Talk:Respiratory System - Upper Respiratory Tract

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Cite this page: Hill, M.A. (2021, March 8) Embryology Respiratory System - Upper Respiratory Tract. Retrieved from


Lungova V & Thibeault SL. (2020). Mechanisms of larynx and vocal fold development and pathogenesis. Cell. Mol. Life Sci. , , . PMID: 32253462 DOI.

Mechanisms of larynx and vocal fold development and pathogenesis

The larynx and vocal folds sit at the crossroad between digestive and respiratory tracts and fulfill multiple functions related to breathing, protection and phonation. They develop at the head and trunk interface through a sequence of morphogenetic events that require precise temporo-spatial coordination. We are beginning to understand some of the molecular and cellular mechanisms that underlie critical processes such as specification of the laryngeal field, epithelial lamina formation and recanalization as well as the development and differentiation of mesenchymal cell populations. Nevertheless, many gaps remain in our knowledge, the filling of which is essential for understanding congenital laryngeal disorders and the evaluation and treatment approaches in human patients. This review highlights recent advances in our understanding of the laryngeal embryogenesis. Proposed genes and signaling pathways that are critical for the laryngeal development have a potential to be harnessed in the field of regenerative medicine. KEYWORDS: Congenital; Embryology; Laryngeal; Vocal cords PMID: 32253462 DOI: 10.1007/s00018-020-03506-x



Establishment of smooth muscle and cartilage juxtaposition in the developing mouse upper airways

Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19444-9. doi: 10.1073/pnas.1313223110. Epub 2013 Nov 11.

Hines EA, Jones MK, Verheyden JM, Harvey JF, Sun X. Author information

Abstract In the trachea and bronchi of the mouse, airway smooth muscle (SM) and cartilage are localized to complementary domains surrounding the airway epithelium. Proper juxtaposition of these tissues ensures a balance of elasticity and rigidity that is critical for effective air passage. It is unknown how this tissue complementation is established during development. Here we dissect the developmental relationship between these tissues by genetically disrupting SM formation (through Srf inactivation) or cartilage formation (through Sox9 inactivation) and assessing the impact on the remaining lineage. We found that, in the trachea and main bronchi, loss of SM or cartilage resulted in an increase in cell number of the remaining lineage, namely the cartilage or SM, respectively. However, only in the main bronchi, but not in the trachea, did the loss of SM or cartilage lead to a circumferential expansion of the remaining cartilage or SM domain, respectively. In addition to SM defects, cartilage-deficient tracheas displayed epithelial phenotypes, including decreased basal cell number, precocious club cell differentiation, and increased secretoglobin expression. These findings together delineate the mechanisms through which a cell-autonomous disruption of one structural tissue can have widespread consequences on upper airway function. KEYWORDS: airway development, tracheomalacia

PMID 24218621

Frontal sinusitis caused by first and second secondary middle turbinates co-existing with an accessory middle turbinate

Jpn J Radiol. 2013 Mar 1. [Epub ahead of print]

Choi JH. Source Department of Otolaryngology Head and Neck Surgery, Sanggye Paik Hospital, College of Medicine, Inje University, 761-1 Sanggye-7-dong Nowon-gu, Seoul, 139-707, Republic of Korea,


The anatomy of the nasal cavity and the paranasal sinuses is complex. After widespread use of endoscopes and computed tomography, many variations have been described. Secondary and accessory middle turbinates (AMTs) can mimic the real middle turbinate. These variations may arise during embryological development. I believe that detailed knowledge of anomalies of the sinonasal tract is critical for successful management, and important in enabling the surgeon to perform safe surgery. Failure to recognize the variants could lead to inadvertent damage to the orbital lamina papyracea during surgery. Knowledge and correct description of anatomical variations of the turbinates by use of computed tomography images will aid achievement of correct diagnosis and surgical management and avoidance of potential complications during endoscopic procedures. To the best of my knowledge, this is the first report in the world literature of sinusitis caused by first and second secondary middle turbinates co-existing with an AMT.

