Inflammatory processes that affect the unified airway can concurrently exert significant influence on the larynx and surrounding mucosal surfaces. Laryngeal inflammation can be present secondary to direct effects of irritants, toxins, and antigens, but can also involve mechanical and infectious effects as well as secondary inflammation from behavioral mechanisms. This review examines laryngeal inflammation in the context of the unified airway and discusses pathophysiologic mechanisms that are central to the development of acute and chronic laryngitis.
Viruses, bacteria, tumors, parasites, antigens (chemical, organic, environmental), and trauma are agents that can cause harm to any body part. If a structure is attacked, the immune system responds by triggering a loco-regional inflammatory reaction. Paradoxically, this common pathologic sign is an indispensable protective process, without which afflicted tissues could not survive. In general, inflammation involves both humoral and cellular reactions to combat the injurious effects of the inciting agent. This important defense mechanism plays a critical role in limiting local and proximal tissue damage and facilitating initial healing and repair. Whereas such triggers are mostly beneficial, severe or protracted inflammation can be quite harmful. Inflamed tissues typically appear erythematous and edematous, and they are usually warm and tender to the touch; normal functions are frequently compromised, and systemic signs such as elevated white blood cell count and fever may co-occur.
The inflammatory process
There are seven sequential mechanisms of tissue inflammation: (1) diminished blood flow secondary to contraction or vasoconstriction of vessels; (2) vasodilation of small blood vessels, which causes increased flow, erythema, and localized heat; (3) protein-rich plasma leakage from dilated vessels into the affected site, which causes edema, hypertension, tenderness, and dysfunction; (4) blood flow stagnation; (5) activation of eosinophil, neutrophil, monocyte, and lymphocyte molecules that adhere to the lining of blood vessels, known as margination or pavementing; (6) emigration of these adhesion molecules within blood vessels into the affected tissue, where they become longer-lasting macrophages; and (7) destruction of the inciting agent of inflammation, which is mediated by these accumulated intracellular materials. These defensive processes include the production of (1) immunoglobulin antibodies, (2) blood-clotting (fibrin) proteins that prevent the spread of inflammation into neighboring tissues, and (3) neutrophils and phagosomes that collectively release powerful chemical enzymes to promote healing and homeostasis. In addition to the above-named plasma proteins and binding molecules, other important chemical mediators contribute to the pathogenesis of inflammation. These include (1) histamine, found abundantly in mast cells, and serotonin, present in blood platelets, which are vasoactive amines that help trigger dilation and leakage of blood vessels; and (2) prostaglandins and leukotrienes, which are constituent arachidonic acid metabolites that also induce powerful vasodilation in the area of tissue injury.
Types of inflammation
There are four fundamental forms of inflammation: acute, chronic, subacute, and granulomatous.
Acute inflammation
Acute inflammation is an essential body defense mechanism. It occurs rapidly, usually within minutes following challenge by either an infectious, traumatic, or antigenic agent. The duration of the acute response is typically brief, but the initial degree of inflammation can be profound. The cardinal localized signs may include erythema, edema, tissue warmth, tenderness, abscess formation, ulceration, and loss of function. Not infrequently, acute infectious inflammatory reactions provoke systemic abnormalities, including elevated white blood cell and lymphocyte counts, fever, and cellulitis. Purulent exudate (pus) may be produced by dying neutrophils within the bloodstream and necrosis of the afflicted tissues may occur in cases of severe acute inflammation. Occasionally, serous or watery blisters form in acutely inflamed tissue. In rare instances, fibrinous exudate is the predominant by-product of a severe inflammatory response. This thick, white, membranous-appearing tissue layer usually invades the surfaces of organs, such as the heart or lung. In the sequelae of the uncommon bacterial infection diphtheria, a suffocating pseudomembrane may form in the pharynx or larynx. Cytologic features of acute infection include dilated and engorged capillary networks, abnormally high (>65%) neutrophil populations, distended tissue spaces, and evidence of fibrin molecules.
Chronic inflammation
Generally, the signs and symptoms of chronic inflammation are less dramatic than those of acute inflammation. Pain and erythema can be minimal, swelling is often mild, and fever is uncommon. However, because chronic inflammation often has a subdued onset and can last for many weeks, it can eventually cause considerable localized tissue fibrosis, scarring, and necrosis. These pathologic sequelae result from the decaying effects of oxidizing chemicals that are continually discharged into the afflicted tissue by the high concentration of neutrophils that accumulate at the injured site. In some cases of chronic inflammation the pathogenesis is an unexpectedly persistent acute reaction. This transformation into a chronic phase may be caused by (1) inability of the body to mount a sufficient defense against a powerful offending agent, or (2) continuous exposure to a noxious agent. Low virulent recurring infections and autoimmune abnormalities commonly result in chronic inflammatory conditions. Tuberculosis, lupus, and rheumatoid arthritis are prime examples of inciting disease entities.
