General histology

Tissues are formed by cells and can be differentiated into four different types: connective tissue, muscle tissue, nerve tissue, and epithelium (epithelial tissue). Epithelium is a component of almost every organ in the body. The subtypes and functions of epithelium will be discussed in this article. Connective, muscle, and nerve tissue are addressed in the respective articles. Epithelium covers all inner and outer surfaces of the body (except joint cavities), namely the skin (epidermis) and all mucous membranes. Based on its predominant function, epithelium can be differentiated into protective surface epithelium and secretory glandular epithelium (exocrine glands). Surface epithelium is named and classified according to various criteria (layers, cell shape, surface characteristics). Glandular tissue can be classified according to its location, shape, secretory mechanism, and the type of secretion associated with it (serous or mucinous). The basement membrane anchors the epithelium to connective tissue and creates a diffusion barrier. The basement membrane is composed of a band-like layer of fibers and large proteins and is tightly bound to the cytoskeleton of cells.

For more information about cellular adaptive responses including apoptosis, necrosis, see the article on cellular changes and adaptive responses.

For images on the histology of both normal and abnormal tissues see the articles virtual histology slide box and virtual histopathology slide box.

There are four basic types of tissues in the body: epithelium, connective tissue, nervous tissue, and muscle tissue.

1. Connective tissue
   • Connective tissue
   • Adipose tissue
   • Cartilage
   • Bone tissue
2. Nervous tissue
   • Neurons
     • Bipolar neurons (e.g., in the retina)
     • Unipolar (pseudounipolar) neurons (e.g., spine and ganglia)
     • Multipolar neurons (e.g., motor cells)
     • Pyramidal cells (e.g., in the hippocampus)
     • Purkinje cells (e.g., in the cerebellum)
   • Neuroglia (neuroglial cells)
     • Astrocytes
     • Oligodendrocytes
     • Schwann cells (produce myelin in the PNS)
     • Microglia
     • Ependymal cells
   • Melanocytes (in the skin and retina; produce melanin)
   • Odontoblasts (in teeth; produce dentin)
   • Chromaffin cells (in the adrenal medulla)
3. Muscle tissue: Muscle tissue is divided into two types based on structure and distribution.
   • Striated muscle
     • Cardiac muscle
     • Skeletal muscle
   • Smooth muscle
4. Epithelium (epithelial tissue)
   • Surface epithelium
   • Glandular epithelium

• Definition: : The epithelium is one of four basic types of tissues and is present in almost all organs of the human body as lining and glandular tissue.
• Classification according to function
  • Surface epithelium
  • Glandular epithelium
• Distribution: covers all inner and outer surfaces of the body (skin and mucous membranes)
  • Exception: synovial membrane (synovium)
    • The synovial membrane is composed of synoviocytes (not epithelial cells!), which line the inner surfaces of joint capsules, synovial bursa, and tendon sheaths.
• Formation: Different types of epithelia are formed from the three germ layers.
  • Ectoderm: epithelium of skin and skin appendages
  • Mesoderm
    • Epithelium of serous membranes (mesothelium): peritoneum, pleural, and pericardial cavities
    • Cells lining the inner surface of blood and lymphatic vessels (endothelium)
  • Endoderm: epithelium of the respiratory and gastrointestinal tract

• Definition: A specialized layer of tissue formed by closely aggregated cells that line the outer surface of organs, blood vessels, the skin, and the inner surface of body cavities. Divided into squamous, cuboidal, and columnar types.
• Functions
  • Protects against mechanical/chemical effects and harmful radiation
  • Resorption: e.g., nutrients in the gastrointestinal tract
• Classification: Surface epithelia are classified according to the number of layers, cell shape, and surface differentiation.

