Anatomy And Physiology

The nose is a prominent structure located on the face between the eyes. The external openings are known as nares or nostrils which open at the back into the nasopharynx and lead to the trachea and oesophagus. The nose is the primary entrance to the respiratory tract, allowing air to enter the body for respiration. It conditions inspired air by filtering, warming, and moistening it. The nose also contains the olfactory organ, essential for the sense of smell.

The nasal cavity is an irregularly-shaped space in the front of the head extending from the bony palate upwards to the cranium (Figure 9.1). The bony framework of the nasal cavity is formed by the fusion of seven bones (Figure 9.2). It produces a chamber approximately 7.5 cm long by 5 cm high, subdivided into the right and left halves by a cartilaginous wall, the nasal septum. The septum consists of the anterior septal cartilage and posteriorly, the vomer and perpendicular plate of the ethmoid bone. It terminates at the nasopharynx.

The floor of the nose and the roof of the mouth are formed by the hard palatine bone and the soft palate, a flap of tissue. The soft palate extends back into the nasopharynx and during swallowing is pressed upward, so that food cannot lodge at the back of the nose, blocking the airway. The ability to breathe through the mouth as well as the nose is extremely beneficial, although the air inspired through the mouth is not humidified, heated and filtered to the same extent as the nose breathed air.

The forward section of the nasal cavity, which is within and above each nostril, is called the vestibule. Behind the vestibule and along each outer wall are three thin, scroll-shaped bony elements forming elevations, the conchae or turbinates, which generally run from front to rear. Each turbinate hangs over an air passage and they serve to increase the surface area of the cavities. The superior, middle and inferior turbinates form flues through which the air flows. The flues are quite narrow, and cause the air to flow in such a way that no part of the airstream is very far from the moist mucous blanket lining the air spaces. The turbulent airflow through this region, and the changes in direction caused by the turbinates, encourage inertial impaction of suspended particles. The width of the air spaces is adjusted by swell bodies in the septum and turbinates. Heating and humidification of inhaled air are important functions of the nose, which are facilitated by the abundant blood flow through

Frontal Sinus

Nasal Bone

Septal Cartilage

Hard Palatine Process of Maxilla

Figure 9.1 Cross section through the nose

Fibrous Fatty Tissue

Nasal Bone

Lower Alai Cartilage

Figure 9.2 Bony structure of the nose

/ \Greater Alar Septal Cartilage Cartilage

Lateral , Nasal Cartilage

Figure 9.2 Bony structure of the nose the arteriovenous anastomoses in the turbinates. The rapid blood flow through the cavernous sinusoids matches the cross-section of the nasal cavity to meet changing demands. Humidification is produced by an abundant fluid supply from the anterior serous glands, seromucous glands, goblet cells and by transudation1. Air can be brought to within 97 to 98% saturation, and inspired ambient air between -20° C and +55° C can be brought to within 10 degrees of body temperature. The majority of the airflow from the nose to the pharynx passes through the middle meatus; however, up to 20% is directed vertically by the internal ostium to the olfactory region from where the airstream arches down to the nasopharynx.

Although the nose is considered by most as primarily as an organ of smell, only a relatively small region is involved in this sense, the rest of the cavity being involved in respiration. The respiratory area is lined with a moist mucous membrane with fine hairlike projections known as cilia, which serve to collect debris. Mucus from cells in the membrane wall also helps to trap particles of dust and bacteria. The olfactory region of the nasal cavity is located beside and above the uppermost turbinate. This area is mostly lined with mucous membrane, but a small segment of the lining contains the nerve cells which are the actual sensory organs. Fibres called dendrites project from the nerve cells into the nasal cavity. They are covered only by a thin layer of moisture which dissolves microscopic particles from odour-emitting substances in the air, and these chemically stimulate the olfactory nerve cells. A receptor potential in the cell is generated initiating a nerve impulse in the olfactory nerves to the brain.

The diameter of the nares is controlled by the ciliator and compressor nares muscles and the levator labii superioris alaeque muscle. The entrance of the nares is guarded by hairs (vibrissae) which filter particles entering the nose. The average cross-sectional area of each nostril is 0.75 cm2. The posterior nasal apertures, the choanae, link the nose with the rhinopharynx and are much larger than the nares, measuring approximately 2.5 cm high by 1.2 cm wide. The nasal cavity widens in the middle and is approximately triangular in shape.

