NASAL PHYSIOLOGY

1. NASAL PHYSIOLOGY SpR teaching 3rd Jan 2012

2. Learning objectives Form Function Quiz

3. Embryology of nose Embryology (4-8 weeks) The frontonasal process inferiorly differentiates into two projections known as �Nasal Placodes� These nasal placodes will be ultimately invaded by growing ectoderm and mesenchyme.� These structures later fuse to become the nasal cavity and primitive choana, separated from the stomodeum by the oronasal membrane.� Neurla crest � nasal placode �primitive/ secondary choanae? bucoonasal membrnae. XXX choanal atresia http://www.slideshare.net/drtbalu/embryology-nose-and-paranasal-sinuses http://emedicine.medscape.com/article/835134-overview#showall http://www.bartleby.com/107/13.htmlNeurla crest � nasal placode �primitive/ secondary choanae? bucoonasal membrnae. XXX choanal atresia http://www.slideshare.net/drtbalu/embryology-nose-and-paranasal-sinuses http://emedicine.medscape.com/article/835134-overview#showall http://www.bartleby.com/107/13.html

4. Embryology (paranasal sinus) 25 � 28 weeks 3 medially directed projections arise from the lateral wall of the nose.� This serves as the beginning of the development of paranasal sinuses The medial projections arising from the lateral wall of the nose forms the following structures: anterior projection forms the agger nasi inferior (maxilloturbinate) projection forms the inferior turbinate and maxillary sinus The superior projection (ethmoidoturbinate) forms the superior turbinate, middle turbinate, ethmoidal air cells and their corresponding drainage channels.� The middle meatus develops between the inferior and middle meatus

5. Embryology of nose http://emedicine.medscape.com/article/874822-overview#showall http://www.drtbalu.co.in/emb_nose.html The middle meatus invaginates laterally to form the embryonic infundibulum and uncinate process.� During the 13th week of development the embryonic infundibulum grows superiorly to form the frontal recess area.� Development of frontal sinus:� The frontal sinus may develop as a direct continuation of embryonic infundibulum and frontal recess superiorly during the 16th week.� It can also develop by upward migration of anterior ethmoidal air cells to penetrate the inferior aspect of the frontal bone between its outer and inner tables.� Pneumatization of frontal bone is a very slow process.� The frontal sinus infact remains as a small blind sac within the frontal bone till the child is about 2 years of age, then secondary pneumatization begins.� From the age of 2 till the child becomes 9 years old secondary pneumatization of frontal bone proceeds.� When the child reaches the age of 9, the development of the frontal sinus has reached completion.� Sometimes frontal sinus may be asymmetrical / aplastic as well.� The embryonic infundibulum may also invade the mesenchyme in the maxillary process forming the primitive maxillary sinus.� Pneumatization of maxillary sinus is faster than that of frontal sinus.� Pneumatization occurs at the expense of erupting upper dentition.� Abnormalities of maxillary pneumatization is associated with anomalies of upper dentition. http://emedicine.medscape.com/article/874822-overview#showall http://www.drtbalu.co.in/emb_nose.html The middle meatus invaginates laterally to form the embryonic infundibulum and uncinate process.� During the 13th week of development the embryonic infundibulum grows superiorly to form the frontal recess area.� Development of frontal sinus:� The frontal sinus may develop as a direct continuation of embryonic infundibulum and frontal recess superiorly during the 16th week.� It can also develop by upward migration of anterior ethmoidal air cells to penetrate the inferior aspect of the frontal bone between its outer and inner tables.� Pneumatization of frontal bone is a very slow process.� The frontal sinus infact remains as a small blind sac within the frontal bone till the child is about 2 years of age, then secondary pneumatization begins.� From the age of 2 till the child becomes 9 years old secondary pneumatization of frontal bone proceeds.� When the child reaches the age of 9, the development of the frontal sinus has reached completion.� Sometimes frontal sinus may be asymmetrical / aplastic as well.� The embryonic infundibulum may also invade the mesenchyme in the maxillary process forming the primitive maxillary sinus.� Pneumatization of maxillary sinus is faster than that of frontal sinus.� Pneumatization occurs at the expense of erupting upper dentition.� Abnormalities of maxillary pneumatization is associated with anomalies of upper dentition.