PMID 23456544


Prenatal Development of the Maxillary Sinus: A Perspective for Paranasal Sinus Surgery

Otolaryngol Head Neck Surg. 2012 Jan 20. [Epub ahead of print]

Nuñez-Castruita A, López-Serna N, Guzmán-López S. Source Department of Embryology, School of Medicine of the Universidad Autónoma de Nuevo León, Monterrey, México. Abstract Objective. To review the prenatal development of the maxillary sinus under the perspective of the sinus surgery.Study Design. Cross-sectional study.Setting. Basic embryology laboratory.Subjects and Methods. Morphometry and morphology of the maxillary sinus and its ostium were studied under stereomicroscopy in 100 human fetuses from the 9th to the 37th week. Fetuses were obtained from the Fetal Collection of the School of Medicine of the Universidad Autónoma de Nuevo León. Approval was granted by the Ethics Committee. Statistics were applied.Results. The maxillary sinus begins its development at the 10th week. On the 37th week, the anterior-posterior diameter has a mean of 4.36 mm; ossification of the medial wall was absent, and the floor was located below the attachment of the inferior turbinate. Septa and recesses were temporarily observed. Some variations in shape were observed; however, only the oval shape persisted. Maxillary sinus hypoplasia was not found, although asymmetry was present in 30% of cases. The ostium was located at the anterior third of the ethmoid infundibulum; its final dimensions were 1.96 mm in length and 0.44 mm in width. The mean length between the ostium to the lamina papyracea and nasolacrimal duct was 1 mm. One case of double maxillary sinus was observed. Significant difference between the variables, in accordance with the age, was found (P = .02).Conclusion. Knowledge of prenatal development of the maxillary sinus improves the perspective of the sinus surgeon and helps the understanding of postnatal anatomy, especially in children.

PMID 22267494


Computed tomography measurements of different dimensions of maxillary and frontal sinuses

BMC Med Imaging. 2011 Apr 5;11:8.

Sahlstrand-Johnson P, Jannert M, Strömbeck A, Abul-Kasim K. Source Department of Oto-Rhino-Laryngology, Faculty of Medicine, Lund University, Skåne University Hospital, Malmö, Sweden.

Abstract BACKGROUND: We have previously proposed the use of Doppler ultrasound to non-invasively stage sinus infection, as we showed that acoustic streaming could be generated in nonpurulent sinus secretions and helped to distinguish it from mucopurulent sinus secretions. In order to continue this development of a clinically applicable Doppler equipment, we need to determine different dimensions of the paranasal sinuses, especially the thickness of the anterior wall of the maxillary sinus (at the canine fossa). To the best of our knowledge, this is the first report on the thickness of the canine fossa. This study aimed to (a) estimate different dimensions of the maxillary and frontal sinuses measured on computed tomography (CT) of the head, (b) define cut-off values for the normal upper and lower limits of the different measured structures, (c) determine differences in age, side and gender, (d) compare manually and automatically estimated maxillary sinuses volumes, and (e) present incidental findings in the paranasal sinuses among the study patients. METHODS: Dimensions of 120 maxillary and frontal sinuses from head CTs were measured independently by two radiologists. RESULTS: The mean value of the maxillary sinus volume was 15.7±5.3 cm3 and significantly larger in males than in females (P=0.004). There was no statistically significant correlation between the volume of maxillary sinuses with age or side. The mean value of the bone thickness at the canine fossa was 1.1±0.4 mm. The automatically estimated volume of the maxillary sinuses was 14-17% higher than the calculated volume. There was high interobserver agreement with regard to the different measurements performed in this study. Different types of incidental findings of the paranasal sinuses were found in 35% of the patients. CONCLUSION: We presented different dimensions of the maxillary and frontal sinuses on CTs. We believe that our data are necessary for further development of a clinically applicable Doppler equipment for staging rhinosinusitis.

