In humans, the vocal cords, also known as vocal folds, are folds of throat tissues that are key in creating sounds through Speech. The length of the vocal cords affects the pitch of voice, similar to a violin string. Open when breathing and vibrating for speech or singing, the folds are controlled via the recurrent laryngeal branch of the vagus nerve. They are composed of twin infoldings of mucous membrane stretched horizontally, from back to front, across the larynx. They vibration, modulating the flow of air being expelled from the lungs during phonation.
The 'true vocal cords' are distinguished from the 'false vocal folds', known as or ventricular folds, which sit slightly superior to the more delicate true folds. These have a minimal role in normal phonation, but can produce deep sonorous tones, screams and growls.
The length of the vocal fold at birth is approximately six to eight millimeters and grows to its adult length of eight to sixteen millimeters by adolescence. DHT, an androgen metabolite of testosterone which is secreted by the gonads, causes changes in the cartilages and musculature of the larynx when present in high enough concentrations, such as during an adolescent boy's puberty: The thyroid prominence appears, the vocal folds lengthen and become rounded, and the epithelium thickens with the formation of three distinct layers in the lamina propria.. These changes are only partially reversible via reconstructive surgery such as chondrolaryngoplasty, feminization laryngoplasty, and laser tuning of the vocal cords.
HA is a bulky, negatively charged glycosaminoglycan, whose strong affinity with water procures hyaluronic acid its viscoelastic and shock absorbing properties essential to vocal biomechanics. Viscosity and elasticity are critical to voice production. Chan, Gray and Titze, quantified the effect of hyaluronic acid on both the viscosity and the elasticity of vocal folds by comparing the properties of tissues with and without HA. The results showed that removal of hyaluronic acid decreased the stiffness of the vocal cords by an average of 35%, but increased their dynamic viscosity by an average of 70% at frequencies higher than 1 Hz. Newborns have been shown to cry an average of 6.7 hours per day during the first 3 months, with a sustained pitch of 400–600 Hz, and a mean duration per day of 2 hours. Similar treatment on adult vocal cords would quickly result in edema, and subsequently aphonia. Schweinfurth and al. presented the hypothesis that high hyaluronic acid content and distribution in newborn vocal cords is directly associated with newborn crying endurance. These differences in newborn vocal fold composition would also be responsible for newborns inability to articulate sounds, besides the fact that their lamina propria is a uniform structure with no vocal ligament. The layered structure necessary for phonation will start to develop during the infancy and until the adolescence.
The in the newborn Reinke's space are immature, showing an oval shape, and a large nucleus-cytoplasm ratio. The rough endoplasmic reticulum and Golgi apparatus, as shown by electron micrographs, are not well developed, indicating that the cells are in a resting phase. The collagenous and reticular fibers in the newborn the vocal cords are fewer than in the adult one, adding to the immaturity of the vocal fold tissue.
In the infant, many fibrous components were seen to extend from the macula flava towards the Reinke's space. Fibronectin is very abundant in the Reinke's space of newborn and infant. Fibronectin is a glycoprotein that is believed to act as a template for the oriented deposition of the collagen fibers, stabilizing the collagen fibrils. Fibronectin also acts as a skeleton for the elastic tissue formation. Reticular and collagenous fibers were seen to run along the edges of the vocal cords throughout the entire lamina propria. Fibronectin in the Reinke's space appeared to guide those fibers and orient the fibril deposition. The elastic fibers remained sparse and immature during infancy, mostly made of microfibrils. The fibroblasts in the infant Reinke's space were still sparse but spindle-shaped. Their rough endoplasmic reticulum and Golgi apparatus were still not well developed, indicating that despite the change in shape, the fibroblasts still remained mostly in a resting phase. Few newly released materials were seen adjacent to the fibroblasts. The ground substance content in the infant Reinke's space seemed to decrease over time, as the fibrous component content increased, thus slowly changing the vocal fold structure.
Testosterone, an androgen secreted by the testes, will cause changes in the cartilages and musculature of the larynx for males during puberty, and to a lesser extent to females sex assignment and others such as intersex individuals as well as those who are androgen deficient if they are given masculinizing hormone therapy. In females, androgens are secreted principally by the adrenal cortex and the ovaries and can have irreversible masculinizing effects if present in high enough concentration. In males, they are essential to male sexuality. In muscles, they cause a hypertrophy of striated muscles with a reduction in the fat cells in , and a reduction in the whole body fatty mass. Androgens are the most important hormones responsible for the passage of the boy-child voice to adult male voice, and the change is irreversible without reconstructive surgery such as feminization laryngoplasty. The thyroid prominence, which contains the vocal cords appears, the vocal folds lengthen and become rounded, and the epithelium thickens with the formation of three distinct layers in the lamina propria.Abitbol, A. & Abitbol, P. (2003). "The Larynx: A Hormonal Target". In Rubin, J. S., Sataloff, R. T., & Korovin, G. S. (eds.), Diagnosis and Treatment of Voice Disorders (pp. 355–380). Clifton Park, New York: Delmar Learning. These changes are also irreversible without surgery, albeit the thyroid/laryngeal prominence, also known as an Adam's apple can be potentially diminished via a tracheal shave or feminization laryngoplasty.