6. Anatomy nose Nasal physiology greatly dependent on anatomy External anatomy Structural thirds Lower and middle play role in nasal valve External nasal valve Internal nasal valve Pseudostratified, columnar, ciliated Glands: serous + goblet http://emedicine.medscape.com/article/874822-overview#showallhttp://emedicine.medscape.com/article/874822-overview#showall

9. Physiological function Warming Countercurrent exchange: The sphenopalatine artery courses anteriorly in the nasal cavity over the turbinates, whereas air flows in a posterior direction forming a countercurrent exchange. 2 opposing motions create a more efficient heat exchange process- 10% of heat loss Through heat exchange, the nasal mucosa maintains the nasal cavity at a range of 31�37� C Humidification Vascular mucosa increases relative humidity to 95% before air reaches the nasopharynx. Physiologic nasal fluids and ciliary function are vital to maintain immune defense through normal mucociliary flow Adults condition more than 14,000 liters of air per day, requiring more than 680 grams of water, approximately 20% of our daily water intake Filtration of environmental particles by vibrissae Voice modification modifying high-frequency sounds and consonants

10. Physiological function Mucociliary flow: Mucus contents Water IgA, IgE, muramidase Mucociliary transport Ciliary flow is a vital component of normal sinonasal function. The ciliary structure in the nose is a 2-layered structure, providing an important defense mechanism. Resting on a pseudostratified ciliated cell layer, mucociliary flow occurs throughout the nose and paranasal sinuses Olfactory system Active sniffing

11. Nasal resistance Differences between races The nose accounts for up to half the total airway resistance Anterior nasal valve = narrowest part The nasal resistance is produced by two resistors in parallel and each cavity has a variable value produced by the nasal cycle The resistance is made up of two elements Fixed: bone, cartilage and attached muscles Variable: mucosa Automatic positive end-expiratory pressure (Auto-PEEP) occurs from the work that is involved in overcoming resistance during expiration postlaryngectomy patients, alveolar collapse is imminent with the loss of nasal airway resistance and Auto-PEEP. The glottis acts as an internal valve to regulate expiratory airflow, thus allowing alveoli to stay open longer during expiration and allowing continued gas exchange Factors affecting resistance: Intrinsic: anatomy, autonomic, posture, exercise Extrinsic: allergen

12. Airflow Inspiratory flow is generally considered as laminar flow Expiratory flow has more components of turbulent flow Turbulent flow facilitates the exchange of heat and moisture. Anterior nasal valve = narrowest Nasal cycle

13. Nasal cycle Consists of alternate nasal blockage between passages. The changes are produced by vascular activity, particularly the volume of blood on the venous sinusoids (capacitance vessels). Cyclical changes occur between four and 12 hours; they are constant for each person. Various factors may modify the nasal cycle and include The autonomic nervous Drugs- antiadrenergic, anticholinergic, antihistamines Hormonal changes, such as puberty and pregnancy Environmental allergies are the most common causes of inflammation of nasal membranes, followed by inhaled irritants (eg, cigarette smoke, perfumes, various chemicals, and other noxious odorants) Anatomic deformities that may have a varying effect on congestion, drainage, and olfaction. Septal deviation and enlarged turbinates can affect airflow into the nasal cavity, transforming it from a laminar pattern to a more turbulent pattern Turbulent airflow causes further irritation to nasal membranes, with a resultant increase in nasal drainage and congestion 80% people have nasal cycle80% people have nasal cycle

14. Tests of Nasal Physiology Include studies of airflow ciliary function olfaction. Airflow: rhinomanometry + acoustic rhinometry Radiologic imaging with CT or MRI assess the cross-sectional area of nasal passages The saccharin test evaluates ciliary function by measuring the time it takes for a drop of saccharin to be tasted in the back of the throat when applied to the anterior tip of the inferior turbinate. Olfaction Multiple tests of olfaction are available, but the University of Pennsylvania Smell Identification Test (UPSIT) is used most commonly. The UPSIT is a 40-item scratch-and-sniff test and is highly validated by age and sex. Recent research into exhaled nitric oxide suggests that in the future, these measurements may prove valuable as non-invasive objective tools for the assessment and management of normal nasal physiology and nasal and sinus disorders

