5 Histology of glands, lymphatics and sinuses

• Basic anatomy
• Salivary glands
  • Components of saliva
  • Dental pellicle
  • Histology of salivary glands
  • Anatomy of salivary glands
  • Clinical applications of gland histology
• Lymphatic system
  • Lymph nodes
  • Tonsils
  • Clinical application of lymphatic histology
• Sinuses
  • Para-nasal sinus anatomy
  • Clinical application of para-nasal sinus histology

Basic anatomy of exocrine glands and lymphatic organs

The average exocrine gland contains simple cuboidal epithelia^← that form grape-shaped or tube-shaped structures called acini. Liquids secreted by the cells of acini  enter a duct, which can be made of a simple cuboidal epithelium or simple columnar epithelium^←. It is possible for larger glands to have regions of stratified cuboidal epithelial cells as well. The outside of the gland is surrounded by a dense connective tissue capsule (not quite thick enough for us to worry about whether the collagen^← fibers are regular or irregular). The connective tissue extends inwards forming trabeculae (or septa, but not to be confused with trabeculae of spongy bone tissue), which divide the organ into lobes.

The average lymphatic organ shares patterns with exocrine glands. A lymphatic organ is surrounded by a dense connective tissue capsule, and that connective tissue extends inwards forming trabeculae. Inside a lymphatic organ, clusters of white blood cells suspended within reticular connective tissue form germinal centers (or nodules) where white blood cells filter cellular debris and scan body fluids for pathogens. If they detect a pathogen, they multiply, release inflammatory signals, and migrate through the body’s connective tissues looking for more pathogens.

Salivary glands

Components of saliva

The major function of salivary glands is to produce saliva, which helps maintain the health of the oral mucosa and teeth, as well as assist in mastication. Acinar epithelial cells transcribe and translate long mucous proteins on the rER^←, modify them in the Golgi apparatus^← to form large glycoproteins, and secrete them. These cells also pump electrolytes from their cytoplasm into the lumen of the acinus, which, along with the glycoproteins, attract water by osmosis. These components make saliva moist but sticky enough to adhere to all surfaces of the oral cavity, rather than sink to the floor of the mouth.

Other molecules are secreted and become a part of saliva. Buffers within saliva help to maintain a stable pH, despite the acidity or alkalinity of different foods, or the acidity of certain oral bacterial secretions. Buffers and electrolytes also help disrupt the formation of bacterial biofilms, which bacteria use to adhere to teeth. The watery nature of saliva helps to moisten food and the oral mucosa, assisting in mastication, speech and swallowing. Watery saliva also helps to limit the population of oral bacteria. People swallow saliva even when they are not eating. This flushes a percentage of oral microorganisms down to the stomach, where certain death awaits in the form of hydrochloric acid and the protein-destroying enzyme pepsin. The enzymes salivary amylase and lysozyme are produced by acinar cells to serve a similar purpose, breaking covalent bonds within the cell walls of viruses and bacteria, or their surface glycoproteins used to adhere to tooth surfaces. Without hours of mechanical digestion by the teeth and stomach, there is very little surface area for salivary amylase to digest carbohydrate molecules for nutritional purposes. Chemical digestion of carbohydrates for nutrition is carried out in the small intestines by the much more abundant pancreatic amylase. Bacteria, however, do not form a bolus (a large solid mass), so their cell walls and surface glycoproteins are open to attack by enzymes without prior mechanical processing. A second function of salivary amylase is to cleave a small amount of small sugars from starch, allowing taste buds to detect them, so salivary amylase and other carbohydrases in saliva function in the sense of gustation as well as in limiting bacterial populations.

Dental pellicle

The dental pellicle is a thin coating of glycoproteins from saliva on the surface of teeth. It prevents excess deposits of Ca²⁺PO₄^3- (calculus deposit minerals) and also prevents demineralization of enamel. Both depositing bumps or eroding crevices allows bacteria to adhere to teeth and avoid being washed into the stomach. Therefore, the dental pellicle can prevent adhesion of bacteria to the tooth surface. However, oral bacteria can adhere to the dental pellicle. Furthermore, saliva contains minerals that produce calculus, making the relationship between saliva, dental pellicle and the oral microbiome complicated. This illustrates the delicate balance that must be maintained in the oral cavity: too many bacteria can lead to gingivitis^← and dental caries, while too few bacteria leave the oral cavity open to colonization by harmful bacteria, leading to gingivitis and dental caries.