There is a steady increase in the elastin content of the lamina propria as humans age (elastin is a yellow scleroprotein, the essential constituent of the elastic connective tissue) resulting in a decrease in the ability of the lamina propria to expand caused by cross-branching of the elastin fibers. Among other things, this leads to the mature voice being better suited to the rigors of opera.
The extracellular matrix of the vocal cord LP is composed of fibrous proteins such as collagen and elastin, and interstitial molecules such as hyaluronic acid, a non-sulfated glycosaminoglycan. While the SLP is rather poor in elastic and collagenous fibers, the ILP and DLP are mostly composed of it, with the concentration of elastic fibers decreasing and the concentration of collagenous fibers increasing as the vocalis muscle is approached. Fibrous proteins and interstitial molecules play different roles within the extracellular matrix. While collagen (mostly type I) provides strength and structural support to the tissue, which are useful to withstanding stress and resisting deformation when subjected to a force, elastin fibers bring elasticity to the tissue, allowing it to return to its original shape after deformation. Interstitial proteins, such as HA, plays important biological and mechanical roles in the vocal cord tissue. In the vocal cord tissue, hyaluronic acid plays a role of shear-thinner, affecting the tissue viscosity, space-filler, shock absorber, as well as wound healing and cell migration promoter. The distribution of those proteins and interstitial molecules has been proven to be affected by both age and gender, and is maintained by the fibroblasts.
Hirano et al. previously found that the newborns did not have a true lamina propria, but instead had cellular regions called maculae flavae, located at the anterior and posterior ends of the loose vocal fold tissue. Boseley and Hartnick examined at the development and maturation of pediatric human vocal fold lamina propria. Hartnick was the first one to define each layer by a change in their cellular concentration. He also found that the lamina propria monolayer at birth and shortly thereafter was hypercellular, thus confirming Hirano's observations. By 2 months of age, the vocal fold started differentiating into a bilaminar structure of distinct cellular concentration, with the superficial layer being less densely populated than the deeper layer. By 11 months, a three-layered structure starts to be noted in some specimens, again with different cellular population densities. The superficial layer is still hypocellular, followed by an intermediate more hypercellular layer, and a deeper hypercellular layer, just above the vocalis muscle. Even though the vocal cords seem to start organizing, this is not representative of the trilaminar structure seen in adult tissues, where the layer are defined by their differential elastin and collagen fiber compositions. By 7 years of age, all specimens show a three-layered vocal fold structure, based on cellular population densities. At this point, the superficial layer was still hypocellular, the middle layer was the hypercellular one, with also a greater content of elastin and collagen fibers, and the deeper layer was less cellularly populated. Again, the distinction seen between the layers at this stage is not comparable to that seen in the adult tissue. The maturation of the vocal cords did not appear before 13 years of age, where the layers could be defined by their differential fiber composition rather than by their differential cellular population. The pattern now show a hypocellular superficial layer, followed by a middle layer composed predominantly of elastin fiber, and a deeper layer composed predominantly of collagen fibers. This pattern can be seen in older specimens up to 17 years of age, and above. While this study offers a nice way to see the evolution from immature to mature vocal cords, it still does not explain what is the mechanism behind it.
Sato et al. carried out a histopathologic investigation of unphonated human vocal cords. Vocal fold mucosae, which were unphonated since birth, of three young adults (17, 24, and 28 years old) were looked at using light and electron microscopy. The results show that the vocal fold mucosae were hypoplastic, and rudimentary, and like newborns, did not have any vocal ligament, Reinke's space, or layered structure. Like newborns, the lamina propria appeared as a uniform structure. Some were present in the macula flava, but started to show some signs of degeneration. The stellate cells synthesized fewer extracellular matrix molecules, and the cytoplasmic processes were shown to be short and shrinking, suggesting a decreased activity. Those results confirm the hypothesis that phonation stimulates stellate cells into producing more extracellular matrix.
Furthermore, using a specially designed bioreactor, Titze et al. showed that fibroblasts exposed to mechanical stimulation have differing levels of extracellular matrix production from fibroblasts that are not exposed to mechanical stimulation. The gene expression levels of extracellular matrix constituents such as fibronectin, MMP1, decorin, fibromodulin, hyaluronic acid synthase 2, and CD44 were altered. All those genes are involved in extracellular matrix remodeling, thus suggesting that mechanical forces applied to the tissue, alter the expression levels of extracellular matrix related genes, which in turn allow the cells present in the tissue to regulate the extracellular matrix constituent synthesis, thus affecting the tissue's composition, structure, and biomechanical properties. In the end, cell-surface receptors close the loop by giving feedback on the surrounding extracellular matrix to the cells, affecting also their gene expression level.
