onnective tissue is a form of fibrous tissue.[1].

It is one of the four types of tissue in traditional classifications (the others

being epithelial, muscle, and nervous tissue).

Collagen is the main protein of connective tissue in animals and the most abundant protein in mammals, making up about
25% of the total protein content.[2]

[edit] Terminology

It is largely a category of exclusion rather than one with a precise defintion, but all or most tissues in this category are
similarly:

 Involved in structure and support.

 Derived from mesoderm, usually.
 Characterized largely by the traits of non-living tissue.

Blood, cartilage, and bone are usually considered connective tissue, but, because they differ so substantially from the
other tissues in this class, the phrase "connective tissue proper" is commonly used to exclude those three. There is also
variation in the classification of embryonic connective tissues; on this page they will be treated as a third and separate
category.

[edit] Classification

Connective tissue can be classified into three categories: proper, embryonic, and specialized. [3]

[edit] Connective tissue proper

Connective tissue proper

Connective tissue proper includes the following five types: loose connective, dense connective, elastic, reticular, and
adipose.[3] They are called "proper" because they are the types usually meant when using the phrase "connective tissue."

 Areolar (or loose) connective tissue holds organs and epithelia in place, and has a variety of
proteinaceous fibers, including collagen and elastin.
 Dense connective tissue forms ligaments and tendons. (Some classification systems include fibrous
connective tissue instead. It is roughly equivalent to dense regular connective tissue.)
 Elastic tissue
 Reticular connective tissue is a network of reticular fibres (fine collagen, type III) that form a soft
skeleton to support the lymphoid organs (lymph nodes, bone marrow, and spleen.)
 Adipose tissue contains adipocytes, used for cushioning, thermal insulation, lubrication (primarily in
the pericardium) and energy storage.

[edit] Embryonic connective tissues

The two types of embryonic connective tissues are mesenchymal and mucous.[4] They are of minimal importance in the
adult.

 Mesenchymal connective tissue

 Mucous connective tissue
[edit] Specialized connective tissues

The category "specialized connective tissue" consists of bone, cartilage, and blood.[3] Although these items are connective
tissue, they are often considered separately.

Specialized connective tissues

 Blood functions in transport. Its extracellular matrix is blood plasma, which transports dissolved
nutrients, hormones, and carbon dioxide in the form of bicarbonate. The main cellular component is red blood
cells.

The following two can be classified as "supportive connective tissue":[5]

 Bone (osseous tissue) makes up virtually the entire skeleton in adult vertebrates.
 Cartilage makes up virtually the entire skeleton in chondrichthyes. In most other vertebrates, it is found
primarily in joints, where it provides cushioning. The extracellular matrix of cartilage is composed primarily of
collagen.

Dense connective tissue, also called dense fibrous tissue, has collagen fibers as its main matrix element. It is mainly
composed of collagen type I. Crowded between the collagen fibers are rows of fibroblasts, fiber-forming cells, that
manufacture the fibers. Dense connective tissue forms strong, rope-like structures such as tendons and ligaments.
Tendons attach skeletal muscles to bones; ligaments connect bones to bones at joints. Ligaments are more stretchy and
contain more elastic fibers than tendons. Dense connective tissue also make up the lower layers of the skin (dermis),
where it is arranged in sheets.

[edit] Fiber types

Not to be confused with muscle fibers

Fiber types as follows:

 collagenous fibers
 elastic fibers
 reticular fibers

[edit] Disorders of connective tissue

Main article: Connective tissue disease

Various connective tissue conditions have been identified; these can be both inherited and environmental.

 Marfan syndrome - a genetic disease causing abnormal fibrillin.

 Scurvy - caused by a dietary deficiency in vitamin C, leading to abnormal collagen.
 Ehlers-Danlos syndrome - deficient type III collagen- a genetic disease causing progressive
deterioration of collagens, with different EDS types affecting different sites in the body, such as joints, heart
valves, organ walls, arterial walls, etc.
 Loeys-Dietz syndrome - a genetic disease related to Marfan syndrome, with an emphasis on vascular
deterioration.
 Pseudoxanthoma elasticum - an autosomal recessive hereditary disease, caused by calcification and
fragmentation of elastic fibres, affecting the skin, the eyes and the cardiovascular system.
 Systemic lupus erythematosus - a chronic, multisystem, inflammatory disorder of probable
autoimmune etiology, occurring predominantly in young women.
  Osteogenesis imperfecta (brittle bone disease) - caused by insufficient production of good quality
collagen to produce healthy, strong bones.
 Fibrodysplasia ossificans progressiva - disease of the connective tissue, caused by a defective gene
which turns connective tissue into bone.
 Spontaneous pneumothorax - collapsed lung, believed to be related to subtle abnormalities in
connective tissue.
 Sarcoma - a neoplastic process originating within connective tissue.

