What is histology?

Types of Tissues

Histology is the study of tissues, which are groups of similar cells that are closely interrelated in their function and are organized together by location and structure. The four major types of tissues are epithelial tissue, connective tissue, muscle tissue, and nervous tissue.

Epithelial tissue (or epithelia) includes those tissues that originate in broad, flat surfaces. Their functions include protection, absorption, and secretion. Epithelia can be one-layered (simple) or multilayered (stratified). Their cells can be flat (squamous), tall and thin (columnar), or equal in height and width (cuboidal). Some simple epithelia have nuclei at two different levels, giving the false appearance of different layers; these tissues are called pseudostratified. Some simple squamous epithelia have special names: The inner lining of most blood vessels is called an endothelium, while the lining of a body cavity is called a mesothelium. Kidney tubules and most small ducts are also lined with simple squamous epithelia. The pigmented layer of the retina and the front surface of the lens of the eye are examples of simple cuboidal epithelia. Simple columnar epithelia form the inner lining of most digestive organs and the linings of the small bronchi and gallbladder. The epithelia lining the Fallopian tube, nasal cavity, and bronchi are ciliated, meaning that the cells have small hairlike extensions called cilia.

The outer layer of skin is a stratified squamous epithelium; other stratified squamous epithelia line the inside of the mouth, esophagus, and vagina. Sweat glands and other glands in the skin are lined with stratified cuboidal epithelia. Most of the urinary tract is lined with a special kind of stratified cuboidal epithelium called a transitional epithelium, which allows a large amount of stretching. Parts of the pharynx, larynx, urethra, and the ducts of the mammary glands are lined with stratified columnar epithelia.

Glands are composed of epithelial tissues that are highly modified for secretion. They may be either exocrine glands (in which the secretions exit by ducts that lead to targets nearby) or endocrine glands (in which the secretions are carried by the bloodstream to targets some distance away). The salivary glands in the mouth, the glandular lining of the stomach, and the sebaceous glands of the skin are exocrine glands. The thyroid gland, the adrenal gland, and the pituitary gland are endocrine glands. The pancreas has both exocrine and endocrine portions; the exocrine parts secrete digestive enzymes, while the endocrine parts, called the islets of Langerhans, secrete the hormones insulin and glucagon.

Connective tissues are tissues containing large amounts of a material called extracellular matrix, located outside the cells. The matrix may be a liquid (such as blood plasma), a solid containing fibers of collagen and related proteins, or an inorganic solid containing calcium salts (as in bone).

Blood and lymph are connective tissues with a liquid matrix (plasma) that can solidify when the blood clots. In addition to plasma, blood contains red cells (erythrocytes), white cells (leukocytes), and the tiny platelets that help to form clots. The many kinds of leukocytes include the so-called granular types (basophils, neutrophils, and eosinophils, all named according to the staining properties of their granules), the monocytes, and the several types of lymphocytes. Lymph contains lymphocytes and plasma only.

Most connective tissues have a solid matrix that includes fibrous proteins such as collagen and also elastic fibers, in some cases. If all the fibers are arranged in the same direction, as in ligaments and tendons, the tissue is called regular connective tissue. The dermis of the skin, however, is an example of an irregular connective tissue in which the fibers are arranged in all directions. Loose connective tissue and adipose (fat) tissue both have very few fibers. The simplest type of loose connective tissue, with the fewest fibers, is sometimes called areolar connective tissue. Adipose tissue
is a connective tissue in which the cells are filled with fat deposits. Hemopoietic (blood-forming) tissue, which occurs in the bone marrow and the thymus, contains the immature cell types that develop into most connective tissue cells, including blood cells. Cartilage tissue matrix contains a shock-resistant
complex of protein and sugarlike (polysaccharide) molecules. Cartilage cells usually become trapped in this matrix and eventually die, except for those closest to the surface. Bone tissue gains its supporting ability and strength from a matrix containing calcium salts. Its typical cells, called osteocytes, contain many long strands by means of which they exchange nutrients and waste products with other osteocytes, and ultimately with the bloodstream. Bone also contains osteoclasts, large cells responsible for bone resorption and the release of calcium into the bloodstream.