Nasal epithelia

Over 60% of the epithelial surface of the nasopharyngeal mucosa is lined by stratified squamous epithelium. In the lateral walls and roof of the nasopharynx there are alternating patches of squamous and ciliated epithelia, separated by islets of transitional epithelium, which are also present in a narrow zone between the oropharynx and the nasopharynx. The lower area of the pharynx is lined with mucous membrane covered by stratified squamous epithelium. The posterior two-thirds of the nasal cavity is lined by pseudostratified epithelium possessing microvilli. These, along with the cilia, prevent drying of the surface and promote transport of water and other substances between the cells and the nasal secretions. The whole of the respiratory region is covered with goblet cells, which are unicellular mucous glands and supply the surface with viscid mucus.

The mucosal lining of the nasal cavity varies in thickness and vascularity. The respiratory region, which lines the majority of the cavity, is highly vascular and the surface of some of the epithelial cell types are covered in microvilli, increasing the area available for drug absorption.

Nasal lymphatic system

The nasopharyngeal region possesses a very rich lymphatic plexus, in which the lymph drains into deep cervical (neck) lymphatics. Besides capillary filtrate, some cerebrospinal fluid also drains into the nasal submucosa, which is partly absorbed by the nasal lymphatics. When the nasal mucosa is damaged by an irritant, the resulting oedema results in an increased flow of lymph.

The lymphatics of the nasopharynx play an important part in the absorption of substances which have been deposited on the nasal mucosa. It is believed that these molecules diffuse mainly through the olfactory region of the mucosa to be taken up by both the blood capillaries and lymphatics.

Nasal secretions

The composition of nasal secretion consists of a mixture of secretory materials from the goblet cells, nasal glands, lacrimal glands and a plasma transudate. In a healthy nose, the mucosa is covered by a thin layer of clear mucus which is secreted from the mucous and serous glands in the mucosa and submucosa. It is renewed approximately every 10 minutes. The mucus blanket is produced by the goblet cells, whose numbers increase with age.

Mucus consists of mucopolysaccharides complexed with sialic acid and may be partially sulphated, particularly in diseased conditions. The main component of mucus is water with 2 to 3% mucin and 1 to 2% electrolytes. Normal nasal secretions contain about 150 mEq.L-1 sodium, 40 mEq.L-1 potassium and 8 mEq.L-1 calcium. Nasal mucus also contains lysozymes, enzymes, IgA, IgE, IgG, albumins, a 'kallikrein-like' substance, protease inhibitor, prostaglandins, lactoferrin, and interferon. The antibodies are present to act on bacterial particles which become trapped in the mucus lining. Many enzymes exist in nasal secretions and Table 9.1 lists the best characterized ones.

Table 9.1 Major enzymes found in nasal secretions cytochrome P-450 dependent monooxygenases, lactate-dehydrogenase, oxidoreductases, hydrolases, acid phosphotase and esterase, NAD+-dependent formaldehyde dehydrogenase, aldehyde dehydrogenase, leucine animopeptidase, phosphoglucomutase, glucose-6-phosphate dehydrogenase, aldolase, lactic dehydrogenase, malic enzymes, glutamic oxaloacetic transaminate, glutamic pyruvic transaminase NAD+-dependent 15-hydroxyprostaglandin dehydrogenase carboxylesterase, lysosomal proteinases and their inhibitors, 8-glucosidase, a-fucosidase and a-galactosidase succinic dehydrogenase, lysozyme steroid hydroxylases

The nasal cycle

The mucosa of each nasal passage has a separate autonomic and sensory innervation. The airflow through each nasal passage is regulated by the tumescence of the venous erectile tissue in the nasal mucosa. Engorgement of the tissue causes a constriction of the nasal passage, thus reducing airflow. This tissue exhibits cycles of constriction causing an alternation of the main airflow from one nasal passage to the other. A nasal cycle is found in about 80% of the population, yet most people are completely unaware of it since the total resistance remains relatively constant. Although the presence of the nasal cycle is well documented, its significance is still only speculated upon. One suggestion for the cycle is that each passage may rest whilst the other takes over conditioning of the inspired air.

As the nasal mucosa shrinks, droplets of secretion appear on the surface, and nasal secretion also follows the nasal cycle. The nasal cycle can be modified or overcome by a variety of endogenous and exogenous factors. Endogenous effects result from stimulation of the autonomic nervous system from fear, exercise and emotions or hormones as in pregnancy. Exogenous influences include ambient temperature, hypercapnia, allergy and infection. In addition, drugs which have sympathomimetic or parasympathomimetic action, release histamine or have antagonistic effects, will influence nasal patency by their action on the nasal vasculature. The amplitude of the nasal cycle is much more pronounced in seated or recumbent subjects compared to subjects who are standing. The nasal cycle can be overridden when recumbent. Lying on the left side will cause the right nostril to become more patent and vice versa.