[edit] Staining of connective tissue

For microscopic viewing, the majority of the connective tissue staining techniques color tissue fibers in contrasting
shades. Collagen may be differentially stained by any of the following techniques:

 Van Gieson's stain

 Masson's Trichrome stain
 Mallory's Aniline Blue stain
 Azocarmine stain
 Krajian's Aniline Blue stain
Index to this page
 Drawings
 1. Epithelial
 2. Muscle
Animal Tissues  3. Connective
o Supporting connective tissue
The development of a fertilized egg into a newborn child o Dense connective tissue
requires an average of 41 rounds of mitosis (241 = 2.2 x 1012). o Loose connective tissue
During this period, the cells produced by mitosis enter different o Adipose tissue
pathways of differentiation; some becoming blood cells, some  4. Nerve
muscle cells, and so on. o Neurons
o Glia
There are more than 100 visibly-distinguishable kinds of
differentiated cells in the vertebrate animal. These are
 5. Blood
organized into tissues; the tissues into organs. Groups of
organs make up the various systems - digestive, excretory, etc. - of the body.

The actual number of differentiated cell types is surely much larger than 100.
 All lymphocytes, for example, look alike but actually represent a variety of different functional types,
e.g., B cells, T cells of various subsets.

 The neurons of the central nervous system must exist in a thousand or more different functional types,
each representing the result of a particular pathway of differentiation.

This page will give a brief introduction to the major types of animal tissues. The links along the left
side of the figure will take you directly to the individual paragraphs indicated.

Epithelial
Muscle
Connective
Nerve
Blood
1. Epithelial

Epithelial tissue is made of closely-packed cells arranged in flat sheets. Epithelia form the surface of the skin, line the
various cavities and tubes of the body, and cover the internal organs.

Subsets of Epithelia

 Epithelia that form the interface between the internal and external environments.
o Skin as well as the lining of the mouth and nasal cavity. These are derived from ectoderm.
o Inner lining of the GI tract, lungs, urinary bladder, exocrine glands, vagina and more. These
are derived from endoderm.

The apical surface of these epithelial cells is exposed to the "external environment", the lumen of the organ or
the air. [View example]

 Mesothelia. These are derived from mesoderm.

o pleura — the outer covering of the lungs and the inner lining of the thoracic (chest) cavity.
o peritoneum — the outer covering of all the abdominal organs and the inner lining of the
abdominal cavity.
o pericardium — the outer lining of the heart.
 Endothelia. The inner lining of the heart, all blood and lymphatic vessels — derived from mesoderm.

The basolateral surface of all epithelia is exposed to the internal environment (ECF). The entire sheet of epithelial cells
is attached to a layer of extracellular matrix that is called the basement membrane or, better (because it is not a membrane
in the biological sense), the basal lamina. [View example]

View showing relationship between the apical and basolateral surfaces of epithelial cells and how they maintain their
distinction.

The function of epithelia always reflects the fact that they are boundaries between masses of cells and a cavity or space.
Some examples:

 The epithelium of the skin protects the underlying tissues from

o mechanical damage
o ultraviolet light
o dehydration
o invasion by bacteria
 The columnar epithelium of the intestine
o secretes digestive enzymes into the intestine;
o absorbs the products of digestion from it.
 An epithelium also lines our air passages and the alveoli of the lungs. It secretes mucus which keeps it
from drying out and traps inhaled dust particles. Most of its cells have cilia on their apical surface that propel the
mucus with its load of foreign matter back up to the throat.

2. Muscle

Three kinds of muscle are found in vertebrates:

 Skeletal muscle is made of long fibers whose contraction provides the force of locomotion and other
voluntary body movements.
 Smooth muscle lines the walls of the hollow structures of the body, such as the intestine, urinary
bladder, uterus, and blood vessels. Its contraction, which is involuntary, reduces the size of these hollow
organs.
 The heart is made of cardiac muscle.

Link to page devoted to the structure and properties of the three kinds of muscles.
3. Connective

The cells of connective tissue are embedded in a great amount of extracellular material. This matrix is secreted by the
cells. It consists of protein fibers embedded in an amorphous mixture of protein-polysaccharide ("proteoglycan")
molecules.

Supporting connective tissue

Gives strength, support, and protection to the soft parts of the body.
 cartilage. Example: the outer ear
 bone. The matrix of bone contains collagen fibers and mineral deposits. The most abundant mineral is
calcium phosphate, although magnesium, carbonate, and fluoride ions are also present. [More on bone]

Dense connective tissue

Often called fibrous connective tissue.

 Tendons connect muscle to bone. [View] The matrix is principally Type I collagen, and the fibers are
all oriented parallel to each other. Tendons are strong but not elastic.
 Ligaments attach one bone to another. They contain both collagen and also the protein elastin. Elastin
permits ligaments to be stretched.

Loose connective tissue

It is distributed throughout the body. It serves as a packing and binding material for most of our organs. Collagen, elastin,
and other proteins are found in the matrix.

Both dense and loose connective tissue is derived from cells called fibroblasts [View], which secrete the extracellular
matrix.

Adipose tissue

Adipose tissue is "fat". There are two kinds found in mammals:

 white adipose tissue (WAT) in which the cells, called adipocytes, have become almost filled with oil.
The oil is confined within a single membrane-bound droplet. Virtually all of the "fat" in adult humans is white
adipose tissue.
 brown adipose tissue (BAT) in which the adipocytes contain many small droplets of oil as well as
many mitochondria.

White adipose tissue and brown adipose tissue differ in function as well as cellular structure. These differences are
described on a separate page. Link to it.

