LECTURE # 1
Marie E. Kavanagh, M.D.
|Upper respiratory tract|
|Brief review of the normal anatomy and histology of the respiratory passages.|
|Pathology of the respiratory passages|
|Inflammatory lesions of the respiratory passages|
|Acute: Viral, Allergic|
|Chronic: Bacterial, Fungal|
|Granulomatous: Tuberculous, Syphilitic, Lepromatous, Scleroma|
|Pathology of the Sinuses|
|Systemic diseases affecting the respiratory passages|
|Tumors of the respiratory passages|
|Pathology of the pharynx|
|Tumors of the nasopharynx|
|Pathology of the larynx|
|Inflammatory lesions of the larynx|
|Pertussis or Whooping cough|
|Tumors of the larynx|
|Papilloma of the larynx|
|Malignant lesions of the larynx|
|Pathology of the trachea and the main bronchi|
|Lower respiratory tract: THE LUNGS|
|Review: Anatomy & Histology of normal lung|
|Pathology of the lung|
|Pulmonary agenesis and hypoplasia|
|Congenital vascular anomalies of the lungs|
|Bronchogenic or Central cysts|
|Pulmonary or peripheral cysts|
|Acquired anomalies of the lower respiratory tract|
PATHOLOGY OF THE RESPIRATORY SYSTEM
Fall 2000M. Kavanagh, M.D.
||The respiratory system includes the upper respiratory segments also called the respiratory passages and the lower respiratory parts made of the lower conducting airways and the lungs. A brief review of the normal anatomy and histology of the different components of the respiratory system is important in order to understand the basic pathologies of the organs.|
The respiratory passages are made of several segments, each segment having a specific role in the function of the system.
* A first segment includes the nasal cavities and the accessory air sinuses.
* A second segment is made of the naso- pharynx and the laryngopharynx.
* A third segment includes the larynx
* A fourth segment is made of the trachea and the upper conducting airways composed of the large bronchi.
The respiratory passages are lined in part by a stratified squamous epithelium and for the most part by a pseudostratified ciliated columnar epithelium rich in goblet cells. The lamina propria which has a rich vascular supply also contains the Bowman glands that are, together with the goblet cells, responsible for the secretion of large amount of mucus. The mucus forms a thin protective layer on the mucosal surface of the passage (mucus blanket)
|ROLE OF THE UPPER RESPIRATORY SEGMENT.
The inhaled air is not at an optimal state when it enters the respiratory tree, it can be harmful to the delicate structures of the terminal units of the system, namely the alveoli. The role of the respiratory passages is not only to conduct the inhaled air to the terminal respiratory units for gaseous exchange with the blood, but also to provide the adequate medium for alterations in the physical composition of the air, minimizing the environmental insult to the terminal units of the lung. Each segment of the respiratory passages has a different function in the alteration of the inhaled air. The major changes that occur can be classified in four categories:
Filtration of particulate matters
Modification of the temperature of the air
Modification of the humidity content
Removal of harmful gases.
||Filtration of particulate matters is done by the fibrissae (the stiff, coarse hairs located at the entrance of the nostrils). The particles that bypass the fibrissae are trapped in the mucus blanket covering the turbinate and the nasal septum. Some particles are swallowed and inactivated in the stomach, the smaller particles are trapped distally in the mucus layer of the respiratory passages. The trapping of the particles is facilitated by the irregularity in the passages allowing for marked variation and sudden change in the direction of the air flow. The mucus containing the particles is evacuated from the passages by the constant unidirectional movement of the ciliae in wave-like beating. Any alteration in the mucus production or any defect in the function of the cilia may affect the entire respiratory tree with serious pathological consequences..|
||The temperature control of the air is done through the rich and complex vascular supply of the respiratory tree, vascular supply that is under autonomic control. The temperature of the inspired air is adjusted within ten (10) degrees of the body temperature when it reaches the alveolar spaces. This is done by heat exchange.|
|The control of the humidity
is also done through the rich vascular supply that provides a 100% humidification
to the inhaled air.
Removal of harmful gaseous substances. Partial removal of certain harmful gaseous substances can be performed to a certain degree at the level of the respiratory passages by diffusion through the blood of the rich vascular supply of the area before entering the more vulnerable segments of the respiratory tree.
A pathology of any segment of the respiratory tree may affect the integrated function of the entire system.
|PATHOLOGY OF THE UPPER RESPIRATORY PASSAGES|
entities usually affect the respiratory passages: The inflammatory diseases
and the neoplastic lesions.
NASAL CAVITIES AND AIR SINUSES
The inflammatory lesions of the nasal cavities, also known as Rhinitis, are the most common disease of the nose ans air sinuses, they are usually infectious or allergic in nature, they are more discomforting than serious if confined to the nasal cavities, but unfortunately the inflammatory process has a tendency to spread to the adjacent organs and lead to more serious complications.
Acute Rhinitis can be caused by:
Chronic Rhinitis can be caused by:Virus: Rhinovirus, adenovirus & the echovirus
The pathologic changes vary with the stage of the disease, three phases are usually described.Fungus: Mucor , Aspergillus
This acute phase of rhinitis is in most cases caused by a virus (common cold) or an allergen (hay fever), it is known as the catarrhal phase of the disease and is often referred to as coryza.
This phase is associated with a profuse mucoid nasal discharge .
Examination of the nasal cavities at this point reveals a red, thickened, edematous mucosal lining, enlargement of the turbinates and narrowing of the nasal cavities. The narrowing of the passages decreases the amount of air reaching the terminal airways which creates a certain degree of hypoxia which in turn causes a reactive switch from nasal to oro-pharyngeal breathing. By bypassing the nasal breathing the protective mechanism provided by this segment of the respiratory tree is lost.
On microscopic examination, the goblet cells are hypertrophic and loaded with mucus secretion, the submucosa is edematous and infiltrated with few inflammatory cells, predominantly neutrophils, lymphocytes, and plasma cells. When an allergen is responsible for the rhinitis, the most abundant type of cells are the eosinophils.