15. Objective tests Rhinomanometry measures air pressure and the rate of airflow during breathing.� These measurements are then used to calculate nasal airway resistance. Acoustic rhinometry uses a reflected sound signal to measure the cross-sectional area and volume of the nasal passage.� Acoustic rhinometry gives an anatomic description of a nasal passage, whereas rhinomanometry gives a functional measure of the pressure/flow relationships during the respiratory cycle.� Both techniques have been used in comparing decongestive action of antihistamines and corticosteroids and for assessment of an individual prior to or following nasal surgery.� Poor correlation between objective tests and symptoms

16. Blood supply to nose

17. Sensory nerves Olfactory nerve � special sensory Trigeminal nerve supplies sensation �Va, Vb some evidence that sensory nerve endings have H1 receptors Cold receptors sense airflow and there are more nerve endings near the nasal. Receptors can be stimulated by the menthol, giving rise to an apparent increase in airflow

18. Autonomic supply to nose

19. Drugs acting on nasal mucosa

20. Paranasal sinuses Mucosa- Respiratory mucosa runs in continuity from the nose. Goblet cells and cilia are less numerous in general but more frequent near the ostia Mucociliary clearance - maxillary sinus is spiral and towards the natural ostium. Drainage of the frontal and sphenoid sinuses is downwards and is aided by gravity Oxygen tensionThe PO2 is lower in the maxillary sinuses than in the nose and it is lower still in the frontal sinuses. If the ostium becomes blocked, the oxygen tension drops further. Ciliary motion remains normal if the blood supply is adequate. If the blood supply is impaired, ciliary activity is reduced and stasis of secretions results. Levels of nitrous oxide are higher in the sinuses than in the nasal cavity

21. Olfaction Olfaction is fully developed at birth, but recognition and learning come late, probably after the age of two years in man Smell is used in four main areas of behaviour Eating:recognition of food types and the initiation of digestion. Initiation of digestion is mediated via the lateral and ventromedial hypothalamus, causes salivation and increases output of gastric acid and enzymes Recognition territorial markings sexual behaviour

22. Accessory olfactory system Many animals, including most mammals and reptiles, but not humans, have two distinct and segregated olfactory systems a main olfactory system, which detects volatile stimuli accessory olfactory system (vomeronasal organ) which detects fluid-phase stimuli Pheromones Snakes use it to smell prey, sticking their tongue out and touching it to the organ Sensory receptors of the accessory olfactory system are located in the vomeronasal organ? accessory olfactory bulb?amygdala and hypothalamus where they may influence aggressive and mating behavior. Unlike in the main olfactory system, the axons that leave the accessory olfactory bulb do not project to the brain's cortex