Histology of salivary glands

Serous acini produce more watery secretions. These are composed of simple cuboidal epithelium^←. Serous acini tend to stain darker pink or purple using a traditional H&E stain.

Mucous acini secrete more glycoproteins, making their secretion thicker and stickier (more mucous). Mucous acini are made of a simple columnar epithelium^←. Mucous acini appear to have bubbles.

Muco-serous acini produce secretions halfway in-between the first two in consistency. These look like mucous acini under the microscope, with an additional bonnet (a hat) of myo-epithelial cells. These cells contract like smooth muscle cells. For most epithelial cells, the actin and myosin genes are found in the  cytoskeleton^← and allow for migration, which is especially important for stem cells^← that move to help repair a wound. Myo-epithelial cells, on the other hand, use some of the DNA instructions for making larger amounts of actin and myosin and organizing them into specialized filaments similar to smooth muscle tissue. This makes myo-epithelial cells appear more like smooth muscle than an epithelium. However, these cells have an epithelial lineage— they differentiate^← from ectoderm, not from a mesenchymal stem cell or myoblast.

All three secretions mix in the oral cavity to produce saliva. These secretions reach the oral cavity by way of different ducts, which can be identified under the microscope by their different types of epithelial cells. We know of no clinical significance to the types of ducts or their cells.

Anatomy of exocrine glands

There are three major and numerous minor salivary glands. The three major salivary glands are listed in Table 5.1.

The parotid glands drain into the oral cavity by way of the parotid duct (or Stensen duct). The ducts travel through the masseter muscle and enters the oral cavity at a papilla on the buccal mucosa usually located lateral to the 2^nd maxillary molar.

The sub-lingual glands and sub-mandibular glands have ducts that share an entrance on the floor of the mouth at the sub-lingual caruncle. The sub-lingual gland also has numerous smaller ducts that open onto the floor of the mouth.

Numerous minor salivary glands are located throughout the oral cavity. They are normally not visible, unless the oral mucosa is hyper-keratinized. Luckily, no one has bothered to name these glands or their ducts, except for the von Ebner salivary glands, which are minor salivary glands associated with the circumvallate lingual papillae. The minor salivary glands are predominantly mucous, with exceptions, which helps their secretions to stick to the roof and sides of the oral cavity.

Clinical application of salivary gland histology

Mumps is a viral infection that causes swelling of the parotid glands and other organs. Vaccination has reduced mumps cases in the US by over 99%. Vaccination against mumps works by triggering the primary immune response against mumps antigens. Unfortunately, mumps outbreaks still occur, often in high-density living areas (such as college dormitories) with a large percentage of unvaccinated individuals. It is difficult to counter  beliefs in pseudoscience which seek to cast doubt on the safety or efficacy of vaccination, although some strategies work better than others.

Hypo-salivation

Hypo-salivation, or decreased saliva production, can be caused by certain diseases, medications, cancer treatments, and aging. It may result in xerostomia, or dry mouth. Because saliva contains growth factors, reduced saliva decreases the healing ability of the oral mucosa, leading to sores. Reduced saliva also reduces limits to growth placed on the oral microbiome, leading to infections and caries. Reduced taste can also be a consequence, which patients might compensate for by flavoring their food with excessive levels of salt (NaCl). Using Monosodium Glutamate (MSG, or NaC₅H₈NO₄) may be used to enhance both flavor and saliva production, and is a significantly healthier option.

Mineralized saliva (sialoliths)

Electrolytes in saliva can precipitate and form salivary gland stones, or sialoliths. Large sialoliths may block the duct of one of the salivary glands, which stops the flow– but not the production– of saliva. As a result, saliva builds up in the gland, causing swelling and possibly inflammation. Blockage of a minor salivary gland produces a swelling within the oral mucosa known as a mucocele (or mucocoele) (Fig. 5.14), while blockage of a major salivary gland produces a ranula (Fig. 5.15). These are fairly common disorders. Inflammation of the parotid gland must be clearly distinguished from mumps before any treatment is given.

Sialography

Sialoliths may be palpated by clinicians. Alternately, an image of the blockage known as a sialograph can be taken by injecting a radiopaque dye as far into the salivary gland duct as it can go (until further flow is blocked by the sialolith). Usually, sialoliths are removed with minimal discomfort. Sialography should not be done in cases of acute infection, as the dye may push infectious exudate into deeper tissues, spreading the infection.

