Bone marrow structure & Blood Development

Department of Histology Faculty of Medicine University of Sriwijaya

Bone and Blood Development

Competencies: Upon completion of this section of the course the student must be able to:
Know the different cells and constituent components of blood. Recognize the differences between cells in blood based upon their morphology. Understand how the structural differences in the cells results in the different functions these cells carry out. Use this information above to determine how the cells would function to provide a defense against unwanted pathogens. Know how each of the cells develops including the origin of the cell and its lineage.

Bone & Blood Development

Blood Plasma (5 6 L) 54% blood volume
water (90%)
proteins (7%) electrolytes, waste products(1% ) nutrients, hormones (2%)

Cells and Platelets 46% blood volume

Red Blood cells 45% White Blood cells 1%

Blood & Blood Development

Formed Elements of Blood:
Red Blood Cells = Hematocrit White Blood cells
Agranular Leukocytes Monocytes Lymphocytes Granular Leukocytes Eosinophils Neutropils Basophils

Buffy Coat

Platelets

White Blood Cells

1. Granular or Multinuclear white blood cells: - Neutrophils, basophils, eosinophils 2. Agranular or Mononuclear white blood cells: - Monocyte - Limphocyte

Test Red Blood Cells Hemoglobin Hematocrit Neutrophils Polys) Eosinophils Basophils Monocytes Lymphocytes Platelets (Segs or

Reference Values

Male = 4.3 5.9 x 1012/L Female = 3.5 5 x 1012/L Male = 140 180 g/L Female = 120 160 g/L Male = 41% - 52% Female = 35% - 47% 50% 75%, 2 8 x 109/L 1% 5%, 0 0.7 x 109/L 0 2%, 0 2 x 109/L 2% - 9%, 0 0.8 x 109/L 20% 44%, 1 4 x 109/L 140,000 - 400,000/cmm 150 350 x 109/L

Bone Marrow
Marrow Stromal Compartment
Adipose cells Fibroblasts Stromal cells Vascular endothelial cells Macrophages Blood vessels.

Hematopoietic cell compartment Hematopoietic cells

Periosteum

Fat cell Sinus

Outer cortical bone

RBCs
Marrow cavity

Granulocytes

Demo Slide Image 1/1

Megakaryo.

Bone marrow, rib, paraffin section - low mags.

Actively hemopoietic (red) marrow is filled with developing RBCs, WBCs, platelets, and lymphocytes. Reticular ct supports the developing cells. Large, light staining fat cells vary in number. Colonies of dark staining cells are developing RBCs, usually situated at the edge of blood-filled sinuses. Megakaryocytes are large pink cells also obvious near the sinuses. The remaining cells are mostly developing granulocytes.

Bone Marrow Smear

Bone Marrow smear at low mag. Whole cells are spread thinly to reveal cellular details for further identification under oil immersion magnification.

Blood Cell Development

Red blood cells, monocyte, granular cells, thrombocyte

Lymphocyte

Blood Cell Development

Red Blood Cells

Red blood cell development changes with the age of an individual. In the embryo, hematopoiesis begins in the yolk sac. In the fetus, it shifts to the liver and the spleen. In adults, blood cells are made in the red bone marrow. 175 billion red cells are normally made each day.

Red Blood Cells

biconcave discs without nuclei 7.8 mm in diameter flexible cytoskeletal proteins impart flexibility remain in circulating blood for 100 120 days

Red Blood Cells

Red Blood Cells

Red Blood Cells

The plasma membrane of a Red Blood Cells is:
40% lipids 50% protein 10% carbohydrates

Texture and flexibility of the membrane is constructed by membranes cytoskeletons : spectrin, actin, band 4.1 and 4.9

Red Blood Cell Development

Erythropoietin growth factor Made by interstitial cells of the kidney Stimulates
E-CFUs Primitive/mature progenitor Proerythroblast

Stimulates maturation of red blood cells Stimulates production of hemoglobin Erythropoietin increases in response to hypoxia or anemia.

Red Blood Cell Development

Reticulocytes
1. 2. 3. 4. 5. Immature erythrocytes Circulate in the blood for 2 days Bigger than RBCs Have a bluer cytoplasm. It takes seven days to go from a proerythroblast to a RBC Number of reticulocyte in marrow is higher than in periphery blood. An increase in reticulocytes may indicate a loss of red blood cells or anemia.