Vocal fold phonatory functions are known to change from birth to old age. The most significant changes occur in development between birth and puberty, and in old age. Hirano et al. previously described several structural changes associated with aging, in the vocal fold tissue. Some of those changes are: a shortening of the membranous vocal fold in males, a thickening of the vocal fold mucosa and cover in females, and a development of edema in the superficial lamina propria layer in both sexes. Hammond et al. observed that the hyaluronic acid content in the vocal fold lamina propria was significantly higher in males than in females. Although all those studies did show that there are clear structural and functional changes seen in the human vocal cords which are associated with gender and age, none really fully elucidated the underlying cause of those changes. In fact, only a few recent studies started to look at the presence and role of hormone receptors in the vocal cords. Newman et al. found that hormone receptors are indeed present in the vocal cords, and show a statistical distribution difference with respect to age and gender. They have identified the presence of androgen, estrogen, and progesterone receptors in , and of the vocal cords, suggesting that some of the structural changes seen in the vocal cords could be due to hormonal influences. In this specific study, androgen and progesterone receptors were found more commonly in males than in females. In others studies, it has been suggested that the estrogen/androgen ratio be partly responsible for the voice changes observed at menopause. As previously said, Hammond et al. showed than the hyaluronic acid content was higher in male than in female vocal cords. Bentley et al. demonstrated that sex skin swelling seen in monkey was due to an increase in hyaluronic acid content, which was in fact mediated by estrogen receptors in dermal fibroblasts. An increase in collagen biosynthesis mediated by the estrogen receptors of dermal fibroblasts was also observed. A connection between hormone levels, and extracellular matrix distribution in the vocal cords depending on age and gender could be made. More particularly a connection between higher hormone levels and higher hyaluronic acid content in males could exist in the human vocal fold tissue. Although a relationship between hormone levels and extracellular matrix biosynthesis in vocal fold can be established, the details of this relationship, and the mechanisms of the influence has not been elucidated yet.
The perceived pitch of a person's voice is determined by a number of different factors, most importantly the fundamental frequency of the sound generated by the larynx. The fundamental frequency is influenced by the length, size, and tension of the vocal folds. This frequency averages about 125 hertz in an adult male, 210 Hz in adult females, and over 300 Hz in children. Depth kymography is an imaging method to visualize the complex horizontal and vertical movements of vocal folds.
The vocal folds generate a sound rich in . The harmonics are produced by collisions of the vocal folds with themselves, by recirculation of some of the air back through the trachea, or both.Ingo Titze, University of Iowa. Some singers can isolate some of those harmonics in a way that is perceived as singing in more than one pitch at the same time—a technique called overtone singing or throat singing such as in the tradition of Tuvan throat singing.
Any injury to human vocal folds elicits a wound healing process characterized by disorganized collagen deposition and, eventually, formation of scar tissue. Verdolini and her group sought to detect and describe acute tissue response of injured rabbit vocal cord model. They quantified the expression of two biochemical markers: interleukin 1 and prostaglandin E2, which are associated with acute wound healing. They found the secretions of these inflammatory mediators were significantly elevated when collected from injured vocal cords versus normal vocal cords. This result was consistent with their previous study about the function of IL-1 and PGE-2 in wound healing. Investigation about the temporal and magnitude of inflammatory response in the vocal cords may benefit for elucidating subsequent pathological events in vocal fold wounding, which is good for clinician to develop therapeutic targets to minimize scar formation. In the proliferative phase of vocal cord wound healing, if the production of hyaluronic acid and collagen is not balanced, which means the hyaluronic acid level is lower than normal, the fibrosis of collagen cannot be regulated. Consequently, regenerative-type wound healing turns to be the formation of scar. Scarring may lead to the deformity of vocal fold edge, the disruption of lipopolysaccharides viscosity and stiffness. Patients suffering from vocal fold scar complain about increased phonatory effort, vocal fatigue, breathlessness, and dysphonia. Vocal fold scar is one of the most challenging problems for otolaryngologists because it is hard to be diagnosed at germinal stage and the function necessity of vocal cords is delicate.
In phonetics, vocal folds is preferred over vocal cords, on the grounds that it is more accurate and illustrative.
==Additional images==
Children
Puberty
Adulthood
Maturation
Maculae flavae
Impact of phonation
Impact of hormones
Old age
Function
Oscillation
Clinical significance
Lesions
Reinke's edema
Wound healing
Terminology
See also
External links
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