1 Epithelial Histology

What is an epithelium?

An epithelium is the type of tissue that covers surfaces, usually the linings of hollow organs in the body, or in the case of the skin, the outer surface of the body. The figure below shows a schematic of a simple epithelium, modeled after the epithelium lining the small intestine.

schematic hollow organ with enlargement showing simple epithelium
A simple epithelium lining a schematic hollow organ.

Epithelia are comprised almost entirely of cells.  The apical surface faces the lumen (inside of a hollow organ) while the basal or basolateral surface is adjacent to the underlying tissue.  In many epithelia, the apical surface is specialized.  For instance, in the small intestine, the apical plasma membrane is folded into microvilli (see below) to increase the surface area for absorption of nutrients. Every epithelium has a basement membrane, that binds the epithelium to the underlying connective tissue.  The basement membrane consists of a thin layer of extracellular proteins that is located next to the basolateral surface.  Blood vessels do not penetrate through the basement membrane.  In practice, the basement membrane is too small to be seen except on an electron micrograph (EM).

 

electron micrograph of basal surface of epidermis showing basement membrane
Electron micrograph showing three keratinocytes (labeled BC for “basal cell”) on the basal surface of the epidermis.  The enlarged inset shows the basement membrane (BM).  Figure 9.3a in Wheater’s Functional Histology, 7th edition (2023).

In many cases, adjacent epithelial cells are linked by tight junctions.  Tight junctions are intercellular proteins that link adjacent cells to prevent the movement of substances between cells.  Tight junctions are usually located near the apical surface of a simple epithelium as shown in the figures below.

schematic epithelium showing tight junctions
Tight junctions divide the cell membrane into apical and basal compartments. Proteins are differentially expressed in the apical membrane and the basolateral membrane.
electron micrograph of intestinal cells showing a tight junction
Pseudocolored transmission electron micrograph of intercellular junctions near the apical surface of the simple columnar epithelium of the small intestine. Tight junction near apical surface colored red. Image EM 298 from Histology Guide: Virtual Histology Lab
https://histologyguide.com/EM-view/EM-298-intercellular-junctions/02-photo-1.html

Another effect of tight junctions is to divide the cell membrane into an apical and basolateral compartments.  As we shall see, different proteins can be expressed in the apical and basolateral membranes to allow the directional movement of substances across the epithelium.

Epidermis of the skin

Skin has three layers:  epidermis, dermis and hypodermis. The outer region is the epidermis, which is the epithelium that forms the surface of the skin.  The middle region is the dermis, which contains dense connective tissue, blood vessels, and nerves.  The innermost layer is the hypodermis, which contains loose connective tissue and adipose tissue, along with sweat glands, blood vessels, and nerves.

 

low magnification section of thick skin showing epidermis, dermis, and hypodermis
A low-magnification view of fingertip (thick) skin showing the three layers: epidermis, dermis, and hypodermis.

The next image is at higher magnifcation and focuses in on the epidermis. The epidermis is classified as a stratified squamous keratinized epithelium.  Cells divide at the basal surface of the epithelium, and as new cells are generated, older cells are pushed towards the apical surface.  As cells move apically, they become very flattened (squamous) and they fill up with an intracellular protein called keratin and die.  For this reason, cells in the epidermis are referred to as keratinocytes.  This type of epithelium is protective, with the keratin layer acting to protect the underlying tissue from abrasion and dehydration.

high magnification view of epidermis showing keratinocytes (purple) and keratin layer (red and blue)
A higher magnification view of the epidermis of the skin. The living skin cells are called keratinocytes (purple). The keratin layer at the apical surface stains red (more hydrated) and blue (dehydrated).

The image below focuses on the keratinocytes at high magnification.  Note that cells appear dark at the apical surface, where they are filling up with keratin.  The epithelium of the epidermis is stratified because it is many cell layers thick, and squamous because cells become flattened as they are pushed apically.  Finally, it is considered keratinized due to the presence of keratin at the apical surface.

high magnification view of epidermis focussing in on keratinocytes
High-magnification view of the epidermis showing keratinocytes (purple cells).

Endothelium of blood vessels

The endothelium is the simple squamous epithelium that lines all blood vessels.  The very smallest vessels, capillaries, are made up of just endothelium.  The image below shows capillaries in the upper part of the dermis.  Note how each white space is outlined by a single layer of thin dark cells; this is the endothelium.

high magnification view of dermis showing capillaries (red arrows)
A high-magnification view of the dermis. Red arrows indicate capillaries. Note that each white space is lined by a single layer of thin cells, the endothelium. Mainly what is visible are the dark, flat nuclei of the endothelial cells.

A healthy and intact endothelium acts as a barrier that isolates the blood from underlying tissue, preventing the formation of a blood clots.  Endothelial cells also release important signaling molecules, affecting processes such as tissue growth and blood flow.

In the brain, the endothelium together with other cells surrounding the capillaries form a functional barrier known as the blood-brain barrier.  Between endothelial cells there are tight junctions , limiting the permeability of the endothelium, and protecting neurons in the brain from toxins and other potentially neuroactive substances in the blood.

 

capillaries in the central nervous system are not leaky
The blood-brain barrier. Tight junctions between endothelial cells in central nervous system capillaries restrict the flow of substances from the blood to the interstitial fluid surrounding neurons. Figure 9.5b in Human Physiology: An Integrated Approach by Dee Silverthorn, 8th edition (2019).