A bacterial invasion usually follows the acute viral or allergic lesion. With the secondary bacterial infection, the nasal discharge becomes mucopurulent or frankly purulent. The bacteria involved are the Staphylococci, the Streptococci, the Hemophilus and the Pneumococci. At this stage, the mucosa may show areas of superficial ulceration, the inflammatory infiltrate is more profuse and consists mainly of PMN leukocytes.
Focal enlargement of the mucosal folds may form projecting structures known as "pseudo polyps" inside the nasal cavities.
Because of the repetitious pattern of recurrence of allergic rhinitis, these polyps were thought to be atopic in nature and were called 'allergic polyps', but only 0.5% of these polyps are found in patients with allergic rhinitis.
All these changes are reversible with appropriate treatment.
After several bouts of acute infection, the condition becomes chronic (chronic Rhinitis), and permanent, the alterations that occur in the different structures are not reversible. The mucosa thins out and shows some degree of atrophy, and the submucosa is progressively replaced by fibrous tissue. At this point, the protective mechanism of the air passage (mucus production and ciliary movement) becomes permanently inadequate, condition known as atrophic rhinitis or rhinitis sica. This latter complication is often seen with infections caused by Klebsiella ozaenae.
In some cases, the nasal epithelium may undergo squamous metaplasia.
This very common condition, most often the result of a trauma, may also be caused by a variety of systemic diseases including hypertension and some hematologic abnormalities like blood dyscrasia, or it could be the result of local inflammatory reactions or neoplastic diseases of the nasal tissue. The bleeding usually originates at the anterior area of the nasal septum known as the "Little area" which may show some dilated submucosal blood vessels. The Little area is also the most vulnerable site of nasal septum ulceration and perforation caused by various factors including trauma, infection, SLE, cocaine abuse (snorting), and malignant tumor.
LESIONS OF THE RESPIRATORY PASSAGES
There are less common infectious microorganisms that are very detrimental to the upper airways because of the extensive and permanent damage that can result from the invasion of the nasal tissue by such microorganisms. They are more often associated with a granulomatous reaction of the upper respiratory tissues. The most common lesions that are studied here include the involvement of the upper respiratory tree by:
Syphilis, Leprosy, Tuberculosis, Rhinoscleroma
LESIONS OF THE NOSE.
Syphilis is a systemic infection caused by the Treponema pallidum
The secondary and tertiary forms of syphilis often affect the nose and the nasopharynx. The lesions vary with the extent of the disease, ranging from a simple ulceration of the mucosa to a complete destruction of the nasal cartilage (vomer) and bone leading to a collapse of the nasal bridges, condition described as "saddle nose" most characteristic of the osteochondritis of congenital syphilis. The typical granuloma can be demonstrated in the lesion
INVOLVEMENT OF THE NOSE.
Leprosy also known as Hansen disease is caused by the Mycobacteria Leprae, an acid fast mycobacteria that thrives in cool temperature, which explained its affinity for the nasal passage. The variant of the disease affecting mainly patients lacking T-cell mediated immunity causes lesions of the upper respiratory area in Lepromatous leprosy. It is characterized by formation of granulomatous masses made of lipid-laden macrophages filled with acid fast bacilli (Lepra cells). The macrophages rather than destroying the bacilli act as microincubators allowing massive growth of the mycobacteria.
The granulomatous infiltrate forming large nodules expands slowly to distort the upper airway resulting in loss of bone structure, condition that can be fatal, the patient can die of asphyxiation due to obstruction of the airway. Collapse of the bridge of the nose and perforation of the nasal septum are common complications (leonine facies or lion-like)
LESIONS OF THE NOSE
The granulomatous lesions characteristic of tuberculosis are often seen in the nasal mucosa of affected individuals. Unlike the syphilitic and leprosic lesions, the tuberculous granulomata do not lead to destruction of the nasal structures, but the scar retraction that occurs after healing may cause some degree of occlusion of the nasal passage.
This is a chronic destructive infection of the nose caused by the Klebsiella rhinoscleromatis also known as von Frisch's bacilli. This disease is very endemic in some part of the world namely Central America, Central Europe and the Middle East and is associated with marked deformity of the facial structures.
On examination of an affected individual, there is some degree of narrowing or even complete closure of the nasal passage, the infected tissue - mainly the nasal mucosa, is firm, thickened, nodular and ulcerated.
On microscopic examination, there is a nodular granulomatous lesion rich in plasma cells, lymphocytes and a characteristic foamy histiocyte known as the Mckulicz's cell that contain phagocytized bacilli.
Most inflammatory reactions of the nasal cavities do not remain confined in the nasal mucosa, they extend to involve the surrounding structures, namely the accessory air sinuses, condition known as sinusitis.
|PATHOLOGY OF THE AIR SINUSES|
OF THE SINUSES OR SINUSITIS.
The reaction of the components of the sinuses to the infectious process is the same as in the nasal cavities. The changes vary with the stage of the disease, and are classified as early and late stages. The symptoms usually become evident during the late stages of the disease.
EARLY STAGE. The acute reaction of the sinuses usually follows an acute stage of rhinitis, most often of viral or allergic origin. During the acute phase of rhinitis, the edematous nasal mucosaaround the drainage foramen of the sinuses closes the opening of the air sinuses. The large amount of mucus being produced by the hyperactive glands and goblet cells accumulates inside the sinus cavities and forms a mucocele that provides an adequate medium for the growth of microbacteria and fungi. Obstruction of the drainage foramen of the maxillary sinuses may also result from a deviated nasal septum or a nasal polyp.
The histological changes during the acute phase of the disease are the same as the ones occurring in the nasal mucosa during acute rhinitis. There is edema and congestion of the soft tissue of the sinuses that is infiltrated with acute inflammatory cells.
With the secondary invasion of the sinuses by microbacteria and fungi
(usually a mixed flora), a chronic form of the disease may develop. The
content of the sinuses becomes mucopurulent or frankly purulent. Suppurative
sinusitis is a severe condition that requires prompt treatment since the
possibility of the spread of the infectious process to the cranial cavity
is always a dreaded complication.
The histopathologic changes include heavy inflammatory infiltrate of the mucosa, edema and congestion of the soft tissue and in severe cases complete necrosis of the mucosal lining.
Severe complications including massive necrosis, mucosal atrophy and involvement of the bone structures may result.
