes of **Basophilic** Leukocytosis
**Rare**- can be seen in **leukemia** chronic myeloid leukemia (myeloproliferative neopl)
84
Causes of **Monocytosis**
**Atypical Bacterial Infections**: endocarditis, malaria, TB **Autoimmune**: SLE IBS (ulcerative collitis)
85
Physiological range for platelets?
150,000-450,000 PLT/uL
86
What would the patient present with in **Thrombocytopenia**?
* 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
Causes of Thrombocytopenia
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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