Blood Formation and Hemopoiesis

Blood Formation

• Blood cells are short-lived and continuously replaced from sources outside the circulation
• Hemopoiesis is the process of blood cell formation
• Hemopoietic organs include the bone marrow, spleen and liver
• Mature blood cells have relatively short lifespans, requiring continuous replacement via hemopoiesis
• Erythrocytes originate from the yolk sac mesoderm earliest in fetal life
• The liver and spleen serve as temporary hemopoietic tissue

Timing of Blood Formation

• By the second month, clavicles ossify and initiate bone marrow development
• Bone marrow becomes the primary hemopoietic tissue, replacing the liver and spleen
• During the second trimester, hemopoiesis occurs mainly in the liver, with the spleen having a minor role
• Skeletal elements ossify and bone marrow develops in medullary cavities in the third trimester
• Bone marrow in specific bones then becomes the major hemopoietic organ

Post-Natal Blood Formation

• After birth and in adults, erythrocytes and granular leucocytes (WBCs) come from the bone marrow
• Lymphocytes and monocytes develop in large numbers in the bone marrow as well

Fetal Hemopoiesis - Mesoblastic Phase

• The mesoblastic phase is detectable in the mesenchyme of the body stalk and neighboring yolk sac areas
• This phase takes place during the 2nd week of life
• Blood islands (erythroblastic) exist
• Mesenchymal cells differentiate into large basophilic cells in clusters

Hepatic Phase of Hemopoiesis

• The hepatic phase takes place from 6 weeks (liver) to 2 months (spleen)
• This phase manifests in the primordium of the liver
• The age of gestation is weeks or months of pregnancy
• Definitive erythroblasts give rise to anucleated erythrocytes which do not have a nucleus

Myeloid Phase

• Granular leucocytes and megakaryocytes appear in the sinusoids of the liver during the 2nd month
• The spleen becomes the site of hemopoiesis
• Blood vessels penetrate cavities in cartilage models of bones as chondrocytes degenerate during the 4th month of gestation
• This is endochondral ossification; hyaline cartilage converts to osteoblast to bone
• Blood formation starts in primitive bone marrow, marking the beginning of the myeloid phase of hemopoiesis
• The bone marrow is the major blood-forming organ from the 4th month of gestation into adult life

Types of Bone Marrow

• Red bone marrow produces blood and hemopoietic cells
• Yellow bone marrow is a type filled with adipocytes and a few hemopoietic cells
• Yellow bone marrow can revert to red marrow under conditions like severe bleeding or hypoxia

Red Bone Marrow

• Newborns have only active, red bone marrow for blood cell production
• In adults, red marrow is in flat bones like the sternum, ribs, clavicle, pelvis, skull, vertebrae, and proximal epiphysis of the femur/humerus
• Red bone marrow facilitates blood extraction if no other option is available (intraosseous blood collection)
• Contains a reticular connective tissue stroma, hemopoietic cords/islands, and sinusoidal capillaries
• Its matrix is rich in collagen type I, proteoglycans, fibronectin, and laminin to help bind cells to the matrix
• This bone marrow type is a site where macrophages phagocytize older, defective erythrocytes, then reprocess heme-bound iron
• Functions in production of immature developmental stage blood cells, destruction of old erythrocytes (the other organ is the spleen)

Yellow Bone Marrow

• Typically found in the medullary cavities of long bones
• Consists of macrophages, undifferentiated mesenchymal cells, reticular cells and rich with adipose cells that do not produce blood cells
• Used as a storage organ since it is rich in fats
• Serves as a reserve of hematopoietic tissue in pathologic conditions cases of abnormal RBC production

Blood Cell Formation - Theories

• Unitarian/Monophyletic Theory states that all blood's formed elements originate from a single stem cell: the hemocytoblast (a pluripotential stem cell)
• Dualistic/Diphyletic Theory states that blood cells come from two stem cells: Myeloblasts (erythrocytes and granular leucocytes) and Lymphoblasts (lymphocytes and monocytes)
• Polyphyletic Theory states there is a primitive stem cell for each type of blood cells

Hemopoietic Stem Cells

• Hemocytoblast is a primitive stem/parent cell and are in myeloid and lymphatic tissues
• Can differentiate into many types of mature blood cells
• Also known as Pluripotential hemopoietic stem cells (PHSC) or a Colony training unit/CFU
• Progeny are unipotential/committed stem cells

Erythropoiesis

• This is red blood cell formation
• Development of a mature erythrocyte takes 3 days, lifespan of RBC is 120 days and increases with blood loss
• Example of terminal cell differentiation; hemoglobin synthesis and creation of enucleated, biconcave corpuscle
• Volume of cell decreases
• Nucleoli gets smaller, eventually invisible
• Nucleus diameter decreases, chromatin more dense
• Number of polyribosomes decreases (basophilia)
• Amount of hemoglobin increases (acidophilic) in cytoplasm
• Quantity of mitochondria diminishes
• The RBC's function is delivery of hemoglobin from organs to heart
• RBC that is oxygenated is carrying hemoglobin
• If hemoglobin is decreased, can cause anemia

