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Practical microscopic courses play an important role in basic medical education since they are very helpful in learning and understanding normal and pathological histology. The feasibility of the courses is, however, limited by the equipment (microscopes, slides, etc.). In addition, histological sections are often not easily available for the students, thus limiting the self-directed learning. Therefore, we developed a computer program with an interface that simulates how histological slides are studied with a light microscope. The program contains app. 300 histological specimens - most of human origin with both routine and special stainings. The microscopic pictures can be moved in x and y axes simulating slide movement using a light microscope. Each histological section can be examined at various magnifications. All of the significant structures are labeled in each section. A subset of structures in each section can be clicked on to access a text which presents important information about the structure. Following the completion of the learning program, a testing feature is available which allows the students to check their diagnostic capability.

General histology refers to the basic tissue structure of the human body. Epithelium, connective, muscle and nerve are the four basic tissues from which organs of the body are constructed. Each tissue is composed of cells and intercellular substances. Approximately 200 cell types are recognized in the human body. Many of these are variants of epithelial, connective, muscle and nerve tissue cell types. The intercellular substance is of two fundamental types. There is intercellular substance that has shape and form (morphologically distinct) such as the collagen fiber, and intercellular substance that has no form or shape (amorphous) at the light microscopic level, such as glycosaminoglycans (ground substance). It is important to learn how to recognize the basic cell types in each of the four basic tissues and to also learn to recognize the amount and type of intercellular substance. The four basic tissues are presented in four chapters. There are eight different types of epithelial tissue, three basic types of connective tissue, three basic types of muscle tissue and two basic types of nerve tissue.

In this first volume of the Virtual Microscope the student is given the opportunity to learn the microscopic architecture of the four basic tissues so that one tissue can be differentially diagnosed over another in a real or test situation.

Epithelial Tissue

Epithelial tissue is composed of cells physically close which are connected by one or all three types of junctions (zonula occludens, zonula adherens, macula adherens) with very little intervening intercellular substance. Epithelial tissue consists of two main types, 1) covering or lining which is composed of single or multi layered cellular sheets that cover the surface of the body or line body cavities, and 2) glandular which is composed of single (unicellular gland) or multiple cells (multicellular gland) which are differentiated to secrete a specific product. The epithelial cells of multicellular glands are arranged into tubes for conduction of secretory product (ducts) and terminal groupings in the shape of tubules, alveoli or acini which integrate their synthetic and secretory activity. Covering or lining epithelium is composed of eight types. They are simple squamous, cuboidal and columnar; stratified squamous, cuboidal and columnar; and two special types, namely, pseudostratified and transitional.

Connective Tissue

In connective tissue it is the intercellular substance (matrix) that attracts ones attention when observed in the light microscope. Connective tissue consists of widely separated and loosely connected cells and two types of intercellular substance, namely, fibers and ground substance. Each type of connective tissue has unique cell types, but it is the intercellular substance that gives each of the connective tissue types their characteristic appearance. There are two general categories of connective tissue; connective tissue proper and specialized connective tissue. Connective tissue proper is classified into two subclasses, loose and dense. Loose connective tissue is distinguished from dense connective tissue by the proportion between fibers and ground substance. Subclasses of dense connective tissue are distinguished by the arrangement and type of fibers. Specialized connective tissue are of two classes, bone and cartilage. Distinguishing between these two types is mainly by recognizing the difference between the morphology of the intercellular substance (matrix).

Muscle Tissue

Muscle tissue consists of three types of cells with very little intercellular substance present as a modified cell coat. There are three types of muscle tissue, namely, skeletal, cardiac and smooth. The cells of skeletal and cardiac muscle have striations which cross the cell at regular intervals perpendicular to the long axis of the cells. The cells of smooth muscle have no striations. Distinguishing between the three types of muscle tissue is strictly based upon recognizing the difference between the three cell types and their arrangement. Skeletal muscle cells are referred to as fibers because they are long and narrow cylinders which do not branch. Skeletal muscle fibers contain many nuclei which are located at the peripheral region of the cell near the cell membrane. Cardiac muscle cells are branched with no more than two nuclei per cell located in the central region of each cell. Smooth muscle cells are fusiform shaped with only one nucleus per cell located in the central region.

