Heme #1: Hematopoiesis

Front 1

Where does hematopoiesis occur in the fetus? At the end of the first trimester?

What about at birth? As an adult?

Back 1

Fetus- yolk sac
At the end of 1st trimester- liver and spleen

At birth- entire skeleton (bone marrow)
Adult- axial skeleton

Front 2

2 major sites from which to obtain bone marrow aspirate?

Back 2

Iliac crest and sternum (axial skeleton)

Front 3

How does the composition of BM change as you age?

Back 3

As you age, fat replaces bone marrow.

Front 4

An increase demand for blood cells (ex: chronic anemia, or myeloproliferative disorders), causes what changes to occur?

Back 4

1. Yellow marrow can become hematopoietically active
2. Extramedullary hematopoiesis (production of blood cells outside the bone marrow, ex: liver, spleen, kidneys).

Front 5

What does the spaces between boney trabeculae hold?

What three things is it composed of?

Back 5

Bone marrow:
1.Hematopoietic cells “chords”
2. Stroma (supporting tissue)
3. Sinusoids

Front 6

Role of stromal cells in hematopoiesis?

Back 6

1. Support hematopoietic “chords”
2. 2. Secrete growth factors (CSF) needed for stem cell survival/maturation

Front 7

T or F

It is abnormal to find hematopoietic stem cells in the peripheral blood.

Back 7

False- a small number circulate here. This is why harvesting stem cells from peripheral blood is possible.

Front 8

What is a pluripotential cell?

What are it’s 2 major divisions?

Back 8

One that can make precursors that differentiate into all different blood cells (Myeloid= erythroid and granulocyte, Lymphoid= lymphocytes and NK cells)

Front 9

How do you identify a hematopoietic stem cell?

Important property of pluripotent cells that allows them to retain their total number?

Back 9

Look for CD34 expression (otherwise they are rare and indistinguishable).

Self-renewal or Asymmetric mitosis

Front 10

How do you identify progenitor cells (ex: myeloid vs. lymphoid)?

Back 10

Add Growth Factors (glycoproteins) and see them grow in vitro (CFUgm= colony forming unit granulocyte, monocyte, BFUe= burst forming unit erythroid)

Front 11

What two growth factors are NOT produced by stromal cells of the bone marrow?

What are Interleukins?

Back 11

EPO (kidney), and Thrombopoeitin (liver)

Interleukin= cytokines produced by leukocytes that act on leukocytes

Front 12

What cytokines maintain the growth & survival or immature blood cells?

Back 12

SCF (stem cell factor), Flt-L (Flt-Ligand), and IL-3

Front 13

What is the mode of action of G-CSF and GM-CSF? (be specific)

Back 13

GF binds to JAK receptor --> it dimerizes --> auto P* and P* STAT proteins -->activated STAT dimers travel to nucleus and transcribe necessary factors needed for cell maturation

Front 14

What cytokine is most often used to mobilize peripheral stem cells? Why?

What are OTHER functions of this cytokine?

Back 14

G-CSF (increased efficacy and decreased toxicity, less broad than GM-CSF)

It also stimulates proliferation, recruitment of cells , suppression of apoptosis, and increases phagocytic ability of polys.

Front 15

What is a primary Granule?

What do the secondary granules of Eos and Basophils contain?

Back 15

Primary= Azurophilic. Lysosomes (contain Myeloperoxidase)
Eos- MBP (major basic protein)
Basophils- Histamine, Leukotriene

Front 16

Stages of Poly formation? How long does the process take? How long do poly’s live?

Back 16

Proliferation: Myeloblast> Promyelocyte > Myelocyte
Maturation: Metamyelocyte>Band>Seg (mature poly)

Process takes ~10 days
In blood for ~10 hrs, can enter tissue, die in about 1 day

Front 17

A person runs all the way to the doctor’s office and immediately has their blood drawn. Their WBCs are elevated but they are completely healthy. Why?

Back 17

Epinephrine causes demargination of WBCs. Only circulating pool of WBCs is measured on a CBC.

Usually it is 50% circulating, 50% marginated

Front 18

What characteristic finding on a CBC would you expect to see when a patient has an acute infection or sepsis?

What findings seen on a peripheral blood smear would be consistent?

Back 18

Left Shift (more bands beings pumped out, even metamyelocytes). Also sharp rise in WBC count.

Toxic granulations (dark primary granules and cytosolic vacuolization) & Dohle bodies (remnants of RER that stay within the cytoplasm)

Front 19

What is a May-Hegglin anomaly? What can it sometimes resemble?

Back 19

AD, GIANT platelets, thrombocytopenia, and WBC inclusions (Dohle body-like)

You can tell that it’s not Dohle b/c not seen in infection and patient doesn’t bleed typically.

Front 20

What is the Pelger-Huet anomaly? What is pseudo-Pelger-Huet

Back 20

Congenital disorder (AD), granulocytes nuclei can’t segment properly “pince-nez” (spectacle cells)

Acquired form= pseudo-Pelger Huet. Seen in myelodysplasia.

Front 21

Hypersegmentation of the polys should trigger what workup in patients?

Back 21

Should strike concern for Megaloblastic anemia. Workup for folic acid or B12 deficiency.

*can also be caused by chemotherapeutic agents that impair DNA synthesis.

Front 22

Baby with silver hair and red eyes (when light is shone on it), also has frequent infections with strep. What condition is this and what do anticipate seeing on a peripheral blood smear?

Back 22

Chediak-Higashi (AR, problem with vesicle transport)
1. Fusion of primary lysosome --> chunky granules
2. Failure to fuse phagosome and lysosome --> infections
3. Abnormal melanosome transport into keratinocytes  OCA (albinism)