Epithelial cells make up primary tissues throughout the body. There are many arrangements of epithelial cells such as squamous, cuboidal, and columnar that organize as simple, stratified, pseudostratified, and transitional. Epithelial cells form from ectoderm, mesoderm, and endoderm, which explains why epithelia line body cavities and cover most of the body and organ surfaces. Since epithelial cells are prevalent throughout the body, their function changes based on their location. For example, epithelial cells in the skin provide protection, whereas, in the gut, they have secretory and absorptive properties. This article seeks to explain the anatomical characteristics of epithelial cells and their functions as well as describe features that are evident upon histological staining.
Epithelial cells have a structural polarity that causes three distinct regions or domains (apical, basal, and lateral). The apical domain faces the lumen of an organ or the external environment. This region often contains a structure that affects the cells function like microvilli, cilia, and stereocilia. Microvilli are finger-like projections that have a core of cross-linked actin filaments that are attached to the terminal web, which is parallel to the apical surface. Cilia are motile projections of the cell surface comprised of two central microtubules encompassed by nine microtubule doublets. Lastly, stereocilia are finger-like projections supported by actin filaments. The basal domain is connected to the basal lamina by hemidesmosomes, which combine with intermediate filaments. The basal lamina separates connective tissue from the epithelium. The lateral domain connects neighboring cells and allows for communication between cells. There are a variety of junctional complexes that connect adjacent cells. Desmosomes are anchoring/adhering junctions that serve to tightly join cells together by integrating with the cytoskeletal structures. Tight junctions are occluding junctions that regulate the movement of fluid and solutes. Gap junctions are communicating junctions, found throughout the lateral domain, create channels that allow small molecules and ions to pass between adjacent cells.
Epithelial cells are organized according to their shape and number of layers. Simple epithelial cells contain one layer, whereas stratified cells contain two or more layers. Pseudostratified epithelial cells contain only one layer of cells, but the cells are of different sizes, so cells appear to be stratified or layered. In regards to the shape of epithelial cells, there are three main shapes, squamous, cuboidal, columnar. Squamous cells are flat sheet-like cells, cuboidal cells are cube-like with an equal width, height, and depth, and columnar cells are taller than they are wide making them rectangular.
Epithelial cells are located throughout the body and have many different functions based on morphology and location. Structures of the apical domain significantly affect function. Microvilli are involved in fluid transport and absorption. The number of microvilli correlates to the absorptive properties of the cell. Cilia transport substances across the surface of epithelial cells. Stereocilia are essential in hearing and balance.
Simple squamous epithelium lines blood vessels (endothelium) or body cavities (mesothelium) and allows for diffusion of molecules like in gas exchange. Simple cuboidal cells have a secretory function and tend to form the lining of ducts. Simple columnar cells are found throughout the intestines and can have either an absorptive or secretory function.
Some stratified forms of these cells have similar functions. For example, stratified cuboidal cells are found in exocrine ducts and still have a secretory function. Stratified columnar cells are present in large exocrine glands. Stratified squamous epithelium does not allow for as much diffusion of nutrients as simple squamous because the nutrients would have to traverse through many layers, but the layers serve to provide protection. There are also two other categories of the epithelium, pseudostratified columnar and transitional (uroepithelium) epithelial cells. The pseudostratified epithelium is often ciliated to aid in the transport of luminal contents. Transitional epithelial cells are present within distensible organs.
Epithelial cell examination is possible via biopsy. Generally, after a sample is collected, it is fixed in formalin, embedded in an embedding medium such as paraffin, sectioned, and stained.
Epithelial cells have specialized cytoskeletons comprised of microtubules, actin filaments, and intermediate filaments. Intermediate filaments provide structural resilience to the cytoskeleton and show tissue-specific expression, unlike microtubules and actin filaments. These intermediate filaments are a useful target for histochemical staining techniques.
There are five main groups of intermediate filaments. Glial filaments are in astrocytes, neurofilaments found in nerves, desmin filaments found in muscles, vimentin filaments seen in the mesenchyme, and keratin, which occur in epithelial cells.
Keratin can be used to not only define the tissue as epithelial cells but differentiate between the types of epithelial cells. For example, keratin 3 is found in corneal epithelium, whereas keratin 20 is present in Merkle cells and umbrella cells of the urothelium. These keratins are crucial to epithelial cells, and mutations in keratin or loss of keratin can cause or predispose a person to many diseases.
Light microscopy (LM) is typically used to visualize stained epithelial cells. LM can be used to determine the morphology of the epithelium present in the tissue specimen. Columnar epithelial cells tend to be rectangular, cuboidal cells appear square, and squamous cells are long and flat. Understanding the appearance of normal, healthy epithelial cells makes it possible to identify when there is pathology present in a tissue specimen.
Electron microscopy (EM) is a form of microscopy that allows a higher magnification than light microscopy (LM). EM allows visualization of many ultrastructural features, such as tight junctions, adherens junctions, desmosomes, hemidesmosomes, and gap junctions, and the basal lamina, which separates the epithelial cells from connective tissue.
One of the biggest concerns with epithelial cells is the potential for malignancy development as adenocarcinoma or papillary carcinoma. Some of the common adenocarcinomas that have high morbidity and mortality rates are lung, prostate, colon, and breast cancer.
Another clinical concern that relates to epithelial cells is metaplasia. Metaplasia is when one type of cell converts to another type due to stressors or changes in the environment. This reaction can be physiological or pathological. Pathologic metaplasia has a higher likelihood of being dysplastic, which can become malignant. One relatively common example of pathologic metaplasia is Barrett's esophagus. The esophagus is normally lined by squamous epithelium. When patients have uncontrolled gastroesophageal reflux disease (GERD), acid from the stomach causes the squamous cells of the esophagus to become mucin-producing columnar cells. The mucin-producing columnar cells are better equipped to handle the stress of the stomach acid, preventing erosion of the esophagus. If the GERD receives proper treatment, the columnar cells may revert to squamous cells; however, if the stressor goes untreated, metaplasia may progress to dysplasia, which can become malignant.
In addition to cancer and metaplasia, other epithelial dysfunction can occur in various organs. In the intestines, Celiac disease and certain bacterial infections can damage the microvilli of epithelial cells lining the intestines. In the lungs of premature infants, the cuboidal cells in the alveoli (type II pneumocytes) have not fully developed, and the surfactant is not produced, making it difficult for the baby to breathe. In the skin, bullous pemphigoid, an autoimmune subepidermal skin blistering disease, essentially renders hemidesmosomes ineffective. Human papillomavirus strains 1-4 can cause warts on the squamous cells of the epidermis. This virus causes an overgrowth of epithelial tissue on a papilla of connective tissue. This vast array of diseases makes understanding epithelial cells clinically significant.
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