Mucociliary clearance of inhaled particles

At the anterior ends of the nasal septum and turbinates, the squamous epithelium is replaced by areas of ciliated epithelium. There are approximately five ciliated to every non-ciliated cell, each ciliated cell having about 200 cilia extending from the anterior surface. Under normal conditions, these cells have a life of four to eight weeks2. Ciliary action clears surface fluid into the nasopharynx, where there is a transition to squamous epithelium. From here the mucus can be wiped off by the action of the soft palate and swallowed. There is also a small area in the anterior nose where ciliary action moves particles forward, from where they can then be removed by sneezing, wiping or blowing the nose. The sneeze reflex is similar to the cough reflex except that it applies to the nasal passages rather than the lower respiratory airways. During a sneeze, the uvula is depressed to channel the air through the nose and mouth to help clear the nasal passages of the irritation.

Efficient mucociliary clearance is a function of the physical properties of the mucus coupled to appropriately functioning cilia. Nasal mucus is secreted into the airway from goblet cells and mucus glands as a homogeneous gel. This floats on a 'sol' or periciliary layer that bathes the cilia, in a similar manner to the mucus lining the upper respiratory tract (Chapter 10). The mucus or gel layer acts like a conveyor belt over the 'sol' layer which is produced from serous glands and by transudation.

The cilia are approximately 6 pm long and the tip of each protrudes through the 'sol' layer into the mucus layer to propel it in an antrograde direction. The coordinated beating of the cilia moves the mucus layer along towards the pharynx. The ciliary beat frequency is estimated to be between 12-20Hz3. Intersubject variations of ciliary beat frequency are small but there is a highly significant correlation between the beat frequency and log of mucus transport time in vivo, indicating that this plays an important role in controlling nasal mucociliary clearance4 5.

The filtering and deposition of airborne particles occurs predominantly by inertial impaction. The regions of highest deposition are those where the airstream bends sharply, allowing the momentum of the particles to deviate from the air path6. Hence, impaction points are present at the internal ostium and start of the rhinopharynx. Nearly all particles of 5-10 pm, and a significant proportion of even very small particles, are deposited, although those less than 2 pm can penetrate to the lungs. Virus-containing droplets often coalesce to exceed 5 to 6 pm in diameter and are therefore retained by the nose7.

Nasal deposition increases with ventilation flow rate and nasal resistance. Children have much higher nasal resistances than adults but lower normal flow rates. Their nasal deposition percentages are lower than adults under similar conditions, so that despite greater nasal resistances, children have a lower particle filtering efficiency.

The average mucus flow rate is estimated to be approximately 5 mm min-1 with a range from 0 to 20 mm min-1. There is some disagreement in the literature concerning the mucus flow in the anterior and posterior halves of the nasal cavity. Earlier studies reported that transit rate tended to increase in the posterior portion, possibly due to less drying of the posterior mucosal surface by the stream of inspired air8, but others report no difference9. 'Slow' and 'fast' movers have been reported and there is a wide variation in mucociliary clearance rate between subjects, but within one person it is fairly consistent over moderate time spans10. The inter-individual and intra-individual changes in nasal clearance with time strongly suggest the important role of environmental factors. This view is supported by studies in monozygotic twins11.

From childhood, the nose is continually challenged by pollution and upper respiratory tract infections. No affects of aging (<60 years old) on mucus flow rate are apparent and even in a group of elderly subjects (age > 60 years), 70% of subjects studied showed no significant change in flow rate. For those who did show change, age could not be proven to be the causative factor12. It therefore seems that the division of 'normal' healthy people into 'slow' and 'fast' movers occurs before adulthood.

Measurement of clearance

Many methods have been used to investigate nasal mucociliary clearance. Initially markers such as sky blue dye13 and saccharin have been used to measure clearance rates14 15. Small amounts of powdered saccharin are placed in the nose and the time between application and detection of the taste is taken as the clearance time. Another method described is the use of aluminium discs of different colours placed on the floor and septum of the right and left nostril, used to measure transit rates in smokers and non-smokers16. A more quantitative method of measuring mucus flow rates is to use gamma scintigraphy to follow the distribution and clearance of radiolabelled formulations8 14 15.