Mesenchyme is an embryonic connective tissue made of wandering amoebalike cells. During embryological development, the mesenchyme cells develop into many different cell types, including hemocytoblasts, which give rise to most blood cells, and fibroblasts, which secrete protein fibers and then usually differentiate into other cell types.

Muscle tissues are tissues that are specially modified for contraction. When a nerve impulse is received, the overlapping fibers of the proteins actin and myosin slide against one another to produce the contraction. The three types of muscle tissue are smooth muscle, cardiac muscle, and skeletal muscle.

Smooth muscle contains cells that have tapering ends and centrally located nuclei. Muscular contractions are smooth, rhythmic, and involuntary, and they are usually not subject to fatigue. The cells are not cross-banded. Smooth muscle occurs in many digestive organs, reproductive organs, skin, and many other organs.

The term “striated muscle” is sometimes used to refer to cardiac and skeletal muscle, both of which have cylindrical fibers marked by cross-bands, which are also called cross-striations. The striations are caused by the lining up of the contractile proteins actin and myosin.

Cardiac muscle occurs only in the heart. Its cross-striated fibers branch and come together repeatedly. Contractions of these fibers are involuntary and rhythmic, and they occur without fatigue. Nuclei are located in the center of each cell; the cell boundaries are marked by dark-staining structures called intercalated disks.

Skeletal muscle occurs in the voluntary muscles of the body. Its cylindrical, cross-striated fibers contain many nuclei but no internal cell boundaries; a multinucleated fiber of this type is called a syncytium. Skeletal muscle is capable of producing rapid, forceful contractions, but it fatigues easily. Skeletal muscle tissue always attaches to connective tissue structures.

Nervous tissues contain specialized nerve cells (neurons) that respond rapidly to stimulation by conducting nerve impulses. All neurons contain RNA-rich granules, called Nissl granules, in the cytoplasm. Neurons with a single long extension of the cell body are called unipolar, those with two long extensions are called bipolar, and those with more than two long extensions are called multipolar. There are two types of extensions: Dendrites conduct impulses toward the cell body, while axons generally conduct impulses away from the cell body. Many axons are surrounded by a multilayered fatty substance called the myelin sheath, which is actually made of many layers of cell membrane wrapped around the axon.

Nervous tissues also contain several types of neuroglia, which are cells that hold nervous tissue together. Many neuroglia have processes (projections) that wrap around the neurons and help nourish them. Among the many types of neuroglia are the tiny microglia and the larger protoplasmic astrocytes, fibrous astrocytes, and oligodendroglia.

Two major tissue types make up most of the brain and spinal cord, or central nervous system. The first type, gray matter, contains the cell bodies of many neurons, along with smaller amounts of axons, dendrites, and neuroglia cells. The second type, white matter, contains mostly the axons, and sometimes also the dendrites, of neurons whose cell bodies lie elsewhere, along with the myelin sheaths that surround many of the axons. Clumps of cell bodies are called nuclei within the brain and ganglia elsewhere. Bundles of axons are called tracts within the central nervous system and nerves in the peripheral nervous system.

Histology as a Diagnostic Tool

Many diseases produce changes in one or more body tissues; these changes are so characteristic that the diagnosis of a disease often depends on the microscopic observation of changes in tissues. For such a diagnosis to be made, the tissue must be sliced very thin on a machine called a microtome. Some tissues are sliced while frozen; others must be hardened (or “fixed”) in chemical solutions. After being sliced, the tissue is usually stained with chemical dyes that make viewing easier. Some tissues are viewed under a light microscope; others are sliced even thinner for viewing by electron microscopy.

Most hospitals have a pathology department that is responsible for these operations. After the tissues are sliced and examined, the pathologist makes a report that usually includes a diagnosis of the disease shown by the tissue samples.