Fungal infections of the sinuses usually occur as a complication of a systemic disease.
|SYSTEMIC DISEASES AFFECTING THE RESPIRATORY PASSAGES|
There are a few lesions of the respiratory passages that are an extension or a complication of more generalized systemic diseases. The most commonly encountered are the nosocomial fungal infections that affect the respiratory passages as a result of a debilitating disease.
Fungal infection, most often fungal sinusitis, are rarely spontaneous, they usually complicate a pre-existing condition, and are often nosocomial .
by the MUCOR a fungus of the Phycomycetes
group is the most commonly found in acidotic diabetic patients, in immunocompromized
patients, and in patients with chronic debilitating diseases. It is often
life threatening and is characterized by the formation of a black crust
covering necrotic tissue in the nasal cavities and specially the sinuses.
and the Rhinosporidia have been responsible for the infection, but are less commonly seen.
An allergic fungal sinusitis may occur in immunocompetent individuals with a history of atopy. This type of sinusitis that is usually caused by the Bipolaris and the Curvularia species, is a non invasive lesion treated by the debridment of the nasal area involved. The rate of recurrence is low and occurs from 8 months to 4 years after surgery.
Regardless of the type of fungus involved, the spores of the fungi first implant in the nasal mucosa then progress to invade the air sinuses. This causes extensive necrosis of the mucosa of the area involved.
another systemic disease probably of immune origin that affects the respiratory
passages. The etiology
of this disease is unknown, it is however characterized by the production
of antineutrophylic cytoplasmic antibodies (ANCA). It affects men
more often than women and cause a generalized type of vasculitis associated
with chronic sinusitis and ulceration of the nasopharynx.
The areas affected show multiple granulomatous lesions that have a necrotic center surrounded by several small nodules. These lesions require surgical removal followed by an immunosuppressive drug treatment with cyclophosphamide.
|In KARTAGENER SYNDROME which is an inherited disorder transmitted as an autosomal recessive trait, there is a defect in the mobility of the cilia of all the ciliated epithelia of the body due to the absence of the dynein arms of the cilia. This lack of mobility of the cilia interferes with the drainage and the clearing of the respiratory passages, which causes impaction of the secretion followed by secondary infection of the air passages leading to bronchiectasis and sinusitis.|
This lesion that affects the upper respiratory tract is considered a form of the peripheral T cell (non Hodgkin) lymphoma, a neoplasm of the natural killer cells. It is often complicated by a lethal bacterial infection which in most cases is associated with bleeding episodes.
The pathological findings consist of extensive ulceration of the upper respiratory tract mucosa with destruction of the underlying cartilage and bone. The blood vessels of the area are often thrombosed, and the surrounding viable tissue is heavily infiltrated with atypical lymphocytes. This lesion is not responsive to antibiotic treatment, chemotherapy however can be useful and gives good results.
|TUMORS OF THE RESPIRATORY PASSAGES|
|Neoplastic lesions of the nasal cavities and of the accessory air sinuses are rare. When discovered, they may originate from any component tissue of the area, they range from a simple nasal polyp to an extensive malignancy that may spread to involve the surrounding structures, or even send distant metastases.|
This lesion, by far the most common growth of the nasal tissue, is not considered a true neoplasm, it is the result of repeated episodes of inflammatory reaction of the nasal mucosa.
Nasal polyps, like the pseudo-polyps are found in about 0.5% of patients with atopic rhinitis, a much lower number than previously thought.
They consist of focal accumulation of edema fluid and inflammatory exudate in the submucosa of the nasal cavity followed by a fibrotic reaction of the surrounding soft tissue (pseudo-polyp becoming permanent).
The polyps range in sizes from a small elevation of the mucosal surface to large protruding masses that are often multiple.
On microscopic examination the core of the lesion is made of edematous loose connective tissue with scattered areas of denser fibrotic areas infiltrated by inflammatory cells, namely lymphocytes, plasma cells, eosinophils and rare neutrophils. The covering epithelium can be hyperplastic or atrophic and may at time show some degree of squamous metaplasia, but it rarely if ever becomes malignant.
LESIONS OF THE UPPER RESPIRATORY PASSAGES
There are three distinct varieties of papillary lesions that may affect the upper respiratory passages, all the lesions arising from the lining epithelium of the area, the nasal cavities are affected in 20% of the cases, the paranasal sinuses in 40% of the cases and both in 40% of the cases.
The epithelial lining of the upper respiratory segment is known as the "Schneiderian membrane" and the lesions are usually called "Schneiderian papillomas".
The three variants that are usually identified are :
The Fungiform papilloma - 50% of cases
This papillomatous lesion occurs most exclusively on the nasal septum of the vestibule of the nose.
It is made of branching finger-like structures composed of a core of fibro-vascular tissue covered with multiple layers of hyperplastic squamous epithelium. On isolated cases, the epithelial lining may be ciliated columnar mixed with mucus cells. Unlike the polyp, the papilloma may undergo malignant transformation.
|INVERTED PAPILLOMA . This neoplasm of epithelial origin is most often located on the lateral wall of the nasal cavities or the paranasal sinuses. This is a potentially aggressive lesion that is in about 20% of the cases associated with an invasive squamous cell carcinoma of the area. It consists of an endophytic pattern of growth made of cords of nonkeratinized squamous epithelium or on rare cases ciliated or transitional epithelium infiltrating into the underlying stroma of the area. It has a tendency to invade the bony structures of the head and, if not adequately removed by surgery, has a high rate of recurrence.|
This variant of the papillomas involves the lateral nasal wall and paranasal sinuses, these lesions are usually exophytic in nature and are made of thin fibrovascular cores covered with 3 to 8 layers of atypical, cylindrical oncocytic cells. About 15% of the cases become overtly malignant.
All the variants of the papilloma, if removed by local excision have a recurrence rate ranging from 25 to 70%.
|JUVENILE ANGIOFIBROMA. This is a rare tumor of vascular origin found exclusively in males, usually during adolescence. The high vascularity of these tumors renders surgical removal very difficult. These tumors contain androgen receptors, explaining their occurrence only in the males.|
TUMORS OF THE UPPER RESPIRATORY PASSAGES
The malignant tumors of the nasal cavities are either of epithelial origin, in which case they are a carcinoma, or rarely of mesenchymal origin, in which case they are a sarcoma. The tumors of epithelial origin can be a squamous cell carcinoma, a transitional cell carcinoma, or an adenocarcinoma.