PMID 21466703


Nasal septum morphology in human fetuses in computed tomography images

Eur J Med Res. 2010 Nov 4;15 Suppl 2:202-5.

Teul I, Slawinski G, Lewandowski J, Dzieciolowska-Baran E, Gawlikowska-Sroka A, Czerwinski F. Source Department of Anatomy, Pomeranian Medical University, Szczecin, Poland. Abstract OBJECTIVES: Nasal septum deformation (NSD) may cause breathing dysfunction. The reason for a septal deviation is the developmental anomaly in growth of the elastic septum or its skeleton. Such a type of deviation is called physiological. Some deviations can result from the prenatal trauma. The aim of the work was the analysis of the anatomy of the nasal cavity with a special interest focused on the nasal septum and its deviation. MATERIAL AND METHODS: The nasal cavity with its bones and septum was analyzed in CT images of 105 spontaneously aborted fetuses (57 males and 48 females) aged 12 and 40 weeks of gestation. We attempted to assess the morphometric development of the nasal cavity with tomographic scanning methods and to detect anatomical variations. RESULTS: In 15 (14.3%) fetuses, NSD were detected on radiological sections. The angle between the virtual line from the sphenoid sinus ostium through limen nasi and the horizontal plane was 33.6 ±2.3°, on average. CONCLUSIONS: NSD may already be found in fetuses. The observation of the nasal cavity development enables to evaluate the growth and symmetry of the nasal septum and to foretell predispositions for dysfunction in the upper respiratory tract.

PMID 21147652

Understanding the formation of maxillary sinus in Japanese human foetuses using cone beam CT

Surg Radiol Anat. 2010 Oct;32(8):745-51. Epub 2010 May 21.

Asaumi R, Sato I, Miwa Y, Imura K, Sunohara M, Kawai T, Yosue T. Source Department of Oral and Maxillofacial Radiology, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20 Fujimi Chiyoda-ku, Tokyo 102-8159, Japan.

Abstract The formation of the maxillary sinus (MS) is tied to the maturation of the craniofacial bones during development. The MS and surrounding bone matrices in Japanese foetal specimens were inspected using cone beam computed tomography relative to the nasal cavity (NC) and the surrounding bones, including the palatine bone, maxillary process, inferior nasal concha and lacrimal bone. The human foetuses analysed were 223.2 ± 25.9 mm in crown-rump length (CRL) and ranged in estimated age from 20 to 30 weeks of gestation. The amount of bone in the maxilla surrounding the MS increased gradually between 20 and 30 weeks of gestation. Various calcified structures that formed the bone matrix were found in the cortical bone of the maxilla, and these calcified structures specifically surrounded the deciduous tooth germs. By 30 weeks of gestation, the uncinate process of the ethmoid bone formed a border with the maxilla. The distance from the midline to the maximum lateral surface border of the MS combined with the width from the midline to the maximum lateral surface border of the inferior nasal concha showed a high positive correlation with CRL in Japanese foetuses. There appears to be a complex correlation between the MS and NC formation during development in the Japanese foetus. Examination of the surrounding bone indicated that MS formation influences maturation of the maxilla and the uncinate process of the ethmoid bone during craniofacial bone development. PMID: 20490493

What's in a name? Eponyms in head and neck imaging

Clin Radiol. 2010 Mar;65(3):237-45. Epub 2009 Dec 22.

