Human Histology Lecture

Connective Tissues Part 1 || Lesson Reviewer || 2nd Year, 2nd Semester [Midterms]
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CONNECTIVE TISSUE
Þ Second type of tissue

Þ Composed of fibroblasts and other cells and an extracellular

matrix (ECM) of various protein fibers, all of which are surrounded
by watery ground substance.
Þ In all types of connective tissue, the extracellular volume exceeds
Mesenchyme consists of a population of
that of the cells. undifferentiated cells, generally elongated
but with many shapes, having large
FUNCTIONS: euchromatic nuclei and prominent nucleoli
that indicate high levels of synthetic activity.
Þ Acts as the binding tissue of the other three types of tissue. These cells are called mesenchymal cells.
Mesenchymal cells are surrounded by an ECM
Þ Maintains the form of organs throughout the body. that they produced and that consists largely of
a simple ground substance rich in hyaluronan
Þ Provides a matrix that supports and physically connects other tissues (hyaluronic acid), but with very little collagen.
and cells together to form the organs of the body.

Þ Interstitial fluid of connective tissue gives metabolic support to cells CELLS OF THE CONNECTIVE TISSUE
as the medium for diffusion of nutrients and waste products.
CONNECTIVE TISSUE CELLS
Þ Major constituent of connective tissue.
EXTRACELLULAR
Þ Consists of different combinations of
MATRIX (ECM)
protein fibers (such as collagens and
elastic fibers) and ground substance.

Þ A complex of anionic, hydrophilic

proteoglycans and glycosaminoglycans
(GAGs), and multi-adhesive glycoproteins
GROUND
(laminin, fibronectin, and others).
SUBSTANCE
Þ A complex material, somewhat like a glue,
that holds everything together.

Þ All connective tissue originates from the

embryonic mesenchyme.
Þ A tissue developing mainly from the
middle layer of the embryo, the
mesoderm (location of mesenchymal cells).
MESENCHYME
Þ Consists largely of viscous ground
substance with few collagen fibers
Þ Embryonic mesenchyme includes stem
cells for other tissues such as blood, the
vascular endothelium, and muscle.
Þ Can be resident or wandering.
RESIDENT Þ Relatively stable; they typically exhibit little
CELL movement and can be regarded as
POPULATION permanent residents of the tissue.
Þ Consists primarily of cells that have migrated
WANDERING
into the tissue from the blood in response to
CELL
specific stimuli.
POPULATION
(Transient cell pop.) Þ Example: macrophages and white blood cells

Þ Undifferentiated and have large nuclei,

with prominent nucleoli and fine
chromatin.
Þ Often said to be “spindle-shaped,” with
MESENCHYME their scant cytoplasm extended as two or
CELLS more thin cytoplasmic processes.
Þ Mesodermal cells migrate from their site
of origin in the embryo surrounding and
penetrating developing organs.
FIBROBLAST
Þ Most common cells in connective tissue.
Þ Produce and maintain most of the tissue’s extracellular
components.
Þ Synthesize and secrete collagen (the most abundant protein of
the body) and elastin, which form large fibers, as well as the
GAGs, proteoglycans, and multi-adhesive glycoproteins that
comprise the ground substance.

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 Human Histology Lecture
Þ Denoted as fibroblast. MACROPHAGES & THE MONONUCLEAR PHAGOCYTE SYSTEM
Þ More abundant and irregularly branched Þ Key component of an organisms’ innate immune defense,
cytoplasm. removing cell debris, neoplastic cells, bacteria, and other
invaders.
ACTIVE Þ Its nucleus is large, ovoid, euchromatic, and
FIBROBLAST has a prominent nucleolus. MACROPHAGES
Þ The cytoplasm has much rough endoplasmic – Have highly developed phagocytic ability and specialized in
reticulum (RER) and a well-developed Golgi turnover of protein fibers and removal of dead cells, tissue debris,
apparatus. or other particulate material, being especially abundant at sites
of inflammation.
Þ Denoted as fibrocyte.
– A typical macrophage measures between 10 and 30 μm in
Þ Smaller than the active fibroblast.
diameter and has an eccentrically located, oval or kidney-shaped
Þ Usually spindle-shaped with fewer processes nucleus.
and much less RER. § Size and shape vary considerably, corresponding to their state of
functional activity.
Þ Contains a darker, more heterochromatic
QUIESCENT
nucleus. – Have different names depending on its location.
FIBROBLAST
o MYO-FIBROBLASTS – Macrophages commonly found in the connective tissue is called
– An elongated, spindly connective tissue HISTIOCYTES.
cell not readily identifiable in routine H&E § Resides in the liver – copper cells.
preparations.
§ Resides in the nervous tissue – microglia.
– Fibroblasts involved in wound healing.
– When macrophages are stimulated (by injection of foreign
substances or by injection), they change their morphologic
characteristics and properties, becoming activated macrophages.
– When adequately stimulated, macrophages may increase in size
and fuse to form multinuclear giant cells.
– Generally, have a well-developed Golgi apparatus and many
lysosomes.

(a) Fibroblasts typically have large active nuclei and eosinophilic cytoplasm that tapers
off in both directions along the axis of the nucleus, a morphology often referred to as cells of the mononuclear phagocytotic system
“spindle-shaped.” Nuclei (arrows) are clearly seen, but the eosinophilic cytoplasmic NAME OF CELL LOCATION
processes resemble the collagen bundles (C) that fill the ECM and are difficult to
distinguish in H&E-stained sections. Macrophage (Histiocyte) Connective tissue
(b) Both active and quiescent fibroblasts may sometimes be distinguished, as in this Perisinusoidal macrophage Liver
section of dermis. Active fibroblasts have large, euchromatic nuclei and basophilic (Kupffer cell)
cytoplasm, while inactive fibro- blasts (or fibrocytes) are smaller with more
heterochromatic nuclei (arrows). The round, very basophilic round cells are in
Alveolar macrophage Lungs
leukocytes. Fetal placental antigen- Placenta
presenting cell (Hoffbauer cell)
Macrophage Spleen, lymph nodes, bone
ADIPOCYTES
marrow, and thymus
Þ L. adeps, fat + Gr. kytos, cell or FAT CELLS
Pleural and peritoneal Serous cavities
Þ Large, mesenchymally derived cells macrophage
Osteoclast Bone
Þ Specialized for cytoplasmic storage of lipids as neutral fats.
Microglia Central nervous system
Þ Less commonly for the production of heat.
Langerhans cell Epidermis
Þ When they accumulate in large numbers, they are called
Fibroblast-derived macrophage Lamina propria of intestine,
ADIPOSE TISSUE.
endometrium of uterus
– Serves to cushion and insulate the skin and other organs. Dendritic cell Lymph nodes, spleen

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 Human Histology Lecture
This photomicrograph shows several Þ Classified based on their location:
macrophages (M) in the connective tissue from
the area of wound healing. They can be Þ Mast cells are especially numerous near
distinguished from other cells by the presence PERIVASCULAR small blood vessels in skin and
of an indented or kidney-shaped nucleus. Note MAST CELLS mesenteries.
several mature neutrophils (N) with segmented
nuclei located in the connective tissue that MUCOSAL Þ Lines the digestive and respiratory tracts in
surround blood vessel filled with red and white the tissue.
MAST CELLS
blood cells in the center of the image.

