Objectives

1. Describe basic histology of bone marrow including the relationship between the endosteum, vascular space, and marrow compartment
2. Identify stages of hematopoiesis
3. Identify different types of blood cells

Blood and Bone Marrow Overview

Blood is a specialized type of connective tissue which flows through the body to provide the needed nutrients, oxygen, hormones, immune system components while removing waste elements as well. Blood is made up of cell derivatives with a protein-rich fluid known as plasma:

• Erythrocytes, or red blood cells (RBCs)- biconcave disc 7-8μm in diameter. Consistent in size in fixed tissue and therefore can be used as a “histologic ruler”. Stain homogeneously with eosin, lack a nucleus. Function: O₂/CO₂ transport
• Leukocytes, or white blood cells (WBCs)
  • Agranulocytes (no granules in the cytoplasm other than occasional azurophilic granule (lysosome))
    • Lymphocytes– precursor for T cells, B cells, NK cells; mature lymphocyte is about the size of a RBC (7-8μm in diameter in blood smear), small lymphocytes have an intense-staining nucleus. Function: wound healing, immunity.
      • T cells– differentiate in the thymus gland.
      • B cells– indistinguishable from B cells in typical blood smear or tissue staining, need to use techniques that target cell-surface markers.
      • NK (natural killer) cells– target specific virus-infected cells and tumor cells
    • Monocytes– precursors for phagocytes in various tissues, largest WBC, about 18μm diameter, indented nucleus. Function: wound healing, phagocytosis.
  • Granulocytes (granules present in cytoplasm)
    • Neutrophils– most numerous WBCs, 10-12μm diameter, multi-lobed nucleus (4 lobes in mature cells), presence of Barr body people with XX sex chromosomes, cytoplasm contains 3 types of granules (azurophilic/primary are the largest, specific/secondary are small and difficult to see in light microscopy, tertiary. Function: phagocytosis.
    • Eosinophils– 10-12μm diameter, bi-lobed nucleus, large eosinophilic granules (primary) which contain crystalloid body and azurophilic/primary granules (lysosomes) found in the cytoplasm. Function: combat parasites, wound healing, chronic infection, allergic reaction.
    • Basophils– least numerous of WBCs, 10-12μm diameter, lobed nucleus obscured by the large granules. Function: allergic reactions (bind IgE), wound healing.
• Thrombocytes, or platelets- small membrane-bound, anucleate fragments of cytoplasm derived from megakaryocytes. Function: coagulation.

Erythrocytes and granular leukocytes have multiple stages of differentiation from their individual progenitor cells that can be visualized in light microscopy:

Each individual granulocyte progenitor cell, erythrocyte progenitor, and megakaryocyte (becomes platelets) progenitor originates from a common myeloid progenitor which differentiates from a hemopoietic stem cell. The different lymphoid cells differentiate from a common lymphoid progenitor which also differentiated from the hemopoietic stem cell.

The process of hematopoiesis, development of RBCs and WBCs and platelets occurs in red bone marrow and some lymph tissues in the adult. During embryogenesis, the hematopoiesis begins in blood islands of the yolk sac around the third week of gestation followed by the second phase in the liver, mostly during the second trimester. The next phase in fetal development occurs in the bone marrow.

Bone Marrow

Bone marrow can be found in the open spaces of bone such as medullary cavities in long bones and trabeculae of spongy bone. Bone marrow is a type of loose connective tissue filled with adipocytes and developing blood cells. There are two types of marrow: red marrow (active in hematopoiesis) and yellow marrow (inactive in hematopoiesis, adipocytes are predominant). The marrow can be found between the endosteum of trabeculae and vascular endothelium. The sinusoidal capillaries allow passage of mature blood cells from the marrow to the systemic circulation.

Viewing blood and bone marrow

Stain- Romanowsky-type stains such as Wright or Wright-Giemsa are typical to observe blood and bone marrow. These type of stains include eosin and oxidized methylene blue dyes.

Blood smears are an easy way to examine the different types of cells in the circulating blood. A drop of blood is placed on a slide and the cover slip is used to smear the blood. Once dry, the dye is applied.

Bone marrow is collected via a core-needle biopsy, typically from the hip bone or sternum (breast bone). The dyes described above can also be applied to examine the different cell types.