Bone

Bone tissue consists of several specific cell types and a hard (calcified) intercellular substance (matrix) into which many collagen fibers are incorporated. The cell types of bone are the osteoprogenitor cell, osteoblast, osteocyte and osteoclast. There are two types of adult bone tissue, cancellous and compact. Cancellous bone consists of a three dimensional meshwork of branching trabeculae which delimit spaces which are filled with bone marrow. Compact bone consists of a solid mass of densely packed lamellae arranged in patterns through which blood vessels run in well defined canals. In this chapter the histological patterns of bone formation are presented. There are two processes by which bone forms, direct and indirect. Formation of bone directly by a direct transformation of mesenchymal tissue into bone is called intramembranous bone formation. Formation of bone indirectly upon and within a cartilage model is called endochondral or chondral bone formation.

Cartilage

Cartilage consists of two specific cell types and a gelled intercellular substance into which collagen or elastic fibers is incorporated. The cell types of cartilage are the chondroblast and the chondrocyte. There are three different classes of cartilage, namely hyaline, elastic and fibrous, distinguished primarily by the appearance and content of the intercellular substance (matrix). The intercellular substance (matrix) may contain a preponderance of collagen fiber bundles (fibrocartilage), a preponderance of elastic fibers (elastic cartilage) or a preponderance of fine collagen fibers (hyaline cartilage).

Nerve Tissue

Nerve tissue consists of two cell types and very little intercellular substance. The two cells types are neurons and glial (supporting) cells. There are two classes of nerve tissue, central and peripheral. This chapter presents only one of these, peripheral nerve tissue. Peripheral nerve tissue is of two types, nerve fibers and ganglia. This chapter focuses on the structure of a peripheral nerve composed of many nerve fibers bundled and wrapped by connective tissue and the structure of ganglia which are organized collections of the cell bodies of nerve fibers.

Learning the histological structure of organs should be focussed on learning how each of the four basic tissues is distributed within the organ. Organs can be divided into solid (glandular or lymphoid) organs and hollow (viscus). Solid organs do not have a major lumen but have minor lumens in structures called ducts or no lumens except in blood vessels in the case of the endocrine glands and lymphoid organs.

Solid organs that are endocrine (pituitary, thyroid, parathyroid, adrenal) or exocrine glands (salivary glands, pancreas, liver, kidney) are predominantly composed of epithelial tissue. In addition to the solid organs presented above there are others. In addition to the hollow organs presented above, there are others. The lymphoid organs can also be considered as solid organs (lymph node, spleen, thymus, tonsil) that, instead of having epithelium as the predominant tissue, have an extensive cellular or reticular network which holds a large population of lymphocytes. Learning how the lymphocytes are distributed and organized is key to understanding the histology of the solid lymphoid organs. Other solid organs are the ovary and testis. The ovary and testis are a type of gland, each producing a secretion of whole cells, the egg and the sperm. In the ovary and testis, the focus of learning the histology is to understand the morphological changes that take place in the transformation from germ cells to the egg and sperm.

Hollow or viscus organs do have a large lumen that either conducts blood or food in the process of being digested. Organs that conduct blood are the various blood vessels and the heart. These organs (arteries, veins, venules, capillaries, heart) have three layers (tunica intima, tunica media, tunica adventitia) of tissue arranged concentrically around the lumen. Learning the variation in the histological composition of these layers and how it differs between the cardiovascular organs is the secret of learning cardiovascular organ histology. Organs that conduct food in the process of being digested are the various segments of the gastrointestinal tract (oral cavity, esophagus, stomach, duodenum, jejunum, ileum, colon). These organs have four layers (tunica mucosa, tunica submucosa, tunica muscularis, tunica serosa or adventitia) of tissue surrounding the lumen. Learning the variation in the composition of these layers and how it differs between the segments of the gastrointestinal tract is the secret for understanding the histology of the gastrointestinal tract. The uterus, oviduct, vas deferens, urinary bladder, ureter also have a lumen that serves to conduct a product of the organ itself, or, as in the case of the uterus/oviduct to conduct eggs and spermatozoa.

A very important concept to understand in learning the histology of organs is that there are over 200 different cell types in the human body and that each of these cells has evolved into a cell that is differentiated to perform a specific function within the histological organization of tissues called an organ. To complete the learning of the histology of organs, the student must know the cell types which perform the functions and that are unique to each of the organs. For example, the mucosa of the stomach has two very important cells, the parietal cell that makes and secretes hydrochloric acid and intrinsic factor, and the chief or zymogen cell which makes and secretes pepsinogen. The student of organ histology must learn where these cells are located, what they look like in stained tissue sections and how they relate to the structure of the entire organ. Cells like the parietal and chief cells of the stomach are the major actors in helping the stomach to achieve its function of breaking down food substances into molecules. The other cells and tissues of the stomach play a supporting role.