Lymphatic system

Very basic overview of the lymphatic system

Lymphatic drainage of the teeth

Fluid travels to the teeth via capillaries. As plasma exudes from the capillaries, it becomes ECF. Veins collect most of this fluid, the rest is collected by lymphatic vessels. ECF absorbed into a lymphatic vessel is called lymph, and it is returned to the circulatory system. Lymphatic vessels are more permeable than capillaries, having mini-valves on their outer edges. Mini-valves allow solids to enter the lymphatic vessels, including cellular debris, microorganisms, and cancer cells. The lymphatic vessels are connected to a number of lymph nodes, which clean up debris and mount an immune response against microorganisms and cancer cells. Knowing the anatomical connections of the lymphatic vessels helps locate areas of infection by the inflammation triggered in down-stream lymph nodes.

Lymph nodes

Lymph nodes are found throughout the body. A large cluster of lymph nodes can be found in the neck, called the cervical lymph nodes, in addition to other locations. Lymph nodes are composed primarily of reticular connective tissue, which provides support for resident clusters of white blood cells. Afferent lymphatic vessels bring lymph to the node, while efferent vessels drain lymph towards the circulatory system.

Tonsillar tissue

Tonsillar tissue is either a pseudostratified epithelium or a non-keratinized stratified squamous epithelium^←, plus reticular connective tissue below. Tonsils are similar to lymph nodes, except there are no lymphatic vessels, and one end of the tonsil is un-encapsulated (the epithelial border). Clusters of white blood cells can be found in germinal centers, suspended within reticular connective tissue.

The tonsils

There are 4 major tonsils located the border of the oral cavity and pharynx: lingual, palatine, pharyngeal and tubal. These tonsils form a ring, called Waldeyer's ring, which serves to identify pathogens that are either ingested or inhaled, and begin an immune response before they reach deeper locations, such as the lungs or stomach. Because of their anatomy (no vessels), tonsils do not filter debris or microorganisms out of bodily fluids, they only identify pathogens. The un-encapsulated side faces the lumen of the pharynx, coming into contact with many foreign molecules.

Clinical applications of lymphatic system histology

Lymphadenopathy of lymph nodes

In the absence of infection, lymph nodes are soft and moveable. However, if white blood cells detect a pathogen, they undergo cell division and release inflammatory molecules. This leads to lymph nodes becoming palpable, possibly visibly swollen, and likely sensitive to touch. The swelling of lymphatic tissue is called lymphadenopathy, and is a non-specific sign of immune system activation.

The mandibular incisors drain into sub-mental lymph nodes. The sub-mental lymph nodes and the rest of the teeth (other than maxillary 3rd molars) drain into sub-mandibular lymph nodes. The sub-mandibular lymph nodes then drain into superior deep cervical nodes. Swelling of some or all of these lymph nodes can indicate active periodontal disease.

Lymphadenopathy of tonsillar tissue

Tonsillar tissue can become inflamed, and when it does it is usually called tonsillitis— when the increased number of white blood cells (living and dead) may be visible as white-ish patches within the inflamed tonsil(s). Tonsillitis is more common in children between pre-school and pre-teens because of the way the immune system develops immunocompetency and tolerance.

Para-nasal sinuses

Basic anatomy of the para-nasal sinuses

The para-nasal sinuses are spaces within the frontal, sphenoid, ethmoid and maxillary bones surrounding the nasal cavity. The maxillary, frontal and sphenoid sinus communicate with (connect to) the nasal cavity via small passageways. The para-nasal sinuses are lined with pseudostratified epithelium. This epithelium produces mucus which traps pathogens and debris. With the aid of cilia, these harmful agents are removed from the body. Within the nasal cavity are 3 bumps called nasal conchae, which divide the nasal cavity into three winding spaces called the nasal meatuses. (for those who are counting, there is a fourth space above the superior nasal conchae called the spheno-ethmoid recess, it is not a meatus because it does not form a pathway from the nasal vestibule to the nasopharynx).

Clinical applications of para-nasal sinus histology

Inflammation within the para-nasal sinuses

When para-nasal sinuses become inflamed (known as sinusitis), the small ducts leading to the nasal sinuses may become obstructed. The increase in fluid that accompanies inflammation has nowhere to drain, leading to pressure within the sinuses. Furthermore, one response of goblet cells to inflammatory signals is to produce more mucous proteins, which again have nowhere to drain.

The posterior maxillary teeth lie close to, or sometimes partly within the maxillary sinuses. Therefore, if inflammation occurs within these sinuses, it can cause discomfort to the significantly more-sensitive teeth. Furthermore, sinus infections may spread to the posterior maxillary teeth.

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