PLASMA CELLS
MAST CELLS Þ B-lymphocyte derived, antibody-producing cells.
Þ Oval or irregularly shaped connective tissue cells. Þ Large, ovoid cells that have basophilic cytoplasm due to their
Þ Between 7 and 20 μm in diameter. richness in RER.

Þ Its cytoplasm is filled with basophilic secretory Þ Next to the nucleus, the Golgi apparatus and centrioles occupy a
granules. region that may appear pale in routine histologic preparations.

Þ The nucleus is centrally situated and often obscured by abundant Þ The nucleus of the plasma cell is generally spherical but
secretory granules. eccentrically placed.
Þ Many of these nuclei contain compact, peripheral regions of
Þ Mast cell granules display METACHROMASIA, which means
heterochromatin alternating with lighter areas of euchromatin, a
that they can change the color of some basic dyes (e.g., toluidine
configuration that can give the nucleus of a plasma cell the
blue) from blue to purple or red.
appearance of a clock face.
– Reason: these secretory granules found in the muscle’s cytoplasm has
a high content of acidic radicals, especially the sulfated Þ At least a few plasma cells; Average lifespan is only 10-20 days.
glycosaminoglycans.
– The granules are poorly preserved by common fixatives, so that mast
cells are frequently difficult to identify.

Þ Functions in the localized release of many bioactive substances

with roles in the local inflammatory response, innate immunity,
and tissue repair.
Þ Important molecules released from these cell’s secretory Antibody-secreting plasma cells are present in variable numbers in the connective tissue of many
organs.
granules includes the following:
(a) Plasma cells are large, ovoid cells, with basophilic cytoplasm. The round nuclei frequently
Þ Sulfated GAG that acts locally as an show peripheral clumps of heterochromatin, giving the structure a “clock-face” appearance.
HEPARIN anticoagulant. (b) Plasma is often more abundant in infected tissues, as in the inflamed lamina propria shown
here. a large pale Golgi apparatus (arrows) at a juxtanuclear site in
Þ Promotes increased vascular each cell is actively involved in the terminal glycosylation of the antibodies (glycoproteins).
Plasma cells leave their sites of origin in lymphoid tissues, move to connective tissue, and
HISTAMINE permeability and smooth muscle produce antibodies that mediate immunity.
contraction. Broncho constrictor.

Þ Activates various mediators of

SERINE LEUKOCYTES
PROTEASES inflammation.
Þ Make up a population of wandering cells in connective tissue.
EOSINOPHIL AND Þ Attracts those leukocytes such as
Þ Leaves blood by migrating between the endothelial cells lining
NEUTROPHIL uranosunophil and neutrophil.
CHROMATIC venules to enter connective tissue by a process called
FACTORS DIAPEDESIS.
Þ Polypeptides directing activities of – This process increases greatly during inflammation, which is a vascular
leukocytes and other cells of the and cellular defensive response to injury or foreign substances,
CYTOKINES
including pathogenic bacteria or irritating chemical substances.
immune system.

Þ Precursors for conversion to Þ CHEMOTAXIS

prostaglandins, leukotrienes, and other – The phenomenon by which specific cell types are attracted by
PHOSPHOLIPID important lipid mediators of the specific molecules, draws much larger number of leukocytes
inflammatory response. into inflamed tissues.

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FIBERS OF THE CONNECTIVE TISSUE FIBRIL-ASSOCIATED COLLAGENS WITH INTERRUPTED
TRIPLE HELIXES (FACITS)
FIBERS Þ Have interruptions in their triple helixes that provide flexibility to
Þ Elongated structures formed from proteins that polymerize after the molecule.
secretion from fibroblasts.
Þ Located on the surface of different fibrils.
Þ Three main types of fibers: collagen, reticular, and elastic fibers.
Þ Collagen types:
– Collagen & reticular fibers are formed by proteins of the collagen family.
– Elastic fibers are composed mainly of the protein elastin. IX XII XIV XVI

Þ These fibers are distributed unequally among the different types XIX XX XXI XXII
of connective tissue, with the predominant fiber type usually
responsible for conferring specific tissue properties. HEXAGONAL NETWROK-FORMING COLLAGENS
Þ Collagen types:

COLLAGEN VIII X
Þ A key element of all connective tissues, as well as epithelial
basement membranes and the external laminae of muscle and TRANSMEMBRANE COLLAGENS
nerve cells. Þ Collagen types:
Þ Extremely strong and resistant to normal shearing and tearing XIII Þ Found in the focal adhesions.
forces.
XVII Þ Found within the hemidesmosomes.
Þ Most abundant protein in the human body, 30% of its dry weight.
XXIII Þ Found in metastatic cancer cells.
Þ A pathological presence of an excess amount of collagen is
XXV Þ A brain-specific collagen.
usually returned to as keloid and it usually happens during scar
formation.
MULTIPLEXINS
Þ Bundles of collagen appear white.
Þ Collagens with multiple triple-helix domains and interruptions.
Þ Birefringent under the polarizing microscope.
Þ Collagen types:
Þ To be renewed, the collagen must first be degraded. Degradation
XV
is initiated by specific enzymes called collagenases, which are Þ Resides in the basement membrane zones.
members of an enzyme class called matrix metalloproteinases XVIII
(MMPs).
Þ 6 classes of collagens are identified on the basis of their BASEMENT MEMBRANE-FORMING COLLAGENS
polymerization pattern: Þ Collagen types:
Þ Responsible for the collagen suprastructure in
FIBRILLAR COLLAGENS IV the basement membrane of epithelial cells.
Þ These often densely fill the connective tissue, forming structures
VI Þ Forms beaded filaments.
such as tendons, organ capsules, and dermis.
Þ Forms anchoring fibrils that attach the
Þ Characterized by uninterrupted glycine–proline–hydroxyproline VII basement to the ECM.
repeats and aggregate to form 68-nm-banded fibrils