New adipocytes in white fat are formed throughout life from a pool of precursor cells. These are needed to replace those
that die (after a life span of about 100 days). Whether the total number of these adipocytes increases in humans
becoming fatter as adults is still uncertain. If not, why do so many of us get fatter as we age? Because of the increased
size of individual adipocytes as they become filled with oil.

The adipocytes of white fat secrete several hormones, including leptin and adiponectin.

4. Nerve

Nerve tissue is composed of

 nerve cells called neurons and
 glial cells.

Neurons

Neurons are specialized for the conduction of nerve impulses. A typical neuron consists of
 a cell body which contains the nucleus;
 a number of short fibers — dendrites — extending from the cell body
 a single long fiber, the axon.
The nerve impulse is conducted along the axon.

Link to a page devoted to neuron structure.

The tips of axons meet:

 other neurons at junctions called synapses

Link to a page describing the properties of synapses.
 muscles (called neuromuscular junctions)
Link here to a page describing the neuromuscular junction.
 glands

Link here to a page describing how neurons work.

Link here to a page describing the types and organization of neurons in the peripheral nervous system.

Glia

Glial cells surround neurons. Once thought to be simply support for neurons (glia = glue), they turn out to serve several
important functions.

There are three types:

 Schwann cells. These produce the myelin sheath that surrounds many axons in the peripheral nervous
system.
 Oligodendrocytes. These produce the myelin sheath that surrounds many axons in the central nervous
system (brain and spinal cord).
 Astrocytes. These — often star-shaped — cells are clustered around synapses and the nodes of Ranvier
where they perform a variety of functions:
o stimulating the formation of new synapses;
o modulating the activity of neurons [Example];
o supplying neurons with materials (e.g. glucose, oxygen) secured from the blood;
o regulating the flow of blood to their region of the brain. It is primarily the metabolic activity
of astrocytes that is being measured in brain imaging by positron-emission tomography (PET) and
functional magnetic resonance imaging (fMRI).

In addition, the central nervous system contains many microglia — mobile cells (macrophages) that respond to damage
(e.g., from an infection) by

 engulfing cell debris

 secreting inflammatory cytokines like tumor necrosis factor (TNF-α) and interleukin-1 (IL-1)

5. Blood

The bone marrow is the source of all the cells of the blood. These include:
 red blood cells (RBCs or erythrocytes)
 five kinds of white blood cells (WBCs or leukocytes)
 platelets (or thrombocytes)

Blood
Blood is a liquid tissue. Suspended in the watery plasma are seven types of cells and cell fragments.
 red blood cells (RBCs) or erythrocytes
 platelets or thrombocytes
 five kinds of white blood cells (WBCs) or leukocytes
o Three kinds of granulocytes
 neutrophils
 eosinophils
  basophils
o Two kinds of leukocytes without granules in their cytoplasm
 lymphocytes
 monocytes

If one takes a sample of blood, treats it with an agent to prevent clotting, and spins it in a
centrifuge,
 the red cells settle to the bottom
 the white cells settle on top of them forming the "buffy coat".

The fraction occupied by the red cells is called the hematocrit. Normally it is
approximately 45%. Values much lower than this are a sign of anemia.

Functions of the blood

Blood performs two major functions:

 transport
through the body
of
o
oxygen
and
carbon
dioxide
o
food
molecules
(glucose,
lipids,
amino
acids)
o
ions (e.g.,
Na+, Ca2+,
HCO3−)
o
wastes
(e.g.,
urea)
o
hormones
o
heat
 defense of
the body against
Link to a diagram showing the actual appearance of these cells (96K)
infections and
other foreign materials. All the WBCs participate in these defenses.

The formation of blood cells (cell types and acronyms are defined below)

All the various types of blood cells

 are produced in the bone marrow (some 1011 of them each day in an adult human!).
 arise from a single type of cell called a hematopoietic stem cell — an "adult" multipotent stem cell.

These stem cells

  are very rare (only about one in 10,000 bone marrow cells);
 are attached (probably by adherens junctions) to osteoblasts lining the inner
surface of bone cavities;
 express a cell-surface protein designated CD34;
 produce, by mitosis, two kinds of progeny:
o more stem cells (A mouse that has had all its blood stem cells
killed by a lethal dose of radiation can be saved by the injection of a single
living stem cell!).
o cells that begin to differentiate along the paths leading to the
various kinds of blood cells.

Which path is taken is regulated by

 the need for more of that type of blood cell which is, in turn, controlled by
appropriate cytokines and/or hormones.

For example, Interleukin-7 (IL-7) is the major cytokine in stimulating bone marrow stem cells to start down the
"lymphoid" path leading to the various lymphocytes (mostly B cells and T cells).

Some of the cytokines that drive the differentiation of the "myeloid" leukocytes are
 Erythropoietin (EPO), produced by the kidneys, enhances the production of red blood cells (RBCs).
 Thrombopoietin (TPO), assisted by Interleukin-11 (IL-11), stimulates the production of
megakaryocytes. Their fragmentation produces platelets.
 Granulocyte-macrophage colony-stimulating factor (GM-CSF), as its name suggests, sends cells
down the path leading to both those cell types. In due course, one path or the other is taken.
o Under the influence of granulocyte colony-stimulating factor (G-CSF), they differentiate
into neutrophils.
o Further stimulated by interleukin-5 (IL-5) they develop into eosinophils.
o Interleukin-3 (IL-3) participates in the differentiation of most of the white blood cells but
plays a particularly prominent role in the formation of basophils (responsible for some allergies).
o Stimulated by macrophage colony-stimulating factor (M-CSF) the granulocyte/macrophage
progenitor cells differentiate into monocytes, macrophages, and dendritic cells (DCs).