Criteria for classification

Layers

• Simple epithelium: a single layer of epithelial cells with all cells attached to the basement membrane
• Pseudostratified epithelium: a single layer of cells with the appearance of multiple layers as a result of the nuclei positioned at different levels
• Stratified epithelium: two or more cell layers with the basal layer attached to the basement membrane

Cell shape

• Explanation: The cell shape of the upper cell layer of a type of epithelium determines the name for the whole epithelium.
• Characteristics
  • Flat (squamous epithelium)
    • Appearance: Upper cells have a squamous (flat) shape (width > height).
    • Examples: skin , esophagus , cervix , serous membrane (e.g., peritoneum)
  • Cube-shaped (cuboidal epithelium)
    • Appearance: Upper cells have a cube-like shape (width = height).
    • Examples: bile ducts , renal tubules
  • Column-shaped (columnar epithelium)
    • Appearance: Upper cells have a rectangular or cylindrical shape (width < height).
    • Examples: intestine , respiratory tract (respiratory epithelium)

Epithelial specialization

Keratinization (horny layer)

• Specialization on the surface of epithelial cells can be differentiated into the horny layer (keratinization) and cell projections (microvilli, stereocilia, kinocilia).
• Keratinized epithelium is only found on the skin (stratum corneum). The epidermis is a keratinized stratified squamous epithelium.

Cell projections

Disorders associated with cell projections

• Motile cilia: primary ciliary dyskinesia (Kartagener syndrome)
• Nonmotile cilia
  • Polycystic kidney disease (PKD)
  • Mitral valve prolapse
  • Retinal degeneration, retinitis pigmentosa
  • Dandy-Walker malformation
  • Polydactyly

Microvilli and stereocilia are comprised of actin filaments, while kinocilia are composed of microtubules.

Special surface epithelia

Some surface epithelia possess more than one of the criteria mentioned above or occur especially often in a number of different organs.

Keratinized stratified squamous epithelium

Keratinized stratified squamous epithelium is only found in the epidermis. (see Skin and skin appendage).

Nonkeratinized squamous epithelium

• Definition: epithelium that does not show keratinization and is composed of multiple cell layers upon a basement membrane
• Structure: There are three different cell layers:
  • Basal layer: a layer of cuboidal to columnar cells that lie on the basement membrane
  • Intermediate layer: multiple layers of polygonal cells
  • Surface layer: multiple layers of squamous cells
• Properties: especially resistant to mechanical stress (e.g., through food passage)
• Distribution
  • Conjunctiva
  • Mucous membranes of the oral cavity, pharynx, esophagus, anal canal, navicular fossa of the urethra, vagina

Urothelium (transitional epithelium)

• Definition: stratified epithelium with cells of variable height and shape
• Structure: There are three cell layers (stratum basale, stratum intermedium, superficial layer) between the basement membrane and the surface.
  • Empty bladder: 5–7 cell layers; cells in the superficial layer (multinucleated umbrella cells) are hemispherical
  • Full bladder: 3–4 cell layers; umbrella cells are flattened
• Properties: adapts to variations in pressure/volumetric load; permeability barrier for urine and substances dissolved in urine
• Distribution
  • Throughout the urinary tract: renal pelvis, ureter, bladder, proximal urethra
  • Exceptions: parts of the male urethra

Respiratory epithelium

• Definition: Ciliated columnar epithelium (pseudostratified columnar epithelium with kinocilia) and numerous interspersed goblet cells
• Structure
  • Basal : basal cells (stem cell reserves of goblet and ciliated cells)
  • Luminal : goblet cells (mucogenic), ciliated cells (bear kinocilia)
• Properties: cleans the airways through mucus secretion and orally directed cilia motion (= mucociliary clearance)
• Distribution: throughout the respiratory tract: nasal cavity, nasopharynx, larynx, trachea, main bronchi to the terminal bronchioli

• Definition: A single cell or group of cells that produce and secrete specific products (e.g., mucin). Glandular epithelium commonly invaginates from surface epithelium into other tissue (e.g., connective tissue), but it is separated from the tissue by the basal lamina. Glandular epithelium can be endocrine (e.g., secrete products in the bloodstream) or exocrine (e.g., secrete products onto a surface).
• Function: Depending on the type of gland, it secretes:
  • Digestive juices containing enzymes (saliva, gastric and pancreatic juices)
  • Sweat
  • Sebum
  • Breast milk
  • Mucous (mucin)
• Classification: Glandular tissue can be classified according to its location, shape, secretory mechanism, and the type of secretion associated with it.