Þ Collagen types: TYPE LOCATION

Þ Most abundant and widely distributed Connective tissue of skin, bone, tendon, ligaments, dentin, sclera,
I fascia, and tension, and stretch organ capsules.
I collagen, forms large, eosinophilic bundles
II Cartilage (hyaline an elastic), notochord, and intervertebral disk.
usually called collagen fibers.
Prominent in loose connective tissue and organs (uterus, liver,
II III spleen, kidney, lung, etc.); smooth muscle; endoneurium; blood
vessels; and fetal skin
III IV Basal laminae of epithelia, kidney glomeruli, and lens capsule

V Distributed uniformly throughout the connective tissue stroma; may

V be related to reticular network
XI XI Cartilage

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 Human Histology Lecture
The large bundles of type I collagen fibrils (C) appear as
acidophilic collagen fibers in connective tissues, where they
may fill the extracellular space. Subunits for these fibers were
secreted by the fibroblasts (arrows) associated with them.
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RETICULAR FIBERS
Þ Provide a supporting framework for the cellular constituents of
various tissues and organs.
Þ Consist mainly of collagen type III.
Þ Characteristically stained black by impregnation with silver salts
(ARGYROPHILIC).
– Seldom visible in hematoxylin and eosin (H&E) preparations.
Þ Forms an extensive network (reticulum) of extremely thin
(diameter 0.5-2 μm), heavily glycosylated fibers.
Þ Occurs in the reticular lamina of basement membranes and
typically also surround adipocytes, smooth muscle and nerve
fibers, and small blood vessels.
Þ Delicate reticular networks serve as the supportive stroma for the
parenchymal secretory cells and rich microvasculature of the liver
and endocrine glands.
Þ Also characterizes the stroma of hemopoietic tissue (bone
marrow) and some lymphoid organs (e.g., spleen and lymph
nodes).
In these silver-stained sections of adrenal cortex (a) and lymph node (b), networks of delicate,
black reticular fibers are prominent. These fibers serve as a supportive stroma in most lymphoid
and hematopoietic organs and many endocrine glands. The fibers consist of type iii collagen that
is heavily glycosylated, producing the black argyrophilia. Cell nuclei are also dark, but cytoplasm
is unstained. X100.
ELASTIC FIBERS
Þ Thinner than the type I collagen fiber and form sparse networks
interspersed with collagen bundles in many organs.
Þ Have physical properties similar to those of rubber, allowing
tissues to be stretched or distended and return to their original
shape.
Þ Allows tissue to respond to stretch and distension.
o ELASTIC LAMELLAE
– Fenestrated sheets found in the wall of large blood vessels,
especially arteries.
Þ Not strongly acidophilic and stain poorly with H&E.
Þ They are stained more darkly than collagen in other stains such
as orcein and aldehyde fuchsin.
 Human Histology Lecture
Þ Composed of two structural components:
§ Central core of elastin
§ Surrounding network of fibrillin microfibrils
Þ Elastin is synthesized by fibroblasts and vascular smooth muscle
cells.
Þ Elastic material is a major extracellular substance in vertebral
ligaments, larynx, and elastic arteries.
MARFAN SYNDROME
Þ Mutations in the fibrillin genes.
Þ A disease characterized by a lack of
resistance in tissues rich in elastic fibers.
Þ Because the walls of large arteries are rich
in elastic components and because the
blood pressure is high in the aorta, patients
with this disease often experience aortic
swellings called aneurysms, which are
life-threatening conditions.
EXTRACELLULAR MATRIX OF CONNECTIVE TISSUE
EXTRACELLULAR MATRIX (ECM)
Þ Is a complex and intricate structural network that surrounds and
supports cells within the connective tissue.
– Provides mechanical and structural support for tissue.
– Influences extracellular communication.
Þ Composed of: fibers + ground substance
GROUND SUBSTANCE
Þ A highly hydrated (with much bound water), transparent,
complex mixture of macro-molecules.
Þ Principally of three classes:
§ GLYCOSAMINOGLYCANS (GAGs)
§ PROTEOGLYCANS
§ MULTIADHESIVE GLYCOPROTEINS
Þ Fills the space between cells and fibers in connective tissue and,
because it is viscous, acts as both a lubricant and a barrier to the
penetrations on invaders.
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gags
Þ Also called MUCOPOLYSACCHARIDES.
Þ Most abundant heteropolysaccharide components of ground
substance.
Þ Long polysaccharides consisting of repeating disaccharide units,
usually a uronic acid and a hexosamine.
Þ GAGs (except hyaluronan) are synthesized by connective tissue
cells as a covalent, posttranslational modification of proteins
called PROTEOGLYCANS.
Þ Largest, almost unique, and most ubiquitous
GAG.
Þ A long polymer of the disaccharide
glucosamine-glucuronate.
Þ Synthesized directly into the ECM by an
HYALURONIC
enzyme complex, hyaluronate synthase.
ACID Þ Allowing diffusion of molecules in connective
tissue and in lubricating various organs and
(HA or
hyaluronan) joints, located in the cell membrane of many
cells.
Þ Forms a dense, viscous network of polymers,
which binds a considerable amount of water,
giving it an important role in allowing diffusion
of molecules in connective tissue and in
lubricating various organs and joints.
proteoglycans
Þ Composed of a core protein to which are covalently attached
various numbers and combinations of the sulfated GAGs.
Þ Synthesized on RER, mature in the Golgi, where the GAG side
chains are added, and secreted from cells by exocytosis.
Þ Small proteoglycan
DECORAN Þ Has few GAG side chains.
Þ Binds fibrils of type I collagen.
Þ Cell surface proteoglycans
Þ Have transmembrane core proteins.
SYNDECAN
Þ Serves as additional attachments of the cell to
the ECM.
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Þ One of the best-known proteoglycans
Þ Very large
Þ Has a core protein bearing many chondroitin
sulfate and keratan sulfate chains.
AGGRECAN
Þ Bound via a link protein to polymer of
hyaluronic acid.
Þ Important in the formation of cartilages.
multiadhesive glycoproteins
Þ Plays an important role in stabilizing the ECM and linking it to
the cell surface.
Þ Possesses binding sites for a variety of ECM proteins such as
collagens, proteoglycans, and GAGs.
Þ Interacts with cell-surface receptors such as integrin and laminin
receptors.
Þ Regulated and modulates functions of the ECM related to cell
movement and cell migration.
Þ Stimulates cell proliferation and differentiation.
Þ Most abundant glycoprotein in connective
tissue.
FIBRONECTIN
Þ Important role in cell attachment to the
ECM.
Þ Present in basal and external laminae.
Þ Possesses binding sites for collagen type IV
LAMININ molecules, heparan sulfate, heparin,
entactin, laminin, and the laminin receptor
on the cell surface.
Þ Appears during embryogenesis, but its
synthesis is switched off in mature tissues.
TENASCIN Þ Reappears during wound healing and is
also found within musculotendinous
junctions and malignant tumors.
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Þ Has binding sites for fibrinogen, heparin,
and EGF-like growth factors; thus, it
participates in cell attachment to the ECM.
Þ Present in the ECM of bone.
Þ Binds to the osteoclasts and attaches them
OSTEOPONTIN to the underlying bone surface.
Þ Important role in sequestering calcium and
promoting calcification of the ECM.
Both of these glycoproteins (and other similar glycoproteins) are multiadhesive, with
binding sites for ECM components and for integrins at cell surfaces, and have important
roles in cell migration and maintaining tissue structure.
(a) Laminin is concentrated in the basal lamina of the stratified epithelium (top) and in
the external laminae surrounding cross- sectioned nerves and muscle fibers. X200.
(b) A fine network of fibronectin is localized more diffusely throughout the ECM.
Interstitial fluid
Þ In addition to the hydrated ground substance of connective
tissue, a small quantity of free interstitial fluid, with ion
composition similar to that of blood plasma, is also present.
Þ Contains plasma proteins of low molecular weight that pass
through the thin walls of capillaries, the smallest blood vessels.
Þ Although only a small proportion of connective tissue proteins
are plasma proteins, it is estimated that as much as one-third of
the body’s plasma proteins are stored in the matrix of connective
tissue because of its volume and wide distribution.
– Capillaries in connective tissue throughout the body bring the various
nutrients required by cells and carry away their metabolic waste products
to the detoxifying and excretory organs, the liver and kidneys. Interstitial
water provides the solvent for these substances.
– Two forces act on the water in capillaries:
Þ Caused by the pumping action of the heart,
which forces water out across the capillary
wall.
HYDROSTATIC
PRESSURE Þ Produced by plasma proteins such as
albumin, which draws back into the
capillaries.
COLLOID Þ Produced by plasma proteins such as
OSMOTIC albumin, which draws water back into the
PRESSURE capillaries.
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LOOSE CONNECTIVE TISSUE
Þ Also called AREOLAR TISSUE
Þ Relatively more ground substance than collagen (< collagen).
Þ Thin and relatively sparse collagen fibers. (cells > fibers)
Þ Most numerous cells are fibroblasts.
Þ Comprises a thick layer (the lamina propria) beneath the
epithelial lining of the digestive system.
Þ Fills the spaces between the muscle and nerve fibers.
Þ Well-vascularized
Water normally passes through capillary walls into the ECM of surrounding connective tissues Þ Has a delicate consistency; flexible & not very resistant to stress.
primarily at the arterial end of a capillary, because the hydrostatic pressure is greater than the
colloid osmotic pressure. However, hydrostatic pressure decreases toward the venous end of the Þ Typically surrounds small blood vessels and occupies areas
capillary, as indicated at the top of the figure. The fall in hydrostatic pressure parallels a rise in adjacent to other types of epithelia.
osmotic pressure of the capillary blood because the plasma protein concentration increases as
water is pushed out across the capillary wall.