Link to a discussion of how transplants of hematopoietic stem cells are used in therapy.

Red Blood Cells (erythrocytes)

The most numerous type in the blood.

 Women average about 4.8 million of these cells per cubic millimeter (mm3; which is the same as a
microliter [µl]) of blood.
 Men average about 5.4 x 106 per µl.
 These values can vary over quite a range depending on such factors as health and altitude. (Peruvians
living at 18,000 feet may have as many as 8.3 x 106 RBCs per µl.)

RBC precursors mature in the bone marrow closely attached to a macrophage.

 They manufacture hemoglobin until it accounts for some 90% of the dry weight of the cell.
 The nucleus is squeezed out of the cell and is ingested by the macrophage.
 No-longer-needed proteins are expelled from the cell in vesicles called exosomes.

This scanning electron micrograph (courtesy of Dr. Marion J. Barnhart) shows the characteristic biconcave shape of red
blood cells.

Thus RBCs are terminally differentiated; that is, they can never divide. They live about 120 days and then are ingested by
phagocytic cells in the liver and spleen. Most of the iron in their hemoglobin is reclaimed for reuse. The remainder of the
heme portion of the molecule is degraded into bile pigments and excreted by the liver. Some 3 million RBCs die and are
scavenged by the liver each second.

Red blood cells are responsible for the transport of oxygen and carbon dioxide.
 Oxygen Transport

In adult humans the hemoglobin (Hb) molecule

 consists of four polypeptides:
o two alpha (α) chains of 141 amino acids and
o two beta (β) chains of 146 amino acids
 Two each of these is attached the prosthetic group heme.
 There is one atom of iron at the center of each heme.
[View]
 One molecule of oxygen can bind to each heme.

The reaction is reversible.

 Under the conditions of lower temperature, higher pH, and
increased oxygen pressure in the capillaries of the lungs, the
reaction proceeds to the right. The purple-red deoxygenated
hemoglobin of the venous blood becomes the bright-red
oxyhemoglobin of the arterial blood.
 Under the conditions of higher temperature, lower pH, and
lower oxygen pressure in the tissues, the reverse reaction is
promoted and oxyhemoglobin gives up its oxygen.

The pressure of oxygen in the lungs is 90–95 torr; in the interior

tissues it is about 40 torr. Therefore, only a portion of the oxygen carried by the red blood cells is normally unloaded in
the tissues. However, vigorous activity can lower the oxygen pressure in skeletal muscles below 40 torr, which causes a
large increase in the amount of oxygen released. This effect is enhanced by the high concentration of carbon dioxide in
the muscles and the resulting lower pH (7.2). The lower carbon dioxide concentration (and hence higher pH) at the lungs
promotes the binding of oxygen to hemoglobin and hence the uptake of oxygen.

Temperature changes also influence the binding of oxygen to hemoglobin. In the relative warmth of the interior organs,
the curve is shifted to the right (like the curve for pH 7.2), helping to unload oxygen. In the relative coolness of the lungs,
the curve is shifted to the left, aiding the uptake of oxygen.

Carbon Dioxide Transport

Carbon dioxide (CO2) combines with water forming carbonic acid, which dissociates into a hydrogen ion (H +) and a
bicarbonate ions:
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3−

95% of the CO2 generated in the tissues is carried in the red blood cells:

 It probably enters (and leaves) the cell by diffusion through the plasma membrane assisted by
facilitated diffusion through transmembrane channels in the plasma membrane. (One of the proteins that forms
the channel is the D antigen that is the most important factor in the Rh system of blood groups.)
 Once inside, about one-half of the CO2 is directly bound to hemoglobin (at a site different from the one
that binds oxygen).
 The rest is converted — following the equation above — by the enzyme carbonic anhydrase into
o bicarbonate ions that diffuse back out into the plasma and
o hydrogen ions (H+) that bind to the protein portion of the hemoglobin (thus having no effect
on pH).

Only about 5% of the CO2 generated in the tissues dissolves directly in the plasma. (A good thing, too: if all the CO2 we
make were carried this way, the pH of the blood would drop from its normal 7.4 to an instantly-fatal 4.5!)

When the red cells reach the lungs, these reactions are reversed and CO2 is released to the air of the alveoli.

Anemia
Anemia is a shortage of
 RBCs and/or
 the amount of hemoglobin in them.

Anemia has many causes. One of the most common is an inadequate intake of iron in the diet.

Blood Groups

Red blood cells have surface antigens that differ between people and that create the so-called blood groups such as the
ABO system and the Rh system.
Link to a discussion of blood groups.

White Blood Cells (leukocytes)

White blood cells

 are much less numerous than red (the ratio between the two is
around 1:700);
 have nuclei;
 participate in protecting the body from infection;
 consist of lymphocytes and monocytes with relatively clear
cytoplasm, and three types of granulocytes, whose cytoplasm is filled
with granules.