Few underlying factors often play a role in the pathogenesis of these tumors.
The adenocarcinomas are more frequently seen in people who have worked in the woodwork and furniture industries and may appear up to 40 years after the initial exposure to the damaging substance.
Genetic abnormalities consisting of the deletion of loci on the short arm of chromosome 3 appear to be a consistent finding in patients affected with nasopharyngeal carcinoma.
On pathological examination, the tumor takes the characteristics of the tissue of origin, the treatment of these tumors depends on their degree of extension, their degree of differentiation and many other factors. It usually follows a mild course with a good prognosis, the survival rate varies from 50 to 80%.
NEUROBLASTOMA or ESTHESIONEUROBLASTOMA
This tumor affecting the nasal cavities has been the subject of great concern since it is usually associated with a chromosome translocation of 11-22, translocation that is also noted in the Ewing tumor of the bone and a trisomy of the chromosome 8 noted in certain cases. The Olfactory neuroblastoma, so called because of its neural crest origin, arises most often from the mucosa covering the superior third portion of the nasal septum.
It usually appears as a polypoid vascular mass with variable histological patterns, it slowly invades the bony structures of the face via the lymphatic channels. The classical lesion consists of a proliferation of small cells separated by a neurofibrillar matrix. This tumor is very sensitive to radiotherapy. The survival rate is about 50% to 70% after 5 years.
|THE NASO-PHARYNX – LARYNGO PHARYNX or HYPOPHARYNX|
is a passageway shared by the digestive and the respiratory system for air
and food, it unites the nasal and oral cavities to the larynx. The portion
considered as part of the respiratory system is known as naso and laryngeo
pharynx, the other segment is the oropharynx. The part of the pharynx subject
to food abrasion is lined with stratified squamous epithelium, the portion
belonging to the respiratory tree is lined with pseudostratified ciliated
One of the role of the pharynx is to provide certain degree of local immune protection to the respiratory and digestive tract through the presence of the lymphoid organs, adenoids and tonsils located on the wall of the pharynx (Waldeyer ring). On the wall of the pharynx are also found the openings for the eustachian tubes.
The local immune protection of the respiratory passages is provided by the adenoids that monitor the inhaled particles and the tonsils that monitor the swallowed particles through the secretion of IgA by these lymphoid organs. This protective mechanism is more effective during childhood.
|PATHOLOGY OF THE PHARYNX|
Acquired immune deficiency, either of viral, chemical or mechanical origin is often associated with atrophy of the lymphoid tissue of the Waldeyer's ring of the pharynx. With the constant increase in the number of AIDS cases, this pathology of the pharynx is becoming very popular and should therefore be considered in the study of the upper respiratory tree.
The pharynx is usually the site of acute inflammatory reaction caused by a pathogenic microorganism. The microorganisms involved can be a virus or a bacteria. The viruses (EB virus & adenovirus ) are the most common (70 to 80% of the cases) and the b hemolytic Streptococci group A and the Staphylococcus aureus cause 20 to 30% of the cases. Because of the broad overlap in the clinical presentation of the bacterial and non bacterial pharyngitis, it is very important to make an early etiological diagnosis, especially in children because of the possible sequelae of a late start of the treatment. The physical characteristics of the acute inflammation may not allow for a specific etiological diagnosis, rapid antigen test studies followed by throat culture is often necessary during the early stage of the infection.
Acute pharyngitis is often associated with severe edema of the soft tissue causing narrowing of the air passage, leading to inadequate aeration of the respiratory units. The edematous reaction often extends to the middle ear through the opening of the auditory canal (eustachian tube).
Pathological examination of the affected area reveals marked edema, hyperemia, and suppurative exudation of the pharyngeal tissue, scattered areas of mucosal ulceration, and crypt abscesses formation. When the Streptococci are the offending agents, the inflammatory process may progress to invade the adjacent structures like the lymphnodes, the mastoid bones, the inner ears and the meninges. The infectious material drains through the lymphatics, resulting in secondary involvement of the tonsils (acute tonsillitis), or of the peritonsillar area (peritonsillar abscess).
Microscopic examination reveals congestion of the blood vessels of the area, edema of the soft tissue that is heavily infiltrated with acute inflammatory cells, namely PMN leukocytes, and macrophages.
The lymphatic drainage of the upper respiratory tree is done through the tonsils, both palatine and pharyngeal. Any infection of the area may affect the tonsils, condition known as tonsillitis more commonly seen in children. It is usually due to a virus or a bacteria, most often the Streptococcus Pyogenes.
On examination, the tonsils (usually the palatine) are enlarged, congested and have a rough external surface that may be covered with inflammatory exudate, exudate also found inside the tonsillar crypts.
On microscopic examination, the inflammatory exudate is made of leukocytes, epithelial debris and bacteria, the surrounding tissue is edematous and congested. In chronic cases there may be some degree of lymphoid hyperplasia.
Treatment with appropriate antibiotics is usually enough, but in chronic condition, following repeated episodes of infection, surgical removal of the tonsils may be necessary.
OF THE NASOPHARYNX
Most neoplastic lesions of the nasopharynx are of epithelial origin and are malignant. They range from a well differentiated squamous cell carcinoma, to a poorly differentiated malignancy which if the most common form.
The carcinoma of the nasopharynx is very prominent in certain ethnic groups, namely among the Southern Chinese where it is mostly seen in children, the African where it is mostly seen In adults, but is rather rare in the USA. The high frequency of this tumor in certain group raises the possibility of a link with a genetic susceptibility to EBV infection that seems to be a common factor to most of the cases in which the Epstein Bar virus genome is present within the malignant cells. Another consistent feature of this tumor as mentioned previously is a partial deletion of the short arm of the chromosome 3 at least on two separate loci.
Rarely a Benign Nasopharyngeal teratoma can be identified (slide).