Stages for RBC Formation

• Proerythroblast (Rubriblast) is earliest stage from pluripotential stem cell/CFU
• Cell is large, rounded containing nucleus uniformly dispersed along with chromatin pattern
• Nucleoli is present with basophilic presence

Basophilic erythroblast (pre-rubricyte)

• Is smaller than Proerythroblast, contains coarse Chromatin, absence of Nucleoli, and is basophilic

Polychromatophilic Erythroblast (Rubricyte)

• Exhibit mixed colors (purplish blue to lilac to gray) with nuclei that are denser than the chromatin's network
• Have a checkerboard appearance and possess hemoglobin
• There is a decrease of basophilia found within the cytoplasm

Normoblast (Acidophilic Erythroblast)

• Is still an immature blast, but the hemoglobin is still exhibiting acidophilia
• Contains smaller densely basophilic Nucleolus, but its cell has become acidic
• Cell becomes pyknosis and is then extruded from cell
• Nucleolus fragments are occasionally called Howell-Jolly bodies which is abnormal if medtechs are present when there is circulation

Reticulocytes

• Youngest erythrocyte with normal value of <1% that contain supravital staining of blue cresyl and possesses pink cytoplasm. In normal H&E it remains undetected
• Good index of formation rate and can appear during patient loss or being treated for anemia
• They circulate (1% of RBC) but loses polyribosomes as matures

Erythrocyte

• The mature RBC is biconcave, anucleated and can be in great numbers in parenchyma and be released in circulation

Granulopoiesis

• For the granular white blood cells
• Involves cytoplasm changes dominated by synthesis in proteins for granules
• These protein are produced in rough ER with successive stages

Myeloblast

• Comes from Pluripotential stem cell; contains deeply basophilic cytoplasm, oval nucleus, as well as has sieve-like appearance
• Most early recognizable cell

Promyelocyte

• Large, ovoid/indented nucleoli, deeply stained
• Basophils are cytoplasmic with azurophilic granules

Myelocyte

• Granules become specified with decrease in size
• Depending if neutrophil, basophilic eosinophilic, there is a reduction in size and will have an indented nucleus

Thrombopoiesis

• The main purpose for Thrombopoiesis is to formulate blood that prevent blood loss as promotes clotting
• Platelets are found in the red bone marrow and is fragmented to have polynuclear with cells called megakaryocytes become platelets

Megakaryoblast

• Contains a round nuclei, and loose chromatin that becomes dispersed in cytoplasm

Promegakaryocytes

• Cytoplasm increase volumes with diminished basophilia

Granulocytes - Metamyelocyte

• Nucleus shows deep indentation
• Cytoplasm has deep pink coloration
• The nucleus shows condensed patterns

Neutrophils

• Nucleus becomes irregular and has band form

Eosinophilic

• Has nuclei that are bilobed frequently

Basophilic

• Nuclei does not become defined

Types of Granulocytes

• Most cells contain lobulated Nuclei, acidophilic granules, and stain
• Neutrophils contain alkaline, phosphate and phagocytins to attack bacteria
• Eosinophils have antihistamine and has bilobed structure to fight worms

B Lymphopoiesis

• The main site is bone marrow as to develop lymphocytes
• Is known as Monopoiesis where cell line shares the granulocytes

Normal Blood

• Blood contains formed elements with plasma
• Plasma helps circulate gases and helps form waste

Serum vs Plasma

• Serum lacks fibrinogen protein due to clotting
• Plasma maintains it, where centrifugation is possible
• Blood smears are made for viewing

Formed Elements

• RBC
• WBC
  • Granular -Neutrophils -Eosinophils -Basophils
  • A granular -Lymphocytes -Monocytes

Lymph

• A collection of tissues that return to blood, but is colorless, no platelets and have greater lymphocytes

Normal RBC

• Have no deformation for capillary passage that results in either Rouleaux Formation (abnormal finding)
• Have properties that bind oxygen with components of erythrocytes, where is increased with Hg or not with hypochromic
• Macrocytic equals to the large size and not to be confused with microcytic (small size)

Types of -cytes

• Erythrocytes are red
• Leucocytes are WBC and helps with counts
• Neutrophil stain has 3-5 lobes per cell

Neutrophil

• Function in destruction of ingested microorganisms, are PMNs with chromatin shape
• Will create "band forms" due to single elongation
• Women are more likely to have "drumstick" for chromostine
• Creates a alkaline that can attack bacteria

Eosinophils

• 1-3% of cells with lifespan for 8-12 days
• Has bilobed Nuceli where cytoplasm is coarse, lysosomes fight worms

Basophils

• Have diameters of 10nm and contain granulocytes with histamine