As a result of the increased protein concentration and decreased hydrostatic pressure, osmotic
pressure at the venous end is greater than hydrostatic pressure and water is drawn back into the
capillary. In this way plasma and interstitial fluid constantly mix, nutrients in blood circulate to
cells in connective tissue, and cellular wastes are removed.

Not all water that leaves capillaries by hydrostatic pressure is drawn back in by osmotic pressure.
This excess tissue fluid is normally drained by the lymphatic capillaries, open-ended vessels that
arise in connective tissue and enter the one-way lymphatic system that eventually delivers the
fluid (now called lymph) back to veins.

EDEMA – excessive accumulation of water in the extracellular spaces of connective tissue.

This water comes from the blood, passing through the capillary walls that become more
permeable during inflammation and normally producing slight swelling.

TYPES OF CONNECTIVE TISSUE

CONNECTIVE TISSUE PROPER
Þ Classified according to the amount of collagen and ground
substance present.
DENSE CONNECTIVE TISSUE
Þ Two general subtypes: Þ More collagen
o Loose connective tissue (areolar tissue) Þ Adapted to offer stress resistance and protection
o Dense connective tissue Þ Same components found in loose connective tissue, but with
– Subcategorized based on the organization of its collagen fibers: fewer cells and a clear predominance of collagen fibers over
§ Dense irregular connective tissue ground substance. (fibers > cells)

§ Dense regular connective tissue Þ Less flexible and far more resistant to stress than LCT.
Þ Filled primarily with randomly distributed bundles of type I
collagen, with some elastic fibers, providing resistance to tearing
Connective Tissue
from all directions as well as some elasticity.

Embryonic Adult Connective

Connective Tissue Tissue dense irregular connective tissue (dict)
Þ Contains mostly collagen fibers.
Loose
Mesenchyme Mucous Dense Specialized
(areolar)
Þ Cells are sparse and are typically of a single type, the fibroblast.

Irregular Regular Reticular Adipose

Þ Fibers are arranged in bundles oriented in various directions (thus,
the term irregular).

Þ Withstands stresses on organs or structures.

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 Human Histology Lecture
Þ Location: RETICULAR TISSUE
Þ Possessed by hollow organs (e.g., the intestinal tract) Þ Produced by modified fibroblasts often called RETICULAR
in which the fiber bundles course in varying planes.
CELLS.
SUBMUCOSA
– This arrangement allows the organ to resist
excessive stretching and distension.
Þ Consists of collagen fibrils and composed abundantly of type III
collagen fibers.
RETICULAR Þ Provides resistance to tearing as a consequence of
LAYER stretching forces from different directions. Þ Forms a soft internal skeleton (stroma) that supports other cell
OF THE DERMIS types including white blood cells, mast cells, and macrophages.
ORGAN Þ This collagen is also known as RETICULIN.
CAPSULES
Þ Location:
BONE MARROW LYMPH NODES SPLEEN
The micrograph shows a silver-stained section of
lymph node in which reticular fibers are seen as
irregular black lines. Reticular cells are also heavily
stained and dark. Most of the smaller, more lightly
stained cells are lymphocytes passing through the
lymph node.