Pathological effects on mucociliary function

Environmental factors are not the sole causes responsible for changes in the efficacy of mucociliary function. There are many pathological disorders which may disrupt the nasal defence mechanism by obstruction, lesions or effects on the nasal mucus or cilia. The most usual are the common cold, closely followed by others such as hayfever, asthma and sinusitis.

Rhinitis

Rhinitis is defined as inflammation of the mucus membranes of the nasal cavity. Acute rhinitis is commonly caused by viral infections and allergic reactions. The commonest and perhaps most inconvenient are the rhinoviruses which cause the 'common cold'. It seems that bacterial infection has remarkably little capacity to disrupt ciliary clearance unless the mucosa is actually destroyed. There is a normal commensal respiratory flora in the nose. Normally, potential pathogens are phagocytosed and cleared by mucus and cilia. If organisms penetrate into the 'sol' layer, however, there is increased opportunity for further penetration and infection of host cells. Viruses are able to disrupt clearance by penetrating the mucosa and cause degeneration and shedding of epithelial cells. Once this damage has occurred, the nasal mucosa is open to bacterial infection by normal commensals.

Cold sufferers exhibit both markedly increased and decreased mucociliary clearance rates. During the hypersecretory phase (rhinorrhea) the clearance is increased and usually during recovery from a cold there is congestion which slows clearance17. The susceptibility to rhinoviruses in women is significantly related to the menstrual cycle, possibly due to changes in mucociliary function during the cycle18.

Allergic rhinitis may be acute and seasonal (hayfever) or chronic (perennial rhinitis). In an allergic person, substances such as pollen or dust may more readily penetrate in and through the surface epithelium. Hayfever is the most common of all allergic diseases, affecting an estimated 10% of the population. The allergy to pollen produces rhinoconjunctivitis, for which the main symptoms are an itchy nose, sneezing and watery rhinorrhea. Mucus clearance time is decreased because nasal secretions become alkaline (pH 8) leading to increased ciliary activity19. There is an increase in water transport towards the epithelial surface and an altered transepithelial potential difference20. The same mechanisms are true for the increase in clearance seen in perennial allergic rhinitis where dust and fumes or some other allergen can provoke sneezing, rhinorrhea and nasal blockage. The physiological reaction to aerial contamination is of such a degree that it exceeds the selfcleaning capacity of the nose, impairing the nasal filter function.

Asthma

Asthmatics and bronchiectasis sufferers, both with and without allergic rhinitis, have an increased nasal mucociliary clearance time. It is therefore thought that there is some sort of mucus abnormality and ciliary malfunction working in concert21. Observations in asthmatics of tracheal mucus transport rates suggest that the mucociliary dysfunction observed after antigen challenge is related to airway anaphylaxis (a hypersensitivity reaction) and its chemical mediators. Pretreatment with sodium cromoglycate, a mast cell stabiliser, prevents the expected antigen induced increase in clearance time, but histamine alone is probably not the main mediator, since it stimulates mucociliary clearance. An alternative possible mediator is known as slow-reacting substance of anaphylaxis (SRS-A).

Sinusitis

Chronic sinusitis is the sequela to acute inflammation. Any condition that interferes with drainage or aeration of a paranasal sinus renders it liable to infection. If the ostium of a sinus is blocked, mucus is accumulated and pressure builds up. The nasal clearance time is increased in this condition due to the increase in quantity of mucus, which is usually highly viscous and adhesive12. However the inflammatory response is associated with changes in the H+ concentration of the nasal mucus, and nasal secretions tend to be alkaline in reaction, therefore increasing ciliary activity19.

Kartegener's syndrome

Kartegener's syndrome is an inherited disorder which comprises transposition of some or all of the major organs, bronchiectasis and sinusitis. The syndrome may also be associated with a variety of structural and functional abnormalities of cilia (the immotile cilia or ciliary dyskinesia syndrome), common due to a deficiency of the dynein arms which normally generate microtubule movement22. Mucociliary flow rate is therefore decreased due to ciliostasis. As well as the defects in nasal cilia associated with genetic disorders, evaluation of cilia from patients with chronic sinusitis, nasal polyposis, rhinitis and cystic fibrosis has demonstrated multiple membrane, microtubular and radial spoke alterations, although the importance of these in the pathologies is not known2.

Sjögrens syndrome

Sjögrens syndrome is an autoimmune disorder predominantly affecting middle-aged or elderly women. The problem is a lymphocytic infiltration into the external secretory glands, which results in atrophy of the acini and consequent reduction of their secretory capacity. There is an increase in mucus transport time. Stasis in the mucus layer is due to the decreased amount of secretion. Normally, particles can become entangled in the mucus, but it seems that in Sjögrens syndrome there is insufficient mucus for this to happen12 23.