The larynx is a box-like structure located between the pharynx and the trachea. It has two major functions:
- Serves as the main organ of phonation.These functions of the larynx are done through the presence of several cartilaginous structures, strong intrinsic and extrinsic muscle fibers, the vocal cords that are ligaments covered with mucosal folds, and the pseudo-stratified ciliated columnar epithelial lining.
OF THE LARYNX
The larynx, like the upper part of the respiratory passages, is subject to two common pathologies : The inflammatory reactions and the neoplasms.
There are few specific symptoms that usually point to a pathology of the larynx. They consist of:
Pain and dysphasia are caused by excessive muscle contraction
NON SPECIFIC LARYNGITIS
This inflammatory reaction of the larynx is in most cases a non specific lesion that is part of a more diffuse pathological process involving the upper or the lower respiratory tree. In heavy smokers however, the larynx may be affected by an isolated type of inflammatory process. Laryngitis whether diffuse or localized may be caused by an infectious organism, like the Streptococcus, the Hemophilus influenzae or it could be a reaction to an allergen. In either case this condition when associated with edema and profuse mucus secretion may interfere with the proper aeration of the lower respiratory tree and may even be life threatening because of the possibility of laryngeal obstruction and suffocation. These life threatening situations are most commonly seen in children who usually develop an acute epiglottiditis and laryngotracheobronchitis (commonly known as croup) in response to an infection by the Hemophilus influenzae or the parainfluenza virus.
|Pathological examination of the larynx during the active phase reveals a red, congested laryngeal mucosa which at time may be covered with a mucous or mucopurulent exudate. The microscopic examination reveals various degree of inflammatory infiltrate of the mucosa. The treatment depends on the etiological factor. In emergency situation, with the possibility of laryngeal obstruction, surgical procedure like a tracheostomy may be necessary.|
INFECTIONS OF THE LARYNX
There are a few childhood diseases that are, with the vaccination campaigns, almost eradicated from certain areas of the world but still endemic in others, namely third world countries. These diseases deserve some mention in this course because of their devastating effect on the upper respiratory tree, the result of toxin production by the microorganisms. They include among others, diphteria and pertussis that affect the pharynx, the larynx and the trachea.
This bacterial infection that was very endemic at one time affects mainly the pharynx, the larynx and the trachea. The laryngeal form is the most common and the most dangerous. It is commonly found in children but may however occur in adults. It is caused by a single-toxin-producing lysogenic gram positive rod Corynebacterium Diphteriae transmitted through aerosol droplets and cutaneous shedding. Most people are asymptomatic carriers, the susceptible individuals, lacking the antibodies to the microorganism, can be identified by the positive reaction to the intradermal injection of diphteria toxin (Schick test), the immune individuals because of the antibodies acquired either by vaccination or previous disease have no cutaneous reaction, a negative reaction. The vaccin does not prevent the colonization of the bacteria but protects against the effect of the toxin.
|This is one
of the upper respiratory diseases that is often associated with life threatening
situations. Other systemic symptoms , asides from the respiratory symptoms
are often present. These include:
Peripheral nerve paralysis (one of the main symptom of this disease) resulting from the neurotoxicity of certain strain of the microorganism
Interference with the synthesis of certain enzymes and polypeptides necessary for the metabolism of fatty acid.
The first stage of the disease that starts after an incubation period of 1 to 7 days is associated with proliferation of the microorganism causing edema and hyperemia of the affected mucosa.
The second stage that occurs later with the production of exotoxin, is characterized by extensive necrosis of the epithelium, necrosis that is associated with the formation of a dense fibrino-suppurative exudate (pseudomembranous inflammation). When the exudate dries out, it forms a superficial membrane or a cast that may detach from the underlying necrotic tissue, and obstruct the airways if aspirated. Underneath the membrane, the necrotic tissue is heavily infiltrated with PMNs, the blood vessels are congested and the surrounding soft tissue is edematous and contains extravasated blood cells. The lymphnodes of the area are usually enlarged.
OR WHOOPING COUGH.
This highly contagious childhood disease caused by a gram negative coccobacillus Bordetella Pertussis is characterized by violent paroxysmal cough followed by a loud inspiratory noise. About five different varieties of toxin
( endotoxin and exotoxin) produced by the bacilli are responsible for the epithelial damage and the neurotoxicity characteristic of the disease. One distinctive feature of the whooping cough is the high lympho that is always present (85 to 90% of lymphocytes) in the affected individual.
stages (3) are identified: Stage 1 or Prodromal stage
Stage 2 or Paroxysmal stage
Stage 3 or End stage
During the catarrhal or prodromal phase, the microorganism that can be identified in a tangle mass on the brush border of the surface epithelium of the upper airway, and within the macrophages of the area ,stimulates the bronchial cells to produce a profuse tenacious mucus. The affinity of the microorganisms to the specific sites is due to the production of filamentous hemagglutinin that binds to the carbohydrate on the surface epithelial cells and the production of CR3 (Mac-1) integrin that attacks the macrophages. The pathological changes of this early phase of the disease, consist of neutrophilic infiltrate of the mucosa of the upper airway.
stage, the paroxysmal phase of the disease associated with the production
of large amount of toxin is characterized by marked necrosis of the mucosa
which, together with the heavy inflammatory infiltrate of the submucosa,
form a thick mucopurulent exudate on the surface of the epithelium.
The last or end stage of the disease startswith further evolution of the process, during which the entire wall of the trachea and the bronchi is infiltrated with PMN leukocytes and the peritracheal lymph follicles are enlarged.
Treatment with erythromycin, to be effective, has to start before the paroxysmal stage, it is not effective and does not alter the clinical course of the disease if given after the symptoms have appear. Encephalitis is a common unexplained complication.
OF THE LARYNX
Benign and malignant tumors can originate in the larynx.
OF THE LARYNX
Like the nasal cavities, the larynx may be the site of a simple polyp,LARYNGEAL POLYP, but unlike the nasal polyp, the laryngeal polyp is a true neoplasm, very common among heavy smokers. Because of the high incidence of this lesion among singers or any individual with constant strain on their vocal cord, it has been called "singer's node" or Reactive nodules.
It usually consists of a pedunculated nodule, not larger than one centimeter in diameter, located most often on the vocal cord.