Macrophages and lymphocytes are predominant in chronically inflamed tissues. These cells assume a synergistic relationship, wherein the latter ones stimulate and mediate functions of the former ones. Activated macrophages engulf various microorganisms and exude chemical mediator substances that contribute to local tissue destruction. In most cases, eosinophils and neutrophils are not active components of the chronic inflammatory process. Conversely, fibroblasts and collagen are almost always prominent cellular substrates causally linked to permanent scarring, disfigurement, and dysfunction of chronically inflamed tissue. The primary cytologic features of chronic inflammation include lymphocytes, macrophages, fibroblasts, and collagen.
Subacute inflammation
Although this entity is not clearly defined, it may be of clinical and diagnostic utility in certain cases. When neither the medical history nor signs and symptoms exhibited by a patient support conclusions of an acute or chronic inflammatory condition, the term subacute may be applied; that is, the clinical presentation and problem rests somewhere in between these two primary inflammation subtypes. For example, the individual with perennial dust allergy who is exposed to an unusually high concentration of dust particles may experience a subacute lower and upper airway inflammatory reaction that requires avoidance behaviors and pharmacologic intervention.
Granulomatous inflammation
Most fungal infections of low virulence produce chronic inflammatory reactions. If these microorganisms are left unchecked they can convert into granulomatous disease, characterized by formation of a discrete granuloma. Granulation tissue is composed of large nucleated epithelioid cell deposits, fibroblasts, and collagen. Prolonged or repetitive physical trauma or intrinsic acidic irritation are common etiologic factors in this condition.
Types of inflammation
There are four fundamental forms of inflammation: acute, chronic, subacute, and granulomatous.
Acute inflammation
Acute inflammation is an essential body defense mechanism. It occurs rapidly, usually within minutes following challenge by either an infectious, traumatic, or antigenic agent. The duration of the acute response is typically brief, but the initial degree of inflammation can be profound. The cardinal localized signs may include erythema, edema, tissue warmth, tenderness, abscess formation, ulceration, and loss of function. Not infrequently, acute infectious inflammatory reactions provoke systemic abnormalities, including elevated white blood cell and lymphocyte counts, fever, and cellulitis. Purulent exudate (pus) may be produced by dying neutrophils within the bloodstream and necrosis of the afflicted tissues may occur in cases of severe acute inflammation. Occasionally, serous or watery blisters form in acutely inflamed tissue. In rare instances, fibrinous exudate is the predominant by-product of a severe inflammatory response. This thick, white, membranous-appearing tissue layer usually invades the surfaces of organs, such as the heart or lung. In the sequelae of the uncommon bacterial infection diphtheria, a suffocating pseudomembrane may form in the pharynx or larynx. Cytologic features of acute infection include dilated and engorged capillary networks, abnormally high (>65%) neutrophil populations, distended tissue spaces, and evidence of fibrin molecules.
Chronic inflammation
Generally, the signs and symptoms of chronic inflammation are less dramatic than those of acute inflammation. Pain and erythema can be minimal, swelling is often mild, and fever is uncommon. However, because chronic inflammation often has a subdued onset and can last for many weeks, it can eventually cause considerable localized tissue fibrosis, scarring, and necrosis. These pathologic sequelae result from the decaying effects of oxidizing chemicals that are continually discharged into the afflicted tissue by the high concentration of neutrophils that accumulate at the injured site. In some cases of chronic inflammation the pathogenesis is an unexpectedly persistent acute reaction. This transformation into a chronic phase may be caused by (1) inability of the body to mount a sufficient defense against a powerful offending agent, or (2) continuous exposure to a noxious agent. Low virulent recurring infections and autoimmune abnormalities commonly result in chronic inflammatory conditions. Tuberculosis, lupus, and rheumatoid arthritis are prime examples of inciting disease entities.
Macrophages and lymphocytes are predominant in chronically inflamed tissues. These cells assume a synergistic relationship, wherein the latter ones stimulate and mediate functions of the former ones. Activated macrophages engulf various microorganisms and exude chemical mediator substances that contribute to local tissue destruction. In most cases, eosinophils and neutrophils are not active components of the chronic inflammatory process. Conversely, fibroblasts and collagen are almost always prominent cellular substrates causally linked to permanent scarring, disfigurement, and dysfunction of chronically inflamed tissue. The primary cytologic features of chronic inflammation include lymphocytes, macrophages, fibroblasts, and collagen.
Subacute inflammation
Although this entity is not clearly defined, it may be of clinical and diagnostic utility in certain cases. When neither the medical history nor signs and symptoms exhibited by a patient support conclusions of an acute or chronic inflammatory condition, the term subacute may be applied; that is, the clinical presentation and problem rests somewhere in between these two primary inflammation subtypes. For example, the individual with perennial dust allergy who is exposed to an unusually high concentration of dust particles may experience a subacute lower and upper airway inflammatory reaction that requires avoidance behaviors and pharmacologic intervention.