dense regular connective tissue

Þ Characterized by ordered and densely packed arrays of fibers and
cells.
Þ Main functional component of tendons, ligaments, and
aponeuroses.
Þ White in the fresh state and almost inextensible.
Þ Separated by very little ground substance.
In the Lymph nodes.↑The diagram shows only the fibers and attached reticular cells. Reticular
Þ Strong, flexible straps or cords that hold together components of fibers of type III collagen are produced and enveloped by the reticular cells, forming an elaborate
network through which interstitial fluid or lymph & wandering cells from blood pass continuously.
the musculoskeletal system.
Þ Consists mostly of type I collagen bundles and fibroblasts aligned MUCOID TISSUE
in parallel for great resistance to prolonged or repeated stresses Þ Embryonic type of connective tissue.
from the same direction.
– The principal component of the fetal umbilical cord, where it
Þ Location: is referred to as WHARTON’S JELLY.
TENDONS Þ Very strong and flexible. Þ Abundant ground substance composed chiefly of hyaluronic acid
Þ Bands or sheets that hold together Þ Is jellylike or gelatinous with sparse collagen fibers and scattered
LIGAMENTS components of the skeletal system. fibroblasts.
Þ Cords connecting muscles to bones Þ Similar to the tissue found in the vitreous chambers of eyes and
APONEUROSES
Þ Sheetlike tendons. pulp cavities of young teeth.
Þ Location:
UMBILICAL CORD FETAL ORGANS

A section of umbilical cord shows large fibroblasts

surrounded by a large amount of very loose ECM
containing mainly ground substances very rich in
hyaluronan, with wisps of collagen. Histologically
mucoid (or mucous) connective tissue resembles
embryonic mesenchyme in many respects and is
rarely found in adult organs.
↑Micrograph shows a longitudinal section of dense regular connective tissue in a tendon. Long,
parallel bundles of collagen fibers fill the spaces between the elongated nuclei of fibrocytes.

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 Human Histology Lecture
Connective Tissues Part 2 || Lesson Reviewer || 2nd Year, 2nd Semester [Midterms]
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ADIPOSE TISSUE
ADIPOSE TISSUE
Þ Connective tissue in which adipocytes or fat cells predominate
Þ Typically found isolated or in small groups within loose or dense
irregular connective tissue but occur in large aggregates in
adipose tissue or “fat” in many organs and body regions.
Þ Normally represents 15% – 20% of the body weight in men,
somewhat more in women.
Þ Serving as storage depots for neutral fats (triglycerides)
Þ Key regulators of the body’s overall energy metabolism
Þ ENDOCRINE TISSUE (tissue that has a relationship with the endocrine organs)

Þ Conducts heat poorly and helps thermally insulate the body
Þ Fills up spaces between other tissues and helps cushion and keep
some organs in place
(a) Large white adipocytes (A) are seen in the connective tissue associated with small blood vessels. The fat cells
are empty because lipid was dissolved away in slide preparation. Nuclei at the cell membranes are visible in
some of the fat cells. (X100; H&E)
(b) Large (empty) adipocytes predominate in this typical white adipose tissue, which shows only a small portion of
microvasculature. In a single histologic section, nuclei of most very large adipocytes are not included.

Þ Helps shape the body surface

BROWN ADIPOSE TISSUE
TWO MAJOR TYPES OF ADIPOSE TISSUE Þ MULTILOCULAR (contains many small lipid inclusions)

WHITE ADIPOSE TISSUE Þ Constitutes 2%-5% of the newborn body weight, located mainly
in the back, neck, and shoulders, but it is greatly reduced during
Þ UNILOCULAR
childhood and adolescence.
Þ Have a signet-ring appearance of cell
Þ Principal function is heat production and warming the blood
Þ Surrounded by a thin external lamina containing type IV – Mediated by the help of small lipid droplets, abundant mitochondria,
collagen. and rich vasculature.
Þ Energy storage, insulation, cushioning of vital organs, and Þ In adults, it is found only in scattered areas, especially around the
secretion of hormones. kidneys, adrenal glands, aorta, and mediastinum.
Þ Consists of cells each containing one large cytoplasmic droplet of
Þ Color of brown fat is due to:
whitish-yellow f at (triglyceride).
– Very abundant mitochondria (containing cytochrome
Þ Because lipid is removed from cells by xylene or other solvents used in
pigment) scattered among the lipid droplets of the fat cells
routine histological techniques, unilocular adipocytes are often empty in
standard light microscopy. – Large number of blood capillaries in this tissue
Þ Its distribution changes significantly through childhood and adult life and is
Þ Cytoplasm contains a great number of lipid droplets of various
partly regulated by sex hormones controlling adipose deposition in the
breasts and thighs. sizes and nuclei are often centrally located.

Þ The color of freshly dissected unilocular adipo. depends on the diet, varying
from white to yellow with the amount of carotenoids dissolved in the lipid.
Þ Location:
§ Subcutaneous layer of connective tissue
Þ Emerges earlier than white fat during fetal development. In humans the
amount of brown fat is maximal relative to body weight at birth, when
thermogenesis is most needed and partially disappears by involution and
apoptosis during childhood. In adults the amount and activity of brown fat
are higher in lean individuals.

§ Mammary fat pad

§ Around the kidneys
§ Bone marrow and between other tissues, where it fills in spaces
§ Hand palms and soles of the feet
§ Beneath the visceral pericardium
§ Orbits around the eyeballs

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 Human Histology Lecture
TERRITORIAL Þ Region that is more removed from the
MATRIX immediate vicinity of the chondrocytes.

INTER Þ Region that surrounds the territorial matrix

TERRITORIAL and occupies the space between groups pf
MATRIX chondrocytes.

ISOGENOUS Þ Clusters of chondrocytes

GROUPS

The differentiation of adipocytes is first seen with the appearance of the preadipocytes. The
preadipocytes are derived from the mesenchymal cells. These cells have the appearance of the
fibroblasts but they accumulate lipid droplets in their cytoplasm. Lipid accumulation are isolated
form one another at first but will soon fuse to form the single large droplet characteristic of
unilocular adipocyte. If it does not fuse, then it becomes the multilocular adipocyte.

