Cartilage is a resilient connective tissue composed of cells embedded in an extracellular matrix that is gel-like and has a rigid consistency.

Important for:

support to softer tissues
formation and growth of long bones

Consists of:

extracellular matrix containing mainly,
collagen and/or elastin fibers

Collagen provides tensile strength and durability, however, proteoglycans are also important. For example, if you inject papain (an enzyme that digests the protein cores of proteoglycans) into the ears of a rabbit, after a few hours the ears will loose their stiffness and droop.

Three types of cartilage - extracellular matrix differs in terms of concentration of collagen and elastin fibers.

                                                                                    Copyright R. Nims & S.C. Kempf 12/2000

1. Hyaline cartilage

a. dominant component of extracellular
b. matrix is collagen.
c. Bluish-white in life
d. translucent
e. important in formation and growth of long bones
f. In adult, mainly found lining outer wall of respiratory system and on surfaces of bone joints where it is called Articular cartilage.
g. Undergoes calcification in bone formation and also as part of aging process.

2. Elastic cartilage

a. high concentration of elastin fibers
b. in extracellular matrix. (Example - external ears)
c. does not calcify

3. Fibrous cartilage (fibrocartilage)

a. found at connection of tendons to bone.
b. contains very large bundles of collagen fibers.
c. resists compression and shear forces.
d. also found in intervertebral discs.


This tissue acts to support softer tissues and also is important in the formation and healing of endochondral bines such as the long bones of the arm and leg. The qualities of the different types of cartilage depend on differences in the concentration of collagen and elastin fibers in the extracellular matrix and on the proteoglycan molecules that these fibers are associated with.

Cartilage is devoid of blood vessels. Thus the nutrition of cells within the cartilage matrix is dependent on the diffusion of nutrients from blood capillaries in the perchondrium and/or adjacent tissues through the matrix.

Hyaline and elastic cartilage are surrounded by a connective tissue capsule called the PERICHONDRIUM that contains the capillaries from which the nutrients diffuse into the cartilage matrix. Articular hyaline cartilage and fibrocartilage do not have a perichondrium.


More information on cartilage:

                                                                                                Copyright R. Nims & S.C. Kempf 12/2000

Hyaline cartilage is the most common cartilage in the body. It is bluish-white and translucent. Important in the formation of long bones of the body in embryo and during growth.

In adult, mainly found lining the respiratory passages such as trachea. Also at ventral ends of ribs and as ARTICULAR CARTILAGE on the bone surfaces within joints.

Dominant component of extracellular matrix is collagen fibers. Other components are sulfated proteoglycans and hyaluronic acid.

Main tissue components

1. perichondrium - vascularized connective tissue sheath surrounding cartilage (except in case of articular cartilage). Rich in collagen. Contains fibroblasts that secrete the materials for the collagen fibers. Inner layer (next to cartilage matrix) contains cells that are thought by some to be fibroblasts and by others to be undifferentiated mesenchyme cells. In either case, these cells can differentiate to form chondroblasts.

2. chondroblasts - immature cartilage cells. Secrete extracellular matrix, but are not yet rigidly embedded in that matrix.

3. chondrocytes - mature cartilage cells that are embedded in rigid extracellular matrix. These cells reside in small spaces within the matrix that are called lacunae. May be more than one cell in a lacuna. Living chondrocytes have an eliptic shape. Organelle systems in cytoplasm are typical of cells that secrete. Chondrocytes in hyaline cartilage that are grouped together are called isogenic groups.



Similar to hyaline cartilage except,

1. matrix impregnated with elastic fibers
2. yellow in color
3. chondrocytes are more closely packed and only one chondrocyte per lacuna. No isogenic groups
4. does not calcify under normal conditions and does not show ossification in old age.
5. exhibits less accumulation of glycogen and lipids than hyaline cartilage.



An irregular, dense, fibrous tissue with thinly dispersed, encapsulated chondrocytes. No perichondrium, so it blends with adjacent connective tissue. Most easily seen in articular disks such as the intervertebral disks. Also found where tendon connects to bone. Shows resistance to compression, durability and high tensile strength.


As the embryo develops, mesenchymal cells will aggregate into closely knit clusters and differentiate into chondroblasts. These cells will begin to secrete collagen and mucopolysaccharide matrix containing chondroitin sulfate. The matrix secretion will cause the chondroblasts to be pushed apart.