Structural dysfunction

Nasal polyps are round, soft, semi-translucent, yellow or pale glistening benign tumours usually attached to the nasal or sinus mucosa by a relatively narrow stalk or pedicle. Their presence prevents efficient humidification, temperature control and particle infiltration of inspired air. The nasal clearance is slowed down due to blockage of the nose and defects in ciliary action or mucus secretion24. There are two types of polyps, neutrophil and eosinophil. Eosinophil or allergic polyps are characterized by eosinophilia, seromucous secretion and steroid responsiveness, whereas neutrophil or infectious polyps demonstrate neutrophilia, purulent secretion and lack of response to steroid treatment1.

Deviation of the nasal septum or rhinoscleroma causes obstruction which decreases clearance. People with deviated septa have longer clearance times (25-35 minutes) compared to normal subjects (9-15 minutes). Inspired air is directed onto a restricted area of mucosa and the flow rate exceeds its capacity to saturate air. This leads to an increased viscosity of the nasal mucus due to dehydration, making it unsuitable for effective ciliary action19. Congenital malformations such as cleft palate can also impair the function of the nose.

Laryngectomies can significantly accelerate peak transport rate in patients especially during the first sixty days after the operation, but the effect lessens with time. This could be partly due to a change in the nasal secretion12.

Flow rates in twenty-four lepers who had differing degrees of nasal pathology indicated that, even with distortion, scarring or erosion of intranasal structures, any remaining intact mucosa which was protected from the direct impact of unmodified air, functioned normally. However heavy crusting of mucous membranes was found to inhibit or prevent mucus flow13.

External factors affecting mucociliary clearance

There is a very wide normal range of mucociliary clearance which can be observed when particulates are introduced into the nose. Some people display the expected rapid, uninterrupted particle movement, whereas others have a slowing or even a halt in particle movement after an initial fast flow, or constantly slow movement or stasis10. A constitutional element in the overall control of nasal mucociliary flow may exist, but the mucus flow rate may also be influenced by many environmental factors25.

Clearance may be altered by substances affecting, or those causing an alteration of, the physical (viscoelastic or rheological) properties of the mucus layer. Without the mucociliary and other nasal defence mechanisms, conditions such as chronic bronchitis, pneumonia and squamous metaplasia of large airways would result.

Cigarette smokers unfortunately do not inhale the smoke through their nostrils, and thus the nasal defence mechanisms are bypassed and the relatively unprotected small airways of the lung are directly accessed. Tobacco smoking is known to affect the bronchial tree but has also been shown to significantly prolong the nasal clearance. However, it does not appear to affect the ciliary beat frequency, suggesting that the defective clearance seen in smokers is due to a reduction in the number of cilia or to a change in the viscoelastic properties of mucus26. The effect of smoking on mucociliary transport of materials in the nose is under controversy. Some workers report that there are no differences in transit rates for smokers and non-smokers8 16, whilst others report significantly longer nasal mucociliary clearance times in smokers (20±10 minutes) compared to non-smokers (11±4 minutes)26 27. However, the difference between the studies diminishes at relative humidities greater than 45%.

The nasal humidification system seems to be so efficient that even the driest air on entering the nasal passages is sufficiently moistened to prevent mucosal injury. However, the state of the ambient air is known to affect the mucociliary transport rate. Moderate decreases in mucus flow rate in the anterior and middle parts of the nose are observed with ambient temperatures above or below 23°C. The nasal resistance also decreases with warm air and increases with cold, as one would expect. However, none of these functional changes are sufficiently great so as to be physiologically important. There are differing opinions as to the effect of relative humidity on nasal mucociliary clearance. Some workers suggest that flow rate is correlated with relative humidity and that it increases from 6 to 9 mm min- 1 when the relative humidity rises above 30%8 27 28. However, other studies have failed to find differences in either mucus flow or in nasal airway resistance, at relative humidities ranging from 10 to 70%, even though temperatures were similar to the previous studies, at around

Other factors such as increased temperature, smog, clouds of dust and mild dehydration do not appreciably affect mucociliary clearance13. However nasal flushing or drinking very hot tea doubled the flow rate. The effect of irritants is greatest on the mucociliary transport in the anterior part of the nose, and for subjects with an initially slow mucus flow rate25 29.

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