Hoang JK, Eastwood JD, Glastonbury CM. Source Department of Radiology, Division of Neuroradiology, Duke University Medical Center, Erwin Road, Durham, NC 27710, USA. Abstract Head and neck (H&N) eponyms serve to honour physicians who have made important contributions. Compared with more descriptive diagnostic names, eponyms can sometimes be confusing, especially to the novice. Adding to the confusion, eponyms are sometimes applied incorrectly. Nevertheless, their use remains common in the medical literature and clinical practice. Familiarity with H&N eponyms is important for accurate communication with radiology colleagues and clinicians. Some eponyms describe potentially fatal infections and their urgency should be appreciated. Other eponyms, such as those for inner ear congenital anomalies, are probably best avoided as they can be used imprecisely and cause confusion. This review summarizes the clinical and imaging findings of some common and important H&N eponyms under the following categories of disease: (1) neck infections, (2) diseases in the temporal bone, (3) orbital diseases, and (4) sinus disease. Copyright (c) 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

PMID 20152281


The upper airway: congenital malformations

Paediatr Respir Rev. 2006;7 Suppl 1:S260-3. Epub 2006 Jun 6.

Daniel SJ. Source Department of Otolaryngology, Head and Neck Surgery, McGill University Health Centre, Montreal Children's Hospital, 2300 Tupper Street, B-240, Montreal, Quebec, Canada H3H 1P3.


The upper airway extends from the nasal aperture to the subglottis and can be the site of multiple types of congenital malformations leading to anatomical or functional obstruction. This can cause severe respiratory distress. Newborns are obligate nasal breathers; therefore nasal obstruction can lead to airway compromise and respiratory distress. The etiologies are varied and include, choanal atresia, pyriform aperture stenosis, and rarely tumors such as glioma, encephalocele, teratoma, or dermoid. More common upper airway congenital anomalies include laryngomalacia, vocal cord paralysis, and subglottic stenosis. Laryngolmalacia is the most common congenital laryngeal anomaly. Inspiratory stridor often does not present until two weeks after birth and resolves by 18 months of age. Most cases are managed with watchful waiting. Severe cases require a surgical intervention. Bilateral vocal cord paralysis is usually idiopathic. In certain cases, paralysis may occur secondary to central nervous system abnormality including Arnold-Chiari malformation, cerebral palsy, hydrocephalus, myelomeningocele, spina bifida, or hypoxia. Severe cases may necessitate endotracheal intubation and tracheostomy. Congenital subglottic stenosis is the third most common laryngeal anomaly. It is defined as a diameter of less than 4mm of the cricoid region in a full-term infant, and less than 3mm in a premature infant. This condition is the most common laryngeal anomaly that requires tracheotomy in newborns. Laryngotracheoplasty may be required to achieve decanulation. Knowledge of the upper airway embryological development and congenital anomalies is off prime importance in assessing the newborn with respiratory distress. In most cases flexible endoscopy establishes the diagnosis. Management is tailored to each condition and its degree of severity.

PMID 16798587


Development, structure and function of the upper airways

Paediatr Respir Rev. 2004 Mar;5(1):2-8.

Pohunek P. Source 2nd Paediatric Department, Division of Paediatric Pulmonology, University Hospital Motol, V Uvalu 84, 150 06 Praha 5, Czech Republic. Abstract The upper airways play an essential role in the conduction of air into the lungs, and influence the properties of the inhaled air by both the anatomical structure and the functional properties of the mucosa, cartilages and neural and lymphatic tissues. The upper airways also play an important role in the protection of the lower airways, in the formation of the sound and host the sense of olfaction. Main events in the development of the upper airways happen during early embryonic periods. Postnatally, the growth of the airways follows the growth of the skeleton of the head and of the neck and thorax. Growth is accelerated mainly during the first 2 years of life; thereafter, it linearly follows the growth of the body. For a profound understanding of the function of the upper airways, it is important to understand the main developmental events during both prenatal and postnatal periods.

PMID 15222948


Formation and enlargement of the paranasal sinuses in normal and cleft lip and palate human fetuses

Cleft Palate Craniofac J. 1997 Nov;34(6):483-9.

Smith TD, Siegel MI, Mooney MP, Burrows AM, Todhunter JS. Source School of Physical Therapy, Slippery Rock University, PA 16057, USA.