23. Olfactory pathway Olfactory sensory neurons project axons to the brain within the olfactory nerve, (cranial nerve I). These axons pass to the olfactory bulb through the cribriform plate, which in turn projects olfactory information to the olfactory cortex and other areas. The axons from the olfactory receptors converge in the outer layer of the olfactory bulb within small (~50 micrometers in diameter) structures called glomeruli. Mitral cells, located in the inner layer of the olfactory bulb, form synapses with the axons of the sensory neurons within glomeruli and send the information about the odor to other parts of the olfactory system, where multiple signals may be processed to form a synthesized olfactory perception. A large degree of convergence occurs, with twenty-five thousand axons synapsing on twenty five or so mitral cells, and with each of these mitral cells projecting to multiple glomeruli. Mitral cells also project to periglomerular cells and granular cells that inhibit the mitral cells surrounding it (lateral inhibition). Granular cells also mediate inhibition and excitation of mitral cells through pathways from centrifugal fibers and the anterior olfactory nuclei. The mitral cells leave the olfactory bulb in the lateral olfactory tract, which synapses on five major regions of the cerebrum: the anterior olfactory nucleus, the olfactory tubercle, the amygdala, the piriform cortex, and the entorhinal cortex. The anterior olfactory nucleus projects, via the anterior commissure, to the contralateral olfactory bulb, inhibiting it. The piriform cortex projects to the medial dorsal nucleus of the thalamus, which then projects to the orbitofrontal cortex. The orbitofrontal cortex mediates conscious perception of the odor. The 3-layered piriform cortex projects to a number of thalamic and hypothalamic nuclei, the hippocampus and amygdala and the orbitofrontal cortex but its function is largely unknown. The entorhinal cortex projects to the amygdala and is involved in emotional and autonomic responses to odor. It also projects to the hippocampus and is involved in motivation and memory. Odor information is stored in long-term memory and has strong connections to emotional memory. This is possibly due to the olfactory system's close anatomical ties to the limbic system and hippocampus, areas of the brain that have long been known to be involved in emotion and place memory, respectively. Olfactory sensory neurons project axons to the brain within the olfactory nerve, (cranial nerve I). These axons pass to the olfactory bulb through the cribriform plate, which in turn projects olfactory information to the olfactory cortex and other areas. The axons from the olfactory receptors converge in the outer layer of the olfactory bulb within small (~50 micrometers in diameter) structures called glomeruli. Mitral cells, located in the inner layer of the olfactory bulb, form synapses with the axons of the sensory neurons within glomeruli and send the information about the odor to other parts of the olfactory system, where multiple signals may be processed to form a synthesized olfactory perception. A large degree of convergence occurs, with twenty-five thousand axons synapsing on twenty five or so mitral cells, and with each of these mitral cells projecting to multiple glomeruli. Mitral cells also project to periglomerular cells and granular cells that inhibit the mitral cells surrounding it (lateral inhibition). Granular cells also mediate inhibition and excitation of mitral cells through pathways from centrifugal fibers and the anterior olfactory nuclei. The mitral cells leave the olfactory bulb in the lateral olfactory tract, which synapses on five major regions of the cerebrum: the anterior olfactory nucleus, the olfactory tubercle, the amygdala, the piriform cortex, and the entorhinal cortex. The anterior olfactory nucleus projects, via the anterior commissure, to the contralateral olfactory bulb, inhibiting it. The piriform cortex projects to the medial dorsal nucleus of the thalamus, which then projects to the orbitofrontal cortex. The orbitofrontal cortex mediates conscious perception of the odor. The 3-layered piriform cortex projects to a number of thalamic and hypothalamic nuclei, the hippocampus and amygdala and the orbitofrontal cortex but its function is largely unknown. The entorhinal cortex projects to the amygdala and is involved in emotional and autonomic responses to odor. It also projects to the hippocampus and is involved in motivation and memory. Odor information is stored in long-term memory and has strong connections to emotional memory. This is possibly due to the olfactory system's close anatomical ties to the limbic system and hippocampus, areas of the brain that have long been known to be involved in emotion and place