As this occurs, the cartilage cells will undergo divisions. This will result in small clusters of chondroblasts within the developing matrix which will also start to secrete matrix and be pushed away from each other. This sort of growth of cartilage is termed interstitial growth due to the fact that the extracellular matrix is secreted into spaces between the cells.


Growth of cartilage can also be appositional, that is a layer of chondroblasts can lay down matrix at the outer edge of a mass of cartilage.

As the cartilage continues to grow, the central regions become more rigid due to various secretory products and the cells in this region become embedded in rigid matrix and take on the characteristics of mature chondrocytes. The outer edge of the cartilage mass becomes invested with additional mesenchymal cells that differentiate into fibroblasts to form a specialized connective tissue covering for the cartilage known as perichondrium. Chondroblasts that differentiate from mesenchyme cells at the inner edge of the perichondirum also secrete matrix causing appositional growth of the cartilage mass.

Similar histogenesis can result in elastic (external ear) or fibrous cartilage (intervertebral discs) in other parts of the body.


Bone is one of the hardest substances in the body. You might look at it and think of it as dead, mineralized material. It's important to realize that bone is a living tissue composed of cells and their associated extracellular matrix. IT IS A CONNECTIVE TISSUE!

Bone structure:

1. periosteum - a layer of connective tissue that covers the bone containing a high concentration of collagen fibers. Two distinct layers. External layer very fibrous, while internal layer is more cellular and vascularized. Some of the collagen fibers penetrate the calcified bone matrix and bind the periosteum to the bone. These fibers are called Sharpey’s Fibers. Cells of this connective tissue play important roles in bone histogenesis and in the healing of fractures.

2. endosteum – similar to the periosteum, but only one cell thick. Lines the internal surfaces of bone.

3. Important roles of the periosteum and endosteum are nutrition of bone cells and provision of osteoblasts for bone histogenesis and repair.

There are 3 different bone cell types.

1. osteoblasts - immature bone cells that synthesize and secrete the osteoid matrix that will calcify to form the bones extracellular matrix. This matrix is composed of glycoproteins and collagen. In areas where these cells occur, they are located on the surfaces of forming bone and are not yet embedded in the extracellular matrix. These cells have cytoplasmic processes that bring them into contact with neighboring osteoblasts, as well as nearby osteocytes. Ultrastructure shows organelle systems typical of secretory cells.

2. osteocytes - mature bone cells. These cells are osteoblasts that have become embedded in calcified bone matrix. They reside in lacunae within the matrix and are in contact with neighboring osteocytes via cytoplasmic processes that extend through small tunnels called canaliculi. Contacting cytoplasmic processes form gap junctions. This communication between osteocytes is important in the tranfer of nutrients to these cells and wastes out of them since they may be far removed from blood capillaries. The cells are flattened and their internal organelles exhibit the characteristics of cells that have reduced synthetic activity.

3. osteoclasts - these are large, multinucleate cells that act to reabsorb bone during specific stages in bone formation and healing, and during the continual reworking of internal bone architecture that occurs throughout life.

Bone matrix - 50% inorganic components composed mainly of various calcium salts. The organic matter composing the other 50% of the matrix is made-up of 95% collagen and a mixture of various glycosaminoglycans associated with proteins.


Two modes of bone formation

1. Endochondral - cartilage template formed that is replaced by bone (e.g. vertebral column, long bones of limbs – most bones in body)

2. Intramembranous - direct formation of bone structure with no cartilagenous template (e.g. flat bones of skull)

In the embryo, osteoblasts are derived from mesenchymal cells. These cells either aggregate where bones are to form (intramembranous bone formation) and lay down the matrix that will later become calcified, or they migrate into pre-existing cartilage "models)" of the presumptive bone and replace the cartilage with a calcareous matrix (endochondral bone formation). Long bone growth is also endochondral in nature. Osteoblasts are different than the chondroblasts that begin the histogenesis of cartilage and should not be confused with them.

As the primordial bone matrix is layed down, the osteoblasts become entrapped in lacunae within the matrix and are then known as mature osteocytes. As bone is being formed, there is also localized removal of the bone matrix by another set of connective tissue cells known as osteoclasts. These cells are thought to differentiate from monocytes and are responsible, in part, for the internal architecture of bones in that they excavate localized portions of the forming bone and make passageways for such things as blood vessels nerves. Osteoclasts will continue to remodel the bone throughout a person’s life.

