Hematopoeisis

what are the three phases of hematopoiesis?

Mesoblastic, hepatic and myeloid

Mesoblastic process of hematopoiesis

Cells from the mesoderm migrate to the yolk sac to produce primitive hematopoietic cells

Hemoglobin production kicks off

Hepatic process of hematopoiesis

Hematopoiesis occurs mainly in the fetal liver giving rise to definitive hematopoietic cells

Fetal hemoglobin (HbF) predominates replacing embryonic Hb. Detectable levels of adult Hb may be present (HbA)

Begins at 5-7 weeks gestation and continues to birth and a little after

Liver is colonized with erythroblasts, granulocytes and monocytes

Spleen is mainly producing lymphoid B cells

Myeloid process of hematopoiesis

Begins in the bone marrow. By the end of 24 weeks gustation, bone marrow becomes primary site of hematopoiesis

Begins at 18-20 weeks gestation

Megakaryocytes will be in this stage

Bone marrow is produced in medulla in bone

Where is adult hematopoietic tissue located?

Bone marrow, lymph nodes, spleen, liver, and thymus

Where is bone marrow located?

Cavities of cortical (compact) bone supported by trabeculae

Red marrow vs yellow marrow

Red: hematopoietically ACTIVE marrow

Yellow: hematopoietically INACTIVE marrow (fat cells, adipocytes)

Retrogression

At birth all bones contain red marrow, as the body ages, red marrow is replaced by yellow marrow. Starts at year 5

What types of cells does BM contain and what types are in each?

Hematopoietic: erythroid, myeloid, megakaryocytic, lymphoid

Stromal: endothelial, adipocytes, macrophages, lymphocytes, osteoblasts, osteoclasts, fibroblasts

Blood vessels: arteries, veins, vascular sinuses

The red marrow is composed of hematopoietic cells arranged in

Extravascular cords and develop in specific niches within the cords

What are the RBC precursor cells?

Erythroblasts

What is the movement of mature blood cells from bone marrow to peripheral circulation?

Adventitial cells —> basement membrane —> endothelial cells —> vascular sinus —> peripheral circulation

Kupffer cells

Specialized macrophages that remove aged red blood cells and foreign debris

The adult liver is capable of producing various blood cells called

Extramedullary hematopoeisis (outside the bone marrow

Happens when bone marrow cannot produce sufficient blood cells due to disease or increased demand

Red pulp vs white pulp

Red: part of spleen responsible for filtering blood, removing old or damaged RBCs and storing immune cells such as macrophages and monocytes (vascular sinuses)

White: immune tissue in spleen, lymphoid tissue, dendritic cells, germinal areas

What happens when RBCs pass through red pulp?

Blood flow is decreased, glucose supplies depleted, RBCs are subject to damage and stress

slow passage + continued RBC metabolism = environmental changes ( increased acidity, decreased glucose, hypoxia) —> increased damage and stress slow passage—> hemolysis and removal of aged RBCs

Spleen’s two methods for removing aged RBCs

Culling: cells are phagocytized

Pitting: splenic macrophages remove inclusions or damaged surface membrane

Splenomegaly

Spleen become enlarged and palpable (chronic leukemias, myeloproliferative diseases)

Splenectomy

Surgical removal of spleen

Useful in cases of excessive RBC destruction

Autosplenectomy

Spleen becomes non functional due to disease (sickle cell disease)

What are the three possible fates of a HSC?

Self renewal, differentiation, apoptosis

Symmetric vs asymmetric division

When the HSC divides, it gives rise to two identical daughter cells. Both cells may follow the path of differentiation (symmetric) or one daughter cells may return to the stem cell pool and the other daughter cell may follow the path of differentiation (asymmetric)

Stochastic model vs instructive model

Stochastic: Suggests whether or not the stem cell commits to self renewal is random. The initial decision to self renew or differentiate.

Instructive: suggests it depends on the micro environment of the bone marrow. Lineage differentiation that occurs later is determined by various signals from the micro environment

Committed progenitors are called

Colony forming units (CFUSs)

Specialized markers to help identify and originate HSCs

CD34+, CD38-, HLA-DR LOW, THY1LOW, LIN-

Hematopoietic growth factors

Or can be named cytokines, regulate the proliferation, differentiation, and maturation of hematopoietic precursor cells (ex IL-3, IL-7)

Inhibiting apoptosis of hematopoietic precursor cells, stimulate precursors to divide and regulate cell differentiation

Colony stimulating factors

Glycoproteins that stimulate bone marrow to produce and regulate WBCs to enchance immune response

Can be used for treating certain diseases by stimulating specific target cells