memory, respectively. Olfactory sensory neurons project axons to the brain within the olfactory nerve, (cranial nerve I). These axons pass to the olfactory bulb through the cribriform plate, which in turn projects olfactory information to the olfactory cortex and other areas. The axons from the olfactory receptors converge in the outer layer of the olfactory bulb within small (~50 micrometers in diameter) structures called glomeruli. Mitral cells, located in the inner layer of the olfactory bulb, form synapses with the axons of the sensory neurons within glomeruli and send the information about the odor to other parts of the olfactory system, where multiple signals may be processed to form a synthesized olfactory perception. A large degree of convergence occurs, with twenty-five thousand axons synapsing on twenty five or so mitral cells, and with each of these mitral cells projecting to multiple glomeruli. Mitral cells also project to periglomerular cells and granular cells that inhibit the mitral cells surrounding it (lateral inhibition). Granular cells also mediate inhibition and excitation of mitral cells through pathways from centrifugal fibers and the anterior olfactory nuclei. The mitral cells leave the olfactory bulb in the lateral olfactory tract, which synapses on five major regions of the cerebrum: the anterior olfactory nucleus, the olfactory tubercle, the amygdala, the piriform cortex, and the entorhinal cortex. The anterior olfactory nucleus projects, via the anterior commissure, to the contralateral olfactory bulb, inhibiting it. The piriform cortex projects to the medial dorsal nucleus of the thalamus, which then projects to the orbitofrontal cortex. The orbitofrontal cortex mediates conscious perception of the odor. The 3-layered piriform cortex projects to a number of thalamic and hypothalamic nuclei, the hippocampus and amygdala and the orbitofrontal cortex but its function is largely unknown. The entorhinal cortex projects to the amygdala and is involved in emotional and autonomic responses to odor. It also projects to the hippocampus and is involved in motivation and memory. Odor information is stored in long-term memory and has strong connections to emotional memory. This is possibly due to the olfactory system's close anatomical ties to the limbic system and hippocampus, areas of the brain that have long been known to be involved in emotion and place memory, respectively. Olfactory sensory neurons project axons to the brain within the olfactory nerve, (cranial nerve I). These axons pass to the olfactory bulb through the cribriform plate, which in turn projects olfactory information to the olfactory cortex and other areas. The axons from the olfactory receptors converge in the outer layer of the olfactory bulb within small (~50 micrometers in diameter) structures called glomeruli. Mitral cells, located in the inner layer of the olfactory bulb, form synapses with the axons of the sensory neurons within glomeruli and send the information about the odor to other parts of the olfactory system, where multiple signals may be processed to form a synthesized olfactory perception. A large degree of convergence occurs, with twenty-five thousand axons synapsing on twenty five or so mitral cells, and with each of these mitral cells projecting to multiple glomeruli. Mitral cells also project to periglomerular cells and granular cells that inhibit the mitral cells surrounding it (lateral inhibition). Granular cells also mediate inhibition and excitation of mitral cells through pathways from centrifugal fibers and the anterior olfactory nuclei. The mitral cells leave the olfactory bulb in the lateral olfactory tract, which synapses on five major regions of the cerebrum: the anterior olfactory nucleus, the olfactory tubercle, the amygdala, the piriform cortex, and the entorhinal cortex. The anterior olfactory nucleus projects, via the anterior commissure, to the contralateral olfactory bulb, inhibiting it. The piriform cortex projects to the medial dorsal nucleus of the thalamus, which then projects to the orbitofrontal cortex. The orbitofrontal cortex mediates conscious perception of the odor. The 3-layered piriform cortex projects to a number of thalamic and hypothalamic nuclei, the hippocampus and amygdala and the orbitofrontal cortex but its function is largely unknown. The entorhinal cortex projects to the amygdala and is involved in emotional and autonomic responses to odor. It also projects to the hippocampus and is involved in motivation and memory. Odor information is stored in long-term memory and has strong connections to emotional memory. This is possibly due to the olfactory system's close anatomical ties to the limbic system and hippocampus, areas of the brain that have long been known to be involved in emotion and place memory, respectively.