Abstract OBJECTIVE: Comparisons of paranasal sinus morphology between humans with and without cleft lip and palate (CLP) have yielded conflicting opinions regarding size differences. Although postnatal samples have been investigated, no studies have compared paranasal sinus volumes between cleft and noncleft human fetuses. METHOD: The nasal cavities of 20 'normal' and 9 CLP human fetuses (8-21 weeks' postmenstrual age) were examined to assess prenatal volumetric changes of the maxillary sinuses, anterior and posterior ethmoidal air cells, and sphenoidal sinuses. Lengths and volumes of right and left maxillary and sphenoidal sinuses were calculated from histologically prepared sections using a computer reconstruction technique, and regression equations were generated to assess the enlargement rates. RESULTS: All paranasal sinuses were found among both normal and CLP specimens in the same locations and in similar age ranges. However, greater shape asymmetry was noted for all sinuses in CLP compared to normal specimens. In the normal sample, results indicated significant (p < .05) correlations between right or left maxillary sinus length (R2 = 0.49, 0.54) and volume (R2 = 0.67, 0.68), and increasing postmenstrual age, but no significant (p > .05) correlations were observed for right or left sphenoidal sinus length or volumes and postmenstrual age. Maxillary sinus length changes were best described by second-order polynomial regression equations, and volume changes were best described by logarithmic equations. When individual right or left sinuses of CLP specimens were compared to the mean of the normal sample, one maxillary sinus was significantly (p < .05) larger, and 9 maxillary sinuses were not significantly (p > .05) different. Sphenoidal sinus lengths and volumes of CLP specimens were within the same range compared to these dimensions for the normal sample. CONCLUSION: Results on normal specimens indicate that maxillary sinuses exhibit second-trimester length and volume increases, whereas sphenoidal sinuses are more variable. This study suggests a similar timing of sinus formation in normal and CLP fetuses, but shape asymmetries are frequently detected among CLP specimens. In particular, the sphenoidal sinuses may be altered in shape and size by adjacent, hypertrophic cartilaginous structures in CLP fetuses. These results indicate that the maxillary sinuses of CLP fetuses are not deficient in size compared to noncleft fetuses.

PMID 9431465

Morphogenic mechanisms in the development of ethmoidal sinuses

Anat Rec. 1997 Sep;249(1):96-102.

Monteiro VJ, Dias MP. Source Department of Anatomy, S.D.M. College of Dental Sciences and Hospital, Sattur, Dharwad, India. Erratum in Anat Rec 1998 Jan;250(1):121. Abstract BACKGROUND: The current teaching in regard to the development of paranasal sinuses is that they are evaginations of the nasal cavity; this seems to totally ignore earlier observations. METHODS: Serial coronal sections of the heads of 23 human fetuses from 18-mm CR length to 282-mm CR length were stained by various methods and studied. RESULTS: The ethmoidal sinuses develop by the formation of 'turbinal cushions' at the 33-mm CR stage. By the 45-mm CR stage, the cushions have grown toward each other and made contact. The epithelium covering the cushions also proliferates to fill up the enclosed space, and it proliferates dorsoventrally as well. The cushions fuse at the 50-mm CR stage. The fusion part of the process should be described as a 'constriction' of the nasal cavity. Next, the epithelium disintegrates and results in the formation of the sinus. This part of the process only can be described as an 'evagination' of the nasal cavity. As the advancing epithelium of the sinus encounters cartilage, it causes disintegration of the developing nasal cartilage. This area of disintegration appears as a spot stained pink with H & E, black with mucicarmine, and yellow with van Gieson's stains, respectively. These spots are seen between the 89-mm and the 225-mm CR stages (both inclusive). CONCLUSIONS: Two mechanisms operate in the development of ethmoidal sinuses: constriction of the nasal cavity by a pair of turbinal cushions, and evagination from the nasal cavity by proliferation and subsequent disintegration of the nasal epithelium.

PMID 9294654