Mesenchymal stem cells differentiate as progenitor cells for all types of connective tissue, A diagram of the transitional area between the perichondrium and the cartilage matrix. Fibroblast-
including preadipocytes. These are initially of at least two types. Preadipocytes developing like progenitor cells in the perichondrium (perichondrial fibroblasts) give rise to larger
within the lateral mesoderm of the embryo produce large number of white adipocytes (forming chondroblasts, which divide and differentiate as chondrocytes. These functional cells produce
matrix components and exist in lacunae surrounded by the matrix. The ECM immediately around
white adipose tissue) and a smaller number of so-called beige adipocytes with cytological features
each lacuna, called the territorial matrix, contains mostly proteoglycans and sparse collagen; that
and gene expression patterns of both white and brown adipocytes. White adipocytes are
more distant from lacunae, the interterritorial matrix, is richer in collagen and may be less
unilocular, with one large lipid droplet occupying most of the cytoplasm. The white adipocyte is
basophilic. If the chondrocytes forms a group, it is called a ISOGENOUS GROUP (two chondrocytes
usually much larger than that shown here in relation to the other cell types.
or more).
Brown adipocytes differentiate from another population Chondrocytes arise from the fibroblast-like progenitor cells in the perichondrium (perichondrial fibroblast). The perichondrial
fibroblast would then differentiate to become your chondroblast. Once this chondroblast starts synthesizing this ECM components,
of preadipocytes located in paraxial embryonic mesoderm and remain multilocular (having many
the chondroblasts is unable to move and be stuck on that space (lacunae) wherein they mature as chondrocytes.
small lipid droplets) with numerous mitochondria (not shown here). Mitochondrial metabolism
of lipid in brown adipocytes releases heat rather than ATP. Cells functioning as brown adipocytes
can also develop from beige adipocytes during adaptation to cold temperatures.
CHONDROGENESIS
Cartilage || Lesson Reviewer || 2nd Year, 2nd Semester [Midterms] Þ The process of cartilage development begins with the
aggregation of chondroprogenitor mesenchymal cells to form a
CARTILAGE mass of rounded, closely apposed cells.
CARTILAGE Þ The dividing cells are typically called chondroblasts and
Þ An avascular tissue that consists of chondrocytes and an extensive chondrocytes when proliferation has ceased.
extracellular matrix.
Þ Its firm consistency allows the tissue to bear mechanical stresses
without permanent distortion.
Þ Avascular (does not receive any blood supply)
Þ A sheath of dense connective tissue that
surrounds the cartilage in most places,
forming an interface between the cartilage
PERICHON- and the tissues supported by the cartilage.
DRIUM
Þ Source of nutrients by the cartilage through The major stages of embryonic cartilage formation, or chondrogenesis, are shown here.
(a) Mesenchyme is the precursor for all types of cartilage. (b) Mitosis and initial cell
diffusion from capillaries in its adjacent
differentiation produces a tissue with condensations of rounded cells called
connective tissue called the perichondrium. chondroblasts. (c) Chondroblasts are then separated from one another again by their
production of the various matrix components, which collectively swell with water and form
Þ Specialized cells that produce and maintain the very extensive ECM. (d) Multiplication of chondroblasts within the matrix gives rise to
CHONDRO- the extracellular matrix. isogenous cell aggregates surrounded by a condensation of territorial matrix. In mature
CYTES cartilage, this interstitial mitotic activity ceases and all chondrocytes typically become more
Þ Located in matrix cavities called LACUNAE. widely separated by their production of matrix.

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 Human Histology Lecture
ELASTIC CARTILAGE
Þ Contains an abundant network of elastic fibers
Þ Collagen type II (which give fresh elastic cartilage a yellowish color)

Þ Elastic material gives the cartilage elastic properties in addition

to the resilience and pliability.
Þ With appropriate staining, it appear as dark bundles distributed
unevenly through the matrix.
Þ More flexible
Þ Location:
– Auricle of the ear
– Walls of the external auditory canal
– Auditory (Eustachian) tubes
MAJOR CARTILAGE TYPES – Epiglottis
HYALINE CARTILAGE – Cuneiform cartilage in the larynx
Þ The most common of the tree forms – Upper respiratory tract
Þ Constitute majority of the fatal skeleton
Þ Homogeneous and semitransparent in the fresh state.
Þ In Adults, located in:
– Articular surface of movable joints
– Walls of larger respiratory passages (nose, larynx, trachea,
bronchi)
– Ventral ends of ribs (where they articulate with the sternum)
The chondrocytes (C) and overall organization of elastic cartilage are similar to those of hyaline cartilage,
– Epiphyseal plates of long bones (where it makes possible longitudinal bone growth) but the matrix (M) also contains elastic fibers that can be seen as darker components with proper
staining. The abundant elastic fibers provide greater flexibility to this type of cartilage. The section in part
b includes perichondrium (P) that is also similar to that of hyaline cartilage. (a) X160; Hematoxylin and
Þ In the Embryo, orcein. (b) X180; Weigert resorcin and van Gieson.
– Forms the temporary skeleton that is gradually replaced by
bone.
FIBROCARTILAGE
Þ Most of the collagen is Type II collagen.
Þ A combination of hyaline cartilage and dense connective tissue
Þ AGGRECAN – most abundant proteoglycan of hyaline cartilage.
Þ Chondrocytes occur singly and in aligned isogenous aggregates
Þ CHONDRONECTIN
Þ Type II collagen
– Structural multiadhesive glycoprotein; another important
component of cartilage matrix. Þ Areas with chondrocytes and hyaline matrix are separated by
– Binds specifically to GAGs, collagen, and integrins, other regions containing bundles of type I collagen and scattered
mediating the adherence of chondrocytes to the ECM. fibroblasts and and dense bundles of type I collagen which confer
extra tensile strength to this tissue.
Þ Chondrocytes occur singly or in small, mitotically derived
isogenous groups. Þ The relative scarcity of proteoglycans overall makes fibrocartilage
matrix more acidophilic than hyaline or elastic cartilage. There is

Þ No distinct surrounding perichondrium.

Þ Location:
– Intervertebral discs
– Attachments of certain ligaments
– Pubic symphysis (all places where it serves as very tough, yet cushioning
support tissue for bone)

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 Human Histology Lecture
§ Harbors cavities containing bone marrow where blood cells
are produced
§ Reservoir of calcium, phosphate, and other ions
§ Bodily movements
Þ Bone tissue is classified as:

COMPACT Þ A compact, dense layer forming the outside of

(DENSE) the bone.
Fibrocartilage varies histologically in different structures but is always essentially a mixture of hyaline cartilage
and dense connective tissue. In a small region of intervertebral disc, the axially arranged aggregates of
BONE Þ Represents 80% of the total bone mass.
chondrocytes (C) are seen to be surrounded by small amounts of matrix and separated by larger regions with
dense collagen and scattered fibroblasts with elongated nuclei (arrows) Þ A spongelike meshwork consisting of
SPONGY trabeculae (thin, anastomosing spicules of
(CANCELLOUS) bone tissue) forming the interior of the bone.
FUNCTIONS OF ALL TYPES OF CARTILAGE BONE
Þ Constituting about 20% of total bone mass.
HYALINE ELASTIC FIBRO
§ Resists compression § Provides § Resists
flexible deformation PERIOSTEUM & ENDOSTEUM
§ Provides cushioning, smooth, and
support under stress Þ A fibrous connective tissue capsule covers the
low-friction surface for joints PERIOSTEUM
outer surface of the bone.
§ Provides structural support in
respiratory system (larynx, trachea, Þ A layer of connective tissue cells that lines the
ENDOSTEUM
and bronchi). bone cavities

§ Forms foundation for development PERFORATING Þ Bundles of periosteal collagen fibers that
(OR SHARPEY)
of fetal skeleton FIBERS penetrate the bone matrix.