Lymphocytes

There are several kinds of lymphocytes (although they all look alike under the
microscope), each with different functions to perform . The most common types
of lymphocytes are
 B lymphocytes ("B cells"). These are responsible for making antibodies.
 T lymphocytes ("T cells"). There are several subsets of these:
o inflammatory T cells that recruit macrophages and neutrophils to
the site of infection or other tissue damage
o cytotoxic T lymphocytes (CTLs) that kill virus-infected and,
perhaps, tumor cells
o helper T cells that enhance the production of antibodies by B cells

Although bone marrow is the ultimate source of lymphocytes, the lymphocytes that will become T cells migrate from the
bone marrow to the thymus [View] where they mature. Both B cells and T cells also take up residence in lymph nodes,
the spleen and other tissues where they

 encounter antigens;
 continue to divide by mitosis;
 mature into fully functional cells.

Monocytes

Monocytes leave the blood and become macrophages and some types of dendritic cells.

This scanning electron micrograph (courtesy of Drs. Jan M. Orenstein and Emma Shelton) shows a single macrophage
surrounded by several lymphocytes.

Macrophages are large, phagocytic cells that engulf

 foreign material (antigens) that enter the body
 dead and dying cells of the body.

Neutrophils

The most abundant of the WBCs. This photomicrograph shows a single neutrophil surrounded by red blood cells.
Neutrophils squeeze through the capillary walls and into infected tissue where they kill the invaders (e.g., bacteria) and
then engulf the remnants by phagocytosis.

This is a never-ending task, even in healthy people: Our throat, nasal passages, and colon harbor vast numbers of
bacteria. Most of these are commensals, and do us no harm. But that is because neutrophils keep them in check.

However,

 heavy doses of radiation

 chemotherapy
 and many other forms of stress

can reduce the numbers of neutrophils so that formerly harmless bacteria begin to proliferate. The resulting
opportunistic infection can be life-threatening.

Eosinophils

The number of eosinophils in the blood is normally quite low (0–450/µl). However, their numbers increase sharply in
certain diseases, especially infections by parasitic worms. Eosinophils are cytotoxic, releasing the contents of their
granules on the invader.

Basophils

The number of basophils also increases during infection. Basophils leave the blood and accumulate at the site of infection
or other inflammation. There they discharge the contents of their granules, releasing a variety of mediators such as:

 histamine
 serotonin
 prostaglandins and leukotrienes

which increase the blood flow to the area and in other ways add to the inflammatory process. The mediators released by
basophils also play an important part in some allergic responses such as
 hay fever and
 an anaphylactic response to insect stings.

Platelets

Platelets are cell fragments produced from megakaryocytes.

Blood normally contains 150,000–400,000 per microliter (µl) or cubic millimeter (mm3). This number is normally
maintained by a homeostatic (negative-feedback) mechanism [Link].

If this value should drop much below 20,000/µl, there is a danger of uncontrolled bleeding.

Some causes:
 certain drugs and herbal remedies;
 autoimmunity. [Link]

When blood vessels are cut or damaged, the loss of blood from the system must be stopped before shock and possible
death occur. This is accomplished by solidification of the blood, a process called coagulation or clotting.

A blood clot consists of

 a plug of platelets enmeshed in a
 network of insoluble fibrin molecules.

Details of the clotting process are in a separate page. Link to it.

Platelets also promote inflammation.

Plasma

Plasma is the straw-colored liquid in which the blood cells are suspended.

Composition of blood plasma

Component Percent
Water ~92
Proteins 6–8
Salts 0.8
Lipids 0.6
Glucose (blood sugar) 0.1

Plasma transports materials needed by cells and materials that must be removed from cells:

 various ions (Na+, Ca2+, HCO3−, etc.

 glucose and traces of other sugars
 amino acids
 other organic acids
 cholesterol and other lipids
 hormones
 urea and other wastes

Most of these materials are in transit from a place where they are added to the
blood (a "source")
 exchange organs like the intestine
 depots of materials like the liver

to places ("sinks") where they will be removed from the blood.

 every cell
 exchange organs like the kidney, and skin.

Serum Proteins

Proteins make up 6–8% of the blood. They are about equally divided between
serum albumin and a great variety of serum globulins.

After blood is withdrawn from a vein and allowed to clot, the clot slowly shrinks. As it does so, a clear fluid called serum
is squeezed out. Thus:

Serum is blood plasma without fibrinogen and other clotting factors.

The serum proteins can be separated by electrophoresis.

 A drop of serum is applied in a band to a thin sheet of supporting material, like paper, that has been
soaked in a slightly-alkaline salt solution.
 At pH 8.6, which is commonly used, all the proteins are negatively charged, but some
more strongly than others.
Link to an explanation of how pH affects the net charge on proteins.
 A direct current can flow through the paper because of the conductivity of the buffer with which it is
moistened.
 As the current flows, the serum proteins move toward the positive electrode.
 The stronger the negative charge on a protein, the faster it migrates.
 After a time (typically 20 min), the current is turned off and the proteins stained to make them visible
(most are otherwise colorless).
 The separated proteins appear as distinct bands.
 The most prominent of these and the one that moves closest to the positive electrode is serum
albumin.
 Serum albumin
 o is made in the liver
o binds many small molecules for transport through the blood
o helps maintain the osmotic pressure of the blood
 The other proteins are the various serum globulins.
 They migrate in the order
o alpha globulins (e.g., the proteins that transport thyroxine and retinol [vitamin A])
o beta globulins (e.g., the iron-transporting protein transferrin)
o gamma globulins.
 Gamma globulins are the least negatively-charged serum proteins. (They are so
weakly charged, in fact, that some are swept in the flow of buffer back toward the negative
electrode.)
 Most antibodies are gamma globulins.
 Therefore gamma globulins become more abundant following infections or
immunizations.