On microscopic examination, the polyp consists of a central core of fibro- vascular connective tissue infiltrated with inflammatory cells, and an external lining made of stratified squamous epithelium that may be ulcerated in areas. This lesion very rarely if ever becomes malignant.
tumor that can develop in the larynx is a PAPILLOMA,
which in most cases is located on the vocal cords.
One physical characteristic of this tumor is a friable often ulcerated external surface that bleeds on contact, specially when located at the edge of the vocal cord.
The papilloma is made of one (adult) or several (children) finger-like projections composed of a central core of fibrous tissue with a rich vascular supply, and a stratified squamous epithelium covering. It has a great similarity with the fungiform papilloma of the nasal passage. Unlike the polyp, however, the papilloma shows great potential for malignant degeneration.
The multiple papilloma found mostly in chidren (juvenile papillomatosis) and rarely in adults (recurring papillomas) is usually caused by the HPV type 6 and 11 . This viral papillomatous lesion is usually multiple, and disappears at puberty in the juvenile form, it does not show great potential for malignant degeneration
The inverted papilloma previously described can also be found in the larynx and should be differentiated from a more aggressive epithelial tumor.
TUMORS OF THE LARYNX.
Most malignancies of the larynx are of epithelial origin, have a 7 to 1 male preponderance, and affect most commonly the vocal cords. Most neoplastic lesions of the larynx originate in areas of epithelial dysplasia resulting from contributing factors that include cigarette smoking, alcohol consumption, asbestos exposure , irradiation exposure , HPV infection and the presence of a papilloma.
OF THE LARYNX
This laryngeal tumor represents 2% of all malignant tumors.
On examination, the malignant lesions range from a small ulceration of the surface epithelium to an extensive invasive lesion that involves the surrounding structures. Based on the extension and location of the tumor, four variants of this neoplasm are recognized, each variant requiring a different treatment approach and carrying variable prognosis.
|- A glottic
carcinoma, the most common variant, is limited to the true vocal cords.
This is a slow growing tumor with a good prognosis that only requires conservative
surgery and radiotherapy. Lymph node metastases are usually not present,
at least in the early stage, since the true vocal cords have a poor lymphatic
- A transglottic carcinoma involves the true and false cords. This tumor is often associated with lymphnodes involvement and requires total laryngostomy.
- A supraglottic carcinoma involves the false cords and the supraglottic ventricle or saccule, sparing usually the true cords. Lymphnodes metastasis is often present. Limited surgery may be attempted at least in the early stage of the lesion.
- An infraglottic also called subglottic carcinoma is usually located underneath the true cords that are extensively involved. The lymphnodes are commonly affected. This variant of the tumor requires total laryngectomy.
In all different locations the tumor may be polypoid, fungating or ulcerative. On microscopic examination, about 95% of the lesions are squamous cell carcinoma; rarely an adenocarcinoma may arise from the mucus glands of the larynx.
This is a rare tumor that arises from the cartilaginous layer of the larynx, namely the thyroid, the cricoid, the arytenoid cartilage.
The tumors are usually low grade non-aggressive chondrosarcoma with a good prognosis when properly resected. However, the myxoid type of chondrosarcoma can be high grade lesions that have to be treated with extensive surgery (total laryngectomy).
|TRACHEA AND BRONCHI|
structures of the respiratory tree extend from the larynx to the lungs parenchyma.
They form a branching inverted tree like structure through multiple subdivisions.
The first division starts at the distal end of the trachea, the carina, that divides to give two main bronchi, the initial subdivision of the main bronchi gives three branches on the right side and two branches on the left. Subsequent multiple subdivisions, about 16, lead to the formation of a terminal bronchiole, that is the last segment of the conducting airways.
The basic components of this part of the conductive airways are the same with only some quantitative variations to accommodate the function of the segment in the system.
layers identified are:
An epithelial layer that varies with the segment
at the level of the trachea and the main bronchi is made of pseudostratified
columnar epithelium actively secreting mucus. The height of the mucosal
layer decreases progressively with each subdivision to become a cuboidal
to flattened non ciliated epithelium at the level of the small bronchioles.
The non ciliated cells of the terminal and respiratory bronchioles are known
as the "Clara cells", they are the source of the bronchoalveolar tumors.
In the wall of the trachea and the bronchi specially at the basal layer, there are few clusters of enterochromaffin cells that have settled in the respiratory system through embryonic migration. Later these cells known as Kulchitsky cells can be the source of very active neoplasms.
The Submucosa, from the trachea to the medium size bronchi contains various amount of mucus secreting glands. These glandular structures are not present in the submucosa of the bronchioles.
layer, at the level of the trachea, is made of C shape plates that leave
a posterior gap filled with loose connective tissue containing few smooth
muscle fibers. At the level of the bronchi the cartilage plates are replaced
by interrupted plates that surround the entire circumference of the bronchus.
The cartilage component is absent at the level of the small bronchi and
The main function of the trachea and the bronchi aside from conducting the air to the lower respiratory units, is clearing the airways of respiratory secretion. This function is carried out by the unidirectional movement of the ciliae that transport the accumulated secretion toward the upper respiratory passage for elimination. The mucus secretion that is being evacuated contains all the inhaled particles that bypassed the protective mechanism of the upper airways, the shed epithelial cells, and all the microorganisms engulfed by the macrophages.
Any alteration in the structure of the ciliae or in the production of the mucus may affect the proper function of the respiratory tree. With retention of the secretion, the nerve endings of the area are stimulated to trigger a cough reflex that remain in action until the entire passage is clear or the reflex is curtailed through medication.
