Hematopoesis

Question 1

Describe where hematopoiesis occurs before birth, in childhood, and in adulthood.

Answer 1

Before birth:
From 0-2 months, occurs in the embryo’s yolk sac.
From 2-7 months, occurs primarily in the spleen and liver.
From 7 months til birth, and for the duration of the adult life, the bone marrow is the primary site of hematopoiesis.
As a person ages, the hematopoiesis tends to occurs more along the axial skeleton: ribs, skull, pelvis, sternum, and vertebrae.

Question 2

Be familiar with hematopoietic stem cells, progenitor cells, and precursor cells.

Answer 2

Multipotent HSC: Asymmetric cell division (1HSC daughter and 1 multipotent progenitor)

Pluripotential SC: CFU-GEMM = granulocyte/erythroid/monocyte/megakaryocyte, the mother of all non-lymphoid blood cells.
CFU-L is the mother of all lymphoid cells.
Can self-renew or commit

Progenitor cells
The myeloid progenitors: 
CFU-GM (Granulocyte/Macrophage);
CFU-G (Granulocyte); 
CFU-M (Monocyte); 
CFU-E (Erythroid); 
CFU-Meg (Megakaryocyte); 
CFU-Eo (Eosinophil); 
CFU-Baso (Basophil). 
Burst Forming Unit-Erythroid (BFU-E) is the progenitor cell that gives rise to CFU-E; the name derives from the impressive, exuberant appearance of the colonies that these cells form. 

Precursors: recognizable, maturing cells that are visible and counted when a marrow specimen is examined (e.g. myeloblasts, myelocytes, orthochromic normoblasts). Precursors are capable, up to a point, of cell division, but cannot self-renew. Precursor cells give rise to the mature, functional cells in the peripheral blood, lymphoid organs, and reticuloendothelial system.

Question 3

Know the major hematopoietic growth factors (HGFs).

Answer 3

• Erythropoietin (EPO) - made by certain kidney cells in response to hypoxia, promotes erythropoiesis
• Thrombopoietin (TPO) - promotes megakaryopoiesis
• Granulocyte-monocyte colony stimulating factor (GM-CSF) - promotes granulopoiesis and monopoiesis
• Granulocyte colony stimulating factor (G-CSF) - promotes granulopoiesis
• Monocyte colony stimulating factor (M-CSF) - promotes monopoiesis
• Interleukin-5 (IL-5) - promotes production of eosinophils
• Interleukin-3 (IL-3) - promotes production of basophils
• Stem Cell Factor – production of mast cells

Question 4

Be familiar with the names, characteristics, and order of progression of the different precursor and mature cell types in the erythroid, granulocytic, monocytic, and megakaryocytic lineages.

Answer 4

RBCs gradually shrink in size, cyto turns from blue to pink, reticulocytes are increased in blood in response to anemia.

Granulocytes: nucleus gradually indents then becomes segmented, granules appearance (lose primary granules and gain secondary ones), color of secondary defines it

Platelets: megakaryocte sticks cytoplasm into sinusoids which breaks apart and that gives rise to platelets

Monocyte: start with blast & become indented.

Common concept: immature cells are called blast (immature chromatin, pale, nucleoli, high N:C ratio), as mature: nuclear size shrinks, low N:C ratio

Question 5

Be familiar with the general time frame of granulopoiesis and erythropoiesis.

Answer 5

Erythro:
2 – 7 days for pronormoblast to mature into orthochromic normoblast
1 more day to extrude the nucleus from the orthochromic normoblast
Reticulocyte further matures for 2 – 3 days in bone marrow before it is released into the peripheral blood
TOTAL: 5 - 11 days?

Granulo: 10 - 14 days?

Question 6

Blood cell lifespans

Answer 6

Erythrocytes: 120 days
Platelets: 8.5 days
Neutrophils: 7 hours half-life

Question 7

Be familiar with the process of bone marrow biopsy and aspirate.

Answer 7

Useful for determining cellularity of the marrow, as well as for performing a marrow cell differential
May detect focal lesions in the marrow, for example granulomas or metastatic carcinoma
May evaluate how well the different lineages appear to be developing/maturing
Done for staging with a new diagnosis of lymphoma
Done to follow disease status in patient’s believed to be in remission, or to monitor the efficacy of a treatment

Question 8

Be familiar with some of the main features a pathologist evaluates when reviewing a bone marrow core biopsy and bone marrow aspirate smears.

Answer 8

• Marrow Differential – percentage of cells of different types, performed using Wright-stained smears of marrow aspirate
• Cell Morphology: appear normal or dysplastic? performed on Wright-stained smears of marrow aspirate
• Iron Content – is marrow iron increased, decreased, or normal, and in what compartment(s) is the iron present?

Marrow Cellularity – % of marrow occupied by cells vs fat

• Myeloid:Erythroid Ratio – normally, the ratio of myeloid cells (granulocytic lineage and monocytic lineage) to erythroid cells is around 2:1 to 4:1. (can also be evaluated by results of marrow differential)
• Megakaryocyte Frequency – are there more or less megakaryocytes than would be expected
• Focal Findings – are there abnormal focal lesions in the marrow space, such as metastatic carcinoma, nodules of lymphoma, or granulomas

Question 9

Be familiar with the concept of marrow cellularity

Answer 9

% of the BM that’s hematopoietically active (producing blood cells). If it’s not active, it’s occupied by adipose tissue (fat).

Decreases with age. Rule is that after the age of 50 your cellularity is roughly 100 minus your age. Take with a grain of salt.