If a precursor of an antibody-secreting cell becomes

cancerous, it divides uncontrollably to generate a
clone of plasma cells secreting a single kind of
antibody molecule. The image (courtesy of
Beckman Instruments, Inc.) shows — from left to
right — the electrophoretic separation of:

1. normal human serum with its diffuse band of gamma globulins;

2. serum from a patient with multiple myeloma producing an IgG myeloma
protein;
3. serum from a patient with Waldenström's macroglobulinemia where the
cancerous clone secretes an IgM antibody;
4. serum with an IgA myeloma protein.
Discussion of the 5 classes of antibody molecules.
 Gamma globulins can be harvested from donated blood (usually pooled from several
thousand donors) and injected into persons exposed to certain diseases such as chicken pox
and hepatitis. Because such preparations of immune globulin contain antibodies against most
common infectious diseases, the patient gains temporary protection against the disease.
[More]

Serum Lipids

Because of their relationship to cardiovascular disease, the analysis of serum lipids has become an important health
measure.

The table shows the range of typical values as well as the values above (or below) which the subject may be at increased
risk of developing atherosclerosis.
LIPID Typical values (mg/dl) Desirable (mg/dl)
Cholesterol (total) 170–210 <200
LDL cholesterol 60–140 <100
HDL cholesterol 35–85 >40
Triglycerides 40–160 <160
 Total cholesterol is the sum of
o HDL cholesterol
o LDL cholesterol and
o 20% of the triglyceride value
 Note that
o high LDL values are bad, but
o high HDL values are good.
 Using the various values, one can calculate a
cardiac risk ratio = total cholesterol divided by HDL cholesterol
 A cardiac risk ratio greater than 7 is considered a warning.
More on cholesterol How cholesterol is taken into cells.

Blood Transfusions

In the United States, in 2001, some 15 million "units" (~475 ml) of blood were collected from blood donors.
 Some of these units ("whole blood") were transfused directly into patients (e.g., to replace blood lost by
trauma or during surgery).
 Most were further fractionated into components, including:
o RBCs. When refrigerated these can be used for up to 42 days.
o platelets. These must be stored at room temperature and thus can be saved for only 5 days.
o plasma. This can be frozen and stored for up to a year.

Ensuring the safety of donated blood

A variety of infectious agents can be present in blood.

 viruses (e.g., HIV-1, hepatitis B and C, HTLV, West Nile virus
 bacteria like the spirochete of syphilis
 protozoans like the agents of malaria and babesiosis
 prions (e.g., the agent of variant Crueutzfeldt-Jakob disease)

and could be transmitted to recipients. To minimize these risks,

 donors are questioned about their possible exposure to these agents;
 each unit of blood is tested for a variety of infectious agents.

Most of these tests are performed with enzyme immunoassays (EIA) — Link — and detect antibodies against the agents.
However, it takes a period of time for the immune system to produce antibodies following infection, and during this
period ("window"), infectious virus is present in the blood. For this reason, blood is now also checked for the presence of
the RNA of these RNA viruses:
 HIV-1
 hepatitis C
 West Nile virus

by the so-called nucleic acid-amplification test (NAT).

Thanks to all these precautions, the risk of acquiring an infection from any of these agents is vanishingly small. Despite
this, some people — in anticipation of need — donate their own blood ("autologous blood donation") prior to surgery.

Blood Typing

Donated blood must also be tested for certain cell-surface antigens that might cause a dangerous transfusion reaction in
an improperly-matched recipient. This is discussed in a separate page — link to it.

Blood Substitutes

Years of research have gone into trying to avoid the problems of blood perishability and safety by developing blood
substitutes. Most of these have focused on materials that will transport adequate amounts of oxygen to the tissues.
 Some are totally synthetic substances.
 Others are derivatives of hemoglobin.

Although some have reached clinical testing, none has as yet proved acceptable for routine use.

Animal Tissues

Levels of Organization

Tissue
Multicellular (large) organisms function more efficiently if cells become specialized for specific functions.

A tissue is composed of cells that function together in a specialized activity.

There are four types of tissues found in animals: epithelial, connective, nerve, and muscle tissue.

Sponges do not have tissues.

Organs

Organs are composed of two or more tissues which function together to perform a common task. For example, the heart
contains all 4 types of tissues.

Sponges and cnidarians do not have organs.

Organ systems

An organ system consists of two or more organs which perform a specific task.

Some organ systems are: the integumentary, nervous, sensory, endocrine, skeletal, muscular, circulatory, immune,
digestive, respiratory, excretory, and reproductive systems.

Embryonic Tissues

Ectoderm, mesoderm, and endoderm are embryonic tissues that give rise to all of the tissues, organs, and organ systems
in the body.

Ectoderm forms the outer layer of skin and nervous system.