The ciliary function is not found at the level of the small bronchioles, contraction is the main defense mechanism of the distal segment of the respiratory tree.
|PATHOLOGY OF THE TRACHEA AND THE MAIN BRONCHI|
|The trachea and the bronchi are commonly affected by pathological lesions that also affect the upper and the lower respiratory tree, the changes varying with the disease process. Most lesions are reviewed here, the congenital anomalies are studied with the pathology of the lungs.|
Acute inflammatory lesion of the trachea, known as TRACHEITIS is often the result of fume inhalation, tracheostomy, or intubation. The etiology varies with the segment affected. The inflammatory lesions of the bronchi, known as BRONCHITIS are most often the result of an infectious process. In adult, the large bronchi are usually affected, while in children the small bronchioles are involved, condition known as BRONCHIOLITIS.
|In case of
BRONCHIOLITIS, the most severe form because of the alterations occuring
in the structure of the bronchioles, the inflammatory reaction usually caused
by the Hemophilus influenzae is associated with the secretion of a tenacious
mucus that may obliterate the small bronchioles and lead to an acute respiratory
distress, situation that is often life threatening.
On examination, the usual pathological findings consist of increased production of mucus and mucosal thickening of the trachea, the bronchi and the bronchioles, with redness ans erosion of the mucosa.
On microscopic examination, the cuboidal lining epithelium of the bronchioles undergoes mucoid metaplasia, and secretes large amount of mucin. The yellowish mucinous droplets accumulate in the lumen of the bronchioles and interfere with perfusion causing the severe respiratory distress characteristic of the disease, this may be life threatening. In the larger bronchi and in the trachea, the blood vessels are congested, the epithelial surface may be ulcerated in areas, and the submucosa is infiltrated with acute inflammatory cells.
This is a condition often encountered during the course of many diseases of the respiratory system, it will be described with the appropriate clinical setting.
The neoplastic lesions of the trachea and the bronchi will be studied with the neoplastic lesions of the lungs.
are not only the essential organs of respiration but they also perform few
other cardinal functions in the general homeostasis of the human body.
A metabolic function is exemplified by the production of surfactant.
An endocrine function consists of secretion of certain hormone (ACE)
An excretory function that helps in the elimination of certain poisonous substances like alcohol and paraldehyde.
THE NORMAL ANATOMY OF THE LUNGS.
The lungs are a paired organs nested in the chest cavity and covered by the pleura
The two main bronchi that emerge from the initial division of the trachea supply the left and the right lung. The right main bronchus is at a slightly more slanted angle than the left, feature that is very important in considering the frequency of aspiration of foreign particles in the right versus the left lung. The initial three branches on the right supply the three right lobes and two branches on the left for the two left lobes of the lungs. Through multiple subdivisions the bronchi form a tree-like structure that provide a framework for the lung parenchyma. The lower lobes of both lungs are more posteriorly located than the upper lobes. All the structures distal to the terminal bronchioles form the lung parenchyma which is made of functioning units known as Acinus (about 50.000). The exchange of gases between the blood and the alveolar air is done at the level of the acinus.
is composed of:
A respiratory bronchiole
An alveolar duct
An alveolar sac and Several alveoli
A cluster of 4 to 5 respiratory bronchioles and their acini form a Pulmonary Lobule, each lobule is separated from the adjacent one by a thin septum of fibrous tissue, several lobules form a Pulmonary lobe, each lobe is demarcated from the adjacent one by intervening visceral pleura.
OF THE LOWER RESPIRATORY AREA. THE ACINUS.
The wall of the respiratory bronchioles is alternately thick and thin, the thick areas contain smooth muscle fibers and the thin areas form the wall of the alveolar sacs. The alveolar sacs are made of several alveoli separated from each other by the alveolar septum which is lined on either sides by epithelial cells, the pneumocytes.
The lining epithelial cells or pneumocytes are of two types:
A layer of squamous cells, the more abundant pneumocytes type l, form a continuous lining interrupted only by the second type of cells - the septal cells or pneumocytes type ll (10%) that seem to be active in the production of surfactant and the repair mechanism of the damaged alveoli. In the alveolar septa are the capillaries. In areas the endothelial lining of the capillaries and the epithelial lining of the alveoli share a common basement membrane, in other areas, the two membranes are separated by a thin layer of loose connective tissue containing smooth muscle fibers, elastic fibers and few lymphocytes.
which in the lung are called dust cells, are also present within
the alveolar spaces, they play an important role in the clearing of the
alveolar spaces. The particulate matters that escape the protective mechanisms
of the upper respiratory passages and reach the alveolar spaces are taken
by the alveolar macrophages. The organic particles are digested by those
macrophages but the inorganic material is transported by the macrophages
in the interstitial tissue of the lungs where it is deposited.
The lymphatic drainage of the lung starts at the level of the respiratory bronchioles, the alveolar walls are devoid of lymphatic vessels.
|PATHOLOGY OF THE LUNGS|
|The lungs are affected by almost all terminal systemic diseases, the changes that occur vary from a mild congestion, to edema, atelectasis to an advanced case of bronchopneumonia. The pathological alterations discussed in this course are more specific and, at time, restricted to the lungs.|
MALFORMATIONS OF THE LUNGS
Congenital anomalies of the lungs are, in most cases, due to a developmental defect of the fetus during intra uterine life.
Several of these birth defects are described in the literature, only the most commonly encountered are described here.
TOTAL OR PARTIAL OF THE LUNG. APLASIA AND HYPOPLASIA.
This consists of a complete absence of both lungs, of one lung or any part of the lung. When complete or extensive this anomaly is not compatible with extrauterine life.
OR BRONCHO-ESOPHAGEAL FISTULA
In the embryo, the gastrointestinal and respiratory tracts begin as a single tube, the primitive foregut that later divides to give two independent systems . Any failure of separation of the two systems leads to an abnormal communication between any part of the respiratory passages and the GI tract , the esophagus being the most commonly affected. The tracheo-esophageal or broncho- esophageal fistula may be life threatening and requires prompt surgical repair when possible. The outcome usually depends on the extent and the location of the malformation.
LOBAR AND EXTRA LOBAR PULMONARY SEQUESTRATION
This is a congenital anomaly in which a part of the lung is isolated from the rest of the organ. The sequestrated portion may be located inside the lung tissue, in which case it known as "intralobar" or it could located outside the lung and is known as "extralobar". About 90% of the cases of pulmonary sequestration occur in the left side and have a 4 to 1 male/female ratio. The isolated segment receives its own blood supply directly from the aorta or through a systemic artery and is not in communication with the bronchial tree.