Classification criteria

Location of glandular tissue

Based on the location of glandular cells in relation to the surface epithelium, glands can be classified as either intraepithelial (located in the surface epithelium) or extraepithelial (located beneath the surface epithelium).

Intraepithelial glands

• Definition: glandular cells that are located within the surface epithelium
• Shapes
  • Goblet cells
    • Definition: single intraepithelial glandular cells with a vacuole that is characteristically filled with mucus (goblet form)
    • Function: secrete mucus (mucins)
    • Distribution
      • Small and large intestines
      • Nasal mucosa and respiratory tract (see respiratory epithelium)
  • Secretory epithelium
    • Definition: conglomerates of columnar epithelial cells with a bright cytoplasm (filled with mucus) and no vacuole
    • Distribution: e.g., the surface epithelium of the stomach and cervical canal is entirely composed of secretory epithelium

Extraepithelial glands

• Definition: glandular cells that are located below the surface epithelium from which they originate
• Examples
  • The three large salivary glands: parotid gland, submandibular gland, sublingual gland
  • Pancreas
  • Lacrimal glands

Typical extraepithelial gland structure

Since extraepithelial glands migrate during embryogenesis from the surface epithelium into the underlying connective tissue, they have an elaborate structure composed of excretory ducts and terminal ends. These components are named below in the sequence corresponding to the path of the secretion (from formation to the opening):

• Terminal ends
  • Definition: A closed glandular section that is connected to the excretory ducts and is the site of secretion production. There are numerous types of terminal ends (see shapes of the terminal ends of exocrine glands below).
  • Function: production and release of secretions into the lumen (the secretion drains from here into the excretory duct system)
• Excretory duct system
  • Definition: ducts lined with epithelial cells that connect glandular cells (in the acinus) with the opening of the gland
  • Function: drainage of secretion; changes in the nature of the secretion (e.g., through the addition/removal of ions)
  • Shapes: Because extraepithelial glands are usually subdivided into lobules (or lobuli) by connective tissue septa, there are various forms of excretory ducts.
    1. Intralobular ducts: narrows ducts composed of a single layer of epithelium within the lobuli that drain secretions from the terminal ends into the larger interlobular ducts.
    2. Interlobular ducts: wide ducts with a single layer of cuboidal to columnar epithelium that extend between the lobuli in the broad connective tissue septa and drain into the excretory ducts
    3. Excretory ducts: thickest and last segment of the duct system with a single to stratified layer of cuboidal to columnar epithelium that collects the secretions of all terminal ends and diverts to the opening of the gland (rare in histological preparations)
       • Example: bilayered, columnar epithelium in the terminal excretory ducts of the glands, including apocrine and eccrine sweat glands as well as esophageal glands

Shapes of the terminal ends of exocrine glands

• Acinar glands
  • Form: berry-like , narrow lumen
  • Examples: parotid gland, pancreas
• Alveolar glands
  • Shape: sac-like , wide lumen
  • Examples: apocrine sweat glands
• Tubular glands
  • Shape: tubular; wide, elongated lumen
  • Examples: gastric glands (foveolas in the stomach), colonic crypts
  • Subtypes
    • Simple branched tubular (e.g., meibomian glands)
    • Coiled tubular (e.g., eccrine sweat glands)
• Mixed forms: tubuloacinar, tubuloalveolar

Secretory mechanisms of exocrine glands

Exocrine glands are intraepithelial glands or extraepithelial glands that release their secretions on the inner (e.g., intestinal lumen) or outer (e.g., skin) surfaces of the body.