A third population of cells involved in bone formation are the cells of the marrow. These are the stem cells for blood cells and all their progeny (see Blood below).



Occurs mainly in bones of the skull.

Mesenchymal cells aggregate and begin to secrete matrix that is characterized by bundles of collagenous fibers. The secreted osteoid matrix has a high affinity for calcium salts, that are brought into the area of bone formation by the circulatory system. These deposit within and on the matrix to form calcified bone. As this calcification takes place, the mesenchymal cells undergo morphological changes. They loose the appearance of mesenchymal cells and round up becoming true osteoblasts. The osteoblasts become oriented in epithelial-like layers along the forming bone. The osteoblasts and the collagen and other components of the intercellular matrix form the organic osteoid framework of the bone.

As a strand of matrix is invested with inorganic salts it forms a spicule of bone. The spicules will merge to form larger calcified structures called trabeculae. These will thicken with the deposition of more osteoid matrix and inorganic salts as the osteoblasts continue their secretion in an appositional manner. This secretion by the osteoblasts is cyclic and results in layers of bone material called lamellae. The deposition of lamellae traps some of the osteoblasts within the osteoid matrix. Once trapped they are considered mature osteocytes. Osteocytes are characterized by cytoplasmic processes that contact similar processes of adjacent osteocytes. Gap juctions form at points of contact allowing transfer of small molecules between cells. This transfer is important in co-ordinating bone growth and in the nourishment of osteocytes which may be separated from blood vessels by a considerable amount of calcified bone. Channals through which cytoplasmic processes of osteocytes extend are called canaliculi.

Growing adjacent trabeculae will contact and fuse forming the structure of the mature bone. As intramembranous bones grow, selective reabsorption of bone material is also occurring due to the activities of osteoclast cells. This results in the formation of much of the internal architecture of the bones, providing spaces for blood vessels and marrow.





Most of the bones in the mammalian body are initially formed by endochondral means. That is to say, a template of hyaline cartilage that is in the shape of a miniature of the bone is layed down prior to the bone’s formation. This deposition of cartilage occurs as previously discussed and is accomplished by the action of chondroblasts functioning in both interstitial and appositional growth capacities.

The typical examples that are used to describe endochondral bone formation are the long bones of the limbs. Perhaps it will be easier to understand their histogenesis if we first consider the general structure of bones. We will consider this structure as it exists in long bones, however, it should be kept in mind that girdle bones, such as the pelvic girdle, and the intramembranous flat bones of the skull are made up of the same basic components, though they may be arranged somewhat differently.

Bones of the body, including the long bones may be considered a rigid form of connective tissue. The cells of this tissue are embedded within a matrix that consists of organic and inorganic components. The organic matrix, or ground substance, consists of collagen fibers for the most part. The inorganic component mostly consists of calcium salts, calcium phosphate (85%), calcium carbonate (10%), and small amounts of calcium and magnesium flouride. While we tend to think of the inorganic components as being the contributing factors in a bone's structural integrity, you should realize that the collagen fibers also contribute significantly to the bones strength and resilience.

Two types of bone tissue can be distingished. These are cancellous, or spongy, bone that lies centrally within the shaft of long bones, and compact or dense bone that lies more peripherally. You should realize that the actual mineralized matrix of these two types of bone is the same. It contains embedded osteocytes that are in communication via gap junctions at their contacting cytoplasmic processes. The difference between spongy and compact bone lies simply in the size of open spaces within the mineralized bone.

The spongy bone consists of slender, irregular trabeculae with large spaces between them where blood vessels, nerves, and marrow cells are located.

Compact bone appears solid, no large cavities within it.

Since the actual mineralized matrix of both types of bone is the same, there is no distinct boundary between spongy and compact bone.

The shaft of a long bone consists of a medullary or central volume of spongy bone surrounded by a thick cortical layer of compact bone. The compact layer can be subdivided into an outer series of sub-layers called periosteal lamellae that were secreted by the periosteal cells during its development and growth, and an inner component consisting of multiple concentric sub-layers surrounding the halversian canals. Radial cavities called Volkmann’s canals also extend through the compact bone. These radial cavities and halversian canals form a network within the compact bone that is continuous with the cavities of the spongy bone. Blood vessels and nerves extend through the channels of this network.

So how is this structure established?