§ Endochondral bone formation and Þ Spaces within the bone matric, each of which
LACUNAE
bone growth contains a bone cell.
Þ Small channels that interconnects the lacunae.
CANALICULI Þ Small tunnels into which the osteocyte extends
numerous processes.

_______________________________________________
Bone || Lesson Reviewer || 2nd Year, 2nd Semester [Midterms]

BONE
BONE
Þ Specialized connective tissue composed of calcified extracellular
material, the bone matrix, and three major cell types.
Þ The feature that distinguishes bone from other connective tissues
is the mineralization of its matrix, which produces an extremely
hard tissue capable of providing support and protection.
– The mineral is calcium phosphate in the form of
HYDROXYAPATITE CRYSTALS.
Þ Function:
§ Main constituent of the adult skeleton
§ Provides solid support for the body
§ Protects vital organs
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 Human Histology Lecture
A schematic overview of the basic features of bone, including the three key cell types: osteocytes, During remodeling of compact bone, osteoclasts act as a cutting cone that tunnels into existing
osteoblasts, and osteoclasts; their usual locations; and the typical lamellar organization of bone matrix. Behind the osteoclasts, a population of osteoblast progenitors enters the newly
bone. formed tunnel and lines its walls. The osteoblasts secrete osteoid in a cyclic manner, producing
• OSTEOBLASTS – secretes the matrix that then hardens by calcification, trapping the layers of new matrix (lamellae), and trapping some cells (future osteocytes) in lacunae. The tunnel
differentiating cells now called osteocytes in individual lacunae. becomes constricted with multiple concentric layers of new matrix, and its lumen finally exists as
only a narrow central canal with small blood vessels. The dashed lines in (a) indicate the levels of
• OSTEOCYTES – maintains the calcified matrix and receive nutrients from microvasculature in
the structures shown in cross section (b). An x-ray image (c) shows the different degrees of
the central canals of the osteons via very small channels called CANALICULI that interconnect
mineralization in osteons and in interstitial lamellae (I).
the lacunae.
• OSTEOCLASTS – monocyte-derived cells in bone required for bone remodeling. BONE CELLS
• PERIOSTEUM – consists of dense connective tissue, with a primarily fibrous layer covering a
Þ The differentiated bone-forming
more cellular layer. Bone is vascularized by small vessels that penetrate the matrix from the
periosteum. (osteoprogenitor) cell that secretes
• ENDOSTEUM – covers all trabeculae around the marrow cavities. components of the initial matrix, called
OSTEOID, that allow matrix mineralization
OSTEOBLASTS
to occur.
OSTEON
Þ or HAVERSIAN SYSTEM Þ Located exclusively at the surfaces of bone
matrix.
Þ Refers to the complex of concentric lamellae surrounding a small
central canal that contains blood vessels, nerves, loose Þ The mature bone cells enclosed by bone
connective tissue, and endosteum. matrix that it previously secreted as an
Þ Outer boundary of each osteon that is osteoblast.
CEMENT LINE collagen-rich layer. Þ Enclosed singly within the lacunae
Þ Channels in lamellar bone through which Þ Flat, almond-shaped osteocytes exhibit
blood vessels and nerves travel from the
PERFORATING significantly less RER, smaller Golgi
periosteal and endosteal surfaces to reach
CANALS complexes, and more condensed nuclear
(VOLKMANN’S the osteonal canal. OSTEOCYTES chromatin.
CANALS) Þ They also connect osteonal canals to one
Þ Maintains the bony matrix
another.
DIAGRAM OF A SECTION OF COMPACT BONE REMOVED FROM THE SHAFT OF A LONG BONE Þ During the transition from osteoblasts to
osteocytes, the cells extend many long
STRUCTURE OF A TYPICAL LONG BONE
dendritic processes, which also become
surrounded by calcifying matrix via narrow
canaliculi radiating from each lacuna.

Þ Responsible for bone resorption.

Þ Very large, motile cells with multiple nuclei
Þ Plays a major role in matrix resorption
during bone growth and remodeling.
OSTEOCLASTS
Þ Found in area of bone undergoing
resorption, osteoclasts lie within
enzymatically etched depression or cavities
in the matrix known as resorption
cavities (a.k.a. HOWSHIP LACUNAE)

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 Human Histology Lecture
OSTEOCLASTS AND THEIR ACTIVITY
Þ In which preexisting matrix of hyaline
cartilage is eroded and invaded by
osteoblasts, which then begin osteoid
production.
ENDO-
Þ In this process ossification first occurs
CHONDRAL
OSSIFICATION
within a BONE COLLAR produced by
osteoblasts that differentiate within the
a) Photo of bone showing two osteoclasts (Ocl) digesting and resorbing bone matrix (B) in perichondrium (transitioning to
relatively large resorption cavities (or HOWSHIP LACUNAE) on the matrix surface. An periosteum) around the cartilage model
osteocyte (Oc) in its smaller lacuna is also shown. (X400; H&E)
diaphysis.
b) Diagram showing an osteoclast’s circumferential sealing zone where integrins tightly bind
the cell to the bone matrix.

LAMELLAR BONE
Þ Most bone in adults, compact or cancellous, is organized as
lamellar bone, characterized by multiple layers or LAMELLAE of
calcified matrix.

DIAGRAM OF IMMATURE AND MATURE BONE. Immature bone does not display an organized
lamellar appearance because of the interlacing arrangement of the collagen fibers. The cells tend to be
randomly arranged, whereas the cells in mature bone are organized in a circular fashion that reflects the
lamellar structure of the Haversian system. Resorption canals in mature bone have their long axes in the
same direction as the Haversian canals.

SCHEMATIC DIAGRAM OF DEVELOPING LONG BONE

ossification centers
PRIMARY Þ The first site where bone begins to form in
O.C. the diaphysis of a long bone.
PHOTOMICROGRAPHS OF DECALCIFIED IMMATURE AND MATURE BONE. Þ Appears later at the epiphyses of the
a. Decalcified immature bone shows the relationship of cells to the extracellular matrix. The immature bone
has more cells, and the matrix is not layered in osteonal arrays.
SECONDARY cartilage model and develop in a similar
b. This cross section of decalcified mature compact bone stained with H&E shows several osteons (O) with O.C. manner.
concentric lamellae.