Mesoderm forms the muscles, connective tissues, skeleton, kidneys, and circulatory and reproductive organs.

Endoderm forms the lining of the gut, respiratory tract, and urinary bladder. It also forms the glands associated with the
gut and respiratory tract.

Junctions

Cells are joined to each other by proteins. The point of connection between two cells is called a junction.

Junctions bind cells together. Some kinds of junctions prevent the passage of molecules between cells. Other kinds of
junctions allow molecules to pass from one cell to another.

Epithelial Tissue

Epithelial tissue covers external surfaces and internal cavities and organs. Glands are also composed of epithelial tissue.
Epithelia forms boundaries. Most substances that move into or out of the body must pass through epithelial tissue.

One surface of the tissue is free and the other adheres to a basement membrane.

The photograph below shows kidney tubules. The cells lining the tubules are epithelial tissue. One surface is attached
(the basal surface) and the other surface is free.

The apical surface of epithelial cells may have tiny projections called microvilli. These function to increase surface area.
For example, microvilli on intestinal cells increase the surface area available for absorption.
Eipthelial cells may have cilia. Cilia can be seen on the cells lining the trachea in the photograph below. They function to
move mucus and trapped particles upward toward the mouth where it will be swallowed, thus keeping the trachea clear of

foreign particles.

Function of Epithelial Tissue

Protection

Epithelial tissue forms the skin of many animals.

Terrestrial vertebrates have keratin in their skin cells making them resistant to water loss.

Ciliated epithelium lines the respiratory tract. Numerous cilia on these cells sweep impurities toward the throat.

Absorption

Absorption is an important function of epithelial tissue. For example, the gut is lined with epithelial tissue and it
functions to absorb nutrients from food. The lungs are also lined with epithelial tissue and it functions to absorb oxygen.

Secretion

Glandular epithelium secretes chemicals.

Endocrine glands secrete hormones directly into the extracellular space.

Exocrine glands often secrete through DUCTS; they secrete mucus, saliva, wax, milk, etc.

Layers

Simple epithelium is one cell thick.

Example: Respiratory surfaces such as the lining of the lungs or the skin of a frog (below) are only
one cell thick so that gasses can pass through quickly.
 Squamous Epithelium - Frog Skin Flat Mount

Click the photograph to view a larger

photograph.

Stratified epithelium has more than one layer. It is found in areas of high abrasion such as the skin or the lining of the
mouth.

Cell division occurs in cells near the basement membrane, pushing older cells toward the surface. Cells lost by abrasion
at the surface are replaced by cells underneath. 

Example: the human skin shown below contains stratified epithelium.

Stratified Squamous Epithelium, Human

sec. X 100

Pseudostratified epithelium appears

to be layered but each cell touches the same basement membrane.
Some cells are elongate; they extend from the basement membrane to the free surface. Other cells are
smaller, causing the tissue to appear stratified. The nuclei in the cells shown below appear to form
multiple layers but the cells are all attached to the same basement membrane.

Pseudostratified Ciliated Columnar

Epithelium

Shape

Epithelial cells are flat (squamous), cube-shaped (cuboidal), or elongated (columnar).

The words that describe layers (previous slides) can be used with words that describe shape. For example, simple
squamous epithelium is one layer of flat cells.

Simple
Squamous
Epithelium

Squamous

Simple squamous epithelium is a single layer of flat cells. It is found in the walls of small blood vessels (capillaries) and
in the air sacs of the lungs (alveoli). Because it is thin, it permits diffusion of substances from one side to the other. For
example, materials can diffuse out of the capillaries. In the lungs, oxygen can diffuse across the alveoli and into the
blood.

Below: The skin of a frog is used for gas exchange. The outer layer of skin is simple squamous
epithelium. The thin, flattened cells promote rapid diffusion of gasses between the air and the blood
vessels underneath the epithelium.

Squamous Epithelium - Frog Skin Flat Mount

Cuboidal

The cells that line the tubules of the kidneys are cuboidal. They function in secretion and absorption. 

The ducts of some glands contain simple cuboidal epithelium.

 Simple Cuboidal Epithelium

Simple Columnar

Simple columnar epithelium is a single layer of elongate cells. It is found in the lining of the gut and
parts of the respiratory tract. It functions in secretion and absorption. The photograph below is a
cross section of the small intestine.

Small Intestine (Jejunum) X 200

Connective Tissue

The cells of connective tissue are separated by non-living material.

Connective tissue binds and supports body parts, protects, fills spaces, stores fat (for energy), and transports materials.

Structure of Loose and Dense Connective Tissue

Loose connective tissue and dense connective tissue contain three kinds of fibers. Collagen fibers provide strength and
flexibility. Collagen is the most abundant protein in animal bodies. Elastic fibers provide elasticity. When stretched, they
return to their original shape. Reticular fibers are small and branched. They provide a support framework for organs such
as the liver and lymph nodes.

The cells of loose and dense connective tissue are called fibroblasts. They produce the fibers and nonliving matrix
material. Macrophages are cells specialized for phagocytizing foreign materials, bacteria, and cleaning up debris.
Macrophages will be discussed in the chapter on the immune system.

Loose Connective Tissue

Loose connective tissue includes areolar, adipose, and reticular connective tissue.