The first step in endochondral bone formation is the histogenesis of a cartilage miniature of the bone. This takes place as discussed above via the action of chondroblasts that have migrated to the area. The chondroblasts secrete a cartilagenous matrix that is laid down both interstitially and appossitionally. The end result is a cartilage template of the bone in miniature that contains chondrocytes embedded within the cartilage matrix.

Actual osteogenesis (bone ossification) begins with the establishment of a periosteum on the shaft (or diaphysis) of the cartilage template and the laying down of an intramembranous collar of bone on the circumference of the cartilage diaphysis. This is followed by hypertrophy (they get bigger) and eventual death of the chondrocytes within the cartilage matrix. As the chondrocytes degenerate they reabsorb some of the surrounding cartilage matrix causing enlargement of the lacunae in which they reside. This process is known as hypertrophication. As this occurs, the chondrocytes loose their ability to maintain the remaining cartilage matrix and it becomes partially calcified. The end result is an area of porous calcified cartilage within the central regions of the diaphysis. As this is occurring, osteoclasts that have arrived in the area via the circulatory system, begin excavating passageways or tunnels through the intramembranous collar surrounding the diaphysis. These passageways provide a means through which blood vessels, nerves and undifferentiated mesenchymes cells can enter into the lacunae (spaces) in the remnants of the cartilage matrix that have been left by the degenerating chondrocytes. The mesenchyme cells will differentiate into osteoblasts and hematopoietic stem cells that are distributed within the bone.

The osteoblasts, blood vessels, and nerves form the osteogenic bud that comes to lie more or less centrally within the diaphysis of the forming bone.

As the invading cells spread out within the diaphysis of the cartilage template and ossification begins, this central volume of active bone deposition is called a primary ossification center.

The osteoblasts begin to secrete osteoid matrix on the remnants of calcified cartilage. The osteoid matrix becomes mineralized forming cancellous bone in the shaft of the diaphysis. Some of the osteoblasts become trapped within the mineralized bone and become mature bone cells, osteocytes. These cells maintain contact with other osteocytes and/or with osteoblasts via contacting cytoplasmic processes that extend through canaliculi the mineralized matrix.

As the cancellous bone is layed down, chondroclasts (which are the cartilagenous equivalent of osteoclasts) reabsorb the calcified cartilage as it is replaced by osteoid matrix (i.e., the calcified chondroid matrix does not form bone!). At this point, it is important to note that this means the actual bone tissue, matrix and mineralization, is the result of the action of a new group of cells, the osteoblasts. NOTE THAT THE CARTILAGE IS NOT TRANSFORMED INTO BONE TISSUE!

The primary ossification center rapidly extends longitudinally within the diaphysis as the shaft of the cartilage template is completely replaced by cancellous bone tissue. As the ossification center extends longitudinally, so does the calcified outer collar of bone layed down by the periostial osteocytes.

As ossification proceeds in the diaphysis, secondary ossification centers form in the cartilage of the bulbuous ends, or epiphyses, at either end of the long bone shaft. Osteogenic tissues in these regions also act to form mineralized bone. This process is similar to the primary ossification we've just discussed with one difference. Since there is no periosteum on the surface of the epiphyses, there is no periostial external collar of bone.

What we have just discussed is endochondral bone formation. This involved the deposition of cancellous, or spongy bone, within a cartilage matrix. This is not the final step in bone formation. In fact, there really is no such thing as a final step in this process.

During and after endochondral bone formation, there is considerable internal remodeling of the architecture of the bone. This is accomplished by the efforts of osteoblasts, osteocytes, and osteoclasts.

Osteoclasts act to reabsorb much of the cancellous bone that has been layed down during endochondral bone formation. As this occurs, channels are hollowed out within the spongy bone structure. These are in addition to the cavities already formed in spongy bone. In more peripheral regions where compact bone will be present, these channels will give rise to the halversian systems as compact or dense bone is laid down within them.

As these peripheral channels are hollowed out, osteoblasts from the marrow invade the channels and form an epithelium on the channel's inner wall. These osteoblasts lay down cyclical layers of osteoid matrix which becomes mineralized and decrease the diameter of the channels. As this occurs, some of the osteoblasts are trapped within the matrix and become osteocytes with the characteristic long cytoplasmic processes that extend through canaliculi in the mineralized bone and contact each other. As this ossification takes place, large cavities like those present in spongy bone are not formed, thus, this kind of bone is called compact or dense bone. Since there is no cartilage precursor to the compact bone, it may be considered intramembranous as far as its mode of formation is concerned.