The development of the intralobar variant starts very early during fetal growth but the symptoms do not become evident until late adolescence. The sequestrated segment is embedded inside the normal lung tissue and is not covered by the pleura.
variant starts its development a little later during fetal growth, but
the symptoms usually appear during the first year of life. The isolated
segment is located outside the main lung and is completely covered with
In both varieties, the clinical significance of this malformation is that the isolated portion of the lung is subject to repeated bouts of infections leading to abscess formation and eventually scar tissue. An accurate diagnosis of this malformation is very important since the signs and symptoms may mimic many other more severe diseases.
When there is a failure of development (hypoplasia) of the cartilage plates in the main or large bronchus, the entire bronchus collapses allowing air to enter but not to exit the respiratory tree. The result is trapping of air in the distal area of the pulmonary system causing inflation of the acini and rupture of the alveolar septa, condition known as emphysema, studied later in the course.
VASCULAR ANOMALIES OF THE LUNGS
The extent of the vascular anomalies of the lungs varies from a small arteriovenous fistula at the level of the capillaries to a complete absence of a major blood vessel which is often associated with cardiac malformations not compatible with extra uterine life.
CYSTS OF THE RESPIRATORY SYSTEM
These are the result of an abnormal detachment of the primitive foregut from which the respiratory system arises. Two different types of cysts can be formed:
|BRONCHOGENIC OR CENTRAL CYST. This type of cyst can be found in any area of the lungs, it can be single or multiple and is often located near a bronchus or a bronchiole. The cystic cavity may be in direct communication with the lumen of the bronchus and is lined with respiratory epithelium, the cavity may be filled with mucus or may contain air. Complications of this lesion consist of secondary infection leading to abscess formation, squamous metaplasia of the lining epithelium of the cyst which may be a basis for the development of a malignant lesion.|
|PULMONARY OR PERIPHERAL CYSTS. These cystic lesions of the lung are often multiple and are not in communication with a bronchus, they are usually located at the periphery of the lungs. A common complication associated with the peripheral cysts is rupture in the pleural spaces. If a large amount of air accumulates in the pleural spaces it may result in pneumothorax with all the complications.|
OF CONGENITAL CYSTS
A cyst of either type if large enough, may compress areas of the lungs with loss of pulmonary air space causing some degree of respiratory distress, the cysts are also a constant source of infection leading to abscess formation. Erosion of a cyst inside a blood vessel may result in massive hemorrhage, and infiltration of the air in the soft tissue may lead to interstitial emphysema.
Atelectasis which is a failure of expansion or collapse of the lung tissue that leads to loss of lung volume may be present at birth (neonatal atelectasis) or may appear after birth (acquired atelectasis).
NEONATAL ATELECTASIS. This constitutes a very important cause of perinatal death. A distinction between a primary and a secondary form of neonatal pulmonary atelectasis is very useful, specially in medico-legal cases
primary form of atelectasis, there
is no initial inflation of the lung tissue, no air has ever penetrated the
respiratory tract. This variety is found mainly in premature infants, and
in babies who have suffered intrauterine hypoxia due to the kinking
of the umbilical cord. It also occurs in infants of diabetic mothers, in
which cases there is a decreased production of surfactant resulting from
a compensatory secretion of insulin by the fetus.
On pathological examination, the lungs are usually collapsed, red blue in color and have a rubbery consistency. This lung sinks when placed in a bucket of water.
On microscopic examination, the alveolar spaces are small and may contain granular material, the alveolar walls are thick.
of neonatal atelectasis, there was an initial inflation of the lungs.
During vaginal delivery or shortly after, aspiration of amniotic fluid or
blood causes obliteration of the terminal bronchioles preventing further
aeration of the lung tissue that leads to a certain degree of atelectasis
.The hypoxia that result causes necrosis of the epithelial cells, vascular
disruption and formation of hyaline membranes. The air that was initially
inspired escapes in part but a residual amount remains trapped in the distal
portion (the physiological dead space) of the lungs which explain the pathological
findings. This condition is often associated with the Respiratory
Distress Syndrome of the newborn.
On examination, the lungs may show alternate areas of inflated tissue next to areas of collapse that give it a mottled appearance. These lungs usually float on water since they have been originally partially inflated and contain some residual air in the alveolar spaces.
On histological examination,the collapsed areas show the features of a primary atelectasis, and the inflated areas show few dilated alveoli with thin flattened walls. Hyaline membrane can be seen coating some of the alveoli.
ANOMALIES OF THE LOWER RESPIRATORY TRACT
ACQUIRED ATELECTASIS. The acquired form of pulmonary atelectasis found mostly in adults is due to so many different factors that it requires an etiological classification. The many different types described include:
OBSTRUCTIVE OR RESORPTION ATELECTASIS is due to a complete or partial obstruction of the airways. The air trapped distal to the obstruction is absorbed and the dependent area of the lung collapses. When the obstruction is complete, it prevents the air from reaching the distal alveolar spaces that fail to expand.
ATELECTASIS .This type of pulmonary atelectasis is due to pressure against
the lung or part of the lung by a filled pleural cavity , an elevated diaphragm,
or a space-occupying pulmonary lesion and pneumothorax. The mediastinum
usually shifts towards the unaffected lung.
CONTRACTION ATELECTASIS. This results from the resistance to expansion of the alveoli due to the presence of scar tissue adjacent or around the alveolar walls. The fibrous tissue composing the scar creates a pulling force in the opposite direction preventing proper dilatation of the alveoli.
PATCHY ATELECTASIS OR MICROATELECTASIS is found in cases of pulmonary surfactant deficiency. The Respiratory Distress Syndrome either in the newborn (Hyaline membrane disease) or in the adult (Diffuse alveolar damage), is often associated with scattered areas of patchy atelectasis of the lungs.
The pathological changes are the same for about all the different types of atelectasis. All or part of the lobes of the lungs may be affected, in the obstructive type, the entire lung may be folded against the mediastinum. The lung tissue is generally shrunken, is rubbery inconsistency, and the non affected areas show some degree of compensatory over-inflation called "compensatory emphysema ".
The atelectatic lung tissue is prone to secondary infection, the atelectasis process however is often reversible with re-inflation of the collapsed alveoli.
File updated August 22, 2001.
© M. Kavanagh, M.D