Columnar epithelium of the small intestine

The small intestine is a tube made up of smooth muscle, connective tissue and an innermost lining that contains the epithelium.  In the digestive tract and other organs in which mucus is secreted on the surface of the epithelium, this lining layer is called a “mucous membrane” or mucosa.  The figure below shows how the tissue layers of the small intestine are organized.

wall of intestine showing layers: mucosa, submucosa, and muscularis
A low-magnification view of the small intestine showing the tissue layers.

The epithelium of the mucosa in the small intestine folds up and down to form protrusions called villi (singular:  villus). The folding of the epithelium increases the surface area available for absorption of nutrients.  It is easiest to see the structure of the intestinal epithelium by focussing on the surface of a villus.

simple columnar epithelium of intestine at high magnification
High magnification view of a villus showing the simple columnar epithelium made up of enterocytes. Mucus-secreting goblet cells (pale blue; bright green arrows) are scattered throughout the epithelium. Note the dark fuzzy appearance at the apical surface that corresponds to the brush border. Black arrows indicate the basal surface of the epithelium.

The image above shows part of a villus at high magnification.  The intestinal epithelium is classified as a simple columnar epithelium because the epithelial cells, enterocytes, are tall and thin.  Scattered among the enterocytes are mucus-secreting cells called goblet cells that stain pale blue.  At the apical surface of the enterocytes, there is a dark line which occurs due to a web of proteins that anchor the microvilli, folds of the apical plasma membrane that further increase the surface area for absorption.  Another term for the microvilli is “brush border”.

Below is an electron micrograph showing a row of enterocytes.  The microvilli are visible as the dark layer at the top of the cells.

electron micrograph of enterocytes
Electron micrograph of enterocytes showing microvilli (Mv) at the apical surface (magnification x4540).  Figure 14.25a in Wheater’s Functional Histology, 7th edition (2023).

Microvilli are folds in the plasma membrane.  This can be seen in a highly magnified electron micrograph focussing on the apical plasma membrane of an enterocyte.

electron micrograph showing microvilli
High magnification electron micrograph showing microvilli (Mv; magnification x5600). Figure 14.25b in Wheater’s Functional Histology, 7th edition (2023).

Goblet cells synthesize and secrete mucus.  Mucus contains glycoproteins (mucins) that are synthesized in the rough endoplasmic reticulum.  The micrograph below shows two goblet cells.  The cytoplasm of the goblet cells appears darker due to the abundant rough endoplasmic reticulum.  The apical part of each cell is filled with pale vesicles containing mucins.

 

2 goblet cells in the intestinal epithelium
Two goblet cells in the intestinal epithelium.  The goblet cells (G) can be recognized by their abundant rough endoplasmic reticulum (rER) and pale secretory vesicles filled with mucins (Mu).  Note the presence of microvilli (Mv) forming the brush border (BB) of the adjacent enterocytes.  Figure 5.17 in Wheater’s Functional Histology, 7th edition (2023).

Pseudostratified ciliated epithelium in the airways

The airway epithelium lines the passages that conduct air into the lungs.  Airways conduct air into the lungs; by contrast, the tiny sacs called alveoli, which are found at the ends of the airways, are where gas exchange occurs.

drawing showing location of airways (right); drawing showing airway epithelium (left)
Right: The ciliated epithelium moves mucus (secreted by goblet cells and submucosal glands) up toward the pharynx. Left: the epithelium contains goblet cells and ciliated epithelial cells. A watery saline layer at the surface of the epithelium helps the cilia to beat freely to move mucus.  Figure 17.5a, b in Human Physiology: An Integrated Approach by Dee Silverthorn, 8th edition

The airway epithelium is classified as a pseudostratified ciliated epithelium.  Although it is a simple epithelium, it appears stratified because nuclei of different cells are at different heights, hence the term “pseudostratified” meaning “falsely (pseudo-) stratified”.  An important function of this epithelium is the movement of mucus out of the respiratory tract.  Mucus, which is secreted by goblet cells and submucosal glands, traps particles and pathogens.  The beating of the cilia, located at the apical surface, moves the mucus toward the pharynx (throat) where it can be swallowed.

The image below shows tissue lining the wall of the trachea.

airway tissue in the trachea
Tissue lining the trachea. The psudostratified ciliated epithelium is at the top.

The pseudostratified ciliated epithelium of the airways can be seen in more detail in this higher-magnification image, also from the trachea.

high magnification view of pseudostratified ciliated epithelium
The airway epithelium in the trachea. The yellow bracket labeled E indicates the epithelium. The red arrows indicate cilia at the apical surface of the epithelium. Bright green arrows indicate goblet cells. Image MH 136 Trachea from Histology Guide: Virtual Histology Lab  http://www.histologyguide.com/slideview/MH-136-trachea/17-slide-1.html

The cilia on the surface of certain epithelial cells can be seen in this scanning electron micrograph.

scanning EM showing cilia and goblet cells on the surface of the airway epithelium in the primary bronchus
Scanning electron micrograph showing the apical surface of the airway epithelium in the primary bronchus. Goblet cells (GC) and cilia (CC) are visible. Figure 12.9 in Wheater’s Functional Histology, 7th edition (2023).

 

 

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Human Physiology in Health and Disease (PBIO 375) Copyright © by Anna Melby. All Rights Reserved.

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