24. Olfactory pathway�. Olfactory receptor?olfactory bulb (mitral cells) and tract?five major regions of the cerebrum anterior olfactory nucleus olfactory tubercle Amygdala piriform cortex?medial dorsal nucleus of the thalamus ?orbitofrontal cortex (mediates conscious perception of the odor) entorhinal cortex ?amygdala (emotional and autonomic responses to odor) ? hippocampus (motivation and memory) Mitral cells also project to periglomerular cells and granular cells that inhibit the mitral cells surrounding it (lateral inhibition) Odour information is stored in long-term memory and has strong connections to emotional memory. This is possibly due to the olfactory system's close anatomical ties to the limbic system and hippocampus, areas of the brain that have long been known to be involved in emotion and place memory, respectively.

25. Mechanism olfaction �lock and key First proposed by Roman philosopher Lucretius (1st Century BCE) Cloning of olfactory receptor proteins by Linda B. Buck and Richard Axel (Nobel Prize in 2004), and subsequent pairing of odor molecules to specific receptor proteins. Each odour receptor molecule recognizes only a particular molecular feature or class of odour molecules. Mammals have about a thousand genes that code for odor reception- each olfactory receptor neuron expresses only one functional odor receptor.

26. Olfactory receptor

27. Perception of smell Combinatorial receptor codes The odorant receptor family is used in a combinatorial manner to detect odorants and encode their unique identities. Different odorants are detected by different combinations of receptors and thus have different receptor codes. These codes are translated by the brain into diverse odour perceptions The immense number of potential receptor combinations is the basis for our ability to distinguish and form memories of more than 10,000 different odorants

28. Summary of characteristics of olfactory system Olfactory area- varies between species (dogs vs man) Man has 200�400 mm2, density 5�104 receptor cells/mm2. Receptor cells have modified cilia to increase surface area. They are derived from the basal cells, regenerating every month ReceptorsOlfaction is mediated by G-protein coupled receptors in the cells which interact with a specific adenyl cyclase (type 111) within the neuroepithelium. Receptors are coded by between 500 and 1000 genes, but each cell has one or two specific receptors ThresholdOlfactory responses show both variations in thresholds and adaptation. Threshold concentrations can vary by 1010 depending on the chemical nature of stimuli. The threshold of perception is lower than identification: a smell is sensed before it is recognized. Thresholds depend on levels of inhibitory activity, which are generated by higher centres. Some animals, particularly dogs, have much lower thresholds. AdaptationOlfactory responses show marked adaptation and thresholds increase with exposure. Recovery of the EOG is rapid when the stimulus is withdrawn. Adaptation is a peripheral and central phenomenon. Cross adaptations are present between odours at high concentrations, whereas cross facilitations occur near threshold values.

29. Disorders of olfaction Anosmia � inability to smell Hyposmia � decreased ability to smell Hyperosmia � an abnormally acute sense of smell. Dysosmia � things smell different than they should Cacosmia � things smell like faeces Parosmia � things smell worse than they should Phantosmia � "hallucinated smell," often unpleasant in nature Olfactory agnosia refers to an inability to recognize an odour sensation, even though olfactory processing, language and general intellectual functions are essentially intact, as in some stroke patients Other less commonly used terms include heterosmia � a condition where all odours smell the same; presbyosmia � a decline in smell sense with age and osmophobia � a dislike or fear of certain smells

30. Smell tests 2 tests are used clinically, threshold and suprathreshold. The latter is normally a forced choice test such as the University of Pennsylvania smell identification test (UPSIT) The clinical importance of testing is to distinguish patients who have a disorder from those who malinger and seek compensation

31. UPSIT 40-item University of Pennsylvania Smell Identification Test (UPSIT) Most widely used olfactory test administered to an estimated 400,000 patients since its development self-administered in 10�15 minutes test consists of four booklets containing ten microencapsulated (�scratch and sniff�) odourants apiece. Test results are in terms of a percentile score of a patient's performance relative to age- and sex-matched controls, and olfactory function can be classified on an absolute basis into one of six categories: normosmia, mild microsmia, moderate microsmia, severe microsmia, anosmia and probable malingering Since chance performance is 10 out of 40, very low UPSIT scores reflect avoidance, and hence recognition, of the correct answer, allowing for determination of malingering. The reliability of this test is very high

32. QUIZ What is the predominant epithelium lining the nasal cavity? Stratified squamous-keratinising Stratified squamous non-keratinising Cuboid Ciliated, pseudostratified columnar What is the parasympathetic supply to the nasal glands? Deep petrosal nerve Great petrosal nerve Vagal nerve Lesser petrosal nerve What is the predominant histamine receptor in the nasal cavity? H1 H2 H3 H4

33. QUIZ Each olfactory receptor recognises how many deodorants with a particular configuration? One Two Three Unlimited Where is the greatest resistance in the nasal cavity? Postnasal space External nasal valve Internal nasal valve Superior meatus Olfactory receptor are or tranduce signals via: G-protein linked to ion channels G-protein linked to protein kinase Ion channels Enzymes