White Blood Cells

1. Granular or Multinuclear white blood cells: - Neutrophils, basophils, eosinophils 2. Agranular or Mononuclear white blood cells: - Monocyte - Limphocyte

Neutrophils

Neutrophils
Two types of granules
Primary or azurophilic granules - essentially lysosomes
Acid phosphatases Acid hydrolases Myeloperoxidase Elastase other lysosomal enzymes

Secondary or specific granules

alkaline phosphatases collagenase lactoferrin Lysozyme

Neutrophils
Involved in phagocytosis and destruction of bacteria . First, secondary or specific granules fuse with the phagosomes and release enzymes into it. Then, primary or azurophilic granules will actively complete the digestion of the particles.

Neutrophils
In an extended inflammatory reaction neutrophils will die. If this reaction is intense then the result is the production of viscous fluid called pus. The lifespan of the neutrophil is
6 7 hours in the blood stream 1 4 days in the connective tissue

An increase in neutrophils in the blood indicates an infection.

Eosinophils
The eosinophil has coarse red granules; its nucleus often has 2 or 3 lobes. Granules have a crystalline core that contains major basic protein and eosinophilic cationic protein, which are involved in the destruction of bacteria and parasites. The rest of the granule contains a number of enzymes that participate in the digestion of bacteria, protozoa, and parasites. These enzymes also are involved in the inactivation of histamine and leukotrienes . remain in the blood for approximately 8 12 hours The azurophilic granules are lysosomes with hydrolytic enzymes. These cells can trigger bronchial asthma

Basophils
12 mm in diameter nucleus can have 2 lobes or be multilobed dark blue granules granules contain enzymes that are involved in the allergic reaction enzymes are histamine, heparin, eosinophilic chemotactic factor, leukotrienes and peroxidase

Basophils can remain in the blood for approximately 8 hours

Basophils
Histamine causes vasodilation. Leukotrienes cause slow and more prolonged vasodilation. Promote migration of white blood cells into the connective tissue. Involved in bronchial asthma and allergic skin reactions.

Monocytes
Monocytes are cells approximately 15 - 20 mm Nucleus usually is kidneyshaped or indented cytoplasm is described as light blue or bluish-gray contain lysosomes in the cytoplasm function is phagocytosis remain in the blood for up to 12 - 100 hours

Monocyte

Lymphocyte
The lymphocyte is a small, round, blue-staining cell. The heterochromatic nucleus is round, dark staining, and nearly fills the cell, Lymphocytes circulate in the blood for less than 12 hours In the connective tissue the lifespan of the lymphocytes is quite variable Larger lymphocytes tend to be cells that have been stimulated by an antigen Go on to produce either T or B lymphocytes

Lymphocyte Development

Sm. Lymphocyte, 6-9

RBC Lymphocyte

Neutrophil

Platelets

Platelet Platelet

Platelets are cell fragments whose size varies between 2 - 4 microns (compare to RBC, 7 , neutrophil 15 ) . They have no nuclei, their cytoplasm stains light blue and is slightly granular.

Platelets
shaped like a disc have an outer zone - hyalomere
Microtubules maintain shape Actin filaments - produce filopodia

inner region containing granules - granulomere

calcium ions, pyrophosphate ADP and ATP fibrinogen, platelet-derived growth factor and other platelet proteins. lysosomal granules

Megakayocytes

Megakaryo.

Bone marrow, paraffin section - low mag.

Megakaryocytes are large pink cells obvious near the sinuses. The remaining cells are mostly developing granulocytes.

Megakayocyte Mature

Megakayocyte, ~ 200

The megakaryocyte begins its development from a megakaryoblast. Early in development it undergoes mitotic divisions to increase its numbers Later it undergoes only endomitotic divisions. The nucleus of these cells is quite variable and multilobed The cytoplasm is abundant and granular Gives rise to thousands of platelets during the cells lifetime

Thrombopoietin = made in the liver and stimulates megakaryocytes from CFUs

Neutrophil

Eosinophil

Basophil

Lymphocytes

Monocyte

Summary slide. Granular leukocytes: neutrophil, eosinophil, basophil. Non-granular leukocytes: lymphocytes, monocyte.

Myeloblast Promyelocyte Myelocyte Metamyelocyte Juvenile

Mature

rare

Proerythroblast Baso-erythroblast Polychrome-

Orthochrome

RBC

Pluripotential Stem Cell

CFU-GEMM

CFU-GM CFU-M CFU-G CFU-Eo CFU-Bas CFU-E Monoblast Myeloblast Proerythroblast Promyelocyte Megakaryoblast Lymphoblasts (T & B) CFU-Meg CFU-L

Basophilic Erythroblast

Myelocytes Polychrome Metamyelocytes Megakaryocyte

Orthochrome

Lymphocyte & Plasma cell

Monocyte Mature granulocytes

RBC

Platelets