• Eccrine secretion
  • Definition: release of ions and small molecules through transmembrane proteins
  • Mechanism: membrane protein transport
  • Distribution: in almost all exocrine gland cells
• Merocrine secretion
  • Definition: release of secretions rich in proteins through fusion of cytosolic vesicles with the cell membrane
  • Mechanism: exocytosis
  • Distribution: : in almost all exocrine glandular cells (e.g., salivary glands, sweat glands)
• Apocrine secretion
  • Definition: release of secretions rich in lipids via budding off of a part of the apical cytoplasm
  • Mechanism: A portion of the cell membrane buds off with cytoplasm containing the secretory product (e.g., milk lipid droplets). As a result, the gland cell becomes smaller.
  • Distribution: : found only in apocrine sweat glands and lactating mammary glands
• Holocrine secretion
  • Definition: release of the entire cytoplasmic content through destruction of the gland cell
  • Mechanism: apoptosis of the glandular cell
  • Distribution: : found only in sebaceous glands

Type of secretion

Depending on the type of secretion, glands can be categorized as serous, mucous, or seromucous.

• Serous glands
  • Secretion: low viscosity and rich in proteins and enzymes
  • Histological characteristics
    • Terminal end: mainly acinar (→ acinar glands)
    • Gland cells: basal part is rich in rough endoplasmic reticulum (basophilic staining), apical granular secretions (eosinophilic staining)
  • Examples: parotid gland, pancreas
• Mucous glands
  • Secretion: viscous and rich in mucin
  • Histological characteristics
    • Terminal end: mainly tubular (→ tubular glands)
    • Gland cells: pale, bright cytoplasm
  • Examples: sublingual gland, esophageal glands, Brunner's glands, all intraepithelial glands
• Seromucous glands
  • Secretion: mainly low viscosity and contains both mucin and enzymes
  • Histological characteristics
    • Terminal end: mainly tubuloacinar; often show a serous demilune
    • Gland cells: characteristics of serous and also mucous cells
  • Examples: submandibular gland

Myoepithelial cells

• Definition: specialized epithelial cells that contain actin and myosin filaments, and contract when stimulated
• Function: contraction (through proteins of the smooth muscles such as actin, myosin, and desmin filaments) → expulsion of the gland secretion
• Appearance: star-shaped, branching
• Distribution: between glandular epithelium in several glands
  • Sweat, salivary, and lacrimal glands
  • Mammary glands
  • Esophageal glands
  • Respiratory tract

References:^[2]

• Definition: : a band-like structure consisting of components of the extracellular matrix that is found between epithelial cells and connective tissue
• Function
  • Anchoring epithelium to connective tissue
  • Diffusion barrier
• Distribution: The basement membrane connects connective tissue with the following cell types:
  • Epithelium and endothelium
  • Glial cells
  • Adipocytes and myocytes
• Structure: The basement membrane consists of the basal lamina; (contains two layers) and the lamina fibroreticularis.
  • Basal lamina (adjacent to the epithelium)
    • Lamina lucida (lamina rara)
      • Integrins
      • Collagen type XVII (BP 180, or bullous pemphigoid protein 180)
    • Lamina densa
      • Collagen type IV
      • Laminin
  • Lamina reticularis (adjacent to the connective tissue)
    • Reticular fibers
    • Anchorage with the basement membrane through collagen type III fibrils

The basal lamina and lamina reticularis form the basement membrane! The basement membrane is usually identified with light microscopy, whereas the basal lamina is identified with electron microscopy!

Microscopy of cells and tissues

• Light microscope: the most commonly used method of examining individual cells (cytology) as well as normal (histology) and pathological tissue (histopathology) for diagnostic and teaching purposes
  • Visualization of structures using stains (e.g., H&E stain)
• Electron microscope: method primarily used for research purposes and in the diagnosis of certain kidney, muscle, and CNS diseases, with a higher resolution than light microscopy
  • Visualization of the structures through compounds of heavy metals (e.g., osmium tetroxide)

For images on the histology of both normal and abnormal tissues see the articles virtual histology slide box and virtual histopathology slide box.