Þ With the primary and secondary ossification center, two regions

BONE FORMATION of cartilage remain:
Þ The development of a bone is traditionally classified as: o The layer of ARTICULAR CARTILAGE within joints which
Þ In which osteoblasts differentiate directly usually persists through adult life and does not contribute to
from mesenchyme and begin secreting bone growth
INTRA- osteoid. o The specially organized EPIPHYSEAL CARTILAGE (also
MEMBRONOUS called EPIPHYSEAL PLATE or GRWOTH PLATE), which
OSSIFICATION
Þ Within the condensed mesenchyme bone
formation begins in OSSIFICATION connects each epiphysis to the diaphysis.
CENTERS. – There are five zones in the epiphyseal plate:

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 Human Histology Lecture
Þ Consists of hyaline cartilage with typical
RESTING ZONE chondrocytes.
Þ In this zone, chondrocytes begin to divide
PROLIFERATIVE rapidly, and forms columns of stacked cells
ZONE parallel to the long axis of the bone.
Þ Contains swollen, degenerative
chondrocytes whose cytoplasm has
HYPERTROPHIC
accumulated glycogen.
CARTILAGE
ZONE Þ This hypertrophy compresses the matrix
into thin septa between the chondrocytes.
Þ In this zone, loss of the chondrocytes by
CALCIFIED apoptosis is accompanied by calcification
CARTILAGE of the septa of cartilage matrix by the
ZONE formation of hydroxyapatite crystals.
Þ Bone tissue first appears.
Þ Capillaries and osteoprogenitor cells
originally from the periosteum invade the
cavities left by the chondrocytes.
OSSIFICATION Þ Many of these cavities will be merged and
ZONE become the marrow cavity
Þ Osteoblasts settle in a layer over the septa
of calcified cartilage matrix and secrete
osteoid over these structures, forming
woven bone.
BONE GROWTH, REMODELLING, AND REPAIR
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Blood || Lesson Reviewer || 2nd Year, 2nd Semester [Midterms]
BLOOD
BLOOD
Þ Also a connective tissue because despite not having any fiber, it
has an extracellular matrix in the form of plasma and it has the
formed elements which are the blood cells and platelets.
Þ The liquid portion of circulating blood is PLASMA, while cells
and platelets comprise the FORMED ELEMENTS.
Þ Upon clotting, some proteins are removed from plasma and
others are released from platelets, forming a new liquid termed
SERUM.
Þ Important protein components of plasma that are secreted within
the LIVER include albumin, diverse 𝜶– and 𝜷–globulins,
proteins of the complement system, and fibrinogen, as well
as the immunoglobulins.
Þ or ERYTHROCYTES
Þ Makes up the hematocrit portion (~45%)
of a blood sample
RED BLOOD
CELLS Þ Are enucleated, biconcave discs 7.5 𝜇m in
(RBCs) diameter, filled with hemoglobin for the
uptake, transport, and release of oxygen.
Þ Normal life span of about 120 days.
Þ Broadly grouped as GRANULOCYTES
(neutrophils, eosinophils basophils) or
WHITE AGRANULOCYTES (lymphocytes,
BLOOD CELLS monocytes).
Þ Plays a key on the immune system.
Þ Small (2–4 𝜇m) cell fragments derived from
megakaryocytes in bone marrow, with a
marginal bundle of actin filaments, alpha
granules and delta granules, and an open
PLATELETS
calicular system of membranous vesicles.
Þ Rapid degranulation on contact with
collagen triggers blood clotting.
 Human Histology Lecture
LEUKOCYTES MONOCYTES
(agranulocyte)

NEUTROPHILS Þ Blood macrophages

(granulocyte)
Þ The most abundant type of leukocyte.
Þ Have polymorphic, multilobed (3–5)
nuclei, and faint pink cytoplasmic
granules.
Þ Contains many factors for highly efficient
phagolysosomal killing and removal of
bacteria.
Þ Largest WBC in the blood
Þ Larger agranulocytes with distinctly
indented or C-shaped (or horseshoe-
shaped) nuclei.
– It also has a ground-glass appearance
due to the presence of azurophilic
granules.
Þ Circulates as precursors of macrophages
and other cells of the mononuclear phagocyte system.

EOSINOPHILS
(granulocyte)

Þ Have bilobed nuclei and eosinophilic red-

orange or red/dark pink specific granules.
Þ Contains factors for destruction of helminthic
parasites and for modulating inflammation.

BASOPHILS
(granulocyte)
Þ Rarest type of circulating leukocyte
Þ Have irregular bilobed (clover-shaped) or S-
shaped nuclei and resemble mast cells with
strongly basophilic dark blue/purple
specific granules.
Þ Contains factors important in allergies and
chronic inflammatory conditions, including HEMOPOIESIS / HEMATOPOIESIS
histamine, heparin, chemokines, and
Þ The process of blood cell formation
various hydrolases.
Þ Begins in the YOLK SAP around the first 2-8 weeks of life
LYMPHOCYTES – Yolk sap is the site of primitive hematopoiesis
(agranulocyte)
Þ Major cell in the numeral immunity Þ By the 6th week around the 2nd & 5th month, the LIVER becomes
(adaptive immune response). the major hematopoietic organ
– The major hematopoietic organ of early and mid-fetal life.
Þ Agranulocytes with many functions as T–
and B–, & K–cell subtypes in the immune – Where the 1st synthesis of fetal hemoglobin begins.
system. Þ Once the baby reaches the 4th month, the BONE MARROW
Þ Ranges widely in size, depending on starts the blood cell production.
their activation state. – After 5th fetal month, it becomes the primary site of
hematopoiesis until postnatal life.
Þ Have roughly spherical nuclei with little,
sky-blue cytoplasm (a.k.a. ROBIN’S EGG Þ As the person ages, blood cell formation becomes confined in the
BLUE) and few organelles. flat bones.
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 Human Histology Lecture

During embryonic and fetal life, erythrocytes are formed in several organs. Essentially, three
major organs involved in hemopoiesis can be sequentially identified: The YOLK SAC in the early
developmental stages of the embryo; the LIVER during the second trimester of pregnancy; and
the BONE MARROW during the third trimester. The spleen participates to a very limited degree
during the second trimester of pregnancy. At birth, most hemopoiesis occurs in the red bone
marrow, as it does in the adult.

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 Human Histology Lecture

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