Granulomatous inflammation
Most fungal infections of low virulence produce chronic inflammatory reactions. If these microorganisms are left unchecked they can convert into granulomatous disease, characterized by formation of a discrete granuloma. Granulation tissue is composed of large nucleated epithelioid cell deposits, fibroblasts, and collagen. Prolonged or repetitive physical trauma or intrinsic acidic irritation are common etiologic factors in this condition.
Unified airway
The respiratory tract is composed of a common system of upper and lower airway linkages, referred to as the unified airway . The larynx is an integral component of this anatomic and physiologic framework. Inflammation that arises anywhere within the unified airway may induce widespread and simultaneous upstream and downstream secondary inflammatory reactions via this interconnected tissue network .
Laryngeal anatomy and physiology
The larynx and vocal folds within act as a biologic conduit for breathing, a physiologic valve for airway protection during swallowing, and an instrument for voice production. Whereas the first two functions depend largely on involuntary or reflexive neuromuscular activities, most vocalizations occur as a result of volitional speaking efforts. Composed of nine cartilages, two synovial joints, and various suspensory extrinsic and voice-generating intrinsic muscles, ligaments, and membranes, the larynx is an extraordinarily complex organ. Fig. 1 illustrates the normal white and glistening vocal folds within the interior of the laryngeal skeleton, owing to their outermost mucosal layer of stratified, nonkeratinizing squamous epithelium. The bodies of the folds, deep to the covers, are formed by components of the thyroarytenoid muscle fibers and high-density fibroblast, elastic, and collagenous tissues. These rapidly mobile structures are enveloped by an intricate matrix of mucous membranes that play an important role in their physiologic integrity and endurance.
Peripheral laryngeal innervation depends primarily on the superior and recurrent branches of the Xth (vagus) cranial nerve pair, which arise from the lower brainstem and exit the skull via the jugular foramen. These laryngeal nerve branches transmit to the central nervous system (1) sensory output information from the muscular and membranous tissues of the larynx within, above, and immediately below the vocal folds, and (2) widespread motor inputs from the central nervous system to the various intrinsic laryngeal muscles. The sensory mechanoreceptor circuitry forms the intrinsic laryngeal monitoring system. Its primary functions are to regulate respiratory and vegetative reflexes, and to relay oscillating discharges from the vocal folds during voice production. These sensory pools establish polysynaptic loops with the laryngeal motor neurons to form a tonic servo-reflex system, which facilitates continuous monitoring and adjustments of voice output.
Diseases of the larynx
Laryngitis
The term laryngitis generically refers to inflammation of the tissues of the larynx. In acute and subacute forms the onset is usually abrupt, and the course of the illness is typically self-limiting; that is, less than 3 weeks. Chronic laryngitis usually develops gradually, and the underlying signs and symptoms can wax and wane over very long periods of time; some granulomatous forms can result from a single traumatic insult, and others may emerge when the larynx is repetitively exposed to the offending agent over a longer duration.
Infectious laryngitis
Viruses, bacteria, and fungi or molds can infect the larynx and cause acute laryngitis.
Viral laryngitis
In general, viruses are transmitted by infected individuals via air droplets during exhalation, sneezing, or coughing. Viral infections of the unified airway are most often caused by the common cold or rhinovirus. Less frequent causal mechanisms include influenza A, B, and C; parainfluenza viruses; adenovirus; measles; and varicella-zoster . In young children (often younger than 2 years) viral croup syndrome, secondary to parainfluenza viruses in most cases, is usually characterized by acute laryngo-tracheo-bronchitis and associated hoarseness or muffled voice, dry barking cough, odynophagia, inspiratory stridor, and dyspnea. Mild to moderate epiglottitis, vocal fold edema, and subglottal swelling may result in narrowing of the upper airway and labored breathing dynamics. Fortunately, the vast majority of viral laryngitis in adults and children is self-limiting, with resolution of signs and symptoms within 1 week post-onset. Use of analgesics, cool mist humidification, and attention to adequate hydration often suffice as treatments. In severe cases, nebulized epinephrine and oral steroid dose packs may be helpful . Fig. 2 illustrates a case of infectious laryngitis. In this patient the history supports a possible viral etiology associated with a severe upper respiratory infection.
Bacterial laryngitis
This condition is most often caused by inhalation of bacteria transmitted by an infected individual. Signs and symptoms of bacterial laryngitis are quite similar to those of viral laryngitis, including sore, dry, and itchy throat; cough; sinusitis and facial pressure; headache; swollen glands; and laryngeal edema and erythema. Although clinically significant stridor and dyspnea rarely occur in such cases, these signs are suggestive of substantial upper airway obstruction, necessitating more aggressive management such as intubation or tracheotomy. Note that the presence of endolaryngeal purulent secretions is more commonly observed in patients with bacterial versus viral laryngitis. In addition to the aforementioned treatments for viral laryngitis, oral or intravenous antibiotic therapy is often administered to patients with suspected bacterial infections. Fig. 3 illustrates the laryngeal appearance of a patient with bacterial laryngitis.