Areolar Connective Tissue

The fibroblasts (cells) of areolar connective tissue are separated by a nonliving, jellylike matrix. The
tissue contains collagen fibers for flexibility and strength, and numerous elastic fibers that enable it
to be stretched.

Areolar connective tissue X

200

Areolar connective tissue is found in the skin and in most internal organs of vertebrates, where it allows the organs to
expand; it also forms a protective covering for muscles, blood vessels, and nerves.

Adipose tissueis a type of loose connective tissue. It has reduced matrix material and contains enlarged
fibroblasts (cells) that store fat. Adipose tissue functions to store energy, insulate, and provide
padding, especially in the skin and around the kidneys and heart.

Adipose Tissue Human sec X 200

Reticular Connective Tissue

Reticular connective tissue contains an abundance of reticular fibers. It provides a supporting framework for organs such
as the lymph nodes, spleen, and liver.

Dense (Fibrous) Connective Tissue

The collagen fibers of dense connective tissue are more closely packed than those of loose
connective tissue.
 White Fibrous Connective Tissue X 200

Regular dense connective tissue contains collagen fibers oriented in one direction to provide strength in that direction. It
is found in tendons and ligaments. Tendons connect muscle to bone; ligaments connect bone to bone.

Irregular dense connective tissue (not shown) contains collagen fibers oriented in many different directions. It is found in
the deep layers of the skin and the tough capsules that surround many of the organs such as the kidneys, adrenal glands,
nerves, bones, and the covering of muscles. It provides support and strength.

Cartilage

The cells of cartilage are embedded in a protein-containing matrix that is strong but flexible.

It contains collagen and elastic fibers.

Hyaline Cartilage X 200

It is resilient; it does not stretch and can resist compression. It is also flexible but maintains its shape.

It is found in the ends of bones where it prevents friction within the joints. In the nose, external ear, and the walls of the
trachea it functions to support the softer tissues.

The intervertebral disks function as shock pads.

The fetal skeleton of vertebrate animals is composed of cartilage before bone forms. The skeleton of cartilaginous fish is
composed of cartilage.

Bone

Bone forms when calcium salts are deposited around protein fibers. The calcium salts provide
rigidity while the fibers provide elasticity and strength.
 Bone, dry ground human c.s. X 100

Blood

Blood is a connective tissue. Like other kinds of connective tissues, it contains cells that are
separated by a non-living material. In this case, the nonliving material is the plasma.

Human Blood, Wright Stain X 1000

Muscle Tissue

Muscle tissue contracts in response to stimulation. It cannot lengthen by itself but is lengthened by the contraction of
other muscles..

Muscle tissue is used for locomotion, food movement in gut, and heat production.

Smooth Muscle

Smooth muscle is involuntary. 

It surrounds the gut and moves food through the digestive tract. 

It surrounds the blood vessels where it controls the distribution of blood. There is not enough blood in the body to fill all
of the blood vessels so some must be contracted while others are filled. For example, after meals, the blood vessels of the
gut are opened while many of those in the skeletal muscles contract. 

The ends of the cells are tapered.

 Smooth Muscle, Human X 200

Skeletal Muscle

Skeletal muscle is voluntary. 

The cells are very long, extending the length of the muscle. They are multinucleate, and striated
(striped).

Skeletal Muscle Teased X 200

Cardiac Muscle

Cardiac muscle is found in the heart.

It is striated and branched.

Cardiac Muscle X 200

Muscle tissue will be discussed in more detail in the chapter on motor systems.

Nervous Tissue

Nervous tissue responds to stimuli and transmits impulses from one body part to another.

Motor Neuron X 200

Nervous tissue will be discussed in more detail in these two chapters: 1) neurons, 2) nervous systems.

Skin

The skin is the largest organ in the body. It protects the tissues underneath, prevents invasion by foreign organisms,
prevents dehydration, helps regulate body temperature, and contains receptors that provide information about the external
environment.

Epidermis

The outer layer, the epidermis, is composed of stratified squamous epithelium. These cells prevent dehydration because
they are filled with a waterproof protein called keratin.

The lower layers of the epidermis are basal cells that continuously divide to replace the layers above. The basal layer also
contains melanocytes which produce melanin, the pigment that darkens skin and protects from ultraviolet radiation in
sunlight.

Dermis

The dermis lies underneath the epidermis and is composed of dense connective tissue.

Hair of mammals originates in hair follicles, which are embedded in the dermis. A smooth muscle called the arrector pili
is attached to the hair follicle. When it contracts, the hair becomes erect. Sebaceous glands secrete an oily substance
(sebum) into the follicle to lubricate the hair and skin.

Sweat glands are found in the dermis and subcutaneous layer. They secrete water to the surface, which cools the body
when it evaporates.

The dermis contains blood vessels and neurons that control the flow of blood through the skin in order to regulate body
temperature. When the body temperature is high, blood flow to these vessels increases. The increased blood flow to the
surface helps the body lose excess heat. When the body temperature is low, blood flow to the dermis decreases. Shivering
occurs as a mechanism to produce heat when the body temperature is low.

The dermis contains receptors for pressure, touch, temperature, vibration, and pain.

Subcutaneous layer
The subcutaneous layer is the deepest layer and is composed of loose connective tissue. 

This layer is actually not part of the skin. 

Adipose tissue in this layer insulates and stores energy in the form of fat.