The final result of this ossification process is the replacement of much of the spongy bone within the shaft of the diaphysis with compact bone which has many halversian canals running through it. Osteoclasts hollow out Volkmann’s canals that extend radially between haversian canals.

The reabsorption and redeposition of compact and spongy bone continues throughout life. Thus, the bones of your body are living, dynamic structures.

FINALLY, we have to consider how bones grow. Obviously, bones don't remain the length that they are at birth.

Let's go back to endochondral bone formation and recall that it was proceeded by the deposition of cartilage. This cartilage was eroded and replaced as the primary and secondary ossification centers did their work. In an area just below the base of each epiphysis, where the tissues of the primary and secondary ossification centers could meet, a plate of activily growing cartilage remains. These epiphyseal plates are responsible for the increase in length of bones during adolescent growth. Cartilage is layed down as in early endochondral bone formation. This cartilage is subsequently eroded and replaced by bone tissue in a process that is essentially the same as what we have just discussed. As adult bone lengths are acheived, the epiphyseal plates cease growth and are completely ossified. See your book and the text Powerpoints for more information on long bone growth.



If blood is prevented from clotting, it can be separated into its two major components by centrifugation (called hematocrit) you get cellular and plasma fractions (52 - 57% plasma , 43 - 48% cells).

Plasma - aqueous solution, large and small molecules other than water form 10% of weight, the rest is water.

Plasma proteins - 7%



alpha, beta, and gamma globulins

gamma globulins are antibodies (immunoglobulins)

Inorganic salts - 0.9%

Other organic molecules - 2.1% (vitamins, amino acids, lipids, hormones, etc.)

Blood cells - two basic types - erythrocytes (red blood cells, hemoglobulin), leukocytes (white blood cells, no hemoglobin). Also platelets which are important in clotting, but these are actually fragments of a type of leukocyte.

Erythrocytes - red blood cells. No nucleus, biconcave disks, about 7.2 um in diameter. Responsible for carrying oxygen bound to hemoglobin to the tissues of the body.

Leukocytes, or white blood cells, can be divided into a number of major sub-types. At light level, these sub-types are distinguished by there structure as characterized by specific staining patterns.

Stains for this purpose were first developed by Dimitri Romanovsky in 1891. These initial stain mixtures were later modified by other investigators, so we have modified Romanovsky type stains called Leishman's or Wright's stains for example.

Components of Romanovsky stain are methylene blue and eosin. Blood cells are classified by the type of stain that binds to them or their components.

1. basophilia - affinity for methylene blue which is a basic stain

2. azurophilia - affinity for azure dyes (purples) which result from the oxidation of methylene blue in the mixture.

3. acidophilia or eosinophilia - affinity for eosin which is an acid satin (yellowish-pink)

4. neutrophilia - affinity for complex dyes that are formed in the mixture that have a salmon-pink to lilac color. The term neutrophilia comes from the early misconception that these dyes were neither acid nor base and thus neutral.


erythrocytes - no nucleus, biconcave disk, high concentration of hemoglobin that makes them acidophilic, about 7.2 um in diameter.

reticulocytes - Young erythrocytes recently released into blood often contain ribosomal RNA that precipitates and stains within the cell.

leukocytes - white blood cells

Stem cells that give rise to the different types of blood cells are located in the bone marrow.

Two major classifications are used for leukocytes.

1. One is based on the presence or absence of the stained granules seen with the light microscope.

a. granulocytes - cells with specific granules that are quite evident by virtue of the fact that they have affinity for specific stains.

b. agranulocytes - blood cells that don't have the specific cytoplasmic granules of granulocytes.

2. The second is based on the morphology of the stained nucleus

a. mononuclear - nucleus is not composed of identifiable lobes.

b. polymorphonuclear - nucleus is composed of two or more distinct lobes.



neutrophils - Compose 60-70% of the leukocytes. First line of cellular defense against microorganisms, especially bacteria. Phagocytose small particles and microorganisms. Cytoplasm contains granules surrounded by a membrane. Nucleus is polymorphonuclear. It has 2-5 lobes linked together by fine threads of nuclear material. Cytoplasm contains both many specific and also some azurophilic granules (though they are often not particularly evident). These contain enzymes that can function in digestion of phagocytosed particles. Neutrophils are capable of amoeboid movement.