Many diseases result in marked changes in the tissue at the microscopic level. Adaptively altered changes, which are usually reversible, include an increase in cell size (hypertrophy), increase in cell numbers (hyperplasia), a change from one cell or tissue type to another (metaplasia), and a decrease in size by withering (atrophy). Prolonged or repeated insults to the tissue may result in altered or atypical growth patterns (dysplasia). Overwhelming or sustained injury results in irreversible changes such as tissue degeneration or death. Tissue degeneration often includes the accumulation of abnormal amounts of fatty, fibrous, or pigmented tissue. Tissue death in a body that goes on living is called necrosis, and it may be of several types. If tissue death exceeds a certain limit, then the death of the organism results. Once this occurs, the tissues usually release protein-digesting enzymes that digest their own cell contents, a process known as autolysis.

Changes to cellular organelles can often be seen with an electron microscope before they become apparent at the light microscope level. Disturbances of the cell membrane may alter the flow of fluids (especially water) and cause changes to occur in the fluid composition of the cytoplasm. Too much fluid may result in swelling and eventually in bursting of the cells; too little fluid results either in shrinkage or in the coagulation of proteins. Swelling may also be induced by the lack of oxygen flow to the mitochondria, which can also result in the deposition of fats or calcium. The increase in the water content of the cells can also cause swelling in the endoplasmic reticulum and the detachment of ribosomes from the surfaces of the rough endoplasmic reticulum. Most damaging of all are the disturbances of the lysosomes, which can release their protein-digesting enzymes and cause autolysis.

At the light microscope level, other changes that may result from disease processes include the coalescence of numerous dropletlike vacuoles into a single, large, fluid-filled space. Other changes that may indicate disease are abnormal cell shapes, changes in the proportion of blood cells, and the rupture of cell membranes or other structures. Substances that may accumulate in diseased cells include glycogen (a sugar storage product), fibrous deposits of collagen and other proteins, and mineral deposits such as calcium salts. Abnormalities of the nucleus may include nuclear fragmentation, loss of the staining properties of the nucleus, or pyknosis, a shrinkage of the nucleus that also includes the clumping of its chromosomal material.

Edema, or tissue swelling, is a condition that can easily be confirmed by microscopic examination of histological sections. The swelling is marked by an increase in the amount of extracellular fluid. In the case of pulmonary edema, the fluid stains pink and fills the usually empty lung spaces (alveoli).

A different type of change is seen in Barrett’s esophagus, a condition caused by the repeated backflow (or reflux) of gastric fluids into the esophagus. The inner lining of the esophagus is usually a stratified squamous epithelium, but in Barrett’s esophagus the surface cells become taller, and the lining is changed into a columnar epithelium resembling that of the stomach.

Most cancers are recognized by abnormalities of the affected tissues, usually including more cells in the process of cell division (mitosis). The most dangerous cancers are marked by large tumors with ill-defined, irregular margins. If the cancer tumor is well-defined, small, and has a smooth, circular margin, the cancer is much less of a threat.

In juvenile diabetes, histological examination of the pancreas reveals a greatly reduced number of pancreatic islets, and those that remain are smaller and more fibrous. Herpes simplex infection causes the epidermal cells of the skin to undergo a buildup of fluid and a consequent balloonlike swelling. Warts of the skin are marked by a thickening of the outermost layer (stratum corneum) of the epidermis. Pernicious anemia, or vitamin B12 deficiency, results in a deterioration of the glands in the stomach lining. Crohn’s disease produces swelling of the affected parts of the intestine, deposition of fat and lymphoid tissue, and ultimately tissue loss and deposition of fibrous scar tissue; the affected parts typically alternate with healthy regions. Cirrhosis of the liver, which is most commonly the result of chronic alcohol abuse, proceeds through a fatty stage (marked by deposition of fatty tissue), a fibrotic stage (marked by small nodules and scars), and an end stage marked by abnormal shrinkage (atrophy) of liver tissue, scars, and larger nodules up to 1 centimeter in diameter. Emphysema, a lung disease found in many smokers, is recognizable histologically by an enlargement of the air spaces and by the presence of black, tarlike deposits within the lung tissue. Fibrocystic changes of the breast may be marked by the deposition of fibrous tissue, by increasing cell numbers, and by the enlargement of the glandular ducts.