eosinophils - Compose 1-4% of the leukocytes, so they are less numerous than neutrophils. Increase in number in allergic reactions. Recognize and phagocytose antigen-antibody complexes and particles that are associated with these complexes that are formed during an immune response. Can migrate using amoeboid movement. May be involved in preventing blood clotting at times when it is best that it not occur. Specific granules are lysosomes that contain enzymes that can degrade phagocytosed particles. The nucleus is usually bilobate (two lobes). Ovoid, eosinophilic (acidophilic) granules are present in cytoplasm. These are much larger than the granules of a neutrophil.

basophils - Compose 0-1% of leukocytes. These cells secrete histamine. Histamine causes dialation of blood vessels and in effect makes them leaky. This allows serum proteins such as antibodies to infiltrate into tissues. Basophils also have limited capacity for amoeboid movement and phagocytosis. They have a large irregular nucleus that is generally S-shaped. The cytoplasm is filled with specific granules larger than those in other granulocytes. Granules are membrane bound and contain histomine and heparin.


lymphocytes - involved in humoral and cell mediated immune responses. Two major catagories, T-lymphocytes that are involved in receptor mediated responses of the immune system and B-lymphocytes that respond to antigens as mediated by T- lymphocytes and produce antibodies against these antigens. In blood smears, lymphocytes form a heterogeneous population that show up as large, medium, and mostly small lymphocytes. Whether these are T- or B- lymphocytes is not apparent in standard stained blood smears. These cells have a spherical nucleus. Their chromatin is condensed and appears as coarse clumps often having a clockface like appearance in tissues, but not in blood smears. Small lymphocytes have very little cytoplasm surrounding their nucleus, while large lymphocytes have a greater amount of cytoplasm. The cytoplasm may contain tiny purple, azurophilic granules, but they are still considered to be agranulocytes.

monocytes - circulating blood cells that can cross plasma membranes and differentiate into macrophages. The nucleus is generally kidney shaped or horseshoe shaped, but it may be oval. It is often positioned off center. The chromatin is not as condensed as in lymphocytes and is often fibrillar in appearance. The nucleus is more lightly stained than in large lymphocytes and may have 2-3 nucleoli. The cytoplasm is basophilic and frequently contains tiny azurophilic granules that may cause the cytoplasm to be a blue-gray color. These cells may look like a band neutrophil in some respects.

megakaryocytes - Large cell with irregularly lobed nucleus. Platelets form as the result of fragmentation of the cytoplasm/plasma membrane of megakaryocytes. Platelets are small, enucleated cell fragments that exist in high concentrations in the blood. Important in healing of cuts and abrasions. These cells are generally only found in the bone marrow.

Other "cellular" blood components

platelets - enucleated disk-like cell fragments that are 2-5 um diameter often appear in clumps in blood smears. Function in clotting.

Blood cells have short life in circulatory system and so they must be continually renewed.

erythrocytes and granulocytes are derived from stem cells in the red bone marrow of healthy mammals.

lymphocytes are derived from stem cells in the bone marrow and also in the lymphatic organs.


Involves what could be called a series of stem cell stages:

Hemocytoblast – multipotent stem cell that gives rise to all types of blood cells. In the case of erythrocyte hematopoiesis, it will divide and one of the two cells formed will become a proerythroblast.

proerythroblast - probably can be considered stem cell for erythrocyte line. Synthesizes proteins to form cytoplasmic components since it divides rapidly. Also very small amounts of hemoglobin. 14-17 um diam. Pinocytosis occurs. Metabolically very active. Proerythroblasts divide many times and form cells that will become basophilic erythroblasts.

basophilic erythroblast - smaller, 13-16 um. undergoes mitotic division. Some hemoglobin synthesized. Many mitochondria. These cells divide many times and form cells that will become polychromatic erythroblasts.

polychromatic erythroblast - smaller, 12-15 um diam. size decrease due to less cytoplasm and smaller nucleus. More hemoglobin. These cells divide many times and form cells that will become normoblasts.

Normoblast - smaller, 8-10 um. nucleus eccentric. Abundance of hemoglobin. Mitochondria and golgi apparatus begin to degenerate. After 3 divisions nucleus is extruded and the cells become reticulocytes.

No further division after this point.

Reticulocyte - young, enucleate erythrocyte. Hemoglobin synthesis continues for short period. Since RNA cannot be renewed from nucleus, synthesis eventually ceases. Remaining organelles are autophagocytosed or exocytosed. Cell becomes a mature erythrocyte.