Systemic lupus erythematosus (SLE), a connective tissue disease, often produces red skin lesions marked by degeneration and flattening of the lower layers of the epidermis, drying and flaking of the outermost layer, dilation of the blood vessels under the skin, and the leakage of red blood cells out of these vessels, adding to the red color. (The word “erythematosus” means “red.”)

Muscular dystrophy has several forms; the most common form is marked in its advanced stages by enlarged muscles in which the muscle tissue is replaced by a fatty substance. Another muscular disease, myasthenia gravis, is often marked by overall enlargement of the thymus and an increase in the number of thymus cells. Myocardial infarction (heart attack ), a form of heart disease marked by damage to the heart muscle, is indicated in histological section by dead, fibrous scar tissue replacing the muscle tissue in the heart wall. In patients with arteriosclerosis, the usually elastic walls of the arteries become thicker and more fibrous and rigid. Many of the same patients also suffer from atherosclerosis, a buildup of deposits on the inside of the blood vessels that partially or completely blocks the flow of blood.

In nervous tissue, damage to peripheral nerves often results in a process called chromatolysis in the cell bodies of the neurons from which these axons arise. The nuclei of these cells enlarge and are displaced to one side, while the Nissl granules disperse and the cell body as a whole undergoes swelling. Increased deposits of fibrous tissue characterize multiple sclerosis and certain other disorders of the nervous system. Some of these diseases are also marked by a degeneration of the myelin sheath around nerve fibers. In the case of a cerebrovascular stroke, impaired blood supply to the brain causes degeneration of the neuroglia, followed by general tissue death and the replacement of the neuroglia by fibrous tissue. Cranial hematoma (abnormal bleeding in any of several possible locations) results in the presence of blood clots (complete with blood cells and connective tissue fibers) in abnormal locations. Alzheimer’s disease is marked by granules of a proteinlike substance called amyloid, often containing aluminum, surrounded by additional concentric layers of similar composition. Advanced stages of alcoholism are marked in brain tissue by the destruction of certain neurons and neuroglia. Poliomyelitis, or polio, is marked by the destruction of nervous tissue in the anterior horn of the spinal cord.

Perspective and Prospects

The microscopic study of tissues began historically with Robert Hooke’s Micrographia (1665) and the studies of Marcello Malpighi (1628–94), but early microscopes were low in quality by today’s standards. As microscopes improved, so did their use in studying tissues. During the 1830s, the Scottish botanist Robert Brown (1773–1858) discovered the cell nucleus. Soon, German biologists Matthias Jakob Schleiden (1804–81) and Theodor Schwann (1810–82) developed the so-called cell theory, which proclaimed that all living things are constructed of cells and that all biological processes are rooted in processes occurring at the level of cells and tissues. The greatest advances in microscopic optics were made between 1870 and 1900, mostly in Germany, and the study of histology benefited greatly.

The great pathologist Rudolf Virchow (1821–1902) was the first to emphasize the structural changes in cells caused by the disease process; he showed that many diseases could be detected at the cellular level under the microscope. This claim, coupled with enthusiasm for the cell theory, aroused great interest in the study of cells throughout Europe and later in America. Advances in tissue-staining techniques in microanatomy were made in various countries over a long period; the Czech histologist and physiologist Jan Evangelista Purkinje (1787–1869) was one of the leaders of this early period. Early in the twentieth century, histologists Santiago Ramón y Cajal (1852–1934) of Spain and Camillo Golgi (1844–1926) of Italy shared the 1906 Nobel Prize in Physiology or Medicine for their detailed work on the tissue structure of the nervous system. In the decades after World War II, the electron microscope became a standard instrument for the ultrafine study of tissue details at and even below the cellular level. Today, pathology laboratories routinely use the microscopic examination of tissues as an important tool in diagnosis.

Bibliography

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"SIU SOM Histology." Southern Illinois University School of Medicine, August 2, 2013.